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| Mendeliome v1.1891 | CRNKL1 | Zornitza Stark Marked gene: CRNKL1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1889 | DCC | Zornitza Stark commented on gene: DCC: Third family reported with biallelic variants and scoliosis, PMID 33141514; novel homozygous frameshift variant (p.Asn800Lysfs*11) in three individuals. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1889 | SLC7A5 | Zornitza Stark Marked gene: SLC7A5 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1888 | SLC7A5 |
Sangavi Sivagnanasundram gene: SLC7A5 was added gene: SLC7A5 was added to Mendeliome. Sources: Other Mode of inheritance for gene: SLC7A5 was set to Unknown Publications for gene: SLC7A5 were set to 29884839 Phenotypes for gene: SLC7A5 were set to Large neutral amino acid transporter deficiency (MIM#600182) Review for gene: SLC7A5 was set to RED Added comment: Classified an inborn error of amino acid metabolism by IEMbase however more evidence is required to support the gene-disease association. Sources: Other |
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| Mendeliome v1.1888 | CRNKL1 |
Mark Cleghorn gene: CRNKL1 was added gene: CRNKL1 was added to Mendeliome. Sources: Other Mode of inheritance for gene: CRNKL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: CRNKL1 were set to complex neurodevelopmental disorder MONDO:0100038 Review for gene: CRNKL1 was set to GREEN Added comment: Unpublished, presented at ESHG June 2024 - Louise Bicknell, University of Otago NZ 8 unrelated families via gene matcher with rare, de novo, missense variants in CRNKL1 severe microcephaly (all, -8 to -11 SD) ID/epilepsy pontocerebellar hypoplasia (6/8) simplified gyration (8/8) 7 variants are missense at p.Arg267 residue 1 variant missense at p.Arg301 RNA-seq on patient fibroblasts - no alteration in gene expression Zebrafish homolog of Arg267 and Arg301 - mimics observed phenotype (reduced brain development), increased in embryo apoptosis RNA seq on affected zebrafish embryos - transcriptome strongly disrupted Splicing analysis in progress CRKNL1 supports U6 structure in spliceosome Sources: Other |
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| Mendeliome v1.1888 | ZNF483 | Zornitza Stark Marked gene: ZNF483 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1886 | ZNF483 |
Mark Cleghorn gene: ZNF483 was added gene: ZNF483 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ZNF483 was set to Unknown Publications for gene: ZNF483 were set to 38951643 Phenotypes for gene: ZNF483 were set to primary ovarian failure MONDO:0005387 Review for gene: ZNF483 was set to AMBER Added comment: PMID: 38951643, ESHG 2024 presentation Large cohort assessing PRS for age of menarche Noted rare PTVs in ZNF483 assoc w earlier menarche No individual case information in this study Sources: Literature |
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| Mendeliome v1.1884 | SENP7 | Zornitza Stark reviewed gene: SENP7: Rating: GREEN; Mode of pathogenicity: None; Publications: 38972567, 37460201; Phenotypes: Arthrogryposis multiplex congenita, MONDO:0015168, SENP7-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1884 | MYZAP |
Zornitza Stark changed review comment from: 10 individuals from four unrelated families with bi-allelic variants in this gene with DCM. Supportive zebrafish model. Note the MYZAP and GCOM1 genes are part of the GRINL1A complex transcription unit. Some of the reported variants affect GCOM1 with postulated effect on MYZAP due to read through transcription (two families), and in the rest of the families MYZAP was affected directly. Sources: Literature; to: 10 individuals from four unrelated families with bi-allelic variants in this gene with DCM. Supportive zebrafish model. The MYZAP gene is part of the GRINL1A complex transcription unit (CTU), or GCOM1, which also includes the downstream POLR2M gene, or GRINL1A.. Some of the reported variants affect GCOM1 with postulated effect on MYZAP due to read through transcription (two families), and in the rest of the families MYZAP was affected directly. Transcription from an upstream promoter within the GRINL1A CTU produces 2 types of alternatively spliced transcripts: MYZAP transcripts, also called GRINL1A upstream (GUP) transcripts, which include only exons from the MYZAP gene, and GRINL1A combined (GCOM) transcripts, which include exons from both the MYZAP gene and the downstream POLR2M gene. Transcription of the POLR2M gene initiates at a downstream promoter within the GRINL1A CTU and produces alternatively spliced POLR2M transcripts, also called GRINL1A downstream (GDOWN) transcripts, which include only exons from the POLR2M gene Sources: Literature |
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| Mendeliome v1.1884 | MYZAP | Zornitza Stark Marked gene: MYZAP as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1883 | MYZAP |
Zornitza Stark gene: MYZAP was added gene: MYZAP was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MYZAP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MYZAP were set to 34899865; 35840178; 38436102; 20093627 Phenotypes for gene: MYZAP were set to Cardiomyopathy, dilated, 2K, MIM# 620894 Review for gene: MYZAP was set to GREEN Added comment: 10 individuals from four unrelated families with bi-allelic variants in this gene with DCM. Supportive zebrafish model. Note the MYZAP and GCOM1 genes are part of the GRINL1A complex transcription unit. Some of the reported variants affect GCOM1 with postulated effect on MYZAP due to read through transcription (two families), and in the rest of the families MYZAP was affected directly. Sources: Literature |
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| Mendeliome v1.1882 | PRODH2 | Zornitza Stark Marked gene: PRODH2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1881 | SELENBP1 | Zornitza Stark Marked gene: SELENBP1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1877 | FDXR | Zornitza Stark edited their review of gene: FDXR: Added comment: Multiple reports of individuals with extra-ocular features, including ID and regression.; Changed publications: 30250212, 28965846, 29040572, 33348459, 37046037, 37481223; Changed phenotypes: Auditory neuropathy and optic atrophy, MIM#617717, Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1876 | SELENBP1 |
Sangavi Sivagnanasundram gene: SELENBP1 was added gene: SELENBP1 was added to Mendeliome. Sources: ClinGen Mode of inheritance for gene: SELENBP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SELENBP1 were set to 29255262 Phenotypes for gene: SELENBP1 were set to extraoral halitosis due to methanethiol oxidase deficiency MONDO:0029144 Review for gene: SELENBP1 was set to GREEN Added comment: 3 unrelated probands in one publication. All reported individuals had a “cabbage-like” breath odour due to the elevated levels of methanethiol and dimethylsulfide in their breath. Knockout mouse model recapitulating the human phenotype including the biochemical characteristics. Classified as Moderate by ClinGen Aminoacidopathy GCEP on 11/11/2022 https://search.clinicalgenome.org/CCID:006103 Sources: ClinGen |
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| Mendeliome v1.1876 | PRODH2 |
Sangavi Sivagnanasundram gene: PRODH2 was added gene: PRODH2 was added to Mendeliome. Sources: ClinGen Mode of inheritance for gene: PRODH2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PRODH2 were set to 27139199 Phenotypes for gene: PRODH2 were set to hydroxyprolinemia MONDO:0009374 Review for gene: PRODH2 was set to RED Added comment: PMID: 27139199 Variants reported in 6 individuals however only 2 cases presented with intermittant biochemical phenotype however the cause remains unclear. The rest of the individuals were asymptomatic suggesting that hydroxyprolinemia is a benign condition. Classified as Limited by ClinGen Aminoacidopathy GCEP on 12/12/2022 https://search.clinicalgenome.org/CCID:005893 Sources: ClinGen |
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| Mendeliome v1.1876 | GAS2 | Zornitza Stark Marked gene: GAS2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1875 | GAS2 |
Zornitza Stark gene: GAS2 was added gene: GAS2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GAS2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GAS2 were set to 33964205 Phenotypes for gene: GAS2 were set to Deafness, autosomal recessive 125, MIM#620877 Review for gene: GAS2 was set to AMBER Added comment: Single family reported with four affected brothers and a splicing variant. Supportive mouse model. Sources: Literature |
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| Mendeliome v1.1874 | KIF1A | Zornitza Stark Phenotypes for gene: KIF1A were changed from Neuropathy, hereditary sensory, type IIC, MIM# 614213; NESCAV syndrome, MIM# 614255; Spastic paraplegia 30, MIM# 610357 to Neuropathy, hereditary sensory, type IIC, MIM# 614213; NESCAV syndrome, MIM# 614255; Spastic paraplegia 30, autosomal dominant MIM# 610357; Spastic paraplegia 30, autosomal recessive 620607 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1873 | KIF1A | Zornitza Stark edited their review of gene: KIF1A: Changed phenotypes: Neuropathy, hereditary sensory, type IIC, MIM# 614213, NESCAV syndrome, MIM# 614255, Spastic paraplegia 30, autosomal dominant MIM# 610357, Spastic paraplegia 30, autosomal recessive 620607 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1873 | SREBF2 | Zornitza Stark Marked gene: SREBF2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1872 | SREBF2 |
Zornitza Stark gene: SREBF2 was added gene: SREBF2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SREBF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SREBF2 were set to 38847193 Phenotypes for gene: SREBF2 were set to Neurocutaneous syndrome, MONDO:0042983, SREBF2-related Review for gene: SREBF2 was set to AMBER Added comment: Two individuals with de novo missense variants, presenting with neurological, cutaneous and skeletal features; supportive functional data. Sources: Literature |
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| Mendeliome v1.1871 | USP25 | Zornitza Stark Marked gene: USP25 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1870 | C10orf71 | Zornitza Stark Marked gene: C10orf71 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1866 | PSMF1 | Zornitza Stark Marked gene: PSMF1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1865 | PSMF1 |
Zornitza Stark gene: PSMF1 was added gene: PSMF1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PSMF1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PSMF1 were set to https://www.medrxiv.org/content/10.1101/2024.06.19.24308302v1 Phenotypes for gene: PSMF1 were set to Complex neurodevelopmental disorder with motor features, MONDO:0100516, PSMF1-related Review for gene: PSMF1 was set to GREEN Added comment: 22 individuals from 15 families reported with a range of neurological phenotypes ranging from early-onset Parkinson's disease; childhood conditions typified by ID and a range of movement disorders; through to perinatal lethal presentations with arthrogryposis multiplex. Genotype-phenotype correlation: biallelic missense variants resulted in the milder phenotypes, while bi-allelic LoF variants in the more severe phenotypes. Supportive functional data. Sources: Literature |
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| Mendeliome v1.1860 | TUBA4A | Bryony Thompson reviewed gene: TUBA4A: Rating: GREEN; Mode of pathogenicity: None; Publications: 38884572, 37418012; Phenotypes: Hereditary ataxia MONDO:0100309, TUBA4A-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1860 | VPS50 |
Ain Roesley changed review comment from: 1x proband Chet for a nonsense p.(Lys5*) and a complex structural variant of a 4.3Mb inversion, flanked by 170kb and 428kb deletions, respectively. The 428kb deletion spans the entire VPS50 gene. Sanger confirmed the Lys5* to be 'homozygous' in the proband. Phenotypes include: microcephaly, nystagmus, seizures, hypoplastic corpus callous, neonatal low GGT cholesatsis, hepatomegaly, failure to thrive; to: 1x proband Chet for a nonsense p.(Lys5*) and a complex structural variant of a 4.3Mb inversion, flanked by 170kb and 428kb deletions, respectively. The 428kb deletion spans the entire VPS50 gene. Sanger confirmed the Lys5* to be 'homozygous' in the proband. Phenotypes include: severe ID, muscular hypotonia, sensorineural hearing impairment, microcephaly, nystagmus, seizures, hypoplastic corpus callous, neonatal low GGT cholesatsis, hepatomegaly, failure to thrive |
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| Mendeliome v1.1860 | SERPINA11 | Ain Roesley Marked gene: SERPINA11 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1860 | SERPINA11 | Ain Roesley Phenotypes for gene: SERPINA11 were changed from to pericardial effusion; pleural effusion | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1859 | SERPINA11 | Ain Roesley edited their review of gene: SERPINA11: Changed phenotypes: pericardial effusion, pleural effusion | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1859 | SERPINA11 |
Ain Roesley gene: SERPINA11 was added gene: SERPINA11 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SERPINA11 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SERPINA11 were set to 38831697 Review for gene: SERPINA11 was set to RED gene: SERPINA11 was marked as current diagnostic Added comment: 1 family with 2 fetuses. 1st fetus presented with isolated pericardial effusion and a TOP was opted. post mortem: mild subcutaneous edema with subtle facial dysmorphic features small gelatinous glistening cyst on the right pericardium. Bilateral pleural effusion and multiple similar cysts were noted on the lung surfaces 2nd fetus also presented with pleural and pericardial effusion and a TOP was opted post mortem findings were similar to fetus#1 homozygous nonsense variant in SERPINA11 was found p.(Tyr224*) Immunofluorescence of lung sections from fetus#1 and a gestation-matched fetus as a control demonstrated undetectable levels of SERPINA11 in the bronchiolar epithelium Sources: Literature |
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| Mendeliome v1.1858 | PSMD11 | Bryony Thompson Marked gene: PSMD11 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1857 | PSMD11 |
Bryony Thompson gene: PSMD11 was added gene: PSMD11 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PSMD11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PSMD11 were set to 38866022; 30733659 Phenotypes for gene: PSMD11 were set to Neurodevelopmental disorder, MONDO:0700092, PSMD11-related Review for gene: PSMD11 was set to GREEN Added comment: PMID: 38866022 - 10 unrelated children with early-onset syndromic intellectual disability and neurodevelopmental delay with recurrent obesity. Cognitive impairment is recapitulated in a drosophila model. Loss of function is the mechanism of disease PMID: 30733659 - 4 probands with ID and different 17q11.2 deletions spanning PSMD11 Sources: Literature |
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| Mendeliome v1.1855 | VPS50 |
Ain Roesley changed review comment from: 1x proband Chet for a nonsense p.(Lys5*) and a complex structural variant of a 4.3Mb inversion, flanked by 170kb and 428kb deletions, respectively. The 428kb deletion spans the entire VPS50 gene. Sanger confirmed the Lys5* to be 'homozygous' in the proband. Phenotypes include: nystagmus, seizures, hypoplastic corpus callous, neonatal low GGT cholesatsis, hepatomegaly, failure to thrive; to: 1x proband Chet for a nonsense p.(Lys5*) and a complex structural variant of a 4.3Mb inversion, flanked by 170kb and 428kb deletions, respectively. The 428kb deletion spans the entire VPS50 gene. Sanger confirmed the Lys5* to be 'homozygous' in the proband. Phenotypes include: microcephaly, nystagmus, seizures, hypoplastic corpus callous, neonatal low GGT cholesatsis, hepatomegaly, failure to thrive |
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| Mendeliome v1.1855 | C10orf71 |
Sangavi Sivagnanasundram gene: C10orf71 was added gene: C10orf71 was added to Mendeliome. Sources: Other Mode of inheritance for gene: C10orf71 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: C10orf71 were set to 38950288 Phenotypes for gene: C10orf71 were set to dilated cardiomyopathy MONDO:0005021 Review for gene: C10orf71 was set to GREEN Added comment: Identified a frameshift variant in a large multigenerational family with 8 affected individuals. Further identified four other loss of function variants in a large Chinese cohort of sporadic DCM cases. >50 unrelated individuals identified with loss of function variants. c10orf71-Knockout mouse model recapitulating DCM human phenotype (impairs cardiac function) in the presence of the frameshift variant. Sources: Other |
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| Mendeliome v1.1853 | USP25 |
Sangavi Sivagnanasundram gene: USP25 was added gene: USP25 was added to Mendeliome. Sources: Other Mode of inheritance for gene: USP25 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: USP25 were set to 38875478 Phenotypes for gene: USP25 were set to USP25-related epilepsy (epilepsy, idiopathic generalized, MONDO:0005579) Mode of pathogenicity for gene: USP25 was set to Other Review for gene: USP25 was set to GREEN Added comment: PMID: 38875478 5 heterozygous variants were identified in 8 individuals from 5 unrelated families all with clinical phenotypes associated with generalised epilepsy. Knock-out mouse model showed increased seizure susceptibility compared to the WT. Both loss of function and gain of function variants can be a mechanism of disease in individuals with USP25-related epilepsy. Sources: Other |
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| Mendeliome v1.1853 | RTN2 | Zornitza Stark Phenotypes for gene: RTN2 were changed from Spastic paraplegia 12, autosomal dominant, 604805; MONDO:0011489; distal hereditary motor neuropathy, MONDO:0018894 to Spastic paraplegia 12, autosomal dominant, 604805; MONDO:0011489; Neuronopathy, distal hereditary motor, autosomal recessive 11, with spasticity, MIM# 620854 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1852 | RBFOX3 | Zornitza Stark Marked gene: RBFOX3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1851 | RBFOX3 |
Zornitza Stark gene: RBFOX3 was added gene: RBFOX3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RBFOX3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RBFOX3 were set to 35951651; 36117209; 24039908 Phenotypes for gene: RBFOX3 were set to Neurodevelopmental disorder (MONDO:0700092), RBFOX3-related Review for gene: RBFOX3 was set to AMBER Added comment: Reported as a candidate gene for epilepsy, particularly Rolandic epilepsy. Two supportive animal models. Sources: Literature |
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| Mendeliome v1.1847 | GRXCR2 | Zornitza Stark edited their review of gene: GRXCR2: Added comment: PMID:33528103 reported another family and an unrelated individual from Cameroon with a different homozygous variant (c.251delC/ p.Ile85SerfsTer33).; Changed rating: GREEN; Changed publications: 24619944, 33528103 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1847 | THBS2 | Zornitza Stark Phenotypes for gene: THBS2 were changed from {Lumbar disc herniation, susceptibility to} 603932; connective tissue disorder MONDO:0003900, THBS2-related to Ehlers-Danlos syndrome, classic type, 3, MIM# 620865 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1846 | ERBB4 |
Zornitza Stark changed review comment from: ALS: at least 4 families reported with SNVs. ID: intragenic deletions in 3 families, some inherited.; to: ALS: at least 4 families reported with SNVs, but LIMITED by ClinGen. ID: intragenic deletions in 3 families, some inherited. Unclear if SNVs cause phenotype. |
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| Mendeliome v1.1846 | MTSS1L | Ain Roesley Phenotypes for gene: MTSS1L were changed from ntellectual developmental disorder with ocular anomalies and distinctive facial features MIM#620086 to Intellectual developmental disorder with ocular anomalies and distinctive facial features MIM#620086 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1845 | MTSS1L | Ain Roesley Phenotypes for gene: MTSS1L were changed from Intellectual disability, MTSS2-related (MONDO#0001071) to ntellectual developmental disorder with ocular anomalies and distinctive facial features MIM#620086 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1840 | SUMF1 |
Achchuthan Shanmugasundram changed review comment from: PMID:38863195 reported three unrelated cases with biallelic SUMF1 variants and retinal dystrophy. One of them was a paediatric patient with an attenuated phenotype, while the other two are adult patients with non-syndromic retinal dystrophy.; to: PMID:38863195 reported three unrelated cases with biallelic SUMF1 variants and retinal dystrophy. One of them was a paediatric patient with an attenuated phenotype, while the other two are adult patients with non-syndromic retinal dystrophy. Retinal dystrophy is part of the multiple sulfatase deficiency phenotype (MIM #272200) typically associated with biallelic variants in SUMF1, and these cases show that presumed hypomorphic variants in SUMF1 may also be associated with non-syndromic retinal dystrophy. |
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| Mendeliome v1.1840 | PRRX1 |
Melanie Marty changed review comment from: > 17 individuals with Craniosynostosis from 14 families had been found to have rare heterozygous variants in PRRX1, loss of function variants (PTCs, start loss and partial/full gene del) or missense variants affecting the homeodomain. > These consisted of three de novo variants, but for the majority of cases the variant was inherited from an unaffected parent, yielding an estimate for the penetrance of craniosynostosis of 12.5%. > These results were also supported by immunofluorescence analyses which showed that missense variants within the PRRX1 homeodomain cause abnormal nuclear localisation (PMID: 37154149) > Authors discuss how the previous reports of agnathia-otocephaly doesn't fit with this new evidence and they showed that a missense variant previously reported in a patient with agnathia-otocephaly p.(Phe113Leu) did not affect nuclear import. Supporting evidence: > Post-natal calvarial stem cells expressing Prrx1 have been shown to reside exclusively in the calvarial suture niche, suggesting a requirement for PRRX1 regarding suture patency during early development (PMID: 28366454) >Prrx1 has been shown to be widely expressed within the mouse coronal suture (PMID: 34376651) >Agnathia-otocephaly complex, 2 x missense variants (1 x het, 1 x hom) and 2 x frameshifts reported (het). The frameshift variants both occur in a poly A tract (PMID: 21294718, PMID: 22674740, PMID: 23444262, PMID: 22211708). Authors of the more recent publication on Craniosynostosis (PMID: 37154149) cast some doubt on the reports for Agnathia-otocephaly, possible explanations discussed are that this condition is AR and a 2nd hit was missed or another cause was not identified such as variants in OTX2. > PMID: 7758948 generated a loss-of-function mutation in the mouse Pmx1 gene. Mice homozygous for the mutant allele died soon after birth and exhibited defects of skeletogenesis, which involved the loss or malformation of craniofacial, limb, and vertebral skeletal structures. ; to: Craniosynostosis (MONDO:0015469), PRRX1-related > 17 individuals with Craniosynostosis from 14 families had been found to have rare heterozygous variants in PRRX1, loss of function variants (PTCs, start loss and partial/full gene del) or missense variants affecting the homeodomain. > These consisted of three de novo variants, but for the majority of cases the variant was inherited from an unaffected parent, yielding an estimate for the penetrance of craniosynostosis of 12.5%. > These results were also supported by immunofluorescence analyses which showed that missense variants within the PRRX1 homeodomain cause abnormal nuclear localisation (PMID: 37154149) > Authors discuss how the previous reports of agnathia-otocephaly doesn't fit with this new evidence and they showed that a missense variant previously reported in a patient with agnathia-otocephaly p.(Phe113Leu) did not affect nuclear import. Supporting evidence: > Post-natal calvarial stem cells expressing Prrx1 have been shown to reside exclusively in the calvarial suture niche, suggesting a requirement for PRRX1 regarding suture patency during early development (PMID: 28366454) >Prrx1 has been shown to be widely expressed within the mouse coronal suture (PMID: 34376651) Agnathia-otocephaly complex, MIM# 202650 >Agnathia-otocephaly complex, 2 x missense variants (1 x het, 1 x hom) and 2 x frameshifts reported (het). The frameshift variants both occur in a poly A tract (PMID: 21294718, PMID: 22674740, PMID: 23444262, PMID: 22211708). Authors of the more recent publication on Craniosynostosis (PMID: 37154149) cast some doubt on the reports for Agnathia-otocephaly, possible explanations discussed are that this condition is AR and a 2nd hit was missed or another cause was not identified such as variants in OTX2. > PMID: 7758948 generated a loss-of-function mutation in the mouse Pmx1 gene. Mice homozygous for the mutant allele died soon after birth and exhibited defects of skeletogenesis, which involved the loss or malformation of craniofacial, limb, and vertebral skeletal structures. |
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| Mendeliome v1.1840 | PRRX1 |
Melanie Marty changed review comment from: > 17 individuals with Craniosynostosis from 14 families had been found to have rare heterozygous variants in PRRX1, loss of function variants (PTCs, start loss and partial/full gene del) or missense variants affecting the homeodomain. > These consisted of three de novo variants, but for the majority of cases the variant was inherited from an unaffected parent, yielding an estimate for the penetrance of craniosynostosis of 12.5%. > These results were also supported by immunofluorescence analyses which showed that missense variants within the PRRX1 homeodomain cause abnormal nuclear localisation (PMID: 37154149) > Authors discuss how the previous reports of agnathia-otocephaly doesn't fit with this new evidence and they showed that a missense variant previously reported in a patient with agnathia-otocephaly p.(Phe113Leu) did not affect nuclear import. Supporting evidence: > Post-natal calvarial stem cells expressing Prrx1 have been shown to reside exclusively in the calvarial suture niche, suggesting a requirement for PRRX1 regarding suture patency during early development (PMID: 28366454) >Prrx1 has been shown to be widely expressed within the mouse coronal suture (PMID: 34376651) >Agnathia-otocephaly complex, 2 x missense variants (1 x het, 1 x hom) and 2 x frameshifts reported (het). The frameshift variants both occur in a poly A tract (PMID: 21294718, PMID: 22674740, PMID: 23444262, PMID: 22211708). Authors of the more recent publication on Craniosynostosis (PMID: 37154149) cast some doubt on the reports for Agnathia-otocephaly, possible explanations discussed are that this condition is AR and a 2nd hit was missed or another cause was not identified such as variants in OTX2.; to: > 17 individuals with Craniosynostosis from 14 families had been found to have rare heterozygous variants in PRRX1, loss of function variants (PTCs, start loss and partial/full gene del) or missense variants affecting the homeodomain. > These consisted of three de novo variants, but for the majority of cases the variant was inherited from an unaffected parent, yielding an estimate for the penetrance of craniosynostosis of 12.5%. > These results were also supported by immunofluorescence analyses which showed that missense variants within the PRRX1 homeodomain cause abnormal nuclear localisation (PMID: 37154149) > Authors discuss how the previous reports of agnathia-otocephaly doesn't fit with this new evidence and they showed that a missense variant previously reported in a patient with agnathia-otocephaly p.(Phe113Leu) did not affect nuclear import. Supporting evidence: > Post-natal calvarial stem cells expressing Prrx1 have been shown to reside exclusively in the calvarial suture niche, suggesting a requirement for PRRX1 regarding suture patency during early development (PMID: 28366454) >Prrx1 has been shown to be widely expressed within the mouse coronal suture (PMID: 34376651) >Agnathia-otocephaly complex, 2 x missense variants (1 x het, 1 x hom) and 2 x frameshifts reported (het). The frameshift variants both occur in a poly A tract (PMID: 21294718, PMID: 22674740, PMID: 23444262, PMID: 22211708). Authors of the more recent publication on Craniosynostosis (PMID: 37154149) cast some doubt on the reports for Agnathia-otocephaly, possible explanations discussed are that this condition is AR and a 2nd hit was missed or another cause was not identified such as variants in OTX2. > PMID: 7758948 generated a loss-of-function mutation in the mouse Pmx1 gene. Mice homozygous for the mutant allele died soon after birth and exhibited defects of skeletogenesis, which involved the loss or malformation of craniofacial, limb, and vertebral skeletal structures. |
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| Mendeliome v1.1840 | PRRX1 |
Melanie Marty changed review comment from: > 17 individuals with Craniosynostosis from 14 families had been found to have rare heterozygous variants in PRRX1, loss of function variants (PTCs, start loss and partial/full gene del) or missense variants affecting the homeodomain. > These consisted of three de novo variants, but for the majority of cases the variant was inherited from an unaffected parent, yielding an estimate for the penetrance of craniosynostosis of 12.5%. > These results were also supported by immunofluorescence analyses which showed that missense variants within the PRRX1 homeodomain cause abnormal nuclear localisation (PMID: 37154149) > Authors discuss how the previous reports of agnathia-otocephaly doesn't fit with this new evidence and they showed that a missense variant previously reported in a patient with agnathia-otocephaly p.(Phe113Leu) did not affect nuclear import. Supporting evidence: > Post-natal calvarial stem cells expressing Prrx1 have been shown to reside exclusively in the calvarial suture niche, suggesting a requirement for PRRX1 regarding suture patency during early development (PMID: 28366454) >Prrx1 has been shown to be widely expressed within the mouse coronal suture (PMID: 34376651) >Agnathia-otocephaly complex, 2 x missense variants (1 x het, 1 x hom) and 2 x frameshifts reported (het). The frameshift variants both occur in a poly A tract (PMID: 21294718, PMID: 22674740, PMID: 23444262, PMID: 22211708).; to: > 17 individuals with Craniosynostosis from 14 families had been found to have rare heterozygous variants in PRRX1, loss of function variants (PTCs, start loss and partial/full gene del) or missense variants affecting the homeodomain. > These consisted of three de novo variants, but for the majority of cases the variant was inherited from an unaffected parent, yielding an estimate for the penetrance of craniosynostosis of 12.5%. > These results were also supported by immunofluorescence analyses which showed that missense variants within the PRRX1 homeodomain cause abnormal nuclear localisation (PMID: 37154149) > Authors discuss how the previous reports of agnathia-otocephaly doesn't fit with this new evidence and they showed that a missense variant previously reported in a patient with agnathia-otocephaly p.(Phe113Leu) did not affect nuclear import. Supporting evidence: > Post-natal calvarial stem cells expressing Prrx1 have been shown to reside exclusively in the calvarial suture niche, suggesting a requirement for PRRX1 regarding suture patency during early development (PMID: 28366454) >Prrx1 has been shown to be widely expressed within the mouse coronal suture (PMID: 34376651) >Agnathia-otocephaly complex, 2 x missense variants (1 x het, 1 x hom) and 2 x frameshifts reported (het). The frameshift variants both occur in a poly A tract (PMID: 21294718, PMID: 22674740, PMID: 23444262, PMID: 22211708). Authors of the more recent publication on Craniosynostosis (PMID: 37154149) cast some doubt on the reports for Agnathia-otocephaly, possible explanations discussed are that this condition is AR and a 2nd hit was missed or another cause was not identified such as variants in OTX2. |
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| Mendeliome v1.1840 | PRRX1 |
Melanie Marty changed review comment from: > 17 individuals with Craniosynostosis from 14 families had been found to have rare heterozygous variants in PRRX1, loss of function variants (PTCs, start loss and partial/full gene del) or missense variants affecting the homeodomain. > These consisted of three de novo variants, but for the majority of cases the variant was inherited from an unaffected parent, yielding an estimate for the penetrance of craniosynostosis of 12.5%. > These results were also supported by immunofluorescence analyses which showed that missense variants within the PRRX1 homeodomain cause abnormal nuclear localisation (PMID: 37154149) > Authors discuss how the previous reports of agnathia-otocephaly doen't fit with this new evidence and they showed that a missense variant previously reported in a patient with agnathia-otocephaly p.(Phe113Leu) did not affect nuclear import. Supporting evidence: > Post-natal calvarial stem cells expressing Prrx1 have been shown to reside exclusively in the calvarial suture niche, suggesting a requirement for PRRX1 regarding suture patency during early development (PMID: 28366454) >Prrx1 has been shown to be widely expressed within the mouse coronal suture (PMID: 34376651) >Agnathia-otocephaly complex, 2 x missense variants (1 x het, 1 x hom) and 2 x frameshifts reported (het). The frameshift variants both occur in a poly A tract (PMID: 21294718, PMID: 22674740, PMID: 23444262, PMID: 22211708).; to: > 17 individuals with Craniosynostosis from 14 families had been found to have rare heterozygous variants in PRRX1, loss of function variants (PTCs, start loss and partial/full gene del) or missense variants affecting the homeodomain. > These consisted of three de novo variants, but for the majority of cases the variant was inherited from an unaffected parent, yielding an estimate for the penetrance of craniosynostosis of 12.5%. > These results were also supported by immunofluorescence analyses which showed that missense variants within the PRRX1 homeodomain cause abnormal nuclear localisation (PMID: 37154149) > Authors discuss how the previous reports of agnathia-otocephaly doesn't fit with this new evidence and they showed that a missense variant previously reported in a patient with agnathia-otocephaly p.(Phe113Leu) did not affect nuclear import. Supporting evidence: > Post-natal calvarial stem cells expressing Prrx1 have been shown to reside exclusively in the calvarial suture niche, suggesting a requirement for PRRX1 regarding suture patency during early development (PMID: 28366454) >Prrx1 has been shown to be widely expressed within the mouse coronal suture (PMID: 34376651) >Agnathia-otocephaly complex, 2 x missense variants (1 x het, 1 x hom) and 2 x frameshifts reported (het). The frameshift variants both occur in a poly A tract (PMID: 21294718, PMID: 22674740, PMID: 23444262, PMID: 22211708). |
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| Mendeliome v1.1840 | PRRX1 |
Melanie Marty changed review comment from: > 17 individuals with Craniosynostosis from 14 families had been found to have rare heterozygous variants in PRRX1, loss of function variants (PTCs, start loss and partial/full gene del) or missense variants affecting the homeodomain. > These consisted of three de novo variants, but for the majority of cases the variant was inherited from an unaffected parent, yielding an estimate for the penetrance of craniosynostosis of 12.5%. > These results were also supported by immunofluorescence analyses which showed that missense variants within the PRRX1 homeodomain cause abnormal nuclear localisation (PMID: 37154149) > Authors discuss how the previous reports of agnathia-otocephaly don't fit with this new evidence and they showed that a missense variant previously reported in a patient with agnathia-otocephaly p.(Phe113Leu) did not affect nuclear import. Supporting evidence: > Post-natal calvarial stem cells expressing Prrx1 have been shown to reside exclusively in the calvarial suture niche, suggesting a requirement for PRRX1 regarding suture patency during early development (PMID: 28366454) >Prrx1 has been shown to be widely expressed within the mouse coronal suture (PMID: 34376651); to: > 17 individuals with Craniosynostosis from 14 families had been found to have rare heterozygous variants in PRRX1, loss of function variants (PTCs, start loss and partial/full gene del) or missense variants affecting the homeodomain. > These consisted of three de novo variants, but for the majority of cases the variant was inherited from an unaffected parent, yielding an estimate for the penetrance of craniosynostosis of 12.5%. > These results were also supported by immunofluorescence analyses which showed that missense variants within the PRRX1 homeodomain cause abnormal nuclear localisation (PMID: 37154149) > Authors discuss how the previous reports of agnathia-otocephaly doen't fit with this new evidence and they showed that a missense variant previously reported in a patient with agnathia-otocephaly p.(Phe113Leu) did not affect nuclear import. Supporting evidence: > Post-natal calvarial stem cells expressing Prrx1 have been shown to reside exclusively in the calvarial suture niche, suggesting a requirement for PRRX1 regarding suture patency during early development (PMID: 28366454) >Prrx1 has been shown to be widely expressed within the mouse coronal suture (PMID: 34376651) >Agnathia-otocephaly complex, 2 x missense variants (1 x het, 1 x hom) and 2 x frameshifts reported (het). The frameshift variants both occur in a poly A tract (PMID: 21294718, PMID: 22674740, PMID: 23444262, PMID: 22211708). |
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| Mendeliome v1.1840 | PRRX1 |
Melanie Marty changed review comment from: > 17 individuals with Craniosynostosis from 14 families had been found to have rare heterozygous variants in PRRX1, loss of function variants (PTCs, start loss and partial/full gene del) or missense variants affecting the homeodomain. > These consisted of three de novo variants, but for the majority of cases the variant was inherited from an unaffected parent, yielding an estimate for the penetrance of craniosynostosis of 12.5%. > These results were also supported by immunofluorescence analyses which showed that missense variants within the PRRX1 homeodomain cause abnormal nuclear localisation (PMID: 37154149) Supporting evidence: > Post-natal calvarial stem cells expressing Prrx1 have been shown to reside exclusively in the calvarial suture niche, suggesting a requirement for PRRX1 regarding suture patency during early development (PMID: 28366454) >Prrx1 has been shown to be widely expressed within the mouse coronal suture (PMID: 34376651); to: > 17 individuals with Craniosynostosis from 14 families had been found to have rare heterozygous variants in PRRX1, loss of function variants (PTCs, start loss and partial/full gene del) or missense variants affecting the homeodomain. > These consisted of three de novo variants, but for the majority of cases the variant was inherited from an unaffected parent, yielding an estimate for the penetrance of craniosynostosis of 12.5%. > These results were also supported by immunofluorescence analyses which showed that missense variants within the PRRX1 homeodomain cause abnormal nuclear localisation (PMID: 37154149) > Authors discuss how the previous reports of agnathia-otocephaly don't fit with this new evidence and they showed that a missense variant previously reported in a patient with agnathia-otocephaly p.(Phe113Leu) did not affect nuclear import. Supporting evidence: > Post-natal calvarial stem cells expressing Prrx1 have been shown to reside exclusively in the calvarial suture niche, suggesting a requirement for PRRX1 regarding suture patency during early development (PMID: 28366454) >Prrx1 has been shown to be widely expressed within the mouse coronal suture (PMID: 34376651) |
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| Mendeliome v1.1840 | AFF2 | Zornitza Stark Phenotypes for gene: AFF2 were changed from Mental retardation, X-linked, FRAXE type 309548 to Intellectual disability, X-linked, FRAXE type, MIM#309548 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1838 | RDH14 | Zornitza Stark Marked gene: RDH14 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1838 | RDH14 |
Zornitza Stark gene: RDH14 was added gene: RDH14 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RDH14 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RDH14 were set to 34848785 Phenotypes for gene: RDH14 were set to Neurodevelopmental disorder, MONDO:0700092, RDH14-related Review for gene: RDH14 was set to RED Added comment: Two related individuals with ID and cerebellar atrophy and homozygous LoF variant reported. Sources: Literature |
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| Mendeliome v1.1837 | HYKK | Zornitza Stark Marked gene: HYKK as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1837 | HYKK |
Zornitza Stark gene: HYKK was added gene: HYKK was added to Mendeliome. Sources: Literature Mode of inheritance for gene: HYKK was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HYKK were set to 23242558 Phenotypes for gene: HYKK were set to inborn disorder of lysine and hydroxylysine metabolism MONDO:0017351 Review for gene: HYKK was set to RED Added comment: No known gene-disease association as classified by ClinGen Aminoacidopathy GCEP on 14/07/2023 - https://search.clinicalgenome.org/CCID:005104 HYKK has been reported as a disorders of lysine, hydroxylysine, and tryptophan metabolism by ICIMD however there are no reported pathogenic variants in this gene to support the gene-disease association. Sources: Literature |
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| Mendeliome v1.1836 | KMO | Zornitza Stark Marked gene: KMO as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1836 | KMO |
Zornitza Stark gene: KMO was added gene: KMO was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KMO was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KMO were set to 28187857; 24189070 Phenotypes for gene: KMO were set to pellagra MONDO:0019975 Review for gene: KMO was set to RED Added comment: Classified as no known disease relationship by ClinGen Aminoacidopathy GCEP on 12/05/2023 - https://search.clinicalgenome.org/CCID:005248 Only two knock out mouse models have ben reported that exhibited behavioural changes including memory impairment and anxiety like behaviour. Not reported as disease causing in any affected individuals at this stage and no evidence of any inborn errors of amino acid metabolism. Sources: Literature |
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| Mendeliome v1.1833 | ATXN7L3 | Zornitza Stark Marked gene: ATXN7L3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1832 | STK33 | Zornitza Stark Marked gene: STK33 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1832 | STK33 |
Zornitza Stark gene: STK33 was added gene: STK33 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: STK33 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: STK33 were set to 34155512; 29155043 Phenotypes for gene: STK33 were set to Spermatogenic failure 93, MIM#620849 Review for gene: STK33 was set to RED Added comment: Four brothers with a homozygous variant and an animal model. Sources: Literature |
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| Mendeliome v1.1831 | NAT6 | Zornitza Stark Marked gene: NAT6 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1831 | NAT6 |
Zornitza Stark gene: NAT6 was added gene: NAT6 was added to Mendeliome. Sources: Literature new gene name tags were added to gene: NAT6. Mode of inheritance for gene: NAT6 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NAT6 were set to 34805998 Phenotypes for gene: NAT6 were set to Auroneurodental syndrome, MIM# 620830 Review for gene: NAT6 was set to RED Added comment: Case report of two brothers with homozygous missense variant and deafness, periodic hypotonia and dental anomalies. HGNC approved name is NAA80. Sources: Literature |
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| Mendeliome v1.1830 | FAM177A1 | Zornitza Stark Marked gene: FAM177A1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1822 | TKFC | Zornitza Stark Phenotypes for gene: TKFC were changed from Triokinase and FMN cyclase deficiency syndrome, MIM#618805; Developmental delay; cataracts; liver dysfunction to Triokinase and FMN cyclase deficiency syndrome, MIM#618805; Inborn error of immunity, MONDO:0003778, TKFC-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1821 | TKFC | Zornitza Stark edited their review of gene: TKFC: Added comment: Single individual reported with homozygous variant and isolated immunodeficiency.; Changed publications: 32004446'38697782; Changed phenotypes: Triokinase and FMN cyclase deficiency syndrome, MIM#618805, Inborn error of immunity, MONDO:0003778, TKFC-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1821 | CYLC1 | Zornitza Stark Marked gene: CYLC1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1819 | FLT3LG | Ain Roesley Marked gene: FLT3LG as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1819 | FLT3LG |
Ain Roesley gene: FLT3LG was added gene: FLT3LG was added to Mendeliome. Sources: Literature Mode of inheritance for gene: FLT3LG was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FLT3LG were set to 38701783 Phenotypes for gene: FLT3LG were set to Increased susceptibility to infections Review for gene: FLT3LG was set to RED gene: FLT3LG was marked as current diagnostic Added comment: 3x sibs from a consanguineous family with a homozygous frameshift variant p.(Ser118Alafs*23) recurrent infections and hypoplastic bone marrow with marked reduction in HPSCs KO mice recapitulated BM findings over a period of 5 (P1), 9 (P2), and 19 (P3) years of follow-up, all 3 were found to have moderate anaemia. Total platelet counts and morphology decreased in 2 siblings. Total WBC oscillated between low and normal Eosinophils, basophils were in normal range Neutrophils were in the lower part of the control range, ocassiannly lower total lymphocyte counts were normal Sources: Literature |
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| Mendeliome v1.1817 | PISD | Sangavi Sivagnanasundram reviewed gene: PISD: Rating: GREEN; Mode of pathogenicity: None; Publications: 38801004; Phenotypes: Liberfarb syndrome MONDO:0030045; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1816 | ATXN7L3 |
Chirag Patel gene: ATXN7L3 was added gene: ATXN7L3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ATXN7L3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ATXN7L3 were set to PMID: 38753057 Phenotypes for gene: ATXN7L3 were set to Neurodevelopmental disorder, MONDO_0100500 Review for gene: ATXN7L3 was set to GREEN gene: ATXN7L3 was marked as current diagnostic Added comment: This study reports 9 unrelated individuals with de novo heterozygous variants in ATXN7L3 identified through WES testing and GeneMatcher. Core clinical features included: global motor and language developmental delay, hypotonia, and dysmorphic features (hypertelorism, epicanthal folds, blepharoptosis, small nose, small mouth, and low-set posteriorly rotated ears). Variable features included: feeding difficulties, seizures, mild periventricular leukomalacia, and structural cardiac abnormalities. A recurrent nonsense variant [p.(Arg114Ter)] was found in 5/9 individuals. The other variants were 1 frameshift [p.(Ser112LysfsTer12)] and 3 missense variants [p.(Ile71Thr), p.(Ser92Arg), and p.(Leu106Pro)]. They investigated the effects of the recurrent nonsense variant [p.(Arg114Ter)] in fibroblasts of an affected individual. ATXN7L3 protein levels were reduced, and deubiquitylation was impaired (as indicated by an increase in histone H2Bub1 levels). This is consistent with the previous observation of increased H2Bub1 levels in Atxn7l3-null mouse embryos, which have developmental delay and embryonic lethality. Pathogenic variants in deubiquitinating enzymes (DUBs) have been implicated in neurodevelopmental disorders (ND) and congenital abnormalities. ATXN7L3 is a component of the DUB module of the SAGA complex, and two other related DUB modules, and serves as an obligate adaptor protein of 3 ubiquitin-specific proteases (USP22, USP27X or USP51). Sources: Literature |
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| Mendeliome v1.1814 | FAM177A1 |
Chirag Patel gene: FAM177A1 was added gene: FAM177A1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: FAM177A1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FAM177A1 were set to PMID: 38767059, 25558065 Phenotypes for gene: FAM177A1 were set to Neurodevelopmental disorder, MONDO_0100500 Review for gene: FAM177A1 was set to GREEN gene: FAM177A1 was marked as current diagnostic Added comment: PMID: 38767059 5 individuals from 3 unrelated families reported with with biallelic loss of function variants in FAM177A1. Clinical features included: global developmental delay, intellectual disability, seizures, behavioural abnormalities, hypotonia, gait disturbance, and macrocephaly. They showed that FAM177A1 localizes to the Golgi complex in mammalian and zebrafish cells. Intersection of the RNA-seq and metabolomic datasets from FAM177A1-deficient human fibroblasts and whole zebrafish larvae demonstrated dysregulation of pathways associated with apoptosis, inflammation, and negative regulation of cell proliferation. PMID: 25558065 A study of 143 multiplex consanguineous families identified a homozygous frameshift variant in FAM177A1 in 1 family with 4 affected siblings with intellectual disability, dolicocephaly, obesity, and macrocephaly. The variant segregated with all 4 affected siblings and parents were confirmed heterozygous carriers. Sources: Literature |
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| Mendeliome v1.1812 | ANO4 | Ain Roesley Marked gene: ANO4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1810 | ANO4 |
Ain Roesley gene: ANO4 was added gene: ANO4 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ANO4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ANO4 were set to 38744284 Phenotypes for gene: ANO4 were set to neurodevelopmental disorder MONDO:0700092, ANO4-related Review for gene: ANO4 was set to GREEN gene: ANO4 was marked as current diagnostic Added comment: aka TMEM16D 5x de novo + 2x inherited missense (73% penetrance + asymptomatic) the ones with de novo variants: all had ID, hypotonia 4x skeletal features (scoliosis, funnel chest, pet plants, hyper extensible joints) all had epilepsy all had abnormal MRI Sources: Literature |
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| Mendeliome v1.1809 | KCND1 | Ain Roesley Marked gene: KCND1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1808 | KCND1 |
Ain Roesley gene: KCND1 was added gene: KCND1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KCND1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: KCND1 were set to 38772379 Phenotypes for gene: KCND1 were set to neurodevelopmental disorder MONDO:0700092, KCND1-related Review for gene: KCND1 was set to GREEN gene: KCND1 was marked as current diagnostic Added comment: 18 males from 17 families 2x de novo missense + 3x maternal NMDs + 12x maternal missense Some functional studies were done 14x ID 4x delayed motor dev 7x muscular hypotonia 6x epilepsy Sources: Literature |
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| Mendeliome v1.1803 | POLD1 | Zornitza Stark Phenotypes for gene: POLD1 were changed from Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome, MIM# 615381; MONDO:0014157; Combined immunodeficiency, MONDO:0015131, POLD1-related to Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome, MIM# 615381; MONDO:0014157; Immunodeficiency 120, MIM# 620836 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1802 | POLD1 | Zornitza Stark edited their review of gene: POLD1: Changed phenotypes: Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome, MIM# 615381, MONDO:0014157, Immunodeficiency 120, MIM# 620836 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1801 | SYCP2L | Zornitza Stark Phenotypes for gene: SYCP2L were changed from Premature ovarian insufficiency to Premature ovarian failure 24, MIM# 620840 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1797 | GABRA4 |
Zornitza Stark edited their review of gene: GABRA4: Added comment: Three more novel de novo missense variants in GABRA4 (NM_000809.4): c.797 C > T, p.(Pro266Leu), c.899 C > A, p.(Thr300Asn), and c.634 G > A, p.(Val212Ile) reported. The p.(Thr300Asn) variant impacts the same codon as the previously reported variant p.(Thr300Ile) and likely arose post-zygotically as evidenced by sequencing oral mucosal cells. Overlapping phenotypes among affected individuals included developmental delay (4/4), epileptiform EEG abnormalities (3/4), attention deficits (3/4), seizures (2/4), autistic features (2/4) and structural brain abnormalities (2/4).; Changed rating: GREEN; Changed publications: 35152403, 38565639; Changed phenotypes: Neurodevelopmental disorder MONDO:0700092, GABRA4-related |
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| Mendeliome v1.1796 | DGCR8 | Andrew Fennell reviewed gene: DGCR8: Rating: AMBER; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: PMID: 34821987; Phenotypes: Early-onset multinodular goiter and schwannomatosis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1796 | TAPBP | Zornitza Stark Phenotypes for gene: TAPBP were changed from Bare lymphocyte syndrome, type I, MIM# 604571 to Bare lymphocyte syndrome, type I, MIM# 604571; MHC class I deficiency 3, MIM# 620814 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1795 | TAPBP | Zornitza Stark edited their review of gene: TAPBP: Changed phenotypes: Bare lymphocyte syndrome, type I, MIM# 604571, MHC class I deficiency 3, MIM# 620814 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1795 | TAP2 | Zornitza Stark Phenotypes for gene: TAP2 were changed from Bare lymphocyte syndrome, type I, due to TAP2 deficiency MIM# 604571; Low CD8; absent MHC I on lymphocytes; Vasculitis; pyoderma gangrenosum; recurrent bacterial/viral respiratory infections; bronchiectasis to MHC class I deficiency 2, MIM# 620813; Bare lymphocyte syndrome, type I, due to TAP2 deficiency MIM# 604571; Low CD8; absent MHC I on lymphocytes; Vasculitis; pyoderma gangrenosum; recurrent bacterial/viral respiratory infections; bronchiectasis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1794 | LIG4 | Santosh Varughese reviewed gene: LIG4: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 11779494, 16088910, 15333585, 20133615; Phenotypes: LIG4 syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1794 | B2M | Zornitza Stark edited their review of gene: B2M: Changed phenotypes: Amyloidosis, hereditary systemic 6, MIM# 620659, Immunodeficiency 43 MIM# 241600, Sinopulmonary infections, Purple-red skin lesions, Decreased serum IgG, Decreased B cells, Absent β2m associated proteins MHC-I, CD1a, CD1b, and CD1c, MONDO:0009434, Amyloidosis, familial visceral, MIM# 105200 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1794 | LYZ | Zornitza Stark Phenotypes for gene: LYZ were changed from Amyloidosis, renal, MIM# 105200 to Amyloidosis, renal, MIM# 105200; Amyloidosis, hereditary systemic 5, MIM# 620658 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1793 | APOA1 | Zornitza Stark Phenotypes for gene: APOA1 were changed from Amyloidosis, 3 or more types MIM#105200; Hypoalphalipoproteinemia, primary, 2 MIM#618463; Hypoalphalipoproteinemia, primary, 2, intermediate MIM#619836 to Amyloidosis, hereditary systemic 3, MIM# 620657; Amyloidosis, 3 or more types MIM#105200; Hypoalphalipoproteinemia, primary, 2 MIM#618463; Hypoalphalipoproteinemia, primary, 2, intermediate MIM#619836 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1791 | RBBP8 | Zornitza Stark edited their review of gene: RBBP8: Added comment: Additional family reported with Jawad syndrome: prev reported founder variant, multi-generational family, abnormal splicing demonstrated.; Changed rating: GREEN; Changed publications: 34270086; Changed phenotypes: Jawad syndrome, MIM# 251255; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1791 | ZDHHC15 | Zornitza Stark Phenotypes for gene: ZDHHC15 were changed from Mental retardation, X-linked 91, 300577; cerebral palsy; intellectual disability; autism spectrum disorder; epilepsy to Intellectual disability, X-linked 91, 300577 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1790 | ZNF41 | Zornitza Stark Marked gene: ZNF41 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1790 | ZNF41 |
Zornitza Stark gene: ZNF41 was added gene: ZNF41 was added to Mendeliome. Sources: Expert Review disputed tags were added to gene: ZNF41. Mode of inheritance for gene: ZNF41 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: ZNF41 were set to 14628291; 23871722 Phenotypes for gene: ZNF41 were set to non-syndromic X-linked intellectual disability MONDO:0019181 Review for gene: ZNF41 was set to RED Added comment: DISPUTED by ClinGen. Shoichet et al. (2003) described a female patient with severe nonsyndromic mental retardation and a de novo balanced translocation t(X;7)(p11.3;q11.21) in whom they cloned the DNA fragment that contained the X chromosomal and the autosomal breakpoint. In silico sequence analysis demonstrated that the ZNF41 gene was disrupted. Expression studies indicated that ZNF41 transcripts were absent in the patient cell line, suggesting that the mental disorder in this patient resulted from loss of functional ZNF41. Screening of patients with mental retardation led to the identification of 2 other ZNF41 mutations that were not found in healthy control individuals. Based on their finding of the mutations in ZNF41 identified by Shoichet et al. (2003) in a total of 7 males in the NHLBI Exome Variant Server, and the additional finding of truncating ZNF41 variants in 1 male and 1 female in that database, Piton et al. (2013) classified the involvement of ZNF41 in mental retardation as highly questionable. Sources: Expert Review |
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| Mendeliome v1.1789 | RBBP8 | James The reviewed gene: RBBP8: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:30561437, 34270086, 32379725; Phenotypes: Jawad syndrome, Pancreatic carcinoma, somatic, Seckel syndrome 2; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1789 | SHROOM4 | Zornitza Stark Phenotypes for gene: SHROOM4 were changed from Stocco dos Santos X-linked mental retardation syndrome, 300434; Intellectual disability to Congenital anomaly of the kidney and urinary tracy (CAKUT), SHROOM4-related, MONDO:0019719; epilepsy, idiopathic generalised, SHROOM4-related, MONDO:0005579 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1787 | AGTR2 | Zornitza Stark Marked gene: AGTR2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1787 | AGTR2 |
Zornitza Stark changed review comment from: Variants in AGTR2 have been reported in individuals presenting various neurodevelopmental phenotypes, including intellectual disability, autistic features, epileptic seizures, speech delay, restlessness, and hyperactivity, as early as 2002. Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found no difference in molecular mechanism, inheritance pattern, or phenotypic variability. Therefore, for the purposes of this curation, all of these features have been lumped into one disease entity, X-linked complex neurodevelopmental disorder. Although eight unique variants, including missense and truncating, have been reported in affected humans, the majority (six) have been ruled out from disease-causality based on high frequency in control populations (Piton et al., PMID 23871722), occurrence in unaffected males (Erdmann et al., PMID 14722754), non-segregation within a family (Bienvenu et al., PMID 12746399), and lack of enrichment in patients in a case-control study (Huang et al., PMID 16283672). Given that the two remaining variants are missense with no supporting functional evidence, and AGTR2 was the only gene sequenced in each case, the ClinGen Intellectual Disability and Autism Working Group recommended awarding 0 points for these variants. There are two AGTR2 mouse models which collectively show altered neuronal spine morphology, spatial memory impairment, delayed learning, and reduced exploratory behavior (PMIDs 18335189 and 7477267). Sources: Expert Review; to: DISPUTED by ClinGen: Variants in AGTR2 have been reported in individuals presenting various neurodevelopmental phenotypes, including intellectual disability, autistic features, epileptic seizures, speech delay, restlessness, and hyperactivity, as early as 2002. Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found no difference in molecular mechanism, inheritance pattern, or phenotypic variability. Therefore, for the purposes of this curation, all of these features have been lumped into one disease entity, X-linked complex neurodevelopmental disorder. Although eight unique variants, including missense and truncating, have been reported in affected humans, the majority (six) have been ruled out from disease-causality based on high frequency in control populations (Piton et al., PMID 23871722), occurrence in unaffected males (Erdmann et al., PMID 14722754), non-segregation within a family (Bienvenu et al., PMID 12746399), and lack of enrichment in patients in a case-control study (Huang et al., PMID 16283672). Given that the two remaining variants are missense with no supporting functional evidence, and AGTR2 was the only gene sequenced in each case, the ClinGen Intellectual Disability and Autism Working Group recommended awarding 0 points for these variants. There are two AGTR2 mouse models which collectively show altered neuronal spine morphology, spatial memory impairment, delayed learning, and reduced exploratory behavior (PMIDs 18335189 and 7477267). Sources: Expert Review |
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| Mendeliome v1.1787 | AGTR2 |
Zornitza Stark gene: AGTR2 was added gene: AGTR2 was added to Mendeliome. Sources: Expert Review disputed tags were added to gene: AGTR2. Mode of inheritance for gene: AGTR2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: AGTR2 were set to X-linked complex neurodevelopmental disorder MONDO:0100148 Review for gene: AGTR2 was set to RED Added comment: Variants in AGTR2 have been reported in individuals presenting various neurodevelopmental phenotypes, including intellectual disability, autistic features, epileptic seizures, speech delay, restlessness, and hyperactivity, as early as 2002. Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found no difference in molecular mechanism, inheritance pattern, or phenotypic variability. Therefore, for the purposes of this curation, all of these features have been lumped into one disease entity, X-linked complex neurodevelopmental disorder. Although eight unique variants, including missense and truncating, have been reported in affected humans, the majority (six) have been ruled out from disease-causality based on high frequency in control populations (Piton et al., PMID 23871722), occurrence in unaffected males (Erdmann et al., PMID 14722754), non-segregation within a family (Bienvenu et al., PMID 12746399), and lack of enrichment in patients in a case-control study (Huang et al., PMID 16283672). Given that the two remaining variants are missense with no supporting functional evidence, and AGTR2 was the only gene sequenced in each case, the ClinGen Intellectual Disability and Autism Working Group recommended awarding 0 points for these variants. There are two AGTR2 mouse models which collectively show altered neuronal spine morphology, spatial memory impairment, delayed learning, and reduced exploratory behavior (PMIDs 18335189 and 7477267). Sources: Expert Review |
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| Mendeliome v1.1786 | AVPR1A | Zornitza Stark Marked gene: AVPR1A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1786 | AVPR1A |
Zornitza Stark gene: AVPR1A was added gene: AVPR1A was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: AVPR1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: AVPR1A were set to 24924430 Phenotypes for gene: AVPR1A were set to Autism spectrum disorder MONDO:0005258 Review for gene: AVPR1A was set to RED Added comment: DISPUTED by ClinGen: The Arginine Vasopressin Receptor 1A (AVPR1A) was considered a candidate gene in autism spectrum disorder (ASD) based on reports focused on linkage intervals and animal models. Additionally, experimental evidence showed that AVPR1A is possibly involved in social behaviors, including affiliation and attachment (PMID: 24924430). However, these association studies were underpowered—sequencing more individuals may have identified variants of functional significance. In two studies, transmission disequilibrium between AVPR1A microsatellites and autism were found but most were not statistically significant (PMID: 12082568, 16520824). In another study, investigators screened AVPR1A exons in 125 independent autistic probands (PMID: 15098001). However, the study did not demonstrate a disease-causing variant in the coding sequence, and the authors noted that differences in AVPR1A at the amino-acid level are unlikely to confer genetic vulnerability to autism. Experimental evidence is available, but, in the absence of human genetic evidence, such data were not utilized in the scoring. In summary, there is no valid genetic evidence to support an association between AVPR1A and autism spectrum disorder. Sources: Expert list |
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| Mendeliome v1.1784 | LCP1 | Zornitza Stark Marked gene: LCP1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1783 | LCP1 |
Zornitza Stark gene: LCP1 was added gene: LCP1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: LCP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: LCP1 were set to 38710235 Phenotypes for gene: LCP1 were set to Bone marrow failure syndrome, MONDO:0000159, LCP1-related Review for gene: LCP1 was set to AMBER Added comment: 3 individuals from single kindred presenting with fevers, recurrent infections ,lymphopenia, neutropenia and thrombocytopenia. Murine model with similar phenotype. heterozygous LCP1c.740 -1G>A splice site variant hypothesized to cause dominant negative mode of inheritance Sources: Literature |
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| Mendeliome v1.1781 | UFSP2 |
Zornitza Stark edited their review of gene: UFSP2: Added comment: PMID: 37214758: Additional patient with spondyloepimetaphyseal dysplasia type Di Rocco: - het missense Cys302Ser - confirmed de novo in segregation analyses - absent in gnomAD - no functional studies on the missense. Four AD missense reported in the literature so far are located in the C-term catalytic domain - 1x hip dysplasia, Beukes type and 3x spondyloepimetaphyseal dysplasia type Di Rocco. The well reported AR missense (associated with neurodevelopmental anomalies and epilepsy) is located in the N-terminal domain possibly involved in substrate binding.; Changed publications: 33473208, 26428751, 28892125, 32755715, 37214758 |
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| Mendeliome v1.1781 | DPP6 | Zornitza Stark Phenotypes for gene: DPP6 were changed from Mental retardation, autosomal dominant 33 (MIM#616311) to Intellectual disability, autosomal dominant 33 (MIM#616311) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1778 | KCNIP4 | Ain Roesley Marked gene: KCNIP4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1778 | KCNIP4 |
Ain Roesley gene: KCNIP4 was added gene: KCNIP4 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KCNIP4 was set to Unknown Publications for gene: KCNIP4 were set to 33826137 Phenotypes for gene: KCNIP4 were set to seizures; epilepsy Review for gene: KCNIP4 was set to RED gene: KCNIP4 was marked as current diagnostic Added comment: single paper describing insertions of L1 retrotransposons in KCNIP4 samples were post-mortem of resected temporal cortex from individuals with idiopathic temporal lobe epilepsy 1x de novo insertion of L1 in KCNIP4 however ddPCR revealed that this did NOT alter KCNIP4 mRNA expression Sources: Literature |
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| Mendeliome v1.1777 | CHRNA7 | Ain Roesley Marked gene: CHRNA7 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1777 | CHRNA7 |
Ain Roesley gene: CHRNA7 was added gene: CHRNA7 was added to Mendeliome. Sources: Literature cnv tags were added to gene: CHRNA7. Mode of inheritance for gene: CHRNA7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CHRNA7 were set to 20979196; 21596161; 21290787 Phenotypes for gene: CHRNA7 were set to intellectual disability; seizures; hypotonia Review for gene: CHRNA7 was set to RED gene: CHRNA7 was marked as current diagnostic Added comment: Homozygous deletion of 15q13.3, which includes CHRNA7, causes ID, hypotonia, seizures, encephalopathy Sources: Literature |
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| Mendeliome v1.1774 | ARMC4 | Zornitza Stark Tag new gene name tag was added to gene: ARMC4. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1774 | ADAMTS18 | Zornitza Stark Marked gene: ADAMTS18 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1773 | SPATA13 | Zornitza Stark Phenotypes for gene: SPATA13 were changed from primary angle-closure glaucoma to primary angle-closure glaucoma MONDO:0001868 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1770 | WDR36 | Sangavi Sivagnanasundram reviewed gene: WDR36: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:006545; Phenotypes: glaucoma 1, open angle, G MONDO:0012357; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1770 | SPATA13 | Sangavi Sivagnanasundram reviewed gene: SPATA13: Rating: AMBER; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:006261; Phenotypes: primary angle-closure glaucoma MONDO:0001868; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1770 | C2orf71 | Sangavi Sivagnanasundram reviewed gene: C2orf71: Rating: ; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005738; Phenotypes: PCARE-related retinopathy MONDO:0800404; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1770 | NTF4 | Sangavi Sivagnanasundram reviewed gene: NTF4: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005684; Phenotypes: glaucoma 1, open angle, O MONDO:0013134; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1770 | FOXD3 | Sangavi Sivagnanasundram reviewed gene: FOXD3: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004877; Phenotypes: aniridia MONDO:0019172; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1770 | ADAMTS18 |
Sangavi Sivagnanasundram gene: ADAMTS18 was added gene: ADAMTS18 was added to Mendeliome. Sources: Other Mode of inheritance for gene: ADAMTS18 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ADAMTS18 were set to https://search.clinicalgenome.org/CCID:004057 Phenotypes for gene: ADAMTS18 were set to microcornea-myopic chorioretinal atrophy (MONDO:0014195) Review for gene: ADAMTS18 was set to GREEN Added comment: Classified DEFINITIVE by ClinGen Retina GCEP on 02/03/20222 - https://search.clinicalgenome.org/CCID:004057 Sources: Other |
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| Mendeliome v1.1770 | TTC25 | Sangavi Sivagnanasundram reviewed gene: TTC25: Rating: ; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005700; Phenotypes: primary ciliary dyskinesia 35 MONDO:0014910; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1770 | CCDC151 | Sangavi Sivagnanasundram reviewed gene: CCDC151: Rating: ; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005699; Phenotypes: primary ciliary dyskinesia 30 MONDO:0014465; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1770 | ARMC4 | Sangavi Sivagnanasundram reviewed gene: ARMC4: Rating: ; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005698; Phenotypes: primary ciliary dyskinesia 23 MONDO:0014193; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1770 | DNAH8 | Sangavi Sivagnanasundram reviewed gene: DNAH8: Rating: ; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004671; Phenotypes: primary ciliary dyskinesia (MONDO:0016575), spermatogenic failure 46 (MONDO:0033673); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1770 | DNAH17 |
Sangavi Sivagnanasundram changed review comment from: Classified DEFINITIVE by ClinGen on 08/09/2022 - https://search.clinicalgenome.org/CCID:004669 Sources: Other; to: Classified DEFINITIVE by ClinGen Motile Ciliopathies GCEP on 08/09/2022 - https://search.clinicalgenome.org/CCID:004669 Sources: Other |
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| Mendeliome v1.1770 | DNAH17 |
Sangavi Sivagnanasundram gene: DNAH17 was added gene: DNAH17 was added to Mendeliome. Sources: Other Mode of inheritance for gene: DNAH17 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DNAH17 were set to https://search.clinicalgenome.org/CCID:004669 Phenotypes for gene: DNAH17 were set to spermatogenic failure 39 (MONDO:0032845) Review for gene: DNAH17 was set to GREEN Added comment: Classified DEFINITIVE by ClinGen on 08/09/2022 - https://search.clinicalgenome.org/CCID:004669 Sources: Other |
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| Mendeliome v1.1770 | SLC52A1 | Bryony Thompson Added comment: Comment on list classification: Moderate gene-disease classification by ClinGen - https://search.clinicalgenome.org/CCID:006192 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1765 | BRWD1 | Sangavi Sivagnanasundram reviewed gene: BRWD1: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004289; Phenotypes: primary ciliary dyskinesia MONDO:0016575; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1764 | DAGLA | Zornitza Stark Marked gene: DAGLA as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1763 | DAGLA |
Zornitza Stark gene: DAGLA was added gene: DAGLA was added to Mendeliome. Sources: Literature Mode of inheritance for gene: DAGLA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DAGLA were set to 35737950 Phenotypes for gene: DAGLA were set to Neuroocular syndrome 2, paroxysmal type, MIM# 168885 Review for gene: DAGLA was set to GREEN Added comment: 9 individuals from 8 families reported with daily paroxysmal spells characterized by eye deviation or nystagmus with abnormal head posturing apparent from birth or early infancy. The episodes tend to be triggered after sleeping, and most patients show improvement of the ocular symptoms over time. Affected individuals also have hypotonia, mild developmental delay, dysarthria, and gait ataxia; most have mildly impaired intellectual development. Seizures are not observed. Sources: Literature |
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| Mendeliome v1.1762 | HOXD12 | Zornitza Stark Marked gene: HOXD12 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1761 | PKHD1L1 | Zornitza Stark Marked gene: PKHD1L1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1758 | EPHX1 | Lauren Rogers reviewed gene: EPHX1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hereditary lipodystrophy, MONDO:0020087, EPHX1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1758 | HOXD12 |
Sangavi Sivagnanasundram gene: HOXD12 was added gene: HOXD12 was added to Mendeliome. Sources: Other Mode of inheritance for gene: HOXD12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: HOXD12 were set to 38663984 Phenotypes for gene: HOXD12 were set to Clubfoot (non-syndromic) MONDO:0007342 Mode of pathogenicity for gene: HOXD12 was set to Other Review for gene: HOXD12 was set to GREEN Added comment: Novel gene-disease association with non-syndromic clubfoot. 10 variants in HOXD12 have been reported in individuals with clubfoot (variants are predominantly missense variants however one rare deletion has been reported). PMID: 38663984 Around 9 individuals from 4 unrelated families have been reported with clubfoot and the variants were shown to segregate. N-terminal region and C-terminal homeobox domain of HOXD12 are known to be clusters for pathogenic variants related to clubfoot. Loss of function variants are less likely to contribute to clubfoot pathogenesis therefore mechanism of disease is suggested as dominant negative but is not confirmed. Sources: Other |
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| Mendeliome v1.1758 | PKHD1L1 |
Sangavi Sivagnanasundram gene: PKHD1L1 was added gene: PKHD1L1 was added to Mendeliome. Sources: Other Mode of inheritance for gene: PKHD1L1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: PKHD1L1 were set to non syndromic hearing loss (MONDO:0020678) Review for gene: PKHD1L1 was set to GREEN Added comment: At least 4 individuals from unrelated families with sensorineural hearing loss (SNHL) (2 of the reported probands were from consanguineous parents). The individuals are either homozygous or compound heterozygous for mutations in PKHD1L1 (missense, frameshift and nonsense mutations have been reported). In vitro functional assessment as well as a mini-gene assay of Gly605Arg was conducted. The mini-gene assay on Gly605Arg showed that exon skipping occurs resulting in an in-frame deletion of 48 aa. Both studies didn't use a positive control however loss of function or disruption to protein stability is the speculated mechanism of disease. Sources: Other |
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| Mendeliome v1.1758 | RAB32 | Bryony Thompson Marked gene: RAB32 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1758 | RAB32 |
Bryony Thompson gene: RAB32 was added gene: RAB32 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RAB32 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RAB32 were set to 38614108 Phenotypes for gene: RAB32 were set to Parkinson disease MONDO:0005180 Mode of pathogenicity for gene: RAB32 was set to Other Review for gene: RAB32 was set to RED Added comment: A single variant in RAB32 - c.213C>G p.(Ser71Arg) with a significant association with PD (odds ratio [OR] 13.17, 95% CI 2.15-87.23; p=0.0055, 6,043 PD cases and 62,549 controls). The variant cosegregated with autosomal dominant PD in 3 families (9 affected individuals), with incomplete penetrance. In vitro studies demonstrate that RAB32 Ser71Arg activates LRRK2 kinase. The variant is reported as a novel reduced penetrance PD risk factor. The 95% CI for the OR estimate are very wide. A confirmatory study is required for this variant. Sources: Literature |
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| Mendeliome v1.1757 | CCDC91 | Bryony Thompson Marked gene: CCDC91 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1756 | CCDC91 |
Bryony Thompson gene: CCDC91 was added gene: CCDC91 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CCDC91 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CCDC91 were set to 38627542 Phenotypes for gene: CCDC91 were set to Punctate palmoplantar keratoderma type III MONDO:0007047 Review for gene: CCDC91 was set to AMBER Added comment: A single 3-generation Chinese acrokeratoelastoidosis family segregates c.1101 + 1 G > A (causes exon 11 skipping). In vitro knockdown experiments in cell lines demonstrated distended Golgi cisternae, cytoplasmic vesicle accumulation, and lysosome presence. Immnunostaining of si-CCDC91-human skin fibroblasts cells demonstrated tropoelastin accumulation in the Golgi and abnormal extracellular aggregates Sources: Literature |
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| Mendeliome v1.1750 | IL27RA | Ain Roesley Marked gene: IL27RA as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1749 | IL27RA |
Ain Roesley gene: IL27RA was added gene: IL27RA was added to Mendeliome. Sources: Literature Mode of inheritance for gene: IL27RA was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IL27RA were set to 38509369 Phenotypes for gene: IL27RA were set to Epstein-Barr virus infection MONDO:0005111 , IL27RA-related Review for gene: IL27RA was set to AMBER gene: IL27RA was marked as current diagnostic Added comment: 3 children from 2 families with severe acute EBV infection. fam1: homozygous for p.(Gln96*) (NMD-pred) fam2: chet for p.(Arg446Gly) and c.1142-2A>C the splice variant in fam2 was found to to result in an in-frame deletion p.(Gln381_Ala395del) the missense in fam2 is hypothesised to be a hypomorphic allele: - out of 15 Homs in the Finnish database, 2 had hospital diagnoses of EBV IM - expression of this variant on its own results in a weak but detectable IL-27RA expression associated with significant increase in STAT1/3 phosphorus in response to IL-27 stimulation borderline amber/green due to functional studies performed Sources: Literature |
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| Mendeliome v1.1746 | SHH | Ain Roesley Phenotypes for gene: SHH were changed from Holoprosencephaly 3, MIM#142945; Microphthalmia with coloboma 5, MIM#611638; Single median maxillary central incisor, MIM#147250 to Holoprosencephaly 3, MIM#142945; Microphthalmia with coloboma 5, MIM#611638; Single median maxillary central incisor, MIM#147250; Hypertelorism, ACC, intellectual disability | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1744 | PRMT9 | Zornitza Stark Marked gene: PRMT9 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1743 | SUPT7L | Zornitza Stark Marked gene: SUPT7L as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1742 | PQLC2 | Zornitza Stark Marked gene: PQLC2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1740 | SLC39A12 | Zornitza Stark Marked gene: SLC39A12 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1739 | SLC4A7 | Zornitza Stark Marked gene: SLC4A7 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1737 | SLC4A7 |
Chirag Patel gene: SLC4A7 was added gene: SLC4A7 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SLC4A7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC4A7 were set to PMID: 35486108, 32594822 Phenotypes for gene: SLC4A7 were set to Retinitis pigmentosa, MONDO:0019200 Review for gene: SLC4A7 was set to AMBER Added comment: Total 4 individuals from 3 families (2 known to be from same ethnic origin: Oriental-Jewish) with adult onset retinitis pigmentosa. All individuals had same homozygous frameshift variant in SLC4A7 gene (p.P670Sfs*6). RNA seq analysis revealed retinal expression in human and mouse samples. Immunohistochemistry of human and mouse retina revealed relatively strong expression in various retinal layers. Western blot analysis in fibroblasts from 1 patient showed absence of encoded protein. Sources: Literature |
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| Mendeliome v1.1736 | SLC39A12 |
Chirag Patel gene: SLC39A12 was added gene: SLC39A12 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SLC39A12 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC39A12 were set to PMID: 35486108 Phenotypes for gene: SLC39A12 were set to Retinitis pigmentosa, MONDO:0019200 Review for gene: SLC39A12 was set to RED Added comment: WES (with targeted analysis of SLC genes) in 913 cases from 785 families with inherited retinal dystrophy. They identified 1 homozygous variant in SLC39A12 in 1 individual with adult-onset mild widespread retinal degeneration with marked macular involvement. No functional data. RNA seq analysis revealed retinal expression in human samples. Immunohistochemistry of human and mouse retina revealed comprehensive expression in various retinal cells including retinal pigment epithelium. Sources: Literature |
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| Mendeliome v1.1734 | PQLC2 |
Chirag Patel gene: PQLC2 was added gene: PQLC2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PQLC2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PQLC2 were set to PMID: 35486108; and online publication GiM Feb 2024 Phenotypes for gene: PQLC2 were set to Retinitis pigmentosa, MONDO:0019200 Review for gene: PQLC2 was set to GREEN gene: PQLC2 was marked as current diagnostic Added comment: HGNC Gene Symbol: SLC66A1 Total 8 individuals from 6 families. Millo et al. (2022)(PMID: 35486108) - WES (with targeted analysis of SLC genes) in 913 cases from 785 families with inherited retinal dystrophy. They identified 2 different homozygous variants in SLC66A1 in 3 individuals from 2 families with adult-onset retinal dystrophy. No functional data. Olinger et al. (2024)(https://www.sciencedirect.com/science/article/pii/S2949774424009804) - CNV analysis of trio and non-trio WGS data from Genomics England 100K genomes project. They identified homozygous 21kb deletion spanning nearly entire SLC66A1 gene in 2 siblings with adult-onset rod-cone dystrophy (parents HTZ carriers). Review of cohort data then identified homozygous LOF variants (1 nonsense, 2 frameshift) in another 3 individuals with rod-cone dystrophy. Sources: Literature |
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| Mendeliome v1.1733 | SUPT7L |
Chirag Patel gene: SUPT7L was added gene: SUPT7L was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SUPT7L was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SUPT7L were set to PMID: 38592547 Phenotypes for gene: SUPT7L were set to Lipodystrophy, MONDO:0006573 Review for gene: SUPT7L was set to RED Added comment: 1 case with generalised lipodystrophy, growth retardation, congenital cataracts, severe developmental delay and progeriod features. Trio WGS identified compound heterozygous variants in SUPT7L (missense causing abnormal splicing + frameshift). Variants validated with Sanger. SUPT7L encodes a component of the core structural module of the STAGA complex - a nuclear multifunctional protein complex that plays a role in various cellular processes (e.g. transcription factor binding, protein acetylation, splicing, and DNA damage control). Immunolabelling in fibroblasts from patient showed complete absence of SUPT7L protein. Transcriptome data from individual revealed downregulation of several gene sets associated with DNA replication, DNA repair, cell cycle, and transcription. Sources: Literature |
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| Mendeliome v1.1732 | PRMT9 |
Chirag Patel gene: PRMT9 was added gene: PRMT9 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PRMT9 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PRMT9 were set to PMID: 38561334 Phenotypes for gene: PRMT9 were set to Neurodevelopmental disorder, MONDO:0100500 Review for gene: PRMT9 was set to RED Added comment: A homozygous variant (G189R) in PRMT9 is reported based on large WGS study in 136 consanguineous families - unclear if only found in 1 family and no clinical information on case(s). PMRTs (protein arginine methyltransferases) catalyse post translational modification via arginine methylation. Functional studies showed that the G189R variant abolishes PRMT9's methyltransferase activity - specifically at the R508 residue of SF3B2 RNA (exclusively methylated by PRMT9) - and leads to heavy PRMT9 ubiquitination, and abnormal splicing activity of SF3B2. Knock out mouse model showed PRMT9 loss in excitatory neurons leads to aberrant synapse development and impaired learning and memory. Sources: Literature |
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| Mendeliome v1.1728 | JAK1 | Zornitza Stark edited their review of gene: JAK1: Added comment: PMID 38563820: 59 individuals presenting with autoimmunity, atopy, colitis, and/or dermatitis and one of four JAK1 variants.; Changed rating: GREEN; Changed publications: 28111307, 28008925, 30671064, 38563820; Changed phenotypes: Autoinflammatory syndrome, MONDO:0019751, JAK1-related, Eosinophilia, Eosinophilic enteritis, Thyroid disease, Poor growth, Viral infections, Susceptibility to mycobacteria and viruses, Autoinflammation, immunde dysregulation, and eosinophilia, MIM# 618999 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1728 | SRPK3 | Zornitza Stark Marked gene: SRPK3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1727 | SRPK3 |
Zornitza Stark gene: SRPK3 was added gene: SRPK3 was added to Mendeliome. Sources: Literature digenic tags were added to gene: SRPK3. Mode of inheritance for gene: SRPK3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: SRPK3 were set to 38429495 Phenotypes for gene: SRPK3 were set to Myopathy, MONDO:0005336, digenic SRPK3- and TTN-related Review for gene: SRPK3 was set to GREEN Added comment: 33 individuals reported with SRPK3 variants but myopathy only occurred when TTN variant also present (most truncating). Zebrafish model supports digenic model of inheritance. Sources: Literature |
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| Mendeliome v1.1725 | OTULIN | Zornitza Stark edited their review of gene: OTULIN: Added comment: Three individuals reported with de novo missense variants and auto inflammatory syndrome. Two had at the same variant, p.Cys129Ser. Experimental data supports dominant negative mechanism. Fourth individual with heterozygous variant in PMID 38129331 and severe fasciitis.; Changed publications: 27523608, 27559085, 35587511, 38630025, 38652464, 38129331 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1725 | SHARPIN | Zornitza Stark Phenotypes for gene: SHARPIN were changed from Autoinflammatory syndrome, MONDO:0019751, SHARPIN-related to Autoinflammation with episodic fever and immune dysregulation, MIM# 620795 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1724 | SHARPIN | Zornitza Stark edited their review of gene: SHARPIN: Changed phenotypes: Autoinflammation with episodic fever and immune dysregulation, MIM# 620795 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1723 | SAR1B | Bryony Thompson commented on gene: SAR1B | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1723 | KIAA1024L | Zornitza Stark Marked gene: KIAA1024L as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1719 | PACSIN3 | Zornitza Stark Marked gene: PACSIN3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1718 | PACSIN3 |
Zornitza Stark gene: PACSIN3 was added gene: PACSIN3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PACSIN3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PACSIN3 were set to 38637313 Phenotypes for gene: PACSIN3 were set to Myopathy, MONDO:0005336, PACSIN3-related Review for gene: PACSIN3 was set to AMBER Added comment: Two unrelated families with LoF variants, one homozygous. Muscle phenotype including raised CK. Supportive mouse model. Sources: Literature |
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| Mendeliome v1.1717 | RNU4-2 |
Zornitza Stark changed review comment from: Emerging evidence that de novo variants in this gene cause ID. Sources: Literature; to: Over 100 individuals with ID found to have de novo variants in this gene. Please note difficult to identify on ES. Sources: Literature |
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| Mendeliome v1.1715 | KIAA1024L |
Achchuthan Shanmugasundram gene: KIAA1024L was added gene: KIAA1024L was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KIAA1024L was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KIAA1024L were set to 35727972 Phenotypes for gene: KIAA1024L were set to Deafness, autosomal recessive 120, OMIM:620238 Review for gene: KIAA1024L was set to GREEN Added comment: New gene name - MINAR2 PMID:35727972 reported 13 patients from four unrelated families with non-syndromic sensorineural hearing loss. Four of these patients had prelingual onset of severe to profound, progressive bilateral hearing loss. The other nine patients had congenital onset of severe to profound bilateral hearing loss, which was not progressive on one patient, while data was not available for the other. Three different homozygous variants (c.144G > A/ p.Trp48Ter, c.412_419delCGGTTTTG/ p.Arg138Valfs*10 and c.393G > T/ p.Lys131Asn) were identified in MINAR2/ KIAA1024L gene in these patients. There is some functional evidence available for the p.Lys131Asn variant. In addition, mice with loss of function of the Minar2 protein present with rapidly progressive sensorineural hearing loss. This gene has also been associated with relevant phenotype in OMIM (MIM #620238). Sources: Literature |
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| Mendeliome v1.1713 | MARS | Zornitza Stark Mode of inheritance for gene: MARS was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1712 | MARS | Zornitza Stark edited their review of gene: MARS: Added comment: The mono-allelic gene-disease associations have LIMITED evidence.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1712 | PMP2 | Zornitza Stark Mode of pathogenicity for gene: PMP2 was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1710 | PMP2 | Zornitza Stark reviewed gene: PMP2: Rating: AMBER; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 26257172, 27009151, 30249361, 31412900, 26828946, 32277537; Phenotypes: Charcot-Marie-Tooth disease, demyelinating, type 1G, 618279; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1709 | ELANE | Zornitza Stark Mode of pathogenicity for gene: ELANE was changed from Other to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1708 | ELANE | Zornitza Stark edited their review of gene: ELANE: Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1708 | SHARPIN | Zornitza Stark Marked gene: SHARPIN as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1708 | SHARPIN | Zornitza Stark Gene: sharpin has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1708 | SHARPIN | Zornitza Stark Classified gene: SHARPIN as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1708 | SHARPIN | Zornitza Stark Gene: sharpin has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1707 | SHARPIN |
Zornitza Stark gene: SHARPIN was added gene: SHARPIN was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SHARPIN was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SHARPIN were set to 38609546 Phenotypes for gene: SHARPIN were set to Autoinflammatory syndrome, MONDO:0019751, SHARPIN-related Review for gene: SHARPIN was set to GREEN Added comment: Two unrelated patients with homozygous frameshift variants presenting with: P1 - recurrent fever, parotitis, joint inflammation, colitis and chronic otitis media necessitating tympanoplasty P2 - recurrent fever episodes with lymphadenopathy and vomiting every 2–3 weeks. Extensive functional data and mouse model. Sources: Literature |
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| Mendeliome v1.1706 | RTN2 | Zornitza Stark Phenotypes for gene: RTN2 were changed from Spastic paraplegia 12, autosomal dominant, 604805; MONDO:0011489 to Spastic paraplegia 12, autosomal dominant, 604805; MONDO:0011489; distal hereditary motor neuropathy, MONDO:0018894 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1703 | PTCRA | Zornitza Stark Marked gene: PTCRA as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1701 | SLC37A3 | Zornitza Stark Marked gene: SLC37A3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1698 | CADM3 | Zornitza Stark edited their review of gene: CADM3: Added comment: Two additional families reported with a different variant, de novo in one family.; Changed rating: GREEN; Changed publications: 38074074 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1698 | EMILIN1 | Chern Lim reviewed gene: EMILIN1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuronopathy, distal hereditary motor, autosomal dominant 10, MIM#620080, Aortic aneurysm, MONDO:0005160, EMILIN1-related, AR.; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1697 | IQSEC2 | Ain Roesley Phenotypes for gene: IQSEC2 were changed from Mental retardation, X-linked 1/78, MIM# 309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347 to Intellectual developmental disorder, X-linked 1 MIM#309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1696 | SLC37A3 |
Achchuthan Shanmugasundram gene: SLC37A3 was added gene: SLC37A3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SLC37A3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC37A3 were set to 28041643; 35486108 Phenotypes for gene: SLC37A3 were set to retinitis pigmentosa, MONDO:0019200 Review for gene: SLC37A3 was set to GREEN Added comment: Three unrelated cases reported with biallelic variants in SLC37A3 gene (One case in PMID:28041643 and two cases in PMID:35486108) and with autosomal recessive retinitis pigmentosa. Sources: Literature |
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| Mendeliome v1.1696 | PTCRA |
Achchuthan Shanmugasundram gene: PTCRA was added gene: PTCRA was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PTCRA was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PTCRA were set to 38422122 Phenotypes for gene: PTCRA were set to Autoimmunity, HP:0002960; lymphopenia, MONDO:0003783 Review for gene: PTCRA was set to GREEN Added comment: PMID:38422122 reported the identification of 10 individuals from seven kindreds from four different ethnicities with biallelic PTCRA variants (homozygous in five kindreds and compound heterozygous in two kindreds). Six of these 10 patients were clinically asymptomatic at their most recent evaluation, while other four patients displayed infection, lymphoproliferation, and/or autoimmunity with an onset during their teens or in adulthood. One of these patients died from SARS-CoV-2 pneumonia at the age of 24 years. Patient 9 had a small thymus on MRI at the age of 2 years, whereas P5 and P6 had no visible thymus at the ages of 13 and 8 years, respectively. Three of the nine patients with pLOF PTCRA variants tested were found to produce autoantibodies, several of which were associated with clinical manifestations. Anti-thyroid autoantibodies and/or clinically overt thyroiditis were found in three of the nine patients. P7, who suffered from recurrent herpes infections, had autoantibodies against type I interferons. Two of those identified variants are hypomorphic and are associated with autoimmunity. In addition, there is extensive functional and epidemiological data available. Sources: Literature |
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| Mendeliome v1.1695 | RTN2 |
Achchuthan Shanmugasundram changed review comment from: PMID:38527963 reported the identification of seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven unrelated families with distal hereditary motor neuropathy. All affected individuals exhibited weakness in the distal upper and lower limbs, lower limb spasticity, hyperreflexia, with an onset in the first decade of life. Nerve conduction studies revealed axonal motor neuropathy with neurogenic changes in the electromyography. Characterisation of C. elegans RTN2 homolog loss-of-function variants demonstrated morphological and behavioural differences compared to the parental strain and treatment with an endoplasmic/sarcoplasmic reticulum Ca(2+) re-uptake inhibitor (2,5-di-tert-butylhydroquinone) rescued key phenotypic differences. Biallelic variants in RTN2 gene have not yet been associated with any phenotypes in OMIM or Gene2Phenotype, while monoallelic variants have been associated with spastic paraplegia (MIM #604805) in OMIM.; to: PMID:38527963 reported the identification of seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven unrelated families with distal hereditary motor neuropathy. All affected individuals exhibited weakness in the distal upper and lower limbs, lower limb spasticity, hyperreflexia, with an onset in the first decade of life. Nerve conduction studies revealed axonal motor neuropathy with neurogenic changes in the electromyography. Characterisation of C. elegans RTN2 homolog loss-of-function variants demonstrated morphological and behavioural differences compared to the parental strain, and treatment with an endoplasmic/sarcoplasmic reticulum Ca(2+) re-uptake inhibitor (2,5-di-tert-butylhydroquinone) rescued key phenotypic differences. Biallelic variants in RTN2 gene have not yet been associated with any phenotypes in OMIM or Gene2Phenotype, while monoallelic variants have been associated with spastic paraplegia (MIM #604805) in OMIM. |
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| Mendeliome v1.1695 | RTN2 |
Achchuthan Shanmugasundram changed review comment from: PMID:38527963 reported the identification of seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven unrelated families with distal hereditary motor neuropathy. All affected individuals (seven males and seven females, aged 9-50 years) exhibited weakness in the distal upper and lower limbs, lower limb spasticity, hyperreflexia, with an onset in the first decade of life. Nerve conduction studies revealed axonal motor neuropathy with neurogenic changes in the electromyography. Characterisation of C. elegans RTN2 homolog loss-of-function variants demonstrated morphological and behavioural differences compared to the parental strain and treatment with an endoplasmic/sarcoplasmic reticulum Ca(2+) re-uptake inhibitor (2,5-di-tert-butylhydroquinone) rescued key phenotypic differences. Biallelic variants in RTN2 gene have not yet been associated with any phenotypes in OMIM or Gene2Phenotype, while monoallelic variants have been associated with spastic paraplegia (MIM #604805) in OMIM.; to: PMID:38527963 reported the identification of seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven unrelated families with distal hereditary motor neuropathy. All affected individuals exhibited weakness in the distal upper and lower limbs, lower limb spasticity, hyperreflexia, with an onset in the first decade of life. Nerve conduction studies revealed axonal motor neuropathy with neurogenic changes in the electromyography. Characterisation of C. elegans RTN2 homolog loss-of-function variants demonstrated morphological and behavioural differences compared to the parental strain and treatment with an endoplasmic/sarcoplasmic reticulum Ca(2+) re-uptake inhibitor (2,5-di-tert-butylhydroquinone) rescued key phenotypic differences. Biallelic variants in RTN2 gene have not yet been associated with any phenotypes in OMIM or Gene2Phenotype, while monoallelic variants have been associated with spastic paraplegia (MIM #604805) in OMIM. |
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| Mendeliome v1.1695 | RTN2 | Achchuthan Shanmugasundram reviewed gene: RTN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 38527963; Phenotypes: distal hereditary motor neuropathy, MONDO:0018894; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1694 | TUBA8 | Sangavi Sivagnanasundram reviewed gene: TUBA8: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:006476; Phenotypes: polymicrogyria with optic nerve hypoplasia (MONDO:0013172); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1691 | CANVAS_ACAGG | Bryony Thompson edited their review of STR: CANVAS_ACAGG: Added comment: Additional 4 unrelated cases homozygous for the (ACAGG)exp and one compound het with AAGGG/ACAGG expansion in a Japanese neuropathy cohort.; Changed rating: GREEN; Changed publications: 33103729, 36061987; Changed phenotypes: cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome MONDO:0044720; Set clinically relevant: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1691 | CAPRIN1 | Zornitza Stark Phenotypes for gene: CAPRIN1 were changed from Neurodevelopmental disorder, CAPRIN1-related MONDO:0700092; Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636 to Neurodevelopmental disorder with language impairment, autism, and attention deficit-hyperactivity disorder, MIM# 620782; Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1690 | KDM5C | Ain Roesley Phenotypes for gene: KDM5C were changed from Mental retardation, X-linked, syndromic, Claes-Jensen type, MIM# 300534; MONDO:0010355 to Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type MIM# 300534; MONDO:0010355 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1689 | PSMA5 | Zornitza Stark Marked gene: PSMA5 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1689 | PSMA5 |
Zornitza Stark gene: PSMA5 was added gene: PSMA5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PSMA5 was set to Other Publications for gene: PSMA5 were set to 37600812 Phenotypes for gene: PSMA5 were set to Inborn error of immunity, MONDO:0003778, PSMA5-related; PRAAS/CANDLE Review for gene: PSMA5 was set to RED Added comment: Single patient with heterozygous PSMB8 variant and de-novo PSMA5 truncating variant (p.Arg168*) with clinical features of CANDLE. Patient also had splice site variant in PSMC5. In silico modelling showing interaction of PSMB8 and PSMA5. PSMA5/a5 is a constitutive component of the 20S core proteasome, ? digenic model of disease. Sources: Literature |
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| Mendeliome v1.1687 | CNOT1 | Sangavi Sivagnanasundram reviewed gene: CNOT1: Rating: AMBER; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004485; Phenotypes: holoprosencephaly 12 with or without pancreatic agenesis MONDO:0032787; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1687 | CENPE | Sangavi Sivagnanasundram reviewed gene: CENPE: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004413; Phenotypes: autosomal recessive primary microcephaly MONDO:0016660; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1687 | PURA | Ain Roesley Phenotypes for gene: PURA were changed from Mental retardation, autosomal dominant 31, MIM# 616158 to Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties (OMIM 616158) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1683 | BANF1 | Zornitza Stark Phenotypes for gene: BANF1 were changed from Nestor-Guillermo progeria syndrome, MIM# 614008 to Nestor-Guillermo progeria syndrome, MIM# 614008; Neurodevelopmental disorder, MONDO:0700092, BANF1-related; Hereditary peripheral neuropathy, MONDO:0020127, BANF1-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1680 | BANF1 |
Zornitza Stark edited their review of gene: BANF1: Added comment: PMID 35982159: Single individual reported with a de novo variant, p.Ala87Thr, and a neurodevelopmental disorder. PMID 36980188: Hereditary peripheral neuropathy, MONDO:0020127, BANF1-related; Changed publications: 32783369, 21549337, 35982159, 36980188; Changed phenotypes: Nestor-Guillermo progeria syndrome, MIM# 614008, Neurodevelopmental disorder, MONDO:0700092, BANF1-related, Hereditary peripheral neuropathy, MONDO:0020127, BANF1-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal |
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| Mendeliome v1.1680 | FILIP1 | Zornitza Stark Phenotypes for gene: FILIP1 were changed from Arthrogryposis multiplex congenita MONDO:0015168, FILIP1 related to Neuromuscular disorder, congenital, with dysmorphic facies, MIM# 620775 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1679 | FILIP1 | Zornitza Stark reviewed gene: FILIP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuromuscular disorder, congenital, with dysmorphic facies, MIM# 620775; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1679 | RNU4-2 | Zornitza Stark Marked gene: RNU4-2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1678 | RNU4-2 |
Zornitza Stark gene: RNU4-2 was added gene: RNU4-2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RNU4-2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: RNU4-2 were set to Neurodevelopmental disorder, MONDO:0700092, RNU4-2 related Review for gene: RNU4-2 was set to GREEN Added comment: Emerging evidence that de novo variants in this gene cause ID. Sources: Literature |
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| Mendeliome v1.1677 | YKT6 | Zornitza Stark Marked gene: YKT6 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1676 | YKT6 |
Zornitza Stark gene: YKT6 was added gene: YKT6 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: YKT6 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: YKT6 were set to 38522068 Phenotypes for gene: YKT6 were set to Syndromic disease, MONDO:0002254, YKT6-related Review for gene: YKT6 was set to AMBER Added comment: Two individuals homozygous for YKT6 [NM_006555.3:c.554A>G p.(Tyr185Cys)] exhibited normal prenatal course followed by failure to thrive, developmental delay and progressive liver disease. Haplotype analysis identified a shared homozygous region flanking the variant, suggesting a common ancestry. The third individual homozygous for YKT6 [NM_006555.3:c.191A>G p.(Tyr64Cys)] exhibited neurodevelopmental disorders and optic atrophy. Supportive functional data in Drosophila. Amber rating due to homozygous missense variants and founder effect in two of the families. Sources: Literature |
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| Mendeliome v1.1675 | SEPHS1 | Zornitza Stark Marked gene: SEPHS1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1674 | SEPHS1 |
Zornitza Stark gene: SEPHS1 was added gene: SEPHS1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SEPHS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SEPHS1 were set to 38531365 Phenotypes for gene: SEPHS1 were set to Neurodevelopmental disorder, MONDO:0700092, SEPHS1-related Review for gene: SEPHS1 was set to GREEN Added comment: Nine individuals from eight families with developmental delay, growth and feeding problems, hypotonia, and dysmorphic features, all with heterozygous missense variants in SEPHS1. Eight of these individuals had a recurrent variant at amino acid position 371 of SEPHS1 (p.Arg371Trp, p.Arg371Gln, and p.Arg371Gly); seven of these variants were known to be de novo. Sources: Literature |
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| Mendeliome v1.1671 | SCA4_ZFHX3_GGC | Bryony Thompson Marked STR: SCA4_ZFHX3_GGC as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1670 | SCA4_ZFHX3_GGC |
Bryony Thompson STR: SCA4_ZFHX3_GGC was added STR: SCA4_ZFHX3_GGC was added to Mendeliome. Sources: Literature Mode of inheritance for STR: SCA4_ZFHX3_GGC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: SCA4_ZFHX3_GGC were set to 38035881; 38197134 Phenotypes for STR: SCA4_ZFHX3_GGC were set to spinocerebellar ataxia type 4 MONDO:0010847 Review for STR: SCA4_ZFHX3_GGC was set to GREEN STR: SCA4_ZFHX3_GGC was marked as clinically relevant Added comment: PMID: 38035881 - repeat expansion is identified in 5 Swedish ataxia families that developed balance and gait disturbances at 15 to 60 years of age and had sensory neuropathy and slow saccades. PMID: 38197134 - Poly-glycine GGC expansion in the last coding exon of ZFHX3 was identified in the original SCA4 Utah pedigree (Swedish origin) in the region of high linkage identified on 16q22. The expansion was also identified in an Iowa ataxia pedigree of Swedish ancestry. The expansion wasn’t identified in 11,258 exomes, 7,650 WGS probands without neurological phenotype, or 803 individuals with ataxia. Grch38 chr16:72787695–72787758 Normal allele <30 repeats, 21 repeats is the most common (derived from 33,094 individuals) Undefined pathogenic 30-48 repeats Definitive pathogenicity 48+ repeats Sources: Literature |
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| Mendeliome v1.1669 | GTF3C5 | Bryony Thompson Marked gene: GTF3C5 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1668 | GTF3C5 |
Bryony Thompson gene: GTF3C5 was added gene: GTF3C5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GTF3C5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GTF3C5 were set to 38520561; 35503477 Phenotypes for gene: GTF3C5 were set to neurodevelopmental disorder MONDO:0700092, GTF3C5-related Review for gene: GTF3C5 was set to GREEN Added comment: 4 families/probands with syndromic ID. Loss of function is the expected PMID: 38520561 - Biallelic variants identified (3 missense & 1 stopgain) in 4 individuals from 3 families presenting with multisystem developmental syndrome including the features: growth retardation, developmental delay, intellectual disability, dental anomalies, cerebellar malformations, delayed bone age, skeletal anomalies, and facial dysmorphism. Gene-disease relationship supported by: reduced protein expression in patient cells, yeast assays, and a zebrafish model PMID: 35503477 - 1 proband with biallelic missense variants and hypomelanosis of Ito, seizures, growth retardation, abnormal brain MRI, developmental delay, and facial dysmorphism Sources: Literature |
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| Mendeliome v1.1664 | MCOLN1 | Zornitza Stark edited their review of gene: MCOLN1: Added comment: PMID 37972748: 23 affected individuals from 13 families with Lisch epithelial corneal dystrophy. WGS in 2 families and then targeted Sanger sequencing in the other families identified 9 rare heterozygous loss of function variants in MCOLN1. Homozygous and compound-heterozygous state of 4 of 9 LECD-associated variants cause Mucolipidosis IV (MLIV), which comprises neurodegeneration as well as corneal opacity of infantile-onset with epithelial autofluorescent lysosomal inclusions. Six parents of 3 patients with MLIV confirmed to carry pathogenic MCOLN1 variants did not have the LECD phenotype. Heterozygous MCOLN1 variants can be associated with incomplete penetrance and variable expressivity of LECD with an estimated penetrance of 0.2% for MCOLN1 loss-of-function variants based on gnomAD.; Changed publications: 37972748; Changed phenotypes: Mucolipidosis IV, MIM# 252650, MONDO:0009653, Lisch epithelial corneal dystrophy, OMIM# 620763; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1664 | CEP295 | Zornitza Stark Marked gene: CEP295 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1664 | PLXNB2 | Zornitza Stark Phenotypes for gene: PLXNB2 were changed from Amelogenesis imperfecta MONDO:0019507, PLXNB2 -related; Sensorineural hearing loss disorder MONDO:0020678, PLXNB2 -related to Syndromic disease MONDO:0002254, PLXNB2 -related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1663 | PLXNB2 | Zornitza Stark Marked gene: PLXNB2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1663 | DOCK4 | Zornitza Stark Marked gene: DOCK4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1662 | TRPV5 | Bryony Thompson Marked gene: TRPV5 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1660 | TRPV5 |
Sangavi Sivagnanasundram changed review comment from: Not a well-established gene-disease association. Has only been reported in one consanguineous family. PMID: 38528055 3 individuals from the same family affected with hypercalciuria. Biallelic Met598Val variant was identified in the proband and his two affect sibs Functional assay using WT and mutant plasmid vectors were transfected into HEK293T cells. The assay showed that the mutant vector had a non-functional TRPV5 channel as compared to the WT however no positive control was used. Sources: Other; to: Not a well-established gene-disease association. Has only been reported in one consanguineous family. PMID: 38528055 3 individuals from the same family affected with hypercalciuria. Biallelic Met598Val variant was identified in the proband and his two affect sibs Functional assay using WT and mutant plasmid vectors were transfected into HEK293T cells. The assay showed that the mutant vector had a non-functional TRPV5 channel as compared to the WT however no positive control was used. PMID: 14679186 TRPV5 knockout mice model was used to assess whether the abolishment of TRPV5 led to a disruption in Ca2+ handling. The effects of the disruption in Ca2+ handling resulted in bone abnormalities in the mice and is likely the cause of idiopathic hypercalciuria. Sources: Other |
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| Mendeliome v1.1660 | DOCK4 |
Sangavi Sivagnanasundram gene: DOCK4 was added gene: DOCK4 was added to Mendeliome. Sources: Other Mode of inheritance for gene: DOCK4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: DOCK4 were set to PMID: 38526744 Phenotypes for gene: DOCK4 were set to DOCK4-related neurodevelopmental disorder (MONDO:0060490) Review for gene: DOCK4 was set to GREEN Added comment: 7 unrelated individuals reported with heterozygous variants (missense or null variants) in DOCK4. The individuals either had ID or DD between mild and moderate with brain abnormalities. Two of the individuals are reportedly compound heterozygous. Functional assay neuro-2A Dock4 knockout cells by using the Alt-R CRISPR-Cas9 system utilizing two different guide RNAs (ko1 and ko2) and one nonspecific control guide RNA (C: control). The assay depicted the loss of function mechanism in the presence of either p.Arg853Leu and p.Asp946_Lys1966delinsValSer* (described as 945VS). Sources: Other |
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| Mendeliome v1.1657 | DISP1 |
Sangavi Sivagnanasundram changed review comment from: Well-establised gene disease association with differing mechanism of disease depending on the type of causative variant. Monoallelic truncating variants that resulted in haploinsufficiency in DISP1 led to mild HPE. However biallelic missense variants that results in a partial loss of function of DISP1 cause HPE as well. PMID: 38529886 25 individuals from 20 unrelated families with a phenotype associated with mild holoprosencephaly (HPE). A total of 23 different variants were identified in DISP1 (missense, frameshift and nonsense). 14 heterozygous individuals , 5 compound heterozygous individuals, 6 homozygous individuals (5 of the individuals were from 3 unrelated consanguineous families). HPE phenotype was also seen prenatally as one of the reported monoallelic individuals was a fetus at 20+6 GW prior to passing due to MTP. ; to: Gene disease association with differing mechanism of disease depending on the type of causative variant. Monoallelic truncating variants that resulted in haploinsufficiency in DISP1 led to mild HPE. However biallelic missense variants that results in a partial loss of function of DISP1 cause HPE as well. PMID: 38529886 25 individuals from 20 unrelated families with a phenotype associated with mild holoprosencephaly (HPE). A total of 23 different variants were identified in DISP1 (missense, frameshift and nonsense). 14 heterozygous individuals , 5 compound heterozygous individuals, 6 homozygous individuals (5 of the individuals were from 3 unrelated consanguineous families). HPE phenotype was also seen prenatally as one of the reported monoallelic individuals was a fetus at 20+6 GW prior to passing due to MTP. |
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| Mendeliome v1.1657 | DISP1 |
Sangavi Sivagnanasundram changed review comment from: Well-establised gene disease association with differing mechanism of disease depending on the type of causative variant. PMID: 38529886 25 individuals from 20 unrelated families with a phenotype associated with mild holoprosencephaly (HPE). A total of 23 different variants were identified in DISP1 (missense, frameshift and nonsense). Monoallelic truncating variants that resulted in haploinsufficiency in DISP1 led to mild HPE. However biallelic missense variants that results in a partial loss of function f DISP1 cause HPE as well.; to: Well-establised gene disease association with differing mechanism of disease depending on the type of causative variant. Monoallelic truncating variants that resulted in haploinsufficiency in DISP1 led to mild HPE. However biallelic missense variants that results in a partial loss of function of DISP1 cause HPE as well. PMID: 38529886 25 individuals from 20 unrelated families with a phenotype associated with mild holoprosencephaly (HPE). A total of 23 different variants were identified in DISP1 (missense, frameshift and nonsense). 14 heterozygous individuals , 5 compound heterozygous individuals, 6 homozygous individuals (5 of the individuals were from 3 unrelated consanguineous families). HPE phenotype was also seen prenatally as one of the reported monoallelic individuals was a fetus at 20+6 GW prior to passing due to MTP. |
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| Mendeliome v1.1657 | FRYL | Ain Roesley Marked gene: FRYL as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1656 | FRYL |
Ain Roesley gene: FRYL was added gene: FRYL was added to Mendeliome. Sources: Literature Mode of inheritance for gene: FRYL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: FRYL were set to 38479391 Phenotypes for gene: FRYL were set to neurodevelopmental disorder MONDO:0700092, FRYL-related Review for gene: FRYL was set to GREEN gene: FRYL was marked as current diagnostic Added comment: 14 individuals, all de novo except 1x duo testing (not present in tested father) 5x missense + 8x fs/stopgain + 1x canonical splice 13/13 with ID/DD (1x deceased) 4/14 seizures 7/14 with cardiac anomalies such as PDA, TOF, VSD, dextrocardia 1x also has a de novo fs variant in SF3B4 1x also has a de novo stop gain variant in SDHA functional studies using flies were performed Sources: Literature |
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| Mendeliome v1.1655 | KCNB2 | Ain Roesley Marked gene: KCNB2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1654 | KCNB2 |
Ain Roesley changed review comment from: 7 individuals, all missense 1x from asymptomatic father 2/5 MRI anomalies 2/5 cardiac anomalies 2/7 urogenital anomalies 7/7 with ID 2/7 epilepsy 2/7 hypotonia Sources: Literature; to: 7 individuals, all missense 5 de novo + 1x inherited from father who has hypotonia + 1x from asymptomatic father 2/5 MRI anomalies 2/5 cardiac anomalies 2/7 urogenital anomalies 7/7 with ID 2/7 epilepsy 2/7 hypotonia Sources: Literature |
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| Mendeliome v1.1654 | KCNB2 |
Ain Roesley gene: KCNB2 was added gene: KCNB2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KCNB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KCNB2 were set to 38503299 Phenotypes for gene: KCNB2 were set to neurodevelopmental disorder MONDO:0700092, KCNB2-related Review for gene: KCNB2 was set to GREEN gene: KCNB2 was marked as current diagnostic Added comment: 7 individuals, all missense 1x from asymptomatic father 2/5 MRI anomalies 2/5 cardiac anomalies 2/7 urogenital anomalies 7/7 with ID 2/7 epilepsy 2/7 hypotonia Sources: Literature |
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| Mendeliome v1.1653 | MAP3K20 | Zornitza Stark Phenotypes for gene: MAP3K20 were changed from Centronuclear myopathy 6 with fiber-type disproportion MIM#617760; Split-foot malformation with mesoaxial polydactyly MIM#616890 to Syndromic disease, MONDO:0002254, MAP3K20-related; Centronuclear myopathy 6 with fiber-type disproportion MIM#617760; Split-foot malformation with mesoaxial polydactyly MIM#616890 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1649 | PLXNB2 |
Chirag Patel gene: PLXNB2 was added gene: PLXNB2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PLXNB2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PLXNB2 were set to PMID: 38458752 Phenotypes for gene: PLXNB2 were set to Amelogenesis imperfecta MONDO:0019507, PLXNB2 -related; Sensorineural hearing loss disorder MONDO:0020678, PLXNB2 -related Review for gene: PLXNB2 was set to GREEN gene: PLXNB2 was marked as current diagnostic Added comment: 8 individuals from 6 families with core features of amelogenesis imperfecta and sensorineural hearing loss. Intellectual disability, ocular disease, ear developmental abnormalities and lymphoedema were also present in multiple cases. WES and WGS identified biallelic pathogenic variants in PLXNB2 (missense, nonsense, splice and a multiexon deletion variants). Variants segregated with disease. PLXNB2 is a large transmembrane semaphorin receptor protein, and semaphorin-plexin signalling controls cellular interactions that are critical during development as well as in adult life stages. Plxnb2 expression was detected in differentiating ameloblasts in mice. Human phenotype overlaps with that seen in Plxnb2 knockout mice. Sources: Literature |
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| Mendeliome v1.1648 | CEP295 |
Chirag Patel gene: CEP295 was added gene: CEP295 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CEP295 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CEP295 were set to PMID: 38154379 Phenotypes for gene: CEP295 were set to Seckel syndrome 11, OMIM # 620767 Review for gene: CEP295 was set to GREEN gene: CEP295 was marked as current diagnostic Added comment: 4 children from 2 unrelated families with Seckel-like syndrome - severe primary microcephaly, short stature, developmental delay, intellectual disability, facial deformities, and abnormalities of fingers and toes. WES identified biallelic pathogenic variants in CEP295 gene (p(Q544∗) and p(R1520∗); p(R55Efs∗49) and p(P562L)). Patient-derived fibroblasts and CEP295-depleted U2OS and RPE1 cells were used to clarify the underlying mechanisms. Depletion of CEP295 resulted in a decrease in the numbers of centrioles and centrosomes and triggered p53-dependent G1 cell cycle arrest. Loss of CEP295 caused extensive primary ciliary defects in both patient-derived fibroblasts and RPE1 cells. The results from complementary experiments revealed that the wild-type CEP295, but not the mutant protein, can correct the developmental defects of the centrosome/centriole and cilia in the patient-derived skin fibroblasts. Sources: Literature |
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| Mendeliome v1.1646 | SASS6 |
Ain Roesley commented on gene: SASS6: PMID: 38501757 1x compound het for a fs and +3 splice variant. Using cDNA RT-ed from mother's RNA, exons 13-15 were amplified and exon 14 was found to be skipped resulting in c.1546_1674del and p.516_558del PMID: 36739862 1x family, compound het for 2 missense Functional studies not performed |
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| Mendeliome v1.1646 | SASS6 | Ain Roesley reviewed gene: SASS6: Rating: GREEN; Mode of pathogenicity: None; Publications: 38501757, 36739862; Phenotypes: Microcephaly 14, primary, autosomal recessive, MIM# 616402; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1646 | FANCI | Ain Roesley Phenotypes for gene: FANCI were changed from Fanconi anemia, complementation group I, MIM# 609053; MONDO:0012186 to Fanconi anemia, complementation group I, MIM# 609053; MONDO:0012186; primary ovarian failure MONDO:0005387, FANCI-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1645 | FANCI | Ain Roesley reviewed gene: FANCI: Rating: AMBER; Mode of pathogenicity: None; Publications: 38483614; Phenotypes: primary ovarian failure MONDO:0005387, FANCI-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1645 | CAPNS1 | Zornitza Stark Marked gene: CAPNS1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1644 | CAPNS1 |
Zornitza Stark gene: CAPNS1 was added gene: CAPNS1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: CAPNS1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CAPNS1 were set to 38230350 Phenotypes for gene: CAPNS1 were set to Hereditary pulmonary arterial hypertension MONDO:0017148, CAPNS1-related Review for gene: CAPNS1 was set to AMBER Added comment: Three individuals from two families reported with homozygous splice site variants. Sources: Expert list |
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| Mendeliome v1.1643 | USP27X | Zornitza Stark Phenotypes for gene: USP27X were changed from Mental retardation, X-linked 105, MIM#300984 to Intellectual disability, X-linked 105, MIM#300984 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1639 | TCN1 | Bryony Thompson Marked gene: TCN1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1638 | TCN1 |
Bryony Thompson gene: TCN1 was added gene: TCN1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TCN1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TCN1 were set to 29764838; 19686235 Phenotypes for gene: TCN1 were set to transcobalamin I deficiency MONDO:0008659 Review for gene: TCN1 was set to AMBER Added comment: Unclear if TC1 deficiency is associated with a clinical phenotype and only found 2 families with genetic findings. 1 confirmed chet (2 truncating variants) with severe TC 1 deficiency (depression and anxiety only reported symptoms, had sickle cell trait) & another family with 2 siblings that are presumed homozygous for a truncating variant (no plasma or serum TC 1 levels but no DNA available for genetic testing) which was found heterozygous in multiple first-degree relatives. Unclear if there is a clinical phenotype. Heterozygous individuals displayed mildly low or low-normal TC 1 serum levels. Also, 4 homozygotes were identified in a study of a loss-of-function variant associated with lower vitamin B12 concentration in African Americans but there was limited ability to assess the clinical impact of the recessive disease Sources: Literature |
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| Mendeliome v1.1634 | FEM1B | Zornitza Stark edited their review of gene: FEM1B: Added comment: Five individuals reported now with same recurrent missense variant, NM_015322.5:c.377G>A NP_056137.1:p.(Arg126Gln). Affected individuals shared a severe neurodevelopmental disorder with behavioral phenotypes and a variable set of malformations, including brain anomalies, clubfeet, skeletal abnormalities, and facial dysmorphism. Overexpression of the the FEM1BR126Q variant but not FEM1B wild-type protein, during mouse brain development, resulted in delayed neuronal migration of the target cells.; Changed rating: GREEN; Changed publications: 31036916, 38465576; Changed phenotypes: Syndromic disease MONDO:0002254, FEM1B-related; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1634 | TRPV5 |
Sangavi Sivagnanasundram gene: TRPV5 was added gene: TRPV5 was added to Mendeliome. Sources: Other Mode of inheritance for gene: TRPV5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TRPV5 were set to PMID: 38528055 Phenotypes for gene: TRPV5 were set to TRPV5-related hypercalciuria (MONDO:0009550) Review for gene: TRPV5 was set to RED Added comment: Not a well-established gene-disease association. Has only been reported in one consanguineous family. PMID: 38528055 3 individuals from the same family affected with hypercalciuria. Biallelic Met598Val variant was identified in the proband and his two affect sibs Functional assay using WT and mutant plasmid vectors were transfected into HEK293T cells. The assay showed that the mutant vector had a non-functional TRPV5 channel as compared to the WT however no positive control was used. Sources: Other |
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| Mendeliome v1.1634 | USP14 | Zornitza Stark Marked gene: USP14 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1633 | USP14 |
Zornitza Stark gene: USP14 was added gene: USP14 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: USP14 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: USP14 were set to 38469793; 35066879 Phenotypes for gene: USP14 were set to Syndromic disease MONDO:0002254, USP14-related Review for gene: USP14 was set to GREEN Added comment: PMID 35066879: 3 fetuses from 2 different branches of a consanguineous family, presenting with distal arthrogryposis, underdevelopment of the corpus callosum, and dysmorphic facial features. Exome sequencing identified a biallelic 4-bp deletion (c.233_236delTTCC; p.Leu78Glnfs*11) in USP14, and sequencing of family members showed segregation with the phenotype. Ubiquitin-specific protease 14 (USP14) encodes a major proteasome-associated deubiquitinating enzyme with an established dual role as an inhibitor and an activator of proteolysis, maintaining protein homeostasis. Usp14-deficient mice show a phenotype similar to lethal human multiple congenital contractures phenotypes, with callosal anomalies, muscle wasting, and early lethality, attributed to neuromuscular junction defects due to decreased monomeric ubiquitin pool. RT-qPCR experiment in an unaffected heterozygote revealed that mutant USP14 was expressed, indicating that abnormal transcript escapes nonsense-mediated mRNA decay. PMID 38469793: biallelic USP14 variants in four individuals from three unrelated families: one fetus, a newborn with a syndromic NDD, and two siblings affected by a progressive neurological disease. Specifically, the two siblings from the latter family carried two compound heterozygous variants c.8T>C p.(Leu3Pro) and c.988C>T p.(Arg330*), while the fetus had a homozygous frameshift c.899_902del p.(Lys300Serfs*24) variant and the newborn patient harbored a homozygous frameshift c.233_236del p.(Leu78Glnfs*11) variant. The fetus and the newborn had extensive brain malformations. Sources: Literature |
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| Mendeliome v1.1631 | PRDX1 | Bryony Thompson Marked gene: PRDX1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1630 | PRDX1 |
Bryony Thompson gene: PRDX1 was added gene: PRDX1 was added to Mendeliome. Sources: Literature digenic tags were added to gene: PRDX1. Mode of inheritance for gene: PRDX1 was set to Other Publications for gene: PRDX1 were set to 29302025; 35190856 Phenotypes for gene: PRDX1 were set to methylmalonic aciduria and homocystinuria type cblC MONDO:0010184 Mode of pathogenicity for gene: PRDX1 was set to Other Review for gene: PRDX1 was set to GREEN Added comment: Only variants affecting the canonical splice acceptor site of intron 5 (e.g. c.515-1G-T, c.515-2A-T) that cause skipping of exon 6 and the polyA termination signal of PRDX1 produce an MMACHC epimutation. The resulting read-through transcript extends through the adjacent MMACHC locus in the antisense orientation. These PRDX1 exon 6 acceptor splice site variants cause disease through digenic inheritance with a pathogenic MMACHC on the other allele. Sources: Literature |
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| Mendeliome v1.1626 | PSMB10 | Zornitza Stark edited their review of gene: PSMB10: Added comment: PMID 38503300: Six individuals with three de novo missense variants. Individuals presented with T-B-NK± severe combined immunodeficiency (SCID) and clinical features suggestive of Omenn syndrome, including diarrhea, alopecia, and desquamating erythematous rash.; Changed publications: 31783057, 37600812, 38503300; Changed phenotypes: Proteasome-associated autoinflammatory syndrome 5, MIM# 619175, Severe combined immunodeficiency, MONDO:0015974, PSMB10-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1624 | CRELD1 | Zornitza Stark Phenotypes for gene: CRELD1 were changed from Developmental and epileptic encephalopathy, MONDO:0100062, CRELD1-related; Atrioventricular septal defect, partial, with heterotaxy syndrome, MIM# 606217 to Jeffries-Lakhani neurodevelopmental syndrome, MIM# 620771; Atrioventricular septal defect, partial, with heterotaxy syndrome, MIM# 606217 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1623 | CRELD1 | Zornitza Stark edited their review of gene: CRELD1: Changed phenotypes: Jeffries-Lakhani neurodevelopmental syndrome, MIM# 620771, Atrioventricular septal defect, partial, with heterotaxy syndrome, MIM# 606217 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1621 | EHHADH | Bryony Thompson reviewed gene: EHHADH: Rating: GREEN; Mode of pathogenicity: None; Publications: 35738466, 38310177, 24401050; Phenotypes: Fanconi renotubular syndrome 3 MONDO:0014275; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1621 | RXFP2 | Katie Ayers reviewed gene: RXFP2: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 37208861, 38430325; Phenotypes: Infertility, cryptorchidism, non-obstructive azoospermia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1621 | KAT6B | Ain Roesley Phenotypes for gene: KAT6B were changed from SBBYSS syndrome MIM#603736; Genitopatellar syndrome MIM#606170 to SBBYSS syndrome MIM#603736; Genitopatellar syndrome MIM#606170; KAT6B-related multiple congenital anomalies syndrome MONDO:0036042 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1618 | SAMD7 | Zornitza Stark Phenotypes for gene: SAMD7 were changed from Macular dystrophy, retinal, SAMD7-related MONDO:0031166 to Macular dystrophy with or without cone dysfunction, MIM# 620762 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1617 | SAMD7 | Zornitza Stark reviewed gene: SAMD7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Macular dystrophy with or without cone dysfunction, MIM# 620762; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1617 | FHL2 | Zornitza Stark Marked gene: FHL2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1616 | FHL2 |
Zornitza Stark gene: FHL2 was added gene: FHL2 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: FHL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: FHL2 were set to 36854411; 25358972 Phenotypes for gene: FHL2 were set to Cardiomyopathy, MONDO:0004994, FHL2-related Review for gene: FHL2 was set to AMBER Added comment: Emerging evidence that variants in this gene may be associated with cardiomyopathy. Reports of HCM and DCM. c.391C>T (p.Arg131Cys) may be recurrent in early-onset DCM. Sources: Expert Review |
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| Mendeliome v1.1614 | ZRSR2 | Zornitza Stark Marked gene: ZRSR2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1613 | ZRSR2 |
Zornitza Stark gene: ZRSR2 was added gene: ZRSR2 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: ZRSR2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: ZRSR2 were set to 38158857 Phenotypes for gene: ZRSR2 were set to Orofacialdigital syndrome MONDO:0015375, ZRSR2-related Review for gene: ZRSR2 was set to GREEN Added comment: Oral-facial-digital (OFD) syndrome with brain anomalies ranging from alobar holoprosencephaly to pituitary anomalies. Six unrelated families with two truncating variants and functional studies: - p.(Gly404GlufsTer23): detected in one family with 2x affected males - p.(Arg403GlyfsTer24): 5 unrelated families, both de novo and inherited Sources: Expert Review |
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| Mendeliome v1.1611 | PTRHD1 | Zornitza Stark Phenotypes for gene: PTRHD1 were changed from Parkinsonism; Intellectual disability to Neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalities, MIM# 620747 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1608 | SLC4A10 | Zornitza Stark Phenotypes for gene: SLC4A10 were changed from Neurodevelopmental disorderMONDO:0700092, SLC4A10-related to Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM# 620746 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1607 | SLC4A10 | Zornitza Stark reviewed gene: SLC4A10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM# 620746; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1606 | RGS6 | Zornitza Stark Phenotypes for gene: RGS6 were changed from Cataract,MONDO:0005129; intellectual disability, MONDO:0001071; microcephaly, MONDO:0001149 to Neurodevelopmental disorder, MONDO:0700092, RGS6-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1605 | ZSCAN10 | Zornitza Stark Marked gene: ZSCAN10 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1604 | CORIN | Zornitza Stark Phenotypes for gene: CORIN were changed from Preeclampsia/eclampsia 5 MIM#614595; ?Cardiomyopathy, familial hypertrophic, 30, atrial (MIM:620734) to Preeclampsia/eclampsia 5 MIM#614595; Cardiomyopathy, familial hypertrophic, 30, atrial (MIM:620734) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1602 | CORIN | Zornitza Stark Phenotypes for gene: CORIN were changed from Preeclampsia/eclampsia 5 MIM#614595 to Preeclampsia/eclampsia 5 MIM#614595; ?Cardiomyopathy, familial hypertrophic, 30, atrial (MIM:620734) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1601 | CELSR3 | Zornitza Stark Marked gene: CELSR3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1600 | CIAO1 | Zornitza Stark Marked gene: CIAO1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1600 | CIAO1 | Zornitza Stark Phenotypes for gene: CIAO1 were changed from Neuromuscular disease, CIAO1-related (MONDO:0019056) to Neurodegenerative disease, MONDO:0005559, CIAO1-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1598 | MMS19 | Zornitza Stark Marked gene: MMS19 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1598 | MMS19 | Zornitza Stark Phenotypes for gene: MMS19 were changed from Neuromuscular disease, MMS19-related (MONDO:0019056) to Neurodegenerative disease, MONDO:0005559, MMS19-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1596 | NARS | Zornitza Stark changed review comment from: AR disorder: assessed as LIMITED by ClinGen (borderline MODERATE).; to: Both MOIs assessed as MODERATE by ClinGen. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1596 | CIAO1 |
Paul De Fazio changed review comment from: PMID:38196629 (note pre-print) describes 4 unrelated patients with core features of progressive muscle weakness, respiratory insufficiency, joint hyperlaxity, ankle tightness, calf pseudohypertrophy, elevated CK, and larning disabilities/difficulties. 2 patients presented with increased iron deposition in the brain. Age of recognition of myopathic symptoms varied from early childhood to adolescence. PMID: 38411040 reports 2 unrelated patients. Patient 1 was born with microcephaly and borderline hypertonia, and died at 18 months of respiratory failure from bronchiolitis. Patient 2 presented with failure to thrive, a hyperkinetic movement disorder, and autism before deteriorating in late teens with muscle weakness, recurrent pneuomonia with respiratory insufficiency, and eventually death due to multi-organ failure with carnificating pneumonia, septic cardiomyopathy, and intracranial hemorrhages. Immune deficiency was ruled out. All variants reported were homozygous or compound heterozygous missense variants, with the exception of one large in-frame deletion of exon 7. Cell line studies showed the variants resulted in reduced protein stability and downstream cellular defects which could be rescued by wild-type CIAO1. Sources: Literature; to: PMID:38196629 (note pre-print) describes 4 unrelated patients with core features of progressive muscle weakness, respiratory insufficiency, joint hyperlaxity, ankle tightness, calf pseudohypertrophy, elevated CK, and larning disabilities/difficulties. 2 patients presented with increased iron deposition in the brain. Age of recognition of myopathic symptoms varied from early childhood to adolescence. Muscle biopsy showed variation in fiber size and an increase in internalized nuclei, as well as scattered degenerating/regenerating fibers and a mild to minimal increase in endomysial fibrosis. Electron microscopy revealed morphologically abnormal mitochondria. PMID: 38411040 reports 2 unrelated patients. Patient 1 was born with microcephaly and borderline hypertonia, and died at 18 months of respiratory failure from bronchiolitis. Patient 2 presented with failure to thrive, a hyperkinetic movement disorder, and autism before deteriorating in late teens with muscle weakness, recurrent pneuomonia with respiratory insufficiency, and eventually death due to multi-organ failure with carnificating pneumonia, septic cardiomyopathy, and intracranial hemorrhages. Immune deficiency was ruled out. All variants reported were homozygous or compound heterozygous missense variants, with the exception of one large in-frame deletion of exon 7. Cell line studies showed the variants resulted in reduced protein stability and downstream cellular defects which could be rescued by wild-type CIAO1. |
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| Mendeliome v1.1596 | MMS19 |
Paul De Fazio gene: MMS19 was added gene: MMS19 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MMS19 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MMS19 were set to 38411040 Phenotypes for gene: MMS19 were set to Neuromuscular disease, MMS19-related (MONDO:0019056) Penetrance for gene: MMS19 were set to unknown Review for gene: MMS19 was set to RED gene: MMS19 was marked as current diagnostic Added comment: Single patient reported with postnatal microcephaly, bilateral cataracts, failure to thrive, progressive spastic tetraparesis, scoliosis, myoclonic epilepsy and precocious puberty. Cerebral MRI at age 4 years showed pontocerebellar atrophy and white matter abnormalities. Patient died age 13 after recurrent respiratory tract infections. A homozygous in-frame deletion p.(Glu213del) was identified. Cell line studies supported pathogenicity of the variant. A zebrafish knockout model also showed a detrimental effect of Mms19 deficincy. Sources: Literature |
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| Mendeliome v1.1596 | CIAO1 |
Paul De Fazio gene: CIAO1 was added gene: CIAO1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CIAO1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CIAO1 were set to 38411040; 38196629 Phenotypes for gene: CIAO1 were set to Neuromuscular disease, CIAO1-related (MONDO:0019056) Penetrance for gene: CIAO1 were set to unknown Review for gene: CIAO1 was set to GREEN gene: CIAO1 was marked as current diagnostic Added comment: PMID:38196629 (note pre-print) describes 4 unrelated patients with core features of progressive muscle weakness, respiratory insufficiency, joint hyperlaxity, ankle tightness, calf pseudohypertrophy, elevated CK, and larning disabilities/difficulties. 2 patients presented with increased iron deposition in the brain. Age of recognition of myopathic symptoms varied from early childhood to adolescence. PMID: 38411040 reports 2 unrelated patients. Patient 1 was born with microcephaly and borderline hypertonia, and died at 18 months of respiratory failure from bronchiolitis. Patient 2 presented with failure to thrive, a hyperkinetic movement disorder, and autism before deteriorating in late teens with muscle weakness, recurrent pneuomonia with respiratory insufficiency, and eventually death due to multi-organ failure with carnificating pneumonia, septic cardiomyopathy, and intracranial hemorrhages. Immune deficiency was ruled out. All variants reported were homozygous or compound heterozygous missense variants, with the exception of one large in-frame deletion of exon 7. Cell line studies showed the variants resulted in reduced protein stability and downstream cellular defects which could be rescued by wild-type CIAO1. Sources: Literature |
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| Mendeliome v1.1596 | THBS2 | Ain Roesley Phenotypes for gene: THBS2 were changed from {Lumbar disc herniation, susceptibility to} 603932 to {Lumbar disc herniation, susceptibility to} 603932; connective tissue disorder MONDO:0003900, THBS2-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1593 | UBAP1L | Seb Lunke Marked gene: UBAP1L as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1591 | DIP2C | Elena Savva Marked gene: DIP2C as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1591 | APOLD1 | Seb Lunke Marked gene: APOLD1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1591 | TOGARAM2 | Zornitza Stark Marked gene: TOGARAM2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1591 | TOGARAM2 | Zornitza Stark Gene: togaram2 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1590 | TOGARAM2 | Zornitza Stark Classified gene: TOGARAM2 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1590 | TOGARAM2 | Zornitza Stark Gene: togaram2 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1589 | UBAP1L |
Ee Ming Wong changed review comment from: - Twelve unrelated families with Hungary, the United States, Israel, Tunisia and the Netherlands with members presenting with autosomal recessive rod-cone or cone-rod dystrophy - Reported variants included splice, nonsense, frameshift and in-frame del variants - Age of disease onset was very variable, with some patients experiencing first symptoms during their fourth decade of life or later. Sources: Literature; to: - Twelve unrelated families with Hungary, the United States, Israel, Tunisia and the Netherlands with members presenting with autosomal recessive rod-cone or cone-rod dystrophy - Reported variants included splice, nonsense, frameshift and in-frame del variants - Age of disease onset was very variable, with some patients experiencing first symptoms during their fourth decade of life or later. Sources: Literature |
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| Mendeliome v1.1589 | CORIN | Daniel Flanagan reviewed gene: CORIN: Rating: RED; Mode of pathogenicity: None; Publications: 37913506, 15637153; Phenotypes: ?Cardiomyopathy, familial hypertrophic, 30, atrial (MIM:620734); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1589 | SNUPN | Seb Lunke Marked gene: SNUPN as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1589 | TOGARAM2 | Zornitza Stark Classified gene: TOGARAM2 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1589 | TOGARAM2 | Zornitza Stark Gene: togaram2 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1588 | UBAP1L |
Ee Ming Wong gene: UBAP1L was added gene: UBAP1L was added to Mendeliome. Sources: Literature Mode of inheritance for gene: UBAP1L was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: UBAP1L were set to PMID: 38293907; 38420906 Phenotypes for gene: UBAP1L were set to Cone-rod dystrophy (MONDO:0015993), UBAP1L-related Review for gene: UBAP1L was set to GREEN gene: UBAP1L was marked as current diagnostic Added comment: - Twelve unrelated families with Hungary, the United States, Israel, Tunisia and the Netherlands with members presenting with autosomal recessive rod-cone or cone-rod dystrophy - Reported variants included splice, nonsense, frameshift and in-frame del variants - Age of disease onset was very variable, with some patients experiencing first symptoms during their fourth decade of life or later. Sources: Literature |
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| Mendeliome v1.1587 | CELSR3 |
Crystle Lee gene: CELSR3 was added gene: CELSR3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CELSR3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CELSR3 were set to PMID: 38429302 Phenotypes for gene: CELSR3 were set to Neurodevelopmental disorder (MONDO#0700092), CELSR3-related Review for gene: CELSR3 was set to GREEN Added comment: PMID: 38429302:12 affected individuals from 11 families reported with bi-allelic variants. Phenotype ranged from CNS anomalies (7/12), CNS and CAKUT (3/12) and CAKUT only (2/12). Only missense variants reported and 1 inframe variant. Functional studies done in zebrafish demonstrate similar structural anomalies of the developing pronephros and neuronal abnormalities to affected individuals PMID: 34951123: 5 het missense variants reported in patients with febrile seizures (FS)/epilepsy. Arg3141Gln present in gnomAD (7 hets). No functional studies. Summarised as potentially associated with febrile seizures (FS)/epilepsy Sources: Literature |
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| Mendeliome v1.1587 | APOLD1 |
Lucy Spencer changed review comment from: PMID: 35638551 1 family with an atypical inherited bleeding disorder characterised by severe spontaneous bleeding episodes in childhood and microcirculatory problems. 4 affected individuals across 2 generations have R49*in APOLD1, another affected individual from a third generation was not able to be sequenced = 4 meiosis. 4 unaffected individuals did not have the variant. This gene has no NMD region, R49* would affect 82% of the protein. Paper is not using the MANE select transcript, alt p. in MANE select is R18* which affects 92% of the MANE select protein Interestingly R49* is created by a delins/2 missense in cis, 1 common R49Q and 1 rare R49W, some UNaffected family members just have the common missense without the other in cis. Immunofluorescence studies in patient platelets showed a 50% reduction of APOLD1 and disrupted cytoskeletal and junctional organization. Sources: Literature; to: PMID: 35638551 1 family with an atypical inherited bleeding disorder characterised by severe spontaneous bleeding episodes in childhood and microcirculatory problems. 4 affected individuals across 2 generations have R49*in APOLD1, another affected individual from a third generation was not able to be sequenced = 4 meiosis. 4 unaffected individuals did not have the variant. This gene has no NMD region, R49* would affect 82% of the protein. Paper is not using the MANE select transcript, alt p. in MANE select is R18* which affects 92% of the MANE select protein Interestingly R49* is created by a delins/2 missense in cis, 1 common R49Q and 1 rare R49W, some UNaffected family members just have the common missense without the other in cis. Immunofluorescence studies in patient platelets showed a 50% reduction of APOLD1 and disrupted cytoskeletal and junctional organization. SiRNA silencing of APOLD1 in HBDEC cells resulted in altered cell shape and size, and were associated with endothelial cell junction dismantling. These cells were also almost devoid of VWF. Sources: Literature |
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| Mendeliome v1.1587 | ZSCAN10 |
Rylee Peters gene: ZSCAN10 was added gene: ZSCAN10 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ZSCAN10 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ZSCAN10 were set to PMID: 38386308 Phenotypes for gene: ZSCAN10 were set to syndromic disease MONDO:0002254 Review for gene: ZSCAN10 was set to GREEN Added comment: Bi-allelic ZSCAN10 loss-of-function variants were identified in seven affected individuals from five unrelated families with syndromic neurodevelopmental disorder. Highly consistent phenotypic features include global developmental delay, behavioural abnormalities, and variable facial asymmetry with outer and inner ear malformations leading to profound SNHL. Facial asymmetry was recapitulated in the Zscan10 mouse model along with inner and outer ear malformations. Sources: Literature |
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| Mendeliome v1.1587 | SLC12A9 | Zornitza Stark Marked gene: SLC12A9 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1586 | SNF8 | Elena Savva Marked gene: SNF8 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1586 | SLC12A9 |
Zornitza Stark gene: SLC12A9 was added gene: SLC12A9 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SLC12A9 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC12A9 were set to 38334070 Phenotypes for gene: SLC12A9 were set to Neurodevelopmental disorder, MONDO:0700092, SLC12A9-related Review for gene: SLC12A9 was set to GREEN Added comment: Three individuals from unrelated families with bi-allelic LoF variants and a neurodevelopment phenotype, skeletal and brain abnormalities, hypopigmentation, dysmorphic features. Sources: Literature |
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| Mendeliome v1.1585 | SNF8 |
Chern Lim gene: SNF8 was added gene: SNF8 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SNF8 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SNF8 were set to 38423010 Phenotypes for gene: SNF8 were set to Neurodevelopmental disorder (MONDO:0700092), SNF8-related Review for gene: SNF8 was set to GREEN gene: SNF8 was marked as current diagnostic Added comment: PMID: 38423010 - Nine individuals from six families presenting with a spectrum of neurodevelopmental/neurodegenerative features caused by bi-allelic variants in SNF8. In total, three putative LoF variants and four missense variants were identified. - The phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy, massive reduction of white matter, hypo-/aplasia of the corpus callosum, neurodevelopmental arrest, and early death. A second cohort shows a milder phenotype with intellectual disability, childhood-onset optic atrophy, or ataxia. All mildly affected individuals shared the same hypomorphic variant, c.304G>A (p.Val102Ile) as compound heterozygous. - Functional studies using fibroblasts derived from patients and zebrafish model showed LoF is the disease mech. Sources: Literature |
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| Mendeliome v1.1585 | TUBA4A | Seb Lunke Marked gene: TUBA4A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1584 | SNUPN |
Suliman Khan gene: SNUPN was added gene: SNUPN was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SNUPN was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SNUPN were set to PMID: 38413582; PMID: 38366623 Phenotypes for gene: SNUPN were set to autosomal recessive limb-girdle muscular dystrophy MONDO:0015152 Review for gene: SNUPN was set to GREEN Added comment: PMID: 38413582: reported 18 children from 15 unrelated families with muscular phenotypes, including proximal upper limb weakness, distal upper and lower limb weakness, and myopathy (EMG) with elevated serum creatinine kinase level. Exome sequencing revealed nine hypomorphic biallelic variants in the SNUPN gene, predominantly clustered in the last coding exon. Functional studies showed that mutant SPN1 failed to oligomerize leading to cytoplasmic aggregation in patients’ primary fibroblasts. PMID: 38366623: reported five individuals from two unrelated families with limb-girdle muscular dystrophy. Sources: Literature |
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| Mendeliome v1.1584 | APOLD1 |
Lucy Spencer gene: APOLD1 was added gene: APOLD1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: APOLD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: APOLD1 were set to 35638551 Phenotypes for gene: APOLD1 were set to Bleeding disorder, vascular-type (MIM#620715) Review for gene: APOLD1 was set to AMBER Added comment: PMID: 35638551 1 family with an atypical inherited bleeding disorder characterised by severe spontaneous bleeding episodes in childhood and microcirculatory problems. 4 affected individuals across 2 generations have R49*in APOLD1, another affected individual from a third generation was not able to be sequenced = 4 meiosis. 4 unaffected individuals did not have the variant. This gene has no NMD region, R49* would affect 82% of the protein. Paper is not using the MANE select transcript, alt p. in MANE select is R18* which affects 92% of the MANE select protein Interestingly R49* is created by a delins/2 missense in cis, 1 common R49Q and 1 rare R49W, some UNaffected family members just have the common missense without the other in cis. Immunofluorescence studies in patient platelets showed a 50% reduction of APOLD1 and disrupted cytoskeletal and junctional organization. Sources: Literature |
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| Mendeliome v1.1584 | RGS6 | Seb Lunke Marked gene: RGS6 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1584 | RGS6 |
Seb Lunke gene: RGS6 was added gene: RGS6 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RGS6 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RGS6 were set to 38332109; 25525169 Phenotypes for gene: RGS6 were set to Cataract,MONDO:0005129; intellectual disability, MONDO:0001071; microcephaly, MONDO:0001149 Review for gene: RGS6 was set to RED Added comment: Original paper from 2015 describes single consanguineous with two siblings affected by cataract, developmental delay, and microcephaly >3SD. A homozygous canonical splice variant predicted to lead to NMD in RGS6 was identified by WGS and linkage (rather than full WGS analysis). The 2024 paper speculates that the phenotype is driven by a change in RGS6 isoform balance rather than LoF using a knock-out mouse model. It is noted that the mice did not have microcephaly, and ID was assessed using social interaction. No mention of cataract in the mice. Sources: Literature |
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| Mendeliome v1.1583 | TOGARAM2 |
Naomi Baker gene: TOGARAM2 was added gene: TOGARAM2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TOGARAM2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TOGARAM2 were set to PMID:38374469 Phenotypes for gene: TOGARAM2 were set to Nonsyndromic genetic hearing loss (MONDO:0019497), TOGARAM2-related Review for gene: TOGARAM2 was set to RED Added comment: Paper reports one individual with bilateral profound hearing loss with a homozygous TOGARAM2 nonsense variant and demonstrated reduced mRNA expression in transfected cells. Sources: Literature |
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| Mendeliome v1.1583 | DIP2C |
Melanie Marty gene: DIP2C was added gene: DIP2C was added to Mendeliome. Sources: Literature Mode of inheritance for gene: DIP2C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DIP2C were set to PMID: 38421105 Phenotypes for gene: DIP2C were set to Neurodevelopmental disorder (MONDO#0700092), DIP2C-related Review for gene: DIP2C was set to GREEN Added comment: PMID: 38421105 - Twenty three patients with het DIP2C variants (10 de novo). All patients had developmental delays affecting expressive language and speech, most had mild dev delay and ID. Four patients had seizures. Additional phenotypic findings were non-specific but recurrent anomalies did include a high anterior hair-line, prominent forehead, and a broad nasal tip. Four patients had cardiac defects (hypertrophic cardiomyopathy, atrial septal defects,and bicuspid aortic valve) Sources: Literature |
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| Mendeliome v1.1583 | NIT1 | Ain Roesley Marked gene: NIT1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1583 | NIT1 | Zornitza Stark Marked gene: NIT1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1581 | TUBA4A |
Sarah Pantaleo gene: TUBA4A was added gene: TUBA4A was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TUBA4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TUBA4A were set to PMID: 38413182 Phenotypes for gene: TUBA4A were set to Congenital myopathy MONDO:0019952 Review for gene: TUBA4A was set to AMBER Added comment: One novel TUBA4A variant in two unrelated Chinese patients with sporadic congenital myopathy. Identified candidate genes using laser capture micro dissection, proteomics, WES, clinical data, myopathological changes, electrophysiological exams and thigh muscle MRIs. The variant is de novo in both patients, c.679C>T, p.(Leu227Phe). The prominent myopathological changes in both patients were muscle fibres with focal myofibrillar disorganisation and rimmed vacuoles. Immunofluorescence showed ubiqution-positive TUBA4A protein aggregates in the muscle fibres with rimmed vacuoles. Overexpression of Leu227Phe resulted in cytoplasmic aggregates which colocalised with ubiquitin in cellular model. Patient 1 is 14yo and had delayed motor development milestones since infancy. Myopathic face, high-arched palate, waddling gait, winged scapula and muscle weakness in four limbs with lower extremities and proximal muscle more severely affected. Follow up at 14yo showed slight improvement in motor function compared with 3yo. Patient 2 is 6yo and presented with motor retardation since birth. At 3yo, presented with mild ptosis and ophthalmoparesis, high-arched palate and muscle weakness involving both proximal and distal in all limbs. No likely pathogenic variants in 116 other protein-encoding genes. Variants confirmed by Sanger sequencing and absent from gnomAD. ACMG predicts likely pathogenic classification. Sources: Literature |
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| Mendeliome v1.1580 | NIT1 |
Paul De Fazio gene: NIT1 was added gene: NIT1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NIT1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NIT1 were set to 38430071 Phenotypes for gene: NIT1 were set to Cerebrovascular disorder, NIT1-related (MONDO:0011057) Penetrance for gene: NIT1 were set to unknown gene: NIT1 was marked as current diagnostic Added comment: 5 unrelated families reported with recessively inherited cerebral small vessel disease had compound hetereozygous or homozygous variants in NIT1. 1 family (3 siblings) had p.(Ala68*) in trans with p.(Arg243Trp), the remaining 4 families (1 individual each) were all homozygous for p.(Arg243Trp). Patients presented in mid-adulthood with progressive movement disorders (e.g. dystonia, chorea, bradykinesia and tremor, gait disturbance, dysarthria) and had abnormal brain MRI findings (honeycomb appearance of the basal ganglia-thalamus complex, due to numerous strongly dilated PVS). 3 patients had non-lobar intracerebral hemorrhage. Slowly progressive cognitive decline was also a key feature. Metabolic analysis in urine confirmed loss of NIT1 enzymatic function. Note p.(Arg243Trp) has 1 homozygote in gnomAD v4, but permitted due to later presentation in reported patients. Sources: Literature |
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| Mendeliome v1.1580 | FEZF2 | Ain Roesley Marked gene: FEZF2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1578 | RREB1 | Zornitza Stark edited their review of gene: RREB1: Added comment: PMID 38332451: de novo LoF variant in an individual with phenotype consistent with the previous reports.; Changed rating: AMBER; Changed publications: 32938917, 38332451; Changed phenotypes: Rasopathy, MONDO:0021060, RREB1-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1578 | FEZF2 |
Ain Roesley gene: FEZF2 was added gene: FEZF2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: FEZF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: FEZF2 were set to 38425142 Phenotypes for gene: FEZF2 were set to neurodevelopmental disorder MONDO:0700092, FEZF2-related Review for gene: FEZF2 was set to GREEN gene: FEZF2 was marked as current diagnostic Added comment: - 7 indiv but 1 has whole gene deletion and 6x SNV (4x PTCs and 2x same missense Arg344Cys) - of the 6x SNV, 4x de novo + 1x from affected father - all have ID/ASD - 1x seizures - 1x hypotonia - 1x motor coordination disorder - 2x enuresis after 7yo Sources: Literature |
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| Mendeliome v1.1577 | ZFX | Zornitza Stark Marked gene: ZFX as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1576 | ZFX |
Zornitza Stark gene: ZFX was added gene: ZFX was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ZFX was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: ZFX were set to 26350204; 26740508; 38325380 Phenotypes for gene: ZFX were set to Neurodevelopmental disorder, MONDO:0700092, ZFX-related Review for gene: ZFX was set to GREEN Added comment: A single ZFX variant has been associated with a neurodevelopmental disorder, that has a Rett syndrome-like phenotype disorder, in a 14 year old male. The ZFX variant was allelic with another X-linked variant in SHROOM4. These variants were inherited from the mother, who had random X inactivation pattern (PMID: 26740508). PMID: 38325380 reports 11 ZFX variants in 18 subjects from 16 unrelated families (14 males and 4 females) with an X-linked neurodevelopmental disorder with recurrent facial gestalt. Seven variants were truncating and the remaining were missense variants within the Zinc finger array. In the pedigree of family 6 (figure 3, PMID: 38325380), it was apparent that there were female carriers of the ZFX variant (GRCh38 chrX: 24229396A>G, c.2438A>G, p.Tyr774Cys) with hyperparathyroidism and two affected males and one affected female, with the neurodevelopmental disorder. It appeared that skewed X-inactivation in the female carriers was responsible for the different phenotypic features. The association between ZFX variants and a novel neurodevelopmental disorder, was further supported by functional studies showing altered transcriptional activity in missense variants and altered behavior in a zebrafish loss-of-function model. Sources: Literature |
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| Mendeliome v1.1575 | NARS | Zornitza Stark commented on gene: NARS: AR disorder: assessed as LIMITED by ClinGen (borderline MODERATE). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1575 | STX4 | Zornitza Stark Phenotypes for gene: STX4 were changed from Non-syndromic genetic hearing loss, MONDO:0019497, STX4-related. to Deafness, autosomal recessive 123, MIM# 620745 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1572 | KLF14 | Bryony Thompson Marked gene: KLF14 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1569 | RFX6 | Bryony Thompson Added comment: Comment on mode of inheritance: Mitchell-Riley syndrome is AR and MODY is AD | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1566 | APPL1 | Bryony Thompson edited their review of gene: APPL1: Added comment: PMID: 36208030 - a study using the UK Biobank comparing individuals with and without diabetes found LoF variants in APPL1 were ‘Inconsistent’ with being high penetrant for diabetes (failed both statistical criteria - enrichment & comparison to maximum credible allele frequency). Refutes previous study.; Changed rating: RED; Changed publications: 26073777, 36208030 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1565 | KLF11 |
Bryony Thompson Added comment: Comment on list classification: Association with monogenic diabetes now Refuted Classification - 02/08/2023. ClinGen Monogenic Diabetes GCEP - https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_b1e38a49-7c12-4514-a2a1-109e04da146f-2023-02-08T170000.000Z?page=1&size=25&search= |
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| Mendeliome v1.1564 | KLF14 |
Hali Van Niel changed review comment from: PMID: 33389382 Case-sibling study of 92 healthy individuals and 92 type 2 diabetes patients found KLF14 SNPs associated with susceptibility to type 2 diabetes PMID: 35081256 Large scale association analysis found type 2 susceptibility of KLF14 SNPS appearing to be driven by reduced insulin sensitivity PMID: 24486580 Global Meta-analysis found risk allele SNP associated with increased risk of type 2 diabetes (in global population) Sources: Other; to: Cannot find any evidence of association with mendelian disease PMID: 33389382 Case-sibling study of 92 healthy individuals and 92 type 2 diabetes patients found KLF14 SNPs associated with susceptibility to type 2 diabetes PMID: 35081256 Large scale association analysis found type 2 susceptibility of KLF14 SNPS appearing to be driven by reduced insulin sensitivity PMID: 24486580 Global Meta-analysis found risk allele SNP associated with increased risk of type 2 diabetes (in global population) Sources: Other |
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| Mendeliome v1.1564 | KLF14 |
Hali Van Niel gene: KLF14 was added gene: KLF14 was added to Mendeliome. Sources: Other Mode of inheritance for gene: KLF14 was set to Unknown Publications for gene: KLF14 were set to 33389382; 35081256; 24486580 Phenotypes for gene: KLF14 were set to diabetes mellitus MONDO:0005015 Review for gene: KLF14 was set to RED Added comment: PMID: 33389382 Case-sibling study of 92 healthy individuals and 92 type 2 diabetes patients found KLF14 SNPs associated with susceptibility to type 2 diabetes PMID: 35081256 Large scale association analysis found type 2 susceptibility of KLF14 SNPS appearing to be driven by reduced insulin sensitivity PMID: 24486580 Global Meta-analysis found risk allele SNP associated with increased risk of type 2 diabetes (in global population) Sources: Other |
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| Mendeliome v1.1562 | YEATS2 | Elena Savva Marked gene: YEATS2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1562 | YEATS2 |
Elena Savva gene: YEATS2 was added gene: YEATS2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: YEATS2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: YEATS2 were set to PMID: 22713812; 31539032 Phenotypes for gene: YEATS2 were set to ?Epilepsy, myoclonic, familial adult, 4 MIM#615127 Review for gene: YEATS2 was set to RED Added comment: PMID: 22713812 - 13 members of a single family with Benign Adult Familial Myoclonic Epilepsy (BAFME). The average age of onset was 19.5 (range 10–33) years for tremor and 25 (range 19–33) years for seizures. PMID: 31539032 - Expansions of TTTTA and insertions of TTTCA repeats in intron 1 of YEATS2 segregated in the same family ^. Sources: Literature |
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| Mendeliome v1.1561 | WASHC4 | Elena Savva Phenotypes for gene: WASHC4 were changed from Mental retardation, autosomal recessive 43, MIM #615817 to Intellectual developmental disorder, autosomal recessive 43 MIM#615817 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1560 | UGGT1 | Elena Savva Marked gene: UGGT1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1560 | UGGT1 |
Elena Savva gene: UGGT1 was added gene: UGGT1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: UGGT1 was set to Unknown Review for gene: UGGT1 was set to RED Added comment: Gene was on the Oliver list for epilepsy genes. No gene-disease association paper has been published. GnomAD NOT constrained for LOF variants. Sources: Literature |
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| Mendeliome v1.1557 | PUM1 | Zornitza Stark Phenotypes for gene: PUM1 were changed from Spinocerebellar ataxia 47, MIM# 617931; Neurodevelopmental disorder, MONDO:0700092, PUM1-related to Spinocerebellar ataxia 47, MIM# 617931; Neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism, MIM# 620719 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1555 | PUM1 | Zornitza Stark edited their review of gene: PUM1: Changed phenotypes: Spinocerebellar ataxia 47, MIM# 617931, Neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism, MIM# 620719 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1555 | TRMT1 | Elena Savva Phenotypes for gene: TRMT1 were changed from Mental retardation, autosomal recessive 68; OMIM #618302 to Intellectual developmental disorder, autosomal recessive 68 MIM#618302 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1552 | HMBS | Zornitza Stark Phenotypes for gene: HMBS were changed from Porphyria, acute intermittent, MIM#176000; Porphyria, acute intermittent, non-erythroid variant, MIM#176000 to Porphyria, acute intermittent, MIM#176000; Porphyria, acute intermittent, non-erythroid variant, MIM#176000; Encephalopathy, porphyria-related MIM#620704; Leukoencephalopathy, porphyria-related, MIM#620711 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1551 | HMBS | Zornitza Stark edited their review of gene: HMBS: Changed phenotypes: Porphyria, acute intermittent, MIM#176000, Porphyria, acute intermittent, non-erythroid variant, MIM#176000, Encephalopathy, porphyria-related MIM#620704, Leukoencephalopathy, porphyria-related, MIM#620711 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1547 | TMTC2 |
Zornitza Stark edited their review of gene: TMTC2: Added comment: Single family reported with bi-allelic variants. Mouse model.; Changed publications: 29671961, 27311106, 37943620, 30188326; Changed phenotypes: Deafness, autosomal recessive 122, MIM# 620714; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal |
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| Mendeliome v1.1547 | TMLHE | Bryony Thompson Added comment: Comment on list classification: ClinGen Disputed gene-disease association Classification - 03/02/2021 by ID & Autism GCEP: https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_7a780ea6-ad4e-417a-a596-27188e327aad-2021-03-02T050000.000Z?page=1&size=25&search= | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1546 | CARD8 | Zornitza Stark Classified gene: CARD8 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1546 | CARD8 | Zornitza Stark Gene: card8 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1545 | CARD8 | Zornitza Stark edited their review of gene: CARD8: Added comment: Additional individual reported with JRA and IBD.; Changed rating: AMBER; Changed publications: 29408806, 37724393 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1544 | ONECUT1 | Bryony Thompson Marked gene: ONECUT1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1543 | ONECUT1 |
Bryony Thompson gene: ONECUT1 was added gene: ONECUT1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ONECUT1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ONECUT1 were set to 37639628; 34663987; 10825208 Phenotypes for gene: ONECUT1 were set to Neonatal diabetes mellitus MONDO:0016391 Review for gene: ONECUT1 was set to GREEN Added comment: 3 unrelated neonatal diabetes cases with homozygous variants & supporting iPSC/mouse models PMID: 37639628 - UK biobank study of ONECUT1 variants in neonatal diabetes mellitus (NDM), MODY, and type 2 diabetes. Identified a case with syndromic NDM with a homozygous frameshift (p.Met289Argfs*8). Rare heterozygous variants were not enriched in individuals with suspected MODY (n=484). Heterozygous null variants were significantly associated with type 2 diabetes (p=0.006) as a potential susceptibility gene. PMID: 34663987 - 2 consanguineous families with homozygous variants (Glu231Ter or Glu231Asp) in cases with syndromic ND. Directed differentiation of human pluripotent stem cells revealed that loss of ONECUT1 impairs pancreatic progenitor formation. PMID: 10825208 - Hnf6 (old gene name) null mice have diabetes Sources: Literature |
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| Mendeliome v1.1542 | HSPA1L | Zornitza Stark Marked gene: HSPA1L as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1541 | SCGN | Zornitza Stark Marked gene: SCGN as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1540 | SIRT1 | Zornitza Stark Marked gene: SIRT1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1539 | TNRC6A | Elena Savva Marked gene: TNRC6A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1538 | SIRT1 |
Achchuthan Shanmugasundram gene: SIRT1 was added gene: SIRT1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SIRT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SIRT1 were set to 23473037 Phenotypes for gene: SIRT1 were set to autoimmune disease, MONDO:0007179 Review for gene: SIRT1 was set to RED Added comment: PMID:23473037 reported the identification of a missense SIRT1 variant (p.Leu107Pro) in five members of a single family and all five of them had autoimmune disorder, four had type I diabetes and one had ulcerative colitis. Sources: Literature |
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| Mendeliome v1.1538 | SCGN |
Achchuthan Shanmugasundram gene: SCGN was added gene: SCGN was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SCGN was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SCGN were set to 31663849 Phenotypes for gene: SCGN were set to ulcerative colitis, MONDO:0005101 Review for gene: SCGN was set to AMBER Added comment: PMID:31663849 reported three siblings with homozygous missense SCGN variant and with early-onset ulcerative colitis. Functional studies demonstrated that SCGN variant identified impacted the localisation of the SNARE complex partner, SNAP25, leading to impaired hormone release. In addition, SCGN knockout mouse model recapitulated impaired hormone release and susceptibility to DSS-induced colitis. Sources: Literature |
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| Mendeliome v1.1538 | HSPA1L |
Achchuthan Shanmugasundram gene: HSPA1L was added gene: HSPA1L was added to Mendeliome. Sources: Literature Mode of inheritance for gene: HSPA1L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: HSPA1L were set to 28126021 Phenotypes for gene: HSPA1L were set to inflammatory bowel disease, MONDO:0005265 Review for gene: HSPA1L was set to GREEN Added comment: PMID:28126021 reported the identification of a heterozygous de novo variant (p.Ser277Leu) in HSPA1L in a patient with inflammatory bowel disease. In addition, five additional rare HSPA1L variants (p.Gly77Ser, p.Leu172del, p.Thr267Ile, p.Ala268Thr, p.Glu558Asp) were identified in six patients from a cohort of 136 IBD patients with WES data. Functional studies showed that all six HSPA1L variant proteins showed decreased chaperone activity in vitro. Moreover, three variants demonstrated dominant negative effects on HSPA1L and HSPA1A protein activity. Sources: Literature |
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| Mendeliome v1.1537 | PRDM8 | Zornitza Stark Marked gene: PRDM8 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1537 | PRDM8 |
Zornitza Stark gene: PRDM8 was added gene: PRDM8 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: PRDM8 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PRDM8 were set to 2296154; 35034233 Phenotypes for gene: PRDM8 were set to Epilepsy, progressive myoclonic, 10 MIM#616640 Review for gene: PRDM8 was set to RED Added comment: - PMID:22961547, 3 individuals from one family, all with myoclonic epilepsy, all had the Phe261Leu variant. This variant is absent from gnomAD V4. - PMID: 35034233, Two individuals from one family, no clinical seizures but presented with myoclonus and abnormal EEG (generalised epileptiform charges), these individuals had the Ala230Gly missense change, which has currently been reported as a VUS. Sources: Expert list |
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| Mendeliome v1.1536 | PRIMA1 | Zornitza Stark Marked gene: PRIMA1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1536 | PRIMA1 |
Zornitza Stark gene: PRIMA1 was added gene: PRIMA1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: PRIMA1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PRIMA1 were set to 26339676 Phenotypes for gene: PRIMA1 were set to Frontal Lobe Epilepsy MONDO:0002612 Review for gene: PRIMA1 was set to RED Added comment: - 2/3 siblings from unaffected parents in PMID: 26339676 were diagnosed with nocturnal frontal lobe epilepsy, which was confirmed by EEG. The affected siblings were homozygous for the c.93+2T>C variant canonical splice site variant. This variant was demonstrated by mini-gene assay to skip exon 2 of PRIMA1. Overall 1 family, 2 individuals with epilepsy and high impact variants in PRIMA1. Sources: Expert list |
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| Mendeliome v1.1534 | PLXNC1 | Zornitza Stark Marked gene: PLXNC1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1534 | PLXNC1 |
Zornitza Stark gene: PLXNC1 was added gene: PLXNC1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: PLXNC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PLXNC1 were set to 36808730 Phenotypes for gene: PLXNC1 were set to Malformations of cortical development Review for gene: PLXNC1 was set to RED Added comment: This gene was included in the genes4epilepsy resource (PMID:36808730) and was reported as being associated with the clinical phenotype "malformations of cortical development". There are no current PubMed articles linking this gene with epilepsy however Sources: Expert list |
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| Mendeliome v1.1533 | CASZ1 | Zornitza Stark Marked gene: CASZ1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1532 | CASZ1 |
Zornitza Stark gene: CASZ1 was added gene: CASZ1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: CASZ1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CASZ1 were set to 28099117; 36293425; 31268246 Phenotypes for gene: CASZ1 were set to Dilated cardiomyopathy, MONDO:0005021, CASZ1-related; left ventricular non compaction Review for gene: CASZ1 was set to GREEN Added comment: Rare cause of paeditric onsent DCM. at least 3 papers report LoF variants, 2 of which each report a novel de novo frameshift variant in children diagnosed with DCM less than 1 and who died at 11 mths ( PMID: 31268246; Guo 2019) and 22mths (PMID: 36293425, Orlova 2022). Another paper (PMID: 28099117, Qiu 2017) reported a nonsense variant that segregated with DCM in a family in an AD fashion (full text not available). Sources: Expert list |
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| Mendeliome v1.1529 | NDUFB9 |
Zornitza Stark edited their review of gene: NDUFB9: Added comment: PMID: 38129218: Thr144Met, listed as ACMG-P, hom in 1x pt with mito complex I deficiency and leukodystrophy, no functional studies, both parents are het. However, this variant has 2 homozygotes in gnomADv4 so unlikely pathogenic.; Changed publications: 22200994, 38129218 |
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| Mendeliome v1.1528 | BET1 | Zornitza Stark Phenotypes for gene: BET1 were changed from Muscular dystrophy, MONDO:0019950, BET1-related; Epilepsy to Muscular dystrophy, congenital, with rapid progression, MIM# 254100 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1527 | BET1 | Zornitza Stark edited their review of gene: BET1: Changed phenotypes: Muscular dystrophy, congenital, with rapid progression, MIM# 254100 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1526 | DLG5 | Zornitza Stark Phenotypes for gene: DLG5 were changed from Ciliopathy, MONDO:0016044, DLG5-related; Cystic kidneys, nephrotic syndrome, hydrocephalus, limb abnormalities, congenital heart disease and craniofacial malformations to Yuksel-Vogel-Bauer syndrome, MIM#620703 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1525 | DLG5 |
Zornitza Stark changed review comment from: Four unrelated families reported, supportive Xenopus animal model data. Sources: Literature; to: Four unrelated families reported, supportive Xenopus animal model data. Cystic kidneys, nephrotic syndrome, hydrocephalus, limb abnormalities, congenital heart disease and craniofacial malformations. Sources: Literature |
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| Mendeliome v1.1525 | ASCC3 | Zornitza Stark Phenotypes for gene: ASCC3 were changed from Neuromuscular syndrome; congenital myopathy to Intellectual developmental disorder, autosomal recessive 81, MIM# 620700 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1521 | RIC1 | Zornitza Stark Phenotypes for gene: RIC1 were changed from Cleft lip; cataract; tooth abnormality; intellectual disability; facial dysmorphism; ADHD to Cleft lip/palate MONDO:0016044, RIC1-related; Cleft lip; cataract; tooth abnormality; intellectual disability; facial dysmorphism; ADHD | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1516 | ACACA | Zornitza Stark reviewed gene: ACACA: Rating: AMBER; Mode of pathogenicity: None; Publications: 36709796; Phenotypes: Acetyl-CoA carboxylase deficiency, MIM# 613933; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1513 | NUP160 |
Melanie Marty changed review comment from: PMID: 30910934 1 x patient with familial steroid-resistant nephrotic syndrome (SRNS) and FSGS carried novel compound-heterozygous variants in NUP160 (R1173X and E803K). Silencing of Drosophila NUP160 specifically in nephrocytes (fly renal cells) led to functional abnormalities, reduced cell size and nuclear volume, and disorganized nuclear membrane structure. These defects were completely rescued by the expression of the wild-type human NUP160 gene in nephrocytes. PMID: 30179222 1 x family (2 sibs) with compound het variants E803K and Arg910X. 1 Sib had SRNS and FSGS, the other had proteinuria. PMID: 33456446 1 x family (2 sibs) with steroid-resistant nephrotic syndrome and chronic kidney disease. Homozygous for NUP160 c.1179+5G>A, confirmed by RT-PCR to cause abnormal splicing [r.1102_1179del;p.(Phe368_Gln393del)]. These individuals also had additional neurological features of intellectual disability and epilepsy. PMID: 38224683 Generated a podocyte-specific Nup160 knockout (Nup160podKO) mouse mode using CRISPR/Cas9 and Cre/loxP technologies. They showed that Nup160podKO mice develop typical signs of NS.; to: PMID: 30910934 1 x patient with familial steroid-resistant nephrotic syndrome (SRNS) and FSGS carried novel compound-heterozygous variants in NUP160 (R1173X and E803K). Silencing of Drosophila NUP160 specifically in nephrocytes (fly renal cells) led to functional abnormalities, reduced cell size and nuclear volume, and disorganized nuclear membrane structure. These defects were completely rescued by the expression of the wild-type human NUP160 gene in nephrocytes. PMID: 30179222 1 x family (2 sibs) with compound het variants E803K and Arg910X. 1 Sib had SRNS and FSGS, the other had proteinuria. PMID: 33456446 1 x family (2 sibs) with SRNS and chronic kidney disease. Homozygous for NUP160 c.1179+5G>A, confirmed by RT-PCR to cause abnormal splicing [r.1102_1179del;p.(Phe368_Gln393del)]. These individuals also had additional neurological features of intellectual disability and epilepsy. PMID: 38224683 Generated a podocyte-specific Nup160 knockout (Nup160podKO) mouse model using CRISPR/Cas9 and Cre/loxP technologies. They showed that Nup160podKO mice develop typical signs of NS. |
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| Mendeliome v1.1513 | SP9 | Zornitza Stark Marked gene: SP9 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1513 | SP9 | Suliman Khan commented on gene: SP9: PMID: 38288683: reported 5 unrelated patients with de novo heterozygous variants (missense and PTV) in SP9 gene. In silico and in vitro studies suggested a novel form of interneuronopathy with variable severity depending on the presence of loss or gain of function variants. Patients with loss-of-function variants had ID, ASD, and epilepsy, whereas missense variants in the second C2H2 binding domain result in hypomorphic and neomorphic DNA binding functions that cause severe epileptic encephalopathy. The author suggested a novel form of interneuronopathy with variable severity depending on the presence of loss or gain of function variants. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1511 | MEI4 |
Lisa Norbart changed review comment from: PMID: 38252283 - 5x compound heterozygous missense variants and 1x homozygous missense variant seen in five individuals across 4 unrelated families affected with female infertility characterised by preimplantation embryonic arrest. Includes one family with two affected sisters with the same compound heterozygous variants. 2/4 families showed inheritance, parental data not available for other two families. Homozygous variant in the consanguineous family appears with a more severe phenotype. In vitro evidence shows variants reduced the interactions between MEI4 and DNA, but no effects on protein levels. In vivo knock-out mouse model showed female mice were infertile, characterised by developmental defects during oogenesis. Sources: Literature; to: PMID: 38252283 - 5x compound heterozygous missense variants and 1x homozygous missense variant seen in five individuals across 4 unrelated families affected with female infertility characterised by preimplantation embryonic arrest. Includes one family with two affected sisters with the same compound heterozygous variants. 2/4 families showed inheritance, parental data not available for other two families. Homozygous variant in the consanguineous family appears with a more severe phenotype. In vitro evidence shows variants reduced the interactions between MEI4 and DNA, but no effects on protein levels. In vivo knock-out mouse model showed female mice were infertile, characterised by developmental defects during oogenesis. Sources: Literature |
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| Mendeliome v1.1511 | RHOXF1 | Zornitza Stark Marked gene: RHOXF1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1510 | MEI4 | Zornitza Stark Marked gene: MEI4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1510 | RHOXF1 |
Chris Ciotta gene: RHOXF1 was added gene: RHOXF1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RHOXF1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: RHOXF1 were set to PMID: 38258527 Phenotypes for gene: RHOXF1 were set to Spermatogenic failure, MONDO:0004983, RHOXF1-related Review for gene: RHOXF1 was set to AMBER Added comment: In a cohort of 1,201 men from China with oligozoospermia and azoospermia, hemizygous RHOXF1 variants were identified in 4 unrelated individuals. Three of these variants were missense variants (V130M, A91V & A156V), all were absent from gnomAD (including version 4) and had deleterious in silicos. The one other variant was a nonsense variant (R160X) which is predicted to escape NMD and truncate the protein. This is seen in gnomAD version 4 in 1 heterozygote female, and absent in other versions. In vitro functional evidence for these variants was provided, the V130M, A156V and R160X mutants demonstrated impaired protein localisation with an increase in the protein in the cytoplasm and impaired nuclear entry, the A91V mutant protein did not share these localisation defects. Further, The V130M mutant protein decreased DMRT1 promotor activity, DMRT1 is considered essential for testicular development and spermatogenesis. However, the R160X variant demonstrated increased activation, three times higher than WT. The two other missense variants had no effect. Sources: Literature |
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| Mendeliome v1.1510 | PRDM6 | Elena Savva Marked gene: PRDM6 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1509 | PRDM6 |
Elena Savva gene: PRDM6 was added gene: PRDM6 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PRDM6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: PRDM6 were set to 38071433; 27716515; 27181681 Phenotypes for gene: PRDM6 were set to Patent ductus arteriosus 3 MIM#617039 Review for gene: PRDM6 was set to GREEN Added comment: Gene is established for patent ductus arteriosus. Only missense reported but supported by functional studies suggesting LOF. PMID: 38071433 - Two families (3 affected, 6 affected) with patent ductus arteriosus with/without additional coarctation of the aorta. Family 1 had a missense, family 2 had a PTC - both regarded as VUSs Additional papers PMID: 27716515;27181681 describe nonsyndromic patent ductus arteriosus for the first time Sources: Literature |
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| Mendeliome v1.1507 | MEI4 |
Lisa Norbart gene: MEI4 was added gene: MEI4 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MEI4 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Publications for gene: MEI4 were set to 38252283 Phenotypes for gene: MEI4 were set to Infertility disorder, MONDO:0005047, MEI4-related Review for gene: MEI4 was set to GREEN Added comment: PMID: 38252283 - 5x compound heterozygous missense variants and 1x homozygous missense variant seen in five individuals across 4 unrelated families affected with female infertility characterised by preimplantation embryonic arrest. Includes one family with two affected sisters with the same compound heterozygous variants. 2/4 families showed inheritance, parental data not available for other two families. Homozygous variant in the consanguineous family appears with a more severe phenotype. In vitro evidence shows variants reduced the interactions between MEI4 and DNA, but no effects on protein levels. In vivo knock-out mouse model showed female mice were infertile, characterised by developmental defects during oogenesis. Sources: Literature |
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| Mendeliome v1.1507 | WDR44 | Seb Lunke Marked gene: WDR44 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1507 | WDR44 | Seb Lunke Added comment: Comment when marking as ready: GoF mentioned but not well established. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1506 | WDR44 |
Andrew Fennell gene: WDR44 was added gene: WDR44 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: WDR44 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: WDR44 were set to PMID: 38191484 Phenotypes for gene: WDR44 were set to Ciliopathy, MONDO:0005308, WDR44-related Review for gene: WDR44 was set to GREEN Added comment: 11 male patients with 6 missense and 1 nonsense variant in WDR44 displaying a wide range of cognitive impairment and variable congenital anomalies associated with primary cilium dysfunction. All patients had learning difficulties with 8 labelled as intellectually disabled (mild-moderate). Other clinical features included anomalies of craniofacial, musculoskeletal, brain, renal and cardiac development. WDR44 is a negative regulator of ciliogenesis. Increased binding is hypothesised to underlie the pathogenicity of WDR44 variants identified in this cohort. Functional data supported impaired ciliogenesis initiation in patient fibroblasts and a zebrafish model. A zebrafish model recapitulated the human phenotype when morphants expressed WDR44 L668S, D669N, S764F, G782C, H839R, and R733* variants. Of note, D648G or N840S did not recapitulate the phenotype in the zebrafish model. The studies supported a GoF mechanism, but the authors could not rule out that LoF of WDR44 contributes to the ciliopathy-like phenotype observed, because protein expression data was only available for a limited number of patients. Sources: Literature |
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| Mendeliome v1.1506 | SAMD7 | Zornitza Stark Marked gene: SAMD7 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1502 | SH2B3 |
Ain Roesley commented on gene: SH2B3: PMID:37206266 2x families - hom missense variant Val402Met: functional performed on patient's fibroblasts demonstrated increased basal pSTAT5, pSTAT3 and increased pJAK2 + pSTAT5 after stimulation with IL-3, GH, GM-CSF and EPO - hom fs Arg148Profs*40 functional performed in zebrafish demonstrated increased number of macrophages and thrombocytes PMID:23908464; 1 fam with 2 affecteds with dev delay + autoimmunity + (1x) ALL, hom for Asp231Gly fs*3 PMID:38152053; JMML cohort - 2x hom missense + 2x het PTCs |
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| Mendeliome v1.1502 | SAMD7 |
Paul De Fazio gene: SAMD7 was added gene: SAMD7 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SAMD7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SAMD7 were set to 38272031 Phenotypes for gene: SAMD7 were set to Macular dystrophy, retinal, SAMD7-related MONDO:0031166 Review for gene: SAMD7 was set to GREEN gene: SAMD7 was marked as current diagnostic Added comment: Five biallelic variants were identified in eight individuals from six families with macular dystrophy with or without cone dysfunction. Three families were consanguineous. Mean age at first presentation was 34.8 years, range 14 to 51. Four variants affected splicing, while one missense variant impaired the repressive activity of SAMD7. All functional work was performed using in vitro assays. Sources: Literature |
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| Mendeliome v1.1502 | CAMK2D | Elena Savva Marked gene: CAMK2D as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1501 | CAMK2D |
Elena Savva gene: CAMK2D was added gene: CAMK2D was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CAMK2D was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: CAMK2D were set to 38272033 Phenotypes for gene: CAMK2D were set to Neurodevelopmental disorder (MONDO#0700092), CAMK2D-related Added comment: PMID: 38272033 - 8 patients (5/8 de novo) with mostly missense and a single splice site variant, ages range from 5 weeks to 20 years old - Most variants functionally shown to have a GOF mechanism causing addition DCM phenotype, LOF is only neurological - Phenotypes include dev delay (mild-severe) (7/7 patients), skeletal anomalies (7/8, scoliosis, kyphosis, involving spine/hands/feet/palate), DCM (6/8), seizures (3/8), visual anomalies (astigmatism, cortical vision impairment, myopia, strabismus 5/5), enlarged brain ventricles (3/5) Sources: Literature |
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| Mendeliome v1.1497 | RBMX | Zornitza Stark edited their review of gene: RBMX: Added comment: PMID 37277488: In-frame deletion reported in a large multiplex Swedish family; Changed publications: 25256757, 34260915, 37277488; Changed phenotypes: Intellectual developmental disorder, syndromic 11, Shashi type, MIM#300238, Gustavson syndrome, MIM# 309555 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1496 | PLA2G16 | Zornitza Stark Phenotypes for gene: PLA2G16 were changed from Lipodystrophy (MONDO:0006573), PLA2G16-related to Lipodystrophy, familial partial, type 9, MIM# 620683 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1493 | MEIOB | Zornitza Stark Phenotypes for gene: MEIOB were changed from Spermatogenic failure 22 MIM#617706; primary ovarian insufficiency to Spermatogenic failure 22 MIM#617706; Premature ovarian failure 23, MIM# 620686 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1491 | MEIOB | Zornitza Stark reviewed gene: MEIOB: Rating: GREEN; Mode of pathogenicity: None; Publications: 35991565, 34392356, 31000419; Phenotypes: Premature ovarian failure 23, MIM# 620686; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1481 | COQ4 | Zornitza Stark Phenotypes for gene: COQ4 were changed from Coenzyme Q10 deficiency, primary, 7, MIM# 616276 to Coenzyme Q10 deficiency, primary, 7, MIM# 616276; Spastic ataxia 10, autosomal recessive, MIM# 620666 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1479 | COQ4 | Zornitza Stark edited their review of gene: COQ4: Added comment: PMIDs 36047608;38014483;38013626: more than 10 families reported with more limited spastic ataxia phenotype, onset from infancy to adulthood.; Changed publications: 25658047, 26185144, 33704555, 36047608, 38014483, 38013626; Changed phenotypes: Coenzyme Q10 deficiency, primary, 7, MIM# 616276, Spastic ataxia 10, autosomal recessive, MIM# 620666 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1479 | SEC61A1 | Zornitza Stark Phenotypes for gene: SEC61A1 were changed from Hyperuricemic nephropathy, familial juvenile, 4, MIM# 617056; Hypogammaglobulinaemia; Neutropaenia to Hyperuricemic nephropathy, familial juvenile, 4, MIM# 617056; Immunodeficiency, common variable, 15, MIM# 620670; Neutropenia, severe congenital, 11, autosomal dominant, MIM# 620674 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1477 | SEC61A1 | Zornitza Stark edited their review of gene: SEC61A1: Added comment: PMID 32325141: single individual with de novo missense and phenotype primarily characterised by severe neutropenia.; Changed publications: 27392076, 32325141, 28782633, 32325141 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1477 | SEC61A1 | Zornitza Stark edited their review of gene: SEC61A1: Changed phenotypes: Hyperuricemic nephropathy, familial juvenile, 4, MIM# 617056, Immunodeficiency, common variable, 15, MIM# 620670, Neutropenia, severe congenital, 11, autosomal dominant, MIM# 620674 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1477 | SEC61A1 | Zornitza Stark edited their review of gene: SEC61A1: Changed phenotypes: Hyperuricemic nephropathy, familial juvenile, 4, MIM# 617056, Immunodeficiency, common variable, 15, MIM# 620670 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1477 | KPNA7 | Elena Savva Phenotypes for gene: KPNA7 were changed from Oocyte/zygote/embryo maturation arrest 17, MIM# 620319; Neurodevelopmental disorder to Oocyte/zygote/embryo maturation arrest 17, MIM# 620319; Neurodevelopmental disorder (MONDO#0700092), KPNA7-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1476 | KIF4A | Elena Savva Phenotypes for gene: KIF4A were changed from Mental retardation, X-linked 100, MIM# 300923; Taurodontism, microdontia, and dens invaginatus (MIM#313490) to Intellectual developmental disorder, X-linked 100 MIM#300923; Taurodontism, microdontia, and dens invaginatus MIM#313490 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1469 | PPFIA3 | Zornitza Stark Marked gene: PPFIA3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1468 | PPFIA3 |
Zornitza Stark gene: PPFIA3 was added gene: PPFIA3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PPFIA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PPFIA3 were set to 37034625 Phenotypes for gene: PPFIA3 were set to Neurodevelopmental disorder, MONDO:0700092, PPFIA3-related Review for gene: PPFIA3 was set to GREEN Added comment: 19 individuals with mono-allelic variants presenting with features including developmental delay, intellectual disability, hypotonia, micro/macrocephaly, autism, and epilepsy. One individual with compound het variants: insufficient evidence for bi-allelic variants causing disease. Sources: Literature |
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| Mendeliome v1.1467 | SLC13A3 | Zornitza Stark Marked gene: SLC13A3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1463 | SPIN4 | Zornitza Stark Marked gene: SPIN4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1461 | GTPBP1 | Zornitza Stark Marked gene: GTPBP1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1460 | CACHD1 | Zornitza Stark Marked gene: CACHD1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1459 | SLC13A3 |
Daniel Flanagan gene: SLC13A3 was added gene: SLC13A3 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: SLC13A3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC13A3 were set to https://www.neurology.org/doi/full/10.1212/NXG.0000000000200101 (No PMID) Phenotypes for gene: SLC13A3 were set to Leukoencephalopathy, acute reversible, with increased urinary alpha-ketoglutarate (MIM# 618384) Review for gene: SLC13A3 was set to GREEN Added comment: Seven patients reported with biallelic SLC13A3 variants, causing acute reversible leukoencephalopathy and α-ketoglutarate accumulation. Patients presented with acute neurological deterioration after a febrile illness. 5/7 with ataxia, 4/7 had seizures, 1/7 developmental delay. Sources: Expert list |
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| Mendeliome v1.1459 | SOX8 | Zornitza Stark Marked gene: SOX8 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1458 | BORCS8 | Zornitza Stark Marked gene: BORCS8 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1457 | SPIN4 |
Belinda Chong gene: SPIN4 was added gene: SPIN4 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SPIN4 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: SPIN4 were set to 36927955 Phenotypes for gene: SPIN4 were set to Lui-Jee-Baron syndrome MIM#301114 Review for gene: SPIN4 was set to AMBER Added comment: PMID 36927955 * Single family, hemizygous frameshift variant (NM_001012968.3, c.312_313AGdel) identified in a male individual with generalized overgrowth of prenatal onset, variant also present in the mother and grandmother (both had adult heights 2 SDS greater than their midparental heights). * In vitro shows loss of function and mice studies recapitulated the human phenotype with generalized overgrowth, including increased longitudinal bone growth. Sources: Literature Sources: Literature |
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| Mendeliome v1.1457 | SOX8 |
Paul De Fazio gene: SOX8 was added gene: SOX8 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SOX8 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SOX8 were set to https://www.neurology.org/doi/full/10.1212/NXG.0000000000200088 Phenotypes for gene: SOX8 were set to Neurodevelopmental disorder (MONDO:0700092), SOX8-related Review for gene: SOX8 was set to RED gene: SOX8 was marked as current diagnostic Added comment: Proband presented to genetics clinic at 27 years of age with BMI -3.4SD, height -2.7SD, head circumference -1.8SD. She had mild intellectual delay and clinical features of a congenital, nonprogressive myopathy with moderate proximal and distal weakness. X-rays showed skeletal dysplasia, including cervical thoracic scoliosis and lumbar scoliosis. She was reported as having had weakness at birth with poor suck, micrognathia, hypotonia, and talipes. She was documented to have significant motor delay as a child. MRI of the brain demonstrated large posterior fossa CSF spaces. Biallelic SOX8 variants biallelic (NM_014587.3:c.422+5G>C; c.583dup p.(His195ProfsTer11)) were identified by WGS. The +5 variant was shown to affect splicing, while the frameshift variant resulted in production of low-level truncated protein (not NMD predicted). Functional studies on patient fibroblasts showed misregulation of downstream SOX8 targets. Sources: Literature |
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| Mendeliome v1.1457 | BORCS8 |
Lauren Rogers changed review comment from: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants. HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease. Sources: Literature; to: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants. 5/5 hypotonia, failure to thrive, global developmental delay, profound intellectual disability, muscle weakness and atrophy, dysmorphic features. 3/5 with microcephaly, 3/5 with seizures, 4/5 with spasticity, 3/5 with scoliosis, 4/4 with optic atrophy. HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease. Sources: Literature |
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| Mendeliome v1.1457 | BORCS8 |
Lauren Rogers gene: BORCS8 was added gene: BORCS8 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: BORCS8 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: BORCS8 were set to 38128568 Phenotypes for gene: BORCS8 were set to Neurodevelopmental disorder (MONDO#0700092), BORCS8-related Review for gene: BORCS8 was set to GREEN Added comment: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants. HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease. Sources: Literature |
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| Mendeliome v1.1457 | GTPBP1 |
Lucy Spencer gene: GTPBP1 was added gene: GTPBP1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GTPBP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GTPBP1 were set to 38118446 Phenotypes for gene: GTPBP1 were set to Neurodevelopmental disorder (MONDO#0700092), GTPBP1-related Review for gene: GTPBP1 was set to GREEN Added comment: PMID: 38118446- Cohort of individuals with variants in GTPBP2 (which has been previously described) and GTPBP1 (new) who have an identical neurodevelopmental syndrome. 4 homozygous individuals from 3 consanguineous families. 2 families have different NMD-predicted nonsense variants and the third has a missense, all are absent from gnomad v4. The shared cardinal features of GTPBP1 and 2 related disease are microcephaly, profound neurodevelopmental impairment, and distinctive craniofacial features. Epilepsy was present in 10 of 20 individuals but its not clear if those individuals had GTPBP1 or 2 variants. Sources: Literature |
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| Mendeliome v1.1457 | PTBP1 | Zornitza Stark Marked gene: PTBP1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1456 | PUS3 | Zornitza Stark Phenotypes for gene: PUS3 were changed from Mental retardation, autosomal recessive 55, MIM# 617051 to Neurodevelopmental disorder with microcephaly and gray sclerae, MIM# 617051 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1454 | PRICKLE2 | Zornitza Stark changed review comment from: LIMITED by ClinGen.; to: LIMITED by ClinGen; however, experimental evidence appears not to have been considered. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1450 | PRICKLE1 | Zornitza Stark edited their review of gene: PRICKLE1: Added comment: LIMITED by ClinGen for AR PME and DISPUTED for AD epilepsy.; Changed rating: RED | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1449 | PRICKLE1 | Zornitza Stark edited their review of gene: PRICKLE1: Added comment: Note all ClinVar entries for this gene are VOUS/LB/B. The variants reported in bi-allelic cases are almost all missense without further supportive data.; Changed rating: AMBER | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1447 | GPT2 | Zornitza Stark Phenotypes for gene: GPT2 were changed from Mental retardation, autosomal recessive 49, MIM#616281 to Neurodevelopmental disorder with microcephaly and spastic paraplegia, MIM# 616281 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1446 | GPT2 | Zornitza Stark edited their review of gene: GPT2: Changed phenotypes: Neurodevelopmental disorder with microcephaly and spastic paraplegia, MIM# 616281 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1446 | POLD1 | Zornitza Stark Phenotypes for gene: POLD1 were changed from Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome, MIM# 615381; MONDO:0014157 to Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome, MIM# 615381; MONDO:0014157; Combined immunodeficiency, MONDO:0015131, POLD1-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1443 | POLD1 | Zornitza Stark edited their review of gene: POLD1: Added comment: Association with combined immunodeficiency: Three individuals from two generations of a consanguineous family reported, some functional data. Another unrelated individual reported in PMID 31449058, more functional data. Third family identified in Melbourne, two affected sibs, compound het variants and combined immunodeficiency.; Changed phenotypes: Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome, MIM# 615381, MONDO:0014157, Combined immunodeficiency, MONDO:0015131, POLD1-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1442 | LCK |
Zornitza Stark edited their review of gene: LCK: Added comment: Additional cases: PMID 38100037: Description of a second unrelated patient with novel biallelic missense LCK c.1393T>C, p.C465R variant in a patient from a consanguineous Syrian family with profound T-cell immune deficiency characterized by complete LCK protein expression deficiency and ensuing proximal TCR signaling-and CD4 and CD8-co-receptor-mediated functional and phenotypical defects. PMID: 27087313 reported 3 siblings of a consanguineous family presenting with recurrent pneumonia and severe viral skin disease leading to malignant transformation. The patients had an intronic LCK c.188-2A>G splice site variant resulting in skipping of exon 3 and mRNA decay. Clinical data alongside with CD4+ T-cell lymphocytopenia suggested a hypomorphic LCK deficiency.; Changed rating: GREEN; Changed publications: 22985903, 1579166, 11021796, 27087313, 38100037 |
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| Mendeliome v1.1441 | CASP2 | Zornitza Stark Phenotypes for gene: CASP2 were changed from neurodevelopmental disorder MONDO:0700092, CASP2-related to Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly, MIM# 620653 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1440 | CASP2 | Zornitza Stark reviewed gene: CASP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly, MIM# 620653; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1436 | MAP1LC3B2 | Zornitza Stark Marked gene: MAP1LC3B2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1436 | MAP1LC3B2 |
Zornitza Stark gene: MAP1LC3B2 was added gene: MAP1LC3B2 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: MAP1LC3B2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MAP1LC3B2 were set to 35748970; 33310865 Phenotypes for gene: MAP1LC3B2 were set to Hereditary susceptibility to infection, MONDO:0015979, MAP1LC3B2 -related; Mollaret’s meningitis (recurrent lymphocytic meningitis) due to HSV2 Review for gene: MAP1LC3B2 was set to RED Added comment: PMID: 35748970 Affects CNS (resident cells and fibroblasts) Impaired autophagy induction after HSV2 infection - increased viral replication and apoptosis of patient fibroblasts. PMID: 33310865 one affected individual with heterozygous variant in MAP1LC3B2 (p.L109M) Sources: Expert Review |
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| Mendeliome v1.1435 | CAPRIN1 | Zornitza Stark Phenotypes for gene: CAPRIN1 were changed from Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636 to Neurodevelopmental disorder, CAPRIN1-related MONDO:0700092; Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1433 | CAPRIN1 | Zornitza Stark edited their review of gene: CAPRIN1: Added comment: Two individuals reported with the same de novo c.1535C > T (p.Pro512Leu) variant and a progressive course.; Changed rating: AMBER; Changed publications: 36136249 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1433 | CAPRIN1 | Zornitza Stark Phenotypes for gene: CAPRIN1 were changed from Neurodevelopmental disorder, CAPRIN1-related MONDO:0700092 to Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1432 | CAPRIN1 | Zornitza Stark reviewed gene: CAPRIN1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1432 | MANF | Zornitza Stark Marked gene: MANF as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1431 | MANF |
Zornitza Stark gene: MANF was added gene: MANF was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: MANF was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MANF were set to 26077850; 33500254; 34815294 Phenotypes for gene: MANF were set to Diabetes, deafness, developmental delay, and short stature syndrome, MIM# 620651 Review for gene: MANF was set to AMBER Added comment: Two individuals reported with homozygous variants. Mouse model recapitulates deafness phenotype. Sources: Expert Review |
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| Mendeliome v1.1428 | GABRA4 | Zornitza Stark Marked gene: GABRA4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1428 | GABRA4 |
Zornitza Stark gene: GABRA4 was added gene: GABRA4 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GABRA4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: GABRA4 were set to 35152403 Phenotypes for gene: GABRA4 were set to Developmental and epileptic encephalopathy MONDO:0100062, GABRA4-related Review for gene: GABRA4 was set to RED Added comment: Single individual with de novo missense variant reported, supportive functional data. Sources: Literature |
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| Mendeliome v1.1427 | PLA2G16 | Zornitza Stark Marked gene: PLA2G16 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1427 | PLA2G16 | Zornitza Stark Added comment: Comment when marking as ready: HGNC name is PLAAT3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1427 | FOXL1 | Zornitza Stark Marked gene: FOXL1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1421 | KIF5B | Zornitza Stark edited their review of gene: KIF5B: Added comment: Four additional patients with three distinct de-novo missense variants and features consistent with osteogenesis imperfecta. All variants are in the Kinesin motor domain (~50% of the protein). Functional data in C. Elegans and cell lines shows impaired protein function. Not clear what distinguishes OI causing variants from other phenotypes for this gene at this stage. Dominant negative effect proposed but not conclusively proven.; Changed publications: 37934770; Changed phenotypes: Skeletal dysplasia, MONDO:0018230, osteogenesis imperfecta, MONDO:0019019 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1421 | PRPF19 | Zornitza Stark Marked gene: PRPF19 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1420 | PLA2G16 | Zornitza Stark Marked gene: PLA2G16 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1416 | RAB1A | Zornitza Stark Marked gene: RAB1A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1415 | RAB1A |
Zornitza Stark gene: RAB1A was added gene: RAB1A was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RAB1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RAB1A were set to 37924809 Phenotypes for gene: RAB1A were set to neurodevelopmental disorder MONDO:0700092, RAB1A-related Review for gene: RAB1A was set to AMBER Added comment: Four families and 5 individuals, 2/5 have speech delay and 4/5 have motor delay. Anxiety in 3/5 and autism in 2/5. Microcephaly in only one individual, spastic paraplegia observed in 2 individuals from one family. In 2 families variants were inherited from an affected parent. Sources: Literature |
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| Mendeliome v1.1411 | FUK |
Zornitza Stark edited their review of gene: FUK: Added comment: PMID: 35718084: Reporting on 3 unrelated patients from literature and 1 new patient. All reported to have mild-severe intellectual disability, developmental delay and brain abnormalities, and 3/4 present with seizures. Phenotypes are childhood onset. Homozygous and compound heterozygous variants have been reported. PMID: 36426412: Reporting on new 1 patient (homozygous missense). Not affected by intellectual disability, developmental delay, or brain abnormalities. Presents with seizures. Loss of function suggested due to depletion of the FUK gene expression.; Changed rating: GREEN; Changed publications: 30503518, 35718084, 36426412 |
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| Mendeliome v1.1411 | SV2A | Zornitza Stark Marked gene: SV2A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1409 | CEP192 | Zornitza Stark Marked gene: CEP192 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1408 | CEP192 |
Chern Lim gene: CEP192 was added gene: CEP192 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CEP192 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: CEP192 were set to 37981762 Phenotypes for gene: CEP192 were set to microcephaly, short stature, limb-extremity dysplasia, and reduced testicular size Review for gene: CEP192 was set to RED gene: CEP192 was marked as current diagnostic Added comment: PMID: 37981762: - In one family, chet missense p.His638Tyr and p.Asn1917Ser segregated with microcephaly, short stature, limb-extremity dysplasia, and reduced testicular size in two affected siblings. Both sibs also fulfilled dx for mosaic variegated aneuploidy (MVA) syndrome and have tetraploidy. - A lower but substantial proportion of MVA/tetraploidy cells was observed in II-1, II-2, and II-4 (who are het for one of the variants). - In the same family, each variants in heterozygous state segregated with infertility and/or reduced testicular size in the proband’s father and maternal uncle. - Variant screening of CEP192 coding regions performed for 1264 unrelated males with idiopathic infertility. - Asn1917Ser was also detected in three additional unrelated infertile males with reduced testicular volumes. - Two other missense and two synonymous variants were repeatedly detected in infertile males. - qPCR showed CEP192 expression was decreased in individuals with c.1912C>T His638Tyr, mini-gene assay showed that c.1912C>T His638Tyr led to the skipping of exon 14, predicted to result in NMD. - Epithelial cells cultured in vitro from patients with biallelic variants showed the number of cells arrested during the prophase increased because of the failure of spindle formation. - Embyronic mouse lethality in Cep192-/- (hom for His638Tyr), Cep192M/M (hom for Asn1917Ser) and Cep192-/M (chet). - Embryos of Cep192M/M mice had significant increase of MVA and tetraploidy cells. - Number of apoptotic cells increased in Cep192M/M embryos compared with that of Cep192+/+, similar result in Cep192-/- embryos. - Male mice with Cep192 heterozygous variants replicated infertility Conclusions: - Association of this gene with autosomal recessive disease has not been established. - Association of monoallelic variants in this gene with infertility is not well established: - Two variants with some supportive evidence from mouse model. Sources: Literature |
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| Mendeliome v1.1408 | SV2A |
Karina Sandoval changed review comment from: Monoallelic variants cause epilepsy. Biallelic variant in this 5yo (Hom p.Arg383Gln) reported to cause severe phenotype of drug-resistant epileptic encephalopathy with microcephaly, DD, movement disorder and growth retardation. Consanguineous. This paper references 5 other families with both AR & AD Family #1 – p.Arg383Gln, AR, 2 affected in family, parents healthy carriers Family #2 – p.Arg570Cys, AD, 2 affected, inherited from affected mother (in gnomAD v2 1 het, absent from gnomAD v3) Family #3 – p.Gly660Arg, AD, de novo Family #4 – p.Gly660Arg, AD, segregated in 11 family members Family #5 (this study) – p.Arg289Ter, AR, parents and 2 sibs asymptomatic carriers Sources: Literature; to: Monoallelic variants cause epilepsy. Biallelic variant in this 5yo with p.Arg289Ter and another 5yo from another paper with homozygous p.Arg383Gln, reported to cause severe phenotype of drug-resistant epileptic encephalopathy with microcephaly, DD, movement disorder and growth retardation. This paper references 5 other families with both AR & AD Family #1 – p.Arg383Gln, AR, 2 affected in family, parents healthy carriers Family #2 – p.Arg570Cys, AD, 2 affected, inherited from affected mother (in gnomAD v2 1 het, absent from gnomAD v3) Family #3 – p.Gly660Arg, AD, de novo Family #4 – p.Gly660Arg, AD, segregated in 11 family members Family #5 (this study) – p.Arg289Ter, AR, parents and 2 sibs asymptomatic carriers Sources: Literature |
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| Mendeliome v1.1408 | SV2A |
Karina Sandoval changed review comment from: Monoallelic variants cause epilepsy. Biallelic variant in this 5yo (Hom p.Arg383Gln) reported to cause severe phenotype of drug-resistant epileptic encephalopathy with microcephaly, DD, movement disorder and growth retardation. Consanguineous. This paper references 5 other families with both AR & AD Family #1 – p.Arg383Gln, AR, 2 affected in family, parents healthy carriers Family #2 – p.Arg570Cys, AD, 2 affected, inherited from affected mother Family #3 – p.Gly660Arg, AD, de novo Family #4 – p.Gly660Arg, AD, segregated in 11 family members Family #5 (this study) – p.Arg289Ter, AR, parents and 2 sibs asymptomatic carriers Sources: Literature; to: Monoallelic variants cause epilepsy. Biallelic variant in this 5yo (Hom p.Arg383Gln) reported to cause severe phenotype of drug-resistant epileptic encephalopathy with microcephaly, DD, movement disorder and growth retardation. Consanguineous. This paper references 5 other families with both AR & AD Family #1 – p.Arg383Gln, AR, 2 affected in family, parents healthy carriers Family #2 – p.Arg570Cys, AD, 2 affected, inherited from affected mother (in gnomAD v2 1 het, absent from gnomAD v3) Family #3 – p.Gly660Arg, AD, de novo Family #4 – p.Gly660Arg, AD, segregated in 11 family members Family #5 (this study) – p.Arg289Ter, AR, parents and 2 sibs asymptomatic carriers Sources: Literature |
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| Mendeliome v1.1405 | DDX17 | Elena Savva Marked gene: DDX17 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1405 | DDX17 |
Melanie Marty gene: DDX17 was added gene: DDX17 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: DDX17 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DDX17 were set to https://www.medrxiv.org/search/DDX17 Phenotypes for gene: DDX17 were set to Neurodevelopmental disorder (MONDO#0700092), DDX17-related Review for gene: DDX17 was set to GREEN Added comment: https://www.medrxiv.org/search/DDX17 (pre-print) 11 patients with het de novo variants in DDX17 (5 NMD, 6 missense). Patient's phenotype included mild-moderate intellectual disability, delayed speech and language development and global developmental delay. 64% had dysmorphic facial features. Some patients also have gross and fine motor delay, generalized hypotonia, stereotypy, and evidence of autism spectrum disorder. Knockdown of Ddx17 in newborn mice showed impaired axon outgrowth and reduced axon outgrowth and branching was observed in primary cortical neurons in vitro. This result was replicated in Crispant Xenopus tadpoles, which had clear functional neural defects and showed an impaired neurobehavioral phenotype. Sources: Literature |
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| Mendeliome v1.1405 | SV2A |
Karina Sandoval gene: SV2A was added gene: SV2A was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SV2A was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Publications for gene: SV2A were set to PMID: 37985816 Phenotypes for gene: SV2A were set to Epilepsy, MONDO:0005027 Review for gene: SV2A was set to GREEN Added comment: Monoallelic variants cause epilepsy. Biallelic variant in this 5yo (Hom p.Arg383Gln) reported to cause severe phenotype of drug-resistant epileptic encephalopathy with microcephaly, DD, movement disorder and growth retardation. Consanguineous. This paper references 5 other families with both AR & AD Family #1 – p.Arg383Gln, AR, 2 affected in family, parents healthy carriers Family #2 – p.Arg570Cys, AD, 2 affected, inherited from affected mother Family #3 – p.Gly660Arg, AD, de novo Family #4 – p.Gly660Arg, AD, segregated in 11 family members Family #5 (this study) – p.Arg289Ter, AR, parents and 2 sibs asymptomatic carriers Sources: Literature |
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| Mendeliome v1.1405 | MARK4 | Elena Savva Classified gene: MARK4 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1405 | MARK4 | Elena Savva Gene: mark4 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1404 | MARK4 | Elena Savva Classified gene: MARK4 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1404 | MARK4 | Elena Savva Gene: mark4 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1403 | RNF213 | Seb Lunke changed review comment from: 14 individuals from 13 unrelated families with (de novo) missensevariants in RNF213 clustering within or around the RING domain. Individuals presented either with early-onset stroke (n=11) or with Leigh syndrome (n=3). No genotype-phenotype correlation could be established. Common features included Global Developmental Delay and Seizures, increased serum lactate, ischemic stroke, Moyamoya phenomenon and carotid/cerebral artery stenosis. Onset of symptoms generally in the first 6 months of life.; to: 14 individuals from 13 unrelated families with (de novo) missensevariants in RNF213 clustering within or around the RING domain. Individuals presented either with early-onset stroke (n=11) or with Leigh syndrome like symptoms (n=3). No genotype-phenotype correlation could be established. Common features included Global Developmental Delay and Seizures, increased serum lactate, ischemic stroke, and carotid/cerebral artery stenosis. Onset of symptoms generally in the first 6 months of life. Moyamoya phenomenon was present in 10/13 individuals. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1403 | MARK4 | Elena Savva Marked gene: MARK4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1403 | MARK4 | Elena Savva Gene: mark4 has been removed from the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1403 | KCNJ3 | Zornitza Stark Marked gene: KCNJ3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1402 | RNF213 | Seb Lunke edited their review of gene: RNF213: Changed phenotypes: Moyamoya disease, MONDO:0016820, pediatric arterial ischemic stroke, MONDO:0018585 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1402 | KCNJ3 |
Daniel Flanagan gene: KCNJ3 was added gene: KCNJ3 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: KCNJ3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KCNJ3 were set to PMID: 37963718 Phenotypes for gene: KCNJ3 were set to Epilepsy (MONDO#0005027), KCNJ3-related Review for gene: KCNJ3 was set to AMBER Added comment: Two de novo missense variants, p.(Leu333Ser) and p.(Arg313Gln), were identified in two unrelated probands with epilepsy. 1/2 had developmental delay. Whole-cell patch-clamp functional studies showed a significantly reduction in current amplitude and density. Kcnj3-knockout mice display hyperactivity and decreased anxiety, while a knock-in mouse line displays spontaneous seizure-like activity. Sources: Expert list |
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| Mendeliome v1.1402 | RNF213 | Seb Lunke reviewed gene: RNF213: Rating: GREEN; Mode of pathogenicity: None; Publications: 37924258; Phenotypes: Leigh syndrome, MONDO:0009723, pediatric arterial ischemic stroke, MONDO:0018585, Moyamoya disease, MONDO:0016820; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1402 | SEL1L | Zornitza Stark Marked gene: SEL1L as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1402 | PPID | Elena Savva Marked gene: PPID as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1401 | PLA2G16 |
Lauren Rogers changed review comment from: 7 patients from 4 unrelated consanguineous families with homozygous loss of function PTC variants. Features: 4/7 metabolic features, 6/7 neurological/skeletal features, 3/7 Psychomotor retardation/intellectual disability, 5/7 demyelinating peripheral neuropathy. Null mouse and patient derived white adipose tissue showed enrichment of arachidonic acid-containing membrane phospholipids and a strong decrease in PPARγ. CRISPR–Cas9-mediated PLAAT3 inactivation in human adipose stem cells induced insulin resistance, altered adipocyte diferentiation with decreased lipid droplet formation and reduced the expression of adipogenic and mature adipocyte markers, including PPARγ. Sources: Literature; to: 7 patients from 4 unrelated consanguineous families with homozygous loss of function PTC variants. Features: 4/7 metabolic features, 6/7 neurological/skeletal features, 3/7 Psychomotor retardation/intellectual disability, 5/7 demyelinating peripheral neuropathy. Null mouse and patient derived white adipose tissue showed enrichment of arachidonic acid-containing membrane phospholipids and a strong decrease in PPARγ. CRISPR–Cas9-mediated PLAAT3 inactivation in human adipose stem cells induced insulin resistance, altered adipocyte differentiation with decreased lipid droplet formation and reduced the expression of adipogenic and mature adipocyte markers, including PPARγ. Sources: Literature |
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| Mendeliome v1.1401 | MARK4 |
Rylee Peters changed review comment from: Missense variant, c.604T>C; p.Phe202Leu, identified in two siblings with childhood-onset neurodevelopmental disorder characterised by global developmental delay, intellectual disability, behavioural abnormalities, and dysmorphic features. The variant is located in the catalytic domain of the kinase, and is inherited from unaffected mosaic mother. Functional investigation revealed that the variant results in a gain-of-function in the ability of MARK4 to phosphorylate tau and leads to up-regulation of the mTORC1 pathway. Sources: Literature; to: Heterozygous missense variant, c.604T>C; p.Phe202Leu, identified in two siblings with childhood-onset neurodevelopmental disorder characterised by global developmental delay, intellectual disability, behavioural abnormalities, and dysmorphic features. The variant is located in the catalytic domain of the kinase, and is inherited from unaffected mosaic mother. Functional investigation revealed that the variant results in a gain-of-function in the ability of MARK4 to phosphorylate tau and leads to up-regulation of the mTORC1 pathway. Sources: Literature |
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| Mendeliome v1.1401 | PLA2G16 |
Lauren Rogers gene: PLA2G16 was added gene: PLA2G16 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PLA2G16 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: PLA2G16 were set to PMID: 37919452 Phenotypes for gene: PLA2G16 were set to Lipodystrophy (MONDO:0006573) Review for gene: PLA2G16 was set to GREEN Added comment: 7 patients from 4 unrelated consanguineous families with homozygous loss of function PTC variants. Features: 4/7 metabolic features, 6/7 neurological/skeletal features, 3/7 Psychomotor retardation/intellectual disability, 5/7 demyelinating peripheral neuropathy. Null mouse and patient derived white adipose tissue showed enrichment of arachidonic acid-containing membrane phospholipids and a strong decrease in PPARγ. CRISPR–Cas9-mediated PLAAT3 inactivation in human adipose stem cells induced insulin resistance, altered adipocyte diferentiation with decreased lipid droplet formation and reduced the expression of adipogenic and mature adipocyte markers, including PPARγ. Sources: Literature |
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| Mendeliome v1.1401 | MARK4 |
Rylee Peters gene: MARK4 was added gene: MARK4 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MARK4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MARK4 were set to PMID: 38041405 Phenotypes for gene: MARK4 were set to neurodevelopmental disorder (MONDO:0700092), MARK4-related Mode of pathogenicity for gene: MARK4 was set to Other Review for gene: MARK4 was set to AMBER gene: MARK4 was marked as current diagnostic Added comment: Missense variant, c.604T>C; p.Phe202Leu, identified in two siblings with childhood-onset neurodevelopmental disorder characterised by global developmental delay, intellectual disability, behavioural abnormalities, and dysmorphic features. The variant is located in the catalytic domain of the kinase, and is inherited from unaffected mosaic mother. Functional investigation revealed that the variant results in a gain-of-function in the ability of MARK4 to phosphorylate tau and leads to up-regulation of the mTORC1 pathway. Sources: Literature |
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| Mendeliome v1.1401 | SEL1L |
Sarah Pantaleo gene: SEL1L was added gene: SEL1L was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SEL1L was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SEL1L were set to PMID: 37943610; PMID: 37943617 Phenotypes for gene: SEL1L were set to Neurodevelopmental disorder, MONDO:0700092, SEL1L-related Penetrance for gene: SEL1L were set to Complete Added comment: Wang paper PMID: 37943610 SEL1L protein is involved in the SEL1L-HRD1 endoplasmic reticulum (ER)-associated degradation. Report two biallelic missense variants in SEL1L in six children from three independent families presenting with developmental delay, intellectual disability, microcephaly, facial dysmorphisms, hypotonia and/or ataxia (termed ERAD-associated neurodevelopment disorder with onset in infancy (ENDI). The variants were hypomorphic and impaired ERAD function. Identified by WES. Parents heterozygous and asymptomatic. P.(Gly585Asp) in Patient 1, p.(Met528Arg) in Patients 2 and 3 (siblings). All variants cause substrate accumulation. The extent of substrate accumulation in knockin cells was modest compared to those in knockout cells, pointing to a hypomorphic nature. They also had a variant in HRD1. Weis paper PMID: 37943617 Third variant p.(Cys141Tyr), biallelic, causing premature death in five patients from a consanguineous family with early-onset neurodevelopmental disorders and agammaglobulinaemia due to severe SEL1L-HRD1 ERAD dysfunction. This variant appears to have a more severe outcome, exhibiting B cell depletion and agammaglobulinaemia, causing the most severe dysfunction among all of the variants described by this group so far. They postulate that functionality of SEL1L-HRD1 ERAD is inversely correlated with disease severity in humans. Their symptoms were dev delay, neurological disorder and agammaglobulinaemia in childhood. Along with severe axial hypotonia, short stature and microcephaly. “Not a complete loss-of-function variant”. Sources: Literature |
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| Mendeliome v1.1401 | FOXL1 |
Lilian Downie gene: FOXL1 was added gene: FOXL1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: FOXL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: FOXL1 were set to PMID: 34633540 Phenotypes for gene: FOXL1 were set to Otosclerosis 11 #MIM620576 Review for gene: FOXL1 was set to RED Added comment: Single paper with variant in large AD family from Newfoundland with otosclerosis, hearing loss onset varied from late teens onwards. Segregation not completely convincing, 1 person with the deletion without otosclerosis. Conductive HL, sometimes mixed, not isolated SNHL. Second family with common haplotype and same 15bp deletion with otosclerosis. Functional studies. High population frequency and 3x homozygotes. Sources: Literature |
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| Mendeliome v1.1401 | PPID |
Elena Savva gene: PPID was added gene: PPID was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PPID was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: PPID were set to 37977818 Phenotypes for gene: PPID were set to Stutter disorder, (MONDO:0000723), PPID-related Review for gene: PPID was set to RED Added comment: PMID: 37977818 - a large family (10 affected confirmed to have the variant) with stuttering/language disorder and a het missense (p.(Pro270Ser)). Mouse K/I model showed microstructural changes in the corticospinal tract Sources: Literature |
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| Mendeliome v1.1400 | ACBD6 |
Lucy Spencer edited their review of gene: ACBD6: Added comment: PMID: 37951597 Much larger cohort with - 45 individuals from 28 families with a neurodevelopmental syndrome with complex and progressive movement disorder phenotype. 18 PTCs and splice, 1 missense 1 in frame insertion. Phenotypes: weight was >50th percentile in 20/34 patients, all mod-severe GDD, facial dysmorphism in 38/40, mild cerebellar ataxia 35/41, limb spasticity/hypertonia 31/41, gait abnormalities in 33/35.; Changed publications: 37951597 |
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| Mendeliome v1.1400 | PRPF19 |
Dean Phelan gene: PRPF19 was added gene: PRPF19 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PRPF19 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PRPF19 were set to PMID: 37962958 Phenotypes for gene: PRPF19 were set to Neurodevelopmental disorder (MONDO:0700092), PRPF19-related Review for gene: PRPF19 was set to GREEN Added comment: PMID: 37962958 Six unrelated individuals with de novo variants. Five had speech language motor delay, four had formal diagnosis of autism, three hypotonia and one fetus with multiple congenital abnormalities. Sources: Literature |
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| Mendeliome v1.1396 | GRIA3 | Zornitza Stark edited their review of gene: GRIA3: Added comment: New manuscript describing ~40 individuals with variants in GRIA3, including affected females. Some variants demonstrated to be LoF and others GoF. LoF variants generally caused a milder phenotype.; Changed publications: 32977175, 17989220, 38038360; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1394 | MRPL39 | Zornitza Stark Marked gene: MRPL39 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1391 | CNTN2 | Zornitza Stark edited their review of gene: CNTN2: Added comment: Additional family, consanguineous, homozygous variants segregated in 3 affected sibs and was not homozygous in unaffected sib. Seizures later childhood onset and mild ID.; Changed rating: GREEN; Changed publications: 23518707, 37359369; Changed phenotypes: Epilepsy, MONDO:0015653, CNTN2-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1390 | FA2H |
Zornitza Stark changed review comment from: Well established gene-disease association, both peripheral and central features (dystonia, dysarthria, cognitive impairment, and epilepsy), childhood-onset, progressive. Sources: Expert Review; to: Well established gene-disease association, both peripheral and central features (dystonia, dysarthria, cognitive impairment, and epilepsy), childhood-onset, progressive. PubMed: 31135052 – 19 patients from 16 families consistent with a complicated form of SPG. PubMed:18463364 – 7 individuals identified from a large consanguineous family with SPG. PubMed: 19068277 – 7 patients from 2 unrelated consanguineous middle eastern families PubMed: 20104589– Multiple affected individuals in an Omani family. Findings indicated that an abnormal hydroxylation of myelin galactocerebroside lipid components can lead to the progression of a severe phenotype. Sources: Expert Review |
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| Mendeliome v1.1390 | FA2H | Zornitza Stark Marked gene: FA2H as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1389 | FA2H |
Zornitza Stark gene: FA2H was added gene: FA2H was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: FA2H was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FA2H were set to 29423566 Phenotypes for gene: FA2H were set to Spastic paraplegia 35, autosomal recessive, MIM#611026 Review for gene: FA2H was set to GREEN Added comment: Well established gene-disease association, both peripheral and central features (dystonia, dysarthria, cognitive impairment, and epilepsy), childhood-onset, progressive. Sources: Expert Review |
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| Mendeliome v1.1388 | EFCAB1 | Zornitza Stark Phenotypes for gene: EFCAB1 were changed from Primary ciliary dyskinesia, MONDO:0016575, EFCAB1-related to Ciliary dyskinesia, primary, 53, MIM# 620642 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1387 | EFCAB1 | Zornitza Stark edited their review of gene: EFCAB1: Added comment: Ciliary dyskinesia, primary, 53, MIM# 620642; Changed phenotypes: Ciliary dyskinesia, primary, 53, MIM# 620642 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1385 | FLII | Zornitza Stark Phenotypes for gene: FLII were changed from Dilated cardiomyopathy MONDO:0005021 to Cardiomyopathy, dilated, 2J, MIM# 620635 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1384 | FLII | Zornitza Stark edited their review of gene: FLII: Changed phenotypes: Cardiomyopathy, dilated, 2J, MIM# 620635 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1383 | KDR | Zornitza Stark Phenotypes for gene: KDR were changed from Pulmonary hypertension; Haemangioma, capillary infantile, somatic 602089 to Pulmonary hypertension; Haemangioma, capillary infantile, somatic 602089; Tetralogy of Fallot, MONDO:0008542 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1381 | KDR |
Zornitza Stark edited their review of gene: KDR: Added comment: PMID 34113005: Exome sequencing in a family with two siblings affected by ToF revealed biallelic missense variants in KDR. Studies in knock-in mice and in HEK 293T cells identified embryonic lethality for one variant when occurring in the homozygous state, and a significantly reduced VEGFR2 phosphorylation for both variants. Rare variant burden analysis conducted in a set of 1,569 patients of European descent with ToF identified a 46-fold enrichment of protein-truncating variants (PTVs) in TOF cases compared to controls (P = 7 × 10-11). At this stage MOI unclear and insufficient evidence for either MOI.; Changed publications: 31980491, 29650961, 18931684, 34113005; Changed phenotypes: Pulmonary hypertension, Haemangioma, capillary infantile, somatic 602089, Tetralogy of Fallot, MONDO:0008542; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal |
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| Mendeliome v1.1381 | DOT1L | Zornitza Stark Marked gene: DOT1L as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1380 | DOT1L |
Zornitza Stark gene: DOT1L was added gene: DOT1L was added to Mendeliome. Sources: Literature Mode of inheritance for gene: DOT1L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DOT1L were set to 37827158 Phenotypes for gene: DOT1L were set to Neurodevelopmental disorder, MONDO:0700092, DOT1L-related Mode of pathogenicity for gene: DOT1L was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: DOT1L was set to GREEN Added comment: Nine individuals reported with seven de novo missense variants. All had DD/ID and variable patterns of associated congenital anomalies. Variants demonstrated to be GoF and lead to increased H3K79 methylation levels in flies and human cells. Sources: Literature |
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| Mendeliome v1.1378 | UNC119 |
Zornitza Stark changed review comment from: Immunodeficiency 13: Single case reported with the missense Gly22Val. The allele frequency of this variant is >2% in the African/African American subpopulation in gnomAD v2.1, including 6 homozygotes. RED for this association. Borderline Green for association with cone-rod dystrophy.; to: Immunodeficiency 13: Single case reported with the missense Gly22Val. The allele frequency of this variant is >2% in the African/African American subpopulation in gnomAD v2.1, including 6 homozygotes. RED for this association. Cone-rod dystrophy: one of the reported variants is missense with no other supporting evidence. |
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| Mendeliome v1.1377 | ARPC5 | Zornitza Stark Phenotypes for gene: ARPC5 were changed from Combined immunodeficiency, ARPC5-related MONDO:0015131 to Immunodeficiency 133 with autoimmunity and autoinflammation, MIM# 620565 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1376 | ARPC5 | Zornitza Stark commented on gene: ARPC5: Features of autoinflammation common: haemolytic anaemia, thrombocytopenia, hepatosplenomegaly, leukocytosis, neutrophilia, and elevated acute phase reactants. More variable systemic features may include coeliac disease or enteropathy, ileus, nephropathy, eczema, and dermatomyositis. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1376 | ARPC5 | Zornitza Stark reviewed gene: ARPC5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency 133 with autoimmunity and autoinflammation, MIM# 620565; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1375 | RRAGC | Zornitza Stark Phenotypes for gene: RRAGC were changed from Dilated cardiomyopathy (MONDO:0005021), RRAGC-related to Long-Olsen syndrome, MIM# 620609 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1369 | ERG | Zornitza Stark Phenotypes for gene: ERG were changed from primary lymphoedema MONDO#0019175, ERG-related to Lymphatic malformation 14, MIM# 620602 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1367 | TOMM7 | Zornitza Stark Phenotypes for gene: TOMM7 were changed from Inborn mitochondrial disorder MONDO:0004069, TOMM7-related to Garg-Mishra progeroid syndrome, MIM# 620601 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1366 | TOMM7 | Zornitza Stark edited their review of gene: TOMM7: Changed phenotypes: Garg-Mishra progeroid syndrome, MIM# 620601 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1366 | MCAT | Zornitza Stark Phenotypes for gene: MCAT were changed from Leber hereditary optic neuropathy, autosomal recessive, MONDO:0030309 to Optic atrophy 15, MIM# 620583 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1364 | MDM4 | Bryony Thompson Marked gene: MDM4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1363 | MDM4 |
Bryony Thompson gene: MDM4 was added gene: MDM4 was added to Mendeliome. Sources: Other Mode of inheritance for gene: MDM4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MDM4 were set to 32300648; 33104793 Phenotypes for gene: MDM4 were set to bone marrow failure syndrome MONDO:0000159, MDM4-related Review for gene: MDM4 was set to AMBER Added comment: A single family was reported to segregate a missense variant (p.Thr454Met) with features suggestive of dyskeratosis congenita, e.g., bone marrow hypocellularity, short telomeres, tongue squamous cell carcinoma, and acute myeloid leukemia. A mouse model of p.Thr454Met showed increased p53 activity, decreased telomere length, and bone marrow failure. Sources: Other |
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| Mendeliome v1.1362 | THOC6 |
Ling Sun changed review comment from: THOC6 homozygous or compound heterozygous variants are associated with Beaulieu-Boycott-Innes syndrome. Clinical spectrum is heterogenous, with major phenotype DD and ID (Note that this gene is already on the ID panel). Some are affected with structural cardiac anomalies, therefore not all individuals with BBIS have cardiac anomalies (hence, not a major phenotype). PMID 35426486: Two siblings with maternally inherited c.[298T>A;700G>T;824G>A], p.[(Trp100Arg);(Val234Leu);(Gly275Asp)] and paternally inherited c.977T>G, p.(Val326Gly) [compound het] PMID: 30476144: A boy with mat UPD homozygous c.(298T>A; 700G>C; 824G>C) A girl with maternally inherited c.(298T>A, 700G>C, 824G>A) and paternally inherited c.569G>A, p.(Gly190Glu) [compount het] PMID: 32282736: A boy with paternally inherited c.664T>C (p.Trp222Arg) and maternally inherited c.945+1 G>A [compound het]; to: THOC6 homozygous or compound heterozygous variants are associated with Beaulieu-Boycott-Innes syndrome. Clinical spectrum is heterogenous, with major phenotype DD and ID (Note that this gene is already on the ID panel). Some are affected with structural cardiac anomalies, therefore not all individuals with BBIS have cardiac anomalies (hence, not a major phenotype, eg. see https://databases.lovd.nl/shared/diseases/03390). PMID 35426486: Two siblings with maternally inherited c.[298T>A;700G>T;824G>A], p.[(Trp100Arg);(Val234Leu);(Gly275Asp)] and paternally inherited c.977T>G, p.(Val326Gly) [compound het] PMID: 30476144: A boy with mat UPD homozygous c.(298T>A; 700G>C; 824G>C) A girl with maternally inherited c.(298T>A, 700G>C, 824G>A) and paternally inherited c.569G>A, p.(Gly190Glu) [compount het] PMID: 32282736: A boy with paternally inherited c.664T>C (p.Trp222Arg) and maternally inherited c.945+1 G>A [compound het] |
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| Mendeliome v1.1362 | THOC6 |
Ling Sun changed review comment from: THOC6 homozygous or compound heterozygous variants are associated with Beaulieu-Boycott-Innes syndrome. Clinical spectrum is heterogenous, with major phenotype DD and ID (Note that this gene is already on the ID panel). Some are affected with structural cardiac anomalies, therefore not all individuals with BBIS have cardiac anomalies (hence, not a major phenotype). PMID 35426486: Two siblings with maternally inherited c.[298T>A;700G>T;824G>A], p.[(Trp100Arg);(Val234Leu);(Gly275Asp)] and paternally inherited c.977T>G, p.(Val326Gly) PMID: 30476144: A boy with mat UPD homozygous c.(298T>A; 700G>C; 824G>C) A girl with maternally inherited c.(298T>A, 700G>C, 824G>A) and paternally inherited c.569G>A, p.(Gly190Glu); to: THOC6 homozygous or compound heterozygous variants are associated with Beaulieu-Boycott-Innes syndrome. Clinical spectrum is heterogenous, with major phenotype DD and ID (Note that this gene is already on the ID panel). Some are affected with structural cardiac anomalies, therefore not all individuals with BBIS have cardiac anomalies (hence, not a major phenotype). PMID 35426486: Two siblings with maternally inherited c.[298T>A;700G>T;824G>A], p.[(Trp100Arg);(Val234Leu);(Gly275Asp)] and paternally inherited c.977T>G, p.(Val326Gly) [compound het] PMID: 30476144: A boy with mat UPD homozygous c.(298T>A; 700G>C; 824G>C) A girl with maternally inherited c.(298T>A, 700G>C, 824G>A) and paternally inherited c.569G>A, p.(Gly190Glu) [compount het] PMID: 32282736: A boy with paternally inherited c.664T>C (p.Trp222Arg) and maternally inherited c.945+1 G>A [compound het] |
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| Mendeliome v1.1362 | THOC6 |
Ling Sun changed review comment from: THOC6 homozygous or compound heterozygous variants are associated with Beaulieu-Boycott-Innes syndrome. Clinical spectrum is heterogenous, with major phenotype DD and ID (Note that this gene is already on the ID panel). Some are affected with structural cardiac anomalies (syndromic phenotype). PMID 35426486: Two siblings with maternally inherited c.[298T>A;700G>T;824G>A], p.[(Trp100Arg);(Val234Leu);(Gly275Asp)] and paternally inherited c.977T>G, p.(Val326Gly) PMID: 30476144: A boy with mat UPD homozygous c.(298T>A; 700G>C; 824G>C) A girl with maternally inherited c.(298T>A, 700G>C, 824G>A) and paternally inherited c.569G>A, p.(Gly190Glu); to: THOC6 homozygous or compound heterozygous variants are associated with Beaulieu-Boycott-Innes syndrome. Clinical spectrum is heterogenous, with major phenotype DD and ID (Note that this gene is already on the ID panel). Some are affected with structural cardiac anomalies, therefore not all individuals with BBIS have cardiac anomalies (hence, not a major phenotype). PMID 35426486: Two siblings with maternally inherited c.[298T>A;700G>T;824G>A], p.[(Trp100Arg);(Val234Leu);(Gly275Asp)] and paternally inherited c.977T>G, p.(Val326Gly) PMID: 30476144: A boy with mat UPD homozygous c.(298T>A; 700G>C; 824G>C) A girl with maternally inherited c.(298T>A, 700G>C, 824G>A) and paternally inherited c.569G>A, p.(Gly190Glu) |
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| Mendeliome v1.1362 | THOC6 | Ling Sun reviewed gene: THOC6: Rating: AMBER; Mode of pathogenicity: None; Publications: 35426486, 30476144; Phenotypes: VSD/ASD, severe aortic and left ventricular hypoplasia, Mild dilation of the right chambers and a mild myocardial hypertrophy secondary to a chronic hypertension, ventriculomegaly; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1362 | DAW1 | Zornitza Stark Phenotypes for gene: DAW1 were changed from Primary ciliary dyskinesia, MONDO:0016575; Visceral heterotaxy, MONDO:0018677 to Primary ciliary dyskinesia, with or without heterotaxy, MIM#620570 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1361 | DAW1 | Zornitza Stark reviewed gene: DAW1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Primary ciliary dyskinesia, with or without heterotaxy, MIM#620570; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1358 | PSMB10 | Zornitza Stark edited their review of gene: PSMB10: Added comment: PMID 37600812: 3 additional unrelated patients with compound heterozygous variants with structural modelling of proteasome assembly.; Changed rating: GREEN; Changed publications: 31783057, 37600812 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1358 | FYB1 | Zornitza Stark Marked gene: FYB1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1357 | FYB1 |
Zornitza Stark gene: FYB1 was added gene: FYB1 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: FYB1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FYB1 were set to 25516138; 25876182 Phenotypes for gene: FYB1 were set to Thrombocytopenia 3, MIM# 273900 Review for gene: FYB1 was set to GREEN Added comment: Two families with LoF variants and segregation reported in the literature. Aware of two additional cases through clinical testing (Prevention Genetics). Good functional evidence, including mouse models. Moderate by ClinGen, though note score was in 'Strong' range and downgraded due to two families in the literature only. Sources: Expert Review |
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| Mendeliome v1.1356 | MCTS1 | Zornitza Stark Marked gene: MCTS1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1355 | MCTS1 |
Zornitza Stark gene: MCTS1 was added gene: MCTS1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MCTS1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: MCTS1 were set to 37875108 Phenotypes for gene: MCTS1 were set to Inherited susceptibility to mycobacterial diseases, MONDO:0019146, MCTS1-related Review for gene: MCTS1 was set to GREEN Added comment: 6 male subjects from 5 kindreds with LOF MCTS-1 variants with MSMD. Extensive ex-vivo functional validation and mouse model. Sources: Literature |
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| Mendeliome v1.1354 | SGSM3 | Zornitza Stark Marked gene: SGSM3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1353 | FMNL2 | Zornitza Stark Marked gene: FMNL2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1351 | FMNL2 |
Achchuthan Shanmugasundram gene: FMNL2 was added gene: FMNL2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: FMNL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: FMNL2 were set to 34043722 Phenotypes for gene: FMNL2 were set to inflammatory bowel disease, MONDO:0005265 Mode of pathogenicity for gene: FMNL2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: FMNL2 was set to AMBER Added comment: A patient was reported with a de novo heterozygous FMNL2 variant (p.Leu136Pro) and with severe very early onset inflammatory bowel disease (IBD). The functional characterisation of this variant showed that FMNL2 L136P protein displayed subcellular mislocalisation and deregulated protein autoinhibition indicating gain-of-function mechanism (PMID:34043722). Sources: Literature |
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| Mendeliome v1.1350 | HIST1H4J | Zornitza Stark Marked gene: HIST1H4J as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1350 | HIST1H4J | Zornitza Stark Added comment: Comment when marking as ready: New gene name: H4C11 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1350 | HIST1H4I | Zornitza Stark Marked gene: HIST1H4I as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1350 | HIST1H4I | Zornitza Stark Added comment: Comment when marking as ready: New gene name: H4C9 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1350 | HIST1H4F | Zornitza Stark Marked gene: HIST1H4F as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1350 | HIST1H4F | Zornitza Stark Added comment: Comment when marking as ready: New gene name H4C6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1350 | HIST1H4D | Zornitza Stark Marked gene: HIST1H4D as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1350 | HIST1H4D | Zornitza Stark Added comment: Comment when marking as ready: New gene name H4C4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1348 | CCDC66 | Ain Roesley Marked gene: CCDC66 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1348 | CCDC66 |
Ain Roesley Added comment: Comment when marking as ready: de novo NMD in another family 5 other de novo missense (D94E absent in nomad, T121A 25 hets, R499C 31 hets, R553Q 59 hets, K803E 40 hets) noted that there's lots of NMD variants in gnomad v4 |
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| Mendeliome v1.1348 | MYO9B | Elena Savva Phenotypes for gene: MYO9B were changed from {Celiac disease, susceptibility to, 4} MIM#609753 to Charcot-Marie-Tooth disease type 2 (MONDO:0018993), MYO9B-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1345 | MYO9B | Melanie Marty reviewed gene: MYO9B: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 36260368; Phenotypes: Charcot-Marie-Tooth disease type 2 (MONDO:0018993), MYO9B-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1344 | HEPHL1 | Ain Roesley Marked gene: HEPHL1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1343 | MIEF1 | Seb Lunke Marked gene: MIEF1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1340 | CCDC66 |
Anna Ritchie gene: CCDC66 was added gene: CCDC66 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CCDC66 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CCDC66 were set to PMID: 37852749 Review for gene: CCDC66 was set to RED Added comment: Nonsense variant (c.172C>T, p.Q58X) segregating in family with 5 affected members with high myopia (HM). Additionally, one family member with the variant displayed no symptoms, hinting at possible incomplete penetrance. Six other rare variants were identified in 200 sporadic high myopia patients that could potentially be linked to HM. A deficiency in CCDC66 might disrupt cell proliferation by influencing the mitotic process during retinal growth, leading to HM. Sources: Literature |
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| Mendeliome v1.1338 | AGPAT3 | Elena Savva Marked gene: AGPAT3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1338 | SGSM3 |
Dean Phelan gene: SGSM3 was added gene: SGSM3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SGSM3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SGSM3 were set to PMID: 37833060 Phenotypes for gene: SGSM3 were set to Neurodevelopmental disorder (MONDO:0700092), SGSM3-related Review for gene: SGSM3 was set to AMBER Added comment: PMID: 37833060 - 13 patients from 8 families of Ashkenazi Jewish origin all had the same homozygous frameshift variant (c.981dup). Predicted to cause NMD. The variant co-segregated with disease in all available family members. The affected individuals displayed mild global developmental delay and mild to moderate intellectual disability. Additional prevalent phenotypes observed included hypotonia, behavioural challenges and short stature. Considered a founder variant (1 in 52 Ashkenazi Jews carry the variant). Also present in other populations but no homozygotes in gnomAD. Sources: Literature |
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| Mendeliome v1.1337 | LRRC23 | Elena Savva Marked gene: LRRC23 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1335 | AGPAT3 |
Ee Ming Wong gene: AGPAT3 was added gene: AGPAT3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: AGPAT3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AGPAT3 were set to 37821758 Phenotypes for gene: AGPAT3 were set to Neurodevelopmental disorder (MONDO#0700092), AGPAT3-related Review for gene: AGPAT3 was set to GREEN gene: AGPAT3 was marked as current diagnostic Added comment: - Single consanguineous family with four individuals with severe intellectual disability and retinitis pigmentosa - All affected individuals were homozygous for a nonsense variant in AGPAT3, healthy unaffected individuals who were tested were heterozygous for the variant - Overexpression of mutant transcript revealed absence of AGPAT3 protein compared to WT transcript via Western blot analysis - KO AGPAT3 mouse demonstrated impaired neuronal migration Sources: Literature |
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| Mendeliome v1.1335 | HEPHL1 |
Naomi Baker gene: HEPHL1 was added gene: HEPHL1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: HEPHL1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HEPHL1 were set to PMID: 31125343; 31293895 Phenotypes for gene: HEPHL1 were set to Abnormal hair, joint laxity, and developmental delay (MIM#261990) Review for gene: HEPHL1 was set to RED Added comment: PMID: 31125343 - Single patient reported with biallelic variants (missense and splice) that presented with abnormal hair and early cognitive delays. Authors also created a knockout mouse, with homozygotes having short, curled whiskers while heterozygotes did not have this phenotype. PMID: 31293895 - Report of curly whiskers (cw) mouse model that has a spontaneous variant (frame shifting single base insertion) in Hephl1. Sources: Literature |
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| Mendeliome v1.1334 | DLG2 | Elena Savva Marked gene: DLG2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1333 | DLG2 |
Elena Savva gene: DLG2 was added gene: DLG2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: DLG2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: DLG2 were set to PMID: 37860969 Phenotypes for gene: DLG2 were set to Intellectual disability (MONDO#0001071), DLG2-related Review for gene: DLG2 was set to AMBER Added comment: PMID: 37860969 - 13 patients from 10 families with neurodevelopmental disorders, dysmorphic features and intragenic deletions including both exonic (minimal affect all transcripts) and UTR regions. Majority of variants were inherited, some de novo. But many NMD PTCs in gnomAD (some looking messy, in noncanonical transcript etc.) Sources: Literature |
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| Mendeliome v1.1332 | CASP2 | Ain Roesley Marked gene: CASP2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1330 | LRRC23 |
Belinda Chong gene: LRRC23 was added gene: LRRC23 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: LRRC23 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LRRC23 were set to 37804054 Phenotypes for gene: LRRC23 were set to Non-syndromic male infertility due to sperm motility disorder MONDO:0017173 Review for gene: LRRC23 was set to RED Added comment: PMID 37804054: A homozygous nonsense mutation in LRRC23 (c.376C>T: p. Arg126X) in an infertile AZS patient whose parents were consanguineous. We verified the adversity of this novel mutation because of its ability to disrupt LRRC23 synthesis and impair RSs integrity. Furthermore, we demonstrated an interaction between LRRC23 and RSPH3 in vitro, indicating that LCCR23 is associated with RS in humans. Meanwhile, the LRRC23-mutant patient had a good prognosis following intracytoplasmic sperm injection. Sources: Literature |
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| Mendeliome v1.1330 | MIEF1 |
Lucy Spencer gene: MIEF1 was added gene: MIEF1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MIEF1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: MIEF1 were set to 33632269 Phenotypes for gene: MIEF1 were set to Optic atrophy 14 (MIM#620550) Review for gene: MIEF1 was set to AMBER Added comment: PMID: 33632269 Inherited optic neuropathies cohort from france with nothing found in OPA1, OPA3 and WFS1 or mtDNA. 2 individuals (55 and 47yo) found to have missense variant in MIEF1, p.Arg146Trp has 35 hets 0 homs in gnomad, p.Tyr240Asn is absent. Both have non-syndromic late onset inherited optic neuropathies characterized by initial loss of peripheral visual fields. Functional studies in HeLa cells- both missense localised to the mitochondria and formed oligomers similar to WT. MIEF1 normally regulates mitochondrial fission dynamics and causes an increase in mitochondrial fusion events, however both missense variants caused a significantly decreased mitochondrial fusion events. Sources: Literature |
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| Mendeliome v1.1330 | CASP2 |
Lisa Norbart gene: CASP2 was added gene: CASP2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CASP2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CASP2 were set to 37880421 Phenotypes for gene: CASP2 were set to neurodevelopmental disorder MONDO:0700092, CASP2-related Penetrance for gene: CASP2 were set to Complete Review for gene: CASP2 was set to GREEN gene: CASP2 was marked as current diagnostic Added comment: 7 patients from 5 families 4 families hom for PTCs, 1 family Chet for splice+PTC RNA studies done for the splice to indicate usage of two cryptic splice donor sites 5/5 have ID/dev delay 1/5 has seizures 2/5 hypotonia 3/5 lissencephaly (pachygyria and cortical thickening) Sources: Literature |
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| Mendeliome v1.1330 | CD81 | Achchuthan Shanmugasundram reviewed gene: CD81: Rating: GREEN; Mode of pathogenicity: None; Publications: 35849269; Phenotypes: Immunodeficiency, common variable, 6, OMIM:613496; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1327 | ELANE | Michelle Torres reviewed gene: ELANE: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 33968054, 3124897; Phenotypes: Neutropaenia, severe congenital 1, autosomal dominant, MIM# 202700, Neutropaenia, cyclic, MIM# 162800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1327 | AXIN1 |
Zornitza Stark edited their review of gene: AXIN1: Added comment: PMID: 37582359 - four families (7 individuals) with three homozygous truncating variants. - all variant shown to result in reduced protein, though 1/3 would be NMD predicted - Probands had macrocephaly (4/6), GDD (3/7), hip dysplasia (5/6), cardiac anomalies eg. VSD/ASD (3/7), cranial hyperostosis and vertebral endplate sclerosis; Changed rating: GREEN; Changed publications: 37582359; Changed phenotypes: Craniometadiaphyseal osteosclerosis with hip dysplasia, MIM# 620558; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal |
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| Mendeliome v1.1325 | HMBS | Zornitza Stark edited their review of gene: HMBS: Added comment: Rare families with bi-allelic disease reported.; Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1324 | GPR156 | Zornitza Stark Phenotypes for gene: GPR156 were changed from Sensorineural hearing loss, MONDO:60700002, GPR156-related to Deafness, autosomal recessive 121, MIM# 620551 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1323 | VRK1 | Zornitza Stark Phenotypes for gene: VRK1 were changed from Pontocerebellar hypoplasia type 1A, MIM# 607596; Adult-onset spinal muscular atrophy without pontocerebellar hypoplasia to Pontocerebellar hypoplasia type 1A, MIM# 607596; Adult-onset spinal muscular atrophy without pontocerebellar hypoplasia; Neuronopathy, distal hereditary motor, autosomal recessive 10, MIM# 620542 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1322 | VRK1 | Zornitza Stark edited their review of gene: VRK1: Changed phenotypes: Pontocerebellar hypoplasia type 1A, MIM# 607596, Adult-onset spinal muscular atrophy without pontocerebellar hypoplasia, Neuronopathy, distal hereditary motor, autosomal recessive 10, MIM# 620542 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1322 | HAND2 | Zornitza Stark Phenotypes for gene: HAND2 were changed from Congenital heart disease to Congenital heart disease, MONDO:0005453, HAND2-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1321 | KDM5B | Zornitza Stark Phenotypes for gene: KDM5B were changed from Mental retardation, autosomal recessive 65 MIM#618109; Intellectual disability and/or autism, autosomal dominant to Mental retardation, autosomal recessive 65 MIM#618109; Neurodevelopmental disorder (MONDO#0700092), KDM5B-related, autosomal dominant | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1319 | PTPN4 |
Bryony Thompson changed review comment from: >3 unrelated probands and supporting mouse model PMID: 17953619 - knockout mouse model has impaired motor learning and cerebellar synaptic plasticity PMID: 25424712 - twins with a de novo whole gene deletion and a Rett-like neurodevelopmental disorder PMID: 30238967 - mosaic de novo variant (p.Leu72Ser) identified in a child with developmental delay, autistic features, hypotonia, increased immunoglobulin E and dental problems. Also supporting mouse assays demonstrating loss of protein expression in dendritic spines DOI: https://doi.org/10.1016/j.xhgg.2021.100033 - missense and truncating variants in six unrelated individuals with varying degrees of intellectual disability or developmental delay. 5 were able to undergo segregation analysis and found to be de novo. Sources: Literature; to: >3 unrelated probands and supporting mouse model PMID: 17953619 - knockout mouse model has impaired motor learning and cerebellar synaptic plasticity PMID: 25424712 - twins with a de novo whole gene deletion and a Rett-like neurodevelopmental disorder PMID: 30238967 - mosaic de novo variant (p.Leu72Ser) identified in a child with developmental delay, autistic features, hypotonia, increased immunoglobulin E and dental problems. Also supporting mouse assays demonstrating loss of protein expression in dendritic spines PMID: 34527963 - missense and truncating variants in six unrelated individuals with varying degrees of intellectual disability or developmental delay. 5 were able to undergo segregation analysis and found to be de novo. Sources: Literature |
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| Mendeliome v1.1318 | ZFHX3 | Zornitza Stark edited their review of gene: ZFHX3: Added comment: 41 individuals with protein truncating variants (PTVs) or (partial) deletions of ZFHX3. Presentations included (mild) ID and/or behavioural problems, postnatal growth retardation, feeding difficulties, dysmorphism (rarely cleft palate). Nuclear abundance of ZFHX3 increases during human brain development and neuronal differentiation in neural stem cells and SH-SY5Y cells, ZFHX3 interacts with the chromatin remodelling BRG1/Brm-associated factor complex and the cleavage and polyadenylation complex. ZFHX3 haploinsufficiency associates with a specific DNA methylation profile in leukocyte-derived DNA, and participates in chromatin remodelling and mRNA processing.; Changed publications: 37292950; Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, ZFHX3-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1316 | EPHA2 | Zornitza Stark Phenotypes for gene: EPHA2 were changed from cataract 6 multiple types MONDO:0007288 to cataract 6 multiple types MONDO:0007288; microphthalmia, MONDO:0021129, EPHA2-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1313 | ADAMTS15 | Zornitza Stark Phenotypes for gene: ADAMTS15 were changed from Arthrogryposis (MONDO:0008779), ADMATS15-related to Arthrogryposis, distal, type 12, MIM# 620545 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1312 | ADAMTS15 | Zornitza Stark reviewed gene: ADAMTS15: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Arthrogryposis, distal, type 12, MIM# 620545; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1312 | DNAJB2 | Elena Savva Phenotypes for gene: DNAJB2 were changed from Spinal muscular atrophy, distal, autosomal recessive, 5, MIM# 614881; MONDO:0014866 to Neuronopathy, distal hereditary motor, autosomal recessive 5 (MIM#614881) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1311 | DNAJB2 | Lauren Rogers reviewed gene: DNAJB2: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuronopathy, distal hereditary motor, autosomal recessive 5 (MIM#614881); Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1311 | SPTAN1 | Zornitza Stark Phenotypes for gene: SPTAN1 were changed from Developmental and epileptic encephalopathy 5, MIM# 613477; Hereditary spastic paraplegia MONDO:0019064, SPTAN1-related; Neuronopathy, distal hereditary motor, 11, autosomal dominant, MIM# 620528 to Developmental and epileptic encephalopathy 5, MIM# 613477; Hereditary spastic paraplegia MONDO:0019064, SPTAN1-related; Neuronopathy, distal hereditary motor, 11, autosomal dominant, MIM# 620528; Autosomal dominant spastic paraplegia-91, with or without cerebellar ataxia (SPG91), MIM#620538 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1310 | SPTAN1 | Zornitza Stark edited their review of gene: SPTAN1: Changed phenotypes: Developmental and epileptic encephalopathy 5, MIM# 613477, Hereditary spastic paraplegia MONDO:0019064, SPTAN1-related, Neuronopathy, distal hereditary motor, 11, autosomal dominant, MIM# 620528, Autosomal dominant spastic paraplegia-91, with or without cerebellar ataxia (SPG91), MIM#620538 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1310 | COQ7 | Zornitza Stark Phenotypes for gene: COQ7 were changed from Coenzyme Q10 deficiency, primary, 8 MIM#616733 to Coenzyme Q10 deficiency, primary, 8 MIM#616733; Neuronopathy, distal hereditary motor, autosomal recessive 9, MIM# 620402 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1308 | COQ7 | Zornitza Stark reviewed gene: COQ7: Rating: GREEN; Mode of pathogenicity: None; Publications: 36758993, 36759155; Phenotypes: Neuronopathy, distal hereditary motor, autosomal recessive 9, MIM# 620402; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1305 | FAM83G | Zornitza Stark Phenotypes for gene: FAM83G were changed from Palmoplantar keratoderma, curly scalp hair and toenail dystrophy to Hereditary palmoplantar keratoderma, MONDO:0019272, FAM83G-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1304 | FAM83G | Zornitza Stark edited their review of gene: FAM83G: Changed phenotypes: Hereditary palmoplantar keratoderma, MONDO:0019272, FAM83G-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1300 | IL23R | Zornitza Stark edited their review of gene: IL23R: Added comment: PMID 36763636: Six individuals from four unrelated Iranian kindreds with AR complete IL-23R deficiency presenting MSMD with complete penetrance. Also some patients with susceptibility to CMC with incomplete penetrance.; Changed rating: GREEN; Changed publications: 30578351, 35829840, 36763636; Changed phenotypes: Immunodeficiency disease, MONDO:0021094, Inherited susceptibility to mycobacterial disease, MONDO:0019146, IL23R-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1296 | IRF1 | Zornitza Stark edited their review of gene: IRF1: Added comment: PMID 36736301: Two unrelated children with recurrent early-onset life-threatening mycobacterial diseases due to multiple mycobacteria (BCG, M. avium). Homozygous LoF vairiants with extensive supporting functional data.; Changed rating: GREEN; Changed publications: 36736301; Changed phenotypes: Inherited susceptibility to mycobacterial disease, MONDO:0019146, IRF1-related; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1296 | IRF4 | Zornitza Stark Phenotypes for gene: IRF4 were changed from Whipple's disease; [Skin/hair/eye pigmentation, variation in, 8] 611724; Combined immunodeficiency to Combined immunodeficiency, MONDO:0015131, IRF4-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1293 | IRF4 | Zornitza Stark edited their review of gene: IRF4: Added comment: PMID 36662884: Seven individuals with profound CID from six kindreds of diverse ethnic origins (Fig. 1A). All affected individuals suffered with early onset (<1 year of age) recurrent sinopulmonary infections, with the opportunistic pathogen Pneumocystis jirovecii causing pneumonia in most individuals. p.T95R variant found in all patients. Extensive functional data including knockout mouse model. The heterozygous IRF4T95R variant found in multiple unrelated families caused a fully penetrant, severe very early-onset immunodeficiency characterized by greatly enhanced susceptibility to opportunistic pathogens such as P. jirovecii and weakly pathogenic mycobacteria.; Changed rating: GREEN; Changed publications: 29537367, 36662884; Changed phenotypes: Combined immunodeficiency, MONDO:0015131, IRF4-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1292 | MCM9 | Zornitza Stark Phenotypes for gene: MCM9 were changed from Ovarian dysgenesis 4, MIM# 616185 to Ovarian dysgenesis 4, MIM# 616185; Hereditary neoplastic syndrome MONDO:0015356 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1289 | CR2 | Zornitza Stark edited their review of gene: CR2: Added comment: PMID:28499783 reported two siblings from consanguineous parents, both with a homozygous frameshift variant in CR2 and with recurrent respiratory infections and hypogammaglobulinaemia.; Changed rating: GREEN; Changed publications: 22035880, 26325596, 28499783 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1287 | HMOX1 | Zornitza Stark edited their review of gene: HMOX1: Added comment: PMID:33066778 provides a third case in support of promoting HMOX1 to green rating. This third case is a boy born to nonconsanguineous parents who presented with early onset asplenia, recurrent infections, and associated flares with bone marrow histiocyte activation with worsening interstitial lung disease and joint pain. This boy harboured compound heterozygous variants (p.L89Sfs*24 and p.Ala88Profs*51).; Changed rating: GREEN; Changed publications: 21088618, 9884342, 20844238, 33066778 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1286 | HYOU1 | Zornitza Stark changed review comment from: PMID:35549617 reported another case with homozgyous variant (p.Arg486Cys) and anemia, thrombocytopenia and severe panleukopenia and immunodeficiency.; to: PMID:35549617 reported another case with homozgyous variant (p.Arg486Cys) and anaemia, thrombocytopenia and severe panleukopenia and immunodeficiency. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1286 | HYOU1 | Zornitza Stark edited their review of gene: HYOU1: Added comment: PMID:35549617 reported another case with homozgyous variant (p.Arg486Cys) and anemia, thrombocytopenia and severe panleukopenia and immunodeficiency.; Changed rating: GREEN; Changed publications: 27913302, 35822684, 35549617 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1285 | ERLIN2 | Zornitza Stark Phenotypes for gene: ERLIN2 were changed from hereditary spastic paraplegia 18 MONDO:0012639; Spastic paraplegia 18A, autosomal dominant, MIM# 620512 to Spastic paraplegia 18, autosomal recessive, MIM# 611225; Spastic paraplegia 18A, autosomal dominant, MIM# 620512 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1284 | ERLIN2 | Zornitza Stark edited their review of gene: ERLIN2: Changed phenotypes: Spastic paraplegia 18, autosomal recessive, MIM# 611225, Spastic paraplegia 18A, autosomal dominant, MIM# 620512; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1284 | ERLIN2 | Zornitza Stark Phenotypes for gene: ERLIN2 were changed from hereditary spastic paraplegia 18 MONDO:0012639 to hereditary spastic paraplegia 18 MONDO:0012639; Spastic paraplegia 18A, autosomal dominant, MIM# 620512 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1283 | ERLIN2 | Zornitza Stark reviewed gene: ERLIN2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 18A, autosomal dominant, MIM# 620512; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1283 | MCM9 | Natalie Tan changed review comment from: Emerging association in individuals with biallelic variants of a combined phenotype of primary ovarian insufficiency and a Lynch-like syndrome/early-onset colorectal cancer (PMID: 26806154, 34556653). Monoallelic carriers have also been reported with a Lynch-like syndrome (32841224). Association of primary ovarian insufficiency with other malignancies is less clear (32613604, 34556653). See PMID 37378315 for review of literature to April 2023.; to: Emerging association in individuals with biallelic variants of a combined phenotype of primary ovarian insufficiency and a Lynch-like syndrome/early-onset colorectal cancer (PMID: 26806154, 34556653). Monoallelic carriers have also been reported with a Lynch-like syndrome (32841224). Association of primary ovarian insufficiency with other malignancies is less clear (32613604, 34556653). See PMID 37378315 for review of literature to April 2023. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1283 | MCM9 | Natalie Tan reviewed gene: MCM9: Rating: GREEN; Mode of pathogenicity: None; Publications: (PMID: 26806154, 34556653, 32841224, 32613604, 37378315); Phenotypes: Primary ovarian insufficiency, Lynch-like syndrome/colorectal cancer; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1280 | ERBIN | Zornitza Stark Phenotypes for gene: ERBIN were changed from Recurrent respiratory infections; Susceptibility to S.aureus; Eczema; Hyperextensible joints; Scoliosis; Arterial dilatation in some to Combined immunodeficiency, MONDO:0015131, ERBIN-related; Recurrent respiratory infections; Susceptibility to S.aureus; Eczema; Hyperextensible joints; Scoliosis; Arterial dilatation in some | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1279 | ERBIN | Zornitza Stark edited their review of gene: ERBIN: Changed phenotypes: Combined immunodeficiency, MONDO:0015131, ERBIN-related, Recurrent respiratory infections, Susceptibility to S.aureus, Eczema, Hyperextensible joints, Scoliosis, Arterial dilatation in some | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1279 | EPHX1 | Zornitza Stark Phenotypes for gene: EPHX1 were changed from Lipoatrophic diabetes to Hereditary lipodystrophy, MONDO:0020087, EPHX1-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1278 | EPHX1 | Zornitza Stark edited their review of gene: EPHX1: Changed phenotypes: Hereditary lipodystrophy, MONDO:0020087, EPHX1-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1274 | EIF4ENIF1 | Zornitza Stark Phenotypes for gene: EIF4ENIF1 were changed from Primary ovarian insufficiency to Primary ovarian insufficiency, MONDO:0005387, EIF4ENIF1-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1269 | STAT6 | Zornitza Stark Phenotypes for gene: STAT6 were changed from Allergic disease, MONDO:0005271, STAT6-related; early-onset multiorgan allergies to Hyper-IgE syndrome 6, autosomal dominant, with atopy and allergies, MIM# 620532 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1268 | SRP68 | Zornitza Stark Marked gene: SRP68 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1267 | SRP68 |
Zornitza Stark gene: SRP68 was added gene: SRP68 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: SRP68 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SRP68 were set to 32273475 Phenotypes for gene: SRP68 were set to Neutropenia, severe congenital, 10, autosomal recessive, MIM# 620534 Review for gene: SRP68 was set to AMBER Added comment: Single individual reported with bi-allelic LoF variants and presenting with infantile-onset severe neutropenia and recurrent infections. Multiple lines of functional evidence provided. Sources: Expert list |
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| Mendeliome v1.1263 | PLS3 | Zornitza Stark edited their review of gene: PLS3: Added comment: PMID 37751738: 8 unrelated families with affected males with an X-linked condition characterised by diaphragm defects, variable anterior body-wall anomalies, and/or facial dysmorphism. All were missense variants. A mouse knock in model of a variant identified in one of the CDH-affected families, c.1497G>C (p.Trp499Cys), shows partial perinatal lethality and recapitulates the key findings of the human phenotype, including diaphragm and abdominal-wall defects. Gain-of-function is a suggested mechanism.; Changed publications: 32655496, 25209159, 29736964, 29884797, 28777485, 24088043, 37751738; Changed phenotypes: Bone mineral density QTL18, osteoporosis - MIM#300910, congenital diaphragmatic hernia MONDO:0005711, PLS3-related; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1263 | EFCAB7 | Zornitza Stark Marked gene: EFCAB7 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1261 | CDC23 | Zornitza Stark Marked gene: CDC23 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1259 | CFAP20 | Ain Roesley Marked gene: CFAP20 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1255 | COG3 | Elena Savva Marked gene: COG3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1255 | EFCAB7 |
Melanie Marty gene: EFCAB7 was added gene: EFCAB7 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: EFCAB7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EFCAB7 were set to PMID: 37684519 Phenotypes for gene: EFCAB7 were set to Polydactyly (MONDO:0021003), EFCAB7-related Review for gene: EFCAB7 was set to AMBER Added comment: PMID: 37684519: two homozygous frameshift variants were identified by exome sequencing in four consanguinous Pakistani families, 3 families with p.(Gly277Valfs*5) and 1 family with p.(Asn451Phefs*2). Variants segregated with disease and het carriers were unaffected. Counting as 2 families to be conservative. Sources: Literature |
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| Mendeliome v1.1254 | CFAP20 |
Sarah Pantaleo gene: CFAP20 was added gene: CFAP20 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CFAP20 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CFAP20 were set to PMID:36329026 Phenotypes for gene: CFAP20 were set to Retinitis pigmentosa (MONDO:0019200) Review for gene: CFAP20 was set to GREEN Added comment: CFAP20 is a ciliopathy candidate. Demonstrate in zebrafish that cfap20 is required for motile cilia function, and in C. elegans, CFAP-20 maintains the structural integrity of non-motile cilia inner junctions, influencing sensory-dependent signalling and development. Human patients and zebrafish with CFAP20 mutations both exhibit retinal dystrophy (retinitis pigments). Hence, CFAP20 functions within a structural./functional hub centred on the inner junction that is shared between motile and non-motile cilia, and is distinct from other ciliopathy-associaetd domains or macromolecular complexes. Describe 8 individuals from 4 independent families with damaging biallelic variants (homozygous or compound heterozygous) in CFAP20 that segregate with retinal dystrophy. All variants cluster to one side of the protein, with two of the residues directly contacting alpha-tubullin. Family 1 - consanguineous set of 3 siblings from Sudan, homozygous for CFAP20 c.305G>A; p.Arg102His (they also had a homozygous variant in DYNC1LI2 however CFAP20 was considered the better candidate. Family 2 - 3 siblings from Spain, 2 with retinal dystrophy, 1 genetically tested and has c.337C>T; p.(Arg113Trp) and c.397delC; p.(Gln133Serfs*5) Family 3 - single affected family member compound het for c.164+1G>A and c.457A>G; p.(Arg153Gly). Family 4 - 3 affected siblings with generalised retinopathy and variable neurological deficits with c.164+1G>A and c.257G>A; p.(Tyr86Cys) For all families, no individuals had signs of polycystic kidney disease; however, not all individuals had kidney imaging. Visual defecit phenotype presented between adolescence and adulthood (17-56 years old). Used HEK293T cell expression studies to demonstrate a statistically significant decline of mutated CFAP20 protein levels (with the exception of p.Arg102His). To test the specific variants, they used the C.elegans orthologues. Sources: Literature |
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| Mendeliome v1.1252 | GPRASP1 | Elena Savva Marked gene: GPRASP1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1252 | MAST4 | Ain Roesley Marked gene: MAST4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1251 | CDC23 |
Michelle Torres gene: CDC23 was added gene: CDC23 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CDC23 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CDC23 were set to 37768355 Phenotypes for gene: CDC23 were set to inherited oocyte maturation defect MONDO#0014769, CDC23-related Review for gene: CDC23 was set to GREEN Added comment: Two missense variants, p.(Y329C) and p.(R330C), detected in three unrelated homozygous infertile females characterised by oocyte maturation defects. In vitro studies using HeLa cells showed either decreased protein levels (Y329C) or impaired localisation (R330C). In vivo studies in mice homozygous for Y329C reproduced patient’s phenotype. Sources: Literature |
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| Mendeliome v1.1251 | GPRASP1 |
Paul De Fazio gene: GPRASP1 was added gene: GPRASP1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GPRASP1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: GPRASP1 were set to 37787182 Phenotypes for gene: GPRASP1 were set to Arteriovenous hemangioma/malformation, GPRASP1-related, MONDO:0001256 Penetrance for gene: GPRASP1 were set to unknown Review for gene: GPRASP1 was set to AMBER gene: GPRASP1 was marked as current diagnostic Added comment: Two hemizygous germline missense variants, p.Arg1167Trp and p.Trp553Cys, were identified in three male patients presenting with spinal AVM, Cobb syndrome, or scalp AVM. The variants were inherited from unaffected heterozygous mothers. Note that p.Arg1167Trp has hemizygous (>70) and homozygous individuals reported in gnomAD. The variants were found to result in LoF in endothelial cells. Endothelial Gprasp1 knockout mice suffered a high probability of cerebral hemorrhage, AVMs, and exhibited vascular anomalies in multiple organs. Sources: Literature |
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| Mendeliome v1.1251 | COG3 |
Daniel Flanagan gene: COG3 was added gene: COG3 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: COG3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: COG3 were set to PMID: 37711075 Phenotypes for gene: COG3 were set to Neurodevelopmental disorder (MONDO#0700092), COG3-related Review for gene: COG3 was set to AMBER Added comment: Two COG3 homozygous missense variants in four individuals from two unrelated consanguineous families. Clinical phenotypes of affected individuals include global developmental delay, severe intellectual disability, microcephaly, epilepsy, facial dysmorphism, and variable neurological findings. Sources: Expert list |
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| Mendeliome v1.1249 | MAST4 |
Ain Roesley gene: MAST4 was added gene: MAST4 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MAST4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MAST4 were set to 36910266; 33057194 Phenotypes for gene: MAST4 were set to neurodevelopmental disorder MONDO:0700092, MAST4-related Penetrance for gene: MAST4 were set to Complete Review for gene: MAST4 was set to GREEN gene: MAST4 was marked as current diagnostic Added comment: PMID: 36910266 - 4 families with 4 affecteds, all de novo missense 2x borderline microcephaly (-2SD) 2x gross motor delay 2x dysmorphism 4x ID + seizures 3x abnormal brain MRI findings PMID: 33057194 - 5x de novos, 4x missense + 1x PTC Cohort of individuals with severe developmental disorder individual phenotypic information not provided Recurrent variants are Thr1471Ile (3x) and Ser1181Phe) Sources: Literature |
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| Mendeliome v1.1248 | ZBTB47 | Elena Savva Marked gene: ZBTB47 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1247 | ZBTB47 |
Elena Savva gene: ZBTB47 was added gene: ZBTB47 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ZBTB47 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: ZBTB47 were set to 37743782 Phenotypes for gene: ZBTB47 were set to Neurodevelopmental disorder (MONDO#0700092), ZBTB47-related Review for gene: ZBTB47 was set to GREEN Added comment: PMID 37743782: - 5 patients with de novo missense, 4/5 have a recurring p.Gly477Lys. Probands have intellectual disability (5/5), seizures (5/5), hypotonia (5/5), gait abnormalities, and variable movement abnormalities (5/5). - Missense variants are positioned close to His and Cys residues involved in forming C2H2 zinc fingers. - No functional studies performed - Minimal PTCs in gnomAD Sources: Literature |
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| Mendeliome v1.1246 | KIF4A | Zornitza Stark Phenotypes for gene: KIF4A were changed from Mental retardation, X-linked 100, MIM# 300923 to Mental retardation, X-linked 100, MIM# 300923; Taurodontism, microdontia, and dens invaginatus (MIM#313490) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1245 | ATP2B2 | Andrew Fennell reviewed gene: ATP2B2: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: PMID: 37675773; Phenotypes: Neurodevelopmental Disorder, MONDO:0700092, ATP2B2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1245 | ATRX | Zornitza Stark Phenotypes for gene: ATRX were changed from Alpha-thalassemia/mental retardation syndrome, MIM# 301040; Intellectual disability-hypotonic facies syndrome, X-linked, MIM# 309580 to ATR-X-related syndrome MONDO:0016980 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1244 | DLG5 | Zornitza Stark Phenotypes for gene: DLG5 were changed from Cystic kidneys, nephrotic syndrome, hydrocephalus, limb abnormalities, congenital heart disease and craniofacial malformations to Ciliopathy, MONDO:0016044, DLG5-related; Cystic kidneys, nephrotic syndrome, hydrocephalus, limb abnormalities, congenital heart disease and craniofacial malformations | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1242 | DGAT2 | Zornitza Stark Phenotypes for gene: DGAT2 were changed from axonal Charcot-Marie-Tooth disease to Charcot-Marie-Tooth disease, MONDO:0015626, DGAT2-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1238 | SPTAN1 | Zornitza Stark Phenotypes for gene: SPTAN1 were changed from Developmental and epileptic encephalopathy 5, MIM# 613477; Hereditary spastic paraplegia MONDO:0019064, SPTAN1-related; hereditary motor neuropathy to Developmental and epileptic encephalopathy 5, MIM# 613477; Hereditary spastic paraplegia MONDO:0019064, SPTAN1-related; Neuronopathy, distal hereditary motor, 11, autosomal dominant, MIM# 620528 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1237 | SPTAN1 | Zornitza Stark edited their review of gene: SPTAN1: Changed phenotypes: Developmental and epileptic encephalopathy 5, MIM# 613477, Hereditary spastic paraplegia MONDO:0019064, SPTAN1-related, Neuronopathy, distal hereditary motor, 11, autosomal dominant, MIM# 620528 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1237 | DAZL | Zornitza Stark Phenotypes for gene: DAZL were changed from Primary ovarian insufficiency to Primary ovarian failure, MONDO:0005387, DAZL-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1236 | DACH2 | Zornitza Stark Phenotypes for gene: DACH2 were changed from Primary ovarian insufficiency to Primary ovarian failure, MONDO:0005387, DACH2-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1233 | CTNNBL1 | Zornitza Stark Phenotypes for gene: CTNNBL1 were changed from Primary Immunodeficiency; Autoimmune Cytopenias; Common variable immunodeficiency to Immunodeficiency 99 with hypogammaglobulinemia and autoimmune cytopenias, MIM# 619846 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1229 | CASP4 | Zornitza Stark Marked gene: CASP4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1229 | CASP4 |
Zornitza Stark gene: CASP4 was added gene: CASP4 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: CASP4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CASP4 were set to 37647624 Phenotypes for gene: CASP4 were set to Hereditary susceptibility to infection, MONDO:0015979, CASP4-related; Susceptibility to meliodiosis Review for gene: CASP4 was set to RED Added comment: Single patient with severe disease secondary to B. pseudomallei requiring ECMO. Adjunctive IFN-γ administration as replacement for its failed induction by IL-18 promptly led to clearance of B. pseudomallei and subsequent weaning of support. Novel homozygous missense mutation in CASP4, at exon 7 c.1030C > T. Peripheral blood mononuclear cells (PBMC) of the patient and her parents showed reduced IFN-γ production, notably to IL-12 stimulation, and decreased IL-18 in response to LPS and increased IL-1B. Cloned cells show impacts on CASP4 activation and pyroptosis. Sources: Expert Review |
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| Mendeliome v1.1228 | IL36RN | Zornitza Stark Phenotypes for gene: IL36RN were changed from Psoriasis 14, pustular, MIM# 614204 to Psoriasis 14, pustular, MIM# 614204; Autoinflammatory syndrome, MONDO:0019751, IL36RN-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1226 | IL36RN | Zornitza Stark edited their review of gene: IL36RN: Added comment: Monoallelic disease: Multiple patients with systemic inflammation with monoallelic variants in IL36RN suggesting a gene dosage effect whereby GPP onset is significantly delayed in subjects with monoallelic mutations but still at high risk of systemic inflammation.; Changed publications: 21848462, 21839423, 22903787, 23648549, 25458002; Changed phenotypes: Psoriasis 14, pustular, MIM# 614204, Autoinflammatory syndrome, MONDO:0019751, IL36RN-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1226 | SNAPC4 | Zornitza Stark Phenotypes for gene: SNAPC4 were changed from Neurodevelopmental disorder (MONDO#0700092), SNAPC4-related to Neurodevelopmental disorder with motor regression, progressive spastic paraplegia, and oromotor dysfunction, MIM# 620515 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1224 | CPEB1 | Zornitza Stark Phenotypes for gene: CPEB1 were changed from Primary ovarian insufficiency to Primary ovarian insufficiency, MONDO:0005387, CPEB1-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1223 | CPA1 | Zornitza Stark Phenotypes for gene: CPA1 were changed from Susceptibility to chronic pancreatitis; Hereditary pancreatitis to Hereditary pancreatitis, MONDO:0008185, CPA1-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1222 | CPA1 | Zornitza Stark edited their review of gene: CPA1: Changed phenotypes: Hereditary pancreatitis, MONDO:0008185, CPA1-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1215 | PPP1R13L | Zornitza Stark Phenotypes for gene: PPP1R13L were changed from Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042 - PPP1R13L-related; Dilated cardiomyopathy, onset in infancy to Arrhythmogenic cardiomyopathy with or without ectodermal abnormalities, MIM#620519 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1214 | PPP1R13L | Zornitza Stark edited their review of gene: PPP1R13L: Changed phenotypes: Arrhythmogenic cardiomyopathy with or without ectodermal abnormalities, MIM#620519 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1214 | DEPDC5 | Zornitza Stark Phenotypes for gene: DEPDC5 were changed from Epilepsy, familial focal, with variable foci 1, MIM#604364 to Epilepsy, familial focal, with variable foci 1, MIM#604364; Developmental and epileptic encephalopathy 111, MIM# 620504 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1209 | CBY1 | Zornitza Stark Phenotypes for gene: CBY1 were changed from intellectual disability; cerebellar ataxia; molar tooth sign; polydactyly; Joubert syndrome to Joubert syndrome, MONDO:0018772, CBY1-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1206 | C1orf194 | Zornitza Stark Phenotypes for gene: C1orf194 were changed from Charcot-Marie-Tooth disease, intermediate or demyelinating to Charcot-Marie-Tooth disease, intermediate or demyelinating, MONDO:0015626, C1orf194-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1205 | C1orf194 | Zornitza Stark edited their review of gene: C1orf194: Changed rating: AMBER; Changed phenotypes: Charcot-Marie-Tooth disease, intermediate or demyelinating, MONDO:0015626, C1orf194; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1204 | BET1 | Zornitza Stark Phenotypes for gene: BET1 were changed from Muscular dystrophy; Epilepsy to Muscular dystrophy, MONDO:0019950, BET1-related; Epilepsy | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1203 | BCL9L | Zornitza Stark Phenotypes for gene: BCL9L were changed from Heterotaxy; Congenital Heart Disease to Heterotaxy syndrome, MONDO:0018677, BCL9L-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1202 | B3GNT2 | Zornitza Stark Phenotypes for gene: B3GNT2 were changed from Muscular dystrophy-dystroglycanopathy to Muscular dystrophy-dystroglycanopathy, MONDO:0018276, B3GNT2-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1201 | B3GNT2 | Zornitza Stark edited their review of gene: B3GNT2: Changed phenotypes: Muscular dystrophy-dystroglycanopathy, MONDO:0018276, B3GNT2-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1198 | ATP2B4 | Zornitza Stark Phenotypes for gene: ATP2B4 were changed from Hereditary spastic paraplegia to Hereditary spastic paraplegia, MONDO:0019064, ATP2B4-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1196 | ASTN2 | Zornitza Stark edited their review of gene: ASTN2: Added comment: Rare CNVs also reported.; Changed publications: 28940097, 34412080 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1195 | ARIH1 | Zornitza Stark Phenotypes for gene: ARIH1 were changed from Thoracic aortic aneurysm to Thoracic aortic aneurysm, MONDO:0005396, ARIH1-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1194 | ARHGAP29 | Zornitza Stark Phenotypes for gene: ARHGAP29 were changed from Cleft palate; cleft lip with or without cleft palate to Clefting disorder, MONDO:0000358, ARHGAP29-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1193 | ARHGAP29 | Zornitza Stark edited their review of gene: ARHGAP29: Changed phenotypes: Clefting disorder, MONDO:0000358, ARHGAP29-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1193 | ARHGAP24 | Zornitza Stark Phenotypes for gene: ARHGAP24 were changed from FSGS to FSGS, MONDO:0005363, ARHGAP24-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1192 | ARHGAP24 | Zornitza Stark edited their review of gene: ARHGAP24: Changed phenotypes: FSGS, MONDO:0005363, ARHGAP24-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1192 | ARFGEF3 | Zornitza Stark Phenotypes for gene: ARFGEF3 were changed from Dystonia to Dystonia, MONDO:0044807, ARFGEF3-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1191 | ARF3 | Zornitza Stark Phenotypes for gene: ARF3 were changed from Global developmental delay; Intellectual disability; Seizures; Morphological abnormality of the central nervous system to Neurodevelopmental disorder, MONDO:0700092, ARF3-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1190 | ARAP3 | Zornitza Stark Phenotypes for gene: ARAP3 were changed from Lymphoedema to Lymphoedema, MONDO:0019297, ARAP3-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1189 | ARAP3 | Zornitza Stark edited their review of gene: ARAP3: Changed phenotypes: Lymphoedema, MONDO:0019297, ARAP3-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1188 | MCCC1 | Bryony Thompson reviewed gene: MCCC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 36822454, 31730530; Phenotypes: 3-Methylcrotonyl-CoA carboxylase 1 deficiency MIM#210200, Organic acidurias; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1186 | ANKRD31 | Zornitza Stark Phenotypes for gene: ANKRD31 were changed from Premature ovarian failure to Premature ovarian failure, MONDO:0019852, ANKRD31-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1182 | AKR1E2 | Zornitza Stark Phenotypes for gene: AKR1E2 were changed from congenital cataracts to Cataract, MONDO:0005129, AKR1E2-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1181 | AKR1E2 | Zornitza Stark edited their review of gene: AKR1E2: Changed phenotypes: Cataract, MONDO:0005129, AKR1E2-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1181 | AKNA | Zornitza Stark Phenotypes for gene: AKNA were changed from Primary ciliary dyskinesia to Primary ciliary dyskinesia, MONDO:0016575, AKNA-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1180 | AKNA | Zornitza Stark reviewed gene: AKNA: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Primary ciliary dyskinesia, MONDO:0016575, AKNA-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1175 | ACADL | Zornitza Stark Phenotypes for gene: ACADL were changed from Pulmonary surfactant dysfunction to Hereditary pulmonary alveoral proteinosis, MONDO:0012580, ACADL-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1174 | ACADL | Zornitza Stark edited their review of gene: ACADL: Changed phenotypes: Hereditary pulmonary alveoral proteinosis, MONDO:0012580, ACADL-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1173 | SEMA3E | Lucy Spencer reviewed gene: SEMA3E: Rating: AMBER; Mode of pathogenicity: None; Publications: 15235037, 31691538, 31464029, 35628442, 32441320; Phenotypes: CHARGE syndrome MONDO:0008965, SEMA3E-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1172 | NR2F2 | Zornitza Stark Phenotypes for gene: NR2F2 were changed from 46,XX sex reversal 5 - MIM#618901; Congenital heart defects, multiple types, 4 - MIM#615779 to Krithika Murali (Victorian Clinical Genetics Services) 46,XX sex reversal 5 - MIM#618901; Congenital heart defects, multiple types, 4 - MIM#615779 Current 46,XX sex reversal 5 - MIM#618901; Congenital heart defects, multiple types, 4 - MIM#615779 Edit; 46,XX sex reversal 5 - MIM#618901; Congenital heart defects, multiple types, 4 - MIM#615779 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1170 | DBR1 | Zornitza Stark Phenotypes for gene: DBR1 were changed from {Encephalitis, acute, infection (viral)-induced, susceptibility to, 11}, MIM# 619441; Viral infections of the brainstem; Ichthyosis (MONDO#0019269), DBR1-related to {Encephalitis, acute, infection (viral)-induced, susceptibility to, 11}, MIM# 619441; Viral infections of the brainstem; Xerosis and growth failure with immune and pulmonary dysfunction syndrome, MIM# 620510 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1169 | KLK11 | Zornitza Stark Marked gene: KLK11 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1168 | KLK11 |
Zornitza Stark gene: KLK11 was added gene: KLK11 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KLK11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KLK11 were set to 36689511; 37212630 Phenotypes for gene: KLK11 were set to Ichthyosis with erythrokeratoderma, MIM# 620507 Review for gene: KLK11 was set to GREEN Added comment: Four families reported: one multiplex with variant segregating with disease in 4 affected and 4 unaffected individuals. Three additional families with de novo variants. Sources: Literature |
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| Mendeliome v1.1167 | GABBR1 | Zornitza Stark Phenotypes for gene: GABBR1 were changed from Neurodevelopmental disorder, GABBR1-related, MONDO:0700092 to Neurodevelopmental disorder with language delay and variable cognitive abnormalities, MIM#620502 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1166 | GABBR1 | Zornitza Stark edited their review of gene: GABBR1: Changed phenotypes: Neurodevelopmental disorder with language delay and variable cognitive abnormalities, MIM#620502 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1165 | FTCD |
Bryony Thompson changed review comment from: Well-established gene-disease association (see OMIM entry). Glutamate formiminotransferase deficiency is classified as a metabolic disorder by the NIH GARD (https://rarediseases.info.nih.gov/diseases/diseases-by-category/14/metabolic-disorders), and is an inborn error of amino acid metabolism. Sources: NHS GMS; to: Glutamate formiminotransferase deficiency is classified as a benign form of folate metabolism disorder and an inborn error of amino acid metabolism without clinically significant phenotype (http://iembase.com/disorder/47). |
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| Mendeliome v1.1165 | MAP1B | Zornitza Stark Phenotypes for gene: MAP1B were changed from Intellectual disability; seizures; PVNH; dysmorphic features; Periventricular nodular heterotopia 9, MIM# 618918 to Intellectual disability; seizures; PVNH; dysmorphic features; Periventricular nodular heterotopia 9, MIM# 618918; Deafness, autosomal dominant 83, MIM# 619808 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1164 | MAP1B | Zornitza Stark edited their review of gene: MAP1B: Added comment: At least 3 families reported with isolated deafness and mono-allelic variants.; Changed phenotypes: Intellectual disability, seizures, PVNH, dysmorphic features, Periventricular nodular heterotopia 9, MIM# 618918, Deafness, autosomal dominant 83, MIM# 619808 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1164 | GJA4 | Zornitza Stark Marked gene: GJA4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1163 | GJA4 |
Zornitza Stark gene: GJA4 was added gene: GJA4 was added to Mendeliome. Sources: Expert Review somatic tags were added to gene: GJA4. Mode of inheritance for gene: GJA4 was set to Other Publications for gene: GJA4 were set to 33912852 Phenotypes for gene: GJA4 were set to Cavernous hemangioma, MONDO:0003155, GJA4-related Review for gene: GJA4 was set to GREEN Added comment: Recurrent somatic GJA4 c.121G>T (p.Gly41Cys) mutation as a driver of hepatic (n=12) and cutaneous (n=3) vascular malformations. Induced changes in cell morphology and activated serum/glucocorticoid-regulated kinase 1 (SGK1), a serine/threonine kinase known to regulate cell proliferation and apoptosis, via non-canonical activation, in lentiviral transduction of primary human endothelial cells. Sources: Expert Review |
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| Mendeliome v1.1162 | COL4A3BP | Zornitza Stark Phenotypes for gene: COL4A3BP were changed from Mental retardation, autosomal dominant 34, MIM# 616351 to Intellectual developmental disorder 34 (MIM#616351) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1158 | DBR1 |
Zornitza Stark edited their review of gene: DBR1: Added comment: PMID: 37656279: - A homozygous missense as a founder recessive DBR1 variant in four consanguineous families. - Total of 7 affected children. WES done for one proband from each family. - Consistent features include prematurity, severe intrauterine growth deficiency, congenital ichthyosis-like presentation (collodion membrane, severe skin peeling and xerosis), and death before the first year of life. - RNA and protein studies using fibroblasts derived from a patient are supportive of pathogenicity: RNA-seq, rt-qPCR and western blotting, showing marked reduction of DBR1 level and intronic RNA lariat accumulation in the patient sample. - Haplotype analysis revealed that the four families all share a haplotype extending at least 2.27 Mb around the c.200A>G p.(Tyr67Cys) DBR1 founder variant. - Authors proposed this is a novel DBR1-related developmental disorder that is distinct from DBR1-related encephalitis susceptibility, and highlighted the apparent lack of correlation with the degree of DBR1 deficiency.; Changed publications: 29474921, 37656279; Changed phenotypes: {Encephalitis, acute, infection (viral)-induced, susceptibility to, 11}, MIM# 619441, Viral infections of the brainstem, Ichthyosis (MONDO#0019269), DBR1-related |
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| Mendeliome v1.1156 | APOO |
Zornitza Stark edited their review of gene: APOO: Added comment: PMID: 37649161 1 family, 2 individuals (male & female) with same NMD variant c.532G>T (p.E178*), maternally inherited (mother unaffected). Both died before 18 months of age with partial agenesis of the corpus callosum, bilateral congenital cataract, hypothyroidism, and severe immune deficiencies. Other phenotypes included partial syndactyly of the 2nd and 3rd toes, wrinkled palm, and sole skin. Functional studies included site directed mutagenesis. This mutation resulted in a highly unstable and degradation prone MIC26 protein, yet the remaining minute amounts of mutant MIC26 correctly localized to mitochondria and interacted physically with other MICOS subunits. MIC26 KO cells expressing MIC26 harboring the respective APOO/MIC26 mutation showed mitochondria with perturbed cristae architecture and fragmented morphology resembling MIC26 KO cells.; Changed publications: 37649161; Changed phenotypes: Mitochondrial disease, MONDO:0044970, APOO-related, Developmental delay, Lactic acidosis, Muscle weakness, Hypotonia, Repetitive infections, Cognitive impairment, Autistic behaviour |
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| Mendeliome v1.1156 | RAB5C |
Rylee Peters changed review comment from: 12 individuals with nine different heterozygous de novo variants in RAB5C. 9 with missense, 1 inframe duplication and 2 stop-gains (clinically more severe). All has mild-severe ID, 4/12 have epilepsy, 6/12 have macrocephaly (more than 3 SD). Sources: Literature; to: 12 individuals with nine different heterozygous de novo variants in RAB5C. 9 with missense, 1 inframe duplication and 2 stop-gains (clinically more severe). All have mild-severe ID, 4/12 have epilepsy, 6/12 have macrocephaly (more than 3 SD). Sources: Literature |
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| Mendeliome v1.1156 | CAP2 | Zornitza Stark Phenotypes for gene: CAP2 were changed from Dilated cardiomyopathy to Cardiomyopathy, dilated, 2I (MIM#620462) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1155 | COL4A3BP |
Ee Ming Wong changed review comment from: - Thirty-one unrelated individuals with twenty-two distinct missense variants. The majority of variants were de novo. - Several variants transfected into HeLa cells demonstrated gain of CERT activity - CERT gain of function in Drosophila melanogaster led to head and brain size defects and impaired locomotor activity, which was corrected by pharmacological inhibition of CERT; to: - current HGNC symbol: CERT1 - Thirty-one unrelated individuals with twenty-two distinct missense variants. The majority of variants were de novo. - Several variants transfected into HeLa cells demonstrated gain of CERT activity - CERT gain of function in Drosophila melanogaster led to head and brain size defects and impaired locomotor activity, which was corrected by pharmacological inhibition of CERT |
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| Mendeliome v1.1153 | CAP2 | Zornitza Stark reviewed gene: CAP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30518548, 33083013, 34862840; Phenotypes: Cardiomyopathy, dilated, 2I (MIM#620462); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1153 | RAB5C | Ain Roesley Marked gene: RAB5C as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1152 | RAB5C |
Rylee Peters gene: RAB5C was added gene: RAB5C was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RAB5C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RAB5C were set to PMID: 37552066 Phenotypes for gene: RAB5C were set to Neurodevelopmental disorder MONDO:0700092, RAB5C-related Penetrance for gene: RAB5C were set to Complete Review for gene: RAB5C was set to GREEN gene: RAB5C was marked as current diagnostic Added comment: 12 individuals with nine different heterozygous de novo variants in RAB5C. 9 with missense, 1 inframe duplication and 2 stop-gains (clinically more severe). All has mild-severe ID, 4/12 have epilepsy, 6/12 have macrocephaly (more than 3 SD). Sources: Literature |
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| Mendeliome v1.1149 | PPP1R3F | Zornitza Stark Marked gene: PPP1R3F as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1145 | FTH1 | Bryony Thompson Added comment: Comment on list classification: Article describing the gene-disease association with neuroferritinopathy now published in HGG advances | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1142 | C3 | Ain Roesley edited their review of gene: C3: Added comment: Multiple individuals reported with mono-allelic variants and aHUS. At least one report of biallelic variants.; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1142 | SOX11 | Zornitza Stark Phenotypes for gene: SOX11 were changed from Coffin-Siris syndrome 9, MIM# 615866; Congenital abnormalities of the kidneys and urinary tract to Intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, MIM# 615866; Congenital abnormalities of the kidneys and urinary tract | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1140 | SOX11 | Zornitza Stark edited their review of gene: SOX11: Added comment: Over 40 additional individuals reported, e.g. PMID 35341651. The phenotype that has emerged over time is distinct from patients with mutations in ARID1B (614556) and Coffin-Siris syndrome-1 (135900). Patients with IDDMOH tend to be microcephalic and have ocular motor apraxia, abnormal eye morphology, or hypogonadotropic hypogonadism.; Changed publications: 29459093, 24886874, 33086258, 33785884, 35642566, 35341651 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1140 | SOX11 | Zornitza Stark edited their review of gene: SOX11: Changed phenotypes: Intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, MIM# 615866, Congenital abnormalities of the kidneys and urinary tract | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1133 | CRELD1 | Zornitza Stark Phenotypes for gene: CRELD1 were changed from Atrioventricular septal defect, partial, with heterotaxy syndrome, MIM# 606217 to Developmental and epileptic encephalopathy, MONDO:0100062, CRELD1-related; Atrioventricular septal defect, partial, with heterotaxy syndrome, MIM# 606217 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1130 | CRELD1 | Zornitza Stark edited their review of gene: CRELD1: Added comment: Emerging association between bi-alleic variants in CRELD1 and DEE.; Changed rating: GREEN; Changed phenotypes: Developmental and epileptic encephalopathy, MONDO:0100062, CRELD1-related, Atrioventricular septal defect, partial, with heterotaxy syndrome, MIM# 606217; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1129 | NEUROG1 | Zornitza Stark Marked gene: NEUROG1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1125 | THPO | Zornitza Stark edited their review of gene: THPO: Added comment: 5 families reported with bi-allelic variants and thrombocytopenia with progression to pancytopenia, aplastic anemia, and bone marrow failure.; Changed publications: 9425899, 10583217, 32150607, 28466964, 24085763, 28559357, 29191945, 36226497; Changed phenotypes: Thrombocythemia 1, MIM# 187950, Thrombocytopenia 9, MIM# 620478, Amegakaryocytic thrombocytopenia, congenital, 2, MIM# 620481; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1125 | NEUROG1 |
Achchuthan Shanmugasundram gene: NEUROG1 was added gene: NEUROG1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NEUROG1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NEUROG1 were set to 23419067; 26077850; 33439489; 36647078 Phenotypes for gene: NEUROG1 were set to Cranial dysinnervation disorder, congenital, with absent corneal reflex and developmental delay, OMIM:620469 Review for gene: NEUROG1 was set to GREEN Added comment: There are four unrelated cases reported with global developmental delay/ intellectual disability. Hence, this gene can be added with green rating in the intellectual disability panel. PMID:23419067 - A homozygous micro deletion of NEUROG1 was identified in a six year-old boy presenting with profound sensorineural deafness, balance disorder, severe disorder of oral motor function, and mild global developmental delay. His IQ was normal. PMID:26077850 - A homozygous NEUROG1 variant (p.Arg116Leu) was identified in a 12 year-old boy presented with syndromic corneal opacity, mild intellectual disability and absent corneal reflex. PMID:33439489 - A homozygous loss-of-function variant (p.Glu68Ter) was identified in a 12 year-old boy presenting with hypotonia, global developmental delay, sensorineural hearing loss, and keratoconjunctivitis due to lack of corneal reflex. This patient had a global IQ of 62 at the age of ten. PMID:36647078 - A female proband was identified with a novel homozygous truncating frameshift variant (p.Thr78ProfsTer122 and was reported with profound global developmental delay, autism spectrum disorder, hearing loss, corneal opacity and no eye blinking. Her sister also had a similar, but less severe phenotype and also harboured the same variant at homozygous state. This gene has been associated with relevant phenotypes in OMIM (MIM #620469), but not in Gene2Phenotype. Sources: Literature |
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| Mendeliome v1.1125 | STAT5B |
Zornitza Stark changed review comment from: Both bi-allelic and mono allelic (GoF) inheritance reported. AD GoF phenotype: increased IgE, growth failure, eczema but no immune defects compared to AR phenotype (modestly decreased T cells, reduced Tregs and function, hypergammaglobulinaemia, increased IgE).; to: Both bi-allelic and mono allelic (GoF) inheritance reported. AD GoF phenotype: increased IgE, growth failure, eczema but no immune defects compared to AR phenotype (modestly decreased T cells, reduced Tregs and function, hypergammaglobulinaemia, increased IgE). Somatic variants also reported. |
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| Mendeliome v1.1124 | PPOX | Zornitza Stark Phenotypes for gene: PPOX were changed from Porphyria variegata , MIM#176200 to Porphyria variegata , MIM#176200; Variegate porphyria, childhood-onset, MIM# 620483 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1121 | PPOX | Zornitza Stark edited their review of gene: PPOX: Added comment: Bi-allelic variants cause childhood onset disease.; Changed publications: 12357337, 32247286, 23324528, 27982422, 9811936, 11286631, 33159949; Changed phenotypes: Porphyria variegata , MIM#176200, Variegate porphyria, childhood-onset, MIM# 620483; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1119 | ACTB | Zornitza Stark Phenotypes for gene: ACTB were changed from Baraitser-Winter syndrome 1 243310; ACTB-related neurodevelopment disorder to Baraitser-Winter syndrome 1 243310; Thrombocytopenia 8, with dysmorphic features and developmental delay, MIM# 620475; ACTB-related neurodevelopment disorder | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1117 | APOL1 |
Zornitza Stark edited their review of gene: APOL1: Added comment: Assigned Definitive gene-disease validity by the ClinGen Glomerulopathy GCEP - Classification - 09/28/2021 Increased risk of kidney and glomerular diseases in persons carrying two of the risk alleles in this gene: G1/G1, G2/G2 and compound heterozygous G1/G2. PMID: 20647424 - first study to identify G1 & G2 alleles associated with risk of renal disease. Comparing participants with zero or 1 risk allele of APOL1 to participants with 2 risk alleles provided an odds ratio for FSGS of 10.5 (CI, 6.0-18.4). This analysis supported a completely recessive pattern of inheritance. PMID: 25993319 - only G1 and G2 confer renal risk, and other common and rare APOL1 missense variants, including the archaic G3 haplotype, do not contribute to sporadic FSGS and HIVAN rs73885319 (G1) OR 9.66, p=9.97E-25 rs60910145 (G1) OR 9.75, p=9.04E-24 rs71785313 (G2) OR 5.69, p=3.39E-06 2 APOL1 risk alleles OR 18.31, p=3.31E-58 PMID: 34350953 - recessive gain-of-function toxicity mouse model recapitulates human kidney disease G1: p.Ser342Gly, AFR/AA gnomAD v2.1 AF 0.2276 (5,671/24,920 alleles, 687 homozygotes) p.Ile384Met, AFR/AA gnomAD v2.1 AF 0.2278 (5,487/24,082 alleles, 662 homozygotes) G2: p.Asn388_Tyr389del, AFR/AA gnomAD v2.1 AF 0.1402(3,402/24,268 alleles, 224 homozygotes AMBER status due to these being susceptibility alleles, and evidence being limited to these specific variants.; Changed rating: AMBER |
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| Mendeliome v1.1117 | GOSR2 |
Achchuthan Shanmugasundram changed review comment from: Four children from two sibships from an extended consanguineous Palestinian family were reported with congenital profound hearing loss, whereas the parents of both sibships are first cousins with normal hearing. The families reported occasional febrile seizures in infancy for each of the deaf children, but these did not persist into adolescence. These affected children were identified with autosomal recessive GOSR2 variant, c.1A > C, p.Met1Leu. This variant appeared once in the gnomAD database, as a heterozygote, and not in any of ~2000 in-house controls of Palestinian ancestry. All previously reported cases with biallelic GOSR2 variants had normal hearing and hence the differences in translation efficiency due to the effect of this variant may be responsible for this hearing loss phenotype (PMID:37074134).; to: This gene should be added in 'Deafness_IsolatedAndComplex' panel with red rating. Four children from two sibships from an extended consanguineous Palestinian family were reported with congenital profound hearing loss, whereas the parents of both sibships are first cousins with normal hearing. The families reported occasional febrile seizures in infancy for each of the deaf children, but these did not persist into adolescence. These affected children were identified with autosomal recessive GOSR2 variant, c.1A > C, p.Met1Leu. This variant appeared once in the gnomAD database, as a heterozygote, and not in any of ~2000 in-house controls of Palestinian ancestry. All previously reported cases with biallelic GOSR2 variants had normal hearing and hence the differences in translation efficiency due to the effect of this variant may be responsible for this hearing loss phenotype (PMID:37074134). |
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| Mendeliome v1.1117 | GOSR2 | Achchuthan Shanmugasundram reviewed gene: GOSR2: Rating: RED; Mode of pathogenicity: None; Publications: 37074134; Phenotypes: hearing loss, autosomal recessive, MONDO:0019588; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1117 | DDRGK1 | Ain Roesley Marked gene: DDRGK1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1116 | DDRGK1 |
Ain Roesley gene: DDRGK1 was added gene: DDRGK1 was added to Mendeliome. Sources: Literature founder tags were added to gene: DDRGK1. Mode of inheritance for gene: DDRGK1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DDRGK1 were set to 28263186; 35377455; 35670300; 36243336 Phenotypes for gene: DDRGK1 were set to Spondyloepimetaphyseal dysplasia, Shohat type (MIM#602557) Review for gene: DDRGK1 was set to GREEN gene: DDRGK1 was marked as current diagnostic Added comment: RNA and protein studies performed for the splice variant. These two variants likely represents founder variants PMID:28263186 reported six individuals from three different families of Iraqi Jewish descent (three patients from family 1 and one individual each from families 2-4) identified with homozygous c.408+1G>A donor splice site loss-of-function mutation in DDRGK1 and presented with Shohat-type spondyloepimetaphyseal dysplasia (SEMD). It is a skeletal dysplasia that affects cartilage development. PMID: 35670300 reported two unrelated cases of Moroccan descent identified with homozygous missense variant c.406G>A and presented with SEMD. PMID:36243336 reported an Omani female patient identified with the same homozygous variant as the Iraqi cases and was reported with SEMD. In addition, studies on both zebrafish and mouse models confirms the physiological role of DDRGK1 in the development and maintenance of the growth plate cartilage and deficiency of DDRGK1 recapitulate the clinical phenotype of short stature and joint abnormalities observed in patients with Shohat type SEMD (PMID:28263186; PMID:35377455). Sources: Literature |
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| Mendeliome v1.1115 | FBXO31 | Zornitza Stark Phenotypes for gene: FBXO31 were changed from Mental retardation, autosomal recessive 45, MIM#615979; Cerebral palsy, MONDO:0006497, FBXO31-related; Spastic-dystonic cerebral palsy, intellectual disability, de novo dominant to Intellectual developmental disorder, autosomal recessive 45 (MIM#615979; Cerebral palsy, MONDO:0006497, FBXO31-related; Spastic-dystonic cerebral palsy, intellectual disability, de novo dominant | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1114 | FBXO31 | Zornitza Stark Phenotypes for gene: FBXO31 were changed from Mental retardation, autosomal recessive 45, MIM#615979; Spastic-dystonic cerebral palsy, intellectual disability, de novo dominant to Mental retardation, autosomal recessive 45, MIM#615979; Cerebral palsy, MONDO:0006497, FBXO31-related; Spastic-dystonic cerebral palsy, intellectual disability, de novo dominant | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1112 | ATP6V0C | Zornitza Stark Phenotypes for gene: ATP6V0C were changed from Epilepsy; Intellectual Disability; microcephaly to Epilepsy, early-onset, with or without developmental delay, MIM#620465; Epilepsy; Intellectual Disability; microcephaly | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1111 | ATP6V0C | Zornitza Stark edited their review of gene: ATP6V0C: Changed phenotypes: Epilepsy, early-onset, with or without developmental delay, MIM#620465, Epilepsy, Intellectual Disability, microcephaly | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1111 | NEB | Achchuthan Shanmugasundram reviewed gene: NEB: Rating: AMBER; Mode of pathogenicity: None; Publications: 12207937, 21798101, 33376055, 37010288; Phenotypes: Arthrogryposis multiplex congenita 6, OMIM:619334; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1111 | ECEL1 | Achchuthan Shanmugasundram reviewed gene: ECEL1: Rating: AMBER; Mode of pathogenicity: None; Publications: 30131190, 37010288; Phenotypes: Arthrogryposis, distal, type 5D, OMIM:615065; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1111 | CCT5 | Bryony Thompson edited their review of gene: CCT5: Added comment: Now two families reported with two different missense variants (Leu224Val and His147Arg).; Changed publications: 16399879, 25124038, 25345891, 33076433, 37237456 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1109 | HNRNPC | Zornitza Stark Marked gene: HNRNPC as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1108 | HNRNPC |
Zornitza Stark gene: HNRNPC was added gene: HNRNPC was added to Mendeliome. Sources: Literature Mode of inheritance for gene: HNRNPC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: HNRNPC were set to 37541189 Phenotypes for gene: HNRNPC were set to Neurodevelopmental disorder (MONDO:0700092), HNRNPC-related Review for gene: HNRNPC was set to GREEN Added comment: 13 individuals with global developmental delay, intellectual disability, behavioral abnormalities, and subtle facial dysmorphology with heterozygous HNRNPC germline variants. Five had an identical in-frame deletion of nine amino acids in the extreme C terminus. Supportive functional data; haploinsufficiency is the mechanism. Sources: Literature |
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| Mendeliome v1.1107 | PSMC3 | Zornitza Stark Phenotypes for gene: PSMC3 were changed from Deafness, cataract, impaired intellectual development, and polyneuropathy, MIM#619354 to neurodevelopmental disorder, MONDO:0700092, PSMC3-related; Deafness, cataract, impaired intellectual development, and polyneuropathy, MIM#619354 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1103 | PSMC3 | Zornitza Stark edited their review of gene: PSMC3: Added comment: PMID:37256937 - 23 individuals with neurodevelopmental disorder was identified with 15 different de novo missense variants. Apart from one child (patient 2), all others had developmental delay characterised by speech delay (19/19) alone or with intellectual disability (16/18) and motor delay (15/19). In addition, structural modeling as well as proteomic and transcriptomic analyses of T cells derived from patients with PSMC3 variants implicated the PSMC3 variants in proteasome dysfunction through disruption of substrate translocation, induction of proteotoxic stress, and alterations in proteins controlling developmental and innate immune program.; Changed rating: GREEN; Changed publications: 32500975, 37256937; Changed phenotypes: neurodevelopmental disorder, MONDO:0700092, PSMC3-related, Deafness, cataract, impaired intellectual development, and polyneuropathy, MIM#619354; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1095 | PDGFD | Zornitza Stark Marked gene: PDGFD as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1095 | PDGFD |
Zornitza Stark gene: PDGFD was added gene: PDGFD was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: PDGFD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PDGFD were set to 33187088; 33971972 Phenotypes for gene: PDGFD were set to Pulmonary arterial hypertension MONDO:0015924, PDGFD-related Review for gene: PDGFD was set to RED Added comment: Rated as LIMITED by ClinGen. 10 unique variants (all missense) that have been reported in 10 probands in 2 publications (PMIDs: 33187088, 33971972) are included in this curation. 9 of these variants were observed in a cohort of 1647 idiopathic pulmonary arterial hypertension (IPAH) patients of European Ancestry as part of a case-control study. Variant aggregation analysis revealed a significant burden (p=0.0000172) of likely gene damaging PDGFD variants in the IPAH cohort as compared to a group of 18,819 European controls (PMID:33971972). Gelinas et al. also reported a missense PDGFD variant in a proband with IPAH (PMID:33187088). There is currently no functional evidence demonstrating a damaging effect of any of the reported PDGFD variants in humans. Sources: Expert list |
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| Mendeliome v1.1094 | KLF2 | Zornitza Stark Phenotypes for gene: KLF2 were changed from Pulmonary arterial hypertension to Pulmonary arterial hypertension MONDO:0015924, KLF2-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1093 | KLF2 | Zornitza Stark edited their review of gene: KLF2: Changed phenotypes: Pulmonary arterial hypertension MONDO:0015924, KLF2-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1093 | FBLN2 | Zornitza Stark Marked gene: FBLN2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1093 | FBLN2 |
Zornitza Stark gene: FBLN2 was added gene: FBLN2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: FBLN2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: FBLN2 were set to 33971972 Phenotypes for gene: FBLN2 were set to Pulmonary arterial hypertension MONDO:0015924, FBLN2-related Review for gene: FBLN2 was set to RED Added comment: LIMITED by ClinGen. Out of a cohort of 1647 idiopathic PAH cases, 3 rare predicted deleterious missense variants were identified in 6 unrelated individuals with one variant recurrent in four individuals. Gene-disease association also supported by tissue expression data. Sources: Expert list |
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| Mendeliome v1.1092 | AQP1 | Zornitza Stark Phenotypes for gene: AQP1 were changed from Pulmonary arterial hypertension to Pulmonary arterial hypertension MONDO:0015924, AQP1-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1089 | AQP1 | Zornitza Stark reviewed gene: AQP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 37007933, 35627312; Phenotypes: Pulmonary arterial hypertension MONDO:0015924, AQP1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1089 | TET2 | Zornitza Stark Phenotypes for gene: TET2 were changed from Dementia; Lymphoma/myeloid malignancy; Immunodeficiency-75 (IMD75), MIM#619126 to Dementia; Lymphoma/myeloid malignancy; Immunodeficiency-75 (IMD75), MIM#619126; Pulmonary arterial hypertension MONDO:0015924, TET2-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1087 | TET2 |
Zornitza Stark changed review comment from: Association with PAH: MODERATE by ClinGen. TET2 was first reported in relation to autosomal dominant pulmonary arterial hypertension (PAH) in 2020 (Potus et al., PMID: 32192357). Out of a cohort of 2572 cases from the PAH biobank, 6 rare predicted deleterious likely germline variants including missense, nonsense, and frameshift variants were identified in 6 unrelated individuals. The relationship between TET2 and PAH is also supported by experimental evidence including tissue expression in controls and patients, biochemical function as a negative regulator of a proinflammatory response, and knock out TET2 mice exhibiting a PH phenotype.; to: Association with PAH: MODERATE by ClinGen/Amber rating here. TET2 was first reported in relation to autosomal dominant pulmonary arterial hypertension (PAH) in 2020 (Potus et al., PMID: 32192357). Out of a cohort of 2572 cases from the PAH biobank, 6 rare predicted deleterious likely germline variants including missense, nonsense, and frameshift variants were identified in 6 unrelated individuals. The relationship between TET2 and PAH is also supported by experimental evidence including tissue expression in controls and patients, biochemical function as a negative regulator of a proinflammatory response, and knock out TET2 mice exhibiting a PH phenotype. |
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| Mendeliome v1.1087 | TET2 |
Zornitza Stark edited their review of gene: TET2: Added comment: Association with PAH: MODERATE by ClinGen. TET2 was first reported in relation to autosomal dominant pulmonary arterial hypertension (PAH) in 2020 (Potus et al., PMID: 32192357). Out of a cohort of 2572 cases from the PAH biobank, 6 rare predicted deleterious likely germline variants including missense, nonsense, and frameshift variants were identified in 6 unrelated individuals. The relationship between TET2 and PAH is also supported by experimental evidence including tissue expression in controls and patients, biochemical function as a negative regulator of a proinflammatory response, and knock out TET2 mice exhibiting a PH phenotype.; Changed publications: 30890702, 31827242, 32330418, 32518946, 32192357; Changed phenotypes: Dementia, Lymphoma/myeloid malignancy, Immunodeficiency-75 (IMD75), MIM#619126, Pulmonary arterial hypertension MONDO:0015924, TET2-related |
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| Mendeliome v1.1087 | HNRNPA2B1 | Zornitza Stark Phenotypes for gene: HNRNPA2B1 were changed from oculopharyngeal muscular dystrophy, MONDO:0008116; Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2 MIM#615422 to oculopharyngeal muscular dystrophy, MONDO:0008116, OMIM#620460; Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2 MIM#615422 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1085 | PRDM10 | Zornitza Stark Phenotypes for gene: PRDM10 were changed from Fibrofolliculoma, HP:0030436; lipomatosis, MONDO:0006574; renal cell carcinoma, MONDO:0005086 to Birt-Hogg-Dube syndrome 2, MIM# 620459 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1084 | PLCB4 | Zornitza Stark Phenotypes for gene: PLCB4 were changed from Auriculocondylar syndrome 2, MIM# 614669 to Auriculocondylar syndrome 2A, MIM# 614669; Auriculocondylar syndrome 2B, MIM# 620458 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1083 | PLCB4 | Zornitza Stark edited their review of gene: PLCB4: Changed phenotypes: Auriculocondylar syndrome 2A, MIM# 614669, Auriculocondylar syndrome 2B, MIM# 620458 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1083 | IL1R1 | Zornitza Stark Marked gene: IL1R1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1083 | IL1R1 |
Zornitza Stark gene: IL1R1 was added gene: IL1R1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: IL1R1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: IL1R1 were set to 37315560 Phenotypes for gene: IL1R1 were set to Chronic recurrent multifocal osteomyelitis 3, MIM# 259680 Review for gene: IL1R1 was set to RED Added comment: Single individual reported with de novo missense variant in this gene and a phenotype of chronic recurrent multifocal osteomyelitis, auto inflammatory in nature. Some functional data presented. Sources: Literature |
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| Mendeliome v1.1082 | STAB1 | Zornitza Stark Marked gene: STAB1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1080 | SMARCA4 | Zornitza Stark Phenotypes for gene: SMARCA4 were changed from Coffin-Siris syndrome 4, MIM# 614609 to Coffin-Siris syndrome 4, MIM# 614609; Otosclerosis MONDO:0005349, SMARCA4-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1079 | SMARCA4 | Zornitza Stark Publications for gene: SMARCA4 were set to 22426308 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1078 | TBC1D31 | Zornitza Stark Marked gene: TBC1D31 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1077 | AQP4 | Zornitza Stark Marked gene: AQP4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1075 | EZH1 | Zornitza Stark Marked gene: EZH1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1074 | EZH1 |
Zornitza Stark gene: EZH1 was added gene: EZH1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: EZH1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: EZH1 were set to 37433783 Phenotypes for gene: EZH1 were set to Neurodevelopmental disorder (MONDO:0700092), EZH1-related Review for gene: EZH1 was set to GREEN Added comment: PMID: 37433783 Variants were identified 19 individuals from 14 unrelated families, all sharing a clinical phenotype of a neurodevelopmental disorder manifested early in life as global motor, speech and cognitive delay leading to intellectual disability, usually non-progressive and co-occurring with dysmorphic facial features. Functional studies have shown that some missense EZH1 variants lead to GOF with increased methyltransferase activity and recessive variants impair EZH1 expression causing loss of function effects. Sources: Literature |
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| Mendeliome v1.1073 | GPRC5B | Zornitza Stark Marked gene: GPRC5B as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1072 | PHF5A | Zornitza Stark Marked gene: PHF5A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1071 | SMARCA4 |
Paul De Fazio changed review comment from: Additional phenotype reported: A single missense variant E1610K (M_001128849.3) was reported in 7 affected members of a family with progressive hearing loss due to otosclerosis and no other clinical features. Variant is absent from gnomAD. Note that unaffected members of the family were not tested. A mouse CRISPR model with the orthologous variant had a similar phenotype.; to: Additional phenotype reported: A single missense variant E1610K (M_001128849.3) was reported in 7 affected members of a family with progressive hearing loss due to otosclerosis and no other clinical features. Variant is absent from gnomAD. Note that unaffected members of the family were not tested - some obligate carriers were apparently unaffected, reflecting incomplete penetrance. A mouse CRISPR model with the orthologous variant had a similar phenotype. |
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| Mendeliome v1.1071 | CANVAS | Dean Phelan reviewed STR: CANVAS: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37450567; Phenotypes: Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (MIM:614575); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1071 | PHF5A |
Daniel Flanagan gene: PHF5A was added gene: PHF5A was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: PHF5A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PHF5A were set to PMID: 37422718 Phenotypes for gene: PHF5A were set to Neurodevelopmental disorder (MONDO#0700092), PHF5A-related Review for gene: PHF5A was set to GREEN Added comment: Nine subjects with congenital malformations, including hypospadias, growth abnormalities, and developmental delay who had de novo PHF5A variants. Prenatally, six subjects had intrauterine growth retardation. All subjects had motor and speech delay and developmental delay. Congenital abnormalities comprised hypospadias in three of four male subjects, and heart defects (3/9), inguinal hernia (3/9), and sacral dimple (3/9). Six of the nine subjects had short stature. Craniofacial dysmorphism is variable in the nine subjects, high forehead and preauricular skin tag(s) in five subjects. Sources: Expert list |
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| Mendeliome v1.1071 | TBC1D31 |
Lilian Downie gene: TBC1D31 was added gene: TBC1D31 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TBC1D31 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TBC1D31 were set to PMID: 37468454 Phenotypes for gene: TBC1D31 were set to congenital anomaly of kidney and urinary tract MONDO:0019719 Review for gene: TBC1D31 was set to RED Added comment: Single paper with homozygous mutations in 3 sibs with CAKUT from consanguineous family Sources: Literature |
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| Mendeliome v1.1071 | AQP4 |
Lucy Spencer gene: AQP4 was added gene: AQP4 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: AQP4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AQP4 were set to 37143309 Phenotypes for gene: AQP4 were set to ?Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting MIM#620448 Review for gene: AQP4 was set to AMBER Added comment: PMID: 37143309 Cohort of patients with an MRI based diagnosis of megalencephalic leukoencephalopathy with subcortical cysts (MLC). Missense variant in AQP4 seen homozygous in 2 siblings and het in the parents. Patients had macrocephaly, developmental delay, hypotonia, epilepsy, and cognitive deficit. Western blots on generated MDCK cell lines showed no detectable expression of AQP4 protein from the cells with the patients variant. Immunofluorescence also showed no membrane expression. Overexpression studies in HEK293T cells showed WT was seen as mainly monomers or dimers where as variant protein formed large aggregates- likely due to the saturation of protein degradation pathways because of the overexpression. Sources: Literature |
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| Mendeliome v1.1071 | GPRC5B |
Lucy Spencer gene: GPRC5B was added gene: GPRC5B was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GPRC5B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: GPRC5B were set to 37143309 Phenotypes for gene: GPRC5B were set to Megalencephalic leukoencephalopathy with subcortical cysts 3 620447 Review for gene: GPRC5B was set to GREEN Added comment: PMID: 37143309 Cohort of 5 patients with an MRI based diagnosis of megalencephalic leukoencephalopathy with subcortical cysts (MLC). 3 unrelated patients had variants in GPRC5B, 2 have the same inframe dup Ile175dup and the third has an in frame dup of Ala177. All 3 were de novo and unaffected siblings did not have the variants. All patients have macrocephaly, delayed motor development, seizures, all had varying degrees of cognitive deficits. 2 also had spasticity, ataxia and dystonia. MRI showed MLC, abnormal and swollen cerebral white matter. Patient cell lines showed reduced regulatory volume decrease, and western blot showed a strong increase in GRPC5B levels in patient lymphoblasts. Together, these findings indicate disturbed volume regulation in lymphoblasts from patients with GPRC5B variants, potentially due to increased GPRC5B levels. Transfected cells caused increased volume-regulated anion channel activity. Sources: Literature |
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| Mendeliome v1.1071 | MAMDC2 | Elena Savva Marked gene: MAMDC2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1070 | COX18 | Elena Savva Marked gene: COX18 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1068 | NAA30 | Zornitza Stark Marked gene: NAA30 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1068 | MAMDC2 |
Belinda Chong gene: MAMDC2 was added gene: MAMDC2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MAMDC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MAMDC2 were set to 37503746 Phenotypes for gene: MAMDC2 were set to Muscular Dystrophy MONDO:0020121, MAMDC2-related Review for gene: MAMDC2 was set to AMBER Added comment: 17 individuals with an autosomal dominant muscular dystrophy belonging to two unrelated families in which different heterozygous truncating variants in the last exon of MAMDC2 co-segregate correctly with the disease. Sources: Literature |
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| Mendeliome v1.1064 | COX18 |
Naomi Baker gene: COX18 was added gene: COX18 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: COX18 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: COX18 were set to PMID:37468577 Phenotypes for gene: COX18 were set to Mitochondrial disease (MONDO:0044970), COX18-related Review for gene: COX18 was set to RED Added comment: Paper reports a single patient with a homozygous COX18 missense variant, with a neonatal form of mitochondrial hypertrophic cardiomyopathy, lactic acidosis, failure to thrive and neurological involvement associated with severe skeletal muscle COX deficiency. Functional studies demonstrated COX deficiency which could be partially rescued with over-expression of COX18. Sources: Literature |
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| Mendeliome v1.1064 | TUFM | Ain Roesley reviewed gene: TUFM: Rating: RED; Mode of pathogenicity: None; Publications: 37461298; Phenotypes: Inherited primary ovarian failure MONDO:0019852, TUFM-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1064 | STAB1 |
Chern Lim gene: STAB1 was added gene: STAB1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: STAB1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: STAB1 were set to 37490907; 28052375 Phenotypes for gene: STAB1 were set to Iron metabolism disease (MONDO:0002279), STAB1-related Review for gene: STAB1 was set to GREEN gene: STAB1 was marked as current diagnostic Added comment: PMID: 37490907 - Biallelic variants identified in 10 individuals from 7 families with unexplained hyperferritinaemia without iron overload. All of them were in good health and had no dysmorphologies, psycho-motor development abnormalities, hearing or vision disorders, or other pathologies. - Homozygous/compound heterozygous variants: missense, frameshift, stopgain, inframe del of 3 AAs, one synonymous. - Samples from three of the patients from two families showed no immunoreactivity with anti-stabilin-1 compared to control liver where high signal was detected in the liver sinusoids (immunohistochemistry analysis). - Patients’ peripheral monocytes and monocyte-derived macrophages showed very little expression of stabilin-1 on CD14+ monocytes and macrophages compared to control subjects (flow cytometry analysis). - These families have also been published in PMID: 28052375. Sources: Literature |
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| Mendeliome v1.1063 | PTPA |
Ee Ming Wong changed review comment from: - Six individuals with later-onset Parkinson disease with no atypical features eg intellectual disability or early cognitive dysfunction - All were heterozygous for missense variants, a second hit not identified: authors suggests these are monoallelic cases - Three of the 5 missense variants have multiple heterozygotes in gnomAD, two of the missense variants have homozygotes in gnomAD, including one with 7 homozygotes.; to: - Six individuals with later-onset Parkinson disease with no atypical features eg intellectual disability or early cognitive dysfunction - All were heterozygous for missense variants, a second hit not identified: authors suggests these are monoallelic cases - Three of the 5 missense variants have multiple heterozygotes in gnomAD, two of the missense variants have homozygotes in gnomAD, including one with 7 homozygotes. |
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| Mendeliome v1.1063 | PTPA | Ee Ming Wong reviewed gene: PTPA: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 37448355; Phenotypes: Intellectual disability, MONDO: 36073231, PTPA-related, Parkisonism; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1062 | SLC4A10 | Krithika Murali Marked gene: SLC4A10 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1062 | SMARCA4 | Paul De Fazio reviewed gene: SMARCA4: Rating: AMBER; Mode of pathogenicity: None; Publications: 37399313; Phenotypes: Otosclerosis MONDO:0005349, SMARCA4-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1062 | NAA30 |
Sarah Pantaleo gene: NAA30 was added gene: NAA30 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NAA30 was set to Unknown Publications for gene: NAA30 were set to PMID: 37387332 Penetrance for gene: NAA30 were set to unknown Added comment: Report a de novo heterozygous NAA30 nonsense variant c.244C>T, p.(Gln82*) in a 5yo boy with GDD, ASD, hypotonia, seizures, tracheal cleft and recurrent respiratory infections. Seizures resolved after two weeks of life. Family history of ASD in older sister. Epilepsy in mother, childhood onset. Biochemical studies performed to assess the functional impact of the premature stop codon on catalytic activity. The variant was found to completely disrupt N-terminal acetyltransferase activity using an in vitro acetylation assay. Variant de novo, “in a gene sensitive to loss of heterozygosity”. Limitation of study - have not established whether this gene variant acts in a dominant or recessive manner. Sources: Literature |
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| Mendeliome v1.1062 | STAT4 | Melanie Marty changed review comment from: Baghdassarian et al (2023) Four patients from three unrelated families with disabling pansclerotic morphea (DPM, a rare inflammatory disorder), 3 x het missense variants identified, AD inheritance. All 4 patients had disease onset before 5 years of age, with signs of mucosal ulcerations and skin sclerosis. All variants occur in the SH2 domain. Functional studies showed a gain of function effect for these variants.; to: Baghdassarian et al (2023) Four patients from three unrelated families with disabling pansclerotic morphea (DPM, a rare inflammatory disorder), 3 x het missense variants identified, AD inheritance. All 4 patients had disease onset before 5 years of age, with signs of mucosal ulcerations and skin sclerosis. These variants occur in the SH2 domain. Functional studies showed a gain of function effect for these variants. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1062 | STAT4 | Melanie Marty commented on gene: STAT4: Baghdassarian et al (2023) Four patients from three unrelated families with disabling pansclerotic morphea (DPM, a rare inflammatory disorder), 3 x het missense variants identified, AD inheritance. All 4 patients had disease onset before 5 years of age, with signs of mucosal ulcerations and skin sclerosis. All variants occur in the SH2 domain. Functional studies showed a gain of function effect for these variants. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1062 | STAT4 | Melanie Marty edited their review of gene: STAT4: Changed phenotypes: Disabling pansclerotic morphea, inflammatory disorder, poor wound healing, fibrosis, cytopenias, hypogammaglobulinemia, squamous-cell carcinoma | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1060 | SENP7 | Elena Savva Marked gene: SENP7 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1060 | SENP7 |
Elena Savva gene: SENP7 was added gene: SENP7 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SENP7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SENP7 were set to PMID: 37460201 Phenotypes for gene: SENP7 were set to Arthrogryposis multiplex congenita, MONDO:0015168, SENP7-related Review for gene: SENP7 was set to AMBER Added comment: PMID: 37460201 - 1 family (4 affecteds, sibling pair and 1st cousin) with fatal arthrogryposis multiplex congenita, early respiratory failure and neutropenia. Fetus could not be tested, so 3 confirmed genetically. - Homozygous for a PTC, decreased mRNA from one sample supports an NMD outcome. - Additional studies performed supporting downstream proteins expression being affected - Neutropenia observed in 2/3 patients Sources: Literature |
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| Mendeliome v1.1059 | STX5 | Ain Roesley Marked gene: STX5 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1057 | SLC4A10 |
Krithika Murali gene: SLC4A10 was added gene: SLC4A10 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SLC4A10 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC4A10 were set to PMID: 37459438 Phenotypes for gene: SLC4A10 were set to Neurodevelopmental disorderMONDO:0700092, SLC4A10-related Review for gene: SLC4A10 was set to GREEN Added comment: PMID: 37459438 Fasham et al 2023 (Brain) report 10 affected individuals from 5 unrelated families with biallelic LoF variants in this gene with a novel neurodevelopmental disorder. Phenotypic features include hypotonia in infancy, delayed psychomotor development, typically severe ID, progressive postnatal microcephaly, ASD traits, corpus callosal abnormalities and 'slit-like' lateral ventricles. These phenotypic features were recapitulated in knockout mice with additional supportive functional studies. Isolated seizures was reported in 2/10 cases. Sources: Literature |
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| Mendeliome v1.1054 | SHQ1 |
Zornitza Stark edited their review of gene: SHQ1: Added comment: Additional individual with isolated, early-onset dystonia reported. It is likely these clinical presentations are part of a spectrum.; Changed rating: GREEN; Changed publications: 34542157, 29178645, 36847845, 37475611 |
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| Mendeliome v1.1054 | STX5 |
Ain Roesley gene: STX5 was added gene: STX5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: STX5 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: STX5 were set to congenital disorder of glycosylation MONDO#0015286, STX5-related Review for gene: STX5 was set to AMBER gene: STX5 was marked as current diagnostic Added comment: 1x family with 3x deceased shortly after death + 3x spontaneous abortions + 2x abortions due to abnormal fatal ultrasound (US). Hom for NM_003164.4:c.163 A > G p.(Met55Val), which results in complete loss of short isoform (which uses Met55 as the start) phenotype: short long bones on US, dysmorphism, skeletal dysplasia, profound hypotonia, hepatomegaly elevated cholesterol. Post-natally they died of progressive liver failure with cholestasis and hyperinsulinemic hypoglycemias Primary human dermal fibroblasts isolated from these patients show defective glycosylation, altered Golgi morphology as measured by electron microscopy, mislocalization of glycosyltransferases, and compromised ER-Golgi trafficking Sources: Literature |
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| Mendeliome v1.1053 | TEP1 | Zornitza Stark Marked gene: TEP1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1052 | TEP1 |
Zornitza Stark gene: TEP1 was added gene: TEP1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TEP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TEP1 were set to 34543729 Phenotypes for gene: TEP1 were set to Cerebral palsy, MONDO:0006497, TEP1-related Review for gene: TEP1 was set to AMBER Added comment: Wang et al. screened a large cohort of more than 600 CP patients from China and found several variants in TEP1, 11 of which were LoF, while no LoF variant was found in the control cohort. These children all had spastic CP. Among these 11 children, 6 children had birth asphyxia and neonatal encephalopathy. Compared to the total group with birth asphyxia (71/667), 6 patients with TEP1 LOF mutations had a significantly greater risk of birth asphyxia. They confirmed TEP1 as a risk factor for CP by cytological and animal models. Uncertain if these are risk alleles vs indicative of a monogenic disorder. Note LoF variants in gnomad. As this was a cohort study, inheritance of these variants is unknown. Sources: Literature |
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| Mendeliome v1.1049 | TINF2 | Sangavi Sivagnanasundram reviewed gene: TINF2: Rating: AMBER; Mode of pathogenicity: None; Publications: https://doi.org/10.1016/j.xhgg.2023.100225; Phenotypes: Multiple Primary Melanomas (MPM); Mode of inheritance: Unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1049 | LAMA3 |
Sangavi Sivagnanasundram changed review comment from: Zhou et al. (2023) - Two heterozygous nonsense variants identified in two individuals of the same family [p.Arg1126Ter and p.Gln1507Ter] that was shown to segregate in the family with reduced penetrance. The authors hypothesize that function of laminin 𝛼3 is altered as it changes its ability to form heterotrimeric laminins. In vivo functional study using CRISPR/Cas-9 mediated LAMA3 knockout mice. Results of the functional assay showed development of tricuspid valve and right ventricle abnormalities in the presence of a homozygous LoF variant in LAMA3.; to: Novel gene-disease association Zhou et al. (2023) - Two heterozygous nonsense variants identified in two individuals of the same family [p.Arg1126Ter and p.Gln1507Ter] that was shown to segregate in the family with reduced penetrance. The authors hypothesize that function of laminin 𝛼3 is altered as it changes its ability to form heterotrimeric laminins. In vivo functional study using CRISPR/Cas-9 mediated LAMA3 knockout mice. Results of the functional assay showed development of tricuspid valve and right ventricle abnormalities in the presence of a homozygous LoF variant in LAMA3. |
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| Mendeliome v1.1049 | DUSP7 |
Sangavi Sivagnanasundram gene: DUSP7 was added gene: DUSP7 was added to Mendeliome. Sources: Other Mode of inheritance for gene: DUSP7 was set to Unknown Publications for gene: DUSP7 were set to https://doi.org/10.1155/2023/4348290 Phenotypes for gene: DUSP7 were set to Acute Myeloid Leukemia (AML) Review for gene: DUSP7 was set to RED Added comment: New gene with an association in AML prognosis. Gao (2023) - Recruitment from three public AML cohorts - GSE71014, TARGET-AML, and TCGA-AML. The study results suggest that with an DUSP7 may affect AML progression in individuals by affecting the recruitment of local immune cells. Sources: Other |
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| Mendeliome v1.1048 | TMEM63B | Zornitza Stark Marked gene: TMEM63B as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1046 | DHX9 | Zornitza Stark Marked gene: DHX9 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1046 | DHX9 | Zornitza Stark Added comment: Comment when marking as ready: LoF variants caused mild NDD phenotypes and nuclear localization signal (NLS) missense variants caused severe NDD. CMT2-associated missense variants caused aberrant nucleolar DHX9 accumulation, a phenomenon previously associated with cellular stress. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1046 | DHX9 | Zornitza Stark Marked gene: DHX9 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1045 | TMEM63B |
Achchuthan Shanmugasundram changed review comment from: There is sufficient evidence for this gene to be included with green rating in intellectual disability and epilepsy panels. 17 unrelated individuals with severe early-onset developmental and epileptic encephalopathy (DEE), intellectual disability, and severe motor and cortical visual impairment were identified with ten distinct heterozygous variants inTMEM63B. The variants occurred de novo in 16/17 individuals for whom parental DNA was available and either missense or in-frame. All individuals had global developmental delay, with moderate-to-profound intellectual disability and severe motor impairment. All individuals had early-onset drug-resistant epilepsy, whose onset ranged from birth to 3 years but occurred within the first year in 14/17 (82%) and in the first month of life in 6/17 (35%). Sources: Literature; to: There is sufficient evidence for this gene to be included with green rating in 'Intellectual disability syndromic and non-syndromic' and 'Genetic epilepsy' panels. 17 unrelated individuals with severe early-onset developmental and epileptic encephalopathy (DEE), intellectual disability, and severe motor and cortical visual impairment were identified with ten distinct heterozygous variants inTMEM63B. The variants occurred de novo in 16/17 individuals for whom parental DNA was available and either missense or in-frame. All individuals had global developmental delay, with moderate-to-profound intellectual disability and severe motor impairment. All individuals had early-onset drug-resistant epilepsy, whose onset ranged from birth to 3 years but occurred within the first year in 14/17 (82%) and in the first month of life in 6/17 (35%). Sources: Literature |
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| Mendeliome v1.1045 | TMEM63B |
Achchuthan Shanmugasundram gene: TMEM63B was added gene: TMEM63B was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TMEM63B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TMEM63B were set to 37421948 Phenotypes for gene: TMEM63B were set to developmental and epileptic encephalopathy, MONDO:0100062 Review for gene: TMEM63B was set to GREEN Added comment: There is sufficient evidence for this gene to be included with green rating in intellectual disability and epilepsy panels. 17 unrelated individuals with severe early-onset developmental and epileptic encephalopathy (DEE), intellectual disability, and severe motor and cortical visual impairment were identified with ten distinct heterozygous variants inTMEM63B. The variants occurred de novo in 16/17 individuals for whom parental DNA was available and either missense or in-frame. All individuals had global developmental delay, with moderate-to-profound intellectual disability and severe motor impairment. All individuals had early-onset drug-resistant epilepsy, whose onset ranged from birth to 3 years but occurred within the first year in 14/17 (82%) and in the first month of life in 6/17 (35%). Sources: Literature |
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| Mendeliome v1.1045 | DHX9 |
Achchuthan Shanmugasundram gene: DHX9 was added gene: DHX9 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: DHX9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DHX9 were set to 37467750 Phenotypes for gene: DHX9 were set to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071; Charcot-Marie-Tooth disease, MONDO:0015626 Review for gene: DHX9 was set to GREEN Added comment: PMID:37467750 - 17 unrelated individuals were identified with de novo, ultra-rare, heterozygous missense or loss-of-function DHX9 variants, of which 14 individuals were reported with a neurodevelopmental disorder (NDD) and three were reported with Charcot-Marie-Tooth disease (CMT). All 14 cases with NDD had developmental delay, of which eight were reported with intellectual disability (4 severe, 1 moderate, 3 mild). Two cases did not have ID, one had borderline ID and three cases were too young (0-5 years old). The three cases with CMT presented with adult-onset axonal neuropathy. Sources: Literature |
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| Mendeliome v1.1045 | KLK1 | Zornitza Stark Phenotypes for gene: KLK1 were changed from [Kallikrein, decreased urinary activity of] 615953 to [Kallikrein, decreased urinary activity of] 615953; Pulmonary arterial hypertension MONDO:0015924 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1042 | KLK1 |
Zornitza Stark edited their review of gene: KLK1: Added comment: Association with PAH: PMID: 31727138 screening of the biobank - 12 individuals with genetic variant in KLK1 relevant to PAH (not all were found to be hereditary). Assay showed that carriers of variants in KLK1 are less clinically severe compared to those who carry variants in BMPR2. PMID: 17573418 Functional study using sensitive and specific type ELISAs to assay multiple panels of human tissue. KLK1 tissue was abundantly expressed in the pancreas and salivary gland and moderately expressed in the lungs. Reviewed by ClinGen Pulmonary Hypertension GCEP on 30/8/2022 with LIMITED evidence supporting gene-disease validity; Changed publications: 31727138, 17573418; Changed phenotypes: [Kallikrein, decreased urinary activity of] 615953, Pulmonary arterial hypertension MONDO:0015924; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
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| Mendeliome v1.1041 | WBP4 | Zornitza Stark Marked gene: WBP4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1040 | WBP4 | Zornitza Stark Marked gene: WBP4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1039 | KDM2A | Zornitza Stark Marked gene: KDM2A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1035 | INTS13 | Zornitza Stark Marked gene: INTS13 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1031 | TUBB4B | Zornitza Stark Phenotypes for gene: TUBB4B were changed from Leber congenital amaurosis with early onset deafness, LCAEOD, OMIM #617879; MONDO:0060650 to Leber congenital amaurosis with early onset deafness, LCAEOD, OMIM #617879; MONDO:0060650; Primary ciliary dyskinesia, MONDO:0016575, TUBB4B-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1030 | CYHR1 | Zornitza Stark Marked gene: CYHR1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1029 | TSPOAP1 | Zornitza Stark Phenotypes for gene: TSPOAP1 were changed from Dystonia, intellectual disability and cerebellar atrophy to Dystonia 22, MIM# 620453 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1027 | NAA60 | Zornitza Stark Marked gene: NAA60 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1026 | POPDC2 | Zornitza Stark Marked gene: POPDC2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1025 | GPATCH11 | Zornitza Stark Marked gene: GPATCH11 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1024 | KCNA3 | Zornitza Stark Marked gene: KCNA3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1023 | FSD1L | Zornitza Stark Marked gene: FSD1L as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1022 | DENND5B | Zornitza Stark Marked gene: DENND5B as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1021 | DMAP1 | Zornitza Stark Marked gene: DMAP1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1020 | VGLL2 | Zornitza Stark Marked gene: VGLL2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1014 | PLCG1 | Zornitza Stark Marked gene: PLCG1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1011 | DCAF15 | Zornitza Stark Marked gene: DCAF15 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1009 | WBP4 |
Chirag Patel gene: WBP4 was added gene: WBP4 was added to Mendeliome. Sources: Other Mode of inheritance for gene: WBP4 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: WBP4 were set to Neurodevelopmental disorder Review for gene: WBP4 was set to GREEN gene: WBP4 was marked as current diagnostic Added comment: ESHG 2023: 11 individuals from 8 families with homozygous LOF variants in WBP4 gene (4 different variants). Presentation of severe DD and ID, hypotonia, abnormal outer ears, and varying congenital anomalies. WBP4 is spliceosome protein which binds/interacts with SNRNP200. In vivo and in vitro studies previously showed WBP4 enhances splicing and regulates alternative splicing. Patient fibroblasts showed loss of expression of WBP4. RNA sequencing analysis showed abnormal splicing patterns. Proposed spliceosomopathy. Sources: Other |
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| Mendeliome v1.1007 | KDM2A |
Chirag Patel gene: KDM2A was added gene: KDM2A was added to Mendeliome. Sources: Other Mode of inheritance for gene: KDM2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: KDM2A were set to Neurodevelopmental disorder Review for gene: KDM2A was set to GREEN gene: KDM2A was marked as current diagnostic Added comment: ESHG 2023: 14 patients with de novo HTZ variants in KDM2A (5 x truncating, 9 x missense) Presentation with DD, ID (mild), seizures, growth retardation, and dysmorphism. Functional studies: -patient blood showed aberrant genome wide methylation profile - potential episignature -HEK293T cells showed altered subcellular localisation of KDM2A -Drosophila models showed variants caused neurotoxicity Sources: Other |
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| Mendeliome v1.1005 | NSUN6 | Chirag Patel changed review comment from: Sufficient evidence for upgrade; to: Drosophila KO showed locomotion defects and reduced learning ability. Sufficient evidence for upgrade | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1003 | INTS13 |
Chirag Patel gene: INTS13 was added gene: INTS13 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: INTS13 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: INTS13 were set to PMID: 36229431 Phenotypes for gene: INTS13 were set to Oral-facial-digital syndrome Review for gene: INTS13 was set to GREEN gene: INTS13 was marked as current diagnostic Added comment: 2 families with 4 affected individuals with Oral-facial-digital (OFD) phenotype. Homozygosity mapping and WES found 2 homozygous variants in INTS13 gene. This is a subunit of the Integrator complex, which associates with RNA Polymerase II and cleaves nascent RNA to modulate gene expression. Variants segregated with disease. Depletion of INTS13 disrupts ciliogenesis in human cultured cells and causes dysregulation of a broad collection of ciliary genes. Knockdown in Xenopus embryos leads to motile cilia anomalies. Sources: Literature |
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| Mendeliome v1.1002 | TUBB4B | Chirag Patel reviewed gene: TUBB4B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Primary ciliary dyskinesia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1001 | DCAF15 |
Chirag Patel gene: DCAF15 was added gene: DCAF15 was added to Mendeliome. Sources: Other Mode of inheritance for gene: DCAF15 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: DCAF15 were set to Cornelia de Lange syndrome Review for gene: DCAF15 was set to AMBER Added comment: ESHG 2023: 3 unrelated cases with CdLS (1 x TOP with MCA, 1 x death @20mths, 1 x living child) Features suggestive of CdLS - DD, microcephaly, CHD, dysmorphism, visual/hearing impairment. WES identified recurrent de novo variant (p.Ser470Phe) in DCAF15 gene. This mediates ubiquitination and degradation of target proteins, and interacts with cohesin complex members (SMC1/SMC3). Protein analysis from individuals showed increased accumulation of ubiquitination-modified proteins and SM3 (GOF mechanism). EpiSign analysis showed same DNA methylation pattern as other CdLS cases/genes. Zebrafish model showed reduced body length, reduced head size, reduced oligodendrocytes, heart defect, aberrant motor neurons, and abnormal response to visual/auditory stimuli. Sources: Other |
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| Mendeliome v1.997 | PMVK |
Zornitza Stark changed review comment from: Association with auto inflammatory syndrome: Five-year-old girl with recurring hyperinflammatory episodes initially presenting at 9mo with fever, arthritis, aphthous stomatitis and maculopapular rash with homozygous variant in PMVK p.Val131Ala (NM_006556.4: c.392T>C) with clinical overlap with MVK deficiency. Supportive functional data. Second patient, 6yo boy with compound heterozygous c.329G >A (p. Arg110Gln) and c.316G >A (p. Val106Met) mutations in trans configuration with similar phenotype.; to: Association with auto inflammatory syndrome: Five-year-old girl with recurring hyperinflammatory episodes initially presenting at 9mo with fever, arthritis, aphthous stomatitis and maculopapular rash with homozygous variant in PMVK p.Val131Ala (NM_006556.4: c.392T>C) with clinical overlap with MVK deficiency. Supportive functional data. Second patient, 6yo boy with compound heterozygous c.329G >A (p. Arg110Gln) and c.316G >A (p. Val106Met) mutations in trans configuration with similar phenotype. Amber for bi-allelic disease association. |
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| Mendeliome v1.997 | PMVK |
Zornitza Stark edited their review of gene: PMVK: Added comment: Association with auto inflammatory syndrome: Five-year-old girl with recurring hyperinflammatory episodes initially presenting at 9mo with fever, arthritis, aphthous stomatitis and maculopapular rash with homozygous variant in PMVK p.Val131Ala (NM_006556.4: c.392T>C) with clinical overlap with MVK deficiency. Supportive functional data. Second patient, 6yo boy with compound heterozygous c.329G >A (p. Arg110Gln) and c.316G >A (p. Val106Met) mutations in trans configuration with similar phenotype.; Changed publications: 26202976, 37364720, 36410683; Changed phenotypes: Porokeratosis 1, multiple types, MIM# 175800, Autoinflammatory syndrome, MONDO:0019751, PMVK-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal |
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| Mendeliome v1.997 | RIPK3 | Zornitza Stark Marked gene: RIPK3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.996 | RIPK3 |
Zornitza Stark gene: RIPK3 was added gene: RIPK3 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: RIPK3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RIPK3 were set to 37083451 Phenotypes for gene: RIPK3 were set to Hereditary susceptibility to infections, MONDO:0015979, RIPK3-related; Recurrent HSV encephalitis Review for gene: RIPK3 was set to AMBER Added comment: Single female patient with independent episodes of HSE at 6 and 17 months of age and with autoimmune encephalitis 1 month after the second episode of HSE with two heterozygous mutations of RIPK3 predicted to be loss of function (pLOF): p. Arg422* (c.1264 C > T, MAF 0.001568, CADD 35) and p. Pro493fs9* (c.1475 C > CC, MAF 0.002611, CADD 24.2). Extensive supportive functional data including RIPK3 knockout human pluripotent stem cell–derived cortical neurons. Sources: Expert Review |
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| Mendeliome v1.995 | ANO1 | Zornitza Stark Phenotypes for gene: ANO1 were changed from Intestinal dysmotility syndrome, MIM# 620045; Impaired intestinal peristalsis; haemorrhagic diarrhoea; dysmorphic features to Intestinal dysmotility syndrome, MIM# 620045; Moyamoya disease, MONDO:0016820, ANO1 related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.992 | ANO1 | Zornitza Stark edited their review of gene: ANO1: Added comment: PMID 37253099: screening analysis of Moyamoya disease (MMD) cohort revealed 8 individuals with variants in the ANO1 gene. Two families had the same rare variant p.Met658Val. The ANO1 rare variants were assessed using patch-clamp recordings, and the majority of variants, including ANO1 p.Met658Val, displayed increased sensitivity to intracellular Ca2+. Patients harboring these gain-of-function ANO1 variants had classic features of MMD, but also had aneurysm, stenosis, and/or occlusion in the posterior circulation. Amber rating due to somewhat conflicting segregation and functional data presented.; Changed publications: 37253099; Changed phenotypes: Intestinal dysmotility syndrome, MIM# 620045, Moyamoya disease, MONDO:0016820, ANO1 related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.991 | CYHR1 |
Chirag Patel gene: CYHR1 was added gene: CYHR1 was added to Mendeliome. Sources: Other Mode of inheritance for gene: CYHR1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CYHR1 were set to Neurodevelopmental disorder and microcephaly Review for gene: CYHR1 was set to AMBER Added comment: ESHG 2023: 5 individuals from 3 families with biallelic LOF variants in CYHR1 (aka ZTRAF1). Presentation with microcephaly, hypotonia, DD, and ID. Expression studies showed mislocalisation of CYHR1. Mutant fibroblasts showed increased lysosomal markers and upregulated lysosomal proteins, leading to impaired autophagy. Zebrafish KO however did not show a phenotype. Sources: Other |
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| Mendeliome v1.989 | NAA60 | Chirag Patel reviewed gene: NAA60: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Primary familial brain calcification; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.989 | NAA60 |
Chirag Patel gene: NAA60 was added gene: NAA60 was added to Mendeliome. Sources: Other Mode of inheritance for gene: NAA60 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: NAA60 were set to Basal ganglia calcification Review for gene: NAA60 was set to GREEN gene: NAA60 was marked as current diagnostic Added comment: ESHG 2023: 10 individuals from 7 families with biallelic variants in NAA60 (missense and framshift). All with primary brain calcification - 4/10 childhood onset (DD, ID), 6/10 adult onset (cerebellar and pyramidal dysfunction, dystonia, parkinsonism, cognitive impairment, psychiatric manifestations). NAA60 catalyses N-terminal acetylation of transmembrane proteins and localises to Golgi apparatus. In vitro assay of variants showed reduced capacity of Nt acetylation. Fibroblast studies showed significantly reduced levels of phosphate importer (SLC20A2). Loss of function variants in SLC20A2 (~50% of PFBC cases) lead to increased extracellular phosphate (which is thought to lead to calcium deposits in brain). Sources: Other |
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| Mendeliome v1.987 | POPDC2 |
Chirag Patel gene: POPDC2 was added gene: POPDC2 was added to Mendeliome. Sources: Other Mode of inheritance for gene: POPDC2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: POPDC2 were set to Sinus node dysfunction Review for gene: POPDC2 was set to GREEN gene: POPDC2 was marked as current diagnostic Added comment: ESHG 2023: 3 families with 7 affected with sinus node dysfunction (bradycardia) and AV block (2/7 HCM). 3 x HMZ variants found in POPDC2 (2 x missense, 1 x indel). Variants predicted to diminish cAMP binding of POPDC2, and shown to disrupt regulation of TREK1 channels (lowering of outward K+ current). POPDC2 is highly expressed in cardiac myocytes, sinoatrial node, and atrioventricular node. Knockdown in zebrafish leads to AV block, and knockout in mice leads to sinus node dysfunction. Sources: Other Sources: Other |
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| Mendeliome v1.985 | GPATCH11 |
Chirag Patel gene: GPATCH11 was added gene: GPATCH11 was added to Mendeliome. Sources: Other Mode of inheritance for gene: GPATCH11 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: GPATCH11 were set to Leber congenital amaurosis and developmental delay Review for gene: GPATCH11 was set to GREEN gene: GPATCH11 was marked as current diagnostic Added comment: ESHG 2023: 3 families with 8 individuals with leber congenital amaurosis, developmental delay, language disorder, and behavioural issues. GPATCH11 localises to nucleus and basal body of primary cilium (similar to other LCA genes). Biallelic variants found in GPATCH11 - 1 splice variant common to all 3 families (1 other variant in 3rd family). Splice variant leads to loss of exon 4 (mRNA studies). Mouse models showed i) abnormal rod/cone responses on ERG; ii) decreased outer nuclear layer in retina, and iii) abnormal associate/episodic memory Sources: Other |
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| Mendeliome v1.982 | KCNA3 |
Chirag Patel gene: KCNA3 was added gene: KCNA3 was added to Mendeliome. Sources: Other Mode of inheritance for gene: KCNA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: KCNA3 were set to Neurodevelopmental disorder Review for gene: KCNA3 was set to GREEN gene: KCNA3 was marked as current diagnostic Added comment: ESHG 2023: 10 individuals with de novo missense variants in KCNA3 (K+ channel) Variable electrophysiology studies of effect of variants (5 x LOF, 4 x GOF, 1 no change) Presentation: abnormal speech development (8/8), ID (6/8), epilepsy (5/8), and ASD (7/8) Sources: Other |
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| Mendeliome v1.980 | FSD1L |
Chirag Patel gene: FSD1L was added gene: FSD1L was added to Mendeliome. Sources: Other Mode of inheritance for gene: FSD1L was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: FSD1L were set to Neurodevelopmental disorder Review for gene: FSD1L was set to GREEN gene: FSD1L was marked as current diagnostic Added comment: ESHG 2023: 8 families with biallelic missense/nonsense variants Presentation only described 1 family/2 affecteds with DD, ID, spastic paraparesis, epilepsy, corpus callosum hypoplasia, and optic nerve hypoplasia Functional assays: -reduced expression of FSD1L in mature neurons (RNA studies) -very low % mature neurons (neuronal differentiation) -reduced neuronal migration Sources: Other |
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| Mendeliome v1.978 | DENND5B |
Chirag Patel gene: DENND5B was added gene: DENND5B was added to Mendeliome. Sources: Other Mode of inheritance for gene: DENND5B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: DENND5B were set to Neurodevelopmental disorder with white matter anomalies Review for gene: DENND5B was set to GREEN gene: DENND5B was marked as current diagnostic Added comment: ESHG 2023: 7 patients/7 families with de novo DENND5B variants (6 missense, 1 splice) DD/ID (mod/profound)(7/7), white matter anomalies (6/7) hypotonia, epilepsy (3/7) DENND5B acts as: -GEF for activation of RAB proteins which are involved in membrane trafficking and neurotransmitter release -regulator of lipid absorption and homeostasis Functional studies showed loss of expression of DENND5B in fibroblasts, abnormal vesicle trafficking, and impaired lipid uptake and intracellular distribution Sources: Other |
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| Mendeliome v1.976 | DMAP1 |
Chirag Patel gene: DMAP1 was added gene: DMAP1 was added to Mendeliome. Sources: Other Mode of inheritance for gene: DMAP1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: DMAP1 were set to Neurodevelopmental disorder Review for gene: DMAP1 was set to GREEN gene: DMAP1 was marked as current diagnostic Added comment: ESHG 2023: 9 patients/8 families with bilallelic variants in DMAP1 (3 missense, 7 LOF) All with DD, speech delay, hypotonia, and ID Some with epilepsy (4/6), FTT (4/5), and brain malformations (3/5) Drosophila showed abnormal behaviour pattern and bang sensitivity Specific methylation episignature also seen Sources: Other |
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| Mendeliome v1.974 | VGLL2 |
Chirag Patel gene: VGLL2 was added gene: VGLL2 was added to Mendeliome. Sources: Other Mode of inheritance for gene: VGLL2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: VGLL2 were set to Syngnathia Review for gene: VGLL2 was set to GREEN gene: VGLL2 was marked as current diagnostic Added comment: ESHG 2023: 4 families/7 affected individuals with isolated unilateral/bilateral syngnathia biallelic truncating variants in VGLL2 But not phenotype in KO mouse or zebrafish models Sources: Other |
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| Mendeliome v1.972 | RDH11 | Elena Savva reviewed gene: RDH11: Rating: AMBER; Mode of pathogenicity: None; Publications: 24916380, 15634683, 30731079, 18326732, 34988992; Phenotypes: Retinal dystrophy, juvenile cataracts, and short stature syndrome, MIM# 616108; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.972 | C1GALT1C1 | Zornitza Stark commented on gene: C1GALT1C1: Two maternal half-brothers with missense variant and aHUS phenotype reported, increasing evidence for association. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.969 | NFE2L2 | Zornitza Stark edited their review of gene: NFE2L2: Changed phenotypes: Immunodeficiency, developmental delay, and hypohomocysteinemia, MIM# 617744, Recurrent respiratory and skin infection, Growth retardation, Developmental delay, borderline ID, White matter cerebral lesions; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.969 | SMAD1 | Bryony Thompson Added comment: Comment on list classification: Disputed gene-disease validity curation by ClinGen PH VCEP 21/11/2022 - Only two probands reported to have PAH and SMAD1 variants. The variants are missense variants without functional data at the time of curation. Thus, SMAD1 is classified as disputed for PAH based upon insufficient genetic evidence over multiple years of research. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.967 | ZNF808 | Krithika Murali Marked gene: ZNF808 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.966 | ZNF808 |
Hazel Phillimore gene: ZNF808 was added gene: ZNF808 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ZNF808 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ZNF808 were set to PMID: 37308312 Phenotypes for gene: ZNF808 were set to non-syndromic neonatal diabetes; MONDO:0016391 Review for gene: ZNF808 was set to GREEN Added comment: PMID: 37308312; Alqahtani, MA. et al. (2023) Clin Genet. doi: 10.1111/cge.14389. Three siblings in one consanguineous Saudi Arabian family with non-syndromic neonatal diabetes, all with a homozygous frameshift variant, NM_001321425.2:c.1448dupA, p.(Tyr483*), in ZNF808. (Same nucleotide and amino acid numbering as for the MANE SELECT transcript, NM_001039886.4). This variant has been entered as likely pathogenic in ClinVar by this group. This variant occurs in the last exon of the gene and is therefore not NMD-predicted. Instead it is predicted to cause a truncated protein. This paper shows a diagram with several other truncating variants in this exon, which were reported in the paper by De Franco, E. et al. (2021). (These patients also had low vitamin D levels, suggesting an association, and is consistent with other studies looking into loci that are associated with vitamin D). De Franco, E. et al. (2021) medRxiv 08.23.21262262. (Exeter, UK): Firstly, this group found a homozygous variant NM_001039886.3:c.637del, p.(Leu213*) that is predicted to cause a truncated protein, and also a homozygous CNV Chr19(GRCh37):g.53057128_53100968del (predicted to cause a deletion of exons 4 and 5) in two unrelated affected individuals. These patients had pancreatic agenesis, defined as insulin-dependent diabetes in the first 6 months of life (neonatal diabetes) and exocrine pancreatic insufficiency. Both were from consanguineous families. Parents were subsequently tested and shown to be heterozygous carriers. They then investigated 232 additional patients who had been diagnosed with neonatal diabetes before the age of 6 months and found ten more homozygous ZNF808 variants. Six were nonsense: p.(Gln194*), p.(Cys233*), p.(Tyr427*), p.(Lys458*), p.(Tyr528*) and p.(Arg727*), and three were frameshift variants: p.(Ala379Valfs*157), p.(Leu588Profs*118), p.(Asn770Ilefs*98) and one was a whole-gene deletion. All the frameshift and nonsense variants occurred in the last exon of the gene, which contains all 23 zinc finger domains; and therefore all of these variants are predicted to result in truncated proteins, and removal of some, if not all, those domains. This group also carried out functional studies using an in vitro model of pancreas development and showed an aberrant activation of many transposable elements (mostly MER11 elements) that would be normally be repressed during early pancreas development. Sources: Literature |
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| Mendeliome v1.966 | SART3 | Krithika Murali Classified gene: SART3 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.966 | SART3 | Krithika Murali Gene: sart3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.965 | SART3 |
Daniel Flanagan gene: SART3 was added gene: SART3 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: SART3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SART3 were set to PMID: 37296101 Phenotypes for gene: SART3 were set to Neurodevelopmental disorder (MONDO#0700092), SART3-related; 46,XY disorder of sex development (MONDO:0020040), SART3-related Review for gene: SART3 was set to GREEN Added comment: Nine individuals from six families presenting with intellectual disability, global developmental delay, a subset of brain anomalies, together with gonadal dysgenesis in 46,XY individuals. Additionally, two individuals had seizures and two had epileptiform activity reported on EEG. Human induced pluripotent stem cells carrying patient variants in SART3 show disruption to multiple signalling pathways, upregulation of spliceosome components and demonstrate aberrant gonadal and neuronal differentiation in vitro. Sources: Expert list |
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| Mendeliome v1.965 | ARPC5 | Elena Savva Classified gene: ARPC5 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.965 | ARPC5 | Elena Savva Gene: arpc5 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.964 | ARPC5 | Elena Savva Classified gene: ARPC5 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.964 | ARPC5 | Elena Savva Gene: arpc5 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.963 | ARPC5 | Elena Savva Marked gene: ARPC5 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.963 | ARPC5 | Elena Savva Gene: arpc5 has been removed from the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.963 | NUDCD2 | Krithika Murali Marked gene: NUDCD2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.963 | NUDCD2 | Seb Lunke Marked gene: NUDCD2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.962 | NUDCD2 |
Ee Ming Wong gene: NUDCD2 was added gene: NUDCD2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NUDCD2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NUDCD2 were set to 37272762 Phenotypes for gene: NUDCD2 were set to Multiple congenital anomalies (MONDO:0019042), NUDCD2-related Penetrance for gene: NUDCD2 were set to unknown Review for gene: NUDCD2 was set to AMBER gene: NUDCD2 was marked as current diagnostic Added comment: - Two unrelated probands, each biallelic for two variants in NUDCD2 (total 3x LoF variants, 1x missense variant) - Immunoblotting of proteins extracted from the primary fibroblasts of one proband with 2x LoF variants demonstrated markedly reduced NUDCD2 levels compared to healthy individuals Sources: Literature |
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| Mendeliome v1.962 | DCAF13 | Seb Lunke Marked gene: DCAF13 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.962 | RAB34 | Elena Savva Marked gene: RAB34 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.962 | RAB34 | Elena Savva Phenotypes for gene: RAB34 were changed from Clefting; corpus callosum; short bones; hypertelorism; polydactyly; cardiac defects; anorectal anomalies to Multiple congenital anomalies, (MONDO:0019042), RAB34-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.961 | ARPC5 |
Paul De Fazio gene: ARPC5 was added gene: ARPC5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ARPC5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ARPC5 were set to 37349293; 37382373 Phenotypes for gene: ARPC5 were set to Combined immunodeficiency, ARPC5-related MONDO:0015131 Review for gene: ARPC5 was set to GREEN gene: ARPC5 was marked as current diagnostic Added comment: 4 individuals from 3 families reported with homozygous LoF variants. All had recurrent and severe infections. Other developmental anomalies were present but seemed variable. PMID:37349293 reports 2 unrelated patients. Both had scoliosis. One had neurodevelopmental delay and brain atrophy. Patient 1 died at 15yo after a sudden episode of hemoptysis and hematochezia. Patient 2 died at 1yo because of progressive neurologic and respiratory disease; an autopsy was not performed. PMID:37382373 reports 2 patients from the same family. One had multiple congenital anomalies including a congenital heart defect (CHD) (patent foramen ovale), cleft palate, and hypoplastic corpus callosum. The sibling also had CHD (moderate pulmonary stenosis and atrial septal defect). Functional studies and a mouse model were supportive of the disease association. Sources: Literature |
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| Mendeliome v1.961 | RPH3A | Seb Lunke Marked gene: RPH3A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.961 | DRG1 | Krithika Murali Marked gene: DRG1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.958 | MIR204 | Elena Savva Marked gene: MIR204 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.958 | DCAF13 |
Michelle Torres gene: DCAF13 was added gene: DCAF13 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: DCAF13 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DCAF13 were set to 36797467 Phenotypes for gene: DCAF13 were set to Neuromuscular disease (MONDO#0019056), DCAF13-related Review for gene: DCAF13 was set to RED Added comment: One consanguineous family, 4x individuals homozygous NM_015420.7(DCAF13)c.907 G > A; p.(Asp303Asn) (3x via WES and 1x via Sanger) with a neuromuscular disorder characterized by a waddling gait, limb deformities, muscular weakness and facial palsy. In silicos analysis of mutant DCAF13 suggests that the amino acid change is deleterious and affects a ß-hairpin turn, within a WD40 domain of the protein which may decrease protein stability. Functional studies were not performed. Previously, a heterozygous variant in DCAF13 with or without a heterozygous missense variant in CCN3, was suggested to cause inherited cortical myoclonic tremor with epilepsy. In addition, a heterozygous DCAF13 variant has been associated with autism spectrum disorder. Sources: Literature |
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| Mendeliome v1.958 | ERI1 | Elena Savva Marked gene: ERI1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.957 | ERI1 |
Elena Savva gene: ERI1 was added gene: ERI1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ERI1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ERI1 were set to 37352860 Phenotypes for gene: ERI1 were set to Spondyloepimetaphyseal dysplasia (MONDO#0100510), ERI1-related, Intellectual disability (MONDO#0001071), ERI1-related Review for gene: ERI1 was set to GREEN Added comment: PMID: 37352860 - 8 individuals from 7 unrelated families - Patients with biallelic missense show a MORE severe spondyloepimetaphyseal dysplasia, syndactyly, brachydactyly/clinodactyly/camptodactyly - Patients with biallelic null/whole gene deletion had mild ID and digit anomalies including brachydactyly/clinodactyly/camptodactyly - Patient chet for a missense and PTC variant has a blended phenotype with short stature, syndactyly, brachydactyly/clinodactyly/camptodactyly, mild ID and failure to thrive - Missense variants were functionally shown to not be able to rescue 5.8S rRNA processing in KO HeLa cells - K/O mice had neonatal lethality with growth defects, brachydactyly. Skeletal-specific K/O had mild platyspondyly, had more in keeping with patients with null variants than missense More severe phenotype hypothesised due to "exonuclease-dead proteins may compete for the target RNA molecules with other exonucleases that have functional redundancy with ERI1, staying bound to those RNA molecules" Sources: Literature |
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| Mendeliome v1.956 | RAB34 |
Sarah Pantaleo gene: RAB34 was added gene: RAB34 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RAB34 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RAB34 were set to PMID: 37384395 Phenotypes for gene: RAB34 were set to Clefting; corpus callosum; short bones; hypertelorism; polydactyly; cardiac defects; anorectal anomalies Penetrance for gene: RAB34 were set to Complete Review for gene: RAB34 was set to GREEN Added comment: Oral-facial-digital syndromes (OFDS) are a group of clinically and genetically heterogenous disorders characterised by defects in the development of the face and oral cavity along with digit anomalies. Pathogenic variants in >20 genes encoding ciliary proteins have been found to cause OFDS. Identified by WES biallelic missense variants in a novel disease-causing ciliary gene RAB34 in four individuals from three unrelated families (aided by GeneMatcher). Affected individuals presented a novel form of OFDS accompanied by cardiac, cerebral, skeletal (eg. Shortening of long bones), and anorectal defects. RAB34 encodes a member of the Lab GTPase superfamily and was recently identified as a key mediator of ciliary membrane formation. Protein products of pathogenic variants clustered near the RAB34 C-terminus exhibit a strong loss of function. Onset is prenatal (multiple developmental defects including short femur, polydactyly, heart malformations, kidney malformations, brain malformations), resulting in medical termination for three probands. In the fourth, the only one alive at birth, proband born at 39+5 weeks, normal growth parameters after pregnancy with polyhydramnios, corpus callosum agenesis and polydactyly. Respiratory distress at birth. All four probands presented typical features of ciliopathy disorders, overlapping with oral, facial and digital abnormalities. All with homozygous missense variants. All absent in gnomAD (in homozygous state). Sanger sequencing confirmed mode of inheritance. Sources: Literature |
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| Mendeliome v1.956 | DRG1 |
Dean Phelan gene: DRG1 was added gene: DRG1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: DRG1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DRG1 were set to PMID: 37179472 Phenotypes for gene: DRG1 were set to Neurodevelopmental disorder (MONDO:0700092), DRG1-related Review for gene: DRG1 was set to GREEN Added comment: PMID: 37179472 - Biallelic variants were identified in four affected individuals from three distinct families with neurodevelopmental disorder with global developmental delay, primary microcephaly, short stature and craniofacial anomalies. Functional studies show the variants result in a loss of function. Sources: Literature |
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| Mendeliome v1.956 | RPH3A |
Lucy Spencer gene: RPH3A was added gene: RPH3A was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RPH3A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RPH3A were set to 37403762; 29441694 Phenotypes for gene: RPH3A were set to Neurodevelopmental disorder (MONDO#0700092), RPH3A-related Review for gene: RPH3A was set to GREEN Added comment: PMID: 37403762- 6 patients with RPH3A variant. All 6 have ID, 4 have epilepsy, 2 with obesity, 1 with dysmorphic features. All 6 have missense variants, 3 shown to be de novo, the other 3 parents were not available for testing. I patient also had language and motor impairment, breathing issues and mixed hypo/hypertonia- he also had variants in CUL4B, PRKAG2, SCN4A, none of these genes cause seizures (which he had). Patch clamp studies on 2 of the missense showed they increased either the number of NMDA receptors on neuron membrane surface or increased their conductance. Study suggests that the variants interrupt the normal role of RPH3A activity at the synaptic NMDAR complex which is needed for the induction of synaptic plasticity and NMDAR-dependant behaviours Previously this gene was reported in PMID: 29441694- 1 girl with learning disabilities, tremors, ataxia, hyperglycemia and muscle fatigability. Chet for 2 RPH3A missense. Functional analysis showed strong and marginal impairment of protein binding for each variant. this is the only biallelic report currently. Sources: Literature |
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| Mendeliome v1.956 | MIR204 |
Chern Lim gene: MIR204 was added gene: MIR204 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MIR204 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MIR204 were set to 26056285; 37321975 Phenotypes for gene: MIR204 were set to Retinal dystrophy and iris coloboma with or without cataract (MIM#616722) Mode of pathogenicity for gene: MIR204 was set to Other Review for gene: MIR204 was set to GREEN gene: MIR204 was marked as current diagnostic Added comment: PMID: 26056285 - Bilateral coloboma and rod-cone dystrophy with or without cataract in nine individuals of a five-generation family. - Heterozygous n.37C>T segregates with the disease in all affected individuals. - Functional analysis including transcriptome analysis showed this variant resulted in significant alterations of miR-204 targeting capabilities. In vivo injection, in medaka fish (Oryzias latipes), of the mutated miR-204 caused a phenotype consistent with that observed in the family. - Authors suggested gain of function is the likely disease mechanism. PMID: 37321975 - Four members of a three-generation family with early-onset chorioretinal dystrophy, heterozygous for n.37C>T. - Additionally, four family members were shown to be affected by albinism resulting from biallelic pathogenic OCA2 variants. - Haplotype analysis excluded relatedness with the family reported in PMID: 26056285. - In silico analysis of the MIR204 n.37C>T variant reveals profound changes to its target mRNAs and suggests a gain-of-function mechanism of miR 204 variant. Sources: Literature |
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| Mendeliome v1.950 | INTS11 | Zornitza Stark Phenotypes for gene: INTS11 were changed from intellectual disability, MONDO:0001071 to Neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities, MIM# 620428 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.948 | NUP54 | Zornitza Stark Phenotypes for gene: NUP54 were changed from Striatonigral degeneration, MONDO:0003122, NUP54-related; Early onset dystonia; progressive neurological deterioration; ataxia; dysarthria; dysphagia; hypotonia to Dystonia 37, early-onset, with striatal lesions, MIM# 620427; Early onset dystonia; progressive neurological deterioration; ataxia; dysarthria; dysphagia; hypotonia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.947 | BRWD1 | Zornitza Stark Phenotypes for gene: BRWD1 were changed from Asthenoteratozoospermia, likely primary ciliary dyskinesia to Ciliary dyskinesia, primary, 51, MIM# 620438 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.946 | SMARCB1 | Achchuthan Shanmugasundram reviewed gene: SMARCB1: Rating: AMBER; Mode of pathogenicity: None; Publications: 25168959, 37010288; Phenotypes: Coffin-Siris syndrome 3, OMIM:614608; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.946 | ARID1A | Achchuthan Shanmugasundram reviewed gene: ARID1A: Rating: AMBER; Mode of pathogenicity: None; Publications: 25168959, 37010288; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.946 | ZC4H2 |
Achchuthan Shanmugasundram changed review comment from: There are ten unrelated patients reported with cleft palate. Hence, this gene should be added with green rating to 'clefting disorders' panel. PMID:31206972 - Of 42 families identified with variants in de novo and inherited heterozygous variants in ZC4H2 gene, eight patients had cleft palate in addition to several other clinical presentations. These included one patient with cleft palate from the DDD study (DECIPHER database) DECIPHER database - Of 13 patients with monoallelic sequence variants, three patients had cleft palate. Cleft palate has been recorded as one of the clinical presentations of female-restricted Wieacker-Wolff syndrome (MIM #301041) in OMIM.; to: There are ten unrelated patients reported with cleft palate. Hence, this gene should be added with green rating to 'clefting disorders' panel. PMID:31206972 - Of 42 families identified with de novo and inherited variants in ZC4H2 gene, eight patients had cleft palate in addition to several other clinical presentations. These included one patient with cleft palate from the DDD study (DECIPHER database) DECIPHER database - Of 13 patients with sequence variants, three patients had cleft palate. Cleft palate has been recorded as one of the clinical presentations of female-restricted Wieacker-Wolff syndrome (MIM #301041) in OMIM. |
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| Mendeliome v1.944 | STAG2 | Achchuthan Shanmugasundram reviewed gene: STAG2: Rating: GREEN; Mode of pathogenicity: None; Publications: 28296084, 29263825, 30158690, 31334757, 33014403, 37010288; Phenotypes: Holoprosencephaly 13, X-linked, OMIM:301043, Mullegama-Klein-Martinez syndrome, OMIM:301022; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.944 | SMARCA4 | Achchuthan Shanmugasundram reviewed gene: SMARCA4: Rating: GREEN; Mode of pathogenicity: None; Publications: 25168959, 37010288; Phenotypes: Coffin-Siris syndrome 4, OMIM:614609; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.943 | POGZ |
Achchuthan Shanmugasundram changed review comment from: Although there are more than three unrelated cases reported with either cleft palate or bifid uvula in total, this phenotype is not consistently present in patients with monoallelic variants in POGZ gene. Hence, this gene should only be added with amber rating in 'Clefting disorders panel'. PMID:26739615 - Five unrelated individuals were identified with de novo truncating variants in POGZ gene, of which one individual had cleft palate and another one had bifid uvula. PMID:31782611 - In this cohort of 22 individuals with 21 different loss of function variants in POGZ, two patients were reported with bifid uvula. DECIPHER database - Of 42 patients with heterozygous sequence variants, one had cleft palate and another one had bifid uvula (PMID:37010288). The OMIM entry for White-Sutton syndrome (MIM #616364) does not currently include cleft lip/ palate as one of the clinical manifestations of this syndrome.; to: Although there are more than three unrelated cases reported with either cleft palate or bifid uvula in total, this phenotype is not consistently present in patients with monoallelic variants in POGZ gene. Hence, this gene should only be added with amber rating in 'Clefting disorders' panel. PMID:26739615 - Five unrelated individuals were identified with de novo truncating variants in POGZ gene, of which one individual had cleft palate and another one had bifid uvula. PMID:31782611 - In this cohort of 22 individuals with 21 different loss of function variants in POGZ, two patients were reported with bifid uvula. DECIPHER database - Of 42 patients with heterozygous sequence variants, one had cleft palate and another one had bifid uvula (PMID:37010288). The OMIM entry for White-Sutton syndrome (MIM #616364) does not currently include cleft lip/ palate as one of the clinical manifestations of this syndrome. |
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| Mendeliome v1.943 | SPTSSA | Zornitza Stark Phenotypes for gene: SPTSSA were changed from complex hereditary spastic paraplegia, MONDO:0015150 to Spastic paraplegia 90B, autosomal recessive , MIM# 620417; Spastic paraplegia 90A, autosomal dominant, MIM# 620416 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.942 | SPTSSA | Zornitza Stark reviewed gene: SPTSSA: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 90B, autosomal recessive , MIM# 620417, Spastic paraplegia 90A, autosomal dominant, MIM# 620416; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.941 | ARID1B |
Achchuthan Shanmugasundram changed review comment from: There are at least three unrelated cases with monoallelic variants in ARID1B gene reported with either cleft palate, cleft uvula or bifid uvula. Hence, this gene can be added with green rating in the Clefting disorders panel. PMID:30349098 - On this web-based survey based on previously reported features of patients with variants in ARID1B gene (143 patients in total), which also included submissions to DECIPHER database, two patients were identified with cleft palate, one with cleft uvula, two with bifid uvula and three with sub mucous cleft. Although variants identified in these patients are reported in this publication, there is no association of individual patients to phenotypes available. One patient with ARID1B variant (c.3183_3184insT/ p.Tyr1062LeufsTer10) was reported with submucous cleft soft palate and two patients with ARID1B variants (c.4155_4156insA/ p.Asn1386LysfsTer18 & c.2620+5G>A) were reported with bifid uvula in DECIPHER database.; to: Although there are more than three unrelated cases with ARID1B monoallelic variants reported with either cleft palate, cleft uvula or bifid uvula, clefting isn not consistently present in patients with ARID1B variants. Hence, this gene can be added with amber rating in the Clefting disorders panel. PMID:30349098 - On this web-based survey based on previously reported features of patients with variants in ARID1B gene (143 patients in total), which also included submissions to DECIPHER database, two patients were identified with cleft palate, one with cleft uvula, two with bifid uvula and three with sub mucous cleft. Although variants identified in these patients are reported in this publication, there is no association of individual patients to phenotypes available. Of >100 patients with ARID1B variants in the DECIPHER database, only one patient (c.3183_3184insT/ p.Tyr1062LeufsTer10) was reported with submucous cleft soft palate and two patients (c.4155_4156insA/ p.Asn1386LysfsTer18 & c.2620+5G>A) were reported with bifid uvula. |
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| Mendeliome v1.941 | ARID1B | Achchuthan Shanmugasundram edited their review of gene: ARID1B: Changed rating: AMBER | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.941 | CHD4 |
Achchuthan Shanmugasundram changed review comment from: This gene should be added to the Clefting disorders panel with a green rating as there are four unrelated cases presenting with either cleft palate and/or bifid uvula. PMID:3138819 reported a patient with heterozygous variant (p.Gln715Ter) in CHD4 that had cleft palate and pierre robin. In addition, another patient identified with heterozygous variant p.Arg1127Gln was reported with bifid uvula. In addition, DDD study reported two patients with likely pathogenic heterozygous variants who had cleft palate in addition to several other clinical presentations including global developmental delay (PMID:37010288); to: Although there are four unrelated cases presenting with either cleft palate and/or bifid uvula, this phenotype is not consistent among patients identified with monoallelic variants in CHD4 gene. Hence, this gene should be added to the Clefting disorders panel with amber rating. PMID:31388190 reported 32 patients with heterozygous variants in CHD4 gene, of which one patient (p.Gln715Ter) had cleft palate and pierre robin. In addition, another patient identified with heterozygous variant p.Arg1127Gln was reported with bifid uvula. In addition, 2 out of 10 patients with pathogenic/ likely pathogenic heterozygous variants from the DDD study were reported with cleft palate in addition to several other clinical presentations including global developmental delay (PMID:37010288). |
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| Mendeliome v1.941 | ARID1B | Achchuthan Shanmugasundram reviewed gene: ARID1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 30349098, 37010288; Phenotypes: Coffin-Siris syndrome 1, OMIM:135900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.939 | KLHL9 | Bryony Thompson Marked gene: KLHL9 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.938 | KLHL9 |
Bryony Thompson changed review comment from: A single German family reported in 2010, segregating a missense variant c.796T>C p.Leu95Phe. In vitro functional assays demonstrated the variant diminishes the binding of KLHL9 to Cul3. Sources: Literature; to: A single German family reported in 2010, segregating a missense variant c.796T>C p.Leu95Phe. In vitro functional assays demonstrated the variant diminishes the binding of KLHL9 to Cul3. Ankle flexion contracture is reported in a mouse model, but there are other significant features present in the homozygous animals too - https://www.mousephenotype.org/data/genes/MGI:2180122 Sources: Literature |
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| Mendeliome v1.938 | KLHL9 |
Bryony Thompson gene: KLHL9 was added gene: KLHL9 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KLHL9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KLHL9 were set to 20554658 Phenotypes for gene: KLHL9 were set to distal myopathy MONDO:0018949 Review for gene: KLHL9 was set to AMBER Added comment: A single German family reported in 2010, segregating a missense variant c.796T>C p.Leu95Phe. In vitro functional assays demonstrated the variant diminishes the binding of KLHL9 to Cul3. Sources: Literature |
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| Mendeliome v1.937 | MYMX | Bryony Thompson Marked gene: MYMX as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.936 | MYMX |
Bryony Thompson gene: MYMX was added gene: MYMX was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MYMX was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MYMX were set to 35642635 Phenotypes for gene: MYMX were set to Carey-Fineman-Ziter syndrome MONDO:0009700 Review for gene: MYMX was set to AMBER Added comment: Single family, two siblings with weakness of the facial musculature, hypomimic face, increased overbite, micrognathia, and facial dysmorphism with homozygous p.Arg46*. The phenotype resembles CFZ syndrome. The variant prevents fusion of myoblasts from patient-derived iPSCs. Mouse model recapitulates a lethal CFZS-like phenotype. Sources: Literature |
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| Mendeliome v1.935 | NOP10 | Zornitza Stark Phenotypes for gene: NOP10 were changed from Dyskeratosis congenita, autosomal recessive 1, MIM#224230; Telomere syndrome MONDO:0100137 to Dyskeratosis congenita, autosomal recessive 1, MIM#224230; Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 9, MIM# 620400 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.932 | NOP10 | Zornitza Stark edited their review of gene: NOP10: Added comment: PMID 32139460: large multiplex family with 4 affected individuals segregating a heterozygous variant.; Changed rating: AMBER; Changed publications: 17507419, 32139460; Changed phenotypes: Dyskeratosis congenita, autosomal recessive 1, MIM#224230, Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 9, MIM# 620400; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.932 | MFN2 | Zornitza Stark Phenotypes for gene: MFN2 were changed from Charcot-Marie-Tooth disease, axonal, type 2A2A, OMIM #609260; Charcot-Marie-Tooth disease, axonal, type 2A2B, OMIM #617087; Hereditary motor and sensory neuropathy VIA, OMIM #601152 to Charcot-Marie-Tooth disease, axonal, type 2A2A 609260; Charcot-Marie-Tooth disease, axonal, type 2A2B, MIM# 617087; Hereditary motor and sensory neuropathy VIA, MIM# 601152; Lipomatosis, multiple symmetric, with or without peripheral neuropathy, MIM# 151800 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.931 | MFN2 | Zornitza Stark edited their review of gene: MFN2: Changed phenotypes: Charcot-Marie-Tooth disease, axonal, type 2A2A 609260, Charcot-Marie-Tooth disease, axonal, type 2A2B, MIM# 617087, Hereditary motor and sensory neuropathy VIA, MIM# 601152, Lipomatosis, multiple symmetric, with or without peripheral neuropathy, MIM# 151800 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.928 | RHOBTB2 | Zornitza Stark reviewed gene: RHOBTB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 37165955; Phenotypes: Epileptic encephalopathy, early infantile, 64, MIM#618004; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.928 | NFATC1 | Zornitza Stark Marked gene: NFATC1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.927 | NFATC1 |
Zornitza Stark gene: NFATC1 was added gene: NFATC1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NFATC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NFATC1 were set to 37249233 Phenotypes for gene: NFATC1 were set to Inborn error of immunity, MONDO:0003778, NFATC1-related; Combined Immune deficiency Review for gene: NFATC1 was set to AMBER Added comment: 3 individuals from a multigenerational consanguineous pedigree with early-onset sinopulmonary infections and bronchiectasis, recurrent viral (warts) and bacterial (folliculitis and abscesses) skin infections, hypogammaglobulinemia, lower CD4+/CD8+ T-cell ratio and lower recent thymic emigrants compared with the age-matched controls. Lymphocyte proliferation responses to PHA and CD3/CD28 stimulations were defective. Single pedigree with supportive functional studies. Sources: Literature |
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| Mendeliome v1.922 | CHRM5 | Zornitza Stark Marked gene: CHRM5 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.922 | MRPL50 | Zornitza Stark Marked gene: MRPL50 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.921 | MOS | Zornitza Stark Marked gene: MOS as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.921 | MOS | Zornitza Stark Phenotypes for gene: MOS were changed from Early embryonic arrest and fragmentation; infertility to Infertility disorder, MONDO:0005047, MOS-related; Early embryonic arrest and fragmentation | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.919 | HMGCR | Zornitza Stark Phenotypes for gene: HMGCR were changed from [Low density lipoprotein cholesterol level QTL 3] to autosomal recessive limb-girdle muscular dystrophy (MONDO: 0015152), HMGCR-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.915 | MOS |
Melanie Marty gene: MOS was added gene: MOS was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MOS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MOS were set to PMID: 34779126; PMID: 34997960; PMID: 36403623; PMID: 35670744 Phenotypes for gene: MOS were set to Early embryonic arrest and fragmentation; infertility Review for gene: MOS was set to GREEN Added comment: PMID: 34779126: 3 x females with infertility with biallelic MOS variants identified. Using oocyte-specific Erk1/2 knockout mice, they verified that MOS-ERK signal pathway inactivation in oocytes caused early embryonic arrest and fragmentation. PMID: 34997960: 2 x females with biallelic MOS variants. Functional studies showed a reduction of protein for two of these variants (missense and frameshift). Functional studies also showed these variants reduced the ability of MOS to phosphorylate its downstream target, extracellular signal-regulated kinase 1/2. PMID: 35670744 1 x additional family (twins) with infertility and abnormal oocyte morphology with large first polar body. Functional studies showed the MOS variants could not activate MEK1/2 and ERK1/2 in oocytes and HEK293 cells. In addition, functional studies also showed when compared with wild-type MOS, the MOS variants decreased the MOS protein level and attenuated the binding capacity with MEK1. PMID: 36403623 1 x female with primary infertility, patient’s oocytes had a large polar body and poor embryonic development, hom missense variant in MOS identified. Sources: Literature |
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| Mendeliome v1.911 | NSUN6 | Elena Savva Marked gene: NSUN6 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.911 | TAPT1 | Paul De Fazio reviewed gene: TAPT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 36697720, 36652330; Phenotypes: Osteochondrodysplasia, complex lethal, Symoens-Barnes-Gistelinck type (MIM#616897); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.910 | PRSS8 | Elena Savva Marked gene: PRSS8 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.908 | PRSS8 |
Lucy Spencer gene: PRSS8 was added gene: PRSS8 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PRSS8 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PRSS8 were set to 36715754 Phenotypes for gene: PRSS8 were set to ichthyosis MONDO:0019269, PRSS8-related Review for gene: PRSS8 was set to AMBER Added comment: PMID: 36715754 1 family with 3 affected sons with congenital ichthyosis, consanguineous parents. All 3 affected members are homozygous for a canonical splice in PRSS8, quantitative RT-PCR showed a significant reduction in normal PRSS8 transcript. A second family with 4 affected members (proband and 3 cousins) with ichthyosis (3 also had autism), also consanguineous. Only the proband was tested who is homozygous for a missense in PTSS8. However this patient also had a TAAR1 missense (no disease association, but the paper suggests this could be responsible for the autism phenotype- KO mice have abnormal learning behaviour). Sources: Literature |
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| Mendeliome v1.908 | UNC79 | Elena Savva Marked gene: UNC79 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.906 | NSUN6 |
Michelle Torres gene: NSUN6 was added gene: NSUN6 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NSUN6 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NSUN6 were set to 37226891 Phenotypes for gene: NSUN6 were set to neurodevelopmental disorder MONDO:0700092, NSUN6-related Review for gene: NSUN6 was set to AMBER Added comment: Three unrelated consanguineous families with developmental delay, intellectual disability, motor delay, and behavioral anomalies. WES detected homozygous variants: - p.(Leu9Glufs*3): even though authors say is is predicted to cause NMD, it actually is NMD escape. No further studies were performed. A deceased affected sibling and parents were NOT tested. - p.(Asp323Asn): Shown to result in a misfolded protein. Methylation assay showed mutant could not catalyze m5C deposition in transcribed tRNACys and tRNAThr substrates in vitro. One of the parents and both unaffected siblings were shown to be carriers. - p.(Glu441Profs*15): truncation (full protein is 470aa) which would result in loss of residues involved in recognition and methylation. Shown to result in a misfolded protein. Parents were shown carriers. Sources: Literature |
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| Mendeliome v1.906 | HMGCR | Naomi Baker reviewed gene: HMGCR: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37167966, 36745799; Phenotypes: autosomal recessive limb-girdle muscular dystrophy (MONDO: 0015152), HMGCR-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.906 | UNC79 |
Krithika Murali gene: UNC79 was added gene: UNC79 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: UNC79 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: UNC79 were set to PMID:37183800 Phenotypes for gene: UNC79 were set to Neurodevelopmental disorderMONDO:0700092 Review for gene: UNC79 was set to AMBER Added comment: PMID:37183800 Bayat et al 2023 report 6 unrelated patients with heterozygous NMD-predicted LoF variants in UNC79 - x1 canonical splice site variant, x5 nonsense/frameshift. 5 were confirmed de novo, 1 not identified in mother - father unavailable for testing. All variants absent in gnomAD and v2 pLI score for UNC79 is 1. Patients with UNC79 variants were identified through GeneMatcher or an international network of Epilepsy and Genetics departments. x1 patient underwent duo exome sequencing, remaining had trio exome sequencing - no other causative variants identified. Phenotypic features included: - 4/6 autistic features - 5/6 patients mild-moderate ID - 4/6 behavioural issues (aggression, stereotypies) - 4/6 epilepsy (focal to bilateral tonic-clonic seizures) - 5/6 hypotonia unc79 knockdown drosophila flies exhibited significantly higher rate of seizure-like behaviour than controls. unc79 haploinsufficiency shown to lead to significant reduction in protein levels of both unc79 and unc80 in mouse brains. Unc79 haploinsufficiency associated with deficiency in hippocampal-dependent learning and memory in mice. Authors have reviewed their own evidence in relation to the gene-disease criteria detailed by Strande et al 2017 and note that their clinical and experimental data provides moderate-level evidence supporting the association between UNC79 and a neurodevelopment disorder including ASD. Amber association favoured due to clinical phenotypic range reported between affected individuals and their lack of specificity. Sources: Literature |
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| Mendeliome v1.904 | NPR1 | Zornitza Stark Marked gene: NPR1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.903 | MRPL50 |
Anna Ritchie gene: MRPL50 was added gene: MRPL50 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MRPL50 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MRPL50 were set to PMID: 37148394 Phenotypes for gene: MRPL50 were set to Mitochondrial disease, MONDO: 004470, MRPL50-related Added comment: A homozygous missense variant (c.335T>A; p.Val112Asp) shared by twin sisters presenting with premature ovarian insufficiency, bilateral high-frequency sensorineural hearing loss, kidney and heart dysfunction. Quantitative proteomics data demonstrated a significant reduction in abundance of MRPL50 protein when compared with controls. Patient fibroblasts have a mild but significant decrease in the abundance of mitochondrial complex I. This data supports a biochemical phenotype associated with MRPL50 variants. Knockdown/knockout of mRpL50 in Drosophila, resulted abnormal ovarian development. Sources: Literature |
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| Mendeliome v1.903 | POU3F2 | Ain Roesley Marked gene: POU3F2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.903 | ACBD6 | Elena Savva Marked gene: ACBD6 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.903 | ACBD6 | Elena Savva Marked gene: ACBD6 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.901 | ACBD6 | Elena Savva Marked gene: ACBD6 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.898 | NPR1 |
Lilian Downie gene: NPR1 was added gene: NPR1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NPR1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NPR1 were set to PMID: 37080586 Phenotypes for gene: NPR1 were set to Genetic hypertension MONDO:0015512 Review for gene: NPR1 was set to GREEN Added comment: 4 sibs with systemic hypertension in the neonatal period - presenting with cardiogenic shock, with homozygous variants (consanguineous parents), parents confirmed heterozygotes. 3/4 infants had increased NT (>3.5) in utero RT-PCR shows dramatic reduction of RNA levels 2 sibs in a second family, normal NT and pregnancy, neonatal systematic hypertension presenting with cardiogenic shock, Sources: Literature |
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| Mendeliome v1.898 | POU3F2 |
Sarah Pantaleo gene: POU3F2 was added gene: POU3F2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: POU3F2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: POU3F2 were set to PMID: 37207645 Phenotypes for gene: POU3F2 were set to Autism spectrum disorder, NDD, and adolescent-onset obesity Penetrance for gene: POU3F2 were set to unknown Mode of pathogenicity for gene: POU3F2 was set to Other Review for gene: POU3F2 was set to GREEN Added comment: We associate ultra-rare variants in POU3F2, encoding a central nervous system transcription factor, with syndromic obesity and neurodevelopment delay in 12 individuals. Demonstrate variant pathogenicity through in vitro analysis. Used exome sequencing, GeneMatcher and Genomics England 100,000 Genomes Project rare disease database. Both truncating and missense variants in over 10 individuals sharing autism spectrum disorder, NDD, and adolescent-onset obesity (may have had other features eg. CAKUT in 2 individuals, diabetes in two) . Affected individuals presented with low-to-normal birth weight and infantile feeding difficulties but developed insulin resistance and hyperplasia during childhood. With the exception of an early truncating variant, the variants showed adequate nuclear translocation but overall disturbed DNA-binding ability and promoter activation. Variants absent from population and clinical databases. Almost all constituted putatively non-inherited de novo variants (8/10). Functional studies provide evidence for loss of function in eight and gain of function in one obesity-associated POU3F2 variant. One variant did not impact POU3F2-promoter activation, leaving the possibility for further path-mechanisms. Sources: Literature |
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| Mendeliome v1.897 | ACBD6 |
Lucy Spencer gene: ACBD6 was added gene: ACBD6 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ACBD6 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ACBD6 were set to 36457943; 21937992; 35446914 Phenotypes for gene: ACBD6 were set to Neurodevelopmental disorder (MONDO#0700092), ACBD6-related Review for gene: ACBD6 was set to GREEN Added comment: PMID: 36457943 2 siblings with a neurodevelopmental disorder: severely delayed development, obesity, pancytopenia, diabetes, liver cirrhosis, intravertebral disc herniation, mild brain atrophy. Consanguineous family both siblings found to have a homozygous frameshift. This paper also mentioned 3 other reported variants in 6 individuals (only 3 unrelated) all homozygous, 2 frameshift, 1 canonical splice. All reported to have a neurodevelopmental disorder, some with limited information but one family also has obesity, spasticity, and dysmorphism. PMIDs: 21937992, 35446914 Sources: Literature |
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| Mendeliome v1.896 | CHRM5 |
Elena Savva gene: CHRM5 was added gene: CHRM5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CHRM5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CHRM5 were set to 37213061 Phenotypes for gene: CHRM5 were set to Congenital anomaly of kidney and urinary tract, (MONDO:0019719), CHRM5-related Review for gene: CHRM5 was set to RED Added comment: PMID: 37213061 - homozygous missense p.(Q184R) in a proband with neurogenic bladder and CAKUT. Additional features were small trabeculated urinary bladder, bilateral severe hydronephrosis, grade V VUR right, chronic kidney disease (stage 4). - Radioligand binding experiments were inconclusive - the missense variant had no effect on receptor expression or binding affinity. - ACh binding assay did show a 2-fold increase (borderline significant), but no effect in secondary messenger accumulation. - Transfected CHO line showed no effect on receptor expression - Described a mouse K/O as having a bladder overactivity No hom PTCs in gnomAD Sources: Literature |
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| Mendeliome v1.894 | AMFR | Zornitza Stark Marked gene: AMFR as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.894 | AMFR | Zornitza Stark Phenotypes for gene: AMFR were changed from Hereditary spastic paraplegia, MONDO:0019064 to Spastic paraplegia 89, autosomal recessive, MIM# 620379 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.892 | AMFR | Zornitza Stark reviewed gene: AMFR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 89, autosomal recessive, MIM# 620379; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.891 | ATP11A | Zornitza Stark edited their review of gene: ATP11A: Added comment: PMID 35278131 reports three additional families with deafness, including segregation in a large pedigree.; Changed rating: GREEN; Changed publications: 35278131 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.891 | SCN4A | Zornitza Stark Phenotypes for gene: SCN4A were changed from Hyperkalemic periodic paralysis, type 2, MIM# 170500; Hypokalemic periodic paralysis, type 2, MIM# 613345; Myasthenic syndrome, congenital, 16, MIM# 614198; Myotonia congenita, atypical, acetazolamide-responsive , MIM#608390; Paramyotonia congenita , MIM#168300 to Congenital myopathy 22A, classic, MIM# 620351; Congenital myopathy 22B, severe fetal, MIM# 620369; Hyperkalemic periodic paralysis, type 2, MIM# 170500; Hypokalemic periodic paralysis, type 2, MIM# 613345; Myasthenic syndrome, congenital, 16, MIM# 614198; Myotonia congenita, atypical, acetazolamide-responsive , MIM#608390; Paramyotonia congenita , MIM#168300 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.890 | SCN4A | Zornitza Stark edited their review of gene: SCN4A: Changed phenotypes: Congenital myopathy 22A, classic, MIM# 620351, Congenital myopathy 22B, severe fetal, MIM# 620369, Hyperkalemic periodic paralysis, type 2, MIM# 170500, Hypokalemic periodic paralysis, type 2, MIM# 613345, Myasthenic syndrome, congenital, 16, MIM# 614198, Myotonia congenita, atypical, acetazolamide-responsive , MIM#608390, Paramyotonia congenita , MIM#168300 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.885 | GIGYF2 | Bryony Thompson reviewed gene: GIGYF2: Rating: RED; Mode of pathogenicity: None; Publications: 18358451, 33239198, 25279164, 20060621, 19250854, 26152800; Phenotypes: {Parkinson disease 11} , OMIM # 607688; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.885 | NDUFA13 | Lucy Spencer reviewed gene: NDUFA13: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex I deficiency, nuclear type 28, MIM# 618249; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.879 | GATAD2A |
Bryony Thompson changed review comment from: https://doi.org/10.1016/j.xhgg.2023.100198 - Five unrelated individuals with a neurodevelopmental disorder identified with 3 missense & 2 LoF (4 de novo & 1 unknown inheritance). The shared clinical features with variable expressivity include global developmental delay (4/4), craniofacial dysmorphism (3/5), structural brain defects (2/3), musculoskeletal anomalies (3/5), vision/hearing defects (2/3), gastrointestinal/renal defects (2/3). Loss of function is the expected mechanism of disease. In vitro assays of one of the missense variants (p.Cys420Tyr) demonstrates disruption of GATAD2A integration with CHD3, CHD4, and CHD5 PMID: 17565372 - null mouse model is embryonic lethal. Sources: Literature; to: PMID: 37181331 - Five unrelated individuals with a neurodevelopmental disorder identified with 3 missense & 2 LoF (4 de novo & 1 unknown inheritance). The shared clinical features with variable expressivity include global developmental delay (4/4), craniofacial dysmorphism (3/5), structural brain defects (2/3), musculoskeletal anomalies (3/5), vision/hearing defects (2/3), gastrointestinal/renal defects (2/3). Loss of function is the expected mechanism of disease. In vitro assays of one of the missense variants (p.Cys420Tyr) demonstrates disruption of GATAD2A integration with CHD3, CHD4, and CHD5 PMID: 17565372 - null mouse model is embryonic lethal. Sources: Literature |
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| Mendeliome v1.879 | NAF1 | Zornitza Stark Phenotypes for gene: NAF1 were changed from Pulmonary fibrosis and/or bone marrow failure, telomere-related MONDO:0000148 to Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 7, MIM# 620365 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.878 | NAF1 | Zornitza Stark reviewed gene: NAF1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 7, MIM# 620365; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.877 | ARFGEF3 | Ain Roesley reviewed gene: ARFGEF3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Dystonia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.877 | RRAGC | Zornitza Stark Phenotypes for gene: RRAGC were changed from Dilated cardiomyopathy; cataract to Dilated cardiomyopathy (MONDO:0005021), RRAGC-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.873 | ATP5O | Zornitza Stark Phenotypes for gene: ATP5O were changed from mitochondrial disease, ATP5F1E-related MONDO:0044970 to Mitochondrial complex V (ATP synthase) deficiency, nuclear type 7, MIM# 620359 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.870 | ATP5O | Zornitza Stark reviewed gene: ATP5O: Rating: GREEN; Mode of pathogenicity: None; Publications: 35621276; Phenotypes: Mitochondrial complex V (ATP synthase) deficiency, nuclear type 7, MIM# 620359; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.869 | AMFR |
Yetong Chen gene: AMFR was added gene: AMFR was added to Mendeliome. Sources: Literature Mode of inheritance for gene: AMFR was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AMFR were set to 37119330 Phenotypes for gene: AMFR were set to Hereditary spastic paraplegia, MONDO:0019064 Review for gene: AMFR was set to GREEN Added comment: PMID 37119330 reports 20 individuals harbouring AMFR variants from 8 unrelated, consanguineous families. All patients had early disease onset (<3 years), including motor delay, lower limb hyperreflexia and spastic paraplegia that match the typical phenotypes of hereditary spastic paraplegia. Sources: Literature |
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| Mendeliome v1.868 | POLD3 | Bryony Thompson Marked gene: POLD3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.868 | POLD3 |
Bryony Thompson gene: POLD3 was added gene: POLD3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: POLD3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: POLD3 were set to 37030525; 36395985; 27524497 Phenotypes for gene: POLD3 were set to Severe combined immunodeficiency MONDO:0015974 Review for gene: POLD3 was set to AMBER Added comment: Homozygous missense variant (NM_006591.3; p.Ile10Thr) identified in a single Lebanese patient, the product of a consanguineous family, presenting with a syndromic severe combined immunodeficiency with neurodevelopmental delay and hearing loss. POLD3 as well as POLD1 and POLD2 expression was abolished in the patient's cells. Null mouse models are embryonic lethal and demonstrate Pold3 is essential for DNA replication in murine B cells. Sources: Literature |
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| Mendeliome v1.864 | SLC4A2 | Zornitza Stark Marked gene: SLC4A2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.863 | SLC4A2 |
Zornitza Stark gene: SLC4A2 was added gene: SLC4A2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SLC4A2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC4A2 were set to 34668226; 20507629 Phenotypes for gene: SLC4A2 were set to Osteopetrosis, autosomal recessive 9, MIM# 620366 Review for gene: SLC4A2 was set to AMBER Added comment: Single individual reported with homozygous missense variant. However, cattle and mouse models support gene-disease association. Sources: Literature |
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| Mendeliome v1.862 | ZCCHC8 | Bryony Thompson Phenotypes for gene: ZCCHC8 were changed from Pulmonary fibrosis to pulmonary fibrosis and/or bone marrow failure, telomere-related MONDO:0000148 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.861 | ZCCHC8 | Bryony Thompson edited their review of gene: ZCCHC8: Changed phenotypes: pulmonary fibrosis and/or bone marrow failure, telomere-related MONDO:0000148 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.858 | ACD | Bryony Thompson Phenotypes for gene: ACD were changed from Dyskeratosis congenita, MIM# 616553 to telomere syndrome MONDO:0100137; dyskeratosis congenita, autosomal dominant 6 MONDO:0014690; Hoyeraal-Hreidarsson syndrome MONDO:0018045 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.855 | ACD | Bryony Thompson reviewed gene: ACD: Rating: GREEN; Mode of pathogenicity: None; Publications: 27807141, 31515401, 30995915, 27528712, 25205116, 24316971, 30064976, 33446513, 25233904; Phenotypes: telomere syndrome MONDO:0100137, dyskeratosis congenita, autosomal dominant 6 MONDO:0014690, Hoyeraal-Hreidarsson syndrome MONDO:0018045; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.855 | RRAGC | Naomi Baker reviewed gene: RRAGC: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:37057673, 27234373, 33057194; Phenotypes: Dilated cardiomyopathy (MONDO:0005021), RRAGC-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.855 | MCAT | Zornitza Stark reviewed gene: MCAT: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Leber hereditary optic neuropathy, autosomal recessive, MONDO:0030309; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.855 | MCAT | Zornitza Stark Phenotypes for gene: MCAT were changed from progressive autosomal recessive optic neuropathy to Leber hereditary optic neuropathy, autosomal recessive, MONDO:0030309 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.854 | DNAH7 | Zornitza Stark Phenotypes for gene: DNAH7 were changed from non-syndromic male infertility due to sperm motility disorder (MONDO#0017173), DNAH7-related to Primary ciliary dyskinesia, MONDO:0016575, DNAH7-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.853 | DNAH7 | Zornitza Stark reviewed gene: DNAH7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Primary ciliary dyskinesia, MONDO:0016575, DNAH7-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.853 | RARA |
Zornitza Stark commented on gene: RARA: PMID: 37086723 identified a recurrent, heterozygous de novo missense variant in the RARA gene - c.865G>A; (p.Gly289Arg) - in two unrelated individuals. The variant is absent from gnomAD, highly conserved, major grantham score (125) and is located in the hormone receptor domain (DECIPHER). Both individuals had severe craniosynostosis (sagittal or bicoronal). Other shared phenotypic features included: - Limb anomalies (rocker-bottom feet, bowing of the legs, and short upper/lower limbs) - Additional craniofacial manifestations(microtia, conductive hearing loss, ankyloglossia, esotropia, hypoplastic nasal bones, and oligodontia) - Other additional anomalies included renal dysplasia with cysts, tracheomalacia, pulmonary arterial hypertension, developmental delays, hypotonia, cryptorchidism, seizures and adrenal insufficiency. The authors postulate a gain of function mechanism. No functional studies provided. The gene encodes the retinoic acid receptor. Overlapping phenotypic features in these 2 affected individuals with retinoic acid embryopathy noted by the authors. |
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| Mendeliome v1.853 | RARA | Zornitza Stark Phenotypes for gene: RARA were changed from Syndromic chorioretinal coloboma to Craniosynostosis - MONDO:0015469; Syndromic chorioretinal coloboma | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.852 | RARA | Zornitza Stark Publications for gene: RARA were set to 31343737 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.851 | RARA | Zornitza Stark Classified gene: RARA as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.851 | RARA | Zornitza Stark Gene: rara has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.850 | RARA |
Zornitza Stark edited their review of gene: RARA: Added comment: PMID: 37086723 identified a recurrent, heterozygous de novo missense variant in the RARA gene - c.865G>A; (p.Gly289Arg) - in two unrelated individuals. The variant is absent from gnomAD, highly conserved, major grantham score (125) and is located in the hormone receptor domain (DECIPHER). Both individuals had severe craniosynostosis (sagittal or bicoronal). Other shared phenotypic features included: - Limb anomalies (rocker-bottom feet, bowing of the legs, and short upper/lower limbs) - Additional craniofacial manifestations(microtia, conductive hearing loss, ankyloglossia, esotropia, hypoplastic nasal bones, and oligodontia) - Other additional anomalies included renal dysplasia with cysts, tracheomalacia, pulmonary arterial hypertension, developmental delays, hypotonia, cryptorchidism, seizures and adrenal insufficiency. The authors postulate a gain of function mechanism. No functional studies provided. The gene encodes the retinoic acid receptor. Overlapping phenotypic features in these 2 affected individuals with retinoic acid embryopathy noted by the authors.; Changed rating: AMBER; Changed publications: 31343737, 37086723; Changed phenotypes: Craniosynostosis - MONDO:0015469, Syndromic chorioretinal coloboma; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
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| Mendeliome v1.850 | PMEPA1 | Zornitza Stark Phenotypes for gene: PMEPA1 were changed from Familial thoracic aortic aneurysm disease (FTAAD); Loeys-Dietz syndrome to Hereditary disorder of connective tissue, MONDO:0023603, PMEPA1-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.849 | PMEPA1 | Zornitza Stark reviewed gene: PMEPA1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Hereditary disorder of connective tissue, MONDO:0023603, PMEPA1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.849 | NAF1 | Bryony Thompson Marked gene: NAF1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.848 | NAF1 |
Bryony Thompson gene: NAF1 was added gene: NAF1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: NAF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: NAF1 were set to 27510903 Phenotypes for gene: NAF1 were set to Pulmonary fibrosis and/or bone marrow failure, telomere-related MONDO:0000148 Review for gene: NAF1 was set to GREEN Added comment: At least 3 probands/families with telomere-related pulmonary fibrosis and a supporting mouse model PMID: 27510903 - 5 individuals from 2 unrelated families with pulmonary fibrosis-emphysema and extrapulmonary manifestations including myelodysplastic syndrome and liver disease, with LoF variants. Truncated NAF1 was detected in cells derived from patients, and, in cells in which a frameshift mutation was introduced by genome editing telomerase RNA levels were reduced. Shortened telomere length also segregated with the variants. A Naf1+/- mouse model had reduced telomerase RNA levels ClinVar - 1 nonsense and 2 splice site variants (ID: 2443185, 1338525, 2443184) called LP by the Genetic Services Laboratory, University of Chicago but no clinical details were provided - SCV002547372.1 - Garcia Pulmonary Genetics Research Laboratory, Columbia University Irving Medical Center - at least one individual with pulmonary fibrosis and leukocyte telomere length (by qPCR) less than 10th percentile age-adjusted Sources: Expert list |
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| Mendeliome v1.847 | PMEPA1 |
Hazel Phillimore changed review comment from: PMID: 36928819; Greene, D. et al. (2023) Nat Med. 29(3):679-688. A paper by Genomics England Research Consortium. Genetic association analysis of 77,539 genomes . Eight families with truncating variants affecting the same stretch of cytosines in this gene. In the 100KGP discovery cohort, in three families with Familial thoracic aortic aneurysm disease (FTAAD) of European ancestry, the variant found was an insertion of a cytosine within a seven-cytosine stretch in the last exon, predicted to cause p.(S209Qfs*3). This variant was also identified independently in eight affected members of three pedigrees of Japanese ancestry in a separate Japanese patient group. Also, this study found a deletion of one of those cytosines causing p.(S209Afs*61), in one individual or family. Also, there was one family in Belgium in which the affected members carried a 5-bp deletion in the same stretch of polycytosines inducing a frameshift p.(P207Qfs*3). Phenotypic analysis of the individuals suggest that the phenotype of these FTAAD individuals and families is more like Loeys-Dietz syndrome. Sources: Literature; to: PMID: 36928819; Greene, D. et al. (2023) Nat Med. 29(3):679-688. A paper by Genomics England Research Consortium. Genetic association analysis of 77,539 genomes . Eight families with truncating variants affecting the same stretch of cytosines in this gene. In the 100KGP discovery cohort, in three families with Familial thoracic aortic aneurysm disease (FTAAD) of European ancestry, the variant found was an insertion of a cytosine within a seven-cytosine stretch in the last exon, predicted to cause p.(S209Qfs*3). This variant was also identified independently in eight affected members of three pedigrees of Japanese ancestry in a separate Japanese patient group. (Note: the variant is present in gnomAD v2.1.1 in 22 heterozygotes as a filtered out variant.). Also, this study found a deletion of one of those cytosines causing p.(S209Afs*61), in one individual or family. Also, there was one family in Belgium in which the affected members carried a 5-bp deletion in the same stretch of polycytosines inducing a frameshift p.(P207Qfs*3). Phenotypic analysis of the individuals suggest that the phenotype of these FTAAD individuals and families is more like Loeys-Dietz syndrome. Sources: Literature |
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| Mendeliome v1.847 | PMEPA1 | Seb Lunke Marked gene: PMEPA1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.846 | LHX2 | Zornitza Stark Marked gene: LHX2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.845 | CNOT9 | Zornitza Stark Marked gene: CNOT9 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.845 | CBX1 | Seb Lunke Marked gene: CBX1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.842 | LHX2 |
Manny Jacobs gene: LHX2 was added gene: LHX2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: LHX2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: LHX2 were set to PMID: 37057675 Phenotypes for gene: LHX2 were set to Neurodevelopmental disorder (MONDO: 0700092) Review for gene: LHX2 was set to GREEN Added comment: PMID: 37057675 Case series of 19 individuals across 18 families. 1 whole gene deletion, 7 missense, 10 predicted LoF variants. Proposed loss-of-function mechanism. Variable phenotype, with variable intellectual disability and behavioural (ASD/ADHD) features. Microcephaly in 7 individuals. 1 variant inherited from a mildly affected parent, all other variants with parental genotype available shown to be de novo. Sources: Literature |
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| Mendeliome v1.842 | DNAH7 | Seb Lunke Marked gene: DNAH7 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.841 | PMEPA1 |
Hazel Phillimore gene: PMEPA1 was added gene: PMEPA1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PMEPA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PMEPA1 were set to PMID: 36928819 Phenotypes for gene: PMEPA1 were set to Familial thoracic aortic aneurysm disease (FTAAD); Loeys-Dietz syndrome Mode of pathogenicity for gene: PMEPA1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: PMEPA1 was set to AMBER Added comment: PMID: 36928819; Greene, D. et al. (2023) Nat Med. 29(3):679-688. A paper by Genomics England Research Consortium. Genetic association analysis of 77,539 genomes . Eight families with truncating variants affecting the same stretch of cytosines in this gene. In the 100KGP discovery cohort, in three families with Familial thoracic aortic aneurysm disease (FTAAD) of European ancestry, the variant found was an insertion of a cytosine within a seven-cytosine stretch in the last exon, predicted to cause p.(S209Qfs*3). This variant was also identified independently in eight affected members of three pedigrees of Japanese ancestry in a separate Japanese patient group. Also, this study found a deletion of one of those cytosines causing p.(S209Afs*61), in one individual or family. Also, there was one family in Belgium in which the affected members carried a 5-bp deletion in the same stretch of polycytosines inducing a frameshift p.(P207Qfs*3). Phenotypic analysis of the individuals suggest that the phenotype of these FTAAD individuals and families is more like Loeys-Dietz syndrome. Sources: Literature |
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| Mendeliome v1.841 | GPR156 | Zornitza Stark Marked gene: GPR156 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.839 | CBX1 |
Daniel Flanagan gene: CBX1 was added gene: CBX1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: CBX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CBX1 were set to PMID: 37087635 Phenotypes for gene: CBX1 were set to Neurodevelopmental disorder (MONDO#0700092), CBX1-related Review for gene: CBX1 was set to GREEN Added comment: Three different de novo missense variants identified in three unrelated individuals with developmental delay, hypotonia, autistic features, and variable dysmorphic features such as broad forehead and head circumference above average. Mutant mice displayed increased latency-to-peak response, suggesting the possibility of synaptic delay or myelination deficits. Functional studies confirmed the reduction of mutant HP1β binding to heterochromatin. Sources: Expert list |
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| Mendeliome v1.838 | SRSF1 | Zornitza Stark Marked gene: SRSF1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.838 | CNOT9 |
Karina Sandoval gene: CNOT9 was added gene: CNOT9 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CNOT9 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: CNOT9 were set to PMID: 37092538 Phenotypes for gene: CNOT9 were set to neurodevelopmental disorder, MONDO:0700092 Review for gene: CNOT9 was set to GREEN Added comment: 7 individuals with de novo variants. In silico predictions of functional relevance. All affected persons have DD/ID, with five of them showing seizures. Other symptoms include. Symptoms: Neuro dev disorder. ID, Epilepsy. All affected persons have DD/ID, with five of them showing seizures. Other symptoms include muscular hypotonia, facial dysmorphism, and behavioral abnormalities. Sources: Literature |
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| Mendeliome v1.837 | DNAH7 |
Chern Lim gene: DNAH7 was added gene: DNAH7 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: DNAH7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DNAH7 were set to 34476482; 35543642 Phenotypes for gene: DNAH7 were set to non-syndromic male infertility due to sperm motility disorder (MONDO#0017173), DNAH7-related Review for gene: DNAH7 was set to GREEN gene: DNAH7 was marked as current diagnostic Added comment: PMID: 34476482 (Wei et al 2021): - Hom/chet missense DNAH7 variants in three unrelated infertile patients with idiopathic asthenozoospermia, presented with primary ciliary dyskinesia (PCD)-associated symptoms. - Functional studies showed expression of DNAH7 in the spermatozoa from the DNAH7-defective patients was significantly decreased. PMID: 35543642 (Gao et al 2022): - One proband with idiopathic asthenozoospermia, presented a history of PCD-like symptoms. Hom frameshift variant predicted to cause NMD, both parents are heterozygous. - Immunofluorescent staining showed DNAH7 signal significantly decreased or was even completely absent in the sperm from the investigated patient. Sources: Literature |
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| Mendeliome v1.837 | INTS11 | Seb Lunke Marked gene: INTS11 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.837 | MRPL39 |
Lilian Downie changed review comment from: AR 3 unrelated individuals, confirmed variants in trans Functional studies on patient fibroblasts Multisystem disease, variable onset 2x infants with a clinical diagnosis of Leigh syndrome (congestive cardiac failure, increased lactates, seizures, apnea, poor feeding, and global developmental delay, leading to early death (< 1 year of age)) Adult with hypertrophic cardiomyopathy, lactic acidosis, ADHD Sources: Literature; to: AR 3 unrelated individuals, confirmed variants in trans Functional studies on patient fibroblasts Multisystem disease, variable onset 2x infants with a clinical diagnosis of Leigh syndrome (congestive cardiac failure, increased lactates, seizures, apnea, poor feeding, and global developmental delay, leading to early death (< 1 year of age)) Adult with hypertrophic cardiomyopathy, lactic acidosis, ADHD Sources: Literature |
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| Mendeliome v1.836 | INTS11 |
Melanie Marty changed review comment from: PMID: 37054711 - 15 individuals from 10 unrelated families with bi-allelic variants in INTS11 with global developmental and language delay, intellectual disability, impaired motor development, and brain atrophy.; to: PMID: 37054711 - 15 individuals from 10 unrelated families with bi-allelic variants in INTS11 with global developmental and language delay, intellectual disability, impaired motor development, and brain atrophy. Functional studies in Drosophila showed that dIntS11 (fly ortholog of INTS11) is essential and expressed in the central nervous systems in a subset of neurons and most glia in larval and adult stages. |
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| Mendeliome v1.836 | SRSF1 |
Paul De Fazio gene: SRSF1 was added gene: SRSF1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SRSF1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: SRSF1 were set to 37071997 Phenotypes for gene: SRSF1 were set to Neurodevelopmental disorder, SRSF1-related MONDO:0700092 Review for gene: SRSF1 was set to GREEN gene: SRSF1 was marked as current diagnostic Added comment: 17 individuals from 16 families reported with mostly de novo variants. Variants were a mixture of missense, nonsense/frameshift (both NMD-predicted and not NMD-predicted) and microdeletions. In one family, only one parent was available for testing. In another family, 2 affected siblings had the variant but the variant was not identified in either parent suggesting germline mosaicism. Functional testing of a subset of variants in Drosophila supported pathogenicity in most, but 2 missense variants showed no functional effect and were classified VUS. Episignature analysis (EpiSign) on patient DNA from blood showed a specific DNA methylation signature in patients with the variants classified pathogenic but not those classified VUS. Phenotypes included mainly neurological abnormalities (mild to moderate ID/dev delay, motor delay, speech delay, and behavioural disorders) and facial dysmorphisms. Other features included hypotonia (11/16), variable brain abnormalities on MRI (6/12), variable cardiac malformations (6/14). urogenital malformations e.g. hypospadias, cryptorchidism (6/13), scoliosis (5/17) and/or variable other skeletal abnormalities (10/17). Sources: Literature |
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| Mendeliome v1.835 | SLC30A9 | Zornitza Stark Marked gene: SLC30A9 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.834 | SLC30A9 |
Lucy Spencer gene: SLC30A9 was added gene: SLC30A9 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SLC30A9 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC30A9 were set to 37041080 Phenotypes for gene: SLC30A9 were set to Birk-Landau-Perez syndrome (MIM#617595) Review for gene: SLC30A9 was set to GREEN Added comment: PMID:37041080 - 2 families previously reported and this paper describes 4 more with biallelic SLC30A9 variants. Original 2 families: 6 affected members all hom for Ala350del, and 1 affected member chet for 2 frameshifts. 4 families from this paper: 2 families have the same homozygous missense (Gly418Val), family 3 has 4 affected sibs hom for Ala350del, family 4 1 affected chet for a frameshift and a synonymous. So 2 fams homs for Ala350del and 2 fams hom for Gly418Val. All have Brik-Landau-Perez syndrome: all with ID, movement disorder and dystonia, and many with oculomotor apraxia, renal abnormalitie, ptosis, some had hearing impairment. Sources: Literature |
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| Mendeliome v1.834 | GPR156 |
Anna Ritchie gene: GPR156 was added gene: GPR156 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GPR156 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GPR156 were set to PMID: 36928819 Phenotypes for gene: GPR156 were set to Sensorineural hearing loss, MONDO:60700002, GPR156-related Review for gene: GPR156 was set to GREEN Added comment: Eight affected individuals from three unrelated families with congenital nonsyndromic bilateral sensorineural hearing loss. Homozygous or compound heterozygous loss of function variants were reported in these families. Sources: Literature |
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| Mendeliome v1.834 | MRPL39 |
Lilian Downie changed review comment from: AR 3 unrelated individuals, confirmed variants in trans Functional studies on patient fibroblasts Multisystem disease, variable onset 2x infants with a clinical diagnosis of Leigh syndrome (MIM 256000) Adult with hypertrophic cardiomyopathy, lactic acidosis, ADHD Sources: Literature; to: AR 3 unrelated individuals, confirmed variants in trans Functional studies on patient fibroblasts Multisystem disease, variable onset 2x infants with a clinical diagnosis of Leigh syndrome (congestive cardiac failure, increased lactates, seizures, apnea, poor feeding, and global developmental delay, leading to early death (< 1 year of age)) Adult with hypertrophic cardiomyopathy, lactic acidosis, ADHD Sources: Literature |
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| Mendeliome v1.834 | MRPL39 |
Lilian Downie gene: MRPL39 was added gene: MRPL39 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MRPL39 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MRPL39 were set to PMID: 37133451 Phenotypes for gene: MRPL39 were set to Leigh syndrome MONDO:0009723 Added comment: AR 3 unrelated individuals, confirmed variants in trans Functional studies on patient fibroblasts Multisystem disease, variable onset 2x infants with a clinical diagnosis of Leigh syndrome (MIM 256000) Adult with hypertrophic cardiomyopathy, lactic acidosis, ADHD Sources: Literature |
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| Mendeliome v1.833 | ERG | Ain Roesley Phenotypes for gene: ERG were changed from to primary lymphoedema MONDO#0019175, ERG-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.831 | ERG | Ain Roesley reviewed gene: ERG: Rating: GREEN; Mode of pathogenicity: None; Publications: 36928819; Phenotypes: primary lymphoedema MONDO#0019175, ERG-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.831 | GATAD2A | Bryony Thompson Marked gene: GATAD2A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.830 | GATAD2A |
Bryony Thompson gene: GATAD2A was added gene: GATAD2A was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GATAD2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: GATAD2A were set to https://doi.org/10.1016/j.xhgg.2023.100198; 17565372 Phenotypes for gene: GATAD2A were set to Neurodevelopmental disorder, MONDO:0700092, GATAD2A-related Review for gene: GATAD2A was set to GREEN Added comment: https://doi.org/10.1016/j.xhgg.2023.100198 - Five unrelated individuals with a neurodevelopmental disorder identified with 3 missense & 2 LoF (4 de novo & 1 unknown inheritance). The shared clinical features with variable expressivity include global developmental delay (4/4), craniofacial dysmorphism (3/5), structural brain defects (2/3), musculoskeletal anomalies (3/5), vision/hearing defects (2/3), gastrointestinal/renal defects (2/3). Loss of function is the expected mechanism of disease. In vitro assays of one of the missense variants (p.Cys420Tyr) demonstrates disruption of GATAD2A integration with CHD3, CHD4, and CHD5 PMID: 17565372 - null mouse model is embryonic lethal. Sources: Literature |
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| Mendeliome v1.828 | KDM5A | Zornitza Stark Marked gene: KDM5A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.827 | YWHAE | Zornitza Stark Marked gene: YWHAE as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.826 | YWHAE |
Zornitza Stark gene: YWHAE was added gene: YWHAE was added to Mendeliome. Sources: Literature SV/CNV tags were added to gene: YWHAE. Mode of inheritance for gene: YWHAE was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: YWHAE were set to 36999555 Phenotypes for gene: YWHAE were set to Neurodevelopmental disorder, MONDO:0700092 Review for gene: YWHAE was set to GREEN Added comment: PMID 36999555 reports 10 patients with YWHAE variants (1 intragenic deletion and 5 large deletions encompassing YWHEA but not PAFAH1B1) who have mild to severe intellectual disability. 3 individuals with SNVs. Mouse model supports gene-disease association. Sources: Literature |
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| Mendeliome v1.824 | KPNA7 | Zornitza Stark Phenotypes for gene: KPNA7 were changed from Epilepsy; intellectual disability to Oocyte/zygote/embryo maturation arrest 17, MIM# 620319; Neurodevelopmental disorder | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.821 | KPNA7 | Zornitza Stark reviewed gene: KPNA7: Rating: AMBER; Mode of pathogenicity: None; Publications: 36647821; Phenotypes: Oocyte/zygote/embryo maturation arrest 17, MIM# 620319; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.821 | ACSL5 | Zornitza Stark Phenotypes for gene: ACSL5 were changed from severe FTT (no OMIM #) to Diarrhoea 13, MIM# 620357 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.819 | INTS11 |
Achchuthan Shanmugasundram gene: INTS11 was added gene: INTS11 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: INTS11 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: INTS11 were set to 37054711 Review for gene: INTS11 was set to GREEN Added comment: Comment on gene rating: This gene should be rated GREEN in Intellectual disability panel as it has 10 unrelated cases and functional evidence in support of this association. PMID:37054711 reported ten unrelated families with biallelic variants in INTS11 gene and they present with intellectual disability, global developmental and language delay, impaired motor development, and brain atrophy. Functional studies in Drosophila showed that dIntS11 (fly ortholog of INTS11) is essential and expressed in the central nervous systems in a subset of neurons and most glia in larval and adult stages. In addition, genes with two variants (p.Arg17Leu and p.His414Tyr) fail to rescue the lethality of null mutants in the Drosophila model, indicating that they are strong loss-of-function variants. The other five variants (p.Gly55Ser, p.Leu138Phe, p.Lys396Glu, p.Val517Met and p.Ile553Glu) rescue lethality but cause a shortened lifespan and bang sensitivity and affect locomotor activity, indicating that they are partial loss-of-function variants. Sources: Literature |
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| Mendeliome v1.817 | MED11 | Zornitza Stark Phenotypes for gene: MED11 were changed from neurodevelopmental disorder MONDO#0700092, MED11-related to Neurodegeneration with developmental delay, early respiratory failure, myoclonic seizures, and brain abnormalities, MIM# 620327 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.816 | MED11 | Zornitza Stark reviewed gene: MED11: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodegeneration with developmental delay, early respiratory failure, myoclonic seizures, and brain abnormalities, MIM# 620327; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.816 | MARS | Zornitza Stark Phenotypes for gene: MARS were changed from Interstitial lung and liver disease, MIM#615486; Charcot-Marie-Tooth disease, axonal, type 2U, MIM# 616280; Trichothiodystrophy 9, nonphotosensitive, MIM# 619692 to Interstitial lung and liver disease, MIM#615486; Charcot-Marie-Tooth disease, axonal, type 2U, MIM# 616280; Trichothiodystrophy 9, nonphotosensitive, MIM# 619692; Spastic paraplegia 70, autosomal recessive, MIM# 620323 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.815 | MARS | Zornitza Stark Publications for gene: MARS were set to 23729695; 24354524; 29655802; 24103465; 25913036; 33909043 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.814 | MARS | Zornitza Stark edited their review of gene: MARS: Added comment: Six individuals from two unrelated families reported with SPG.; Changed publications: 23729695, 24354524, 29655802, 24103465, 25913036, 24482476, 34585293; Changed phenotypes: Interstitial lung and liver disease, MIM#615486, Charcot-Marie-Tooth disease, axonal, type 2U, MIM# 616280, Spastic paraplegia 70, autosomal recessive, MIM# 620323 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.814 | WARS | Zornitza Stark Phenotypes for gene: WARS were changed from Neuronopathy, distal hereditary motor, type IX (OMIM:617721); juvenile to adult onset (15-23 years); Neurodevelopmental disorder (MONDO:0700092), WARS-related to Neuronopathy, distal hereditary motor, type IX (OMIM:617721); juvenile to adult onset (15-23 years); Neurodevelopmental disorder withmicrocephaly and speech delay, with or without brain abnormalities, MIM# 620317 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.812 | DNAJB4 | Zornitza Stark Phenotypes for gene: DNAJB4 were changed from Congenital myopathy 21 with early respiratory failure, MIM# 620326 to Congenital myopathy 21 with early respiratory failure, MIM# 620326; distal myopathy MONDO:0018949 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.809 | DNAJB4 | Zornitza Stark Phenotypes for gene: DNAJB4 were changed from Myopathy, MONDO:0005336, DNAJB4-related to Congenital myopathy 21 with early respiratory failure, MIM# 620326 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.808 | DNAJB4 | Zornitza Stark reviewed gene: DNAJB4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital myopathy 21 with early respiratory failure, MIM# 620326; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.807 | KDM5A |
Achchuthan Shanmugasundram gene: KDM5A was added gene: KDM5A was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KDM5A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: KDM5A were set to 21937992; 33350388 Phenotypes for gene: KDM5A were set to autism spectrum disorder, MONDO:0005258; intellectual disability, MONDO:0001071 Review for gene: KDM5A was set to GREEN Added comment: PMID:21937992 reported a family with recessive missense KDM5A variant presenting with an undefined developmental disorder characterised with intellectual disability and facial dysmorphisms. PMID:33350388 reported nine patients from seven unrelated families identified with variants in KDM5A, of which three unrelated patients harboured heterozygous variants, while six patients from four unrelated families had homozygous variants. These patients presented with autism spectrum disorder (ASD) and a spectrum of neurodevelopmental phenotypes including intellectual disability, lack of speech, developmental delay and motor impairment. In addition, loss of KDM5A has resulted in repetitive behaviors, sociability deficits, cognitive dysfunction, and abnormal dendritic morphogenesis in mice. This gene has already been associated with phenotype in Gene2Phenotype (biallelic inheritance with 'limited' rating), but not in OMIM. Sources: Literature |
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| Mendeliome v1.807 | ROBO1 | Zornitza Stark Phenotypes for gene: ROBO1 were changed from Congenital heart disease; Pituitary anomalies; Nystagmus 8, congenital, autosomal recessive, MIM# 257400; intellectual disability, MONDO:0001071 to Pituitary hormone deficiency, combined or isolated, 8, MIM# 620303; Nystagmus 8, congenital, autosomal recessive, MIM# 257400; Neurooculorenal syndrome, MIM# 620305 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.806 | ROBO1 | Zornitza Stark edited their review of gene: ROBO1: Changed phenotypes: Pituitary hormone deficiency, combined or isolated, 8, MIM# 620303, Nystagmus 8, congenital, autosomal recessive, MIM# 257400, Neurooculorenal syndrome, MIM# 620305 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.805 | ROBO1 | Zornitza Stark Phenotypes for gene: ROBO1 were changed from Congenital heart disease; Pituitary anomalies to Congenital heart disease; Pituitary anomalies; Nystagmus 8, congenital, autosomal recessive, MIM# 257400; intellectual disability, MONDO:0001071 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.803 | ROBO1 |
Zornitza Stark edited their review of gene: ROBO1: Added comment: Association with ID: GREEN for bi-allelic variants: PMID:28286008 reported a boy with compound heterozygous variants that was presented with developmental delay in 13 months and had severe intellectual disability and hyperactivity at nine years of age. He was nonverbal and wheelchair dependent because of spastic diplegia and ataxia. PMID:30692597 reported a five year old boy identified with a homozygous ROBO1 variant who had combined pituitary hormone deficiency, psychomotor developmental delay, severe intellectual disability, sensorineural hearing loss, strabismus and characteristic facial features. PMID:35227688 reported eight patients including the boy reported in PMID:30692597. Of the other seven patients, three were presented with intellectual disability. Of these three patients, two harboured compound heterozygous and one harboured homozygous variants. PMID:35348658 reported a patient identified with monoallelic de novo variant (p.D422G) who presented with early-onset epileptic encephalopathy and had severe developmental delay.; Changed phenotypes: Congenital heart disease, Pituitary anomalies, Nystagmus 8, congenital, autosomal recessive, MIM# 257400, intellectual disability, MONDO:0001071 |
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| Mendeliome v1.803 | ROBO1 | Zornitza Stark changed review comment from: PMID 35348658: three male siblings from the same family with nystagmus with a homozygous missense variant p.Ser1522Leu.; to: PMID 35348658: three male siblings from the same family with nystagmus with a homozygous missense variant p.Ser1522Leu. This association is RED. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.803 | ROBO1 | Zornitza Stark edited their review of gene: ROBO1: Added comment: PMID 35348658: three male siblings from the same family with nystagmus with a homozygous missense variant p.Ser1522Leu.; Changed publications: 28592524, 30530901, 30692597, 33270637, 28402530, 35348658; Changed phenotypes: Congenital heart disease, Pituitary anomalies, Nystagmus 8, congenital, autosomal recessive, MIM# 257400 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.799 | RYR3 | Zornitza Stark Phenotypes for gene: RYR3 were changed from Nemaline myopathy; fetal akinesia; arthrogryposis to Congenital myopathy 20, MIM# 620310 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.794 | MAP3K3 | Zornitza Stark Marked gene: MAP3K3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.793 | MAP3K3 |
Zornitza Stark gene: MAP3K3 was added gene: MAP3K3 was added to Mendeliome. Sources: Literature somatic tags were added to gene: MAP3K3. Mode of inheritance for gene: MAP3K3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MAP3K3 were set to 33729480; 35355835; 33891857; 36995941; 10700190; 25728774 Phenotypes for gene: MAP3K3 were set to Cerebral malformation, MONDO:0016054, MAP3K3-related Mode of pathogenicity for gene: MAP3K3 was set to Other Review for gene: MAP3K3 was set to GREEN Added comment: Recurrent somatic missense variant (p.I441M) identified in sporadic cases of cerebral and spinal cavernous malformation. Recent publication demonstrates that this missense variant can drive CCM formation (in vitro and in vivo studies). Sources: Literature |
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| Mendeliome v1.792 | VWA8 | Zornitza Stark Marked gene: VWA8 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.791 | MKL2 | Zornitza Stark Marked gene: MKL2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.790 | ACTC1 | Zornitza Stark Marked gene: ACTC1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.789 | ACTC1 | Zornitza Stark reviewed gene: ACTC1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Atrial septal defect 5 MIM#612794, Cardiomyopathy, dilated, 1R MIM#613424, Cardiomyopathy, hypertrophic, 11 MIM#612098, ACTC1 related distal arthrogryposis MONDO:0019942; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.785 | POLR1A | Zornitza Stark commented on gene: POLR1A: Evidence for association of bi-allelic variants with leukodystrophy is moderate. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.785 | FILIP1 | Zornitza Stark Marked gene: FILIP1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.785 | FILIP1 | Zornitza Stark Phenotypes for gene: FILIP1 were changed from Arthrogryposis multiplex congenita MONDO:0015168 to Arthrogryposis multiplex congenita MONDO:0015168, FILIP1 related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.782 | BIN1 | Bryony Thompson Added comment: Comment on mode of inheritance: ClinGen Definititive for semidominant for centronuclear myopathy by the Congenital myopathy GCEP - Classification - 04/27/2020 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.781 | VWA8 |
Dean Phelan gene: VWA8 was added gene: VWA8 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: VWA8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: VWA8 were set to PMID: 37012052 Phenotypes for gene: VWA8 were set to Retinitis pigmentosa (MONDO:0019200), VWA8-related Review for gene: VWA8 was set to AMBER Added comment: PMID: 37012052 - Single family with 11 affected patients, 9 - 87y, all presented initial symptoms of night blindness, visual field defects and reduced visual acuity later, macular changes, including macular degeneration and dystrophy. A heterozygous two-loci variant in VWA8 c.3070G>A;c.4558C>T (p.Gly1024Arg; p.Arg1520Ter) was identified and segregated with disease. Expression studies showed reduced protein expression. Zebrafish knockout model displayed an RP phenotype. Sources: Literature |
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| Mendeliome v1.781 | MKL2 |
Dean Phelan gene: MKL2 was added gene: MKL2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MKL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MKL2 were set to PMID: 37013900 Phenotypes for gene: MKL2 were set to Neurodevelopmental disorder (MONDO:0700092), MKL2-related Mode of pathogenicity for gene: MKL2 was set to Other Review for gene: MKL2 was set to AMBER Added comment: PMID: 37013900 - de novo missense variants in MKL2 (now known as MRTFB) were identified in two patients with mild dysmorphic features, intellectual disability, global developmental delay, speech apraxia, and impulse control issues. Functional studies in a Drosophila model suggest a gain of function disease mechanism. Sources: Literature |
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| Mendeliome v1.781 | RNH1 | Seb Lunke Marked gene: RNH1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.780 | ESAM | Seb Lunke Marked gene: ESAM as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.777 | CEP162 | Zornitza Stark Marked gene: CEP162 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.776 | CRIPT |
Karina Sandoval changed review comment from: PMID: 37013901 identified 6 individuals with Rothmund-Thomson syndrome, two new identified and 4 were already published. 5 were hom, 1 was chet, all with different variants. Additionally all presented with neuro dev delay and seizures. CRIPT-deficient fibroblasts showed an unremarkable mitotic progression and unremarkable number of mitotic errors, c.132del p.(Ala45Glyfs*82), hom c.227G>A, p.(Cys76Tyr), hom c.133_134insGG,p.(Ala45Glyfs*82),hom c.141del p.(Phe47Leufs*84), hom c.8G>A p.(Cys3Tyr), 1,331 bp del exon 1, chet c.7_8del; p.(Cys3Argfs*4), hom; to: PMID: 37013901 identified 6 individuals with Rothmund-Thomson syndrome characterised by poikiloderma, sparse hair, small stature, skeletal defects, cancer, cataracts, resembling features of premature aging. Two new variants identified and 4 were already published. 5 were hom, 1 was chet, all with different variants. All CRIPT individuals fulfilled the diagnostic criteria for RTS, and additionally had neurodevelopmental delay and seizures. CRIPT-deficient fibroblasts showed an unremarkable mitotic progression and unremarkable number of mitotic errors, c.132del p.(Ala45Glyfs*82), hom c.227G>A, p.(Cys76Tyr), hom c.133_134insGG,p.(Ala45Glyfs*82),hom c.141del p.(Phe47Leufs*84), hom c.8G>A p.(Cys3Tyr), 1,331 bp del exon 1, chet c.7_8del; p.(Cys3Argfs*4), hom |
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| Mendeliome v1.776 | CEP162 |
Paul De Fazio gene: CEP162 was added gene: CEP162 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CEP162 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CEP162 were set to 36862503 Phenotypes for gene: CEP162 were set to Retinitis pigmentosa MONDO:0019200, CEP162-related Penetrance for gene: CEP162 were set to unknown Review for gene: CEP162 was set to AMBER gene: CEP162 was marked as current diagnostic Added comment: 2 patients from reportedly unrelated consanguineous Moroccan families with the same homozygous frameshift variant reported with late-onset retinal degeneration. Patient 1 was diagnosed with RP at age 60, patient 2 at age 69. Both reported loss of visual acuity in the years prior. Immunoblotting of cell lysates from patient fibroblasts showed that some mutant transcript escaped NMD. Functional testing showed that the truncated protein could bind microtubules but was unable to associate with centrioles or its interaction partner CEP290. Patient fibroblasts were shown to have delayed ciliation. Mutant protein was unable to rescue loss of cilia in CEP162 knockdown mice supporting that the mutant protein does not retain any ciliary function, however additional data supported that the truncated protein was able to bind microtubules and function normally during neuroretinal development. The authors suggest this likely underlies the late-onset RP in both patients. Rated Amber because only a single variant has been reported in patients who may or may not be related (same ethnic background). Sources: Literature |
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| Mendeliome v1.776 | ACTC1 |
Lilian Downie gene: ACTC1 was added gene: ACTC1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ACTC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ACTC1 were set to PMID: 36945405 Phenotypes for gene: ACTC1 were set to Atrial septal defect 5 MIM#612794; Cardiomyopathy, dilated, 1R MIM#613424; Cardiomyopathy, hypertrophic, 11 MIM#612098; ACTC1 related distal arthrogryposis MONDO:0019942 Review for gene: ACTC1 was set to GREEN Added comment: ClinGen definitive association with HCM, moderate for DCM 5 new families (8 individuals) with a distral arthrogryposis phenotype (PMID: 36945405) multiple congenital contractures, neck pterygia, scoliosis, and congenital heart defects/cardiomyopathy facial features: microretrognathia, ptosis, downslanting palpebral fissures, low-set ears, and a long nasal bridge All missense variants Sources: Literature |
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| Mendeliome v1.776 | DOCK11 | Seb Lunke Marked gene: DOCK11 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.775 | ESAM |
Chern Lim gene: ESAM was added gene: ESAM was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ESAM was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ESAM were set to 36996813 Phenotypes for gene: ESAM were set to Neurodevelopmental disorder (MONDO#0700092), ESAM-related Review for gene: ESAM was set to GREEN gene: ESAM was marked as current diagnostic Added comment: PMID 36996813 - Thirteen affected individuals, including four fetuses, from eight unrelated families, with homozygous loss-of-function-type variants in ESAM – 2 of the variants are frameshifts, 1x nonsense, 1x canonical splice. - Affected individuals have profound global developmental delay/unspecified intellectual disability, epilepsy, absent or severely delayed speech, varying degrees of spasticity, ventriculomegaly, and ICH/cerebral calcifications, the latter being also observed in the fetuses. - One of the frameshift variant c.115del (p.Arg39Glyfs*33), was detected in six individuals from four unrelated families from the same geographic region in Turkey (southeastern Anatolia), suggesting a founder effect. - The c.451+1G>A variant was detected in three individuals from two independent families with the same ethnic origin (Arab Bedouin) Sources: Literature |
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| Mendeliome v1.775 | SNAPC4 | Zornitza Stark Marked gene: SNAPC4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.774 | SNAPC4 |
Ee Ming Wong changed review comment from: - Ten individuals from eight families with neurodevelopmental disorder found to be compound heterozygous for variants in SNAPC4 - Identified variants included 6x missense, 1x nonsense, 1x frameshift and 6x splice - Depletion of SNAPC4 levels in HeLa cell lines via genomic editing led to decreased snRNA expression and global dysregulation of alternative splicing, similarly observed in patient fibroblasts Sources: Literature; to: - Ten individuals from eight families with neurodevelopmental disorder found to be biallelic for variants in SNAPC4 - Identified variants included 6x missense, 1x nonsense, 1x frameshift and 6x splice - Depletion of SNAPC4 levels in HeLa cell lines via genomic editing led to decreased snRNA expression and global dysregulation of alternative splicing, similarly observed in patient fibroblasts Sources: Literature |
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| Mendeliome v1.774 | DOCK11 |
Lucy Spencer gene: DOCK11 was added gene: DOCK11 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: DOCK11 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: DOCK11 were set to 36952639 Phenotypes for gene: DOCK11 were set to autoimmune disease MONDO:0007179, DOCK11-related Review for gene: DOCK11 was set to GREEN Added comment: 8 male patients from 7 unrelated families all with hemizygous DOCK11 missense variants. 6 mothers were tested and found to carry the same missense. Early onset autoimmuniy with cytopenia, systemic lupus erythematosus, and skin and digestive manifestations. Patients platelets had abnormal morphology and spreading as well as impaired CDC42 activity. In vitro activated T cells and B lymphoblastoid cell lines (B-LCL) of patients exhibited aberrant protrusions and abnormal migration speed in confined channels concomitant with altered actin polymerization during migration. A DOCK11 knock-down recapitulated these abnormal cellular phenotypes in monocytes-derived dendritic cells (MDDC) and primary activated T cells from healthy controls. 6 of the variants are either absent or have only 1 het in gnomad v2, but one of them has 2 hemis and 1 het. The patient with this variant R1885C does seem to be more mild. Sources: Literature |
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| Mendeliome v1.774 | FILIP1 | Paul De Fazio edited their review of gene: FILIP1: Changed phenotypes: Arthrogryposis multiplex congenita MONDO:0015168, FILIP1 related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.774 | RNH1 |
Krithika Murali changed review comment from: PMID: 36935417 report two siblings from a consanguineous Somali family with homozygous RNH1 splice site variant (c.615-2A>C) with congenital cataracts, global developmental delay, hypotonia, seizures (focal and generalised) and regression in the context of infection. RT-PCR and RNASeq of skeletal muscle supported exon 7 skipping with an in-frame deletion involving 57 amino acids with reduced expression on Western blot analysis. Sources: Literature; to: PMID: 36935417 report two siblings from a consanguineous Somali family with homozygous RNH1 splice site variant (c.615-2A>C) with congenital cataracts, global developmental delay, hypotonia, seizures (focal and generalised) and regression in the context of infection. RT-PCR and RNASeq of skeletal muscle supported exon 7 skipping with an in-frame deletion involving 57 amino acids with reduced expression on Western blot analysis. No antenatal features reported. Sources: Literature |
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| Mendeliome v1.774 | SNAPC4 |
Ee Ming Wong gene: SNAPC4 was added gene: SNAPC4 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SNAPC4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SNAPC4 were set to 36965478 Phenotypes for gene: SNAPC4 were set to Neurodevelopmental disorder (MONDO#0700092), SNAPC4-related Review for gene: SNAPC4 was set to GREEN gene: SNAPC4 was marked as current diagnostic Added comment: - Ten individuals from eight families with neurodevelopmental disorder found to be compound heterozygous for variants in SNAPC4 - Identified variants included 6x missense, 1x nonsense, 1x frameshift and 6x splice - Depletion of SNAPC4 levels in HeLa cell lines via genomic editing led to decreased snRNA expression and global dysregulation of alternative splicing, similarly observed in patient fibroblasts Sources: Literature |
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| Mendeliome v1.773 | RNH1 |
Krithika Murali gene: RNH1 was added gene: RNH1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RNH1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RNH1 were set to PMID: 36935417 Phenotypes for gene: RNH1 were set to RNH1-related disorder Review for gene: RNH1 was set to AMBER Added comment: PMID: 36935417 report two siblings from a consanguineous Somali family with homozygous RNH1 splice site variant (c.615-2A>C) with congenital cataracts, global developmental delay, hypotonia, seizures (focal and generalised) and regression in the context of infection. RT-PCR and RNASeq of skeletal muscle supported exon 7 skipping with an in-frame deletion involving 57 amino acids with reduced expression on Western blot analysis. Sources: Literature |
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| Mendeliome v1.769 | MB | Elena Savva Marked gene: MB as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.769 | MB |
Elena Savva gene: MB was added gene: MB was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: MB were set to 35527200; 30918256 Phenotypes for gene: MB were set to Myopathy, sarcoplasmic body MIM#620286 Mode of pathogenicity for gene: MB was set to Other Review for gene: MB was set to GREEN Added comment: PMID: 30918256: - Recurrent c.292C>T (p.His98Tyr) in fourteen members of six European families with AD progressive myopathy. - Mutant myoglobin has altered O2 binding, exhibits a faster heme dissociation rate and has a lower reduction potential compared to wild-type myoglobin. - GOF hypothesised - 2/3 of myoglobin knockout mice die in utero, 1/3 live to adulthood with little sign of functional effects, likely due to multiple compensatory mechanisms. PMID: 35527200: - single adult patient with myoglobinopathy - same recurring p.His98Tyr variant Sources: Literature |
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| Mendeliome v1.768 | FILIP1 |
Paul De Fazio gene: FILIP1 was added gene: FILIP1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: FILIP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FILIP1 were set to 36943452 Phenotypes for gene: FILIP1 were set to Arthrogryposis multiplex congenita MONDO:0015168 Penetrance for gene: FILIP1 were set to unknown Review for gene: FILIP1 was set to GREEN gene: FILIP1 was marked as current diagnostic Added comment: 3 families, all consanguineous, reported with 3 different homozygous loss of function variants (2x NMD-predicted nonsense, 1x intragenic deletion of exons 3-6 of 6). In one family, the variant segregated in 3 affected siblings. Phenotypes consist of congenital contractures affecting shoulder, elbow, hand, hip, knee and foot as well as scoliosis, reduced palmar and plantar skin folds, microcephaly (-1.5 to -4 SD), and facial dysmorphism. Sources: Literature |
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| Mendeliome v1.765 | NPPA |
Chern Lim changed review comment from: PMID: 36303204: - 1x Brugada patient with heterozygous R107X (NMD-predicted, 5 hets in gnomADv3), regarded as ACMG-LP. PMID: 19646991: - NPPA S64R missense in one fam with familial AF, heterozygous in two affected family members but was absent in unaffected family members and their controls. This variant has 195 hets in gnomADv3. PMID: 23275345: - Segregation of the homozygous p.R150Q mutation of the NPPA gene with the phenotype in the 6 families with autosomal recessive AD cardiomyopathy (ADCM). This variant has no homozygotes in gnomAD. ClinGen gene curation: for autosomal recessive DCM - No Known Disease Relationship (09/04/2020).; to: PMID: 36303204: - 1x Brugada patient with heterozygous R107X (NMD-predicted, 5 hets in gnomADv3), regarded as ACMG-LP. PMID: 19646991: - NPPA S64R missense in one fam with familial AF, heterozygous in two affected family members but was absent in unaffected family members and their controls. This variant has >200 hets in gnomADv3. PMID: 23275345: - Segregation of the homozygous p.R150Q mutation of the NPPA gene with the phenotype in the 6 families with autosomal recessive AD cardiomyopathy (ADCM). This variant has no homozygotes in gnomAD. ClinGen gene curation: for autosomal recessive DCM - No Known Disease Relationship (09/04/2020). |
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| Mendeliome v1.763 | PPCS | Bryony Thompson reviewed gene: PPCS: Rating: GREEN; Mode of pathogenicity: None; Publications: 35616428, 29754768; Phenotypes: Cardiomyopathy, dilated, 2C, MIM# 618189; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.763 | PPCDC | Bryony Thompson Marked gene: PPCDC as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.763 | PPCDC |
Bryony Thompson gene: PPCDC was added gene: PPCDC was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PPCDC was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PPCDC were set to 36564894 Phenotypes for gene: PPCDC were set to dilated cardiomyopathy MONDO:0005021 Review for gene: PPCDC was set to RED Added comment: Single family reported with two siblings with a fatal cardiac phenotype including dilated cardiomyopathy with biallelic variants p.Thr53Pro and p.Ala95Val. Patient-derived fibroblasts showed an absence of PPCDC protein, and nearly 50% reductions in CoA levels. The cells showed clear energy deficiency problems, with defects in mitochondrial respiration, and mostly glycolytic ATP synthesis. Functional studies performed in yeast suggest these mutations to be functionally relevant. Sources: Literature |
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| Mendeliome v1.762 | ELOC | Bryony Thompson Marked gene: ELOC as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.761 | EPHA10 | Bryony Thompson Marked gene: EPHA10 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.760 | RNF212B | Bryony Thompson Marked gene: RNF212B as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.759 | SLC25A36 | Bryony Thompson Marked gene: SLC25A36 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.757 | NCAPG2 |
Zornitza Stark changed review comment from: Two families and functional evidence (zebrafish model). Sources: Literature; to: Two families and functional evidence (zebrafish model). Rated as LIMITED by ClinGen; one of the families had a homozygous missense variant. Internal case identified by VCGS but dual diagnosis. Sources: Literature |
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| Mendeliome v1.757 | NPPA | Chern Lim reviewed gene: NPPA: Rating: AMBER; Mode of pathogenicity: None; Publications: 36303204, 19646991, 23275345; Phenotypes: Atrial fibrillation, familial, 6 (MIM#612201), AD, Atrial standstill 2 (MIM#615745), AR; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.757 | RNF212B |
Sangavi Sivagnanasundram gene: RNF212B was added gene: RNF212B was added to Mendeliome. Sources: Other Mode of inheritance for gene: RNF212B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RNF212B were set to https://doi.org/10.1016/j.xhgg.2023.100189 Phenotypes for gene: RNF212B were set to Infertility disorder, MONDO:0005047 Review for gene: RNF212B was set to AMBER Added comment: Homozygous nonsense mutation (R150X) causative of oligoasthenotheratozoospermia (OAT) identified in three unrelated individuals (two of Jewish decent from the same consanguineous family). Drosophila ZIP3/RNF212 related gene paralogs (vilya, narya, nenya) showed loss of function in the RNF212B protein and promoted formation of DNA double-stand breaks. The mutant was shown to result in a reduction in fertility in the Drosophila paralogs. Note: RNF212B is reported to be exclusively expressed in the testes only compared to RNF212 which is reported in both the testes and ovaries. Sources: Other |
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| Mendeliome v1.756 | HCK | Zornitza Stark Phenotypes for gene: HCK were changed from Autoinflammatory syndrome, MONDO:0019751, HCK-related to Autoinflammation with pulmonary and cutaneous vasculitis, MIM#620296 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.755 | HCK | Zornitza Stark edited their review of gene: HCK: Changed phenotypes: Autoinflammation with pulmonary and cutaneous vasculitis, MIM#620296 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.755 | PLXND1 | Zornitza Stark Phenotypes for gene: PLXND1 were changed from Möbius syndrome, MONDO:0008006; Congenital heart disease, MONDO:0005453, PLXND1-related to Möbius syndrome, MONDO:0008006; Congenital heart defects, multiple types, 9, MIM# 620294 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.754 | PLXND1 | Zornitza Stark edited their review of gene: PLXND1: Changed phenotypes: Möbius syndrome, Congenital heart defects, multiple types, 9, MIM# 620294 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.753 | PRDM10 | Zornitza Stark Marked gene: PRDM10 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.752 | PRDM10 |
Achchuthan Shanmugasundram gene: PRDM10 was added gene: PRDM10 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PRDM10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PRDM10 were set to 36440963 Phenotypes for gene: PRDM10 were set to Fibrofolliculoma, HP:0030436; lipomatosis, MONDO:0006574; renal cell carcinoma, MONDO:0005086 Review for gene: PRDM10 was set to RED Added comment: PMID:36440963 reported a family presenting with skin and mucosal lesions, extensive lipomatosis and renal cell carcinomas. The proband was initially diagnosed with Birt-Hogg-Dubé syndrome (BHD, MIM #135150) based on the presence of fibrofolliculomas, but no pathogenic germline variant was detected in FLCN, the gene associated with BHD. A heterozygous missense variant (p.Cys677Tyr) was identified, which co-segregated with the phenotype in the family. Functional studies show that Cys677Tyr loses affinity for a regulatory binding motif in the FLCN promoter, abrogating cellular FLCN mRNA and protein levels. Overexpressing inducible PRDM10Cys677Tyr in renal epithelial cells altered the transcription of multiple genes, showing overlap but also differences with the effects of knocking out FLCN. This gene has not yet been associated with phenotypes either in OMIM or in Gene2Phenotype. Sources: Literature |
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| Mendeliome v1.752 | SLC26A7 | Zornitza Stark Marked gene: SLC26A7 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.748 | STX4 | Zornitza Stark Phenotypes for gene: STX4 were changed from to Non-syndromic genetic hearing loss, MONDO:0019497, STX4-related. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.744 | ARF1 | Zornitza Stark Publications for gene: ARF1 were set to 28868155; 34353862 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.743 | STX4 | Achchuthan Shanmugasundram reviewed gene: STX4: Rating: AMBER; Mode of pathogenicity: None; Publications: 36355422; Phenotypes: Hearing impairment, HP:0000365; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.743 | ARF1 | Achchuthan Shanmugasundram edited their review of gene: ARF1: Changed publications: 36345169 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.743 | ARF1 | Achchuthan Shanmugasundram reviewed gene: ARF1: Rating: ; Mode of pathogenicity: None; Publications: 3634516; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.743 | THAP11 | Zornitza Stark Marked gene: THAP11 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.743 | THAP11 |
Zornitza Stark gene: THAP11 was added gene: THAP11 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: THAP11 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: THAP11 were set to 28449119 Phenotypes for gene: THAP11 were set to Inborn disorder of cobalamin metabolism and transport, MONDO:0019220, THAP11-related Review for gene: THAP11 was set to RED Added comment: Single individual reported with homozygous missense variant, supportive functional data. Sources: Expert Review |
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| Mendeliome v1.742 | RNPC3 | Zornitza Stark Phenotypes for gene: RNPC3 were changed from Growth hormone deficiency; Intellectual disability to Pituitary hormone deficiency, combined or isolated, 7, MIM# 618160 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.741 | RNPC3 | Zornitza Stark edited their review of gene: RNPC3: Changed phenotypes: Pituitary hormone deficiency, combined or isolated, 7, MIM# 618160 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.738 | MNX1 | Zornitza Stark Phenotypes for gene: MNX1 were changed from Currarino syndrome, MIM# 176450 to Currarino syndrome, MIM# 176450; Permanent neonatal diabetes mellitus, MONDO:0100164, MNX1-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.736 | IRS4 | Zornitza Stark Marked gene: IRS4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.735 | IRS4 |
Zornitza Stark gene: IRS4 was added gene: IRS4 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: IRS4 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: IRS4 were set to 30061370 Phenotypes for gene: IRS4 were set to Hypothyroidism, congenital, nongoitrous, 9, MIM# 301035 Review for gene: IRS4 was set to GREEN Added comment: Nongoitrous congenital hypothyroidism-9 (CHNG9) is characterized by a small thyroid gland with low free T4 (FT4) levels and inappropriately normal levels of thyroid-stimulating hormone (TSH). Five unrelated families reported. Sources: Expert Review |
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| Mendeliome v1.734 | HECTD4 | Zornitza Stark Marked gene: HECTD4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.734 | HECTD4 | Zornitza Stark Phenotypes for gene: HECTD4 were changed from Neurodevelopmental disorder overlapping Angelman syndrome, no OMIM# to Neurodevelopmental disorder with seizures, spasticity, and complete or partial agenesis of the corpus callosum, MIM# 620250 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.733 | HECTD4 | Zornitza Stark reviewed gene: HECTD4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with seizures, spasticity, and complete or partial agenesis of the corpus callosum, MIM# 620250; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.732 | SPTLC1 | Zornitza Stark Phenotypes for gene: SPTLC1 were changed from Neuropathy, hereditary sensory and autonomic, type IA, MIM# 162400; Serine palmitoyl transferase deficiency (Disorders of complex lipid synthesis) to Juvenile amyotrophic lateral sclerosis-27, MIM#620285; Neuropathy, hereditary sensory and autonomic, type IA, MIM# 162400; Serine palmitoyl transferase deficiency (Disorders of complex lipid synthesis) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.731 | SPTLC1 | Zornitza Stark edited their review of gene: SPTLC1: Changed phenotypes: Juvenile amyotrophic lateral sclerosis-27, MIM#620285, Neuropathy, hereditary sensory and autonomic, type IA, MIM# 162400, Serine palmitoyl transferase deficiency (Disorders of complex lipid synthesis) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.727 | REPS1 | Zornitza Stark Marked gene: REPS1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.727 | REPS1 |
Zornitza Stark gene: REPS1 was added gene: REPS1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: REPS1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: REPS1 were set to 29395073 Phenotypes for gene: REPS1 were set to Neurodegeneration with brain iron accumulation 7 , MIM# 617916 Review for gene: REPS1 was set to RED Added comment: Two siblings reported with compound het missense variants in this gene and a neurodegenerative course in childhood. Sources: Literature |
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| Mendeliome v1.722 | TLN1 | Zornitza Stark Phenotypes for gene: TLN1 were changed from idiopathic spontaneous coronary artery dissection MONDO:0007385 to idiopathic spontaneous coronary artery dissection MONDO:0007385; thrombocytopenia, MONDO:0002049, TLN1-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.720 | DPYSL2 | Zornitza Stark Marked gene: DPYSL2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.719 | DPYSL2 |
Zornitza Stark gene: DPYSL2 was added gene: DPYSL2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: DPYSL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DPYSL2 were set to 27249678; 35861646 Phenotypes for gene: DPYSL2 were set to intellectual disability, MONDO:0001071, DPYSL2-related Review for gene: DPYSL2 was set to AMBER Added comment: Two unrelated cases with monoallelic variants in DPYSL2/ CRMP2, supported by functional studies. However, the evidence is not sufficient for green rating as there are variants reported in other (but different) genes in the two patients. PMID:35861646 reported two cases identified with heterozygous variants (patient1: c.1693C>T (p.Arg565Cys); patient 2: c.42C>A (p.Ser14Arg). These patients had overlapping phenotypes including dysmorphic features, severe global developmental delay and hypoplasia of the corpus callosum. In addition, patient 2 was bed-ridden and could not roll out and had a history of myoclonic seizures and status epilepticus. It should be noted that patient 1 is compound heterozygous for 2 missense variants in the EFCAB5 gene and was hemizygous for a maternally inherited missense variant in the GPKOW gene and patient 2 had 1 de novo missense variant in the COBLL1 gene and was compound heterozygous for 2 missense variants in the POTEF gene. The severity of the phenotypes between the two cases differs significantly and the additional variants may have possibly contributed to this phenotype. Brain-specific Crmp2 knockout mice display neuronal development deficits and behavioural impairments associated with hypoplasia of the corpus callosum. In addition, functional studies performed in zebrafish and cell lines that the CRMP2 variants lead to the loss-of-function of CRMP2 protein and can cause intellectual disability. Sources: Literature |
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| Mendeliome v1.718 | RBSN | Zornitza Stark Marked gene: RBSN as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.717 | RBSN |
Zornitza Stark gene: RBSN was added gene: RBSN was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RBSN was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RBSN were set to 25233840; 29784638; 35652444 Phenotypes for gene: RBSN were set to intellectual disability, MONDO:0001071, RBSN-related Review for gene: RBSN was set to GREEN Added comment: Four unrelated families reported, consistent feature is ID. PMID:25233840 reported a 6.5 year old female patient with a homozygous missense variant c.1273G > A (p.Gly425Arg) and her clinical presentation included intractable seizures, developmental delay, microcephaly, dysostosis, osteopenia, craniofacial dysmorphism, macrocytosis and megaloblastoid erythropoiesis. PMID:29784638 reported three siblings with homozygous variant c.289G>C (p.Gly97Arg) in RBSN. The proband presented global developmental delay, had complete 46,XY male-to-female sex reversal and died at age 20 months after multiple infections. The other 2 affected siblings underwent unrelated-donor bone marrow or stem cell transplantation at 8 and 6.5 months of age, respectively. Both have severe intellectual disability and are nonambulatory and nonverbal. PMID:35652444 reported two unrelated families (three siblings from a family of Iranian descent identified with homozygous variant c.547G>A (p.Gly183Arg) and four members from a family of indigenous Cree descent identified with homozygous variant c.538C>G (p.Arg180Gly)) with overlapping phenotypes including developmental delay, intellectual disability, distal motor axonal neuropathy and facial dysmorphism. Sources: Literature |
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| Mendeliome v1.716 | SRPRA | Zornitza Stark Marked gene: SRPRA as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.715 | SRPRA |
Zornitza Stark gene: SRPRA was added gene: SRPRA was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SRPRA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SRPRA were set to 36223592 Phenotypes for gene: SRPRA were set to Schwachman-Diamond syndrome MONDO:0009833, SRPA-related Review for gene: SRPRA was set to AMBER Added comment: De novo variant; zebrafish model. Schwachman-Diamond like. Sources: Literature |
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| Mendeliome v1.714 | SRP19 | Zornitza Stark Marked gene: SRP19 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.711 | ATP5B |
Zornitza Stark changed review comment from: Two families only, clinical presentation with dystonia; incomplete penetrance observed. Some functional data. Note also PMID 36239646 reporting de novo variant in identical twins with hypermetabolism. Sources: Literature; to: PMID 36860166: Two families only, clinical presentation with dystonia; incomplete penetrance observed. Some functional data. Note also PMID 36239646 reporting de novo variant in identical twins with hypermetabolism. Sources: Literature |
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| Mendeliome v1.711 | ATP5B |
Zornitza Stark changed review comment from: Two families only, clinical presentation with dystonia; incomplete penetrance observed. Some functional data. Sources: Literature; to: Two families only, clinical presentation with dystonia; incomplete penetrance observed. Some functional data. Note also PMID 36239646 reporting de novo variant in identical twins with hypermetabolism. Sources: Literature |
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| Mendeliome v1.711 | EPHA10 |
Achchuthan Shanmugasundram changed review comment from: Comment on rating: This gene should be rated RED as this gene has been associated with post-lingual autosomal dominant non-syndromic hearing loss from a single family, and supported by functional studies. PMID:36048850 reported the identification of a heterozygous non-coding variant c.-81_-73delinsAGC cosegregating with hearing loss. Although variants have been identified in KIF17 and USP48 in several members of this family, they did not cosegregate with hearing loss. One affected member of this family had an ideal hearing restoration after cochlear implantation. Epha10 was expressed in mouse cochlea at both transcription and translation levels. In addition, EPHA10 mRNA was detected upregulated in patients compared with controls by qRT-PCR. Overexpression of Eph (the homolog of human EPHA10) altered the structure and function of chordotonal organ (equivalent to mammalian auditory organs) in fly model. These functional evidence suggests that 'gain of function' may be responsible for the hearing loss phenotype. This gene has not yet been associated with any phenotypes in OMIM or Gene2Phenotype. Sources: Literature; to: Comment on rating: This gene should be rated RED as this gene has been associated with post-lingual autosomal dominant non-syndromic hearing loss from a single family, and supported by functional studies. PMID:36048850 reported the identification of a heterozygous non-coding variant c.-81_-73delinsAGC cosegregating with hearing loss. Although variants have been identified in KIF17 and USP48 in several members of this family, they did not cosegregate with hearing loss. One affected member of this family had an ideal hearing restoration after cochlear implantation. Epha10 was expressed in mouse cochlea at both transcription and translation levels. In addition, EPHA10 mRNA was detected upregulated in patients compared with controls by qRT-PCR. Overexpression of Eph (the homolog of human EPHA10) altered the structure and function of chordotonal organ (equivalent to mammalian auditory organs) in fly model. Particularly, Eph overexpressed flies had a poorer performance compared to controls in negative geotaxis assay. These functional evidence suggests that 'gain of function' may be responsible for the hearing loss phenotype. This gene has not yet been associated with any phenotypes in OMIM or Gene2Phenotype. Sources: Literature |
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| Mendeliome v1.711 | OXR1 |
Achchuthan Shanmugasundram changed review comment from: Comment on gene rating: This gene should be rated AMBER as there is one case and supportive functional data to associate OXR1 with hearing loss. A four years old girl was identified with a novel homozygous missense variant (c.233A > G, p.Lys78Arg) in OXR1 gene and was reported with sensorineural hearing loss. Functional studies in zebrafish model showed that the ortholog orx1b gene is expressed in the statoacoustic ganglion (SAG, a sensory ganglion of ear) and posterior lateral line ganglion (pLL). In addition, knockdown of oxr1b resulted in a significant developmental defect of SAG and pLL and this phenotype was rescued by co-injection of wild-type human OXR1 mRNAs, but not mutant OXR1 (c.233A > G) mRNAs.; to: Comment on gene rating: This gene should be rated AMBER as there is one case and supportive functional data to associate OXR1 with hearing loss. A four years old girl was identified with a novel homozygous missense variant (c.233A > G, p.Lys78Arg) in OXR1 gene and was reported with sensorineural hearing loss. Functional studies in zebrafish model showed that the ortholog orx1b gene is expressed in the statoacoustic ganglion (SAG, a sensory ganglion of ear) and posterior lateral line ganglion (pLL). In addition, knockdown of oxr1b resulted in a significant developmental defect of SAG and pLL and this phenotype was rescued by co-injection of wild-type human OXR1 mRNAs, but not mutant OXR1 (c.233A > G) mRNAs. This gene has not yet been associated with hearing loss either in OMIM or in Gene2Phenotype. |
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| Mendeliome v1.711 | EPHA10 |
Achchuthan Shanmugasundram changed review comment from: Comment on rating: This gene should be rated RED as this gene has been associated with post-lingual autosomal dominant non-syndromic hearing loss from a single family, and supported by functional studies. PMID:36048850 reported the identification of a heterozygous non-coding variant c.-81_-73delinsAGC cosegregating with hearing loss. Although variants have been identified in KIF17 and USP48 in several members of this family, they did not cosegregate with hearing loss. One affected member of this family had an ideal hearing restoration after cochlear implantation. Epha10 was expressed in mouse cochlea at both transcription and translation levels. In addition, EPHA10 mRNA was detected upregulated in patients compared with controls by qRT-PCR. Overexpression of Eph (the homolog of human EPHA10) altered the structure and function of chordotonal organ (equivalent to mammalian auditory organs) in fly model. These functional evidence suggests that 'gain of function' may be responsible for the hearing loss phenotype. This gene has not yet been associated with any phenotypes in OMIM or Gene2Phenotype. Sources: Literature; to: Comment on rating: This gene should be rated RED as this gene has been associated with post-lingual autosomal dominant non-syndromic hearing loss from a single family, and supported by functional studies. PMID:36048850 reported the identification of a heterozygous non-coding variant c.-81_-73delinsAGC cosegregating with hearing loss. Although variants have been identified in KIF17 and USP48 in several members of this family, they did not cosegregate with hearing loss. One affected member of this family had an ideal hearing restoration after cochlear implantation. Epha10 was expressed in mouse cochlea at both transcription and translation levels. In addition, EPHA10 mRNA was detected upregulated in patients compared with controls by qRT-PCR. Overexpression of Eph (the homolog of human EPHA10) altered the structure and function of chordotonal organ (equivalent to mammalian auditory organs) in fly model. These functional evidence suggests that 'gain of function' may be responsible for the hearing loss phenotype. This gene has not yet been associated with any phenotypes in OMIM or Gene2Phenotype. Sources: Literature |
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| Mendeliome v1.711 | OXR1 | Achchuthan Shanmugasundram reviewed gene: OXR1: Rating: AMBER; Mode of pathogenicity: None; Publications: 36130215; Phenotypes: sensorineural hearing loss disorder, MONDO:0020678; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.711 | EPHA10 |
Achchuthan Shanmugasundram gene: EPHA10 was added gene: EPHA10 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: EPHA10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: EPHA10 were set to 36048850 Phenotypes for gene: EPHA10 were set to postlingual non-syndromic genetic hearing loss, MONDO:0016298 Mode of pathogenicity for gene: EPHA10 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: EPHA10 was set to RED Added comment: Comment on rating: This gene should be rated RED as this gene has been associated with post-lingual autosomal dominant non-syndromic hearing loss from a single family, and supported by functional studies. PMID:36048850 reported the identification of a heterozygous non-coding variant c.-81_-73delinsAGC cosegregating with hearing loss. Although variants have been identified in KIF17 and USP48 in several members of this family, they did not cosegregate with hearing loss. One affected member of this family had an ideal hearing restoration after cochlear implantation. Epha10 was expressed in mouse cochlea at both transcription and translation levels. In addition, EPHA10 mRNA was detected upregulated in patients compared with controls by qRT-PCR. Overexpression of Eph (the homolog of human EPHA10) altered the structure and function of chordotonal organ (equivalent to mammalian auditory organs) in fly model. These functional evidence suggests that 'gain of function' may be responsible for the hearing loss phenotype. This gene has not yet been associated with any phenotypes in OMIM or Gene2Phenotype. Sources: Literature |
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| Mendeliome v1.711 | ATP5B | Zornitza Stark Marked gene: ATP5B as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.708 | SHQ1 | Zornitza Stark edited their review of gene: SHQ1: Added comment: Fourth family reported in PMID 36847845 with hypotonia and paroxysmal dyskinesia.; Changed publications: 34542157, 29178645, 36847845 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.708 | YWHAZ | Zornitza Stark Marked gene: YWHAZ as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.708 | YWHAZ |
Zornitza Stark gene: YWHAZ was added gene: YWHAZ was added to Mendeliome. Sources: Literature Mode of inheritance for gene: YWHAZ was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: YWHAZ were set to 36001342 Phenotypes for gene: YWHAZ were set to Intellectual disability, MONDO:0001071 Review for gene: YWHAZ was set to RED Added comment: PMID:36001342 reported one large three-generation family with intellectual disability and global developmental delay, where all affected members were identified with a heterozygous missense variant (c.147A>T/ p.Lys49Asn) in YWHAZ gene. Although there were 10 other rare variants located in 10 genes (ARHGAP4, AGPS, APOL3, CES3, DACT2, ECH1, FAM71E2, KREMEN1, YWHAZ, ZFYVE26) that co-segregated with the ID/GDD phenotype were identified in the family, they were either not present in all affected members or present in unaffected members. In addition, computational modeling and knockdown/ knockin studies with Drosophila also confirmed the role of this YWHAZ variant in intellectual disability. Sources: Literature |
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| Mendeliome v1.706 | PLXND1 | Zornitza Stark Phenotypes for gene: PLXND1 were changed from Möbius syndrome to Möbius syndrome, MONDO:0008006; Congenital heart disease, MONDO:0005453, PLXND1-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.703 | PLXND1 | Zornitza Stark edited their review of gene: PLXND1: Changed phenotypes: Möbius syndrome, Congenital heart disease, MONDO:0005453, PLXND1-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.703 | ZNF143 | Zornitza Stark Marked gene: ZNF143 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.703 | ZNF143 |
Zornitza Stark gene: ZNF143 was added gene: ZNF143 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ZNF143 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ZNF143 were set to 27349184 Phenotypes for gene: ZNF143 were set to Combined methylmalonic acidemia and homocystinuria, cblX like 1, MONDO:0002012, ZNF143-related Review for gene: ZNF143 was set to RED Added comment: Single individual reported with compound heterozygous variants. Sources: Literature |
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| Mendeliome v1.702 | PLXND1 |
Achchuthan Shanmugasundram changed review comment from: 10 individuals including four foetal cases from five unrelated families were identified with biallelic variants in PLXND1 gene and they presented with cardiac defects. The most frequent defect is common arterial trunk (CAT), which is also known as truncus arteriosus, a conotruncal malformation characterized by a single vessel exiting both ventricles. This gene has already been associated with PLXND1-related cardiac malformation syndrome with the confidence category of 'strong' in DD panel of Gene2Phenotype. However, no relevant phenotypes have been currently reported in OMIM.; to: 10 individuals including four foetal cases from five unrelated families were identified with biallelic variants in PLXND1 gene and they presented with cardiac defects. The most frequent defect is common arterial trunk (CAT), which is also known as truncus arteriosus, a conotruncal malformation characterized by a single vessel exiting both ventricles. This gene has already been associated with PLXND1-related cardiac malformation syndrome with the confidence category of 'strong' in DD panel of Gene2Phenotype. However, no relevant phenotypes have been currently reported in OMIM. |
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| Mendeliome v1.702 | PLXND1 |
Achchuthan Shanmugasundram changed review comment from: 10 individuals including four foetal cases from five unrelated families were identified with biallelic variants in PLXND1 gene and they presented with cardiac defects. The most frequent defect is common arterial trunk (CAT), which is also known as truncus arteriosus, a conotruncal malformation characterized by a single vessel exiting both ventricles.; to: 10 individuals including four foetal cases from five unrelated families were identified with biallelic variants in PLXND1 gene and they presented with cardiac defects. The most frequent defect is common arterial trunk (CAT), which is also known as truncus arteriosus, a conotruncal malformation characterized by a single vessel exiting both ventricles. This gene has already been associated with PLXND1-related cardiac malformation syndrome with the confidence category of 'strong' in DD panel of Gene2Phenotype. However, no relevant phenotypes have been currently reported in OMIM. |
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| Mendeliome v1.702 | PLXND1 | Achchuthan Shanmugasundram edited their review of gene: PLXND1: Changed phenotypes: Truncus arteriosus, HP:0001660 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.702 | KIF5B | Achchuthan Shanmugasundram reviewed gene: KIF5B: Rating: ; Mode of pathogenicity: None; Publications: 36018820; Phenotypes: dilated cardiomyopathy, MONDO:0005021, ophthalmoplegia, MONDO:0003425, myopathy, MONDO:0005336, Hypotonia, HP:0001252, Seizure, HP:0001250; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.702 | CYB561 | Zornitza Stark Marked gene: CYB561 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.701 | CYB561 |
Zornitza Stark gene: CYB561 was added gene: CYB561 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: CYB561 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CYB561 were set to 29343526; 31822578 Phenotypes for gene: CYB561 were set to Orthostatic hypotension 2, MIM# 618182 Review for gene: CYB561 was set to GREEN Added comment: Three families reported. Severe orthostatic hypotension, recurrent hypoglycemia, and low norepinephrine levels. The disorder has onset in infancy or early childhood. Treatment: L-threo-3,4-dihydroxyphenylserine (droxidopa) Sources: Expert Review |
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| Mendeliome v1.699 | MCF2L | Zornitza Stark Marked gene: MCF2L as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.698 | MCF2L |
Michelle Torres gene: MCF2L was added gene: MCF2L was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MCF2L was set to Unknown Publications for gene: MCF2L were set to 36760094 Phenotypes for gene: MCF2L were set to vascular malformation MONDO:0024291, MCF2L-related Review for gene: MCF2L was set to RED Added comment: Three families with Systemic malformation (resulting in a left to right shunt instead of the right to left shunt seen in individuals with HHT) had missense variants in the MCF2L gene (families 1, 2 and 7). Family 1 (Val875Met: v2 & v3: 113 hets) did no present PA (pulmonary artery). Family 2 (Cys199Gly : v2 & v3: 260 hets, 1 hom) did no present PA (pulmonary artery). Family 7: Leu130Pro (1 het, 0 hom), segregated in family 7 with SA-PA (systemic artery to the pulmonary artery), with 5x affected tested (Sanger or WES). Unaffected and other 6x individuals affected were not tested. Sources: Literature |
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| Mendeliome v1.698 | TEFM | Zornitza Stark Marked gene: TEFM as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.697 | SLC25A36 |
Krithika Murali gene: SLC25A36 was added gene: SLC25A36 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SLC25A36 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC25A36 were set to 34971397; 34576089; 31036718 Phenotypes for gene: SLC25A36 were set to Hyperinsulinemic hypoglycemia, familial, 8 - MIM#620211 Review for gene: SLC25A36 was set to GREEN Added comment: Solute carrier family 25 members 33 (SLC25A33) and 36 (SLC25A36) are the only known mitochondrial pyrimidine nucleotide carriers in humans PMID: 34971397 Sharoor et al 2022 report 2 siblings with hyperinsulinism, hypoglycemia and hyperammonemia from early infancy with homozygous SLC25A36 c.284 + 3 A > T variant identified through WES. Functional studies support LoF. PMID: 34576089 report a 12-year-old patient with hypothyroidism, hyperinsulinism, hyperammonemia, chronical obstipation, short stature, along with language and general developmental delay. WES identified SLC25A36 gene homozygous c.803dupT, p.Ser269llefs*35 variant. Functional analysis of mutant SLC25A36 protein in proteoliposomes showed a virtually abolished transport activity. Immunoblotting results suggest that the mutant SLC25A36 protein in the patient undergoes fast degradation. Supplementation with uridine lead to some improvement in clinical course. PMID: 31036718 deficiencies in SLC25A36 in mouse embryonic stem cells have been associated with mtDNA depletion as well as mitochondrial dysfunction Sources: Literature |
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| Mendeliome v1.695 | TEFM |
Ee Ming Wong gene: TEFM was added gene: TEFM was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TEFM was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TEFM were set to 36823193 Phenotypes for gene: TEFM were set to Mitochondrial disease (MONDO#0044970), TEFM-related Review for gene: TEFM was set to GREEN gene: TEFM was marked as current diagnostic Added comment: - Seven TEFM variants (4 missense, 2 fs, 1 in-frame del) in seven individuals across five unrelated families - Muscle and primary fibroblast from the affected individuals have reduced levels of promoter distal mitochondrial RNA transcripts - TEFM knockdown in zebrafish embryos resulted in neuromuscular junction abnormalities and abnormal mitochondrial function Sources: Literature |
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| Mendeliome v1.691 | HMGB1 |
Ain Roesley edited their review of gene: HMGB1: Added comment: PMID:36755093 4 new families with de novo protein truncating variants. In addition with PMID 34159400 ( all de novos) c.556_559delGAAG;p.(Glu186Argfs*42) - 1 family c.551_554delAGAA;p.(Lys184Argfs*44) - 4 families; Changed rating: GREEN; Changed publications: 34159400, 36755093; Changed phenotypes: brachyphalangy, polydactyly, and tibial aplasia/hypoplasia MIM#163905; Set current diagnostic: yes |
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| Mendeliome v1.689 | LGR4 |
Elena Savva changed review comment from: PMID: 36538378 - hom canonical splice variant in an infant with failure to thrive, severe salt-wasting crises associated with isolated hypoaldosteronism, nail anomalies, short stature, and deafness. Multiple affected siblings but all deceased, two normal siblings found to be het or wildtype. Functional studies proved INFRAME exon 6 skipping, patients cell shad minimal protein. Conditional K/O mouse model showed reduced expression of Wnt target genes, adrenal hypoplasia and aberrant zonal differentiation gnomAD: no hom PTCs PMID: 32493844 - 6 patients with delayed puberty, supported by functional studies on mice displaying impaired Wnt/β-catenin signaling. Recurring missense p.G363C present in 4/6 families, but super common in the population (67 homozygotes).; to: PMID: 36538378 - hom canonical splice variant in an infant with failure to thrive, severe salt-wasting crises associated with isolated hypoaldosteronism, nail anomalies, short stature, and deafness. Multiple affected siblings but all deceased, two normal siblings found to be het or wildtype. Functional studies proved INFRAME exon 6 skipping, patients cell shad minimal protein. Conditional K/O mouse model showed reduced expression of Wnt target genes, adrenal hypoplasia and aberrant zonal differentiation gnomAD: no hom PTCs PMID: 32493844 - 6 patients with delayed puberty, supported by functional studies on mice displaying impaired Wnt/β-catenin signaling. Recurring missense p.G363C present in 4/6 families, but super common in the population (67 homozygotes). |
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| Mendeliome v1.689 | LGR4 |
Elena Savva edited their review of gene: LGR4: Added comment: PMID: 36538378 - hom canonical splice variant in an infant with failure to thrive, severe salt-wasting crises associated with isolated hypoaldosteronism, nail anomalies, short stature, and deafness. Multiple affected siblings but all deceased, two normal siblings found to be het or wildtype. Functional studies proved INFRAME exon 6 skipping, patients cell shad minimal protein. Conditional K/O mouse model showed reduced expression of Wnt target genes, adrenal hypoplasia and aberrant zonal differentiation gnomAD: no hom PTCs PMID: 32493844 - 6 patients with delayed puberty, supported by functional studies on mice displaying impaired Wnt/β-catenin signaling. Recurring missense p.G363C present in 4/6 families, but super common in the population (67 homozygotes).; Changed publications: PMID: 32493844, 36538378; Changed phenotypes: {Bone mineral density, low, susceptibility to} MIM#615311; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal |
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| Mendeliome v1.689 | USMG5 | Bryony Thompson Marked gene: USMG5 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.688 | USMG5 |
Bryony Thompson gene: USMG5 was added gene: USMG5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: USMG5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: USMG5 were set to 29917077; 30240627 Phenotypes for gene: USMG5 were set to Mitochondrial complex V (ATP synthase) deficiency, nuclear type 6 MIM#618683 Review for gene: USMG5 was set to AMBER Added comment: A homozygous splice site mutation in 4 patients from 3 unrelated families of Ashkenazi Jewish descent. Experimental analyses demonstrated that the splice variant leads to loss of protein expression and haplotype analysis suggested a founder effect. In situ cryo-ET analysis of the mitochondria of a homozygous affected case showed profound disturbances of mitochondrial crista ultrastructure. Sources: Literature |
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| Mendeliome v1.686 | ATG4D | Zornitza Stark Marked gene: ATG4D as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.684 | ELOC |
Achchuthan Shanmugasundram gene: ELOC was added gene: ELOC was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ELOC was set to Unknown Publications for gene: ELOC were set to 35323939 Phenotypes for gene: ELOC were set to von Hippel-Lindau disease, MONDO:0008667; renal cell carcinoma, MONDO:0005086; retinal hemangioblastoma, MONDO:0003343 Review for gene: ELOC was set to RED Added comment: Comment on gene classification: This gene should be rated red as there is only one case with germline variant found so far. A female patient was identified with a germline de novo missense variant in ELOC gene (c.236A>G/ p.Tyr79Cys) and satisfied the clinical diagnostic criteria for von Hippel-Lindau (VHL) disease. The patient had left retinal haemangioblastomas, renal cell carcinomas, cyst of the right kidney, spinal haemangioblastoma, a haemangioblastoma at the cervicomedullary junction and Henoch-Schonlein purpura (PMID:35323939). This is the only germline variant detected in ELOC gene and was associated with VHL so far. However, ~20 somatic ELOC variants have been reported to be associated with renal cell carcinomas so far. This gene has not yet been associated with relevant phenotypes in OMIM or Gene2Phenotype. Sources: Literature |
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| Mendeliome v1.684 | ATG4D |
Suliman Khan gene: ATG4D was added gene: ATG4D was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ATG4D was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ATG4D were set to PMID: 36765070 Phenotypes for gene: ATG4D were set to neurodevelopmental disorder; Abnormal facial shape Penetrance for gene: ATG4D were set to unknown Review for gene: ATG4D was set to GREEN Added comment: PMID: 36765070 reported three individuals from two unrelated families with a neurodevelopmental disorder characterized by speech and motor impairment with a similar facial gestalt comprising almond-shaped eyes, depressed nasal bridge, and a prominent Cupid’s bow with variable disease severity and progression. NGS analysis revealed bi-allelic loss-of-function variants in ATG4D gene. Based on the clinical, bioinformatic, and functional data, the author concluded that bi-allelic loss-of-function variants in ATG4D contribute to the pathogenesis of syndromic neurodevelopmental disorder. Sources: Literature |
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| Mendeliome v1.684 | TRPM3 | Zornitza Stark Phenotypes for gene: TRPM3 were changed from Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skeletal anomalies, with or without seizures, MIM# 620224 to Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skeletal anomalies, with or without seizures, MIM# 620224; Cataract 50 with or without glaucoma, MIM#620253 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.682 | TRPM3 | Zornitza Stark edited their review of gene: TRPM3: Added comment: Publications 25090642; 33484482: Single multi-generational family reported with a missense variant in this gene and cataract. Mouse model of same variant supports association. Amber for this association.; Changed publications: 31278393, 25090642, 33484482; Changed phenotypes: Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skeletal anomalies, with or without seizures, MIM# 620224, Cataract 50 with or without glaucoma, MIM#620253 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.680 | PPM1K | Zornitza Stark edited their review of gene: PPM1K: Added comment: PMID: 36706222 reported a patient with MSUD with mild findings and elevated BCAA levels carrying a novel homozygous start-loss variant in PPM1K; Changed rating: AMBER; Changed publications: 23086801, 36706222 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.680 | ARHGAP35 | Zornitza Stark Phenotypes for gene: ARHGAP35 were changed from neurodevelopmental disorder, ARHGAP35-related MONDO#0700092; Developmental defect of the eye (MONDO:0020145), ARHGAP35-related to Hypogonadotropic hypogonadism, MONDO:0015770, ARHGAP35-related; neurodevelopmental disorder, ARHGAP35-related MONDO#0700092; Developmental defect of the eye (MONDO:0020145), ARHGAP35-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.679 | ARHGAP35 | Zornitza Stark Publications for gene: ARHGAP35 were set to 33057194; 36450800 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.678 | ARHGAP35 | Zornitza Stark reviewed gene: ARHGAP35: Rating: GREEN; Mode of pathogenicity: None; Publications: 36178483; Phenotypes: Hypogonadotropic hypogonadism, MONDO:0015770, ARHGAP35-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.678 | EFCAB1 | Zornitza Stark Marked gene: EFCAB1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.678 | EFCAB1 | Zornitza Stark Phenotypes for gene: EFCAB1 were changed from Primary ciliary dyskinesia and heterotaxy, no OMIM # to Primary ciliary dyskinesia, MONDO:0016575, EFCAB1-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.677 | EFCAB1 | Zornitza Stark reviewed gene: EFCAB1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Primary ciliary dyskinesia, MONDO:0016575, EFCAB1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.677 | CST6 | Zornitza Stark Marked gene: CST6 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.671 | WNT11 | Zornitza Stark Marked gene: WNT11 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.668 | MRPS7 | Zornitza Stark edited their review of gene: MRPS7: Added comment: Now second publication (PMID: 36421788) describes sisters with an overlapping phenotype including sensorineural deafness and premature ovarian insufficiency. They both had compound heterozygous (one missense, one nonsense) MRPS7 variants.; Changed rating: AMBER; Changed publications: 25556185, 36421788 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.668 | STAT6 | Zornitza Stark Marked gene: STAT6 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.667 | STAT6 |
Zornitza Stark gene: STAT6 was added gene: STAT6 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: STAT6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: STAT6 were set to 36216080; 36758835 Phenotypes for gene: STAT6 were set to Allergic disease, MONDO:0005271, STAT6-related; early-onset multiorgan allergies Review for gene: STAT6 was set to GREEN Added comment: Two families reported with GoF variants and extensive functional data. Sources: Literature |
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| Mendeliome v1.666 | LTV1 | Zornitza Stark Marked gene: LTV1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.665 | LTV1 |
Achchuthan Shanmugasundram gene: LTV1 was added gene: LTV1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: LTV1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LTV1 were set to 34999892 Phenotypes for gene: LTV1 were set to Inflammatory poikiloderma with hair abnormalities and acral keratoses, OMIM:620199 Review for gene: LTV1 was set to AMBER Added comment: Comment on classification of gene: This gene should be rated amber as it has been implicated in inflammatory poikiloderma with hair abnormalities and acral keratoses as identified from two unrelated families harbouring the same biallelic variant and supported by functional studies. PMID:34999892 reported four UK women of South Asian origin (three Pakistani sisters and an unrelated Indian woman) identified with homozygous variant c.503A>G, (p.Asn168Ser) and presented with poikiloderma, hair abnormalities, and acral keratoses, which the authors named as inflammatory poikiloderma with hair abnormalities and acral keratoses (IPHAK). Both in silico modelling and splicing assays from a patient sample showed that this variant is responsible for splicing defects and defects in LTV1 alter the export of nascent ribosomal subunits to the cytoplasm in yeast. This gene has already been associated with relevant phenotype (MIM #620199) in OMIM, but not in Gene2Phenotype. Sources: Literature |
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| Mendeliome v1.665 | WNT11 |
Achchuthan Shanmugasundram gene: WNT11 was added gene: WNT11 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: WNT11 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: WNT11 were set to 34875064 Phenotypes for gene: WNT11 were set to osteoporosis, MONDO:0005298; osteoarthritis, MONDO:0005178; recurrent fractures Review for gene: WNT11 was set to GREEN Added comment: Comment on gene classification: The rating of this gene can be added as green as this gene has been implicated in early-onset osteoporosis from three unrelated cases and was supported by evidence from functional studies. All three patients harboured heterozygous variants in WNT11 gene. Three unrelated cases are reported in PMID: 34875064. A four year-old boy harbouring de novo heterozygous loss-of-function variant c.677_678dupGG (p.Leu227Glyfs*22) was reported with low BMD, osteopenia and several fractures. A 51 year-old woman and her 69 year-old mother were identified with a heterozygous missense variant c.217G>A (p.Ala73Thr). The woman was reported with bone fragility, several fractures, osteoarthritis and osteoporosis, while her mother also had several osteoporotic fractures. A 61 year-old woman that was reported with lumbar spine osteoarthritis had several fractures since 55 years of age was identified with a heterozygous missense variant c.865G>A (p.Val289Met). This was also supported by results from functional studies, where cell lines with the loss-of-function variant generated by CRISPR-Cas9 showed reduced cell proliferation and osteoblast differentiation in comparison to wild-type. The expression of genes in the Wnt canonical and non-canonical pathways was inhibited in these mutant cells. This gene has not yet been reported with any phenotypes either in OMIM or in G2P. Sources: Literature |
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| Mendeliome v1.663 | GOLGA2 | Zornitza Stark Phenotypes for gene: GOLGA2 were changed from Neuromuscular disorder to Developmental delay with hypotonia, myopathy, and brain abnormalities, MIM 620240 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.656 | EFCAB1 |
Chirag Patel gene: EFCAB1 was added gene: EFCAB1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: EFCAB1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EFCAB1 were set to PMID: 36727596 Phenotypes for gene: EFCAB1 were set to Primary ciliary dyskinesia and heterotaxy, no OMIM # Review for gene: EFCAB1 was set to GREEN Added comment: WES in 3 individuals with laterality defects and respiratory symptoms, identified homozygous pathogenic variants in CLXN (EFCAB1). They found Clxn expressed in mice left-right organizer. Transmission electron microscopy depicted outer dynein arm (ODA) defects in distal ciliary axonemes. Immunofluorescence microscopy revealed absence of CLXN from the ciliary axonemes, absence of the ODA components DNAH5, DNAI1 and DNAI2 from the distal axonemes, as well as mislocalization or absence of DNAH9. Additionally, CLXN is undetectable in ciliary axonemes of individuals with defects in the outer dynein arm docking (ODA-DC) machinery: ODAD1, ODAD2, ODAD3 and ODAD4. Moreover, SMED-EFCAB1-deficient planaria displayed ciliary dysmotility. Sources: Literature |
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| Mendeliome v1.654 | KBTBD13 | Bryony Thompson reviewed gene: KBTBD13: Rating: AMBER; Mode of pathogenicity: None; Publications: 36335629; Phenotypes: Cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.654 | KLHL24 | Zornitza Stark Phenotypes for gene: KLHL24 were changed from Epidermolysis bullosa simplex, generalized, with scarring and hair loss OMIM#617294; dilated cardiomyopathy; Hypertrophic cardiomyopathy to Epidermolysis bullosa simplex, generalized, with scarring and hair loss OMIM#617294; dilated cardiomyopathy; Cardiomyopathy, familial hypertrophic, 29, with polyglucosan bodies, MIM# 620236 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.653 | ASNA1 | Zornitza Stark Marked gene: ASNA1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.651 | RRAGD | Zornitza Stark Marked gene: RRAGD as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.651 | RRAGD | Zornitza Stark Phenotypes for gene: RRAGD were changed from Kidney tubulopathy; dilated cardiomyopathy; hypomagnesaemia; renal salt-wasting; nephrocalcinosis to Inherited renal tubular disease, MONDO:0015962, RRAGD-related; dilated cardiomyopathy; hypomagnesaemia; renal salt-wasting; nephrocalcinosis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.650 | PMEL | Zornitza Stark Marked gene: PMEL as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.649 | ASNA1 |
Naomi Baker gene: ASNA1 was added gene: ASNA1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ASNA1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ASNA1 were set to 31461301; 16797549 Phenotypes for gene: ASNA1 were set to Dilated cardiomyopathy, MONDO:0001644, ASNA1-related Review for gene: ASNA1 was set to RED Added comment: Two siblings reported with biallelic variants - there were two variants on the paternal allele (c.867C>G p.(Cys289Trp) and c.913C>T p.(Gln305*)) and one variant on the maternal allele (c.488T>C p.(Val163Ala)). Unaffected sibling was heterozygous for maternal allele. Western blotting demonstrated reduced protein expression. Knockout of asna1 in zebrafish mode resulted in cardiac defects and early lethality. The Asna1 knockout mice displayed early embryonic lethality, consistent with a role of Asna1 in early embryonic development. Sources: Literature |
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| Mendeliome v1.649 | RRAGD |
Hazel Phillimore changed review comment from: PMID: 34607910; Schlingmann, KP. et al. (2021) J Am Soc Nephrol. 32(11):2885-2899. Five missense variants in RRAGD identified in eight children (some early infant onset) from unrelated families. The variants were recurrent or affecting the same amino acid, i.e., p.S76L, S76W, p.T97P, p.P119L, p.P119R and p.I221K note: these are absent in gnomAD v2.1.1, and are very highly conserved residues. All variants are located in the N-terminal G-domain and affect sequence motifs involved in nucleotide binding The children had a tubulopathy characterised by hypomagnesemia, hypokalaemia, salt wasting, and nephrocalcinosis, and six had dilated cardiomyopathy. Most occurred de novo. Two were familial. One family with two affected siblings showed low level mosaicism in the mother. In vitro studies using transfected HEK293 cells showed increased binding to RPTOR and MTOR. Sources: Literature; to: PMID: 34607910; Schlingmann, KP. et al. (2021) J Am Soc Nephrol. 32(11):2885-2899. Six missense variants in RRAGD identified in eight children (some early infant onset) from unrelated families. The variants were recurrent or affecting the same amino acid, i.e., p.S76L, S76W, p.T97P, p.P119L, p.P119R and p.I221K note: these are absent in gnomAD v2.1.1, and are very highly conserved residues. All variants are located in the N-terminal G-domain and affect sequence motifs involved in nucleotide binding The children had a tubulopathy characterised by hypomagnesemia, hypokalaemia, salt wasting, and nephrocalcinosis, and six had dilated cardiomyopathy. Most occurred de novo. Two were familial. One family with two affected siblings showed low level mosaicism in the mother. In vitro studies using transfected HEK293 cells showed increased binding to RPTOR and MTOR. Sources: Literature |
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| Mendeliome v1.649 | RRAGD |
Hazel Phillimore gene: RRAGD was added gene: RRAGD was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RRAGD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RRAGD were set to PMID: 34607910 Phenotypes for gene: RRAGD were set to Kidney tubulopathy; dilated cardiomyopathy; hypomagnesaemia; renal salt-wasting; nephrocalcinosis Review for gene: RRAGD was set to GREEN Added comment: PMID: 34607910; Schlingmann, KP. et al. (2021) J Am Soc Nephrol. 32(11):2885-2899. Five missense variants in RRAGD identified in eight children (some early infant onset) from unrelated families. The variants were recurrent or affecting the same amino acid, i.e., p.S76L, S76W, p.T97P, p.P119L, p.P119R and p.I221K note: these are absent in gnomAD v2.1.1, and are very highly conserved residues. All variants are located in the N-terminal G-domain and affect sequence motifs involved in nucleotide binding The children had a tubulopathy characterised by hypomagnesemia, hypokalaemia, salt wasting, and nephrocalcinosis, and six had dilated cardiomyopathy. Most occurred de novo. Two were familial. One family with two affected siblings showed low level mosaicism in the mother. In vitro studies using transfected HEK293 cells showed increased binding to RPTOR and MTOR. Sources: Literature |
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| Mendeliome v1.649 | PMEL |
Paul De Fazio gene: PMEL was added gene: PMEL was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PMEL was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PMEL were set to 36166100; 36207673 Phenotypes for gene: PMEL were set to Oculocutaneous albinism, PMEL-related MONDO:0018910 Review for gene: PMEL was set to RED gene: PMEL was marked as current diagnostic Added comment: A consanguineous family with oculocutaneous albinism and Hirschsprung disease was found to have a biallelic LoF variant in PMEL, which although NMD-predicted was found not to result in NMD by RT-PCR. Some evidence that polymorphisms in this gene influence pigmentation in cattle. Sources: Literature |
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| Mendeliome v1.649 | SPTSSA | Seb Lunke Marked gene: SPTSSA as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.649 | SPTSSA | Seb Lunke Added comment: Comment on list classification: Three individuals but only two variants with different inheritance. Amber despite functional data. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.648 | SPTSSA |
Seb Lunke gene: SPTSSA was added gene: SPTSSA was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SPTSSA was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: SPTSSA were set to 36718090 Phenotypes for gene: SPTSSA were set to complex hereditary spastic paraplegia, MONDO:0015150 Review for gene: SPTSSA was set to AMBER Added comment: Three unrelated individuals with common neurological features of developmental delay, progressive motor impairment, progressive lower extremity spasticity, and epileptiform activity or seizures. Other additional features varied. Two of the individuals had the same de-novo missense, Thr51Ile, while the third was homozygous for a late truncating variant, Gln58AlafsTer10. The patient with the hom variant was described as less severe. Functional studies in fibroblasts showed dysregulation of the sphingolipid (SL) synthesis pathway, showing that both variants impair ORMDL regulation of the pathway leading to various levels of increased SL. Over expression of human SPTSSA was shown to lead to motor development in flies, rescued by expression of ORMDL for WT SPTSSA but not mutant SPTSSA. The de-novo missense were shown to impact regulation more than the hom truncation, while the truncated region was shown to previously to be important for ORMDL regulation. Mice with a hom KO of the functional equivalent sptssb had early onset ataxia and died prematurely, with evidence of axonic degeneration. Sources: Literature |
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| Mendeliome v1.647 | MIR145 | Zornitza Stark Marked gene: MIR145 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.646 | TRU-TCA1-1 | Zornitza Stark Marked gene: TRU-TCA1-1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.642 | CAMLG | Seb Lunke Marked gene: CAMLG as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.636 | CCDC84 | Zornitza Stark Marked gene: CCDC84 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.635 | MIR145 |
Lucy Spencer gene: MIR145 was added gene: MIR145 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MIR145 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: MIR145 were set to 36649075 Phenotypes for gene: MIR145 were set to multisystemic smooth muscle dysfunction syndrome (MONDO:0013452), MIR145-related Review for gene: MIR145 was set to RED Added comment: PMID: 36649075- a patient whose fetal ultrasound revealed polyhydramnios, enlarged abdomenand bladder, and prune belly syndrome. During infancy/childhood profound gastrointestinal dysmotility, cerebrovascular disease, and multiple strokes. Described as a multisystemic smooth muscle dysfunction syndrome. Patient was found to have a de novo SNP in MIR145 NR_029686.1:n.18C>A. The MIR145transcript is processed into two microRNAs, with the variant position at nucleotide 3 of miR-145-5p. Transfection of an siRNA against mutant miR145-5p induced a notable decrease in the expression of several cytoskeletal proteins including transgelin, calponin, and importantly, smooth muscle actin. Hybridization analysis and miR RNA-seq demonstrated a decrease in expression of miR145-5p in the presence of mutant miR145-5p. RNA-seq showed that the differentially expressed genes were substantially different between patient and control fibroblasts. Sources: Literature |
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| Mendeliome v1.632 | CAMLG |
Manny Jacobs gene: CAMLG was added gene: CAMLG was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CAMLG was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CAMLG were set to PMID: 35262690 Phenotypes for gene: CAMLG were set to Congenital disorder of glycosylation type IIz, 620201 Penetrance for gene: CAMLG were set to unknown Review for gene: CAMLG was set to RED Added comment: PMID: 35262690 (2022) Report one patient with hom splice variant. No other reported patients. GDD, seizures, contractures, hypotonia and brain malformations. Sources: Literature |
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| Mendeliome v1.630 | HTR2C | Zornitza Stark Marked gene: HTR2C as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.630 | TRU-TCA1-1 |
Paul De Fazio gene: TRU-TCA1-1 was added gene: TRU-TCA1-1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TRU-TCA1-1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TRU-TCA1-1 were set to 26854926; 34956927 Phenotypes for gene: TRU-TCA1-1 were set to Hyperthyroidism MONDO:0004425 Review for gene: TRU-TCA1-1 was set to AMBER gene: TRU-TCA1-1 was marked as current diagnostic Added comment: PMID 26854926: male 8 year old proband investigated for abdominal pain, fatigue, muscle weakness, and thyroid dysfunction (raised T4, normal T3, raised reverse T3) suggestive of impaired deiodinase activity in combination with low plasma selenium levels. Homozygosity mapping led to identification of a a single nucleotide change, C65G, in TRU-TCA1-1, a tRNA in the selenocysteine incorporation pathway. This mutation resulted in reduction in expression of stress-related selenoproteins. A methylribosylation defect at uridine 34 of mutant tRNA observed in patient cells was restored by cellular complementation with normal tRNA. PMID 34956927: a 10 year old originally investigated for Hashimoto's disease was found to be homozygous for the same C65G variant identified in the previous paper, inherited from the father in what was concluded to be paternal isodisomy. Sources: Literature |
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| Mendeliome v1.629 | HTR2C |
Zornitza Stark gene: HTR2C was added gene: HTR2C was added to Mendeliome. Sources: Literature Mode of inheritance for gene: HTR2C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: HTR2C were set to 36536256 Phenotypes for gene: HTR2C were set to Obesity disorder, MONDO:0011122, HTR2C-related Review for gene: HTR2C was set to GREEN Added comment: Exome sequencing of 2,548 people with severe obesity and 1,117 control individuals without obesity identified 13 rare variants in the gene encoding 5-HT2CR (HTR2C) in 19 unrelated people (3 males and 16 females). Eleven variants caused a loss of function in HEK293 cells. All people who carried variants had hyperphagia and some degree of maladaptive behavior. Obesity was severe, childhood-onset. Knock-in male mice harboring a human loss-of-function HTR2C variant developed obesity and reduced social exploratory behavior; female mice heterozygous for the same variant showed similar deficits with reduced severity. Sources: Literature |
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| Mendeliome v1.628 | CCDC84 |
Lucy Spencer gene: CCDC84 was added gene: CCDC84 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CCDC84 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CCDC84 were set to 34009673 Phenotypes for gene: CCDC84 were set to Mosaic variegated aneuploidy syndrome 4 (MIM#620153) Review for gene: CCDC84 was set to AMBER Added comment: PMID: 34009673- patients with constitutional mosaic aneuploidy were found to have biallelic mutations in CENATAC(CCDC84). 2 adult siblings with mosaic aneuploidies, microcephaly, dev delay, and maculopathy. Both chet for a missense and a splice site deletion- but the paper days these both result in the creation of a novel splice site that leads to frameshifts and loss of the c-terminal 64 amino acids. Gene is shown to be part of a spliceosome. CENATAC depletion or expression of disease mutants resulted in retention of introns in ~100 genes enriched for nucleocytoplasmic transport and cell cycle regulation, and caused chromosome segregation errors. Functional analysis in CENATAC-depleted HeLa cells demonstrated chromosome congression defects and subsequent mitotic arrest, which could be fully rescued by wildtype but not mutant CENATAC. Expression of the MVA-associated mutants exacerbated the phenotype, suggesting that the mutant proteins dominantly repress the function of any residual wildtype protein. Sources: Literature |
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| Mendeliome v1.628 | THBS1 | Zornitza Stark Marked gene: THBS1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.627 | OGDH | Sarah Pantaleo reviewed gene: OGDH: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 36520152; Phenotypes: Oxoglutarate dehydrogenase deficiency, MIM# 203740; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.627 | NPTX1 | Ain Roesley Marked gene: NPTX1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.626 | THBS1 |
Zornitza Stark gene: THBS1 was added gene: THBS1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: THBS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: THBS1 were set to 36453543 Phenotypes for gene: THBS1 were set to Congenital glaucoma MONDO:0020366, THBS1-related Review for gene: THBS1 was set to GREEN Added comment: Missense alleles altering p.Arg1034, a highly evolutionarily conserved amino acid, in 3 unrelated and ethnically diverse families affected by congenital glaucoma. Thbs1R1034C-mutant mice had elevated intraocular pressure (IOP), reduced ocular fluid outflow, and retinal ganglion cell loss. Histology revealed an abundant, abnormal extracellular accumulation of THBS1 with abnormal morphology of juxtacanalicular trabecular meshwork (TM), an ocular tissue critical for aqueous fluid outflow. Functional characterization showed that the THBS1 missense alleles found in affected individuals destabilized the THBS1 C-terminus, causing protein misfolding and extracellular aggregation. Analysis using a range of amino acid substitutions at position R1034 showed that the extent of aggregation was correlated with the change in protein-folding free energy caused by variations in amino acid structure. Sources: Literature |
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| Mendeliome v1.625 | NPTX1 |
Ain Roesley gene: NPTX1 was added gene: NPTX1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NPTX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: NPTX1 were set to 34788392; 35288776; 35285082; 35560436 Phenotypes for gene: NPTX1 were set to cerebellar ataxia MONDO#0000437, NPTX1-related Review for gene: NPTX1 was set to GREEN gene: NPTX1 was marked as current diagnostic Added comment: PMID:34788392 5 families with multigenerational segregations - late onset ataxia 4 families with p.(Gly389Arg) + 1x p.(Glu327Gly) functional studies done Note: case report of a family member published elsewhere (PMID:35288776) PMID:35285082 1x de novo in a male with late-onset, slowly progressive cerebellar ataxia, oculomotor apraxia, choreiform dyskinesias, and cerebellar cognitive affective syndrome p.(Arg143Leu) PMID:35560436 1x de novo in a female with early-onset ataxia and cerebellar atrophy since infancy p.(Gln370Arg) Sources: Literature |
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| Mendeliome v1.624 | GET4 | Elena Savva Marked gene: GET4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.623 | USP48 | Zornitza Stark Phenotypes for gene: USP48 were changed from non-syndromic hearing loss; nonsyndromic genetic deafness, MONDO:0019497 to Deafness, autosomal dominant 85, MIM# 620227 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.621 | AGR2 | Zornitza Stark Phenotypes for gene: AGR2 were changed from CF-like disorder to Recurrent respiratory infections and failure to thrive with or without diarrhea (RIFTD), MIM#620233 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.620 | AGR2 | Zornitza Stark edited their review of gene: AGR2: Changed phenotypes: Recurrent respiratory infections and failure to thrive with or without diarrhea (RIFTD), MIM#620233 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.619 | SARS | Zornitza Stark Phenotypes for gene: SARS were changed from neurodevelopmental disorder MONDO#070009, SARS1-related to neurodevelopmental disorder MONDO#070009, SARS1-related; Genetic peripheral neuropathy MONDO#0020127, SARS1-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.618 | SARS | Zornitza Stark Publications for gene: SARS were set to 28236339; 34570399; 35790048; 36041817 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.617 | SARS | Zornitza Stark Mode of inheritance for gene: SARS was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.616 | DRC1 | Zornitza Stark Phenotypes for gene: DRC1 were changed from Ciliary dyskinesia, primary, 21, MIM# 615294; Male infertility to Ciliary dyskinesia, primary, 21, MIM# 615294; Spermatogenic failure 80, MIM# 620222 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.615 | DRC1 | Zornitza Stark edited their review of gene: DRC1: Changed phenotypes: Ciliary dyskinesia, primary, 21, MIM# 615294, Spermatogenic failure 80, MIM# 620222 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.614 | LY96 | Zornitza Stark Marked gene: LY96 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.614 | LY96 |
Zornitza Stark gene: LY96 was added gene: LY96 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: LY96 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LY96 were set to 36462957 Phenotypes for gene: LY96 were set to Inborn error of immunity, MONDO:0003778, LY96-related Review for gene: LY96 was set to RED Added comment: Single individual with infantile colitis associated with failure-to-thrive, bloody diarrhoea, and perianal abscesses since the age of 4 months. Later developed bronchiectasis and persistent pneumonia, which required lobectomy at the age of 6 years. Found to have homozygous inflame deletion. Brother with same deletion presented with recurrent otitis media and pneumonia but exhibited no signs of intestinal inflammation. Sources: Expert Review |
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| Mendeliome v1.611 | FGF13 | Zornitza Stark edited their review of gene: FGF13: Added comment: PMID 34184986: 3 individuals reported with moderate to severe ID and maternally inherited 5' variant c.-32C-G; Changed publications: 33245860, 34184986 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.611 | ZNF668 | Zornitza Stark Phenotypes for gene: ZNF668 were changed from DNA damage repair defect; microcephaly; growth deficiency; severe global developmental delay; brain malformation; facial dysmorphism to Neurodevelopmental disorder with poor growth, large ears, and dysmorphic facies, MIM# 620194 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.610 | ZNF668 | Zornitza Stark reviewed gene: ZNF668: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with poor growth, large ears, and dysmorphic facies, MIM# 620194; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.608 | NAE1 | Zornitza Stark Marked gene: NAE1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.607 | NAE1 |
Zornitza Stark gene: NAE1 was added gene: NAE1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NAE1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NAE1 were set to 36608681 Phenotypes for gene: NAE1 were set to Neurodevelopmental disorder, MONDO:0700092, NAE1-related Review for gene: NAE1 was set to GREEN Added comment: Four individuals reported with bi-allelic variants and intellectual disability, ischiopubic hypoplasia, stress-mediated lymphopenia and neurodegeneration. Sources: Literature |
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| Mendeliome v1.606 | SLC26A6 | Zornitza Stark Marked gene: SLC26A6 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.606 | SLC26A6 | Zornitza Stark Phenotypes for gene: SLC26A6 were changed from Enteric hyperoxaluria and nephrolithiasis to Primary hyperoxaluria, MONDO:0002474, SLC26A6-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.604 | SLC26A6 | Zornitza Stark reviewed gene: SLC26A6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Primary hyperoxaluria, MONDO:0002474, SLC26A6-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.604 | TRPC5 | Zornitza Stark Marked gene: TRPC5 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.601 | TRPC5 |
Hazel Phillimore gene: TRPC5 was added gene: TRPC5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TRPC5 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: TRPC5 were set to PMID: 36323681; 24817631; 23033978; 33504798; 28191890 Phenotypes for gene: TRPC5 were set to Intellectual disability; autistic spectrum disorder Review for gene: TRPC5 was set to AMBER Added comment: PMID: 36323681; Leitão E. et al. (2022) Nat Commun.13(1):6570: Missense variant NM_012471.2:c.523C>T, p.(Arg175Cys in three brothers with intellectual disability (ID) and autistic spectrum disorder (ASD), inherited from an asymptomatic mother and absent in the maternal grandparents. Whole cell patch clamp studies of HEK293 created by site-directed mutagenesis showed increased current of this calcium channel (constitutively opened). (This variant is absent in gnomAD v2.1.1). Also, the nonsense variant, c.965G> A, p.(Trp322*) was found in a high functioning ASD male (maternally inherited), NMD-predicted. Other papers and TRPC5 variants that were cited to associate this gene with X-linked ID and/or ASD include: PMID: 24817631; Mignon-Ravix, C. et al. (2014) Am. J.Med. Genet. A 164A: 1991–1997: A hemizygous 47-kb deletion in Xq23 including exon 1 of the TRPC5 gene. He had macrocephaly, delayed psychomotor development, speech delay, behavioural problems, and autistic features. Maternally inherited, and a family history compatible with X-linked inheritance (i.e., maternal great uncle was also affected, although not tested). In addition, PMID: 36323681; Leitão E. et al. (2022) cites papers with the variants p.(Pro667Thr), p.(Arg71Gln) and p.(Trp225*). NB. p.(Pro667Thr) is absent in gnomAD (v2.1.1), p.(Arg71Gln) is also absent (the alternative variant p.(Arg71Trp) is present once as heterozygous only). p.(Trp225*) is absent, and it should be noted that PTCs / LoF variants are very rare (pLI = 1). However, looking further into the three references, the evidence is not as clear or as accurate as was stated. The missense variant c.1999C>A, p.(Pro667Thr), was stated as de novo, but was actually maternally inherited but was still considered a candidate for severe intellectual disability (shown in the Appendix, Patient 93, with severe speech delay, autism spectrum disorder and Gilles de la Tourette). This patient also has a de novo MTF1 variant. Reference: PMID: 23033978; de Ligt, J. et al. (2012) N. Engl. J. Med. 367: 1921–1929). Missense variant (de novo): c.212G>A, p.(Arg71Gln), was found as part of the Deciphering Developmental Disorders (DDD) study and is shown in individual 164 in Supplementary Table 2 of PMID: 33504798; Martin, HC. et al. (2021) Nat. Commun.12: 627. Also displayed in DECIPHER (DDD research variant) with several phenotype traits, but ID and ASD are not specifically mentioned. Nonsense variant: c.674G>A. p.(Trp225*) was stated as de novo but was inherited (reference PMID: 28191890; Kosmicki, JA. et al. (2017) Nat. Genet. 49: 504–510. Supplement Table 7). This was a study of severe intellectual delay, developmental delay / autism. (NB. The de novo p.(Arg71Gln) variant from the DDD study is also listed (subject DDD 342 in Supplement 4 / Table 2). Sources: Literature |
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| Mendeliome v1.601 | ZMYM3 | Zornitza Stark Marked gene: ZMYM3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.601 | BSN |
Krithika Murali changed review comment from: Ye et al 2022, Neurogenetics identified 4 unrelated individuals with epilepsy and compound heterozygous BSN variants via trio WES (combination of null and missense). Homozygous knockout mouse models showed abnormal CNS transmission and seizure activity. None of the identified variants were present in population databases as homozygotes. One individual had ID and microcephaly but all other individuals with biallelic variants had normal development. In addition, heterozygous variants were identified in unrelated affected individuals - 2 apparently co-segregating missense variants and 2 de novo null variants. These variants were either absent in population databases or rare. The authors note that affected individuals with heterozygous variants had milder disease - either requiring no therapy or monotherapy only. Heterozygous knockout mice had no phenotype and there were not enough affected individuals in the families to truly determine co-segregation. In addition, carrier parents of individuals with biallelic variants did not appear to be affected. Association between biallelic variants and epilepsy stronger than for monoallelic. Sources: Literature; to: Ye et al 2022, Neurogenetics - https://jmg.bmj.com/content/early/2022/12/12/jmg-2022-108865 Identified 4 unrelated individuals with epilepsy and compound heterozygous BSN variants via trio WES (combination of null and missense). Homozygous knockout mouse models showed abnormal CNS transmission and seizure activity. None of the identified variants were present in population databases as homozygotes. One individual had ID and microcephaly but all other individuals with biallelic variants had normal development. In addition, heterozygous variants were identified in unrelated affected individuals - 2 apparently co-segregating missense variants and 2 de novo null variants. These variants were either absent in population databases or rare. The authors note that affected individuals with heterozygous variants had milder disease - either requiring no therapy or monotherapy only. Heterozygous knockout mice had no phenotype and there were not enough affected individuals in the families to truly determine co-segregation. In addition, carrier parents of individuals with biallelic variants did not appear to be affected. Association between biallelic variants and epilepsy stronger than for monoallelic. Sources: Literature |
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| Mendeliome v1.597 | BSN | Zornitza Stark Marked gene: BSN as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.597 | BSN | Zornitza Stark Added comment: Comment when marking as ready: We are aware of additional mono-allelic cases. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.595 | UHRF1 |
Chern Lim changed review comment from: PMID: 29574422 Begemann et al. 2018 - Het missense in mother and proband, family recruited due to detection of multilocus imprinting disturbance (MLID) in offspring. Proband is one of discordant monozygotic twin. SRS: NH-CSS 5/6; also kidney failure in infancy, bilateral renal dysplasia. Variant present in both twins, no functional studies done on the missense.; to: PMID: 29574422 Begemann et al. 2018 - Het missense in mother and proband, family recruited due to detection of multilocus imprinting disturbance (MLID) in offspring. Proband is one of discordant monozygotic twin. SRS: NH-CSS 5/6; also kidney failure in infancy, bilateral renal dysplasia. Variant present in both twins, no functional studies done on the missense. Her cotwin was clinically and epigenetically normal |
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| Mendeliome v1.595 | ARHGAP35 | Zornitza Stark Phenotypes for gene: ARHGAP35 were changed from neurodevelopmental disorder, ARHGAP35-related MONDO#0700092 to neurodevelopmental disorder, ARHGAP35-related MONDO#0700092; Developmental defect of the eye (MONDO:0020145), ARHGAP35-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.594 | ARHGAP35 | Zornitza Stark Publications for gene: ARHGAP35 were set to 33057194 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.593 | ARHGEF38 | Zornitza Stark Marked gene: ARHGEF38 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.593 | ARHGEF38 | Zornitza Stark Gene: arhgef38 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.593 | UHRF1 |
Chern Lim edited their review of gene: UHRF1: Added comment: PMID: 36458887 Unoki et al. 2022 - One patient with compound het missense and nonsense variants, both parents are carriers (hets). - The patient has chromosome instability with hypomethylation of the pericentromeric satellite-2 repeats and facial anomalies as typical symptoms of the ICF syndrome, but did not exhibit immunodeficiency, and developed an adrenocortical adenoma; characteristics that were atypical. - Genome-wide methylation analysis revealed the patient had a centromeric/pericentromeric hypomethylation, which is the main ICF signature, but also had a distinctive hypomethylation pattern compared to patients with the other ICF syndrome subtypes. - Structural and biochemical analyses revealed that the R296W variant disrupted the protein conformation and strengthened the binding affinity of UHRF1 with its partner LIG1, and reduced ubiquitylation activity of UHRF1 towards its ubiquitylation substrates, histone H3 and PAF15.; Changed publications: 36458887; Changed phenotypes: chromosome instability; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal |
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| Mendeliome v1.593 | ARHGEF38 | Zornitza Stark Mode of inheritance for gene: ARHGEF38 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.592 | ARHGEF38 | Zornitza Stark Classified gene: ARHGEF38 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.592 | ARHGEF38 | Zornitza Stark Gene: arhgef38 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.591 | EIF4A2 | Zornitza Stark Marked gene: EIF4A2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.590 | ARHGAP35 | Dean Phelan reviewed gene: ARHGAP35: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 36450800; Phenotypes: Developmental defect of the eye (MONDO:0020145), ARHGAP35-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.589 | ARHGEF38 |
Paul De Fazio gene: ARHGEF38 was added gene: ARHGEF38 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ARHGEF38 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: ARHGEF38 were set to 36493769 Phenotypes for gene: ARHGEF38 were set to Cleft lip/palate MONDO:0016044, ARHGEF38-related Review for gene: ARHGEF38 was set to AMBER gene: ARHGEF38 was marked as current diagnostic Added comment: PMID:36493769 identified an intragenic deletion by high-res microarray of the same exon (exon 3) in 4 individuals with non-syndromic cleft lip/palate. Deletion of exon 3 is present in 6 individuals in gnomAD. Inheritance information was not available. Knockdown and knockout of the gene in Xenopus and Zebrafish resulted in craniofacial malformations in a large proportion (but not 100%) of embryos. Sources: Literature |
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| Mendeliome v1.589 | COBLL1 | Zornitza Stark Marked gene: COBLL1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.588 | COBLL1 |
Paul De Fazio gene: COBLL1 was added gene: COBLL1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: COBLL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: COBLL1 were set to 36493769 Phenotypes for gene: COBLL1 were set to Cleft lip/palate MONDO:0016044, COBLL1-related gene: COBLL1 was marked as current diagnostic Added comment: PMID:36493769 identified the same multi-exon intragenic deletion by high-res microarray in 3 individuals with non-syndromic cleft lip/palate. The deletion is absent from gnomAD. Inheritance information was only available for 1 individual, in whom it was inherited from an unaffected father. Note that the gene is not quite LOF constrained in gnomAD. Knockdown and knockout of the gene in Xenopus and Zebrafish resulted in craniofacial malformations in a large proportion (but not 100%) of embryos. Sources: Literature |
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| Mendeliome v1.588 | BSN |
Krithika Murali gene: BSN was added gene: BSN was added to Mendeliome. Sources: Literature Mode of inheritance for gene: BSN was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: BSN were set to Epilepsy MONDO:0005027 Review for gene: BSN was set to GREEN Added comment: Ye et al 2022, Neurogenetics identified 4 unrelated individuals with epilepsy and compound heterozygous BSN variants via trio WES (combination of null and missense). Homozygous knockout mouse models showed abnormal CNS transmission and seizure activity. None of the identified variants were present in population databases as homozygotes. One individual had ID and microcephaly but all other individuals with biallelic variants had normal development. In addition, heterozygous variants were identified in unrelated affected individuals - 2 apparently co-segregating missense variants and 2 de novo null variants. These variants were either absent in population databases or rare. The authors note that affected individuals with heterozygous variants had milder disease - either requiring no therapy or monotherapy only. Heterozygous knockout mice had no phenotype and there were not enough affected individuals in the families to truly determine co-segregation. In addition, carrier parents of individuals with biallelic variants did not appear to be affected. Association between biallelic variants and epilepsy stronger than for monoallelic. Sources: Literature |
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| Mendeliome v1.588 | EIF4A2 |
Dean Phelan gene: EIF4A2 was added gene: EIF4A2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: EIF4A2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: EIF4A2 were set to PMID: 36528028 Phenotypes for gene: EIF4A2 were set to Neurodevelopmental disorder (MONDO:0700092), EIF4A2-related Mode of pathogenicity for gene: EIF4A2 was set to Other Review for gene: EIF4A2 was set to GREEN Added comment: PMID: 36528028 - EIF4A2 variants were observed in 15 individuals from 14 families. Affected individuals had a range of symptoms including global developmental delay (9/15), ID (7/15), epilepsy (11/15) and structural brain alterations (10/15). Monoallelic and biallelic variants were reported and functional studies showed both LOF and GOF disease mechanisms. Sources: Literature |
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| Mendeliome v1.588 | PHLDB1 | Seb Lunke Marked gene: PHLDB1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.587 | PHLDB1 |
Seb Lunke gene: PHLDB1 was added gene: PHLDB1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PHLDB1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PHLDB1 were set to 36543534 Phenotypes for gene: PHLDB1 were set to osteogenesis imperfecta, MONDO:0019019 Review for gene: PHLDB1 was set to AMBER Added comment: 5 children from two consanguineous families with recurrent fractures and/or osteopaenia, platyspondyly, short and bowed long bones, and widened metaphyses. Metaphyseal and vertebral changes regressed after early childhood, and no fractures occurred under bisphosphonate treatment. Two independent nonsense variants were identified in the families, NM_001144758.3:c.2392dup (p.Leu798Profs*4) and NM_001144758.3:c.2690_2693del (p.Leu897Glnfs*24). RT-PCR and western blot analysis confirmed loss of transcript and protein product, respectively, but no further functional data provided. Sources: Literature |
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| Mendeliome v1.586 | OXGR1 | Zornitza Stark Marked gene: OXGR1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.583 | OXGR1 |
Sarah Pantaleo gene: OXGR1 was added gene: OXGR1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: OXGR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: OXGR1 were set to PMID:35671463 Phenotypes for gene: OXGR1 were set to Nephrolithiasis/nephrocalcinosis MONDO:0008171, OXGR1-related Penetrance for gene: OXGR1 were set to unknown Review for gene: OXGR1 was set to AMBER Added comment: Candidate disease gene for human calcium oxalate nephrolithiasis. Performed exome sequencing and directed sequencing of the OXGR1 locus in a worldwide nephrolithiasis/nephrocalcinosis (NL/NC) cohort, and putatively deleterious rare OXGR1 variants were functionally characterised. A heterozygous OXGR1 missense variant (c.371T>G; p.Leu124Arg) co-segregated with calcium oxalate NL and/or NC disease in an autosomal dominant inheritance pattern within a multi-generational family with five affected individuals. Interrogation of the OXGR1 locus in 1,107 additional NL/NC families identified five additional deleterious dominant variants in five families with calcium oxalate NL/NC. Rare, potentially deleterious OXGR1 variants were enriched in NL/NC subjects relative to ExAC controls. Four missense variants and one frameshift variant. Four of five NL/NC-associated missense variants revealed impaired AKG-dependent calcium ion uptake, demonstrating loss of function. Rare, dominant loss-of-function OXGR1 variants are associated with recurrent calcium oxalate NL/NC disease. Six potentially deleterious variants were identified in six of 1,108 NL/NC families (0.54%). Limitations: only probands were able to be recruited for four of six families. In the future, it will be important to determine whether any of the affected family members share the identified OXGR1 variant. They also observe OXGR1 variants in 0.16% of ExAC subjects (selected on the basis of the absence of paediatric disease). Sources: Literature |
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| Mendeliome v1.582 | CCIN | Seb Lunke Marked gene: CCIN as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.580 | CCIN |
Chern Lim gene: CCIN was added gene: CCIN was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CCIN was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CCIN were set to 36546111; 36527329 Phenotypes for gene: CCIN were set to Teratozoospermia Review for gene: CCIN was set to GREEN gene: CCIN was marked as current diagnostic Added comment: Two papers with three unrelated patients with teratozoospermia: PMID: 36546111 - Two families reported: One with homozygous missense (fam is consanguineous) and another with compound heterozygous missense + nonsense variants, patients suffering from teratozoospermia. - Homozygous CcinH42L/H42L and compound heterozygous CcinR432W/C447* knock-in mice generated. Spermatozoa from homozygous male mice exhibited abnormalities of sperm head shape revealed by Diff-Quick staining. When mated with WT mice, both homozygous CcinH42L/H42L and compound heterozygous CcinR432W/C447* male mice were infertile, whereas the mutant female mice could generate offspring and displayed no defects in fertility. PMID: 36527329 - One consanguineous family reported: homozygous missense, with asthenoteratozoospermia. - Transfected HEK cells showed reduced CCIN protein level. Sources: Literature |
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| Mendeliome v1.580 | TRA2B | Seb Lunke Marked gene: TRA2B as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.576 | TRA2B |
Elena Savva gene: TRA2B was added gene: TRA2B was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TRA2B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: TRA2B were set to PMID: 36549593 Phenotypes for gene: TRA2B were set to Neurodevelopmental disorder, TRA2B-related (MONDO#0700092) Review for gene: TRA2B was set to GREEN Added comment: PMID: 36549593 - 12 individuals with ID and dev delay. Additional features include infantile spams 6/12, hypotonia 12/12, dilated brain ventricles 6/12, microcephaly 5/12 - All variants result in the loss of 1/2 transcripts (start-losses or PTCs upstream of a second translation start position). Shorter transcript expression is increased, longer transcript expression is decreased. - Apparently het mice K/O are normal, but complete K/O cannot develop embryonically. - DN mechanism suggested Sources: Literature |
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| Mendeliome v1.574 | TUFT1 | Zornitza Stark Marked gene: TUFT1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.573 | TUFT1 |
Zornitza Stark gene: TUFT1 was added gene: TUFT1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TUFT1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TUFT1 were set to https://doi.org/10.1093/bjd/ljac026 Phenotypes for gene: TUFT1 were set to Ectodermal dysplasia, MONDO:0019287, TUFT1-related Review for gene: TUFT1 was set to AMBER Added comment: 9 individuals from three families reported with woolly hair and skin fragility. One of the variants, c.60+1G>A was present in two of the families, founder effect demonstrated by haplotype analysis. Another loss of function variant present in the third family. Some functional data but mostly expression studies. Sources: Literature |
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| Mendeliome v1.572 | ZMYM3 |
Belinda Chong gene: ZMYM3 was added gene: ZMYM3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ZMYM3 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: ZMYM3 were set to 36586412; 24721225 Phenotypes for gene: ZMYM3 were set to Neurodevelopmental disorders (NDDs) Review for gene: ZMYM3 was set to GREEN Added comment: PMID: 36586412 Using the MatchMaker Exchange - Described 27 individuals with rare, variation in the ZMYM3. Most individuals were males, 17 of which have a maternally inherited variant; six individuals (4 male, 2 female) with de novo variants. Overlapping features included developmental delay, intellectual disability, behavioural abnormalities, and a specific facial gestalt in a subset of males. Variants in almost all individuals are missense, including six that recurrently affect two residues. Four unrelated probands were identified with inherited variation affecting Arg441 (R441W), a site at which variation has been previously seen in NDD-affected siblings (24721225), and two individuals have de novo variation resulting in p.Arg1294Cys (c.3880C>T). ChIP-seq experiments on one variant, p.Arg1274Trp, indicate dramatically reduced genomic occupancy, supporting a hypomorphic effect. Sources: Literature |
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| Mendeliome v1.572 | KMT2D | Zornitza Stark Phenotypes for gene: KMT2D were changed from Kabuki syndrome 1, MIM# 147920; KMT2D-associated syndrome to Kabuki syndrome 1, MIM# 147920; Branchial arch abnormalities, choanal atresia, athelia, hearing loss, and hypothyroidism syndrome (BCAHH), MIM#620186 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.571 | KMT2D | Zornitza Stark edited their review of gene: KMT2D: Changed phenotypes: Kabuki syndrome 1, MIM# 147920, Branchial arch abnormalities, choanal atresia, athelia, hearing loss, and hypothyroidism syndrome (BCAHH), MIM#620186 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.571 | BUB1 | Zornitza Stark Phenotypes for gene: BUB1 were changed from Neurodevelopmental disorder, BUB1-related MONDO:0700092 to Primary microcephaly-30 (MCPH30), MIM#620183 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.570 | BUB1 | Zornitza Stark edited their review of gene: BUB1: Changed phenotypes: primary microcephaly-30 (MCPH30), MIM#620183 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.570 | GOSR2 | Zornitza Stark Phenotypes for gene: GOSR2 were changed from Epilepsy, progressive myoclonic 6 , MIM#614018 to Epilepsy, progressive myoclonic 6 , MIM#614018; Muscular dystrophy, congenital, with or without seizures, MIM# 620166 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.569 | GOSR2 | Zornitza Stark edited their review of gene: GOSR2: Added comment: PMIDs 29855340; 33639315: at least three families reported with a muscular dystrophy presentation as well as seizures.; Changed publications: 21549339, 24458321, 30363482, 29855340, 33639315; Changed phenotypes: Epilepsy, progressive myoclonic 6 , MIM#614018, Muscular dystrophy, congenital, with or without seizures, MIM# 620166 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.567 | TSPEAR | Zornitza Stark Phenotypes for gene: TSPEAR were changed from Ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis, MIM#618180 to Ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis, MIM#618180; Selective tooth agenesis-10 (STHAG10), MIM#620173 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.566 | TSPEAR | Zornitza Stark Publications for gene: TSPEAR were set to 27736875; 30046887 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.565 | TSPEAR | Zornitza Stark edited their review of gene: TSPEAR: Added comment: More than 5 individuals reported with selective tooth agenesis.; Changed rating: GREEN; Changed publications: 30046887, 32112661, 34042254; Changed phenotypes: Selective tooth agenesis-10 (STHAG10), MIM#620173; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.563 | SLC26A6 |
Arina Puzriakova gene: SLC26A6 was added gene: SLC26A6 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SLC26A6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: SLC26A6 were set to 35115415; 21170874; 32660969 Phenotypes for gene: SLC26A6 were set to Enteric hyperoxaluria and nephrolithiasis Added comment: Cornière et al. 2022 (PMID: 35115415) identified a single family with a heterozygous missense VUS (c.1519C>T/p.R507W) in the SLC26A6 gene. However, the variant was found in 5 out of 280 674 alleles reported in gnomAD (Europeans and South Asians). In vitro studies showed that the variant affects both SLC26A6 transport activity and membrane surface expression, in turn reducing Cl− dependant oxalate transport. Cotransfection studies indicated a dominant-negative effect on WT. Slc26a6 null mice similarly displayed hyperoxalemia and hyperoxaluria which were caused by defective intestinal back-secretion of dietary oxalate (PMID: 21170874; 32660969) SLC26A6 is currently not associated with any human phenotype in OMIM or G2P. Sources: Literature |
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| Mendeliome v1.563 | WDFY3 | Zornitza Stark Phenotypes for gene: WDFY3 were changed from Microcephaly 18, primary, autosomal dominant, MIM#617520 to Microcephaly 18, primary, autosomal dominant, MIM#617520; Neurodevelopmental disorder with macrocephaly | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.559 | CLDN5 | Zornitza Stark Mode of pathogenicity for gene: CLDN5 was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.554 | SETD2 |
Zornitza Stark edited their review of gene: SETD2: Added comment: PMID 32710489: 12 unrelated patients, ranging from 1 month to 12 years of age, with a multisystemic neurodevelopmental disorder associated with a specific de novo heterozygous mutation in the SETD2 gene (R1740W). Key clinical features: severely impaired global development apparent from infancy, feeding difficulties with failure to thrive, small head circumference, and dysmorphic facial features. Affected individuals have impaired intellectual development and hypotonia; they do not achieve walking or meaningful speech. Other neurologic findings may include seizures, hearing loss, ophthalmologic defects, and brain imaging abnormalities. There is variable involvement of other organ systems, including skeletal, genitourinary, cardiac, and possibly endocrine. Further 3 unrelated patients identified with mild to moderately impaired intellectual development associated with a specific de novo heterozygous mutation in the SETD2 gene (R1740Q). These are distinct clinically from Luscan-Lumish syndrome, which is characterised by overgrowth.; Changed publications: 29681085, 32710489; Changed phenotypes: Luscan-Lumish syndrome, MIM#616831, Rabin-Pappas syndrome,MIM# 620155, Intellectual developmental disorder, autosomal dominant 70, MIM# 620157 |
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| Mendeliome v1.554 | RPS15 | Zornitza Stark Marked gene: RPS15 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.552 | CLDN5 | Suliman Khan reviewed gene: CLDN5: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: PMID: 36477332; Phenotypes: seizures, developmental delay, microcephaly, brain calcifications; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.548 | HSPG2 | Zornitza Stark Phenotypes for gene: HSPG2 were changed from Dyssegmental dysplasia, Silverman-Handmaker type; Schwartz-Jampel syndrome, type 1 to Schwartz-Jampel syndrome, type 1, MIM# 255800; MONDO:0009717; Dyssegmental dysplasia, Silverman-Handmaker type, MIM# 224410; MONDO:0009140 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.547 | IL2RB |
Zornitza Stark changed review comment from: Five families reported. Sources: Expert list; to: Five families reported. Affected individuals present in infancy with features of both abnormal activation of certain immune signaling pathways, resulting in lymphoid proliferation, dermatitis, enteropathy, and hypergammaglobulinemia, as well as features of immunodeficiency, such as recurrent infections and increased susceptibility to viral infections, especially CMV. Laboratory studies show increased NK cells that show impaired differentiation, as well as abnormal T cell populations or responses. Some patients may die in childhood; hematopoietic bone marrow transplantation is curative. Sources: Expert list |
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| Mendeliome v1.544 | RPS6KB1 | Zornitza Stark Marked gene: RPS6KB1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.544 | RPS6KB1 | Zornitza Stark Phenotypes for gene: RPS6KB1 were changed from Hypertrophic cardiomyopathy to Hypertrophic cardiomyopathy, MONDO:0005045, RPS6KB1-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.542 | TNNC2 | Zornitza Stark Marked gene: TNNC2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.541 | TNNC2 |
Zornitza Stark gene: TNNC2 was added gene: TNNC2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TNNC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TNNC2 were set to 33755597 Phenotypes for gene: TNNC2 were set to Congenital myopathy, MONDO:0019952, TNNC2-related Review for gene: TNNC2 was set to GREEN Added comment: Two families reported: Family 1: 4 individuals, three generations; missense variant p.(Asp34Tyr) Family 2: de novo variant, missense p.(Met79Ile) Physiological studies in myofibers isolated from patients’ biopsies revealed a markedly reduced force response of the sarcomeres to [Ca2+]. This pathomechanism was further confirmed in experiments in which contractile dysfunction was evoked by replacing TnC in myofibers from healthy control subjects with recombinant, mutant TnC. Conversely, the contractile dysfunction of myofibers from patients was repaired by replacing endogenous, mutant TnC with recombinant, wild-type TnC. Borderline Green: sufficient segregation in Fam 1 plus de novo status in Fam 2, plus functional data. Sources: Literature |
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| Mendeliome v1.540 | CHUK | Zornitza Stark Phenotypes for gene: CHUK were changed from Popliteal pterygium syndrome, Bartsocas-Papas type 2, MIM# 619339; Cocoon syndrome, MIM# 613630; AEC-like syndrome to Combined immunodeficiency, MONDO:0015131, CHUK-related; Popliteal pterygium syndrome, Bartsocas-Papas type 2, MIM# 619339; Cocoon syndrome, MIM# 613630; AEC-like syndrome | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.538 | CHUK | Zornitza Stark edited their review of gene: CHUK: Changed phenotypes: Combined immunodeficiency, MONDO:0015131, CHUK-related, Popliteal pterygium syndrome, Bartsocas-Papas type 2, MIM# 619339, Cocoon syndrome, MIM# 613630, AEC-like syndrome | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.538 | CHUK | Zornitza Stark edited their review of gene: CHUK: Added comment: PMID 34533979: single individual reported with homozygous missense variant in this gene and recurrent infections, skeletal abnormalities, absent secondary lymphoid structures, reduced B cell numbers, hypogammaglobulinemia, and lymphocytic infiltration of intestine. Supportive functional data.; Changed publications: 25691407, 20961246, 10195895, 10195896, 29523099, 28513979, 34533979 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.535 | LIG1 | Zornitza Stark Phenotypes for gene: LIG1 were changed from Combined immunodeficiency; Lymphopaenia; Hypogammaglobulinaemia; Recurrent bacterial and viral infections; Growth retardation; Sun sensitivity, radiation sensitivity; Macrocytosis to Immunodeficiency 96, MIM# 619774; Lymphopaenia; Hypogammaglobulinaemia; Recurrent bacterial and viral infections; Growth retardation; Sun sensitivity, radiation sensitivity; Macrocytosis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.534 | NLGN4X | Zornitza Stark Marked gene: NLGN4X as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.534 | NLGN4X | Zornitza Stark Added comment: Comment when marking as ready: Definitive assessment by ClinGen noted, as well as 'limited' assessments by G2P and Genomics England. Many of the variants are multi-gene deletions; phenotypes are not well delineated, with several individuals not having ID. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.531 | MPC2 | Zornitza Stark Marked gene: MPC2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.530 | MPC2 |
Zornitza Stark gene: MPC2 was added gene: MPC2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MPC2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MPC2 were set to 36417180 Phenotypes for gene: MPC2 were set to mitochondrial pyruvate carrier deficiency, MONDO:0013877, MPC2-related Review for gene: MPC2 was set to AMBER Added comment: Four patients from two unrelated consanguineous families reported with homozygous variants (missense and stop-loss). Siblings from family 1 were diagnosed prenatally with diffuse subcutaneous oedema, cardiomegaly, corpus callosum agenesis, ventriculomegaly and hypoplasia of the cerebellum. Siblings from family 2 had slightly different presentations, which included anoxo-ischemic encephalopathy, isolated dyspnea, neonatal respiratory distress, neonatal jaundice, hypotonia, visual impairment, microcephaly; both siblings had severe delayed psychomotor development. Immunoblot analysis of protein expression in lysates from patient-derived fibroblasts demonstrated reduced MPC1 and MPC2 protein levels. Sources: Literature |
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| Mendeliome v1.528 | ARF3 | Zornitza Stark Publications for gene: ARF3 were set to 34346499 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.527 | ARF3 | Zornitza Stark Classified gene: ARF3 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.527 | ARF3 | Zornitza Stark Gene: arf3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.526 | TIMMDC1 | Paul De Fazio reviewed gene: TIMMDC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 36349561, 33278652; Phenotypes: Mitochondrial complex I deficiency, nuclear type 31 MIM#618251; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.526 | LEMD2 | Seb Lunke Phenotypes for gene: LEMD2 were changed from Marbach-Rustad progeroid syndrome, OMIM# 619322; progeroid disorder to Marbach-Rustad progeroid syndrome, OMIM# 619322; arrhythmogenic right ventricular cardiomyopathy, MONDO:0016587; Cataract 46, juvenile-onset, OMIM# 212500 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.523 | LEMD2 | Seb Lunke reviewed gene: LEMD2: Rating: AMBER; Mode of pathogenicity: None; Publications: 31061923, 26788539, 30905398, 36377660; Phenotypes: Marbach-Rustad progeroid syndrome, OMIM# 619322, arrhythmogenic right ventricular cardiomyopathy, MONDO:0016587, Cataract 46, juvenile-onset, OMIM# 212500; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.523 | NUP54 | Zornitza Stark Marked gene: NUP54 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.523 | NUP54 | Zornitza Stark Phenotypes for gene: NUP54 were changed from Early onset dystonia; progressive neurological deterioration; ataxia; dysarthria; dysphagia; hypotonia to Striatonigral degeneration, MONDO:0003122, NUP54-related; Early onset dystonia; progressive neurological deterioration; ataxia; dysarthria; dysphagia; hypotonia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.520 | FEM1C | Zornitza Stark Marked gene: FEM1C as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.519 | DCLRE1B | Zornitza Stark Phenotypes for gene: DCLRE1B were changed from Dyskeratosis congenita and Hoyeraal-Hreidarsson (HH) syndrome to Dyskeratosis congenita, autosomal recessive 8, MIM# 620133 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.515 | NUP54 | Zornitza Stark Mode of pathogenicity for gene: NUP54 was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.513 | NUP54 |
Hazel Phillimore gene: NUP54 was added gene: NUP54 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NUP54 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NUP54 were set to PMID: 36333996 Phenotypes for gene: NUP54 were set to Early onset dystonia; progressive neurological deterioration; ataxia; dysarthria; dysphagia; hypotonia Mode of pathogenicity for gene: NUP54 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: NUP54 was set to AMBER Added comment: From PMID: 36333996.; Harrer, P. et al. (2022) Ann Neurol. doi: 10.1002/ana.26544. Three patients from unrelated families with dystonia and/or Leigh(-like) syndromes, with biallelic variants in NUP54, in the C-terminal protein region that interacts with NUP62. Onset was between 12 months and 5 years. All had progressive neurological deterioration with dystonia, ataxia, dysarthria, dysphagia, hypotonia. Patient / Family A (consanguineous) was homozygous for c.1073T>G p.(Ile358Ser). Patient / Family B was compound heterozygous for c.1073T>G p.(Ile358Ser) and c.1126A>G p.(Lys376Glu). Patient / Family C was compound heterozygosity for c.1410_1412del p.(Gln471del) and two missense variants c.1414G>A, p.(Glu472Lys); c.1420C>T, p.(Leu474Phe) The phenotypes were similar to those of NUP62 including early-onset dystonia with dysphagic choreoathetosis, and T2-hyperintense lesions in striatum. Brain MRIs showed T2/FLAIR hyperintensities in the dorsal putamina. Western blots showing reduced expression of NUP54 and its interaction partners NUP62/NUP58 in patient fibroblasts. Sources: Literature |
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| Mendeliome v1.513 | GABRA3 | Zornitza Stark Marked gene: GABRA3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.512 | ARF3 | Dean Phelan reviewed gene: ARF3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 36369169, 34346499; Phenotypes: Neurodevelopmental disorder (MONDO:0700092), ARF3-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.511 | NPC1 |
Naomi Baker gene: NPC1 was added gene: NPC1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NPC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NPC1 were set to 36417180 Phenotypes for gene: NPC1 were set to mitochondrial pyruvate carrier deficiency, MONDO:0013877, MPC2-related Review for gene: NPC1 was set to AMBER Added comment: Four patients from two unrelated consanguineous families reported with homozygous variants (missense and stop-loss). Siblings from family 1 were diagnosed prenatally with diffuse subcutaneous oedema, cardiomegaly, corpus callosum agenesis, ventriculomegaly and hypoplasia of the cerebellum. Siblings from family 2 had slightly different presentations, which included anoxo-ischemic encephalopathy, isolated dyspnea, neonatal respiratory distress, neonatal jaundice, hypotonia, visual impairment, microcephaly; both siblings had severe delayed psychomotor development. Immunoblot analysis of protein expression in lysates from patient-derived fibroblasts demonstrated reduced MPC1 and MPC2 protein levels. Sources: Literature |
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| Mendeliome v1.510 | EMILIN1 | Zornitza Stark Phenotypes for gene: EMILIN1 were changed from Neuronopathy, distal hereditary motor, type X, MIM# 620080 to Neuronopathy, distal hereditary motor, type X, MIM# 620080; Aortic aneurysm, MONDO:0005160, EMILIN2-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.507 | EMILIN1 | Karina Sandoval reviewed gene: EMILIN1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 36351433; Phenotypes: Neuronopathy, distal hereditary motor, type X, MIM# 620080, Peripheral neuropathy, aortic aneurysm; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.507 | GABRA3 |
Sarah Pantaleo gene: GABRA3 was added gene: GABRA3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GABRA3 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: GABRA3 were set to PMID: 29053855 Phenotypes for gene: GABRA3 were set to Epilepsy, intellectual disability, dysmorphic features, Penetrance for gene: GABRA3 were set to Incomplete Review for gene: GABRA3 was set to GREEN Added comment: Six variants in GABRA3 encoding the alpha3-subunit of the GABA(A) receptor. Five missense variants and one micro duplication were detected in four families and two sporadic cases presenting with a range of epileptic seizure types, a varying degree of intellectual disability and developmental delay, sometimes with dysmorphic features or nystagmus. The variants co-segregated mostly but not completely with the phenotype in the families, indicating in some cases incomplete penetrance, involvement of other genes, or presence of phenocopies. Overall, males were more severely affected and there were three asymptomatic female mutation carriers compared to only one male without a clinical phenotype. Mechanism suggested - three detected missense variants are localised in the extracellular GABA-binding NH2-terminus, one in the M2-M3 linker and one in the M4 transmembrane segment of the alpha3-subunit. Functional studies in Xenopus leaves oocytes revealed a variable but significant reduction of GABA-evoked anion currents for all mutants compared to wild-type receptors. The degree of current reduction correlated partially with the phenotype. Results reveal that rare loss-of-function variants in GABRA3 increase the risk for a varying combination of epilepsy, intellectual disability/developmental delay and dysmorphic features, presenting in some pedigrees with an X-linked inheritance pattern. Sources: Literature |
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| Mendeliome v1.507 | TCEAL1 | Zornitza Stark Marked gene: TCEAL1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.505 | TCEAL1 |
Melanie Marty changed review comment from: 7 individuals (males and females) with de novo variants involving TCEAL1 with an X-linked dominant neurodevelopmental syndrome. Individuals had hypotonia, abnormal gait, developmental delay/intellectual disability especially affecting expressive language, autistic-like behavior, and mildly dysmorphic facial features. Additional features included strabismus, refractive errors, variable nystagmus, gastroesophageal reflux, constipation, dysmotility, recurrent infections, seizures, and structural brain anomalies. 1 additional male individual with a maternally inherited missense variant (unaffected mother), which was considered a VUS. This individual had hypertonia and spasticity without syndromic features. 4 PTCs, 2 CNVs, 2 missense reported. Sources: Literature; to: 7 individuals (males and females) with de novo variants involving TCEAL1 with an X-linked dominant neurodevelopmental syndrome. Individuals had hypotonia, abnormal gait, developmental delay/intellectual disability especially affecting expressive language, autistic-like behavior, and mildly dysmorphic facial features. Additional features included strabismus, refractive errors, variable nystagmus, gastroesophageal reflux, constipation, dysmotility, recurrent infections, seizures, and structural brain anomalies. 1 additional male individual with a maternally inherited missense variant (unaffected mother), which was considered a VUS. This individual had hypertonia and spasticity without syndromic features. 4 PTCs, 2 CNVs, 2 missense reported. Sources: Literature |
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| Mendeliome v1.504 | TCEAL1 |
Melanie Marty changed review comment from: 7 individuals (males and females) with de novo variants involving TCEAL1 with an X-linked dominant neurodevelopmental syndrome. Individuals had hypotonia, abnormal gait, developmental delay/intellectual disability especially affecting expressive language, autistic-like behavior, and mildly dysmorphic facial features. Additional features included strabismus, refractive errors, variable nystagmus, gastroesophageal reflux, constipation, dysmotility, recurrent infections, seizures, and structural brain anomalies. 1 additional male individual with a maternally inherited missense variant (unaffected mother), which was considered a VUS. This individual had hypertonia and spasticity without syndromic features. 4 PTCs, 2 CNVs, 2 missense reported. Sources: Literature; to: 7 individuals (males and females) with de novo variants involving TCEAL1 with an X-linked dominant neurodevelopmental syndrome. Individuals had hypotonia, abnormal gait, developmental delay/intellectual disability especially affecting expressive language, autistic-like behavior, and mildly dysmorphic facial features. Additional features included strabismus, refractive errors, variable nystagmus, gastroesophageal reflux, constipation, dysmotility, recurrent infections, seizures, and structural brain anomalies. 1 additional male individual with a maternally inherited missense variant (unaffected mother), which was considered a VUS. This individual had hypertonia and spasticity without syndromic features. 4 PTCs, 2 CNVs, 2 missense reported. Sources: Literature |
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| Mendeliome v1.504 | TCEAL1 |
Melanie Marty changed review comment from: 7 individuals (males and females) with de novo variants involving TCEAL1. Individuals had hypotonia, abnormal gait, developmental delay/intellectual disability especially affecting expressive language, autistic-like behavior, and mildly dysmorphic facial features. Additional features included strabismus, refractive errors, variable nystagmus, gastroesophageal reflux, constipation, dysmotility, recurrent infections, seizures, and structural brain anomalies. 1 additional male individual with a maternally inherited missense variant (unaffected mother), which was considered a VUS. This individual had hypertonia and spasticity without syndromic features. 4 PTCs, 2 CNVs, 2 missense reported. Sources: Literature; to: 7 individuals (males and females) with de novo variants involving TCEAL1 with an X-linked dominant neurodevelopmental syndrome. Individuals had hypotonia, abnormal gait, developmental delay/intellectual disability especially affecting expressive language, autistic-like behavior, and mildly dysmorphic facial features. Additional features included strabismus, refractive errors, variable nystagmus, gastroesophageal reflux, constipation, dysmotility, recurrent infections, seizures, and structural brain anomalies. 1 additional male individual with a maternally inherited missense variant (unaffected mother), which was considered a VUS. This individual had hypertonia and spasticity without syndromic features. 4 PTCs, 2 CNVs, 2 missense reported. Sources: Literature |
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| Mendeliome v1.504 | SHROOM4 | Alison Yeung reviewed gene: SHROOM4: Rating: GREEN; Mode of pathogenicity: None; Publications: 36379543, 35663265; Phenotypes: Congenital anomaly of the kidney and urinary tracy (CAKUT), SHROOM4-related, MONDO:0019719, epilepsy, idiopathic generalised, SHROOM4-related, MONDO:0005579; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.504 | UQCRH |
Chern Lim gene: UQCRH was added gene: UQCRH was added to Mendeliome. Sources: Literature Mode of inheritance for gene: UQCRH was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: UQCRH were set to 34750991 Phenotypes for gene: UQCRH were set to Mitochondrial complex III deficiency, nuclear type 11, MIM#620137 Review for gene: UQCRH was set to AMBER gene: UQCRH was marked as current diagnostic Added comment: PMID: 34750991: - Two affected cousins, presented with recurrent episodes of severe lactic acidosis, hyperammonaemia, hypoglycaemia and encephalopathy. - Both have a 2.2 kb homozygous deletion of exons 2 and 3 of UQCRH, predicted to culminate in an in-frame deletion exons 2 and 3 of the four-exon UQCRH gene, resulting in a shortened product. - Mouse model with the equivalent homozygous Uqcrh deletion (Uqcrh-/-) also presented with lactic acidosis and hyperammonaemia, but had a more severe, non-episodic phenotype, resulting in failure to thrive and early death. - Patient fibroblasts and Uqcrh-/- mouse tissues showed a CIII defect. - Expression of wild-type UQCRH in patient fibroblasts ameliorates the CIII defect. Sources: Literature |
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| Mendeliome v1.504 | FEM1C |
Paul De Fazio gene: FEM1C was added gene: FEM1C was added to Mendeliome. Sources: Literature Mode of inheritance for gene: FEM1C was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: FEM1C were set to 36336956; 28135719; 33398170; 33398168 Phenotypes for gene: FEM1C were set to Neurodevelopmental disorder, FEM1C-related MONDO:0700092 Review for gene: FEM1C was set to GREEN gene: FEM1C was marked as current diagnostic Added comment: PMID:36336956 describes a 9-year-old boy with severe DD, lack of speech, pyramidal signs, and limb ataxia who had a de novo missense variant Asp126His in FEM1C ascertained by WES. The equivalent variant introduced into the nematode C.elegans resulted in disabled locomotion caused by synaptic abnormalities and not muscle dysfunction. An alternate change Asp126Val was reported in the DDD study de novo in a patient with uncharacterised developmental delay (PMID:28135719). The Asp126 residue (but not either of the variants above specifically) was shown to be functionally important by in vitro studies (PMID:33398170;33398168). The residue is highly conserved and located in a region of missense constraint. Borderline green, 2 patients and an animal model. Note all evidence points to the Asp126 residue being of specific importance. Sources: Literature |
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| Mendeliome v1.504 | TCEAL1 |
Melanie Marty gene: TCEAL1 was added gene: TCEAL1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TCEAL1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: TCEAL1 were set to PMID: 36368327 Phenotypes for gene: TCEAL1 were set to hypotonia, abnormal gait, developmental delay, intellectual disability, autism, dysmorphic facial features. Review for gene: TCEAL1 was set to GREEN Added comment: 7 individuals (males and females) with de novo variants involving TCEAL1. Individuals had hypotonia, abnormal gait, developmental delay/intellectual disability especially affecting expressive language, autistic-like behavior, and mildly dysmorphic facial features. Additional features included strabismus, refractive errors, variable nystagmus, gastroesophageal reflux, constipation, dysmotility, recurrent infections, seizures, and structural brain anomalies. 1 additional male individual with a maternally inherited missense variant (unaffected mother), which was considered a VUS. This individual had hypertonia and spasticity without syndromic features. 4 PTCs, 2 CNVs, 2 missense reported. Sources: Literature |
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| Mendeliome v1.504 | KDM2B |
Ain Roesley changed review comment from: 27 individuals from 22 families were recruited 12 SNV classified LP/P, all de novo except 2 familial cases 5 variants were classified as VUS if more than 1 het is present in gnomAD or does result in a KDM2B-specific episignature (therefore suggesting normal function) Sources: Literature; to: 27 individuals from 22 families were recruited 13 SNV classified LP/P, all de novo except 2 familial cases 5 variants were classified as VUS if more than 1 het is present in gnomAD or does result in a KDM2B-specific episignature (therefore suggesting normal function) Sources: Literature |
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| Mendeliome v1.504 | KDM2B | Ain Roesley Marked gene: KDM2B as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.503 | MAN2A2 | Zornitza Stark Marked gene: MAN2A2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.503 | KDM2B |
Ain Roesley gene: KDM2B was added gene: KDM2B was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KDM2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KDM2B were set to 36322151 Phenotypes for gene: KDM2B were set to neurodevelopmental disorder MONDO#070009, KDM2B-related Review for gene: KDM2B was set to GREEN gene: KDM2B was marked as current diagnostic Added comment: 27 individuals from 22 families were recruited 12 SNV classified LP/P, all de novo except 2 familial cases 5 variants were classified as VUS if more than 1 het is present in gnomAD or does result in a KDM2B-specific episignature (therefore suggesting normal function) Sources: Literature |
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| Mendeliome v1.502 | MAN2A2 |
Zornitza Stark gene: MAN2A2 was added gene: MAN2A2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MAN2A2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MAN2A2 were set to 36357165 Phenotypes for gene: MAN2A2 were set to Congenital disorder of glycosylation, MONDO:0015286, MAN2A2-reated Review for gene: MAN2A2 was set to RED Added comment: Single consanguineous family reported with homozygous truncating variant in two brothers with ID. Supportive biochemical data only. Sources: Literature |
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| Mendeliome v1.501 | ARPC4 | Zornitza Stark Phenotypes for gene: ARPC4 were changed from Neurodevelopmental disorder, ARPC4-related MONDO#0700092 to Developmental delay, language impairment, and ocular abnormalities, MIM# 620141 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.500 | ARPC4 | Zornitza Stark edited their review of gene: ARPC4: Changed phenotypes: Developmental delay, language impairment, and ocular abnormalities, MIM# 620141 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.499 | UBE3C | Zornitza Stark Marked gene: UBE3C as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.498 | KIF26A | Zornitza Stark Marked gene: KIF26A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.495 | UBE3C |
Chirag Patel gene: UBE3C was added gene: UBE3C was added to Mendeliome. Sources: Literature Mode of inheritance for gene: UBE3C was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: UBE3C were set to PMID: 36401616 Phenotypes for gene: UBE3C were set to Neurodevelopmental disorder overlapping Angelman syndrome, no OMIM# Review for gene: UBE3C was set to GREEN Added comment: 3 patients/2 families with syndromic neurodevelopmental, seizure, and movement disorders and neurobehavioral phenotypes. WES found bi-allelic variants in UBE3C. The RNA studies in some patients with LoF variants provided evidence for the LoF effect. Sources: Literature |
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| Mendeliome v1.493 | HECTD4 |
Chirag Patel gene: HECTD4 was added gene: HECTD4 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: HECTD4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HECTD4 were set to PMID: 36401616 Phenotypes for gene: HECTD4 were set to Neurodevelopmental disorder overlapping Angelman syndrome, no OMIM# Review for gene: HECTD4 was set to GREEN Added comment: 7 patients/5 families with syndromic neurodevelopmental, seizure, and movement disorders and neurobehavioral phenotypes. WES found bi-allelic variants in HECTD4. The RNA studies in some patients with LoF variants provided evidence for the LoF effect. Sources: Literature |
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| Mendeliome v1.491 | KIF26A |
Chirag Patel gene: KIF26A was added gene: KIF26A was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KIF26A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KIF26A were set to PMID: 36228617 Phenotypes for gene: KIF26A were set to Congenital brain malformations, no OMIM # Review for gene: KIF26A was set to GREEN Added comment: 5 unrelated patients with biallelic loss-of-function variants in KIF26A (found through WES), exhibiting a spectrum of congenital brain malformations (schizencephaly, corpus callosum anomalies, polymicrgyria, and ventriculomegaly). Combining mice and human iPSC-derived organoid models, they discovered that loss of KIF26A causes excitatory neuron-specific defects in radial migration, localization, dendritic and axonal growth, and apoptosis, offering a convincing explanation of the disease etiology in patients. Single-cell RNA sequencing in KIF26A knockout organoids revealed transcriptional changes in MAPK, MYC, and E2F pathways. Sources: Literature |
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| Mendeliome v1.489 | PIGN |
Zornitza Stark edited their review of gene: PIGN: Added comment: Large cohort study of 21 new and review of 40 previously published cases in PMID 36322149 Biallelic-truncating variants were detected in 16 patients-10 with Fryns syndrome, 1 with MCAHS1, 2 with Fryns syndrome/MCAHS1, and 3 with neurologic phenotype. There was an increased risk of prenatal or neonatal death within this group (6 deaths were in utero or within 2 months of life; 6 pregnancies were terminated). Incidence of polyhydramnios, congenital anomalies (eg, diaphragmatic hernia), and dysmorphism was significantly increased. Biallelic missense or mixed genotype were reported in the remaining 45 cases-32 showed a neurologic phenotype and 12 had MCAHS1. No cases of diaphragmatic hernia or abdominal wall defects were seen in this group except patient 1 in which we found the missense variant p.Ser893Arg to result in functionally null alleles, suggesting the possibility of an undescribed functionally important region in the final exon.; Changed publications: 36322149; Changed phenotypes: Multiple congenital anomalies-hypotonia-seizures syndrome 1, MIM# 614080, MONDO:0013563, Fryns syndrome |
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| Mendeliome v1.486 | SPTAN1 |
Zornitza Stark edited their review of gene: SPTAN1: Added comment: PMID 36331550: further 31 individuals reported with mono-allelic variants. Three phenotypes observed: 1. DEE 2. Isolated DD/ID 3. HSP or ataxia; Changed publications: 20493457, 22258530, 32811770, 35150594, 34526651, 31515523, 36331550 |
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| Mendeliome v1.486 | SEC16B | Zornitza Stark Marked gene: SEC16B as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.483 | NDUFB7 | Zornitza Stark Phenotypes for gene: NDUFB7 were changed from Congenital lactic acidosis; hypertrophic cardiomyopathy to Mitochondrial complex I deficiency nuclear type 39 (MC1DN39), MIM#620135; Congenital lactic acidosis; hypertrophic cardiomyopathy | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.482 | NDUFB7 | Zornitza Stark reviewed gene: NDUFB7: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex I deficiency nuclear type 39 (MC1DN39), MIM#620135; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.481 | KCNJ16 | Zornitza Stark Phenotypes for gene: KCNJ16 were changed from Renal tubulopathy; deafness to Inherited renal tubular disease, MONDO:0015962, KCNJ16-related; Renal tubulopathy; deafness | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.480 | KCNJ16 | Zornitza Stark edited their review of gene: KCNJ16: Changed phenotypes: Inherited renal tubular disease, MONDO:0015962, KCNJ16-related, Renal tubulopathy, deafness | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.480 | AFDN | Zornitza Stark Marked gene: AFDN as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.480 | AFDN |
Zornitza Stark gene: AFDN was added gene: AFDN was added to Mendeliome. Sources: Literature Mode of inheritance for gene: AFDN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: AFDN were set to 36384317 Phenotypes for gene: AFDN were set to Cleft lip/palate, MONDO:0016044, AFDN-related Review for gene: AFDN was set to RED Added comment: Over-representation of rare AFDN missense variants reported in a cohort of CL/P individuals of African and Brazilian origin. However, almost all of the variants reported have hets in gnomad. The one that is novel has alternative missense at the same aa position. Sources: Literature |
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| Mendeliome v1.478 | FOXI1 | Zornitza Stark reviewed gene: FOXI1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: autosomal recessive distal renal tubular acidosis MONDO:0018440; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.478 | CLEC3B | Zornitza Stark Marked gene: CLEC3B as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.477 | CLEC3B |
Chirag Patel gene: CLEC3B was added gene: CLEC3B was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CLEC3B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CLEC3B were set to PMID: 35331648 Phenotypes for gene: CLEC3B were set to Macular dystrophy, retinal, 4, OMIM #619977 Review for gene: CLEC3B was set to GREEN Added comment: 12 affected individuals from 5 multigenerational Japanese families in a small village in Miyazaki diagnosed with autosomal dominant maculoretinopathy. WES identified a pathogenic variant (p.Ala180Asp) in CLEC3B, which encodes tetranectin, a plasminogen kringle-4 binding protein. Variant cosegregated with the ocular phenotype. Mice that received subretinal injections with CLEC3B variant displayed multiple subretinal hyperreflective deposits, reduced retinal thickness, and decreased electroretinographic responses. The optokinetic tracking response indicated that spatial frequency was significantly lower (P < .05), implying impaired visual function in the mice. Sources: Literature |
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| Mendeliome v1.476 | PDIA6 | Chirag Patel edited their review of gene: PDIA6: Added comment: 2nd patient with large polycystic kidneys, death and end stage renal failure at 18 months, microcephaly, bilateral inguinal hernias, umbilical hernia, developmental delay, bilateral sensorineural hearing loss, visual impairment, steatorrhea, fibrotic changes in liver, and insulin-dependent diabetes. WGS found homozygous stop-gain variant (Tyr368*) in PDIA6. Segregation not performed.; Changed rating: AMBER; Changed publications: PMID: 35856135; Changed phenotypes: Polycystic kidney disease, infancy-onset diabetes, and microcephaly | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.476 | ARPC4 | Zornitza Stark Phenotypes for gene: ARPC4 were changed from Microcephaly; mild motor delays; significant speech impairment to Neurodevelopmental disorder, ARPC4-related MONDO#0700092 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.475 | ARPC4 | Zornitza Stark reviewed gene: ARPC4: Rating: GREEN; Mode of pathogenicity: None; Publications: 35047857; Phenotypes: Neurodevelopmental disorder, ARPC4-related MONDO#0700092; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.474 | SPTBN5 |
Zornitza Stark edited their review of gene: SPTBN5: Added comment: Some of the missense variants are present at high population frequencies, not compatible with Mendelian disease. Gene is tolerant of LoF in gnomad, raising questions about the pathogenicity of the LoF variant. Commentaries questioning gene-disease relationship PMID: 36117916; 36238261; Changed rating: RED |
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| Mendeliome v1.473 | MTSS1 | Zornitza Stark Marked gene: MTSS1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.472 | MTSS1 |
Zornitza Stark gene: MTSS1 was added gene: MTSS1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MTSS1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MTSS1 were set to 36067766 Phenotypes for gene: MTSS1 were set to Intellectual disability, MTSS1-related (MONDO#0001071) Review for gene: MTSS1 was set to GREEN Added comment: Five individuals with the same heterozygous de novo variant in MTSS2 (NM_138383.2: c.2011C>T [p.Arg671Trp]) identified by exome sequencing. The individuals presented with global developmental delay, mild intellectual disability, ophthalmological anomalies, microcephaly or relative microcephaly, and shared mild facial dysmorphisms. Immunoblots of fibroblasts from two affected individuals revealed that the variant does not significantly alter MTSS2 levels. We modeled the variant in Drosophila and showed that the fly ortholog missing-in-metastasis (mim) was widely expressed in most neurons and a subset of glia of the CNS. Loss of mim led to a reduction in lifespan, impaired locomotor behavior, and reduced synaptic transmission in adult flies. Expression of the human MTSS2 reference cDNA rescued the mim loss-of-function (LoF) phenotypes, whereas the c.2011C>T variant had decreased rescue ability compared to the reference, suggesting it is a partial LoF allele. However, elevated expression of the variant, but not the reference MTSS2 cDNA, led to similar defects as observed by mim LoF, suggesting that the variant is toxic and may act as a dominant-negative allele when expressed in flies. Sources: Literature |
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| Mendeliome v1.471 | TPR | Zornitza Stark Phenotypes for gene: TPR were changed from intellectual disability, MONDO:0001071; cerebellar ataxia, MONDO:0000437; microcephaly, MONDO:0001149 to Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042, TPR-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.470 | TPR | Zornitza Stark Marked gene: TPR as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.469 | SMC5 | Zornitza Stark Marked gene: SMC5 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.468 | SMC5 |
Zornitza Stark gene: SMC5 was added gene: SMC5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SMC5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SMC5 were set to 36333305 Phenotypes for gene: SMC5 were set to Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042, SLF2-related; Atelis syndrome; microcephaly; short stature; ID Review for gene: SMC5 was set to GREEN Added comment: Four individuals from three families with a chromosome breakage disorder and bi-allelic variants in this gene. However, three of the individuals had the same homozygous missense variant. Evidence for functional impact of the variant was limited. However, zebrafish model recapitulated the phenotype and was not rescued by the introduction of this variant, arguing for functional effect. Borderline Amber/Green Sources: Literature |
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| Mendeliome v1.467 | SLF2 | Zornitza Stark Marked gene: SLF2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.466 | SLF2 |
Zornitza Stark gene: SLF2 was added gene: SLF2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SLF2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLF2 were set to 36333305 Phenotypes for gene: SLF2 were set to Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042, SLF2-related; Atelis syndrome; microcephaly; short stature; ID Review for gene: SLF2 was set to GREEN Added comment: Seven individuals from 6 families with a chromosome breakage disorder and bi-allelic variants in this gene (LoF). Functional data including zebrafish model. Sources: Literature |
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| Mendeliome v1.465 | TPR |
Achchuthan Shanmugasundram gene: TPR was added gene: TPR was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TPR was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TPR were set to 34494102 Phenotypes for gene: TPR were set to intellectual disability, MONDO:0001071; cerebellar ataxia, MONDO:0000437; microcephaly, MONDO:0001149 Review for gene: TPR was set to RED Added comment: This gene should be added to the following diseases: Intellectual disability, microcephaly and ataxia. Comment on classification of this gene: This gene should be added with a RED rating as the association is based on biallelic variants identified from a report of two siblings. Two siblings harbouring variants c.6625C>T/ p.Arg2209Ter (identified in heterozygous state in both siblings and father) and c.2610 + 5G > A (identified in heterozygous state in both siblings and mother) were reported with ataxia, microcephaly and severe intellectual disability. Functional analyses in patient fibroblasts provide evidence that the variants affect TPR splicing, reduce steady-state TPR levels, abnormal nuclear pore composition and density, and altered global RNA distribution. This gene has not yet been associated with any phenotypes either in OMIM or in Gene2Phenotype. Sources: Literature |
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| Mendeliome v1.465 | NF1 | Achchuthan Shanmugasundram reviewed gene: NF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34476477; Phenotypes: Neurofibromatosis, type 1, MIM# 162200, MONDO:0018975, renovascular hypertension, MONDO:0006947; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.463 | IRF2BP2 | Zornitza Stark edited their review of gene: IRF2BP2: Added comment: Reports of additional patients: 4yo with chronic diarrhea, severe eczema, anemia, failure to thrive, fevers, short stature, recurrent infections, cataracts, hypodontia, hypotrichosis alopecia, hypogammaglobulinemia. The 33-year-old male presented with recurrent respiratory infections since childhood, colitis and RA beginning at age 25 years.; Changed rating: GREEN; Changed publications: 27016798, 32048120, 36193988, 33864888; Changed phenotypes: Immunodeficiency, common variable, 14, MIM# 617765 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.462 | ATP5F1 | Zornitza Stark Marked gene: ATP5F1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.462 | ATP5F1 |
Zornitza Stark gene: ATP5F1 was added gene: ATP5F1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: ATP5F1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ATP5F1 were set to 36239646 Phenotypes for gene: ATP5F1 were set to Hypermetabolism due to uncoupled mitochondrial oxidative phosphorylation-2 (HUMOP2), MIM#620085 Review for gene: ATP5F1 was set to RED Added comment: Identical twins reported with a de novo missense variant in this gene and hyper metabolism: normal thyroid function, hyperphagia, tachypnea, increased basal temperature, and increased sweating. Biochemical studies demonstrated increased mitochondrial oxygen consumption with inefficient production of ATP in the final steps of oxidative phosphorylation due to an uncoupling defect Sources: Expert list |
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| Mendeliome v1.460 | CACNA1I | Zornitza Stark Phenotypes for gene: CACNA1I were changed from Neurodevelopmental disorder to Neurodevelopmental disorder with variable intellectual disability and speech impairment, with or without seizures (NEDISS), MIM#620114 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.459 | CACNA1I | Zornitza Stark reviewed gene: CACNA1I: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with variable intellectual disability and speech impairment, with or without seizures (NEDISS), MIM#620114; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.459 | RPS6KB1 |
Arina Puzriakova gene: RPS6KB1 was added gene: RPS6KB1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RPS6KB1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: RPS6KB1 were set to 34916228 Phenotypes for gene: RPS6KB1 were set to Hypertrophic cardiomyopathy Review for gene: RPS6KB1 was set to GREEN Added comment: Jain et al. 2022 (PMID: 34916228) reported on two unrelated HCM families with the same heterozygous missense RPS6KB1 variant (p.G47W), and subsequently three further unrelated probands with HCM harbouring distinct heterozygous variants (p.Q49K, p.Y62H, respectively). Variants segregated with disease, were predicted pathogenic by silico analyses and were ultrarare or absent in population databases. Functional studies in the HL-1 (mouse cardiomyocytes) cells showed that the patient-specific RPS6KB1 mutant significantly increased cell size and activated rpS6 and ERK1/2 signalling cascades. The relationship between RPS6KB1 and cardiac hypertrophy has also been explored in feline and mice models (PMID: 15226426; 17976640) Sources: Literature |
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| Mendeliome v1.459 | HK1 | Zornitza Stark edited their review of gene: HK1: Added comment: PMID 36333503: 14 non-coding de novo variants affecting a 42-bp conserved region encompassed by a regulatory element in intron 2 of the hexokinase 1 gene (HK1) identified in individuals with hyperinsulinism.; Changed publications: 19536174, 30778173, 25316723, 25190649, 31621442, 32814480, 7655856, 12393545, 33361148, 31119733, 27282571, 36333503; Changed phenotypes: Hyperinsulinism MONDO:0002177, HK1-related, Neuropathy, hereditary motor and sensory, Russe type , MIM#605285, Haemolytic anaemia due to hexokinase deficiency, MIM# 235700, Neurodevelopmental disorder with visual defects and brain anomalies, MIM# 618547, Retinitis pigmentosa 79, MIM# 617460 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.459 | FRA10AC1 | Zornitza Stark Phenotypes for gene: FRA10AC1 were changed from Neurodevelopmental disorder, MONDO:0700092, FRA10AC1-related to Neurodevelopmental disorder with growth retardation, dysmorphic facies, and corpus callosum abnormalities, MIM# 620113 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.458 | FRA10AC1 | Zornitza Stark edited their review of gene: FRA10AC1: Changed phenotypes: Neurodevelopmental disorder with growth retardation, dysmorphic facies, and corpus callosum abnormalities, MIM# 620113 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.458 | ITPR3 | Zornitza Stark Phenotypes for gene: ITPR3 were changed from Charcot-Marie-Tooth disease to Charcot-Marie-Tooth disease, demyelinating, type 1J, MIM# 620111 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.455 | ITPR3 | Zornitza Stark edited their review of gene: ITPR3: Added comment: Additional family with 3 individuals in 2 generations reported in PMID 24627108.; Changed rating: GREEN; Changed publications: 32949214, 24627108; Changed phenotypes: Charcot-Marie-Tooth disease, demyelinating, type 1J, MIM# 620111 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.453 | WDR5 | Bryony Thompson Marked gene: WDR5 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.452 | WDR5 |
Bryony Thompson gene: WDR5 was added gene: WDR5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: WDR5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: WDR5 were set to DOI:https://doi.org/10.1016/j.xhgg.2022.100157 Phenotypes for gene: WDR5 were set to Neurodevelopmental disorder MONDO:0700092, WDR5-related Mode of pathogenicity for gene: WDR5 was set to Other Review for gene: WDR5 was set to GREEN Added comment: Six different missense variants were identified (de novo) in 11 affected individuals with neurodevelopmental disorders, with a broad spectrum of additional features, including epilepsy, aberrant growth parameters, skeletal and cardiac abnormalities. In vivo and in vitro functional suggest that loss-of-function is not the mechanism of disease. The mechanism of disease is yet to be established. Sources: Literature |
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| Mendeliome v1.451 | KPNA3 | Zornitza Stark Phenotypes for gene: KPNA3 were changed from Hereditary Spastic Paraplegia, infantile onset to Spastic paraplegia-88 (SPG88), MIM#620106 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.450 | KPNA3 | Zornitza Stark reviewed gene: KPNA3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia-88 (SPG88), MIM#620106; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.450 | JARID2 | Zornitza Stark Phenotypes for gene: JARID2 were changed from Intellectual disability to Developmental delay with variable intellectual disability and dysmorphic facies (DIDDF), MIM#620098 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.449 | JARID2 | Zornitza Stark edited their review of gene: JARID2: Changed phenotypes: Developmental delay with variable intellectual disability and dysmorphic facies (DIDDF), MIM#620098 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.447 | DNAJB4 | Zornitza Stark Marked gene: DNAJB4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.446 | DNAJB4 |
Karina Sandoval gene: DNAJB4 was added gene: DNAJB4 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: DNAJB4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DNAJB4 were set to PMID: 36264506 Phenotypes for gene: DNAJB4 were set to Myopathy, MONDO:0005336, DNAJB4-related Review for gene: DNAJB4 was set to GREEN Added comment: 4 individuals from 3 unrelated families with bi-allelic LoF/missense variants in this gene, and either childhood/adult onset of muscle weakness and respiratory failure. One had HCM. Functional studies including mouse model. Sources: Literature |
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| Mendeliome v1.444 | MYCBP2 | Zornitza Stark Marked gene: MYCBP2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.443 | CAMSAP1 | Zornitza Stark Marked gene: CAMSAP1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.442 | THAP1 |
Michelle Torres commented on gene: THAP1: Monoallelic is well established with reduced penetrance. Biallelic was seen in 3 families generally with severe and early onset dystonia: PMID: 36205328: consanguineous family (gene panel), proband homozygous for p.Lys162Asn with early onset multifocal dystonia with severe oromandibular/laryngeal dysfunction; both parents were confirmed carriers with milder features (47 yo father with tightness and difficulty with fine motor tasks, 41 yo mother with tightness). PMID: 21425335: 3 siblings are homozygous for the p.Leu32His with early-onset generalized dystonia. Carriers were unaffected. PMID: 20211909: a homozygous variant was identified in an individual with with writer's dystonia initially and then developing segmental dystonia, onset at 57 yo, parents could not be tested. |
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| Mendeliome v1.442 | CAMSAP1 |
Naomi Baker gene: CAMSAP1 was added gene: CAMSAP1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CAMSAP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CAMSAP1 were set to 36283405 Phenotypes for gene: CAMSAP1 were set to lissencephaly spectrum disorders (MONDO:0018838), CAMSAP1-related Review for gene: CAMSAP1 was set to GREEN Added comment: Five unrelated families with bi-allelic loss-of-function variants. Clinical features of the syndrome include a characteristic craniofacial appearance, primary microcephaly, lissencephaly, agenesis or severe hypogenesis of the corpus callosum, severe neurodevelopmental delay, cortical visual impairment, and seizures. Sources: Literature |
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| Mendeliome v1.442 | MYCBP2 |
Suliman Khan gene: MYCBP2 was added gene: MYCBP2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MYCBP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MYCBP2 were set to PMID: 36200388 Phenotypes for gene: MYCBP2 were set to Neurodevelopmental disorder, MONDO:0700092, MYCBP2-related; corpus callosum abnormalities Penetrance for gene: MYCBP2 were set to Complete Review for gene: MYCBP2 was set to GREEN Added comment: PMID: 36200388 reported eight patients with neurodevelopmental disorder including corpus callosum abnormalities, developmental delay, intellectual disability, epilepsy, and autistic features. Each patient harbored a de novo LOF variant in MYCBP2 gene. Functional study supported a direct link between MYCBP2 and neurodevelopmental spectrum disorder specifically corpus callosum defects. Sources: Literature |
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| Mendeliome v1.442 | KLHL20 | Zornitza Stark Marked gene: KLHL20 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.441 | KLHL20 |
Dean Phelan gene: KLHL20 was added gene: KLHL20 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KLHL20 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KLHL20 were set to PMID: 36214804 Phenotypes for gene: KLHL20 were set to Neurodevelopmental disorder (MONDO:0700092), KLHL20-related Review for gene: KLHL20 was set to GREEN Added comment: PMID: 36214804 - 14 patients with de novo missense variants in KLHL20. The patients had mild to severe ID, febrile seizures or epilepsy, autism spectrum disorder, hyperactivity and subtle dysmorphic facial features. Sources: Literature |
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| Mendeliome v1.441 | FICD | Alison Yeung Marked gene: FICD as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.440 | FICD |
Alison Yeung gene: FICD was added gene: FICD was added to Mendeliome. Sources: Literature Mode of inheritance for gene: FICD was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FICD were set to 36136088 Phenotypes for gene: FICD were set to Hereditary motor neurone disease, FICD-related, MONDO:0024257 Review for gene: FICD was set to GREEN Added comment: Three unrelated families with recurrent homozygous missense variant: p.Arg374His One further family with Chet variants: p.Arg 374His and p.Gly370GlufsTer53 Fibroblasts from patients with FICD variants have abnormally increased levels of AMPylated and thus inactivated BiP. Onset of symptoms in childhood with progressive course. Presentation with severe lower limb spasticity and mild upper limb spascticity, nerve conduction test shows motor neuropathy. Sources: Literature |
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| Mendeliome v1.439 | FOXI3 | Zornitza Stark Marked gene: FOXI3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.437 | FOXI3 |
Paul De Fazio gene: FOXI3 was added gene: FOXI3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: FOXI3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: FOXI3 were set to 36260083 Phenotypes for gene: FOXI3 were set to Dysostosis with predominant craniofacial involvement (MONDO:0800085) Penetrance for gene: FOXI3 were set to Incomplete Review for gene: FOXI3 was set to GREEN gene: FOXI3 was marked as current diagnostic Added comment: Ten affected individuals from 4 families reported with monoallelic variants, 2 with missense variants affecting the nuclear localisation sequence and 2 with frameshift variants. The missense variants were associated with isolated microtia with aural atresia and affected subcellular localisation of the protein, while the frameshift variants were associated with microtia and mandubular hypoplasia, suggesting dosage sensitivity. Rated green but CAUTION for incomplete penetrance. 3 of the 4 families had unaffected carriers. Family 1 in particular had 25 genotyped individuals, of which 15 were carriers, of which 5 were affected. Sources: Literature |
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| Mendeliome v1.436 | TOMM7 |
Zornitza Stark edited their review of gene: TOMM7: Added comment: Second family reported in PMID 36282599: single affected individual with homozygous missense variant; clinical presentation with progeroid features but functional data supports underlying mitochondrial aetiology. Maintain Amber rating as the two patients have quite disparate clinical presentations.; Changed publications: 36282599 |
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| Mendeliome v1.436 | CBFB | Ain Roesley Marked gene: CBFB as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.435 | CBFB |
Ain Roesley gene: CBFB was added gene: CBFB was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CBFB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CBFB were set to 36241386 Phenotypes for gene: CBFB were set to cleidocranial dysplasia (MONDO#0007340), CBFB-related Penetrance for gene: CBFB were set to Complete Review for gene: CBFB was set to GREEN gene: CBFB was marked as current diagnostic Added comment: 5 families with 8 individuals, including 2 de novos and 1 intragenic exon 4 deletion In 1 family, the mother did not report skeletal concerns but had dental abnormalities during childhood Sources: Literature |
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| Mendeliome v1.430 | SFTPA1 | Zornitza Stark edited their review of gene: SFTPA1: Added comment: Additional 3 families reported with mono-allelic variants.; Changed rating: GREEN; Changed publications: 31601679, 30854216, 28869238, 26792177, 32855221 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.428 | FGL2 | Zornitza Stark Marked gene: FGL2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.427 | FGL2 |
Zornitza Stark gene: FGL2 was added gene: FGL2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: FGL2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FGL2 were set to 36243222 Phenotypes for gene: FGL2 were set to Autoinflammatory syndrome, MONDO:0019751, FGL2-related Review for gene: FGL2 was set to AMBER Added comment: Child with early onset systemic inflammation, autoantibodies, and vasculitis. Homozygous truncating variant, functional studies include rescue experiments. Sources: Literature |
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| Mendeliome v1.421 | CLCN7 |
Zornitza Stark changed review comment from: Two individuals reported with same missense variant and hypopigmentation, organomegaly, and delayed myelination and development. Variant is GoF. No osteopetrosis, biopsy findings from skin and other organs are consistent with a lysosomal storage disorder. IUGR, prematurity and polyhydramnios are features. Bi-allelic variants in this gene are associated with osteopetrosis.; to: Two individuals reported with same missense variant and hypopigmentation, organomegaly, and delayed myelination and development. Variant is GoF. No osteopetrosis, biopsy findings from skin and other organs are consistent with a lysosomal storage disorder. IUGR, prematurity and polyhydramnios are features. Mono- and bi-allelic variants in this gene are associated with osteopetrosis. |
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| Mendeliome v1.421 | HNRNPH1 | Zornitza Stark Phenotypes for gene: HNRNPH1 were changed from HNRNPH1‐related syndromic intellectual disability; early onset high myopia, MONDO:0001384 to Neurodevelopmental disorder with craniofacial dysmorphism and skeletal defects, MIM# 620083 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.418 | PRDM16 | Paul De Fazio reviewed gene: PRDM16: Rating: GREEN; Mode of pathogenicity: None; Publications: 29367541, 29447731, 30847666, 33082984, 32183154, 33500567, 34540771, 34350506, 34935411; Phenotypes: Cardiomyopathy, dilated, 1LL MIM#615373, Left ventricular noncompaction 8 MIM#615373; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.418 | WNK4 |
Zornitza Stark changed review comment from: More than 5 unrelated families reported.; to: More than 5 unrelated families reported. Caution: assessed as MODERATE by ClinGen. Although at least 9 individuals have been reported, all the reported variants are missense without other supportive functional or segregation data. |
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| Mendeliome v1.418 | EMILIN1 | Zornitza Stark Phenotypes for gene: EMILIN1 were changed from peripheral neuropathy to Neuronopathy, distal hereditary motor, type X, MIM# 620080 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.417 | EMILIN1 | Zornitza Stark reviewed gene: EMILIN1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuronopathy, distal hereditary motor, type X, MIM# 620080; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.416 | CCDC34 | Zornitza Stark Marked gene: CCDC34 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.415 | CCDC34 |
Zornitza Stark gene: CCDC34 was added gene: CCDC34 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: CCDC34 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CCDC34 were set to 34348960 Phenotypes for gene: CCDC34 were set to Spermatogenic failure 76, MIM# 620084 Review for gene: CCDC34 was set to GREEN Added comment: Two unrelated individuals reported with homozygous frameshift variants. Mouse model recapitulated phenotype. Sources: Expert list |
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| Mendeliome v1.414 | ACTN2 | Bryony Thompson reviewed gene: ACTN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 17097056, 20022194, 25173926, 25224718, 22767232, 27287556, 28436997, 31333075, 31956495, 32973354, 34802252, 33500567, 36078153, 36116040; Phenotypes: intrinsic cardiomyopathy MONDO:0000591; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.411 | NFAT5 | Zornitza Stark edited their review of gene: NFAT5: Added comment: Two additional individuals with missense variants reported in PMID 36238298: one with EBV infection with hepatitis and enterocolitis, and one with fatal HLH.; Changed rating: AMBER; Changed publications: 25667416, 36238298; Changed phenotypes: Immune deficiency disease, MONDO:0003778, NFAT5-related, Recurrent infections, Autoimmune enterocolopathy, EBV susceptibility, HLH | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.411 | PSMC1 | Zornitza Stark Phenotypes for gene: PSMC1 were changed from 35861243; spastic paraplegia; severe developmental delay; severe intellectual disability; hearing loss; micropenis; undescended testes to Neurodevelopmental disorder with poor growth, spastic tetraplegia, and hearing loss , MIM# 620071 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.410 | PSMC1 | Zornitza Stark edited their review of gene: PSMC1: Changed phenotypes: Neurodevelopmental disorder with poor growth, spastic tetraplegia, and hearing loss , MIM# 620071 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.408 | FGF14 | Zornitza Stark Phenotypes for gene: FGF14 were changed from Vestibulocerebellar disorder with predominant ocular signs, MIM# 193003 to Spinocerebellar ataxia 27, MIM# 609307; Vestibulocerebellar disorder with predominant ocular signs, MIM# 193003 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.407 | FGF14 | Zornitza Stark edited their review of gene: FGF14: Changed phenotypes: Spinocerebellar ataxia 27, MIM# 609307, Vestibulocerebellar disorder with predominant ocular signs, MIM# 193003 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.407 | FGF14 | Zornitza Stark Phenotypes for gene: FGF14 were changed from Spinocerebellar ataspinocerebellar ataxia type 27 MONDO:0012247; hereditary episodic ataxia MONDO:0016227 to Vestibulocerebellar disorder with predominant ocular signs, MIM# 193003 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.406 | FGF14 | Zornitza Stark reviewed gene: FGF14: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Vestibulocerebellar disorder with predominant ocular signs, MIM# 193003; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.406 | IMPA1 | Bryony Thompson Marked gene: IMPA1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.405 | IMPA1 |
Bryony Thompson gene: IMPA1 was added gene: IMPA1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: IMPA1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IMPA1 were set to 26416544; 24554717; 32839513; 17460611 Phenotypes for gene: IMPA1 were set to intellectual disability, autosomal recessive 59 MONDO:0015020 Review for gene: IMPA1 was set to AMBER Added comment: A homozygous frameshift variant identified in a large Brazilian consanguineous family with ID, also supporting functional studies and null mouse models. Sources: Literature |
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| Mendeliome v1.404 | ARNT2 | Bryony Thompson Marked gene: ARNT2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.404 | ARNT2 | Bryony Thompson Gene: arnt2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.404 | ARNT2 | Bryony Thompson Classified gene: ARNT2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.404 | ARNT2 | Bryony Thompson Gene: arnt2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.403 | ARNT2 |
Bryony Thompson gene: ARNT2 was added gene: ARNT2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ARNT2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ARNT2 were set to 11381139; 24022475 Phenotypes for gene: ARNT2 were set to Webb-Dattani syndrome MONDO:0014404 Review for gene: ARNT2 was set to AMBER Added comment: A homozygous frameshift (c.1373_1374dupTC) in six affected children from a highly consanguineous family with a syndromic phenotype including microcephaly with fronto-temporal lobe hypoplasia, multiple pituitary hormone deficiency, seizures, severe visual impairment and abnormalities of the kidneys and urinary tract. In a Arnt2(-/-) mouse model embryos die perinatally and exhibit impaired hypothalamic development. Sources: Literature |
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| Mendeliome v1.402 | FRMD5 | Zornitza Stark Marked gene: FRMD5 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.401 | FRMD5 |
Zornitza Stark gene: FRMD5 was added gene: FRMD5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: FRMD5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: FRMD5 were set to 36206744 Phenotypes for gene: FRMD5 were set to Neurodevelopmental disorder MONDO:0700092, FRMD5-related Review for gene: FRMD5 was set to GREEN Added comment: Eight individuals reported with missense variants in this gene, de novo in 6 where parents were available. Clinical presentation was with ID, seizures, ataxia. Fly model. Sources: Literature |
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| Mendeliome v1.397 | TOMM7 | Zornitza Stark Phenotypes for gene: TOMM7 were changed from growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy MONDO:0014911 to Inborn mitochondrial disorder MONDO:0004069, TOMM7-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.396 | TOMM7 | Bryony Thompson Marked gene: TOMM7 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.395 | TOMM7 |
Bryony Thompson gene: TOMM7 was added gene: TOMM7 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TOMM7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TOMM7 were set to DOI:https://doi.org/10.1016/j.xhgg.2022.100148 Phenotypes for gene: TOMM7 were set to growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy MONDO:0014911 Review for gene: TOMM7 was set to AMBER Added comment: A single case identified with a homozygous variant in TOMM7 (c.73T>C, p.Trp25Arg) that presented with syndromic short stature, skeletal abnormalities, muscle hypotonia, microvesicular liver steatosis, and developmental delay. A mouse model of the missense variant demonstrated a bioenergetic defect and a phenotype of mitochondrial diseases. It also strongly suggested that the variant is hypomorphic because mice homozygous for this variant showed a milder phenotype than those with a homozygous Tomm7 deletion. Sources: Literature |
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| Mendeliome v1.393 | SEPT4 | Bryony Thompson Marked gene: SEPT4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.392 | SEPT4 |
Bryony Thompson gene: SEPT4 was added gene: SEPT4 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SEPT4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SEPT4 were set to 36135717; 15737931; 15737930 Phenotypes for gene: SEPT4 were set to male infertility MONDO:0005372 Review for gene: SEPT4 was set to GREEN Added comment: Two unrelated cases with primary male infertility (asthenoteratozoospermia) from consanguineous Chinsese families with 2 difference homozygous stopgain variants (Patient 1: c.721A>T, p.R241* and Patient 2: c.205C>T, p.R69*). Multiple supporting mouse models where the male mice are sterile. Sources: Literature |
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| Mendeliome v1.391 | FAM20B | Bryony Thompson Marked gene: FAM20B as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.390 | FAM20B |
Bryony Thompson gene: FAM20B was added gene: FAM20B was added to Mendeliome. Sources: Other Mode of inheritance for gene: FAM20B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FAM20B were set to 30847897; 30105814; 22732358; 27405802 Phenotypes for gene: FAM20B were set to Desbuquois dysplasia MONDO:0015426 Review for gene: FAM20B was set to AMBER Added comment: Two siblings from a single family with neonatal short limb dysplasia resembling Desbuquois dysplasia. One of the siblings underwent genetic testing and compound heterozygous variants were identified in FAM20B ((NM_014864: c.174_178delTACCT p.T59Afs*19/c.1038delG p.N347Mfs*4). Multiple mouse models reported with skeletal abnormalities. Sources: Other |
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| Mendeliome v1.389 | EXOC6B | Bryony Thompson Marked gene: EXOC6B as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.388 | EXOC6B |
Bryony Thompson gene: EXOC6B was added gene: EXOC6B was added to Mendeliome. Sources: Literature Mode of inheritance for gene: EXOC6B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EXOC6B were set to 26669664; 30284759; 36150098 Phenotypes for gene: EXOC6B were set to Spondyloepimetaphyseal dysplasia with joint laxity MONDO:0019675 Review for gene: EXOC6B was set to GREEN Added comment: 6 affected individuals from 4 families, and supporting assays in patient cells PMID: 26669664 - 2 brothers with spondyloepimetaphyseal dysplasia (SEMD), multiple joint dislocations at birth, severe joint laxity, scoliosis, gracile metacarpals and metatarsals, delayed bone age and poorly ossified carpal and tarsal bones from a consanguineous family, with a homozygous nonsense variant [c.906T>A/p.(Tyr302*)] PMID: 30284759 - 2 sisters with dislocations of the hips and knees, long slender fingers with distal tapering, significant motor disability but normal (older sister) or low-normal intelligence (younger sister), with a homozygous in-frame deletion of exons 9-20 PMID: 36150098 - 2 unrelated probands from consanguineous families, one with a homozygous frameshift exon 20 deletion and one with a homozygous nonsense variant (c.401T>G p.Leu134Ter). Function assessment of patient fibroblast cell lines indicated abrogation of exocytosis leading to impaired primary ciliogenesis Sources: Literature |
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| Mendeliome v1.385 | VPS33A |
Bryony Thompson changed review comment from: PMID: 28013294 - 13 cases homozygous for VPS33A c.1492C>T p.(Arg498Trp) from non-consanguineous Yakuti families with a Mucopolysaccharidoses-like disease (coarse facial features, skeletal abnormalities, hepatosplenomegaly, respiratory problems, intellectual disability, and excess secretion of urinary glycosaminoglycans). Lysosomal over-acidification and heparan sulphate accumulation were detected in patient-derived and VPS33A-depleted HeLa cells. PMID: 27547915 - 2 affected siblings homozygous for VPS33A p.(Arg498Trp) from a consanguineous Turkish family PMID: 31936524 - 1 homozygous case from a non-consanguineous Yakuti family PMID: 36153662 - an attenuated juvenile case with a new homozygous missense variant VPS33A c.599G>C p.(Arg200Pro). Urinary glycosaminoglycan analysis revealed increased heparan, dermatan sulphates, and hyaluronic acid and decreased abundance of VPS33A in patient-derived fibroblasts; to: Now two missense variants reported with disease in at least 15 probands/families PMID: 28013294 - 13 cases homozygous for VPS33A c.1492C>T p.(Arg498Trp) from non-consanguineous Yakuti families with a Mucopolysaccharidoses-like disease (coarse facial features, skeletal abnormalities, hepatosplenomegaly, respiratory problems, intellectual disability, and excess secretion of urinary glycosaminoglycans). Lysosomal over-acidification and heparan sulphate accumulation were detected in patient-derived and VPS33A-depleted HeLa cells. PMID: 27547915 - 2 affected siblings homozygous for VPS33A p.(Arg498Trp) from a consanguineous Turkish family PMID: 31936524 - 1 homozygous case from a non-consanguineous Yakuti family PMID: 36153662 - an attenuated juvenile case with a new homozygous missense variant VPS33A c.599G>C p.(Arg200Pro). Urinary glycosaminoglycan analysis revealed increased heparan, dermatan sulphates, and hyaluronic acid and decreased abundance of VPS33A in patient-derived fibroblasts |
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| Mendeliome v1.385 | DPH5 | Zornitza Stark Marked gene: DPH5 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.383 | VPS33A | Bryony Thompson reviewed gene: VPS33A: Rating: GREEN; Mode of pathogenicity: None; Publications: 28013294, 27547915, 31936524, 36153662; Phenotypes: Mucopolysaccharidosis-like syndrome with congenital heart defects and hematopoietic disorders MONDO:0015012; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.383 | SLC12A6 | Zornitza Stark Phenotypes for gene: SLC12A6 were changed from Andermann syndrome; Agenesis of the corpus callosum with peripheral neuropathy, MIM#21800; Intermediate CMT to Andermann syndrome; Agenesis of the corpus callosum with peripheral neuropathy, MIM#21800; Charcot-Marie-Tooth disease, axonal, type 2II , MIM#620068 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.382 | SLC12A6 | Zornitza Stark edited their review of gene: SLC12A6: Changed phenotypes: Andermann syndrome, Agenesis of the corpus callosum with peripheral neuropathy, MIM#21800, Charcot-Marie-Tooth disease, axonal, type 2II , MIM#620068 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.376 | SCNM1 | Elena Savva Marked gene: SCNM1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.375 | SCNM1 |
Elena Savva gene: SCNM1 was added gene: SCNM1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SCNM1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SCNM1 were set to PMID: 36084634 Phenotypes for gene: SCNM1 were set to Ciliopathy, SCNM1-related, MONDO:0005308 Review for gene: SCNM1 was set to GREEN Added comment: Iturrate (2022): three unrelated families (4 affected) w/ OFD, polydactyly, syndactyly and brachydactyly. All had biallelic variants (fs, missense, AluYc1 sequence insertion) and were consanguinous - the missense variant was shown to have a splice outcome Sources: Literature |
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| Mendeliome v1.374 | LETM1 | Zornitza Stark Marked gene: LETM1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.372 | LETM1 |
Ee Ming Wong gene: LETM1 was added gene: LETM1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: LETM1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LETM1 were set to 36055214 Phenotypes for gene: LETM1 were set to Mitochondrial disease MONDO#0044970, LETM1-related gene: LETM1 was marked as current diagnostic Added comment: -18 affected individuals from 11 unrelated families harbouring ultra-rare bi-allelic missense and loss-of-function LETM1 variants -Most of the affected individuals (14/18, 78%) had an infantile-onset disease manifestation, and 4/18 (22%) presented first symptoms between the ages of 1.5 and 2 years -Variant types included missense, frameshift, stop loss, in-frame deletion and splice defect -From biochemical and morphological studies, bi-allelic LETM1 variants are associated with defective mitochondrial K efflux, swollen mitochondrial matrix structures, and loss of important mitochondrial oxidative phosphorylation protein components Sources: Literature |
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| Mendeliome v1.372 | GABRG1 | Seb Lunke Marked gene: GABRG1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.372 | GABBR1 | Zornitza Stark Marked gene: GABBR1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.371 | GABBR1 |
Zornitza Stark gene: GABBR1 was added gene: GABBR1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GABBR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: GABBR1 were set to 36103875 Phenotypes for gene: GABBR1 were set to Neurodevelopmental disorder, GABBR1-related, MONDO:0700092 Review for gene: GABBR1 was set to GREEN Added comment: Four individuals with de novo variants in this gene and varying severity of DD/ID, seizures and hypotonia. Sources: Literature |
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| Mendeliome v1.370 | DUT | Seb Lunke Marked gene: DUT as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.369 | DUT |
Daniel Flanagan gene: DUT was added gene: DUT was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: DUT was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DUT were set to 28073829; 35611808 Phenotypes for gene: DUT were set to Bone marrow failure and diabetes mellitus syndrome (MIM#620044) Review for gene: DUT was set to GREEN Added comment: Homozygous missense (p.(Tyr142Cys)) identified in eight affected individuals from four unrelated consanguineous families (French, Egyptian, two Libyan) with diabetes and bone marrow failure. DUT silencing in human and rat pancreatic b-cells results in apoptosis via the intrinsic cell death pathway. p.(Tyr142Cys) has 11 heterozygotes and no homozygotes in gnomAD. Sources: Expert list |
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| Mendeliome v1.369 | CENPP | Seb Lunke Marked gene: CENPP as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.369 | CENPP |
Seb Lunke changed review comment from: Sources: Literature; to: Single family with dominant SNHL segregated through 5 family members. Truncating variant in NM_001012267.3(CENPP):c.849T>A (p.Cys283Ter). Note: misannotated as nonsense variant in paper. Sources: Literature |
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| Mendeliome v1.369 | CENPP |
Seb Lunke gene: CENPP was added gene: CENPP was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CENPP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CENPP were set to 36071244 Phenotypes for gene: CENPP were set to autosomal dominant nonsyndromic hearing loss; MONDO:0019587 Review for gene: CENPP was set to RED Added comment: Sources: Literature |
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| Mendeliome v1.368 | SLC13A1 | Zornitza Stark Marked gene: SLC13A1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.368 | GABRG1 |
Anna Ritchie gene: GABRG1 was added gene: GABRG1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GABRG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: GABRG1 were set to PMID: 36121006 Phenotypes for gene: GABRG1 were set to Developmental and epileptic encephalopathy MONDO:0100062 Added comment: 2-year-old patient with epileptic encephalopathy, hypotonia, and global developmental delays. Clinical trio exome sequencing showed a novel, de novo missense variant in the GABRG1 gene. Sources: Literature |
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| Mendeliome v1.367 | MED11 | Ain Roesley Marked gene: MED11 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.366 | MED11 |
Ain Roesley gene: MED11 was added gene: MED11 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MED11 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MED11 were set to 36001086 Phenotypes for gene: MED11 were set to neurodevelopmental disorder MONDO#0700092, MED11-related Review for gene: MED11 was set to GREEN gene: MED11 was marked as current diagnostic Added comment: 7 affected from 5 families (3x consang) with the same recurrent variant of p.(Arg109*). Protein truncating, NOT NMD as proven by RT-PCR and western blot. Zebrafish knockout model recapitulates key clinical phenotypes NO evidence of founder effect from haplotype analysis 7/7 cerebral dysgyria, cortical atrophy 5/7 limb contracture 4/7 epilepsy 3/7 families with IUGR 3/7 GDD 3/7 hearing loss 3/7 undescended testis 2/7 nystagmus 1/7 congenital cataract Sources: Literature |
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| Mendeliome v1.364 | SLC13A1 |
Lucy Spencer gene: SLC13A1 was added gene: SLC13A1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SLC13A1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC13A1 were set to 36175384 Phenotypes for gene: SLC13A1 were set to sulfation-related bone disorder MONDO:0019688, SLC13A1-related Review for gene: SLC13A1 was set to RED Added comment: PMID: 36175384- 1 patient with a homozygous nonsense variant in SLC13A1. Patient has enlargements of the joints, and spondylo-epi-metaphyseal radiological abnormalities in early childhood, which improved with age. Also autistic features and hyposulfatemia and hypersulfaturia, and reduced serum cholesterol sulfate. However the variant in this individual (Arg12Ter) has 569 hets and 1 hom in gnomad. Also this patient was homozygous for CFTR Ala455Gly which is a known pathogenic variant associated with a less severe CF phenotype. Sources: Literature |
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| Mendeliome v1.363 | NAPB | Alison Yeung Marked gene: NAPB as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.362 | FKBP6 | Zornitza Stark Marked gene: FKBP6 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.361 | MTSS1L | Elena Savva Marked gene: MTSS1L as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.361 | SARS |
Ee Ming Wong edited their review of gene: SARS: Added comment: -Two missense variants within the aminoacylation domain identified in 16 affected individuals from 3 distinct CMT families -Mutant SerRS proteins exhibited reduced aminoacylation activity and abnormal SerRS dimerization, which suggests the impairment of total protein synthesis and induction of eIF2α phosphorylation; Changed rating: GREEN; Changed publications: 36088542; Changed phenotypes: Genetic peripheral neuropathy MONDO#0020127, SARS1-related |
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| Mendeliome v1.361 | FOSL2 | Zornitza Stark Marked gene: FOSL2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.359 | MTSS1L |
Elena Savva gene: MTSS1L was added gene: MTSS1L was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MTSS1L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MTSS1L were set to PMID: 36067766 Phenotypes for gene: MTSS1L were set to Intellectual disability, MTSS2-related (MONDO#0001071) Review for gene: MTSS1L was set to GREEN Added comment: Alt gene name: MTSS2 Huang (2022): recurring de novo missense variant (p.R671W) causing syndromic intellectual disability in 5 unrelated individuals. - Individuals present with GDD, mild ID (5/5), nystagmus (3/5), optic atrophy (1/5), ptosis (2/5), sensorineural hearing loss (2/4), microcephaly or relative microcephaly (5/5), and shared mild facial dysmorphisms. - Overexpression supports a DN mechanism Sources: Literature |
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| Mendeliome v1.358 | DAW1 | Alison Yeung Marked gene: DAW1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.357 | DAW1 |
Alison Yeung gene: DAW1 was added gene: DAW1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: DAW1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DAW1 were set to 36074124 Phenotypes for gene: DAW1 were set to Primary ciliary dyskinesia, MONDO:0016575; Visceral heterotaxy, MONDO:0018677 Review for gene: DAW1 was set to GREEN Added comment: Biallelic variants identified in two unrelated families. Zebrafish model recapitulates PCD and heterotaxy phenotype Sources: Literature |
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| Mendeliome v1.356 | RABGAP1 | Zornitza Stark Marked gene: RABGAP1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.354 | NAPB |
Paul De Fazio gene: NAPB was added gene: NAPB was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NAPB was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NAPB were set to 26235277; 28097321; 33189936 Phenotypes for gene: NAPB were set to Developmental and epileptic encephalopathy 107 MIM#620033 Review for gene: NAPB was set to GREEN gene: NAPB was marked as current diagnostic Added comment: PMID 26235277: homozygous nonsense variant identified in a 6 year old girl by trio WES with early-onset epileptic encephalopathy characterised by multifocal seizures and profound GDD PMID 28097321: exome sequencing in 152 consanguineous families with at least one member affected with ID. Homozygous nonsense variant identified in a patient with profound ID, seizures, feeding difficulties in infancy, muscularhypotonia, microcephaly, and impaired vision PMID 33189936: homozygous canonical splice variant identified by trio exome sequencing in two siblings with seizures, intellectual disability and global developmental delay, microcephaly (<-3SD), and muscular hypotonia. Sources: Literature |
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| Mendeliome v1.354 | FKBP6 |
Dean Phelan gene: FKBP6 was added gene: FKBP6 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: FKBP6 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FKBP6 were set to PMID: 36150389 Phenotypes for gene: FKBP6 were set to Spermatogenic failure (MONDO:0004983), FKBP6-related Review for gene: FKBP6 was set to GREEN Added comment: PMID: 36150389 - large cohort study of men with severe spermatogenic failure (SPGF), identified six individuals with rare bi-allelic loss of function variants in FKBP6. RT-qPCR and immunofluorescence confirmed lack of FKBP6 expression. In mice, Fkbp6 has also been shown to be essential for spermatogenesis. Sources: Literature |
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| Mendeliome v1.348 | NSD2 | Zornitza Stark edited their review of gene: NSD2: Added comment: PMID 36189577: two individuals reported with a GoF variant, p.Glu1099Lys, and a distinct phenotype: intellectual disability, coarse/ square facial gestalt, abnormalities of the hands, and organomegaly.; Changed phenotypes: Rauch-Steindl syndrome, MIM# 619695, Microcephaly, intellectual disability, Neurodevelopmental disorder, NSD2-associated, GoF, MONDO:0700092 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.348 | FOSL2 |
Krithika Murali gene: FOSL2 was added gene: FOSL2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: FOSL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: FOSL2 were set to 36197437 Phenotypes for gene: FOSL2 were set to Neurodevelopmental disorder, MONDO:0700092, FOSL2-related Review for gene: FOSL2 was set to GREEN Added comment: PMID 36197437 Cospain et al 2022 report 11 individuals from 10 families with heterozygous PTC variants in exon 4/4 of the FOSL2 gene. All variants were predicted to escape NMD resulting in a truncated protein, with the truncation occurring proximal to the C-terminal domain (supportive functional studies). In 10/11 families the variant occurred de novo in a single affected proband. In one family with 2 affected siblings, the variant was present in the siblings but absent in the unaffected parent likely due to gonadal mosaicism. Clinical features included: - Cutis aplasia congenital of the scalp (10/11) - Tooth enamel hypoplasia and discolouration (8/9) - Multiple other ectodermal features also noted e.g. small brittle nails, hypotrichosis/hypertrichosis, lichen sclerosis - 5 individuals had cataracts (mostly bilateral, congenital/early childhood onset) - 6/9 IUGR - 5/9 postnatal growth restriction - 7/9 developmental delay/ID - 5/7 ADHD/ASD - 2/9 seizures Sources: Literature |
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| Mendeliome v1.346 | TRAF3 | Zornitza Stark edited their review of gene: TRAF3: Added comment: PMID 35960817: Nine individuals from five unrelated families with childhood-onset immune diseases and recurrent infections. All patients had suffered recurrent ear and sinopulmonary infections, including pneumonias from encapsulated bacteria Streptococcus pneumoniae and Haemophilus influenza, resulting in early-onset bronchiectasis in several individuals; Changed rating: GREEN; Changed publications: 20832341, 35960817; Changed phenotypes: Autoinflammatory syndrome, TRAF3-related, MONDO:0019751, hypergammaglobulinemia, lymphadenopathy, splenomegaly, Sjögren’s syndrome, {?Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 5}, MIM# 614849 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.346 | KCNK3 | Krithika Murali reviewed gene: KCNK3: Rating: GREEN; Mode of pathogenicity: None; Publications: 36195757; Phenotypes: eurodevelopmental disorder, MONDO:0700092, KCNK3-related, developmental delay with sleep apnoea (DDSA), Pulmonary hypertension, primary, 4-MIM#615344; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.346 | COQ4 |
Zornitza Stark changed review comment from: Primary coenzyme Q10 deficiency-7 (COQ10D7) is an autosomal recessive disorder resulting from mitochondrial dysfunction. Most patients have onset of severe cardiac or neurologic symptoms soon after birth. IUGR reported. At least 9 unrelated families reported.; to: Primary coenzyme Q10 deficiency-7 (COQ10D7) is an autosomal recessive disorder resulting from mitochondrial dysfunction. Most patients have onset of severe cardiac or neurologic symptoms soon after birth. IUGR reported. At least 9 unrelated families reported. Treatment: CoQ10 supplementation can limit disease progression and reverse some clinical manifestations. |
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| Mendeliome v1.346 | ADAMTS19 | Zornitza Stark Phenotypes for gene: ADAMTS19 were changed from Non-syndromic heart valve disease to Cardiac valvular dysplasia 2, MIM# 620067 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.345 | ADAMTS19 | Zornitza Stark edited their review of gene: ADAMTS19: Changed phenotypes: Cardiac valvular dysplasia 2, MIM# 620067 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.344 | DPH2 | Zornitza Stark Phenotypes for gene: DPH2 were changed from Diphthamide-deficiency syndrome to Developmental delay with short stature, dysmorphic facial features, and sparse hair 2, MIM# 620062; Diphthamide-deficiency syndrome | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.343 | DPH2 | Zornitza Stark reviewed gene: DPH2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental delay with short stature, dysmorphic facial features, and sparse hair 2, MIM# 620062; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.343 | ARSB | Zornitza Stark Tag clinical trial tag was added to gene: ARSB. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.343 | ARSB | Zornitza Stark Tag treatable tag was added to gene: ARSB. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.343 | ARG1 | Zornitza Stark Tag treatable tag was added to gene: ARG1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.342 | ACVR1 |
Zornitza Stark changed review comment from: Fibrodysplasia ossificans progressiva is a rare autosomal dominant disease with complete penetrance involving progressive ossification of skeletal muscle, fascia, tendons, and ligaments. FOP has a prevalence of approximately 1 in 2 million worldwide, and shows no geographic, ethnic, racial, or gender preference. Individuals with FOP appear normal at birth except for great toe abnormalities: the great toes are short, deviated, and monophalangic. Ossification occurs progressively over the course of a lifetime in an inevitable and unpredictable episodic manner. Multiple unrelated families reported. The R206H variant is recurrent. Note variants in this gene are also associated with congenital heart disease, PMID 29089047.; to: Fibrodysplasia ossificans progressiva is a rare autosomal dominant disease with complete penetrance involving progressive ossification of skeletal muscle, fascia, tendons, and ligaments. FOP has a prevalence of approximately 1 in 2 million worldwide, and shows no geographic, ethnic, racial, or gender preference. Individuals with FOP appear normal at birth except for great toe abnormalities: the great toes are short, deviated, and monophalangic. Ossification occurs progressively over the course of a lifetime in an inevitable and unpredictable episodic manner. Multiple unrelated families reported. The R206H variant is recurrent. Clinical trial with palovarotene Note variants in this gene are also associated with congenital heart disease, PMID 29089047. |
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| Mendeliome v1.342 | ALDOB | Zornitza Stark reviewed gene: ALDOB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fructose intolerance, hereditary, MIM# 229600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.342 | ATP7A |
Zornitza Stark changed review comment from: ATP7A-related copper transport disorders are classically separated in three pathologies according to their severity, all inherited in an X-linked recessive manner: Menkes disease (MD, OMIM #309400) which represent more than 90% of cases; occipital Horn Syndrome (OHS, OMIM #304150) and ATP7A-related distal motor neuropathy also named X-linked distal spinal muscular atrophy-3 (SMAX3, OMIM #300489). Although there is no clear cut correlation between Cu and ceruloplasmin levels in ATP7A related disorders, these three entities probably represent a continuum partly depending on residual functional ATP7A protein.; to: ATP7A-related copper transport disorders are classically separated in three pathologies according to their severity, all inherited in an X-linked recessive manner: Menkes disease (MD, OMIM #309400) which represent more than 90% of cases; occipital Horn Syndrome (OHS, OMIM #304150) and ATP7A-related distal motor neuropathy also named X-linked distal spinal muscular atrophy-3 (SMAX3, OMIM #300489). Although there is no clear cut correlation between Cu and ceruloplasmin levels in ATP7A related disorders, these three entities probably represent a continuum partly depending on residual functional ATP7A protein. Treatment for Menkes disease: subcutaneous injections of copper histidine or copper chloride ClinGen has assessed as moderate evidence for actionability. Neonatal treatment with subcutaneous copper-histidine (initiated before 30 days of life) is recommended for asymptomatic males with a diagnosis of MD, but is not recommended for symptomatic boys or after 30 days of life. Treatment should be continued indefinitely. In an open-label clinical trial, 12 patients with MD treated with copper-histidine within 22 days of life had 92% survival after a mean follow-up of 4.6 years compared to 13% in a historical control group of 15 patients treated after a late diagnosis (mean age at diagnosis: 163 ± 113 days, range: 42 to 390). Two of the 12 patients with earlier treatment had normal neurological development. A second open-label trial of 35 presymptomatic patients receiving copper-histidine at less than a month of age reported significant improvement of four major neurodevelopmental (gross motor, fine motor/adaptive, personal/social, and language) domains and a non-significant lower mortality (28.5% vs 50%) at age of 3 years (or age of death) compared to 22 patients treated later and after onset of symptoms. |
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| Mendeliome v1.342 | ATRX | Zornitza Stark Phenotypes for gene: ATRX were changed from Alpha-thalassemia/mental retardation syndrome; Mental retardation-hypotonic facies syndrome, X-linked to Alpha-thalassemia/mental retardation syndrome, MIM# 301040; Intellectual disability-hypotonic facies syndrome, X-linked, MIM# 309580 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.341 | PDCD6IP | Zornitza Stark Phenotypes for gene: PDCD6IP were changed from Neurodevelopmental disorder MONDO:0700092; Microcephaly; intellectual disability to Microcephaly 29, primary, autosomal recessive, MIM# 620047; Microcephaly; intellectual disability | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.340 | PDCD6IP | Zornitza Stark edited their review of gene: PDCD6IP: Changed phenotypes: Microcephaly 29, primary, autosomal recessive, MIM# 620047, Microcephaly, intellectual disability | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.340 | PDCD6IP | Zornitza Stark edited their review of gene: PDCD6IP: Changed phenotypes: Microcephaly 29, primary, autosomal recessive , MIM# 620047, Microcephaly, intellectual disability | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.340 | DPP9 | Zornitza Stark Marked gene: DPP9 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.339 | DPP9 |
Zornitza Stark gene: DPP9 was added gene: DPP9 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: DPP9 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DPP9 were set to 36112693 Phenotypes for gene: DPP9 were set to Autoinflammatory syndrome MONDO:0019751, DPP9-related; recurrent fevers; repeated infections; herpes susceptibility; cytopenias Review for gene: DPP9 was set to GREEN Added comment: Three unrelated families with Hatipoğlu syndrome with biochemical and cellular assays, mouse and zebrafish models. Immunological features of recurrent fevers, repeated infections, herpes susceptibility, cytopenias. Sources: Expert Review |
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| Mendeliome v1.338 | ARSA |
Zornitza Stark Tag treatable tag was added to gene: ARSA. Tag clinical trial tag was added to gene: ARSA. |
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| Mendeliome v1.338 | ARPC1B | Zornitza Stark Tag treatable tag was added to gene: ARPC1B. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.338 | AQP2 |
Zornitza Stark changed review comment from: Dominant disease is caused by variants exerting a dominant negative effect, whereas recessive disease is caused by bi-allelic loss of function variants.; to: Dominant disease is caused by variants exerting a dominant negative effect, whereas recessive disease is caused by bi-allelic loss of function variants. Onset in infancy. Causes severe dehydration, can be life-threatening. Treatment: hydration, low-salt, low-protein diet, thiazide diuretics, amiloride, indomethacin. Clinical trials. |
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| Mendeliome v1.338 | APRT |
Zornitza Stark changed review comment from: APRT deficiency is an autosomal recessive metabolic disorder that can lead to accumulation of the insoluble purine 2,8-dihydroxyadenine (DHA) in the kidney, which results in crystalluria and the formation of urinary stones. Clinical features include renal colic, hematuria, urinary tract infection, dysuria, and, in some cases, renal failure. The age at onset can range from 5 months to late adulthood; however, as many as 50% of APRT-deficient individuals may be asymptomatic.; to: APRT deficiency is an autosomal recessive metabolic disorder that can lead to accumulation of the insoluble purine 2,8-dihydroxyadenine (DHA) in the kidney, which results in crystalluria and the formation of urinary stones. Clinical features include renal colic, hematuria, urinary tract infection, dysuria, and, in some cases, renal failure. The age at onset can range from 5 months to late adulthood; however, as many as 50% of APRT-deficient individuals may be asymptomatic. Treatable: allopurinol or febuxostat, low purine diet. |
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| Mendeliome v1.338 | ANO1 | Zornitza Stark Phenotypes for gene: ANO1 were changed from Impaired intestinal peristalsis; haemorrhagic diarrhoea; dysmorphic features to Intestinal dysmotility syndrome, MIM# 620045; Impaired intestinal peristalsis; haemorrhagic diarrhoea; dysmorphic features | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.337 | ABCC6 | Zornitza Stark Phenotypes for gene: ABCC6 were changed from Pseudoxanthoma elasticum, MIM# 264800; Pseudoxanthoma elasticum, forme fruste, MIM#177850 to Arterial calcification, generalized, of infancy, 2, MIM# 614473; Pseudoxanthoma elasticum, MIM# 264800; Pseudoxanthoma elasticum, forme fruste, MIM#177850 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.335 | ABCC6 | Zornitza Stark edited their review of gene: ABCC6: Added comment: GACI is a treatable disorder.; Changed rating: GREEN; Changed publications: 33005041, 34355424; Changed phenotypes: Arterial calcification, generalized, of infancy, 2, MIM# 614473; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.333 | GIF | Zornitza Stark Marked gene: GIF as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.333 | GIF | Zornitza Stark Added comment: Comment when marking as ready: New HGNC approved name is CBLIF. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.333 | PTPA | Zornitza Stark Marked gene: PTPA as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.332 | PTPA |
Zornitza Stark gene: PTPA was added gene: PTPA was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PTPA was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PTPA were set to 36073231 Phenotypes for gene: PTPA were set to Intellectual disability, MONDO: 36073231, PTPA-related Review for gene: PTPA was set to AMBER Added comment: Biallelic PTPA pathogenic variants lead to a form of ID with later-onset parkinsonism based on 4 individuals from 2 families in the literature. Affected individuals were homozygous for missense variants demonstrated to result to reduced mRNA and protein levels as well as PP2A complex activation. Drosophila studies support an age-dependent locomotor dysfunction. Variants in other PP2A-complex-related genes also lead to NDDs. Summary provided below. There is currently no associated phenotype in OMIM, G2P, PanelApp UK or SysID. Consider inclusion in relevant panels (ID, Parkinsonism/movement disorders, etc) with amber rating pending further reports. ------ Fevga, Tesson et al (2022 - PMID: 36073231) describe the features of 4 individuals, from 2 unrelated families, with biallelic pathogenic PTPA variants. These presented with normal or delayed early milestones, learning disability and ID (mild to moderate) followed by progressive signs of parkinsonism (at the age of 11 yrs in 2 sibs, 15 yrs in another individual). Motor symptoms were responsive to levodopa and later to deep brain stimulation. Linkage analysis in one consanguineous family followed by exome revealed homozygosity for a missense PTPA variant (NM_178001:c.893T>G/p.Met298Arg). Exome sequencing in affected subjects from the 2nd family revealed homozygosity for a further missense variant (c.512C>A/p.Ala171Asp). There were no other candidate variants for the phenotype following parental / segregation studies. Role of the gene: As the authors discuss, PTPA (or PPP2R4) is ubiquitously expressed in all tissues incl. brain and encodes a phosphotyrosyl phosphatase activator of the dimeric form of protein phosphatase-2A (PP2A). PP2A in turn, is the major Ser/Thr phosphatase in brain targeting a large number of proteins involved in diverse functions. Activation of PP2A is dependent on its methylation, which is negatively regulated by the PP2A-specific methylesterase (PME-1). By binding to PME-1, PTPA counteracts the negative influence of the former on PP2A. Pathogenic variants in genes encoding subunits/regulators of the PP2A complex (e.g. PPP2R1A or PPP2CA) are associated with neurodevelopmental disorders. Variant studies: Upon overexpression of wt and both variants in a HEK-293 cell line the authors demonstrated that both variants resulted in significantly reduced mRNA and protein levels (which for Ala171Asp were attributed to increased proteasomal degradation). Both variants were shown to result in impaired PP2A complex activation compared to wt. Drosophila / animal models: Pan-neuronal RNAi-mediated knockdown of ptpa in Drosophila resulted in an age-dependent locomotor dysfunction, reversible with L-DOPA treatment. Previous studies in mice suggest cognitive/electrophysiological impairments upon downregulation of PP2A activity in transgenic mice. Sources: Literature |
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| Mendeliome v1.328 | PKHD1 | Zornitza Stark edited their review of gene: PKHD1: Added comment: Notę heterozygous carriers reported to have liver cysts and nephrocalcinosis, gene-disease association considered MODERATE by ClinGen.; Changed publications: 28375157, 21945273; Changed phenotypes: Polycystic kidney disease 4, with or without hepatic disease, MIM# 263200, Nephrocalcinosis, MONDO:0001567, PKHD1-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.325 | PPP2R5C |
Teresa Zhao changed review comment from: - ClinVar: two de novo missense variants (p.E177K and p.H188R), one has been reported for intellectual disability - PMID 25972378: inframe del (T157del) found in a de novo individual with ID, facial asymmetry, conductive HL, overgrowth - VCGS proband: additional de novo missense variant (p.K299E) found in one individual with syndromic intellectual disability; to: - ClinVar: two de novo missense variants (p.E177K and p.H188R), one has been reported for intellectual disability - PMID 25972378: inframe del (T157del) found in a de novo individual with ID, facial asymmetry, conductive HL, overgrowth - VCGS proband: additional de novo missense variant (p.K299E) found in one individual with syndromic intellectual disability |
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| Mendeliome v1.325 | MYH8 | Ain Roesley reviewed gene: MYH8: Rating: RED; Mode of pathogenicity: None; Publications: 15590965, 17041932, 15282353; Phenotypes: Carney complex variant MIM#60883; Mode of inheritance: None; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.323 | NODAL |
Zornitza Stark edited their review of gene: NODAL: Added comment: NODAL is a good biological candidate for heterotaxy disorders, and this is supported by animal models. The gene is depleted for LoF variants in gnomad. The missense variants reported in PMIDs 9354794 and 19064609 are present at a high population frequency in gnomad, including some in homozygous case: their association with disease is DISPUTED. A total of at least 7 families reported with severe CHD and high impact variants (stop gain, frameshift and canonical splice site). However, almost invariably these were inherited from unaffected or questionably affected parents (e.g. self reports of heart murmur in childhood), raising questions about whether these variants contribute to disease under a monogenic or polygenic model and/or about penetrance. Discussed at GenCC on 13/9/2022 and agreed on MODERATE assessment.; Changed rating: AMBER; Changed publications: 9354794, 19064609, 29368431, 19933292, 11311163, 30293987 |
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| Mendeliome v1.323 | OOEP | Bryony Thompson Phenotypes for gene: OOEP were changed from Multi locus imprinting disturbance in offspring to Multi locus imprinting disturbance in offspring; female infertility due to oocyte meiotic arrest MONDO:0044626 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.320 | OOEP | Bryony Thompson reviewed gene: OOEP: Rating: AMBER; Mode of pathogenicity: None; Publications: 35946397, 18804437; Phenotypes: female infertility due to oocyte meiotic arrest MONDO:0044626; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.318 | UBAP2L |
Zornitza Stark changed review comment from: Based on Jia et al (2022 - PMID: 35977029) speech, motor delay as well as ID are observed in individuals harboring de novo pLoF variants in UBAP2L. The gene encodes a regulator of the stress granule (SG) assembly. Extensive evidence is provided on the effect of variants as well as the role of UBAP2L and other genes for components and/or regulation of SG in pathogenesis of NDDs. Among others a Ubap2l htz deletion mouse model (behavioral and cognitive impairment, abnormal cortical development due to impaired SG assembly, etc). Data from 26 previous studies, aggregating 40,853 probands with NDDs (mostly DD/ID, also ASD) suggest enrichment for DNMs in UBAP2L or other genes previously known and further shown to be important for SG formation (incl. G3BP1/G3BP2, CAPRIN1). Sources: Literature; to: Based on Jia et al (2022 - PMID: 35977029) speech, motor delay as well as ID are observed in 11 individuals harboring de novo pLoF variants in UBAP2L. The gene encodes a regulator of the stress granule (SG) assembly. Extensive evidence is provided on the effect of variants as well as the role of UBAP2L and other genes for components and/or regulation of SG in pathogenesis of NDDs. Among others a Ubap2l htz deletion mouse model (behavioral and cognitive impairment, abnormal cortical development due to impaired SG assembly, etc). Data from 26 previous studies, aggregating 40,853 probands with NDDs (mostly DD/ID, also ASD) suggest enrichment for DNMs in UBAP2L or other genes previously known and further shown to be important for SG formation (incl. G3BP1/G3BP2, CAPRIN1). Sources: Literature |
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| Mendeliome v1.318 | UBAP2L | Zornitza Stark Marked gene: UBAP2L as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.317 | UBAP2L |
Zornitza Stark gene: UBAP2L was added gene: UBAP2L was added to Mendeliome. Sources: Literature Mode of inheritance for gene: UBAP2L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: UBAP2L were set to 35977029 Phenotypes for gene: UBAP2L were set to Neurodevelopmental disorder, MONDO:0700092, UBAP2L-related Review for gene: UBAP2L was set to GREEN Added comment: Based on Jia et al (2022 - PMID: 35977029) speech, motor delay as well as ID are observed in individuals harboring de novo pLoF variants in UBAP2L. The gene encodes a regulator of the stress granule (SG) assembly. Extensive evidence is provided on the effect of variants as well as the role of UBAP2L and other genes for components and/or regulation of SG in pathogenesis of NDDs. Among others a Ubap2l htz deletion mouse model (behavioral and cognitive impairment, abnormal cortical development due to impaired SG assembly, etc). Data from 26 previous studies, aggregating 40,853 probands with NDDs (mostly DD/ID, also ASD) suggest enrichment for DNMs in UBAP2L or other genes previously known and further shown to be important for SG formation (incl. G3BP1/G3BP2, CAPRIN1). Sources: Literature |
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| Mendeliome v1.316 | ALDH1A2 | Zornitza Stark Phenotypes for gene: ALDH1A2 were changed from congenital heart defects; diaphragmatic eventration; pulmonary hypoplasia; dysmorphic features to Diaphragmatic hernia 4, with cardiovascular defects, MIM# 620025 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.315 | ALDH1A2 | Zornitza Stark reviewed gene: ALDH1A2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Diaphragmatic hernia 4, with cardiovascular defects, MIM# 620025; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.314 | SLC31A1 | Zornitza Stark Marked gene: SLC31A1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.312 | PDZD8 | Zornitza Stark Marked gene: PDZD8 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.310 | SLC31A1 |
Daniel Flanagan gene: SLC31A1 was added gene: SLC31A1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: SLC31A1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC31A1 were set to PMID: 35913762 Phenotypes for gene: SLC31A1 were set to Neurodevelopmental disorder, SLC31A1-related (MONDO#0700092) Review for gene: SLC31A1 was set to RED Added comment: SLC31A1 is also referred to as CTR1. Monozygotic twins with hypotonia, global developmental delay, seizures, and rapid brain atrophy, consistent with profound central nervous system copper deficiency. Homozygous for a novel missense variant (p.(Arg95His)) in copper transporter CTR1, both parents heterozygous. A mouse knock-out model of CTR1 deficiency resulted in prenatal lethality. Sources: Expert list |
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| Mendeliome v1.310 | HNRNPH1 | Zornitza Stark Phenotypes for gene: HNRNPH1 were changed from HNRNPH1‐related syndromic intellectual disability to HNRNPH1‐related syndromic intellectual disability; early onset high myopia, MONDO:0001384 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.308 | TMEM163 | Zornitza Stark Marked gene: TMEM163 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.304 | NBAS | Zornitza Stark edited their review of gene: NBAS: Added comment: PMID 35902954 - Biallelic NBAS variants identifed in three HLH patients who harbored no pathogenic variants in any of the known HLH genes. Functionally, impaired NK-cell cytotoxicity and degranulation were revealed in both NBAS biallelic variant patients and in an NBAS-defcient NK-cell line. Knockdown of NBAS in an NK-cell line (IMC-1) using short hairpin RNA (shRNA) resulted in loss of lytic granule polarization and a decreased number of cytotoxic vesicles near the Golgi apparatus.; Changed publications: 31761904, 35902954; Changed phenotypes: Short stature, optic nerve atrophy, and Pelger-Huet anomaly, MIM# 614800, Infantile liver failure syndrome 2, MIM# 616483, Haemophagocytic lymphohistiocytosis (HLH), MONDO:0015541 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.304 | TYMS | Zornitza Stark Marked gene: TYMS as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.303 | COX11 | Zornitza Stark Marked gene: COX11 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.302 | COX11 |
Zornitza Stark gene: COX11 was added gene: COX11 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: COX11 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: COX11 were set to 36030551 Phenotypes for gene: COX11 were set to Mitochondrial disease (MONDO:0044970), COX11-related Review for gene: COX11 was set to GREEN Added comment: PMID: 36030551 - Biallelic variants in COX11 associated with infantile-onset mitochondrial encephalopathies in two unrelated consanguineous families, one with homozygous missense variant, another with homozygous frameshift variant. - Functional studies supported pathogenicity of the missense variant, and showed that mutant COX11 fibroblasts had decreased ATP levels which could be rescued by CoQ10. - RNA studies suggested the mutant transcript with p.(Val12Glyfs*21) is not degraded by nonsense mediated decay. Sources: Literature |
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| Mendeliome v1.301 | SARS | Zornitza Stark Publications for gene: SARS were set to 28236339; 34570399; 35790048 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.300 | TMEM147 | Zornitza Stark Marked gene: TMEM147 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.299 | SAT1 | Zornitza Stark Phenotypes for gene: SAT1 were changed from to Systemic lupus erythematosus, MONDO:0007915, SAT1-related; Keratosis follicularis spinulosa decalvans | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.291 | GATA1 | Zornitza Stark edited their review of gene: GATA1: Added comment: PMID 36029112: De novo GATA1 initiation codon variant (c.3G>A) identified in a Diamond-Blackfan Anaemia patient. Functional evidence showed that the variant does not affect the GATA1 mRNA but brings about a shorter GATA1 isoform (GATA1s) and reduced full-length functional GATA1 protein (GATA1fl), thereby contributing to an erythropoietic defect. Four other GATA1 variants (c.2T>C, c.220G>C, c.220delG, c.220+2T>C) found in eight families have been described as DBA phenotype.; Changed publications: 36029112; Changed phenotypes: Thrombocytopaenia, X-linked, with or without dyserythropoietic anaemia, MIM# 300367, Haemolytic anaemia due to elevated adenosine deaminase, MIM# 301083, Anemia, X-linked, with/without neutropenia and/or platelet abnormalities, MIM# 300835, Diamond-Blackfan anemia (MONDO:0015253) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.291 | LGI3 | Zornitza Stark Marked gene: LGI3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.291 | LGI3 | Zornitza Stark Phenotypes for gene: LGI3 were changed from Global developmental delay; Intellectual disability; Distal deformities; Diminished reflexes; Facial myokymia; Hyporeflexia/areflexi to Neurodevelopmental disorder, MONDO:0700092, LGI3-related; Global developmental delay; Intellectual disability; Distal deformities; Diminished reflexes; Facial myokymia; Hyporeflexia/areflexi | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.289 | TMEM147 |
Naomi Baker gene: TMEM147 was added gene: TMEM147 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TMEM147 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TMEM147 were set to PMID: 36044892 Phenotypes for gene: TMEM147 were set to Neurodevelopmental disorder (MONDO:0700092), TMEM147-related Review for gene: TMEM147 was set to GREEN Added comment: PMID: 36044892; Twelve different variants reported in 23 affected individuals from 15 unrelated families with biallelic variants. All individuals had global developmental delay and intellectual disability. Consistent facial dysmorphisms included coarse facies, prominent forehead, board depressed nasal root, tented mouth, long smooth philtrum, and low-set ears. In vitro studies of missense variants demonstrated accelerated protein degradation via the autophagy-lysosomal pathway, while analysis of primary fibroblasts and granulocytes provided functional evidence of ER and nuclear envelope dysfunction. Sources: Literature |
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| Mendeliome v1.289 | SARS | Ee Ming Wong reviewed gene: SARS: Rating: RED; Mode of pathogenicity: Other; Publications: 36041817; Phenotypes: neurodevelopmental disorder, MONDO#070009, SARS1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.289 | ADAMTS15 | Zornitza Stark Marked gene: ADAMTS15 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.288 | CAPRIN1 | Zornitza Stark Marked gene: CAPRIN1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.287 | CBLB | Alison Yeung Marked gene: CBLB as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.286 | CBLB |
Alison Yeung gene: CBLB was added gene: CBLB was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CBLB was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CBLB were set to 36006710 Phenotypes for gene: CBLB were set to Autoimmune disease, MONDO:0007179 Review for gene: CBLB was set to GREEN Added comment: Distinct homozygous mutations in CBLB were identified in three unrelated children with early onset autoimmunity. Mice homozygous for the CBL-B p.H257L mutation, which corresponds to the patient's p.H285L mutation, had T and B cell hyper-proliferation in response to antigen receptor cross-linking. Sources: Literature |
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| Mendeliome v1.285 | TYMS |
Lucy Spencer gene: TYMS was added gene: TYMS was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TYMS was set to Other Publications for gene: TYMS were set to 35931051 Phenotypes for gene: TYMS were set to Dyskeratosis congenita MONDO:0015780 Review for gene: TYMS was set to RED Added comment: 8 families with dyskeratosis congenita and heterozygous variants in TYMS. 4 PTCs, 2 missense and 1 splice (2 families had the same frameshift). However in all families 1 unaffected parent was also heterozygous for the same TYSM variant. The other parent in 3 of these families was then shown to carry a heterozygous variant in ENOSF1 which each affected child was also heterozygous for. ENOSF1 has been shown to modify TYMS expression at the RNA level by acting as an antisense molecule to TYMS. ENOSF1 partially overlaps TYMS on chromosome 18 and is transcribed in the opposite direction to TYMS. This paper is suggesting digenic inheritance. The TYMS wild type parent from another family was seen to have a TYMSOS variant which was also observed along with the TYMS variant in their 2 affected children. Immunoblotting showed a stark reduction in TYMS protein level in the cells of affected probands when compared to the parent carrier, wild-type parent, and the controls. Lymphoblastoid cells from affected probands have severe TYMS deficiency, altered cellular deoxyribonucleotide triphosphate pools, and hypersensitivity to the TYMS-specific inhibitor 5-fluorouracil. These defects in the nucleotide metabolism pathway resulted in genotoxic stress, defective transcription, and abnormal telomere maintenance. Gene-rescue studies in cells from affected probands revealed that post-transcriptional epistatic silencing of TYMS is occurring via elevated ENOSF1. Sources: Literature |
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| Mendeliome v1.285 | LGI3 | Melanie Marty edited their review of gene: LGI3: Changed phenotypes: Global developmental delay, Intellectual disability, Distal deformities, Diminished reflexes, Facial myokymia, Hyporeflexia/areflexia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.285 | HNRNPH1 |
Hazel Phillimore changed review comment from: PMID: 35989590; Ouyang, J. et al. (2022): Two loss of function variants c.2dup, p.(M1?) and c.121dup, p.(Q41Pfs*20), were found in two individuals with early onset high myopia. They were in cohort of 928 probands with early onset high myopia. The pedigrees for these probands indicate that no other relatives were affected. However, it does not appear that any relatives were tested for these variants. These variants were reported to be absent in gnomAD. Note: there is actually 1 heterozygote for an alternative variant that is predicted to cause p.(Met1?) in gnomADv2). In gnomAD, there are very few LOF variants. (LOF shows pLI = 1). The group also studied knockdown of this gene in zebrafish, which resulted in ocular coloboma.; to: PMID: 35989590; Ouyang, J. et al. (2022): Two loss of function variants c.2dup, p.(M1?) and c.121dup, p.(Q41Pfs*20), were found in two individuals with early onset high myopia. They were in cohort of 928 probands with early onset high myopia. The pedigrees for these probands indicate that no other relatives were affected. However, it does not appear that any relatives were tested for these variants. These variants were reported to be absent in gnomAD. Note: there is actually 1 heterozygote for an alternative variant that is predicted to cause p.(Met1?) in gnomADv2. In gnomAD, there are very few LOF variants. (LOF shows pLI = 1). The group also studied knockdown of this gene in zebrafish, which resulted in ocular coloboma. |
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| Mendeliome v1.285 | HNRNPH1 | Hazel Phillimore reviewed gene: HNRNPH1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 35989590; Phenotypes: early onset high myopia, blindness; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.285 | TMEM163 |
Teresa Zhao changed review comment from: Four unrelated families with a hypomyelinating leukodystrophy phenotype. Genomic testing identified three distinct heterozygous missense variants in TMEM163 with two unrelated individuals sharing the same de novo variant. All have global developmental delay, three of them have seizures and two have ID. Sources: Literature; to: Four unrelated families with a hypomyelinating leukodystrophy phenotype. Genomic testing identified three distinct heterozygous missense variants in TMEM163 with two unrelated individuals sharing the same de novo variant. All have global developmental delay, three of them have seizures. Sources: Literature |
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| Mendeliome v1.285 | MET | Zornitza Stark Phenotypes for gene: MET were changed from Renal cell carcinoma, papillary, 1, familial and somatic, MIM# 605074; Papillary renal cell carcinoma MONDO:0017884 to Arthrogryposis, distal, type 11 (MIM#620019), AD; Renal cell carcinoma, papillary, 1, familial and somatic, MIM# 605074; Papillary renal cell carcinoma MONDO:0017884 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.283 | MET |
Zornitza Stark changed review comment from: PMID 30777867: Four-generation Chinese arthrogryposis pedigree with only upper limb involvement. MET c.3701A>G p.Y1234C segregated as heterozygous in 11 affected family members and was absent from 12 unaffected family members. Variant is absent from gnomad. Functional studies showed this variant caused failure of phosphorylation and loss of tyrosine kinase activity of MET receptor. A mouse model was also created with this variant, mutated mice were found to be smaller than WT mice and had reduced myofibres. These mouse models also had defective migration of muscle progenitor cells and impaired proliferation of secondary myoblasts. Phenotypes in this family included camptodactyly, absent flexion crease, and limited forearm supination.; to: PMID 30777867: Four-generation Chinese arthrogryposis pedigree with only upper limb involvement. MET c.3701A>G p.Y1234C segregated as heterozygous in 11 affected family members and was absent from 12 unaffected family members. Variant is absent from gnomad. Functional studies showed this variant caused failure of phosphorylation and loss of tyrosine kinase activity of MET receptor. A mouse model was also created with this variant, mutated mice were found to be smaller than WT mice and had reduced myofibres. These mouse models also had defective migration of muscle progenitor cells and impaired proliferation of secondary myoblasts. Phenotypes in this family included camptodactyly, absent flexion crease, and limited forearm supination. AMBER for this association |
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| Mendeliome v1.283 | MET |
Zornitza Stark edited their review of gene: MET: Added comment: PMID 30777867: Four-generation Chinese arthrogryposis pedigree with only upper limb involvement. MET c.3701A>G p.Y1234C segregated as heterozygous in 11 affected family members and was absent from 12 unaffected family members. Variant is absent from gnomad. Functional studies showed this variant caused failure of phosphorylation and loss of tyrosine kinase activity of MET receptor. A mouse model was also created with this variant, mutated mice were found to be smaller than WT mice and had reduced myofibres. These mouse models also had defective migration of muscle progenitor cells and impaired proliferation of secondary myoblasts. Phenotypes in this family included camptodactyly, absent flexion crease, and limited forearm supination.; Changed publications: 30777867 |
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| Mendeliome v1.283 | TMEM163 |
Teresa Zhao gene: TMEM163 was added gene: TMEM163 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TMEM163 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: TMEM163 were set to PMID: 35953447 Phenotypes for gene: TMEM163 were set to Hypomyelinating leukodystrophy Review for gene: TMEM163 was set to GREEN Added comment: Four unrelated families with a hypomyelinating leukodystrophy phenotype. Genomic testing identified three distinct heterozygous missense variants in TMEM163 with two unrelated individuals sharing the same de novo variant. All have global developmental delay, three of them have seizures and two have ID. Sources: Literature |
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| Mendeliome v1.283 | LGI3 |
Melanie Marty gene: LGI3 was added gene: LGI3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: LGI3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LGI3 were set to PMID: 35948005 Phenotypes for gene: LGI3 were set to Global developmental delay; Intellectual disability; Distal deformities; Diminished reflexes; Facial myokymia; Hyporeflexia/areflexi Review for gene: LGI3 was set to GREEN Added comment: Sixteen individuals from eight unrelated families with loss-of-function (LoF) bi-allelic variants in LGI3. Lgi3-null mice showed reduced and mis-local-ized Kv1 channel complexes in myelinated peripheral axons. Sources: Literature |
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| Mendeliome v1.280 | BUD13 | Alison Yeung Marked gene: BUD13 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.279 | BUD13 |
Alison Yeung gene: BUD13 was added gene: BUD13 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: BUD13 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: BUD13 were set to 35670808 Phenotypes for gene: BUD13 were set to Lipodystrophy, MONDO:0006573 Review for gene: BUD13 was set to AMBER Added comment: 5 individuals with a lipodystrophy phenotype with a typical facial appearance, corneal clouding, achalasia, progressive hearing loss, and variable severity. Although 3 individuals showed stunted growth, intellectual disability, and died within the first decade of life, 2 are adults with normal intellectual development. All individuals harbored an identical homozygous nonsense variant affecting the retention and splicing complex component BUD13. Individuals from only two Algerian families. Sources: Literature |
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| Mendeliome v1.276 | NOTCH1 |
Chern Lim changed review comment from: PMID: 35947102: - Seven unrelated patients with leukoencephalopathy and calcifications, germline heterozygous de novo gain-of-function variants in NOTCH1. - Missense and small inframe insertion variants in the negative regulatory region.; to: PMID: 35947102: - Seven unrelated patients with leukoencephalopathy and calcifications, germline heterozygous de novo gain-of-function variants in NOTCH1. - Other clinical features include intellectual disability, spasticity and etc. Childhood onset in most individuals however 15y and 40y reported in two individuals. - Missense and small inframe insertion variants in the negative regulatory region. |
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| Mendeliome v1.276 | ADAMTS15 |
Naomi Baker changed review comment from: PMID: 35962790; Four different homozygous variants identified in five affected individuals from four unrelated consanguineous families presenting with congenital flexion contractures of the interphalangeal joints and hypoplastic or absent palmar creases. All patients also had a mild appearance of fetal finger pads and clinodactyly of the fifth finger. Other reported phenotypes include: ontractures of knee, Achilles tendon, and ankle (4/5), spine involvement (kyphoscoliosis and/or spinal stiffness) (4/5), and orthodontic features (small mouth, dental crowding, missing teeth, or arched palate) (4/5). Sources: Literature; to: PMID: 35962790; Four different homozygous variants identified in five affected individuals from four unrelated consanguineous families presenting with congenital flexion contractures of the interphalangeal joints and hypoplastic or absent palmar creases. All patients also had a mild appearance of fetal finger pads and clinodactyly of the fifth finger. Other reported phenotypes include: contractures of knee, Achilles tendon, and ankle (4/5), spine involvement (kyphoscoliosis and/or spinal stiffness) (4/5), and orthodontic features (small mouth, dental crowding, missing teeth, or arched palate) (4/5). Sources: Literature |
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| Mendeliome v1.276 | ADAMTS15 |
Naomi Baker gene: ADAMTS15 was added gene: ADAMTS15 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ADAMTS15 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ADAMTS15 were set to PMID: 35962790 Phenotypes for gene: ADAMTS15 were set to Arthrogryposis (MONDO:0008779), ADMATS15-related Review for gene: ADAMTS15 was set to GREEN Added comment: PMID: 35962790; Four different homozygous variants identified in five affected individuals from four unrelated consanguineous families presenting with congenital flexion contractures of the interphalangeal joints and hypoplastic or absent palmar creases. All patients also had a mild appearance of fetal finger pads and clinodactyly of the fifth finger. Other reported phenotypes include: ontractures of knee, Achilles tendon, and ankle (4/5), spine involvement (kyphoscoliosis and/or spinal stiffness) (4/5), and orthodontic features (small mouth, dental crowding, missing teeth, or arched palate) (4/5). Sources: Literature |
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| Mendeliome v1.276 | CAPRIN1 |
Paul De Fazio gene: CAPRIN1 was added gene: CAPRIN1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CAPRIN1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: CAPRIN1 were set to 35979925 Phenotypes for gene: CAPRIN1 were set to Neurodevelopmental disorder, CAPRIN1-related MONDO:0700092 Review for gene: CAPRIN1 was set to GREEN gene: CAPRIN1 was marked as current diagnostic Added comment: 12 individuals reported with ID and language impairment. Other features included seizures (4 individuals), hands and feet malformations (5 individuals), breathing problems (6 individuals), ocular problems (4 individuals) and hearing problems (3 individuals). All of the variants were nonsense (NMD-predicted) or splicing variants. 10 were de novo, 1 was inherited from an affected father. Functional studies supported pathogenicity. Sources: Literature |
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| Mendeliome v1.276 | LHX8 |
Alison Yeung gene: LHX8 was added gene: LHX8 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: LHX8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: LHX8 were set to 36029299 Phenotypes for gene: LHX8 were set to Inherited premature ovarian failure, MONDO:0019852, LHX8-related Review for gene: LHX8 was set to GREEN Added comment: Heterozygous LOF variants identified in 6 families with premature ovarian failure due to oocyte maturation arrest. Sources: Literature |
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| Mendeliome v1.271 | LEF1 | Zornitza Stark edited their review of gene: LEF1: Added comment: Monoallelic variants in LEF1 reported in 11 affected individuals from 4 unrelated families, and a biallelic variant reported in an affected individual from a consanguineous family. The phenotypic spectrum included various limb malformations, such as radial ray defects, polydactyly or split hand/foot, and ectodermal dysplasia. Haploinsufficiency or loss of DNA binding postulated to be responsible for a mild to moderate phenotype, whereas loss of β-catenin binding caused by biallelic variants postulated to be associated with a severe phenotype.; Changed rating: GREEN; Changed publications: 32022899, 35583550; Changed phenotypes: Syndromic disease, MONDO:0002254, LEF1-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.271 | REEP1 | Zornitza Stark Phenotypes for gene: REEP1 were changed from Neuronopathy, distal hereditary motor, type VB MIM#614751; Spastic paraplegia 31, autosomal dominant MIM#610250; Charcot-Marie-Tooth; severe congenital distal SMA with diaphragmatic paralysis; congenital axonal neuropathy and diaphragmatic palsy to Spinal muscular atrophy, distal, autosomal recessive, 6, MIM#620011; Neuronopathy, distal hereditary motor, type VB MIM#614751; Spastic paraplegia 31, autosomal dominant MIM#610250 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.270 | REEP1 | Zornitza Stark reviewed gene: REEP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinal muscular atrophy, distal, autosomal recessive, 6, MIM#620011; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.270 | CCDC82 | Zornitza Stark Marked gene: CCDC82 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.270 | CCDC82 | Zornitza Stark Phenotypes for gene: CCDC82 were changed from Intellectual disability and spastic paraparesis, no OMIM # to Neurodevelopmental disorder, MONDO:0700092, CCDC82-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.268 | NPNT | Zornitza Stark Marked gene: NPNT as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.265 | KIF5B | Zornitza Stark Marked gene: KIF5B as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.264 | COL9A3 | Zornitza Stark Phenotypes for gene: COL9A3 were changed from Epiphyseal dysplasia, multiple, 3, with or without myopathy, MIM# 600969; Stickler syndrome AR; Deafness AD; Peripheral vitreoretinal degeneration and retinal detachment, AD to Epiphyseal dysplasia, multiple, 3, with or without myopathy, MIM# 600969; Stickler syndrome, type VI, MIM# 620022; Deafness AD; Peripheral vitreoretinal degeneration and retinal detachment, AD | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.261 | CCDC82 |
Chirag Patel gene: CCDC82 was added gene: CCDC82 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CCDC82 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CCDC82 were set to PMID: 35373332, 35118659, 27457812 Phenotypes for gene: CCDC82 were set to Intellectual disability and spastic paraparesis, no OMIM # Review for gene: CCDC82 was set to GREEN Added comment: 4 consanguineous families with 9 affected individuals with developmental delay/intellectual disability, and 2 families had spasticity and 1 had epilepsy. WES identified 3 homozgyous truncating variants, segregating with disease and parents as carriers. No functional studies. Sources: Literature |
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| Mendeliome v1.259 | NPNT |
Chirag Patel gene: NPNT was added gene: NPNT was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NPNT was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NPNT were set to PMID: 35246978, 34049960, 17537792 Phenotypes for gene: NPNT were set to Renal agenesis, no OMIM # Review for gene: NPNT was set to GREEN Added comment: 3 consanguineous families with multiple affecteds with bilateral renal agenesis. Whole-exome sequencing (WES)-based homozygosity mapping identified 2 homozygous truncating variants. Reverse transcription polymerase chain reaction data showing complete nonsense-mediated decay of the NPNT transcript. Loss of nephronectin (NPNT) is known to lead to failure of metanephric kidney development with resulting renal agenesis in murine models. Sources: Literature |
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| Mendeliome v1.257 | KIF5B |
Chirag Patel gene: KIF5B was added gene: KIF5B was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KIF5B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KIF5B were set to PMID: 35342932 Phenotypes for gene: KIF5B were set to Kyphomelic dysplasia, no OMIM # Review for gene: KIF5B was set to GREEN Added comment: 4 individuals with Kyphomelic dysplasia (severe bowing of the limbs, sharp angulation of the femora and humeri, short stature, narrow thorax, distinctive facial features, and neonatal respiratory distress. WES found de novo heterozygous missense variants in KIF5B encoding kinesin-1 heavy chain. All variants involved conserved amino acids in or close to the ATPase activity-related motifs in the catalytic motor domain of the KIF5B protein. No functional studies of variants. Previously 2 animal model experiments showed that loss of function of KIF5B can cause kyphomelic dysplasia. First, chondrocyte-specific knockout of Kif5b in mice was shown to produce a disorganized growth plate, leading to bone deformity. Second, double mutants disrupting the two zebrafish kif5b caused abnormal skeletal morphogenesis and the curvature of Meckel's and ceratohyal cartilages. Sources: Literature |
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| Mendeliome v1.253 | ACADS | Zornitza Stark changed review comment from: Definitive by ClinGen.; to: Definitive by ClinGen. However, largely just causes a biochemical abnormality, and association with clinical disease is debated. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.253 | FOCAD | Zornitza Stark Marked gene: FOCAD as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.252 | FOCAD |
Zornitza Stark gene: FOCAD was added gene: FOCAD was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: FOCAD was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FOCAD were set to 35864190 Phenotypes for gene: FOCAD were set to Liver disease, severe congenital, MIM# 619991 Review for gene: FOCAD was set to GREEN Added comment: Moreno Traspas et al 2022 reported 14 children from ten unrelated families with syndromic form of pediatric liver cirrhosis. Genome/exome sequencing analysis reveled biallelic variants in the FOCAD gene. Most of the mutations were nonsense, frameshift, or splice site alterations, predicted to result in a loss of function, but there were also 3 missense variants at highly conserved residues. Western blot analysis of dermal fibroblasts derived from 2 patients showed near absent FOCAD expression in cellular extracts. There were also decreased levels of the SKIC2 protein, suggesting that FOCAD may contribute to the stability of RNA helicase (OMIM: 619991). Sources: Expert Review |
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| Mendeliome v1.248 | ZMYND8 | Zornitza Stark Marked gene: ZMYND8 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.247 | ZMYND8 |
Zornitza Stark gene: ZMYND8 was added gene: ZMYND8 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: ZMYND8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ZMYND8 were set to 35916866; 32530565 Phenotypes for gene: ZMYND8 were set to Neurodevelopmental disorder, MONDO:0700092, ZMYND8-related; Delayed speech and language development; Motor delay; Intellectual disability; Abnormality of cardiovascular system morphology; Hearing abnormality; Abnormality of vision; Abnormality of the face; Seizures Review for gene: ZMYND8 was set to GREEN Added comment: Dias et al (2022 - PMID: 35916866) describe the phenotype of 11 unrelated individuals with monoallelic de novo (or suspected de novo) missense (N=9) or truncating (N=2) ZMYND8 variants. One of these subjects was previously reported by Suzuki et al (2020 - PMID: 32530565). Features included speech delay/language difficulties (9/11), motor delay (9/11), ID (in 10/11 - profound in 1, moderate in 2), CHD (7/11 - PDA, VSD, ASD, pulmonary stenosis, etc), hearing or vision impairment (7/11). Seizures were reported in few (in text 5/11, table 2/11). Variable non-familial facial features were present in (9/11). As the authors discuss, ZMYND8 encodes a multidomain protein playing a role in transcription regulation, chromatin remodeling, regulation of super enhancers, DNA damage response/tumor suppression. The protein is broadly expressed in brain and shows highest expression in early development. Molecular modeling and/or a yeast two-hybrid system were suggestive of disrupted interaction of ZMYND8 with Drebrin (missense variants in PWWP domain) or GATAD2A (variants in MYND domain). Neuronal Zmynd8 knockdown in Drosophila resulted in deficits in habituation learning. Sources: Expert Review |
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| Mendeliome v1.246 | TRAC | Seb Lunke Added comment: Comment on list classification: Single variant reported to date in 6 patients; 2 unrelated children from consanguineous families of Pakistani descent (PMID: 21206088); 1 non-consanguineous family from North-west India (PMID: 33909184) and 1 consanguineous parents of East Indian (https://lymphosign.com/doi/10.14785/lymphosign-2022-0001) Also note annotation issues in certain variant curation and annotation tools. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.242 | PRIM1 | Zornitza Stark Phenotypes for gene: PRIM1 were changed from Microcephalic primordial dwarfism, MONDO:0017950 to Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, MIM# 620005 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.241 | PRIM1 | Zornitza Stark edited their review of gene: PRIM1: Changed phenotypes: Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, MIM# 620005 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.241 | SMG9 | Zornitza Stark Phenotypes for gene: SMG9 were changed from Heart and brain malformation syndrome, MIM# 616920 to Heart and brain malformation syndrome, MIM# 616920; Neurodevelopmental disorder with intention tremor, pyramidal signs, dyspraxia, and ocular anomalies, MIM# 619995 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.239 | SMG9 | Zornitza Stark edited their review of gene: SMG9: Added comment: PMID 35087184: 5 individuals from 3 unrelated Finnish families reported with same homozygous missense variant (founder effect) and predominantly neurological phenotype. Uncertain if this is a distinct disorder or part of a spectrum with the previously reported cases.; Changed publications: 27018474, 31390136, 35087184; Changed phenotypes: Heart and brain malformation syndrome, MIM# 616920, Neurodevelopmental disorder with intention tremor, pyramidal signs, dyspraxia, and ocular anomalies, MIM# 619995 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.239 | THUMPD1 | Zornitza Stark Phenotypes for gene: THUMPD1 were changed from Syndromic disease, MONDO:0002254, THUMPD1-related to Neurodevelopmental disorder with speech delay and variable ocular anomalies, MIM# 619989 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.238 | THUMPD1 | Zornitza Stark reviewed gene: THUMPD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with speech delay and variable ocular anomalies, MIM# 619989; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.238 | OTULIN | Zornitza Stark Phenotypes for gene: OTULIN were changed from Autoinflammation, panniculitis, and dermatosis syndrome, MIM# 617099; Susceptibility to infection with Staphylococcus aureus; Hereditary predisposition to infections, MONDO:0015979, OTULIN-related to Autoinflammation, panniculitis, and dermatosis syndrome, MIM# 617099; Immunodeficiency 107, susceptibility to invasive staphylococcus aureus infection, MIM# 619986 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.233 | SPTBN5 |
Zornitza Stark changed review comment from: Identified as a candidate gene in a sacral agenesis cohort. PMID 32732226: compound het variants identified in a fetus with multicystic kidney and oligohydramnios detected by fetal ultrasound. Autopsy showed multiple congenital abnormalities including hygroma coli, spina bifida, polycystic kidneys, facial dysmorphism, common mesenterin, rachischisis, sacral vertebral agenesis. Sources: Literature; to: Bi-allelic variants: Identified as a candidate gene in a sacral agenesis cohort. PMID 32732226: compound het variants identified in a fetus with multicystic kidney and oligohydramnios detected by fetal ultrasound. Autopsy showed multiple congenital abnormalities including hygroma coli, spina bifida, polycystic kidneys, facial dysmorphism, common mesenterin, rachischisis, sacral vertebral agenesis. Sources: Literature |
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| Mendeliome v1.233 | SPTBN5 |
Zornitza Stark edited their review of gene: SPTBN5: Added comment: Monoallelic variants: - Four probands from unrelated families (1x Pakistani and 3x Italian) with de novo heterozygous SPTBN5 variants - 3x missense variants and 1x LoF variant were reported - Phenotypes include intellectual disability (mild to severe), aggressive tendencies and variable features such as craniofacial and physical dysmorphisms, autistic behavior, and gastroesophageal reflux; Changed rating: GREEN; Changed publications: 35782384, 32732226, 28007035; Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, SPTBN5-related, Sacral agenesis, congenital anomalies; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
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| Mendeliome v1.233 | CPS1 | Zornitza Stark Phenotypes for gene: CPS1 were changed from to Carbamoylphosphate synthetase I deficiency MIM#237300 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.231 | CPS1 | Zornitza Stark reviewed gene: CPS1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Pulmonary hypertension, neonatal, susceptibility to} 615371; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.231 | OTULIN | Zornitza Stark Phenotypes for gene: OTULIN were changed from Autoinflammation, panniculitis, and dermatosis syndrome, MIM# 617099 to Autoinflammation, panniculitis, and dermatosis syndrome, MIM# 617099; Susceptibility to infection with Staphylococcus aureus; Hereditary predisposition to infections, MONDO:0015979, OTULIN-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.228 | OTULIN | Zornitza Stark changed review comment from: Autoinflammatory disorder presenting in the newborn period with recurrent fever, erythematous rash with painful nodules, painful joints, diarrhoea and lipodystrophy.; to: Bi-allelic variants: Autoinflammatory disorder presenting in the newborn period with recurrent fever, erythematous rash with painful nodules, painful joints, diarrhoea and lipodystrophy. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.228 | OTULIN | Zornitza Stark edited their review of gene: OTULIN: Added comment: PMID 35587511: Multiple individuals reported with haploinsufficiency of OTULIN and severe staphylococcal disease, with life-threatening skin or pulmonary necrosis. Functional data.; Changed publications: 27523608, 27559085, 35587511; Changed phenotypes: Autoinflammation, panniculitis, and dermatosis syndrome, MIM# 617099, Susceptibility to infection with Staphylococcus aureus, Hereditary predisposition to infections, MONDO:0015979, OTULIN-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.228 | NOX1 |
Zornitza Stark gene: NOX1 was added gene: NOX1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NOX1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: NOX1 were set to 29091079; 32064493 Phenotypes for gene: NOX1 were set to Inflammatory bowel disease, MONDO:0005265, NOX1-related Review for gene: NOX1 was set to AMBER Added comment: 8 IBD patients with early onset of IBD with progressive and severe colonic disease, refractory to conventional therapy and functional studies suggesting variant-dependent loss of NOX1-mediated superoxide generation. However, high frequency of nonsynonymous mutations in NOX1 suggests that NOX1 is not a highly penetrant Mendelian disorder and that other genetic modifiers or environmental factors may contribute to disease pathogenesis. The variant reported in PMID 32064493 is present in 6 hets in gnomad. Sources: Literature |
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| Mendeliome v1.227 | BICD2 | Zornitza Stark Phenotypes for gene: BICD2 were changed from Spinal muscular atrophy, lower extremity-predominant, 2A, autosomal dominant, MIM# 615290; MONDO:0014121; Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, MIM# 618291 to Neurodevelopmental disorder (MONDO#0700092), BICD2-related; Spinal muscular atrophy, lower extremity-predominant, 2A, autosomal dominant, MIM# 615290; MONDO:0014121; Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, MIM# 618291 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.224 | KIF15 | Alison Yeung Phenotypes for gene: KIF15 were changed from ?Braddock-Carey syndrome 2 - MIM#619981 to Braddock-Carey syndrome 2 - MIM#619981 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.223 | KIF15 | Alison Yeung Marked gene: KIF15 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.222 | SARS | Ain Roesley Publications for gene: SARS were set to 28236339; 34570399 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.222 | SARS | Ain Roesley Classified gene: SARS as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.222 | SARS | Ain Roesley Gene: sars has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.222 | SARS | Ain Roesley Phenotypes for gene: SARS were changed from Intellectual disability to neurodevelopmental disorder MONDO#070009, SARS1-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.221 | PSMC1 | Zornitza Stark Marked gene: PSMC1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.221 | PSMC1 | Zornitza Stark Phenotypes for gene: PSMC1 were changed from spastic paraplegia; severe developmental delay; severe intellectual disability; hearing loss; micropenis; undescended testes to 35861243; spastic paraplegia; severe developmental delay; severe intellectual disability; hearing loss; micropenis; undescended testes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.220 | SARS | Ain Roesley reviewed gene: SARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 35790048; Phenotypes: neurodevelopmental disorder MONDO#070009, SARS1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.220 | PSMC1 | Zornitza Stark Mode of pathogenicity for gene: PSMC1 was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.218 | PSMC1 | Zornitza Stark commented on gene: PSMC1: Single family only, homozygous missense variant. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.218 | WARS | Seb Lunke Publications for gene: WARS were set to PMID: 28369220; 31321409; 31069783. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.217 | DOHH | Zornitza Stark Marked gene: DOHH as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.217 | WARS | Seb Lunke Phenotypes for gene: WARS were changed from Neuronopathy, distal hereditary motor, type IX (OMIM:617721); juvenile to adult onset (15-23 years); distal wasting; distal weakness; length-dependent motor axonal degeneration to Neuronopathy, distal hereditary motor, type IX (OMIM:617721); juvenile to adult onset (15-23 years); Neurodevelopmental disorder (MONDO:0700092), WARS-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.215 | WARS | Seb Lunke Mode of inheritance for gene: WARS was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.213 | SLITRK2 | Zornitza Stark Marked gene: SLITRK2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.213 | KIF15 | Krithika Murali reviewed gene: KIF15: Rating: AMBER; Mode of pathogenicity: None; Publications: 28150392; Phenotypes: ?Braddock-Carey syndrome 2 - MIM#619981; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.213 | WARS | Anna Ritchie reviewed gene: WARS: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35815345, PMID: 35790048; Phenotypes: Neurodevelopmental disorder (MONDO:0700092), WARS-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.212 | PSMC1 |
Hazel Phillimore gene: PSMC1 was added gene: PSMC1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PSMC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PSMC1 were set to PMID: 35861243 Phenotypes for gene: PSMC1 were set to spastic paraplegia; severe developmental delay; severe intellectual disability; hearing loss; micropenis; undescended testes Mode of pathogenicity for gene: PSMC1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: PSMC1 was set to AMBER Added comment: Homozygosity mapping on one large consanguineous Bedouin kindred showed three affected children (out of the ten) to be homozygous for NM_002802.3:c.983T>C; p.(Ile328Thr). Drosophila rescue experiments were carried out. Transgenic studies using drosophila with the silenced ortholog Rpt2 gene were rescued by the human wild-type PSMC1. Three of the ten offspring of healthy consanguineous parents of Bedouin Israeli ancestry were affected with a similar phenotype of failure to thrive, developmental delay and severe intellectual disability, spastic tetraplegia with central hypotonia, chorea, as well as hearing loss. None of the three achieved verbal communication or ambulation (sitting / standing) at any age. They had mild dysmorphism of borderline dolichocephaly and microcephaly, prominent bushy eyebrows, flat midface, long nasal bridge and micrognathia. All three had micropenis with undescended testes. One of the affected (as a toddler) underwent thorough endocrinological analysis: testosterone and gonadotropin levels were low. Sources: Literature |
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| Mendeliome v1.212 | KIF15 |
Krithika Murali gene: KIF15 was added gene: KIF15 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KIF15 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KIF15 were set to 28150392 Phenotypes for gene: KIF15 were set to ?Braddock-Carey syndrome 2 - MIM#619981 Review for gene: KIF15 was set to GREEN Added comment: PMID 28150392 Sleiman et al 2017 report one individual with homozygous R501* variant (NMD-predicted) from a consanguineous family. The child had thrombocytopenia, PRS, microcephaly -3SD by age 6, dysmorphic facies, bilateral external auditory canal atresia and deafness, microphthalmia, clinodactyly, short stature. Variant absent from gnomAD. Parents confirmed to be carriers and unaffected siblings were carriers/homozygous wild-type. No other SNVs reported in ClinVar. Variant is absent from gnomAD. Authors note phenotypic similarities with Braddock-Carey syndrome (21q22 contiguous deletion also involving RUNX1). Sources: Literature |
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| Mendeliome v1.212 | BMP3 | Seb Lunke Marked gene: BMP3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.211 | BMP3 |
Seb Lunke gene: BMP3 was added gene: BMP3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: BMP3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: BMP3 were set to 35089417 Phenotypes for gene: BMP3 were set to coloboma, MONDO:0001476; microphthalmia, MONDO:0021129 Review for gene: BMP3 was set to AMBER Added comment: Single missense variant identified segregating with disease following WES screen in a family with coloboma and/or microphthalmia in BMP3. Two additional unrelated patients identified with different missense in BMP3. Pathogenicity however largely on in-silicos, with one of the 3 missense having 29 hets in gnomAD. Additional functional work in bmp3 -/- zebra fish and some supporting evidence but not conclusive Sources: Literature |
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| Mendeliome v1.210 | C18orf32 | Alison Yeung Marked gene: C18orf32 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.209 | ALG5 | Zornitza Stark Marked gene: ALG5 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.208 | ALG5 |
Chern Lim gene: ALG5 was added gene: ALG5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ALG5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ALG5 were set to 35896117 Phenotypes for gene: ALG5 were set to Cystic renal disease MONDO:0002473, ALG5-related Review for gene: ALG5 was set to GREEN gene: ALG5 was marked as current diagnostic Added comment: PMID:35896117: - Five unrelated families, including 23 affected individuals with non-enlarged cystic kidneys and few or no liver cysts, 8 of them reached end-stage kidney disease from 62 to 91 years of age. Variant confirmed in all but one individual. - Various variant types: frameshift, nonsense, two missense, splice. - Functional studies showed haploinsufficiency is the disease mechanism. Sources: Literature |
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| Mendeliome v1.208 | DOHH |
Daniel Flanagan gene: DOHH was added gene: DOHH was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: DOHH was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DOHH were set to PMID: 35858628 Phenotypes for gene: DOHH were set to Neurodevelopmental disorder, DOHH-related (MONDO#0700092) Review for gene: DOHH was set to GREEN Added comment: Bi-allelic missense and truncating DOHH variants segregating with disease in five affected individuals from four unrelated families. Clinical features were developmental delay and/or intellectual disability (5/5), microcephaly (5/5), visual impairment (nystagmus (3/5), strabismus (3/5), and cortical visual impairment (1/5)) and congenital heart malformations (3/5 individuals). Sources: Expert list |
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| Mendeliome v1.208 | SLITRK2 |
Paul De Fazio gene: SLITRK2 was added gene: SLITRK2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SLITRK2 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: SLITRK2 were set to 35840571 Phenotypes for gene: SLITRK2 were set to Neurodevelopmental disorder, SLITRK2-related MONDO:0700092 Review for gene: SLITRK2 was set to GREEN gene: SLITRK2 was marked as current diagnostic Added comment: 6 missense variants and 1 nonsense variant (NOT NMD-predicted, single-exon gene) reported in 7 males and 1 female with neurodevelopmental disorders. Phenotypes included dev delay, mild to severe ID, delayed or absent speech, seizures and brain MRI anomalies (in some patients). The nonsense variant was identified in two affected brothers but not in the mother, suggesting it was de novo in the maternal germline. The variant in the one affected female was de novo. All other variants in hemizygous males were inherited from an unaffected mother. In one case, the variant was also identified in the unaffected grandmother. Functional studies showed some but not all variants displayed impaired membrane transport and impaired excitatory synapse-promoting effects. Conditional knockout mice exhibited impaired long-term memory and abnormal gait. Sources: Literature |
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| Mendeliome v1.208 | RFC1 | Ain Roesley Phenotypes for gene: RFC1 were changed from Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome OMIM 614575 to Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome MIM#614575 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.206 | C18orf32 |
Naomi Baker gene: C18orf32 was added gene: C18orf32 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: C18orf32 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: C18orf32 were set to PMID:35107634 Phenotypes for gene: C18orf32 were set to Neurodevelopmental disorder (MONDO:0700092), C18orf32-related Review for gene: C18orf32 was set to RED Added comment: Two siblings reported as affected, although sequencing only performed in one sibling, with homozygous loss-of-function variant identified. Clinical presentation included developmental delay, recurrent lower respiratory tract infections, sparse rough hair, roving eye movements, hypotonia, bilateral ankle contractures and inverted nipples. Sources: Literature |
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| Mendeliome v1.205 | RFC1 | Ain Roesley reviewed gene: RFC1: Rating: AMBER; Mode of pathogenicity: None; Publications: 35883251; Phenotypes: Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome MIM#614575; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.204 | ADGRL1 | Elena Savva Marked gene: ADGRL1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.204 | ADGRL1 |
Elena Savva gene: ADGRL1 was added gene: ADGRL1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ADGRL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: ADGRL1 were set to PMID: 35907405 Phenotypes for gene: ADGRL1 were set to Neurodevelopmental disorder, ADGRL1-related (MONDO#0700092) Review for gene: ADGRL1 was set to GREEN Added comment: PMID: 35907405 - 9 patients w/ ADHD (3/9), autism (4/9), mild-moderate ID (5/9) and epilepsy (2/9) and facial dysmorphism (7/9). Variants include missense (4) and PTCs (5), and were either de novo (7/9) or inherited from parents with learning difficulties/ID (2/9). Functional studies on both PTCs and missense variants show significant reductions in calcium signalling and surface protein. Het null mouse model shows neurological and developmental abnormalities, with hom null mice non-viable. Sources: Literature |
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| Mendeliome v1.202 | EHHADH |
Zornitza Stark edited their review of gene: EHHADH: Added comment: https://clinmedjournals.org/articles/jcnrc/journal-of-clinical-nephrology-and-renal-care-jcnrc-3-027.pdf Second case report, same variant, de novo. Also, experimental evidence. Assessed as MODERATE by ClinGen.; Changed rating: AMBER |
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| Mendeliome v1.198 | CWH43 | Zornitza Stark Marked gene: CWH43 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.196 | ADGRA3 | Zornitza Stark Marked gene: ADGRA3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.185 | IKZF1 | Zornitza Stark Phenotypes for gene: IKZF1 were changed from Immunodeficiency, common variable, 13 MIM# 616873; recurrent bacterial respiratory infections; Thrombocytopaenia; immunodeficiency; Hypogammaglobulinaemia; decrease B-cells; decrease B-cell differentiation; decrease memory B/T cells; Low Ig; pneumocystis early CID onset to Immunodeficiency, common variable, 13 MIM# 616873; recurrent bacterial respiratory infections; Thrombocytopaenia; immunodeficiency; Hypogammaglobulinaemia; decrease B-cells; decrease B-cell differentiation; decrease memory B/T cells; Low Ig; pneumocystis early CID onset; Immune dysregulation | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.183 | IKZF1 | Zornitza Stark edited their review of gene: IKZF1: Added comment: PMID 35333544: Eight individuals harboring heterozygous IKZF1R183H or IKZF1R183C variants associated with GOF effects reported. The clinical phenotypes and pathophysiology associated with IKZF1R183H/C differ from those of previously reported patients with IKZF1HI, IKZF1DN, and IKZF1DD and should therefore be considered as a novel IKAROS-associated disease entity. This condition is characterized by immune dysregulation manifestations including inflammation, autoimmunity, atopy, and polyclonal PC proliferation.; Changed publications: 21548011, 26981933, 29889099, 31057532, 7923373, 11805317, 35333544; Changed phenotypes: Immunodeficiency, common variable, 13 MIM# 616873, recurrent bacterial respiratory infections, Thrombocytopaenia, immunodeficiency, Hypogammaglobulinaemia, decrease B-cells, decrease B-cell differentiation, decrease memory B/T cells, Low Ig, pneumocystis early CID onset, Immune dysregulation | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.180 | IKZF2 | Zornitza Stark edited their review of gene: IKZF2: Added comment: Iranian male with homozygous missense variant with recurrent infection, hypogammaglobulinaemia. Extends inheritance to AR. Supportive functional data.; Changed publications: 34920454, 34826259; Changed phenotypes: Immunodeficiency, MONDO:0021094, IKZF2-related, Immune dysregulation; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.180 | TMEM63C | Zornitza Stark Marked gene: TMEM63C as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.180 | TMEM63C | Zornitza Stark Phenotypes for gene: TMEM63C were changed from Hereditary spastic paraplegia, MONDO:0019064, TMEM63C-related to Spastic paraplegia 87, autosomal recessive, MIM# 619966 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.179 | TMEM63C | Zornitza Stark reviewed gene: TMEM63C: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 87, autosomal recessive, MIM# 619966; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.179 | EIF2B1 | Elena Savva reviewed gene: EIF2B1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31882561; Phenotypes: Leukoencephalopathy with vanishing white matter MIM#603896, permanent neonatal/early onset diabetes and transient liver dysfunction; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.179 | ARFGEF1 | Zornitza Stark Phenotypes for gene: ARFGEF1 were changed from Intellectual disability; Epilepsy to Developmental delay, impaired speech, and behavioral abnormalities, MIM# 619964 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.178 | ARFGEF1 | Zornitza Stark edited their review of gene: ARFGEF1: Changed phenotypes: Developmental delay, impaired speech, and behavioral abnormalities, MIM# 619964 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.176 | WASL | Zornitza Stark Marked gene: WASL as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.176 | WASL |
Zornitza Stark gene: WASL was added gene: WASL was added to Mendeliome. Sources: Literature Mode of inheritance for gene: WASL was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: WASL were set to 33571872 Phenotypes for gene: WASL were set to Parkinson's disease, MONDO:0005180, WASL-related Review for gene: WASL was set to RED Added comment: Single family reported, where bi-allelic variants segregated with PD in three affected individuals. Sources: Literature |
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| Mendeliome v1.173 | PMM2 |
Zornitza Stark edited their review of gene: PMM2: Added comment: Association with HIPKD: Cabezas et al (2017) reported co-occurrence of hyperinsulinaemic hypoglycaemia and polycystic kidney disease (HIPKD in 17 children from 11 unrelated families. Patients presented with hyperinsulinaemic hypoglycaemia in infancy and enlarged kidneys with multiple kidney cysts. Some progressed to ESKD and some had liver cysts. Whole-genome linkage analysis in 5 informative families identified a single significant locus on chromosome 16p13.2. Sequencing of the coding regions of all linked genes failed to identify biallelic mutations. Instead, they found in all patients a promoter mutation (c.-167G>T) in PMM2, either homozygous or in trans with PMM2 coding mutations. They found deglycosylation in cultured pancreatic β cells altered insulin secretion. In vitro, the PMM2 promoter mutation associated with decreased transcriptional activity in patient kidney cells and impaired binding of the transcription factor ZNF143. In silico analysis suggested an important role of ZNF143 for the formation of a chromatin loop including PMM2. They proposed that the PMM2 promoter mutation alters tissue-specific chromatin loop formation, with consequent organ-specific deficiency of PMM2 leading to the restricted phenotype of HIPKD. None of the patients exhibited the typical clinical or diagnostic features of CDG1A. Serum transferrin glycosylation was normal in 11 patients who had assessment.; Changed publications: 28108845, 28373276, 32595772; Changed phenotypes: Congenital disorder of glycosylation, type Ia (MIM#212065), Hyperinsulinaemic Hypoglycaemia and Polycystic Kidney Disease (HIPKD), MONDO:0020642, PMM2-related |
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| Mendeliome v1.173 | SLCO2A1 | Zornitza Stark Phenotypes for gene: SLCO2A1 were changed from Hypertrophic osteoarthropathy, primary, autosomal dominant, MIM# 167100; Hypertrophic osteoarthropathy, primary, autosomal recessive 2, MIM# 614441 to Hypertrophic osteoarthropathy, primary, autosomal dominant, MIM# 167100; Hypertrophic osteoarthropathy, primary, autosomal recessive 2, MIM# 614441; Inflammatory bowel disease, MONDO:0005265, SLCO2A1-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.171 | SLCO2A1 | Zornitza Stark edited their review of gene: SLCO2A1: Added comment: PMID 29313109: Over 40 Japanese individuals reported with bi-allelic variants in this gene and multiple small intestinal ulcers of nonspecific histology. Some overlap with the hypertrophic osteoarthropathy also associated with bi-allelic variants in this gene. Mild digital clubbing or periostosis was found in 13 patients (28%), with five male patients fulfilling the major diagnostic criteria of PHO.; Changed publications: 23509104, 27134495, 33852188, 22331663, 27134495, 29313109; Changed phenotypes: Hypertrophic osteoarthropathy, primary, autosomal dominant, MIM# 167100, Hypertrophic osteoarthropathy, primary, autosomal recessive 2, MIM# 614441, Inflammatory bowel disease, MONDO:0005265, SLCO2A1-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.169 | C20orf24 | Zornitza Stark Marked gene: C20orf24 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.169 | C20orf24 |
Zornitza Stark gene: C20orf24 was added gene: C20orf24 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: C20orf24 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: C20orf24 were set to 35614220; 24194475 Phenotypes for gene: C20orf24 were set to Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome 2, MIM# 616994 Review for gene: C20orf24 was set to RED Added comment: Bi-allelic LoF variant identified in patient originally reported in PMID 24194475. HGNC approved name is RAB5IF. Sources: Literature |
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| Mendeliome v1.164 | PPP1R13L | Zornitza Stark Phenotypes for gene: PPP1R13L were changed from Dilated cardiomyopathy, onset in infancy to Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042 - PPP1R13L-related; Dilated cardiomyopathy, onset in infancy | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.163 | CHD5 | Elena Savva Phenotypes for gene: CHD5 were changed from Intellectual disability; Epilepsy to Parenti-Mignot neurodevelopmental syndrome MIM#619873 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.162 | CHD5 | Elena Savva reviewed gene: CHD5: Rating: GREEN; Mode of pathogenicity: None; Publications: 33944996; Phenotypes: Parenti-Mignot neurodevelopmental syndrome MIM#619873; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.162 | GINS3 | Zornitza Stark Marked gene: GINS3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.161 | GINS3 |
Zornitza Stark gene: GINS3 was added gene: GINS3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GINS3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GINS3 were set to 35603789 Phenotypes for gene: GINS3 were set to Meier-Gorlin syndrome, MONDO:0016817, GINS3-related Review for gene: GINS3 was set to GREEN Added comment: 7 individuals from 5 families reported, presenting with prenatal and postnatal growth deficiency as well as other features. Three unique missense variants identified, two affecting p.Asp24. These variants are thought to be hypomorphic. Supportive mouse model. Sources: Literature |
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| Mendeliome v1.159 | C9orf84 | Zornitza Stark Marked gene: C9orf84 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.158 | C9orf84 |
Zornitza Stark changed review comment from: 8 families reported with bi-allelic variants in this gene and spermatogenic failure. Sources: Literature; to: 8 families reported with bi-allelic variants in this gene and spermatogenic failure. A male germ cell-specific Shoc1 knockout mouse model recapitulates the phenotype (germline knockout: early lethality). HGNC approved name is SHOC1. Sources: Literature |
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| Mendeliome v1.158 | C9orf84 |
Zornitza Stark gene: C9orf84 was added gene: C9orf84 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: C9orf84 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: C9orf84 were set to 32741963; 32900840; 35485979 Phenotypes for gene: C9orf84 were set to Spermatogenic failure 75, MIM# 619949 Review for gene: C9orf84 was set to GREEN Added comment: 8 families reported with bi-allelic variants in this gene and spermatogenic failure. Sources: Literature |
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| Mendeliome v1.155 | KMT2B | Zornitza Stark edited their review of gene: KMT2B: Added comment: Nine individuals reported in PMID 33150406 with heterozygous variants in this gene and intellectual disability, speech delay, microcephaly, growth delay, feeding problems, and dysmorphic features, including epicanthic folds, posteriorly rotated ears, syndactyly/clinodactyly of toes, and fifth finger clinodactyly, normal MRIs and NO dystonia.; Changed publications: 27839873, 27992417, 33150406; Changed phenotypes: Dystonia 28, childhood-onset 617284, MONDO:0015004, Intellectual developmental disorder, autosomal dominant 68, MIM# 619934 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.155 | LMAN2L | Zornitza Stark Phenotypes for gene: LMAN2L were changed from Mental retardation, autosomal recessive, 52; OMIM #616887 to Mental retardation, autosomal recessive, 52 OMIM #616887; Intellectual developmental disorder, autosomal dominant 69 , MIM# 617863 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.154 | LMAN2L | Zornitza Stark edited their review of gene: LMAN2L: Changed phenotypes: Mental retardation, autosomal recessive, 52 OMIM #616887, Intellectual developmental disorder, autosomal dominant 69 , MIM# 617863 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.154 | CDH2 | Zornitza Stark edited their review of gene: CDH2: Changed phenotypes: Intellectual disability, corpus callosum abnormalities, congenital abnormalities, Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, MIM# 618929, Attention deficit-hyperactivity disorder 8 , MIM# 619957 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.154 | CDH2 | Zornitza Stark Phenotypes for gene: CDH2 were changed from Intellectual disability; corpus callosum abnormalities; congenital abnormalities; Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, MIM# 618929 to Intellectual disability; corpus callosum abnormalities; congenital abnormalities; Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, MIM# 618929; Attention deficit-hyperactivity disorder 8 , MIM# 619957 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.152 | CDH2 | Zornitza Stark edited their review of gene: CDH2: Added comment: PMID 34702855: three sibs with homozygous missense and strikingly severe ADHD. Mouse model of same variant recapitulated the phenotype. AMBER for bi-allelic association (segregation and functional data).; Changed publications: 31585109, 34702855; Changed phenotypes: Intellectual disability, corpus callosum abnormalities, congenital abnormalities, Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, MIM# 618929:Attention deficit-hyperactivity disorder 8 , MIM# 619957; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.151 | KITLG | Zornitza Stark Phenotypes for gene: KITLG were changed from Deafness, autosomal dominant 69, unilateral or asymmetric, MIM# 616697 to Deafness, autosomal dominant 69, unilateral or asymmetric, MIM# 616697; deafness; heterochromia iridis; hypopigmentation of the skin; hyperpigmentation of the skin; Waardenburg syndrome,MONDO:0018094, KITLG-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.148 | CLDN5 | Zornitza Stark Marked gene: CLDN5 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.147 | CLDN5 |
Zornitza Stark gene: CLDN5 was added gene: CLDN5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CLDN5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CLDN5 were set to 35714222 Phenotypes for gene: CLDN5 were set to alternating hemiplegia, MONDO:0016210, CLDN5-related Mode of pathogenicity for gene: CLDN5 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: CLDN5 was set to AMBER Added comment: PMID: 35714222; Hashimoto, Y. et al. (2022): Two unrelated cases (early-onset) with alternating hemiplegia with microcephaly were shown to have the same de novo variant, NM_001363066.2:c.178G>A, p.(Gly60Arg). One with Jewish / Tunisian ancestry: Onset was at 8 months, three episodes of febrile tonic-clonic 1 seizures of the four limbs, with eye rolling, loss of consciousness, transient left and right post-2 ictal hemiparesis and vomiting. The other with Asian / European ancestry: Onset was at 30 months with three iterative episodes of febrile and non-febrile hemiplegia and loss of 18 consciousness. The recurrent episodes alternatively involved the left-and 19 right-hand side, then generalised and were followed by post ictal hemiparesis. CT scans of both showed brain calcifications and aberrant blood flow patterns. Transfected cell lines with this variant, c178G>A, showed higher chloride ion permeability and lower sodium ion permeability when compared to wildtype. Sources: Literature |
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| Mendeliome v1.143 | HCK | Zornitza Stark Marked gene: HCK as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.140 | TBX21 |
Zornitza Stark changed review comment from: Single individual reported with disseminated disease following BCG vaccination, who subsequently developed severe persistent reactive airway disease and eosinophilia that responded to steroid treatment. Homozygous variant identified. Association with asthma and nasal polyps pertains to promoter SNPs.; to: Single individual reported with disseminated disease following BCG vaccination, who subsequently developed severe persistent reactive airway disease and eosinophilia that responded to steroid treatment. Homozygous variant identified. Functional data. Association with asthma and nasal polyps pertains to promoter SNPs. |
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| Mendeliome v1.138 | KITLG | Dean Phelan reviewed gene: KITLG: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 35543077, 28504826, 19375057, 21368769; Phenotypes: deafness, heterochromia iridis, hypopigmentation of the skin, hyperpigmentation of the skin, Waardenburg syndrome,MONDO:0018094, KITLG-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.138 | NFATC2 | Zornitza Stark Marked gene: NFATC2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.137 | NFATC2 |
Paul De Fazio gene: NFATC2 was added gene: NFATC2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NFATC2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NFATC2 were set to 35789258 Phenotypes for gene: NFATC2 were set to Skeletal system disorder MONDO:0005172 Review for gene: NFATC2 was set to RED gene: NFATC2 was marked as current diagnostic Added comment: Patient born to consanguineous parents homozygous for a frameshift variant. No other (unaffected) members of the family were homozygous. Family history of recurrent childhood deaths. After a healthy birth the patient developed painless decreased range of motion at 1.5yrs leading to difficulty with ambulation at 3yrs. Formal orthopedic assessment at age 15 years demonstrated a neurodevelopmentally normal young man with marked bilateral fixed flexion contractures of knees, hips, and ankles. The main musculoskeletal findings were painless contractures of the large and small joints of the upper and lower limbs, osteochondromas, and osteopenia. Patient was diagnosed with B-cell lymphoma at age 18. Patient CD8+ T-cells show impaired polyfunctionality, and the patient had an accumulation of non-functional memory CD4+ T-cells. TFH cell function was also impaired. Sources: Literature |
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| Mendeliome v1.137 | PIK3C2B | Zornitza Stark Marked gene: PIK3C2B as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.136 | CCDC155 | Zornitza Stark Marked gene: CCDC155 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.136 | CCDC155 | Zornitza Stark Phenotypes for gene: CCDC155 were changed from Non-obstructive azoospermia; Premature ovarian insufficiency to Non-obstructive azoospermia; Premature ovarian insufficiency; Infertility disorder, MONDO:0005047, CCDC155-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.134 | PIK3C2B |
Krithika Murali gene: PIK3C2B was added gene: PIK3C2B was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PIK3C2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PIK3C2B were set to PMID:35786744 Phenotypes for gene: PIK3C2B were set to familial partial epilepsy - MONDO#0017704 Review for gene: PIK3C2B was set to AMBER Added comment: No OMIM gene disease association. Gozzelino et al.(2022) Brain - report enrichment of ultra-rare PIK3C2B variants in focal epilepsy cohorts, including one variant shown to be de novo (G1294Q). Segregation data not provided for all cases. The p.G1345S variant was inherited from an affected father. The p.K584* variant was inherited from an unaffected father suggesting incomplete penetrance. Functional studies supported a LoF mechanism and mouse model studies suggestive of mTORC1 pathway hyperactivation. Sources: Literature |
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| Mendeliome v1.134 | CCDC155 |
Melanie Marty gene: CCDC155 was added gene: CCDC155 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CCDC155 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CCDC155 were set to 35674372; 35708642; 29790874; 35587281 Phenotypes for gene: CCDC155 were set to Non-obstructive azoospermia; Premature ovarian insufficiency Review for gene: CCDC155 was set to GREEN Added comment: Current HGNC name is KASH5 Summary: 4 families reported with non-obstructive azoospermia or premature ovarian insufficiency. Functional studies have been performed and mouse models recapitulate the phenotype. PMID: 35674372 CNV and frameshift variants in KASH5 were identified in a non-obstructive azoospermia affected patient and in his infertile sister by whole-exome sequencing and CNV array. Kash5 knockout mouse displayed similar phenotypes, including a meiotic arrest at a zygotene-like stage and impaired pairing and synapsis. PMID: 35708642 Hom splice identified in KASH5 in 2 sisters with premature ovarian insufficiency. In vitro studies found the variant disturbed the nuclear membrane localization of KASH5 and its binding with SUN1. Moreover, the Kash5 C-terminal deleted mice revealed defective meiotic homolog pairing and accelerated depletion of oocytes. PMID: 29790874 2 brothers with non-obstructive azoospermia with hom missense in CCDC155 35587281 2 siblings with hom missense in CCDC155 non-obstructive azoospermia and premature ovarian insufficiency. Sources: Literature |
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| Mendeliome v1.134 | SLC30A7 | Alison Yeung Marked gene: SLC30A7 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.130 | SLC30A7 |
Naomi Baker gene: SLC30A7 was added gene: SLC30A7 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SLC30A7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SLC30A7 were set to PMID: 35751429 Phenotypes for gene: SLC30A7 were set to Joubert syndrome (MONDO:0018772), SLC30A7-related Review for gene: SLC30A7 was set to AMBER Added comment: PMID: 35751429: Two individuals reported with de novo variants, one missense and one delins resulting in missense. The first individual is a female with history of unilateral postaxial polydactyly, classic molar tooth sign on MRI, macrocephaly, ataxia, ocular motor apraxia, neurodevelopmental delay, and precocious puberty. The second individual had bilateral postaxial polydactyly, molar tooth sign, macrocephaly, developmental delay, and an extra oral frenulum. No functional studies reported. Sources: Literature |
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| Mendeliome v1.130 | CHMP3 | Zornitza Stark Marked gene: CHMP3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.129 | PABPC1 | Elena Savva Marked gene: PABPC1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.128 | PABPC1 |
Elena Savva gene: PABPC1 was added gene: PABPC1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PABPC1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: PABPC1 were set to PMID: 35511136 Phenotypes for gene: PABPC1 were set to Neurodevelopmental disorder, PABPC1-related (MONDO#0700092) Review for gene: PABPC1 was set to GREEN Added comment: PMID: 35511136 - 4 probands with an overlapping phenotype of DD, expressive speech delay, and autistic features and heterozygous de novo variants that cluster in the PABP domain of PABPC1. Electroporation of mouse embryo brains showed that Pabpc1 knockdown decreases the proliferation of neural progenitor cells. Wild-type Pabpc1 could rescue this disturbance, whereas 3 of the 4 variants did not. Sources: Literature |
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| Mendeliome v1.127 | WNK3 | Zornitza Stark Marked gene: WNK3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.126 | CHMP3 |
Chern Lim gene: CHMP3 was added gene: CHMP3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CHMP3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CHMP3 were set to PMID: 35710109 Phenotypes for gene: CHMP3 were set to Hereditary spastic paraplegia (MONDO:0019064), CHMP3-related Review for gene: CHMP3 was set to AMBER gene: CHMP3 was marked as current diagnostic Added comment: PMID: 35710109 - Single large family with consanguinity, homozygous missense variant in 5 affected individuals with intellectual and progressive motor disabilities, seizures and spastic quadriplegia. - Functional studies showed reduced CHMP3 protein in patient's fibroblasts, lenti-rescue study showed improved cellular phenotypes associated with impaired autophagy. Sources: Literature |
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| Mendeliome v1.126 | WNK3 |
Lucy Spencer gene: WNK3 was added gene: WNK3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: WNK3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: WNK3 were set to 35678782 Phenotypes for gene: WNK3 were set to Neurodevelopmental disorder, WNK3-related (MONDO#0700092) Added comment: 6 maternally inherited hemizygous variants, 3 missense, 2 canonical splice, and a nonsense. Seen in 14 individuals from 6 families, all 14 are male who inherited hemizygous variants from their unaffected heterozygous mothers. The variants cosegregated with disease in 3 families with multiple affected individuals. All 14 patients have ID, 11 have speech delay, 10 have facial abnormalities, 5 have seizures, 6 with microcephaly and 7 with anomalies in brain imaging. Sources: Literature |
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| Mendeliome v1.126 | WNT7B | Zornitza Stark Marked gene: WNT7B as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.125 | WNT7B |
Zornitza Stark gene: WNT7B was added gene: WNT7B was added to Mendeliome. Sources: Literature Mode of inheritance for gene: WNT7B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: WNT7B were set to 35790350 Phenotypes for gene: WNT7B were set to Pulmonary hypoplasia, Diaphragmatic anomalies, Anophthalmia/microphthalmia and Cardiac defects syndrome; Multiple congenital anomalies/dysmorphic features syndrome MONDO:0043005, WNT7B-related Review for gene: WNT7B was set to GREEN Added comment: Three families reported with fetuses with multiple congenital anomalies and bi-allelic LoF variants. Two of the families had at the same variant. Supportive zebrafish model. Sources: Literature |
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| Mendeliome v1.123 | TMEM63C |
Elena Savva gene: TMEM63C was added gene: TMEM63C was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TMEM63C was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TMEM63C were set to PMID: 35718349 Phenotypes for gene: TMEM63C were set to Hereditary spastic paraplegia, MONDO:0019064, TMEM63C-related Review for gene: TMEM63C was set to GREEN Added comment: PMID: 35718349 - Four NMD PTCs observed in at least 3 unrelated patients. Two segregated strongly in highly consanguineous families. Common clinical details include mild ID, spastic paraplegia, hypereflexia, spasticity, delayed motor development. Single patient was microcephalic Sources: Literature |
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| Mendeliome v1.122 | MAL | Zornitza Stark Marked gene: MAL as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.121 | MAL |
Zornitza Stark gene: MAL was added gene: MAL was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MAL was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MAL were set to 35217805 Phenotypes for gene: MAL were set to Leukodystrophy MONDO:0019046, MAL-related Review for gene: MAL was set to AMBER Added comment: Single family with two affected siblings reported, with homozygous missense variant, some functional data. Sources: Literature |
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| Mendeliome v1.119 | RELN | Zornitza Stark edited their review of gene: RELN: Added comment: PMID 35769015: 13 individuals from seven families with monoallelic (heterozygous) variants of RELN and frontotemporal or temporal-predominant lissencephaly variant. Some individuals with monoallelic variants had moderate frontotemporal lissencephaly, but with normal cerebellar structure and intellectual disability with severe behavioural dysfunction. However, one adult had abnormal MRI with normal intelligence and neurological profile. Additional 7 individuals from 4 families with bi-allelic variants.; Changed publications: 35769015 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.119 | TAF8 |
Zornitza Stark changed review comment from: 8 individuals reported from 5 families, four of which were consanguineous. Clinical features included severe psychomotor retardation with almost absent development, feeding problems, microcephaly, growth retardation, spasticity and epilepsy. Six had the c.781-1G > A variant in homozygous state. This is likely to be a founder variant. One family with different compound heterozygous variants. Sources: Literature; to: 8 individuals reported from 5 families, four of which were consanguineous. Clinical features included severe psychomotor retardation with almost absent development, feeding problems, microcephaly, growth retardation, spasticity and epilepsy. Six had the c.781-1G > A variant in homozygous state. Unclear if this is a founder variant, families of different ethnicities. One family with different compound heterozygous variants. Sources: Literature |
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| Mendeliome v1.119 | TAF8 | Zornitza Stark Marked gene: TAF8 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.118 | TAF8 |
Zornitza Stark gene: TAF8 was added gene: TAF8 was added to Mendeliome. Sources: Literature founder tags were added to gene: TAF8. Mode of inheritance for gene: TAF8 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TAF8 were set to 29648665; 35759269 Phenotypes for gene: TAF8 were set to Neurodevelopmental disorder, MONDO:0700092, TAF8-related Review for gene: TAF8 was set to GREEN Added comment: 8 individuals reported from 5 families, four of which were consanguineous. Clinical features included severe psychomotor retardation with almost absent development, feeding problems, microcephaly, growth retardation, spasticity and epilepsy. Six had the c.781-1G > A variant in homozygous state. This is likely to be a founder variant. One family with different compound heterozygous variants. Sources: Literature |
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| Mendeliome v1.117 | PNPT1 | Zornitza Stark Phenotypes for gene: PNPT1 were changed from Combined oxidative phosphorylation deficiency 13 (MIM#614932); Deafness, autosomal recessive 70 (MIM#614934) to Combined oxidative phosphorylation deficiency 13 (MIM#614932); Deafness, autosomal recessive 70 (MIM#614934); Spinocerebellar ataxia 25, MIM# 608703 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.114 | PNPT1 | Zornitza Stark edited their review of gene: PNPT1: Added comment: Three families reported with heterozygous variants and SCA25. Incomplete penetrance in one of the families. In the third family, the variant was inherited from an asymptomatic 80+ year old. Note bi-allelic variants in this gene cause a mitochondrial disorder. Exact mechanism through which mono-allelic variants cause SCA25 not elucidated: authors speculate abnormal accumulation of mitochondrial RNA with subsequent leakage into the cytosol that may trigger a type 1 interferon response leading to neuroinflammation with neuronal dysfunction or neuronal loss.; Changed rating: AMBER; Changed publications: 35411967; Changed phenotypes: Spinocerebellar ataxia 25, MIM# 608703; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.114 | TTC25 | Arina Puzriakova reviewed gene: TTC25: Rating: GREEN; Mode of pathogenicity: None; Publications: 27486780, 31765523, 33715250, 33746037, 34215651; Phenotypes: Ciliary dyskinesia, primary, 35, OMIM:617092; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.113 | RHOG | Zornitza Stark Marked gene: RHOG as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.111 | TNFSF13 | Zornitza Stark Marked gene: TNFSF13 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.111 | TNFSF13 |
Zornitza Stark gene: TNFSF13 was added gene: TNFSF13 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TNFSF13 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TNFSF13 were set to 32298700 Phenotypes for gene: TNFSF13 were set to Hypogammaglobulinaemia, MONDO:0015977, TNSF13-related Review for gene: TNFSF13 was set to RED Added comment: Single individual, consanguineous parents. Sources: Literature |
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| Mendeliome v1.110 | POU2AF1 | Zornitza Stark Marked gene: POU2AF1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.110 | POU2AF1 |
Zornitza Stark gene: POU2AF1 was added gene: POU2AF1 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: POU2AF1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: POU2AF1 were set to 33571536 Phenotypes for gene: POU2AF1 were set to Agammaglobulinaemia, MONDO:0015977, POU2AF1-related Review for gene: POU2AF1 was set to RED Added comment: Single individual from consanguineous parents lacking immunoglobulins despite normal total B-cell numbers. Sources: Expert Review |
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| Mendeliome v1.109 | CD28 | Zornitza Stark Marked gene: CD28 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.108 | CD28 |
Zornitza Stark changed review comment from: Rare homozygous CD28 variant segregates with severe verrucosis in three relatives and supportive functional data. Sources: Expert Review; to: Rare homozygous CD28 variant segregates with severe verrucosis in three relatives and supportive functional data. CD28-deficient mice are susceptible to cutaneous infections with the mouse papillomavirus MmuPV1. Sources: Expert Review |
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| Mendeliome v1.108 | CD28 |
Zornitza Stark gene: CD28 was added gene: CD28 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: CD28 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CD28 were set to 34214472 Phenotypes for gene: CD28 were set to Hereditary predisposition to infections, MONDO:0015979, CD28-related; isolated susceptibility to cutaneous α- and γ-HPVs Review for gene: CD28 was set to RED Added comment: Rare homozygous CD28 variant segregates with severe verrucosis in three relatives and supportive functional data. Sources: Expert Review |
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| Mendeliome v1.106 | IKZF3 | Zornitza Stark edited their review of gene: IKZF3: Added comment: Additional multigenerational family where novel missense variant segregated with disease in 4 individuals.; Changed rating: GREEN; Changed publications: 34155405, 34694366 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.106 | COPG1 | Zornitza Stark Marked gene: COPG1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.105 | COPG1 |
Zornitza Stark gene: COPG1 was added gene: COPG1 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: COPG1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: COPG1 were set to 33529166 Phenotypes for gene: COPG1 were set to Combined immunodeficiency MONDO:0015131, COPG1-related Review for gene: COPG1 was set to RED Added comment: Five Omani siblings, born to consanguineous parents, homozygous missense. Homozygous Copg1K652E mice had increased ER stress in activated T and B cells, poor antibody responses, and normal numbers of T cells that proliferated normally, but underwent increased apoptosis upon activation. Exposure of the mutants to pet store mice caused weight loss, lymphopenia, and defective T cell proliferation that recapitulated the findings in the patients. The ER stress-relieving agent tauroursodeoxycholic acid corrected the immune defects of the mutants and reversed the phenotype they acquired following exposure to pet store mice. Sources: Expert Review |
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| Mendeliome v1.104 | TSPAN7 |
Zornitza Stark edited their review of gene: TSPAN7: Added comment: Two families reported with LoF variants and ID: Abidi FE et al. 2002 Jun (PMID:12070254); Zemni R et al. 2000 Feb (PMID:10655063) Assessed as MODERATE by ClinGen.; Changed rating: AMBER; Changed publications: 12070254, 10655063 |
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| Mendeliome v1.104 | IFNAR2 | Zornitza Stark Publications for gene: IFNAR2 were set to 26424569 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.103 | IFNAR2 | Zornitza Stark Classified gene: IFNAR2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.103 | IFNAR2 | Zornitza Stark Gene: ifnar2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.102 | IFNAR2 | Zornitza Stark edited their review of gene: IFNAR2: Added comment: Five children from Greenland, Canada, and Alaska presenting with viral diseases, including life-threatening COVID-19 or influenza, in addition to meningoencephalitis and/or hemophagocytic lymphohistiocytosis following live-attenuated viral vaccination; Changed rating: GREEN; Changed publications: 26424569, 35442417 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.102 | IFNAR1 | Zornitza Stark Phenotypes for gene: IFNAR1 were changed from Severe disease caused by Yellow Fever vaccine and Measles vaccine to Immunodeficiency 106, susceptibility to viral infections, MIM# 619935; Severe disease caused by Yellow Fever vaccine and Measles vaccine | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.101 | IFNAR1 | Zornitza Stark Publications for gene: IFNAR1 were set to 31270247 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.100 | IFNAR1 | Zornitza Stark Classified gene: IFNAR1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.100 | IFNAR1 | Zornitza Stark Gene: ifnar1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.99 | IFNAR1 | Zornitza Stark edited their review of gene: IFNAR1: Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.99 | IFNAR1 | Zornitza Stark edited their review of gene: IFNAR1: Added comment: Seven children from five unrelated kindreds; Changed publications: 31270247, 35442418; Changed phenotypes: Immunodeficiency 106, susceptibility to viral infections, MIM# 619935, Severe disease caused by Yellow Fever vaccine and Measles vaccine | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.96 | NEK8 | Zornitza Stark edited their review of gene: NEK8: Added comment: ESHG 2022: 12 families with paediatric renal cystic disease (enlarged kidneys, kidney cysts, ESKF <20yrs) -3 recurrent HTZ variants in NEK8 kinase domain (Arg45Trp, Ile150Met, Lys157Gln) -suspected dominant negative effect -patient fibroblasts show normal ciliogenesis and normal localisation and expression of NEK8 (Note carriers of AR-NEK8 disease do not show renal manifestations, as variants are LOF); Changed phenotypes: Renal-hepatic-pancreatic dysplasia 2, MIM# 615415, MONDO:0014174, Familial renal cystic disease MONDO:0019741, NEK8-related, dominant; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.89 | DDR2 |
Zornitza Stark changed review comment from: Bi-allelic variants in this gene are associated with a severe perinatal skeletal dysplasia. Mono-allelic variants cause Warburg-Cinotti syndrome, which is characterized by progressive corneal neovascularization, keloid formation, chronic skin ulcers, wasting of subcutaneous tissue, flexion contractures of the fingers, and acroosteolysis. Four unrelated families reported with missense variants, which were activating.; to: Bi-allelic variants in this gene are associated with a severe perinatal skeletal dysplasia. LoF. Mono-allelic variants cause Warburg-Cinotti syndrome, which is characterized by progressive corneal neovascularization, keloid formation, chronic skin ulcers, wasting of subcutaneous tissue, flexion contractures of the fingers, and acroosteolysis. Four unrelated families reported with missense variants, which were activating. GoF. |
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| Mendeliome v1.85 | EPHA2 | Elena Savva reviewed gene: EPHA2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34638995, 19005574, 19649315, 19306328, 33671840; Phenotypes: Early-Onset Cataract, cataract 6 multiple types MONDO:0007288; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.82 | GRIA1 | Zornitza Stark edited their review of gene: GRIA1: Added comment: Single individual reported with bi-allelic LoF variant. RED/AMBER for bi-allelic variants.; Changed publications: 28628100, 23033978, 26350204, 24896178, 35675825; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.81 | MSH5 | Zornitza Stark Phenotypes for gene: MSH5 were changed from Premature ovarian failure 13, MIM#617442; Premature ovarian failure 13, MIM#617442 to Spermatogenic failure 74, MIM# 619937; Premature ovarian failure 13, MIM#617442 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.80 | MSH5 | Zornitza Stark Phenotypes for gene: MSH5 were changed from Premature ovarian failure 13 MIM#617442 to Premature ovarian failure 13, MIM#617442; Premature ovarian failure 13, MIM#617442 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.79 | GCH1 | Zornitza Stark Phenotypes for gene: GCH1 were changed from Hyperphenylalaninemia, BH4-deficient, B, MIM# 233910; Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, MIM# 128230 to Hyperphenylalaninemia, BH4-deficient, B, MIM# 233910; Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, MIM# 128230; Hereditary spastic paraplegia MONDO:0019064, GCH1-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.77 | GCH1 | Zornitza Stark reviewed gene: GCH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21935284, 24509643, 33713342; Phenotypes: Hereditary spastic paraplegia MONDO:0019064, GCH1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.75 | KCNA5 | Zornitza Stark edited their review of gene: KCNA5: Added comment: Multiple families reported. At least one with LoF variant, rest missense. The missense variants are present in the population, ranging from 2 to 40 individuals in gnomad, which raises doubt about their pathogenicity.; Changed rating: AMBER | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.74 | GATA1 | Zornitza Stark edited their review of gene: GATA1: Added comment: Variants in GATA1 are associated with a number of haematological disorders, which probably represent a spectrum rather than distinct entities.; Changed phenotypes: Thrombocytopaenia, X-linked, with or without dyserythropoietic anaemia, MIM# 300367, Haemolytic anaemia due to elevated adenosine deaminase, MIM# 301083, Anemia, X-linked, with/without neutropenia and/or platelet abnormalities, MIM# 300835 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.74 | NR4A2 | Zornitza Stark Phenotypes for gene: NR4A2 were changed from Intellectual disability; epilepsy to Intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism, MIM# 619911 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.73 | NR4A2 | Zornitza Stark edited their review of gene: NR4A2: Changed phenotypes: Intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism, MIM# 619911 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.69 | KCNJ1 | Zornitza Stark reviewed gene: KCNJ1: Rating: GREEN; Mode of pathogenicity: None; Publications: 8841184, 19096086, 7635463, 12086641, 9580661, 12122007; Phenotypes: Bartter syndrome, type 2, MIM#241200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.68 | PRDM13 | Zornitza Stark Phenotypes for gene: PRDM13 were changed from Chorioretinal atrophy, progressive bifocal, MIM# 600790; Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism, MIM# 619761 to Chorioretinal atrophy, progressive bifocal, MIM# 600790; Pontocerebellar hypoplasia, type 17, MIM# 619909; Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism, MIM# 61976 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.66 | PRDM13 | Zornitza Stark edited their review of gene: PRDM13: Added comment: Note only single family reported with Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism, MIM# 61976 -- this likely lies on the same spectrum as Pontocerebellar hypoplasia, type 17, MIM# 619909 rather than being a distinct disorder.; Changed publications: 30710461, 34730112; Changed phenotypes: Retinal dystrophy, Chorioretinal atrophy, progressive bifocal, MIM# 600790, Pontocerebellar hypoplasia, type 17, MIM# 619909, Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism, MIM# 61976; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.65 | RBFOX2 |
Chern Lim changed review comment from: - PMID: 26785492: Analysed CHD (1213 congenital heart disease trios) and control (autism spectrum disorder) trios for de novo mutations. Found RBFOX2 gene had significantly more damaging de novo variants than expected: 3 de novo LoF variants (eg. nonsense, frameshift, or canonical splice disruptions). All 3 probands have hypoplastic left heart syndrome (HLHS). No further patient-specific clinical or variant info were available. Same cohort later included in PMID: 32368696, listed 4 de novo variants in this gene, in patients with left ventricular outflow tract obstruction (LVOTO) or conotruncal defects (CTDs). - PMID: 27670201: RNA expression study showed the silenced allele harbours a nonsense RBFOX2 variant (Arg287*), CHD patient heart tissue sample, same patient published in PMID: 26785492. - PMID: 27485310: Functional studies using heart tissue sample from HLHS patient with NM_001031695.2:c.859C>T p.(Arg287*) showed subcellular mislocalisation, impacting its nuclear function in RNA splicing. - PMID: 25205790: De novo 111.3kb del chr22:36038076-36149338 (hg19) which includes APOL5,APOL6,RBFOX2, in a patient with HLHS. - PMID: 35137168: Rbfox2 conditional knockout mouse model recapitulated several molecular and phenotypic features of HLHS.; to: - PMID: 26785492: Analysed CHD (1213 congenital heart disease trios) and control (autism spectrum disorder) trios for de novo mutations. Found RBFOX2 gene had significantly more damaging de novo variants than expected: 3 de novo LoF variants (1x nonsense, 1x frameshift, 1x canonical splice variants). All 3 probands have hypoplastic left heart syndrome (HLHS) and no extra-cardiac features. Same cohort later included in PMID: 32368696, listed one additional de novo variant in this gene (missense variant) in a patient with conotruncal defects (CTDs). - PMID: 27670201: RNA expression study showed the silenced allele harbours a nonsense RBFOX2 variant (Arg287*), CHD patient heart tissue sample, same patient published in PMID: 26785492. - PMID: 27485310: Functional studies using heart tissue sample from HLHS patient with NM_001031695.2:c.859C>T p.(Arg287*) showed subcellular mislocalisation, impacting its nuclear function in RNA splicing. - PMID: 25205790: De novo 111.3kb del chr22:36038076-36149338 (hg19) which includes APOL5,APOL6,RBFOX2, in a patient with HLHS. - PMID: 35137168: Rbfox2 conditional knockout mouse model recapitulated several molecular and phenotypic features of HLHS. |
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| Mendeliome v1.52 | RRM1 | Seb Lunke Marked gene: RRM1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.52 | BUB1 | Zornitza Stark Marked gene: BUB1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.52 | RRM1 | Seb Lunke Added comment: Comment on list classification: 3 families but only 2 Hom variants, not convinced they are definitely unrelated. 4th probed inconclusive. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.50 | PAN2 | Zornitza Stark Marked gene: PAN2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.49 | RRM1 |
Daniel Flanagan gene: RRM1 was added gene: RRM1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: RRM1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RRM1 were set to 35617047 Phenotypes for gene: RRM1 were set to Multiple mitochondrial DNA deletion syndrome (MONDO:0016797) Review for gene: RRM1 was set to GREEN Added comment: Homozygous missense were identified in 4 four probands (p.Arg381Cys or p.Arg381His) from three families, who presented with ptosis and ophthalmoplegia, plus other manifestations and multiple mtDNA deletions in muscle. Heterozygous carriers were unaffected. An additional proband was heterozygous for a different RRM1 missense (p.Asn427Lys), another variant not identified. Sources: Expert list |
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| Mendeliome v1.49 | LMOD2 | Seb Lunke Marked gene: LMOD2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.49 | LMOD2 | Seb Lunke Phenotypes for gene: LMOD2 were changed from Dilated cardiomyopathy to Dilated cardiomyopathy, MONDO:0005021 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.48 | ATOH1 | Zornitza Stark Marked gene: ATOH1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.47 | PAN2 |
Naomi Baker gene: PAN2 was added gene: PAN2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PAN2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PAN2 were set to PMID:35304602; 29620724 Phenotypes for gene: PAN2 were set to Neurodevelopmental disorder, MONDO:0700092, PAN2-related Review for gene: PAN2 was set to GREEN Added comment: PMID:35304602 reports five individuals from 3 families with biallelic (homozygous) loss-of-function variants. Clinical presentation incudes mild-moderate intellectual disability, hypotonia, sensorineural hearing loss, EEG abnormalities, congenital heart defects (tetralogy of Fallot, septal defects, dilated aortic root), urinary tract malformations, ophthalmological anomalies, short stature with other skeletal anomalies, and craniofacial features including flat occiput, ptosis, long philtrum, and short neck. PMID:29620724 reports one individual with biallelic (homozygous) loss-of-function variant who presented with global developmental delay, mild hypotonia, craniosynostosis, severe early-onset scoliosis, imperforate anus, and double urinary collecting system. Sources: Literature |
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| Mendeliome v1.47 | ATOH1 | Zornitza Stark Phenotypes for gene: ATOH1 were changed from Pontocerebellar hypoplasia; developmental delay; hearing loss to Pontocerebellar hypoplasia MONDO:0020135, ATOH1-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.46 | PTPN13 | Ain Roesley Marked gene: PTPN13 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.45 | PTPN13 |
Ain Roesley gene: PTPN13 was added gene: PTPN13 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PTPN13 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PTPN13 were set to 35643866 Phenotypes for gene: PTPN13 were set to bone marrow failure syndrome MONDO#0000159, PTPN13-related Review for gene: PTPN13 was set to AMBER gene: PTPN13 was marked as current diagnostic Added comment: 2 families Family A: 3 affecteds only 2 sequenced. Hom for a missense 3/3 Anaemia, 1x thrombocytopaenia, 1x severe neutropaenia, bone marrow with pure red cell aplasia noted that the sibling who wasn't sequenced had normal bone marrow morphology Family B: Chet for a missense and inframe del of 1 amino acid Persistent hypogammaglobulinemia after transplant (at least 14 months after) with normal blood counts and Pre-B ALL with MLL rearrangement In vitro studies of individual variants were LoF, including defective erythroid and megakaryocytic differentiation, consistent with anaemia and thrombocytopaenia reported in family A Sources: Literature |
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| Mendeliome v1.44 | ATOH1 |
Chloe Stutterd gene: ATOH1 was added gene: ATOH1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ATOH1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ATOH1 were set to 35518571 Phenotypes for gene: ATOH1 were set to Pontocerebellar hypoplasia; developmental delay; hearing loss Penetrance for gene: ATOH1 were set to unknown Review for gene: ATOH1 was set to AMBER Added comment: Single report of novel homozygous missense variant in functional domain segregating with disease in two affected siblings with pontocerebellar hypoplasia, developmental delay and hearing loss. Similar phenotype previously reported in animal model with biallelic missense variant affecting same functional domain. Homology modelling predicts this missense variant affects binding capability of the bHLH domain to the DNA. Gene encodes a core transcription factor in developing cerebellum, brainstem, dorsal spinal cord and ear. Sources: Literature |
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| Mendeliome v1.44 | BUB1 |
Paul De Fazio gene: BUB1 was added gene: BUB1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: BUB1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: BUB1 were set to 35044816; 19772675; 19117986; 23209306 Phenotypes for gene: BUB1 were set to Intellectual disability and microcephaly Review for gene: BUB1 was set to GREEN gene: BUB1 was marked as current diagnostic Added comment: 2 unrelated patients with ID, microcephaly, short stature, dysmorphic features reported with biallelic variants: P1 (3yo male): homozygous start-loss variant (2 hets and 0 hom in gnomAD). Functional testing showed a small amount of full-length protein was translated, and BUB1 recruitment to kinetochores was nearly undetectable. P2 (16yo female): compound heterozygous for a canonical splice variant (1 het and no hom in gnomAD) and an NMD-predicted frameshift variant (absent from gnomAD). The splice variant was shown to result in an in-frame deletion of 54 amino acids in the kinase domain. P2 cells have reduced protein levels but essentially no kinase activity. BUB1 patient cells have impaired mitotic fidelity. Homozygous Bub1 disruption in mice is embryonic lethal (PMID:19772675). A hypomorphic mouse is viable with increased tumourigenesis with ageing and aneuploidy (PMID:19117986). A kinase-dead mouse does not show increased tumourigenesis but does have a high frequency of aneuploid cells (PMID:23209306) Sources: Literature |
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| Mendeliome v1.44 | LMOD2 |
Melanie Marty gene: LMOD2 was added gene: LMOD2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: LMOD2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LMOD2 were set to PMID: 31517052; PMID: 34888509; PMID: 35082396; PMID: 35188328; PMID: 26487682 Phenotypes for gene: LMOD2 were set to Dilated cardiomyopathy Review for gene: LMOD2 was set to GREEN Added comment: 4 unrelated families with early onset dilated cardiomyopathy, autosomal recessive inheritance, functional studies showing loss of protein and a mouse model reported. PMID: 31517052 1 x neonate with DCM, homozygous nonsense variant identified. PMID: 34888509 2 x neonatal deaths (from 1 family) related to dilated cardiomyopathy (DCM), compound heterozygous loss-of-function variants identified. PMID:35082396 2 x siblings with DCM who died shortly after birth due to heart failure, homozygous canonical splice variant identified. Functional studies show loss of donor site and loss of protein. PMID: 35188328 1 x child (9 months) with DCM, with homozygous frameshift variant. Functional studies showed absence of LMOD2 protein (western blot). PMID: 26487682 Lmod2 null (knockout) mice present with short cardiac thin filaments and die at ~3 weeks due to dysfunctional, dilated hearts Sources: Literature |
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| Mendeliome v1.40 | SEMA6B |
Dean Phelan commented on gene: SEMA6B: PMID: 35604360 - 14 heterozygous variants were observed in 16 unrelated individuals referred for intellectual disability. Majority of the variants 9/14 were PTCs in the last exon and predicted to escape NMD. Functional studies of selected variants and shRNA knock down studies showed mislocalisation and abnormal protein function. |
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| Mendeliome v1.40 | GIMAP6 | Elena Savva Marked gene: GIMAP6 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.38 | HEATR3 | Zornitza Stark Marked gene: HEATR3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.37 | IREB2 | Lucy Spencer reviewed gene: IREB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 35602653; Phenotypes: Neurodegeneration, early-onset, with choreoathetoid movements and microcytic anemia, MIM#618451; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.37 | HEATR3 | Zornitza Stark Phenotypes for gene: HEATR3 were changed from Bone marrow failure, short stature, facial and acromelic dysmorphic features, and mild intellectual disability to DiMONDO:0015253 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.35 | GIMAP6 |
Elena Savva gene: GIMAP6 was added gene: GIMAP6 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GIMAP6 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GIMAP6 were set to PMID: 35551368; 33328581 Phenotypes for gene: GIMAP6 were set to Autophagy, immune competence and inflammation Review for gene: GIMAP6 was set to AMBER Added comment: PMID: 35551368, PMID: 33328581 - K/O mice show autophagy, redox regulation, and polyunsaturated fatty acid (PUFA)–containing lipids and die prematurely from microangiopathic glomerulosclerosis with immunodeficiency. - 2 unrelated families (3 patients) w/ a homozygous missense (p.Gly153Val) and nonsense (p.Trp86*). All unaffected siblings were heterozygous. Patient 1 (missense) presented with Coombs-positive hemolytic anemia, hepatosplenomegaly, Cranial MRI showed bilateral effusions, sulcal hyperintensity, and lateral parietal subcortical acute focal ischemic lesions. Patient 2 (nonsense) presented with recurrent purulent otitis media and a chronic wet cough, persistent jaundice, recurrent chest and ear infections, lingular consolidation, mild bronchiectasis, bibasilar bronchial wall thickening, right peribronchial consolidation, right lower lobe bronchiectasis, bilateral axillary lymphadenopathy, and splenomegaly. Patient 3 (nonsense) presented with suffered headaches, abdomen pain, mouth ulcers, and recurrent infections - Functional studies show patient 1 (missense) with reduced protein expression on western blot, and patient 2/3 (nonsense) with no protein expression. T cells of Pt 1 were similar to mouse K/O model (elevated basal LC3-II, reduced autophagic flux). gnomAD: 0 homozygous PTCs, but a very common canonical splice which is present in the non-canonical transcript Sources: Literature |
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| Mendeliome v1.34 | HEATR3 |
Chern Lim gene: HEATR3 was added gene: HEATR3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: HEATR3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HEATR3 were set to PMID: 35213692 Phenotypes for gene: HEATR3 were set to Bone marrow failure, short stature, facial and acromelic dysmorphic features, and mild intellectual disability Review for gene: HEATR3 was set to GREEN gene: HEATR3 was marked as current diagnostic Added comment: PMID: 35213692: - 4 unrelated individuals with biallelic HEATR3 variants (missense and splice site variants), exhibiting bone marrow failure, short stature, facial and acromelic dysmorphic features, and mild intellectual disability. - Functional analysis showed HEATR3 variants destabilised the protein, resulting in a reduction of nuclear uL18 and impaired ribosome biogenesis. Sources: Literature |
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| Mendeliome v1.34 | TRIM47 | Zornitza Stark Marked gene: TRIM47 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.34 | TRIM47 |
Zornitza Stark gene: TRIM47 was added gene: TRIM47 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TRIM47 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TRIM47 were set to 35511193 Phenotypes for gene: TRIM47 were set to Genetic cerebral small vessel disease MONDO:0018787 Review for gene: TRIM47 was set to RED Added comment: GWAS data: Combined evidence from summary-based Mendelian randomization studies and profiling of human loss-of-function allele carriers showed an inverse relation between TRIM47 expression in the brain and blood vessels and extensive small vessel disease severity. Observed significant enrichment of Trim47 in isolated brain vessel preparations compared to total brain fraction in mice, in line with the literature showing Trim47 enrichment in brain endothelial cells at single cell level. Functional evaluation of TRIM47 by small interfering RNAs-mediated knockdown in human brain endothelial cells showed increased endothelial permeability, an important hallmark of cerebral small vessel disease pathology. Sources: Literature |
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| Mendeliome v1.33 | PRDM13 | Zornitza Stark Phenotypes for gene: PRDM13 were changed from Retinal dystrophy; Chorioretinal atrophy, progressive bifocal, MIM# 600790; intellectual disability, MONDO:0001071, PRDM13-associated; ataxia with cerebellar hypoplasia, MONDO:0016054, PRDM13-associated; congenital hypogonadotropic hypogonadism, MONDO:0015770 to Chorioretinal atrophy, progressive bifocal, MIM# 600790; Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism, MIM# 619761 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.31 | MESP1 | Zornitza Stark Phenotypes for gene: MESP1 were changed from Congenital heart disease to Congenital heart disease MONDO:0005453 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.29 | SPTAN1 | Zornitza Stark Phenotypes for gene: SPTAN1 were changed from Developmental and epileptic encephalopathy 5, MIM# 613477; hereditary motor neuropathy to Developmental and epileptic encephalopathy 5, MIM# 613477; Hereditary spastic paraplegia MONDO:0019064, SPTAN1-related; hereditary motor neuropathy | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.28 | SPTAN1 | Zornitza Stark edited their review of gene: SPTAN1: Added comment: Leveille et al (2019) - 2 patients with HSP with biallelic missense SPTAN1 variants Previously described zebrafish, mouse, and rat animal models of SPTAN1 deficiency, all consistently showing axonal degeneration, fitting the pathological features of HSP in humans. Xie et al (2022) - 1 patient with complicated HSP and homozygous SPTAN1 mutation. Healthy parents and sister all carried the heterozygous mutation. Van de Vondel et al (2022) - 22 patients from 14 families with five novel heterozygous SPTAN1 variants. Presentations ranged from cerebellar ataxia, intellectual disability, epilepsy, and spastic paraplegia. A recurrent missense mutation (p.Arg19Trp) in 15 patients with spastic paraplegia. Through protein modeling they showed that mutated amino acids are located at crucial interlinking positions, interconnecting the three-helix bundle of a spectrin repeat.; Changed publications: 20493457, 22258530, 32811770, 35150594, 34526651, 31515523; Changed phenotypes: Developmental and epileptic encephalopathy 5, MIM# 613477, Hereditary spastic paraplegia MONDO:0019064, SPTAN1-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.18 | TULP3 | Zornitza Stark Phenotypes for gene: TULP3 were changed from progressive degenerative liver fibrosis with variable fibrocystic kidney disease; hypertrophic cardiomyopathy MONDO:0005045 to Hepatorenocardiac degenerative fibrosis, MIM# 619902 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.17 | TULP3 | Zornitza Stark reviewed gene: TULP3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hepatorenocardiac degenerative fibrosis, MIM# 619902; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.15 | IKBKG |
Zornitza Stark edited their review of gene: IKBKG: Added comment: X-linked systemic autoinflammatory disease (SAIDX) is characterized by the onset of systemic autoinflammation in the first months of life. Features include lymphadenopathy, hepatosplenomegaly, fever, panniculitis, and nodular skin rash. Additional manifestations may include inflammation of the optic nerve, intracranial hemorrhage, and lipodystrophy. Laboratory studies show hypogammaglobulinemia, increased or decreased white blood cell count, autoimmune cytopenias, elevated serum inflammatory markers, and a type I interferon signature. 6 unrelated boys and a girl reported. All variants resulted in absence of the domain encoded by exon 5 (NEMOdelEx5). Note variants in this gene are associated with immunodeficiency +/- ectodermal features and with IP.; Changed phenotypes: Ectodermal dysplasia and immunodeficiency 1, MIM# 300291, Immunodeficiency 33 , MIM#300636, Incontinentia pigmenti, MIM# 308300, Autoinflammatory disease, systemic, X-linked, MIM# 301081 |
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| Mendeliome v1.14 | MYO9A | Zornitza Stark edited their review of gene: MYO9A: Added comment: This gene-disease association has been reviewed as part of GenCC discordance resolution: note at least two of the variants reported have homozygotes with gnomad, which would be out of keeping for a severe paediatric disorder.; Changed rating: AMBER | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.12 | FAT2 | Elena Savva reviewed gene: FAT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33884300, 29053796; Phenotypes: Spinocerebellar ataxia 45, MIM#617769; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.11 | COPB2 | Zornitza Stark Phenotypes for gene: COPB2 were changed from Microcephaly 19, primary, autosomal recessive, MIM# 617800; Osteoporosis and developmental delay to Microcephaly 19, primary, autosomal recessive, MIM# 617800; Osteoporosis, childhood- or juvenile-onset, with developmental delay, MIM# 619884 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.10 | ATP13A3 | Zornitza Stark Phenotypes for gene: ATP13A3 were changed from Pulmonary arterial hypertension to Primary pulmonary hypertension 5, MIM#265400 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.9 | ATP13A3 | Zornitza Stark edited their review of gene: ATP13A3: Changed phenotypes: Primary pulmonary hypertension 5, MIM#265400 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.9 | RBFOX2 | Zornitza Stark Marked gene: RBFOX2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.9 | RBFOX2 | Zornitza Stark Phenotypes for gene: RBFOX2 were changed from Hypoplastic left heart syndrome (HLHS) to Hypoplastic left heart syndrome (HLHS) MONDO:0004933 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.7 | PROSER1 | Zornitza Stark Marked gene: PROSER1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.7 | PROSER1 |
Zornitza Stark gene: PROSER1 was added gene: PROSER1 was added to Mendeliome. Sources: Expert Review founder tags were added to gene: PROSER1. Mode of inheritance for gene: PROSER1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PROSER1 were set to 35229282 Phenotypes for gene: PROSER1 were set to Syndromic disease MONDO:0002254, PROSER1-related Review for gene: PROSER1 was set to RED Added comment: 4 children from 3 related families with developmental delay, hypotonia, seizures, failure-to-thrive, strabismus, drooling, recurrent otitis media, hearing impairment, genitourinary malformations, and common facial features (arched eyebrows, prominent eyes, broad nasal bridge, low-hanging columella, open mouth, thick lower lip, protruding tongue, large low-set ears, and parietal bossing). WES revealed a homozygous frame-shift variant (p.Thr612Glnfs*22) in PROSER1. This encodes the proline and serine rich protein 1, part of the histone methyltransferases KMT2C/KMT2D complexes. PROSER1 stabilizes TET2, a member of the TET family of DNA demethylases which is involved in recruiting the enhancer-associated KMT2C/KMT2D complexes and mediating DNA demethylation, activating gene expression. Therefore, PROSER1 may play vital and potentially general roles in gene regulation. No functional assays and 3 related families, likely founder effect. Sources: Expert Review |
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| Mendeliome v1.6 | SPATA22 | Zornitza Stark Marked gene: SPATA22 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.5 | SPATA22 |
Zornitza Stark gene: SPATA22 was added gene: SPATA22 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: SPATA22 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SPATA22 were set to 35285020 Phenotypes for gene: SPATA22 were set to Premature ovarian insufficiency and nonobstructive azoospermia; Genetic infertility MONDO:0017143 Review for gene: SPATA22 was set to AMBER Added comment: 1 consanguineous family with two premature ovarian insufficiency (POI) and two nonobstructive azoospermia (NOA) patients. WES identified a homozygous variant in SPATA22 (c.400C>T:p.R134X). Histological analysis and spermatocyte spreading assay demonstrated that the spermatogenesis was arrested at a zygotene-like stage in the proband with NOA. 2nd patient found with idiopathic POI and compound heterozygous variants in SPATA22 (c.900+1G>A and c.31C>T:p.R11X). Sources: Expert Review |
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| Mendeliome v1.3 | RDH11 | Zornitza Stark edited their review of gene: RDH11: Added comment: 2nd case reported: 1 Chinese patient with retinitis pigmentosa, juvenile cataracts, intellectual disability, and myopathy. Trio-based WES and whole genomic CNV detection found compound heterozygous variants in RDH11 (p.Leu313Pro and c.75-3C>A) with biparental inheritance. Variant c.75-3C>A was confirmed to be a splice-site mutation by cDNA sequencing. It caused exon 2 skipping, resulting in a frameshift mutation and premature translation termination (p.Lys26Serfs*38). They found mislocalization of RDH11 protein in muscle cells of the patient by using immunofluorescence staining. Retinol dehydrogenase 11 (RDH11) is an 11-cis-retinol dehydrogenase that has a well-characterized, albeit auxiliary role in the retinoid cycle. Diseases caused by mutations in the RDH11 gene are very rare, and only one affected family with eye and intelligence involvement has been reported.; Changed rating: AMBER; Changed publications: 24916380, 15634683, 30731079, 18326732, 34988992 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3 | ETV2 |
Ain Roesley changed review comment from: 1 family with 4 fetus-es, cHet for a fs (NMD-predicted) and a missense 3/4 vertebral malformations 2/4 Tetralogy of Fallot 1/4 arterial septal defect 1/4 ventricular septal defect, aortic dilatation 1/4 pre-axial polydactyly Sources: Literature; to: 1 family with 4 fetus-es all cHet for a fs (NMD-predicted) and a missense 3/4 vertebral malformations 2/4 Tetralogy of Fallot 1/4 arterial septal defect 1/4 ventricular septal defect, aortic dilatation 1/4 pre-axial polydactyly Sources: Literature |
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| Mendeliome v1.2 | ZNF526 | Zornitza Stark Phenotypes for gene: ZNF526 were changed from Intellectual disability; Microcephaly; Cataracts; Epilepsy; Hypertonia; Dystonia to Dentici-Novelli neurodevelopmental syndrome, MIM# 619877 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1 | POLR3F | Zornitza Stark Phenotypes for gene: POLR3F were changed from Severe VZV infection to Immunodeficiency 101 (varicella zoster virus-specific), MIM# 619872 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.0 | POLR3F | Zornitza Stark edited their review of gene: POLR3F: Changed phenotypes: Immunodeficiency 101 (varicella zoster virus-specific), MIM# 619872 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14798 | GLRX3 | Zornitza Stark Marked gene: GLRX3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14797 | DNM1L | Zornitza Stark Marked gene: DNM1L as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14797 | DNM1L | Zornitza Stark Phenotypes for gene: DNM1L were changed from to Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1 - MIM#614388 (AD, AR); Optic atrophy 5 - MIM#610708 (AD) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14795 | DNASE1L3 | Zornitza Stark Marked gene: DNASE1L3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14794 | DNASE1 | Zornitza Stark Marked gene: DNASE1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14791 | DNAJC6 | Zornitza Stark Marked gene: DNAJC6 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14791 | DNAJC6 | Zornitza Stark Phenotypes for gene: DNAJC6 were changed from to Parkinson disease 19a, juvenile-onset - MIM#615528; Parkinson disease 19b, early-onset - MIM#615528 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14786 | DNAJC5 | Zornitza Stark Marked gene: DNAJC5 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14784 | DNAJC3 | Zornitza Stark Marked gene: DNAJC3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14784 | DNAJC3 | Zornitza Stark Phenotypes for gene: DNAJC3 were changed from to Ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus - MIM#616192 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14781 | DNAJC21 | Zornitza Stark Marked gene: DNAJC21 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14781 | DNAJC21 | Zornitza Stark Phenotypes for gene: DNAJC21 were changed from to Bone marrow failure syndrome 3 - MIM#617052 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14779 | DNM2 | Zornitza Stark Marked gene: DNM2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14779 | DNM2 | Zornitza Stark Phenotypes for gene: DNM2 were changed from to Charcot-Marie-Tooth disease, axonal type 2M, MIM# 606482; Charcot-Marie-Tooth disease, dominant intermediate B, MIM# 606482; MONDO:0011674 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14775 | DPY19L2 | Zornitza Stark Marked gene: DPY19L2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14774 | AVPR2 | Zornitza Stark Marked gene: AVPR2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14773 | AVP | Zornitza Stark Marked gene: AVP as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14772 | DRAM2 | Zornitza Stark Marked gene: DRAM2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14767 | DRD2 | Zornitza Stark Marked gene: DRD2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14767 | ATP6V1E1 | Zornitza Stark Marked gene: ATP6V1E1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14764 | DRD3 | Zornitza Stark Marked gene: DRD3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14763 | DRD3 | Zornitza Stark Phenotypes for gene: DRD3 were changed from to {Essential tremor, hereditary, 1} - MIM#190300; {Schizophrenia, susceptibility to} - MIM#181500 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14760 | ATP2A1 | Zornitza Stark Marked gene: ATP2A1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14758 | DSC3 | Zornitza Stark Marked gene: DSC3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14755 | ADD1 | Zornitza Stark Marked gene: ADD1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14753 | DSCAM | Zornitza Stark Marked gene: DSCAM as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14748 | DSE | Zornitza Stark Marked gene: DSE as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14745 | DSG4 | Zornitza Stark Marked gene: DSG4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14742 | DSPP | Zornitza Stark Marked gene: DSPP as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14740 | DUOX2 | Zornitza Stark Marked gene: DUOX2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14738 | GDNF | Elena Savva Marked gene: GDNF as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14738 | DUOXA2 | Zornitza Stark Marked gene: DUOXA2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14736 | ENPP1 | Zornitza Stark Marked gene: ENPP1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14736 | EPOR | Zornitza Stark Marked gene: EPOR as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14736 | EPRS | Zornitza Stark Marked gene: EPRS as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14736 | EPS8 | Zornitza Stark Marked gene: EPS8 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14736 | EPS8 | Zornitza Stark Phenotypes for gene: EPS8 were changed from to Autosomal recessive nonsyndromic hearing loss 102 MONDO:0014428 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14733 | ETFB | Zornitza Stark Marked gene: ETFB as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14732 | EXT1 | Zornitza Stark Marked gene: EXT1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14732 | EXT1 | Zornitza Stark Phenotypes for gene: EXT1 were changed from to hereditary multiple osteochondromas MONDO:0005508; exostoses, multiple, type 1 MONDO:0007585 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14731 | EYA4 | Zornitza Stark Marked gene: EYA4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14731 | EYS | Zornitza Stark Marked gene: EYS as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14728 | FXR1 | Zornitza Stark Marked gene: FXR1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14728 | ETV2 | Ain Roesley Marked gene: ETV2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14728 | ETV2 |
Ain Roesley gene: ETV2 was added gene: ETV2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ETV2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ETV2 were set to 33359164 Phenotypes for gene: ETV2 were set to multiple fetal anomalies; congenital heart disease MONDO:000545, ETV2-related; vertebral malformations Review for gene: ETV2 was set to RED gene: ETV2 was marked as current diagnostic Added comment: 1 family with 4 fetus-es, cHet for a fs (NMD-predicted) and a missense 3/4 vertebral malformations 2/4 Tetralogy of Fallot 1/4 arterial septal defect 1/4 ventricular septal defect, aortic dilatation 1/4 pre-axial polydactyly Sources: Literature |
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| Mendeliome v0.14727 | GABRB2 | Zornitza Stark Marked gene: GABRB2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14726 | GALNT2 | Zornitza Stark Marked gene: GALNT2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14725 | GALNT3 | Zornitza Stark Marked gene: GALNT3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14722 | GALT | Zornitza Stark Marked gene: GALT as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14719 | GAMT | Zornitza Stark Marked gene: GAMT as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14716 | GAN | Zornitza Stark Marked gene: GAN as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14713 | GBA2 | Zornitza Stark Marked gene: GBA2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14713 | GBA2 | Zornitza Stark Phenotypes for gene: GBA2 were changed from to Spastic paraplegia 46, autosomal recessive, MIM# 614409; MONDO:0013737 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14710 | GCDH | Zornitza Stark Marked gene: GCDH as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14710 | GCDH | Zornitza Stark Phenotypes for gene: GCDH were changed from to Glutaric aciduria, type I MIM#231670; Organic acidurias | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14707 | GCH1 | Zornitza Stark Marked gene: GCH1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14704 | GCK | Zornitza Stark Marked gene: GCK as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14704 | GCK | Zornitza Stark Phenotypes for gene: GCK were changed from to Diabetes mellitus, noninsulin-dependent, late onset, AD (MIM#125853); Diabetes mellitus, permanent neonatal 1, AR (MIM#606176); Hyperinsulinemic hypoglycemia, familial, 3, AD (MIM#602485); MODY, type II, AD (MIM#125851) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14701 | GCNT2 | Zornitza Stark Marked gene: GCNT2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14700 | GCNT2 | Zornitza Stark Phenotypes for gene: GCNT2 were changed from to Cataract 13 with adult i phenotype, OMIM # 116700 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14697 | GDAP1 | Zornitza Stark Marked gene: GDAP1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14697 | GDAP1 | Zornitza Stark Phenotypes for gene: GDAP1 were changed from to Charcot-Marie-Tooth disease, axonal, type 2K 607831, MIM# Charcot-Marie-Tooth disease, axonal, with vocal cord paresis, MIM# 607706; Charcot-Marie-Tooth disease, recessive intermediate, A, MIM# 608340; Charcot-Marie-Tooth disease, type 4A, MIM# 214400 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14695 | GATAD1 | Elena Savva Phenotypes for gene: GATAD1 were changed from to ?Cardiomyopathy, dilated, 2B MIM#614672 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14694 | GATAD1 | Elena Savva Marked gene: GATAD1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14693 | FBXW4 | Elena Savva Marked gene: FBXW4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14692 | AURKC | Elena Savva Marked gene: AURKC as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14691 | ATPAF2 | Elena Savva Marked gene: ATPAF2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14691 | ATP2C2 | Elena Savva Marked gene: ATP2C2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14691 | AHSG | Elena Savva Marked gene: AHSG as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14689 | GDF2 | Zornitza Stark Marked gene: GDF2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14689 | GDF2 | Zornitza Stark Phenotypes for gene: GDF2 were changed from to Telangiectasia, hereditary hemorrhagic, type 5 OMIM # 615506; pulmonary arteriovenous malformations | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14686 | GDF9 | Zornitza Stark Marked gene: GDF9 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14686 | GDF9 | Zornitza Stark Phenotypes for gene: GDF9 were changed from to Premature ovarian failure 14, OMIM# 618014 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14683 | GEMIN4 | Zornitza Stark Marked gene: GEMIN4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14683 | GEMIN4 | Zornitza Stark Phenotypes for gene: GEMIN4 were changed from to Neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities, MIM# 617913 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14680 | GFM2 | Zornitza Stark Marked gene: GFM2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14677 | GIF | Zornitza Stark Marked gene: GIF as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14672 | SLC26A1 | Elena Savva Marked gene: SLC26A1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14670 | PRKAG3 | Elena Savva Marked gene: PRKAG3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14670 | GINS1 | Zornitza Stark Marked gene: GINS1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14667 | U2AF2 | Elena Savva Marked gene: U2AF2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14667 | TDP1 | Elena Savva Marked gene: TDP1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14666 | TIA1 | Elena Savva Marked gene: TIA1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14666 | PLD3 | Elena Savva Marked gene: PLD3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14666 | RBM7 | Elena Savva Marked gene: RBM7 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14666 | MFAP5 | Elena Savva Marked gene: MFAP5 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14666 | MMGT1 | Elena Savva Marked gene: MMGT1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14666 | FRA12A | Elena Savva Marked STR: FRA12A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14666 | GIGYF2 | Elena Savva Marked gene: GIGYF2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14666 | FRA12A | Elena Savva Phenotypes for STR: FRA12A were changed from Mental retardation, FRA12A type MIM#136630 to Intellectual developmental disorder, autosomal dominant, FRA12A type MIM#136630 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14665 | MEPE | Elena Savva Marked gene: MEPE as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14665 | LRIF1 | Elena Savva Marked gene: LRIF1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14665 | GIGYF2 | Elena Savva Phenotypes for gene: GIGYF2 were changed from to {Parkinson disease 11} MIM#607688 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14663 | DMGDH | Elena Savva Marked gene: DMGDH as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14663 | DMGDH | Elena Savva Phenotypes for gene: DMGDH were changed from to Dimethylglycine dehydrogenase deficiency MIM#605850; Disorders and variants of other enzymes that oxidise xenobiotics | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14662 | DCAF8 | Elena Savva Marked gene: DCAF8 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14662 | CCT5 | Elena Savva Marked gene: CCT5 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14662 | ATG5 | Elena Savva Marked gene: ATG5 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14662 | USP8 | Elena Savva Marked gene: USP8 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14662 | LRP5 | Krithika Murali reviewed gene: LRP5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Exudative vitreoretinopathy 4 - MIM#601813 (AD, AR), Hyperostosis, endosteal - MIM#144750 (AD), Osteopetrosis, autosomal dominant 1 - MIM#607634(AD), Osteoporosis-pseudoglioma syndrome - MIM#259770 (AR), Osteosclerosis - #144750 (AD), Polycystic liver disease 4 with or without kidney cysts - MIM#617875 (AD), van Buchem disease, type 2 - MIM#607636; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14660 | LYRM7 | Krithika Murali reviewed gene: LYRM7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex III deficiency, nuclear type 8 - MIM#615838; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14659 | MSX1 | Elena Savva Marked gene: MSX1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14657 | GJA1 | Zornitza Stark Marked gene: GJA1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14654 | GJA5 | Zornitza Stark Marked gene: GJA5 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14651 | LRP2 |
Chirag Patel commented on gene: LRP2: Donnai-Barrow syndrome (DBS) was first described as a distinct disorder characterized by diaphragmatic hernia, exomphalos, absent corpus callosum, myopia, agenesis of the corpus callosum and proteinuria, and sensorineural deafness. Kantarci et al. (2007) identified biallelic LRP2 mutations in 6 families with Donnai-Barrow syndrome and one family with facio-oculo-acoustico-renal syndrome. |
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| Mendeliome v0.14651 | LRP2 | Chirag Patel reviewed gene: LRP2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 17632512; Phenotypes: Donnai-Barrow syndrome, MIM#222448; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14651 | ATPAF2 | Krithika Murali reviewed gene: ATPAF2: Rating: RED; Mode of pathogenicity: None; Publications: 14757859; Phenotypes: ?Mitochondrial complex V (ATP synthase) deficiency, nuclear type 1 - MIM#604273; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14650 | ADD1 |
Chirag Patel gene: ADD1 was added gene: ADD1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ADD1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Publications for gene: ADD1 were set to PMID: 34906466 Phenotypes for gene: ADD1 were set to Intellectual disability, corpus callosum dysgenesis, and ventriculomegaly; no OMIM # Review for gene: ADD1 was set to GREEN Added comment: 4 unrelated individuals affected by ID and/or complete or partial agenesis of corpus callosum, and enlarged lateral ventricles. WES found loss-of-function variants - 1 recessive missense variant and 3 de novo variants. The recessive variant is associated with ACC and enlarged lateral ventricles, and the de novo variants were associated with complete or partial agenesis of corpus callosum, mild ID and attention deficit. Human variants impair ADD1 protein expression and/or dimerization with ADD2. Add1 knockout mice recapitulate corpus callosum dysgenesis and ventriculomegaly phenotypes. Three adducin genes (ADD1, ADD2, and ADD3) encode cytoskeleton proteins that are critical for osmotic rigidity and cell shape. ADD1, ADD2, and ADD3 form heterodimers (ADD1/ADD2, ADD1/ADD3), which further form heterotetramers. Adducins interconnect spectrin and actin filaments to form polygonal scaffolds beneath the cell membranes and form ring-like structures in neuronal axons. Adducins regulate mouse neural development, but their function in the human brain is unknown Sources: Literature |
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| Mendeliome v0.14647 | ATPAF2 | Chirag Patel reviewed gene: ATPAF2: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 14757859; Phenotypes: ?Mitochondrial complex V (ATP synthase) deficiency, nuclear type 1, OMIM# 604273; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14647 | GJA5 |
Chirag Patel commented on gene: GJA5: Gollob et al. (2006) presented evidence that tissue-specific mutations in the GJA5 gene may predispose the atria to fibrillation. They identified a heterozygous missense mutation in blood and cardiac tissue in patient with AF. They also found 3 heterozygous missense mutations in cardiac tissue only in 3 other patients, indicating a somatic source of the genetic defects Yang et al. (2010) identified a heterozygous nonsense mutationin a 64-year-old female patient who was diagnosed with paroxysmal AF at 32 years of age. The mutation was detected in 6 additional affected family members, but was not found in 6 unaffected family members or in 200 ethnically matched controls. Yang et al. (2010) identified 3 heterozygous missense mutations in 3 probands with AF. The mutations segregated with disease in all 3 families and were not found in 200 ethnically matched controls. Sun et al. (2013) identified a heterozygous missense mutation in a 42-year-old woman who had been diagnosed with AF at age 40 years. The mutation was also detected in her father, who had been diagnosed with lone AF at 41 years of age, but it was not found in unaffected family members, in 200 controls, or in the dbSNP database. Functional analysis demonstrated that the I75F mutant is unable to form functional gap junction channels and also impairs coupling when expressed with wildtype CX40 or CX43. |
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| Mendeliome v0.14647 | GEMIN4 | Chirag Patel reviewed gene: GEMIN4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25558065, 30237576, 27878435; Phenotypes: Neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities, MIM# 617913; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14647 | GJB2 | Zornitza Stark Marked gene: GJB2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14647 | GJB2 | Zornitza Stark Phenotypes for gene: GJB2 were changed from to Bart-Pumphrey syndrome, MIM#149200; Deafness, autosomal dominant 3A, MIM#601544; Deafness, autosomal recessive 1A, MIM#220290; Hystrix-like ichthyosis with deafness, MIM#602540; Keratitis-ichthyosis-deafness syndrome, MIM#148210; Keratoderma, palmoplantar, with deafness, MIM#148350; Vohwinkel syndrome, MIM# 124500 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14644 | GJB3 | Zornitza Stark Marked gene: GJB3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14644 | GJB3 | Zornitza Stark Phenotypes for gene: GJB3 were changed from to Erythrokeratodermia variabilis et progressiva 1, MIM# 133200 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14642 | GJB2 | Chirag Patel reviewed gene: GJB2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 11179004, 9529365, 14985372, 19941053, 11354642; Phenotypes: Bart-Pumphrey syndrome, MIM#149200, Deafness, autosomal dominant 3A, MIM#601544, Deafness, autosomal recessive 1A, MIM#220290, Hystrix-like ichthyosis with deafness, MIM#602540, Keratitis-ichthyosis-deafness syndrome, MIM#148210, Keratoderma, palmoplantar, with deafness, MIM#148350, Vohwinkel syndrome, MIM# 124500; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14640 | GJB3 | Zornitza Stark reviewed gene: GJB3: Rating: GREEN; Mode of pathogenicity: None; Publications: 9843209, 10594760, 10798362, 12019212; Phenotypes: Erythrokeratodermia variabilis et progressiva 1, MIM# 133200; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14640 | GJB3 | Chirag Patel reviewed gene: GJB3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 9843209, 10798362, 10594760, 17446259, 9843210; Phenotypes: Erythrokeratodermia variabilis et progressiva 1, OMIM #133200, Deafness, autosomal dominant 2B, OMIM # 612644; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14640 | GNB5 | Chirag Patel reviewed gene: GNB5: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27523599, 27677260, 28697420, 29368331; Phenotypes: Intellectual developmental disorder with cardiac arrhythmia, OMIM #617173, Language delay and ADHD/cognitive impairment with or without cardiac arrhythmia, OMIM # 617182, Early infantile epileptic encephalopathy (EIEE); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14640 | GJB4 | Zornitza Stark Marked gene: GJB4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14640 | GJB4 | Zornitza Stark Phenotypes for gene: GJB4 were changed from to Erythrokeratodermia variabilis et progressiva 2, MIM# 617524 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14637 | GJB4 | Zornitza Stark reviewed gene: GJB4: Rating: GREEN; Mode of pathogenicity: None; Publications: 11017804, 12648223, 19291775; Phenotypes: Erythrokeratodermia variabilis et progressiva 2, MIM# 617524; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14637 | GJB6 | Zornitza Stark Marked gene: GJB6 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14634 | GK | Zornitza Stark Marked gene: GK as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14631 | GLCCI1 | Zornitza Stark Marked gene: GLCCI1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14628 | GLE1 | Zornitza Stark Marked gene: GLE1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14625 | GLIS3 | Zornitza Stark Marked gene: GLIS3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14622 | GLUL | Zornitza Stark Marked gene: GLUL as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14619 | GLYCTK | Zornitza Stark Marked gene: GLYCTK as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14616 | GMPPA | Zornitza Stark Marked gene: GMPPA as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14616 | GMPPA | Zornitza Stark Phenotypes for gene: GMPPA were changed from to Alacrima, achalasia, and mental retardation syndrome, MIM# 615510 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14613 | GMPPA | Zornitza Stark reviewed gene: GMPPA: Rating: GREEN; Mode of pathogenicity: None; Publications: 24035193, 28574218; Phenotypes: Alacrima, achalasia, and mental retardation syndrome, MIM# 615510; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14613 | GMPPB | Zornitza Stark Marked gene: GMPPB as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14613 | GMPPB | Zornitza Stark Phenotypes for gene: GMPPB were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 615350; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 14 615351; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 615352 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14611 | GMPPB | Zornitza Stark reviewed gene: GMPPB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 615350, Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 14 615351, Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 615352; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14611 | GNAS | Zornitza Stark Marked gene: GNAS as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14611 | GNAS | Zornitza Stark Phenotypes for gene: GNAS were changed from to Osseous heteroplasia, progressive (166350) AD; Pituitary adenoma 3, multiple types, somatic (617686); Pseudohypoparathyroidism Ia (103580) AD; Pseudohypoparathyroidism Ib (603233) AD; Pseudohypoparathyroidism Ic (612462) AD; Pseudopseudohypoparathyroidism (612463) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14609 | GNAS | Zornitza Stark reviewed gene: GNAS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Osseous heteroplasia, progressive (166350) AD, Pituitary adenoma 3, multiple types, somatic (617686), Pseudohypoparathyroidism Ia (103580) AD, Pseudohypoparathyroidism Ib (603233) AD, Pseudohypoparathyroidism Ic (612462) AD, Pseudopseudohypoparathyroidism (612463); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14609 | GNAT1 | Zornitza Stark Marked gene: GNAT1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14609 | GNAT1 | Zornitza Stark Phenotypes for gene: GNAT1 were changed from to Night blindness, congenital stationary, autosomal dominant 3, MIM# 610444; Night blindness, congenital stationary, type 1G, MIM# 616389 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14606 | GNAT1 | Zornitza Stark reviewed gene: GNAT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 8673138, 17584859, 22190596, 26472407, 11095744, 11095744, 30051303; Phenotypes: Night blindness, congenital stationary, autosomal dominant 3, MIM# 610444, Night blindness, congenital stationary, type 1G, MIM# 616389; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14606 | GNB3 | Zornitza Stark Marked gene: GNB3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14606 | GNB3 | Zornitza Stark Phenotypes for gene: GNB3 were changed from to Night blindness, congenital stationary, type 1H, MIM# 617024 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14603 | GNB3 | Zornitza Stark reviewed gene: GNB3: Rating: GREEN; Mode of pathogenicity: None; Publications: 27063057, 17065478; Phenotypes: Night blindness, congenital stationary, type 1H, MIM# 617024; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14603 | GNMT | Zornitza Stark Marked gene: GNMT as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14600 | GOSR2 | Zornitza Stark Marked gene: GOSR2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14597 | GOT1 | Zornitza Stark Marked gene: GOT1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14597 | GOT1 | Zornitza Stark Phenotypes for gene: GOT1 were changed from to Aspartate aminotransferase, serum level of, QTL1, MIM# 614419 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14595 | GOT1 | Zornitza Stark reviewed gene: GOT1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Aspartate aminotransferase, serum level of, QTL1, MIM# 614419; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14595 | GPC4 | Zornitza Stark Marked gene: GPC4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14592 | GPNMB | Krithika Murali reviewed gene: GPNMB: Rating: GREEN; Mode of pathogenicity: None; Publications: 31226264, 29336782, 31260093, 34551863, 33687658; Phenotypes: Amyloidosis, primary localized cutaneous, 3 - MIM#617920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14592 | GDF2 | Chirag Patel reviewed gene: GDF2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 23972370, 27081547, 32573726, 32992168, 34611981, 33834622, 32669404, 26056270, 23972370; Phenotypes: Telangiectasia, hereditary hemorrhagic, type 5 OMIM # 615506, pulmonary arteriovenous malformations; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14592 | GCNT2 | Chirag Patel reviewed gene: GCNT2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 15161861, 27936067, 12424189, 28224043; Phenotypes: Cataract 13 with adult i phenotype, OMIM # 116700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14592 | GCK | Chirag Patel reviewed gene: GCK: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 19790256; Phenotypes: Diabetes mellitus, noninsulin-dependent, late onset, AD (MIM#125853), Diabetes mellitus, permanent neonatal 1, AR (MIM#606176), Hyperinsulinemic hypoglycemia, familial, 3, AD (MIM#602485), MODY, type II, AD (MIM#125851); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14591 | GDF9 | Chirag Patel reviewed gene: GDF9: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29044499, 8849725, 33036707; Phenotypes: Premature ovarian failure 14, OMIM# 618014; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14589 | GIGYF2 | Chirag Patel reviewed gene: GIGYF2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 18358451; Phenotypes: {Parkinson disease 11} , OMIM # 607688; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14589 | HEY2 | Zornitza Stark Marked gene: HEY2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14589 | HEY2 | Zornitza Stark Phenotypes for gene: HEY2 were changed from congenital heart defects and thoracic aortic aneurysms to congenital heart disease MONDO:0005453; thoracic aortic aneurysms | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14588 | IL18BP | Zornitza Stark Marked gene: IL18BP as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14588 | ITPKB | Zornitza Stark Marked gene: ITPKB as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14587 | MUC7 | Zornitza Stark Marked gene: MUC7 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14585 | MYF6 | Zornitza Stark Marked gene: MYF6 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14585 | MYF6 | Zornitza Stark Phenotypes for gene: MYF6 were changed from to Centronuclear myopathy, MONDO:0018947 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14582 | PDCD6IP | Zornitza Stark Marked gene: PDCD6IP as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14580 | POU5F1 | Zornitza Stark Marked gene: POU5F1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14580 | GBA2 | Chirag Patel reviewed gene: GBA2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 23332916, 23332917, 29524657; Phenotypes: Spastic paraplegia 46, autosomal recessive, MIM# 614409, MONDO:0013737; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14579 | SGK3 | Zornitza Stark Marked gene: SGK3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14579 | GATAD1 | Chirag Patel reviewed gene: GATAD1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 21965549; Phenotypes: ?Cardiomyopathy, dilated, 2B, OMIM # 614672; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14579 | DMPK | Zornitza Stark Marked gene: DMPK as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14579 | NOP56 | Zornitza Stark Marked gene: NOP56 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14579 | GPD1 | Zornitza Stark Marked gene: GPD1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14576 | GPHN | Zornitza Stark Marked gene: GPHN as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14575 | GPNMB | Zornitza Stark Marked gene: GPNMB as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14575 | GPNMB | Zornitza Stark Phenotypes for gene: GPNMB were changed from to Amyloidosis, primary localized cutaneous, 3, MIM# 617920 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14572 | GPNMB | Zornitza Stark reviewed gene: GPNMB: Rating: GREEN; Mode of pathogenicity: None; Publications: 29336782; Phenotypes: Amyloidosis, primary localized cutaneous, 3, MIM# 617920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14572 | GREM1 | Zornitza Stark Marked gene: GREM1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14568 | MRAP | Zornitza Stark Marked gene: MRAP as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14565 | MPZL2 | Zornitza Stark Marked gene: MPZL2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14562 | MPZ | Zornitza Stark Marked gene: MPZ as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14562 | MPZ | Zornitza Stark Phenotypes for gene: MPZ were changed from to Charcot Marie Tooth disease, dominant intermediate D, 60779; Neuropathy, congenital hypomyelinating, 605253; Charcot Marie Tooth disease, type 2J, 607736; Dejerine Sottas disease, 145900; Charcot Marie Tooth disease, type 1B, 118200; Charcot Marie Tooth disease, type 2I, 607677; HMSN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14559 | MPV17 | Zornitza Stark Marked gene: MPV17 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14559 | MPV17 | Zornitza Stark Phenotypes for gene: MPV17 were changed from to Charcot-Marie-Tooth disease, axonal, type 2EE, MIM# 618400 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14556 | MPO | Zornitza Stark Marked gene: MPO as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14553 | MPC1 | Zornitza Stark Marked gene: MPC1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14553 | MPC1 | Zornitza Stark Phenotypes for gene: MPC1 were changed from to Mitochondrial pyruvate carrier deficiency, MIM# 614741 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14550 | MPC1 | Zornitza Stark reviewed gene: MPC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22628558, 34873722; Phenotypes: Mitochondrial pyruvate carrier deficiency, MIM# 614741; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14550 | MOG | Zornitza Stark Marked gene: MOG as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14550 | MOG | Zornitza Stark Phenotypes for gene: MOG were changed from to Narcolepsy 7 , MIM# 614250 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14546 | MOG | Zornitza Stark reviewed gene: MOG: Rating: RED; Mode of pathogenicity: None; Publications: 21907016; Phenotypes: Narcolepsy 7 , MIM# 614250; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14546 | MOCS3 | Zornitza Stark Marked gene: MOCS3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14542 | MOCS1 | Zornitza Stark Marked gene: MOCS1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14541 | MNX1 | Zornitza Stark Marked gene: MNX1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14541 | MNX1 | Zornitza Stark Phenotypes for gene: MNX1 were changed from to Currarino syndrome, MIM# 176450 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14538 | MMP2 | Zornitza Stark Marked gene: MMP2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14538 | MMP2 | Zornitza Stark Phenotypes for gene: MMP2 were changed from to Multicentric osteolysis, nodulosis, and arthropathy, MIM# 259600 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14535 | MMP2 | Zornitza Stark reviewed gene: MMP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 11431697, 15691365, 17059372, 17400654; Phenotypes: Multicentric osteolysis, nodulosis, and arthropathy, MIM# 259600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14533 | ATP6V1A | Elena Savva Marked gene: ATP6V1A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14532 | ATP6AP2 | Elena Savva Phenotypes for gene: ATP6AP2 were changed from ?Parkinsonism with spasticity, X-linked MIM#300911; Congenital disorder of glycosylation, type IIr MIM#301045; Intellectual developmental disorder, X-linked, syndromic, Hedera type MIM#300423 to ?Parkinsonism with spasticity, X-linked MIM#300911; Congenital disorder of glycosylation, type IIr MIM#301045; Intellectual developmental disorder, X-linked, syndromic, Hedera type MIM#300423 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14531 | ATP6AP2 | Elena Savva Marked gene: ATP6AP2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14531 | ATP6AP2 | Elena Savva Phenotypes for gene: ATP6AP2 were changed from to ?Parkinsonism with spasticity, X-linked MIM#300911; Congenital disorder of glycosylation, type IIr MIM#301045; Intellectual developmental disorder, X-linked, syndromic, Hedera type MIM#300423 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14530 | ATP6AP2 | Elena Savva reviewed gene: ATP6AP2: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 23595882; Phenotypes: ?Parkinsonism with spasticity, X-linked MIM#300911, Congenital disorder of glycosylation, type IIr MIM#301045, Intellectual developmental disorder, X-linked, syndromic, Hedera type MIM#300423; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14530 | MMADHC | Zornitza Stark Marked gene: MMADHC as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14530 | MMADHC | Zornitza Stark Phenotypes for gene: MMADHC were changed from to Homocystinuria, cblD type, variant 1 MIM#277410; Methylmalonic aciduria and homocystinuria, cblD type MIM#277410; Methylmalonic aciduria, cblD type, variant 2 MIM#277410; Disorders of cobalamin absorption, transport and metabolism | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14527 | MMACHC | Zornitza Stark Marked gene: MMACHC as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14524 | MMAB | Zornitza Stark Marked gene: MMAB as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14522 | MMAA | Zornitza Stark Marked gene: MMAA as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14520 | MLPH | Zornitza Stark Marked gene: MLPH as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14517 | MITF | Zornitza Stark Marked gene: MITF as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14517 | MITF | Zornitza Stark Phenotypes for gene: MITF were changed from to COMMAD syndrome, MIM# 617306; Tietz albinism-deafness syndrome, MIM# 103500; Waardenburg syndrome, type 2A, MIM# 193510 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14514 | MITF | Zornitza Stark reviewed gene: MITF: Rating: GREEN; Mode of pathogenicity: None; Publications: 27889061, 32541011; Phenotypes: COMMAD syndrome, MIM# 617306, Tietz albinism-deafness syndrome, MIM# 103500, Waardenburg syndrome, type 2A, MIM# 193510; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14514 | MIR936 | Zornitza Stark Marked gene: MIR936 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14513 | MIR184 | Zornitza Stark Marked gene: MIR184 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14510 | MIR183 | Zornitza Stark Marked gene: MIR183 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14506 | ATP2C1 | Elena Savva Marked gene: ATP2C1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14505 | ATP6V0A1 | Elena Savva Marked gene: ATP6V0A1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14505 | MIR182 | Zornitza Stark Marked gene: MIR182 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14504 | MIP | Zornitza Stark Marked gene: MIP as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14504 | MIP | Zornitza Stark Phenotypes for gene: MIP were changed from to Cataract 15, multiple types, MIM# 615274 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14501 | MIP | Zornitza Stark reviewed gene: MIP: Rating: GREEN; Mode of pathogenicity: None; Publications: 10802646, 16564824, 33530927, 30214549; Phenotypes: Cataract 15, multiple types, MIM# 615274; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14501 | MIF | Zornitza Stark Marked gene: MIF as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14500 | MIF | Zornitza Stark Phenotypes for gene: MIF were changed from to {Rheumatoid arthritis, systemic juvenile, susceptibility to}, MIM# 604302 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14498 | MIF | Zornitza Stark reviewed gene: MIF: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Rheumatoid arthritis, systemic juvenile, susceptibility to}, MIM# 604302; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14498 | MGME1 | Zornitza Stark Marked gene: MGME1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14495 | MFN2 | Zornitza Stark Marked gene: MFN2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14494 | MFF | Zornitza Stark Marked gene: MFF as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14491 | METTL23 | Zornitza Stark Marked gene: METTL23 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14488 | MET | Zornitza Stark Marked gene: MET as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14488 | MET | Zornitza Stark Phenotypes for gene: MET were changed from to Renal cell carcinoma, papillary, 1, familial and somatic, MIM# 605074; Papillary renal cell carcinoma MONDO:0017884 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14486 | MET | Zornitza Stark edited their review of gene: MET: Changed phenotypes: Renal cell carcinoma, papillary, 1, familial and somatic, MIM# 605074, Papillary renal cell carcinoma MONDO:0017884 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14486 | MET | Zornitza Stark reviewed gene: MET: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Papillary renal cell carcinoma MONDO:0017884; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14486 | ATG16L1 | Elena Savva Marked gene: ATG16L1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14486 | MERTK | Zornitza Stark Marked gene: MERTK as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14483 | MEIS1 | Zornitza Stark Marked gene: MEIS1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14482 | ATP1A1 | Elena Savva Phenotypes for gene: ATP1A1 were changed from Charcot-Marie-Tooth disease, axonal, type 2DD MIM#618036; Hypomagnesemia, seizures, and mental retardation 2 MIM#618314 to Charcot-Marie-Tooth disease, axonal, type 2DD MIM#618036; Hypomagnesemia, seizures, and mental retardation 2 MIM#618314 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14481 | ATP2A2 | Elena Savva Marked gene: ATP2A2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14479 | ATL3 | Elena Savva Phenotypes for gene: ATL3 were changed from Neuropathy, hereditary sensory, type IF, MIM# 615632 to Neuropathy, hereditary sensory, type IF, MIM# 615632 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14478 | ATP2A2 | Elena Savva Phenotypes for gene: ATP2A2 were changed from to Acrokeratosis verruciformis MIM#101900; Darier disease MIM#124200 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14476 | ATP1A1 | Elena Savva Phenotypes for gene: ATP1A1 were changed from to Charcot-Marie-Tooth disease, axonal, type 2DD MIM#618036; Hypomagnesemia, seizures, and mental retardation 2 MIM#618314 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14475 | ATP1A1 | Elena Savva Marked gene: ATP1A1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14475 | ATL3 | Elena Savva Phenotypes for gene: ATL3 were changed from to Neuropathy, hereditary sensory, type IF, MIM# 615632 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14474 | ATL3 | Elena Savva Marked gene: ATL3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14474 | ATP2A2 | Elena Savva reviewed gene: ATP2A2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 24336169; Phenotypes: Acrokeratosis verruciformis MIM#101900, Darier disease MIM#124200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14472 | ATF1 | Elena Savva Marked gene: ATF1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14471 | MEIOB | Zornitza Stark Marked gene: MEIOB as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14471 | ASPN | Elena Savva Marked gene: ASPN as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14471 | MEGF8 | Zornitza Stark Marked gene: MEGF8 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14471 | MEGF8 | Zornitza Stark Phenotypes for gene: MEGF8 were changed from to Carpenter syndrome, MIM#614976 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14468 | MEGF8 | Zornitza Stark reviewed gene: MEGF8: Rating: GREEN; Mode of pathogenicity: None; Publications: 23063620; Phenotypes: Carpenter syndrome, MIM#614976; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14468 | MEFV | Zornitza Stark Marked gene: MEFV as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14465 | MED23 | Zornitza Stark Marked gene: MED23 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14462 | MED13 | Zornitza Stark Marked gene: MED13 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14459 | MECP2 | Zornitza Stark Marked gene: MECP2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14456 | MCM9 | Zornitza Stark Marked gene: MCM9 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14456 | MCM9 | Zornitza Stark Phenotypes for gene: MCM9 were changed from to Ovarian dysgenesis 4, MIM# 616185 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14453 | MCM9 | Zornitza Stark reviewed gene: MCM9: Rating: GREEN; Mode of pathogenicity: None; Publications: 25480036, 26771056, 33538981, 33095795; Phenotypes: Ovarian dysgenesis 4, MIM# 616185; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14453 | MCM8 | Zornitza Stark Marked gene: MCM8 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14453 | ASPN | Elena Savva Phenotypes for gene: ASPN were changed from {Lumbar disc degeneration} MIM#603932; {Osteoarthritis susceptibility 3} MIM#607850 to {Lumbar disc degeneration} MIM#603932; {Osteoarthritis susceptibility 3} MIM#607850 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14453 | ASPN | Elena Savva Phenotypes for gene: ASPN were changed from to {Lumbar disc degeneration} MIM#603932; {Osteoarthritis susceptibility 3} MIM#607850 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14451 | ARV1 | Elena Savva Marked gene: ARV1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14451 | ARV1 | Elena Savva Gene: arv1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14450 | ARV1 | Elena Savva Phenotypes for gene: ARV1 were changed from to DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 38 MIM#61720; Dilated cardiomyopathy | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14449 | ARV1 | Elena Savva Publications for gene: ARV1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14449 | ARV1 | Elena Savva Mode of inheritance for gene: ARV1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14448 | MCM8 | Zornitza Stark Phenotypes for gene: MCM8 were changed from to Premature ovarian failure 10, MIM# 612885 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14445 | MCM8 | Zornitza Stark reviewed gene: MCM8: Rating: GREEN; Mode of pathogenicity: None; Publications: 25437880, 25873734; Phenotypes: Premature ovarian failure 10, MIM# 612885; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14445 | MCM6 | Zornitza Stark Marked gene: MCM6 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14442 | OAS1 | Zornitza Stark Phenotypes for gene: OAS1 were changed from Autoinflammatory immunodeficiency; infantile-onset pulmonary alveolar proteinosis; hypogammaglobulinaemia to Immunodeficiency 100 with pulmonary alveolar proteinosis and hypogammaglobulinaemia, MIM#618042 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14441 | OAS1 | Zornitza Stark edited their review of gene: OAS1: Changed phenotypes: Immunodeficiency 100 with pulmonary alveolar proteinosis and hypogammaglobulinaemia, MIM#618042 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14441 | MCEE | Zornitza Stark Marked gene: MCEE as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14438 | MCCC2 | Zornitza Stark Marked gene: MCCC2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14438 | MCCC2 | Zornitza Stark Phenotypes for gene: MCCC2 were changed from to 3-Methylcrotonyl-CoA carboxylase 2 deficiency MIM#210210; Organic acidurias | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14435 | MCCC2 | Zornitza Stark reviewed gene: MCCC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31730530; Phenotypes: 3-Methylcrotonyl-CoA carboxylase 2 deficiency MIM#210210, Organic acidurias; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14435 | MCCC1 | Zornitza Stark Marked gene: MCCC1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14435 | MCCC1 | Zornitza Stark Phenotypes for gene: MCCC1 were changed from to 3-Methylcrotonyl-CoA carboxylase 1 deficiency MIM#210200; Organic acidurias | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14432 | MCCC1 | Zornitza Stark reviewed gene: MCCC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31730530; Phenotypes: 3-Methylcrotonyl-CoA carboxylase 1 deficiency MIM#210200, Organic acidurias; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14432 | MC3R | Zornitza Stark Marked gene: MC3R as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14429 | MC2R | Zornitza Stark Marked gene: MC2R as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14426 | MBL2 | Zornitza Stark Marked gene: MBL2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14422 | MATR3 | Zornitza Stark Marked gene: MATR3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14419 | MAP3K1 | Zornitza Stark Marked gene: MAP3K1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14416 | MAK | Zornitza Stark Marked gene: MAK as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14413 | MAGT1 | Zornitza Stark Marked gene: MAGT1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14413 | MAGT1 | Zornitza Stark Phenotypes for gene: MAGT1 were changed from to Congenital disorder of glycosylation, type Icc (MIM# 301031); Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia (MIM# 300853) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14410 | MAGT1 | Zornitza Stark reviewed gene: MAGT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31036665, 31714901; Phenotypes: Congenital disorder of glycosylation, type Icc (MIM# 301031), Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia (MIM# 300853); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14410 | GREM1 | Krithika Murali reviewed gene: GREM1: Rating: AMBER; Mode of pathogenicity: None; Publications: 22561515, 26493165, 21128281, 29804199; Phenotypes: hereditary mixed polyposis syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14410 | MNX1 | Abhijit Kulkarni reviewed gene: MNX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32571425, 33836786 , 11528505; Phenotypes: Currarino syndrome, MIM# 176450; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14410 | MAGI2 | Zornitza Stark Marked gene: MAGI2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14407 | MYO3A | Zornitza Stark Marked gene: MYO3A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14407 | OPHN1 | Zornitza Stark Marked gene: OPHN1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14407 | OPHN1 | Zornitza Stark Phenotypes for gene: OPHN1 were changed from to Mental retardation, X-linked, with cerebellar hypoplasia and distinctive facial appearance, MIM#300486 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14404 | OPHN1 | Zornitza Stark commented on gene: OPHN1: OPHN1 variants cause cerebellar hypoplasia and distinctive facial appearance, macrocephaly is a feature. At least 8 families reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14404 | PAH | Zornitza Stark Marked gene: PAH as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14401 | PCDH12 | Zornitza Stark Marked gene: PCDH12 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14398 | PEPD | Zornitza Stark Marked gene: PEPD as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14395 | PEX10 | Zornitza Stark Marked gene: PEX10 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14392 | PCK1 | Zornitza Stark Marked gene: PCK1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14392 | PCK1 | Zornitza Stark Phenotypes for gene: PCK1 were changed from to Phosphoenolpyruvate carboxykinase deficiency, cytosolic MIM#261680; Disorders of gluconeogenesis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14389 | QDPR | Zornitza Stark Marked gene: QDPR as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14389 | REEP1 | Zornitza Stark Marked gene: REEP1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14389 | REEP1 | Zornitza Stark Phenotypes for gene: REEP1 were changed from to Neuronopathy, distal hereditary motor, type VB MIM#614751; Spastic paraplegia 31, autosomal dominant MIM#610250; Charcot-Marie-Tooth; severe congenital distal SMA with diaphragmatic paralysis; congenital axonal neuropathy and diaphragmatic palsy | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14386 | RLBP1 | Zornitza Stark Marked gene: RLBP1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14383 | RMND1 | Zornitza Stark Marked gene: RMND1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14381 | RNASEH1 | Zornitza Stark Marked gene: RNASEH1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14379 | RBFOX2 |
Chern Lim edited their review of gene: RBFOX2: Added comment: - PMID: 26785492: Analysed CHD (1213 congenital heart disease trios) and control (autism spectrum disorder) trios for de novo mutations. Found RBFOX2 gene had significantly more damaging de novo variants than expected: 3 de novo LoF variants (eg. nonsense, frameshift, or canonical splice disruptions). All 3 probands have hypoplastic left heart syndrome (HLHS). No further patient-specific clinical or variant info were available. Same cohort later included in PMID: 32368696, listed 4 de novo variants in this gene, in patients with left ventricular outflow tract obstruction (LVOTO) or conotruncal defects (CTDs). - PMID: 27670201: RNA expression study showed the silenced allele harbours a nonsense RBFOX2 variant (Arg287*), CHD patient heart tissue sample, same patient published in PMID: 26785492. - PMID: 27485310: Functional studies using heart tissue sample from HLHS patient with NM_001031695.2:c.859C>T p.(Arg287*) showed subcellular mislocalisation, impacting its nuclear function in RNA splicing. - PMID: 25205790: De novo 111.3kb del chr22:36038076-36149338 (hg19) which includes APOL5,APOL6,RBFOX2, in a patient with HLHS. - PMID: 35137168: Rbfox2 conditional knockout mouse model recapitulated several molecular and phenotypic features of HLHS.; Changed publications: PMID: 26785492, 27670201, 27485310, 25205790, 35137168, 26785492 |
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| Mendeliome v0.14378 | RNASEH2A | Zornitza Stark Marked gene: RNASEH2A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14378 | RNASEH2A | Zornitza Stark Phenotypes for gene: RNASEH2A were changed from to Aicardi-Goutieres syndrome 4 MIM#610333 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14375 | RNF139 | Zornitza Stark Marked gene: RNF139 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14375 | RNF139 | Zornitza Stark Phenotypes for gene: RNF139 were changed from to Renal cell carcinoma MIM#144700 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14371 | RP1 | Zornitza Stark Marked gene: RP1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14368 | RP2 | Zornitza Stark Marked gene: RP2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14365 | RP9 | Zornitza Stark Marked gene: RP9 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14360 | RYR1 | Zornitza Stark Marked gene: RYR1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14360 | RYR1 | Zornitza Stark Phenotypes for gene: RYR1 were changed from to {Malignant hyperthermia susceptibility 1} MIM#145600; Central core disease, MIM# 117000; King-Denborough syndrome , MIM#619542; Minicore myopathy with external ophthalmoplegia , MIM#255320; Neuromuscular disease, congenital, with uniform type 1 fiber, MIM# 117000 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14357 | RYR1 | Zornitza Stark reviewed gene: RYR1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Central core disease, MIM# 117000, King-Denborough syndrome , MIM#619542, Minicore myopathy with external ophthalmoplegia , MIM#255320, Neuromuscular disease, congenital, with uniform type 1 fiber, MIM# 117000; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14357 | SACS | Zornitza Stark Marked gene: SACS as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14357 | SACS | Zornitza Stark Phenotypes for gene: SACS were changed from to Spastic ataxia, Charlevoix-Saguenay type MIM#270550 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14355 | SCN11A | Zornitza Stark Marked gene: SCN11A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14355 | SCN11A | Zornitza Stark Phenotypes for gene: SCN11A were changed from to Neuropathy, hereditary sensory and autonomic, type VII, MIM# 615548; Episodic pain syndrome, familial, 3, MIM# 615552 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14352 | SCN11A | Zornitza Stark edited their review of gene: SCN11A: Changed phenotypes: Neuropathy, hereditary sensory and autonomic, type VII, MIM# 615548, Episodic pain syndrome, familial, 3, MIM# 615552 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14352 | TMC8 | Zornitza Stark Marked gene: TMC8 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14345 | RBFOX2 |
Chern Lim gene: RBFOX2 was added gene: RBFOX2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RBFOX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RBFOX2 were set to PMID: 26785492; 27670201; 27485310; 25205790; 35137168 Phenotypes for gene: RBFOX2 were set to Hypoplastic left heart syndrome (HLHS) Review for gene: RBFOX2 was set to AMBER gene: RBFOX2 was marked as current diagnostic Added comment: - PMID: 26785492: Analysed CHD (1213 congenital heart disease trios) and control (autism spectrum disorder) trios for de novo mutations. Found RBFOX2 gene had significantly more damaging de novo variants than expected: 3 de novo LoF variants (eg. nonsense, frameshift, or canonical splice disruptions). All 3 probands have hypoplastic left heart syndrome (HLHS). No further patient-specific clinical or variant info were available. - PMID: 27670201: RNA expression study showed the silenced allele harbours a nonsense RBFOX2 variant (Arg287*), CHD patient heart tissue sample, same patient published in PMID: 26785492. - PMID: 27485310: Functional studies using heart tissue sample from HLHS patient with NM_001031695.2:c.859C>T p.(Arg287*) showed subcellular mislocalisation, impacting its nuclear function in RNA splicing. - PMID: 25205790: De novo 111.3kb del chr22:36038076-36149338 (hg19) which includes APOL5,APOL6,RBFOX2, in a patient with HLHS. - PMID: 35137168: Rbfox2 conditional knockout mouse model recapitulated several molecular and phenotypic features of HLHS. Sources: Literature |
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| Mendeliome v0.14345 | GRIA4 | Ain Roesley Marked gene: GRIA4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14344 | GRID2 | Ain Roesley Marked gene: GRID2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14344 | GRID2 | Ain Roesley Phenotypes for gene: GRID2 were changed from to Spinocerebellar ataxia, autosomal recessive 18 MIM#616204 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14343 | GRID2 | Ain Roesley reviewed gene: GRID2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32622959, 32170608; Phenotypes: Spinocerebellar ataxia, autosomal recessive 18 MIM#616204; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14343 | GRIN2D | Ain Roesley Marked gene: GRIN2D as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14341 | ARV1 | Abhijit Kulkarni reviewed gene: ARV1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35227294, 27270415, 25558065; Phenotypes: DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 38 ( MIM:61720) Dilated cardiomyopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14341 | UGT1A1 | Zornitza Stark Marked gene: UGT1A1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14341 | UGT1A1 | Zornitza Stark Phenotypes for gene: UGT1A1 were changed from to Bilirubin UDP-glucuronosyltransferase 1 deficiency (Disorders of bile acid metabolism and transport); Crigler-Najjar syndrome, type I 218800; Crigler-Najjar syndrome, type II 606785 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14339 | UNC13D | Zornitza Stark Marked gene: UNC13D as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14339 | UNG | Zornitza Stark Marked gene: UNG as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14337 | UQCC2 | Zornitza Stark Marked gene: UQCC2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14337 | UQCC2 | Zornitza Stark Phenotypes for gene: UQCC2 were changed from to Mitochondrial complex III deficiency, nuclear type 7 - MIM#615824 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14334 | UQCRB | Zornitza Stark Marked gene: UQCRB as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14334 | UQCRB | Zornitza Stark Phenotypes for gene: UQCRB were changed from to Mitochondrial complex III deficiency, nuclear type 3, MIM# 615158 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14331 | UROD | Zornitza Stark Marked gene: UROD as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14331 | UROD | Zornitza Stark Phenotypes for gene: UROD were changed from to Porphyria cutanea tarda; Porphyria, hepatoerythropoietic (MIM#176100) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14328 | MAGED2 | Zornitza Stark Marked gene: MAGED2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14328 | MAGED2 | Zornitza Stark Phenotypes for gene: MAGED2 were changed from to Bartter syndrome, type 5, antenatal, transient, MIM# 300971 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14325 | MAGED2 | Zornitza Stark reviewed gene: MAGED2: Rating: GREEN; Mode of pathogenicity: None; Publications: 27120771; Phenotypes: Bartter syndrome, type 5, antenatal, transient, MIM# 300971; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14325 | MRPS2 | Zornitza Stark Marked gene: MRPS2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14322 | MSH3 | Zornitza Stark Marked gene: MSH3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14319 | MSRB3 | Zornitza Stark Marked gene: MSRB3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14316 | MTAP | Zornitza Stark Marked gene: MTAP as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14316 | MTAP | Zornitza Stark Phenotypes for gene: MTAP were changed from to Diaphyseal medullary stenosis with malignant fibrous histiocytoma, MIM# 112250 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14312 | MTAP | Zornitza Stark reviewed gene: MTAP: Rating: AMBER; Mode of pathogenicity: None; Publications: 22464254; Phenotypes: Diaphyseal medullary stenosis with malignant fibrous histiocytoma, MIM# 112250; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14312 | MTFMT | Zornitza Stark Marked gene: MTFMT as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14312 | MTFMT | Zornitza Stark Phenotypes for gene: MTFMT were changed from to Combined oxidative phosphorylation deficiency 15, MIM# 614947; Mitochondrial complex I deficiency, nuclear type 27, MIM# 618248 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14309 | MTFMT | Zornitza Stark reviewed gene: MTFMT: Rating: GREEN; Mode of pathogenicity: None; Publications: 21907147, 23499752, 24461907, 22499348; Phenotypes: Combined oxidative phosphorylation deficiency 15, MIM# 614947, Mitochondrial complex I deficiency, nuclear type 27, MIM# 618248; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14309 | MTHFD1 | Zornitza Stark Marked gene: MTHFD1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14305 | MTHFR | Zornitza Stark Marked gene: MTHFR as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14302 | MTM1 | Zornitza Stark Marked gene: MTM1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14302 | MTM1 | Zornitza Stark Phenotypes for gene: MTM1 were changed from to Myopathy, centronuclear, X-linked, MIM# 310400 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14299 | MTM1 | Zornitza Stark reviewed gene: MTM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 10790201; Phenotypes: Myopathy, centronuclear, X-linked, MIM# 310400; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14299 | MTO1 | Zornitza Stark Marked gene: MTO1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14295 | MTOR | Zornitza Stark Marked gene: MTOR as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14291 | DNAJC6 | Krithika Murali reviewed gene: DNAJC6: Rating: GREEN; Mode of pathogenicity: None; Publications: 22563501, 23211418, 26528954; Phenotypes: Parkinson disease 19a, juvenile-onset - MIM#615528, Parkinson disease 19b, early-onset - MIM#615528; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14291 | DNAJC3 | Krithika Murali changed review comment from: Well-established association with monogenic diabetes with growth restriction, hypothyroidism, neuropathy, sensorineural hearing loss and cerebellar ataxia also reported affected individuals (PMID 33486469 Lytrvi et al 2021 report 2 additional families and summarise the phenotypic features of 4 previously reported families).; to: Well-established association with monogenic diabetes. Growth restriction, hypothyroidism, neuropathy, sensorineural hearing loss and cerebellar ataxia also reported in affected individuals (PMID 33486469 Lytrvi et al 2021 report 2 additional families and summarise the phenotypic features of 4 previously reported families). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14291 | DNAJC3 | Krithika Murali reviewed gene: DNAJC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 33486469, 34630333, 34654017, 32738013; Phenotypes: ?Ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus - MIM#616192; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14291 | DNAJC21 | Krithika Murali reviewed gene: DNAJC21: Rating: GREEN; Mode of pathogenicity: None; Publications: 29700810, 28062395, 27346687; Phenotypes: Bone marrow failure syndrome 3 - MIM#617052; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14291 | DNM1L | Krithika Murali reviewed gene: DNM1L: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1 - MIM#614388 (AD, AR), Optic atrophy 5 - MIM#610708 (AD); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14291 | DRD3 | Krithika Murali reviewed gene: DRD3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Essential tremor, hereditary, 1} - MIM#190300, {Schizophrenia, susceptibility to} - MIM#181500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14291 | DSCAM |
Krithika Murali edited their review of gene: DSCAM: Added comment: No OMIM gene disease association. Variants predominantly identified from large cohort studies with limited phenotypic information. Associations with ID, ASD, Hirschsprung disease reported. One homozygous splice site variant reported with no parental phenotypes provided. PMID 34253863 Lim et al 2021 - 12 yo proband with severe autism spectrum disorder diagnosed age 3, de novo heterozygous c.2051 del p.(L684X) variant identified (absent from gnomAD). Skin fibroblast human iPSC cells generated from proband and healthy controls. Forebrain-like induced neuronal cells showed reduced mRNA expression for NMDA-R subunits. PMID 28600779 Monies et al 2017 - Homozygous splice site variant identified in proband from consanguineous Saudi family. Proband had growth restriction, microcephaly, developmental delay. Parental phenotype not provided. PMID 30095639 and PMID 23671607 - report association between DSCAM polymorphisms and Hirschsprung disease in Chinese and European populations. PMID 27824329 Wang et al 2016 - 2 denovo mutations in mixed ID/ASD cohort of 1,045; including comparison of previously published cases 6 LOF out of 4,998 cases. PMID 28191889 2 denovo LOF in 13,407 mixed ID/ASD cases plus 4 previosly published cases our ot 6158; conclude denovo LOF enriched in cases vs controls PMID 21904980; mouse model – het LOF mice show hydrocephalus, decreased motor function and impaired motor learning ability, Evidence for missense lacking currently; Changed publications: 34253863, 32807774, 28600779, 21904980, 28191889, 27824329, 30095639, 23671607 |
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| Mendeliome v0.14291 | MTTP | Zornitza Stark Marked gene: MTTP as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14288 | MUT | Zornitza Stark Marked gene: MUT as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14285 | MVK | Zornitza Stark Marked gene: MVK as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14282 | MXI1 | Zornitza Stark Marked gene: MXI1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14281 | MYD88 | Zornitza Stark Marked gene: MYD88 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14278 | MYH14 | Zornitza Stark Marked gene: MYH14 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14278 | MYH14 | Zornitza Stark Phenotypes for gene: MYH14 were changed from to Deafness, autosomal dominant 4A, MIM# 600652; Peripheral neuropathy, myopathy, hoarseness, and hearing loss 614369 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14275 | MYH14 | Zornitza Stark reviewed gene: MYH14: Rating: GREEN; Mode of pathogenicity: None; Publications: 15015131, 25719458, 31045651, 28221712, 34681017, 21480433, 31653586, 31631044, 31231018; Phenotypes: Deafness, autosomal dominant 4A, MIM# 600652, Peripheral neuropathy, myopathy, hoarseness, and hearing loss 614369; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14275 | MYH3 | Zornitza Stark Marked gene: MYH3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14275 | MYH3 | Zornitza Stark Phenotypes for gene: MYH3 were changed from to Arthrogryposis, distal, type 2A (Freeman-Sheldon) 193700; Arthrogryposis, distal, type 2B3 (Sheldon-Hall) 618436; Contractures, pterygia, and spondylocarpostarsal fusion syndrome 1A 178110; Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1B 618469 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14272 | MYH3 | Zornitza Stark reviewed gene: MYH3: Rating: GREEN; Mode of pathogenicity: None; Publications: 25957469, 26544689, 21531865, 18695058; Phenotypes: Arthrogryposis, distal, type 2A (Freeman-Sheldon) 193700, Arthrogryposis, distal, type 2B3 (Sheldon-Hall) 618436, Contractures, pterygia, and spondylocarpostarsal fusion syndrome 1A 178110, Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1B 618469; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14272 | MYO1E | Zornitza Stark Marked gene: MYO1E as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14269 | WNT1 | Zornitza Stark Marked gene: WNT1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14266 | WNK4 | Zornitza Stark Marked gene: WNK4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14263 | WNK1 | Zornitza Stark Marked gene: WNK1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14263 | WNK1 | Zornitza Stark Phenotypes for gene: WNK1 were changed from to Neuropathy, hereditary sensory and autonomic, type II, MIM# 201300; MONDO:0024309; Pseudohypoaldosteronism, type IIC, MIM# 614492 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14260 | WNK1 |
Zornitza Stark changed review comment from: Well established gene-disease association. Note mono-allelic variants are associated with pseudohypoaldosteronism; to: Well established gene-disease associations. |
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| Mendeliome v0.14260 | WNK1 | Zornitza Stark edited their review of gene: WNK1: Changed phenotypes: Neuropathy, hereditary sensory and autonomic, type II, MIM# 201300, MONDO:0024309, Pseudohypoaldosteronism, type IIC, MIM# 614492; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14260 | WDR4 | Zornitza Stark Marked gene: WDR4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14256 | WDR36 |
Zornitza Stark changed review comment from: Multiple individuals reported. However, note one of the earliest reported variants p.Asp658Gly is present in >1,000 individuals in gnomad, and another, p.Ala449Thr is present in >2000.; to: Multiple individuals reported. Adult-onset. However, note one of the earliest reported variants p.Asp658Gly is present in >1,000 individuals in gnomad, and another, p.Ala449Thr is present in >2000. |
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| Mendeliome v0.14256 | WDR36 |
Zornitza Stark changed review comment from: Multiple individuals reported. However, note one of the earliest reported variants p.Asp658Gly is present in >1,000 individuals in gnomad.; to: Multiple individuals reported. However, note one of the earliest reported variants p.Asp658Gly is present in >1,000 individuals in gnomad, and another, p.Ala449Thr is present in >2000. |
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| Mendeliome v0.14256 | WDR36 | Zornitza Stark Marked gene: WDR36 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14253 | WASHC5 | Zornitza Stark Marked gene: WASHC5 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14253 | WASHC5 | Zornitza Stark Phenotypes for gene: WASHC5 were changed from to Ritscher-Schinzel syndrome 1, MIM# 220210; Spastic paraplegia 8, autosomal dominant, MIM# 603563 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14250 | WASHC5 | Zornitza Stark reviewed gene: WASHC5: Rating: GREEN; Mode of pathogenicity: None; Publications: 17160902, 23455931, 30778698, 24065355, 33456446; Phenotypes: Ritscher-Schinzel syndrome 1, MIM# 220210, Spastic paraplegia 8, autosomal dominant, MIM# 603563; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14250 | WASF1 | Zornitza Stark Marked gene: WASF1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14250 | WASF1 | Zornitza Stark Phenotypes for gene: WASF1 were changed from to Neurodevelopmental disorder with absent language and variable seizures , MIM#618707 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14247 | WASF1 | Zornitza Stark reviewed gene: WASF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29961568, 34845217, 34478686, 34356165; Phenotypes: Neurodevelopmental disorder with absent language and variable seizures , MIM#618707; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14247 | WAC | Zornitza Stark Marked gene: WAC as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14244 | FXYD2 | Bryony Thompson Marked gene: FXYD2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14239 | RIPPLY2 | Zornitza Stark Marked gene: RIPPLY2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14236 | FXN | Bryony Thompson Marked gene: FXN as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14236 | MYOC | Zornitza Stark Marked gene: MYOC as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14236 | MYOC | Zornitza Stark Phenotypes for gene: MYOC were changed from to Glaucoma 1A, primary open angle, MIM# 137750 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14233 | MYOC | Zornitza Stark reviewed gene: MYOC: Rating: GREEN; Mode of pathogenicity: None; Publications: 9005853, 9535666, 15108121; Phenotypes: Glaucoma 1A, primary open angle, MIM# 137750; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14232 | MYOCD |
Zornitza Stark changed review comment from: Congenital megabladder (MGBL) is characterized by a massively dilated bladder with disrupted smooth muscle in the bladder wall. MGBL is a sex-limited trait with 95% male predominance, likely the result of differences in urethra and bladder development and length differences in urethra between males and females. Seven affected males from three families. Five females and one male with the variant were unaffected, suggesting incomplete penetrance. Additional family in PMID 35005812 as part of a large prenatal renal cohort.; to: Congenital megabladder (MGBL) is characterized by a massively dilated bladder with disrupted smooth muscle in the bladder wall. MGBL is a sex-limited trait with 95% male predominance, likely the result of differences in urethra and bladder development and length differences in urethra between males and females. Seven affected males from three families. Five females and one male with the variant were unaffected, suggesting incomplete penetrance. Additional family in PMID 35005812 as part of a large prenatal renal cohort. Mono allelic disease in males (megabladder), bi-allelic disease in males and females (megabladder and congenital heart disease). Mouse models. |
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| Mendeliome v0.14232 | MYOCD | Zornitza Stark Marked gene: MYOCD as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14229 | MYOT | Zornitza Stark Marked gene: MYOT as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14229 | MYOT | Zornitza Stark Phenotypes for gene: MYOT were changed from to Myopathy, myofibrillar, 3, MIM# 609200; Myopathy, spheroid body, MIM# 182920 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14226 | MYOT | Zornitza Stark reviewed gene: MYOT: Rating: GREEN; Mode of pathogenicity: None; Publications: 10958653, 15111675, 16380616, 33250842, 32509353, 29924655; Phenotypes: Myopathy, myofibrillar, 3, MIM# 609200, Myopathy, spheroid body, MIM# 182920; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14223 | FXN | Bryony Thompson edited their review of gene: FXN: Added comment: Well-established gene-disease association. 96% of cases are caused by biallelic intronic GAA triplet repeat expansion and 4% are attributable to biallelic single nucleotide variants and small indels. Loss of function is the mechanism of disease.; Changed rating: GREEN; Changed publications: 20301458, 26704351; Changed phenotypes: Friedreich ataxia MONDO:0100339; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Set current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14223 | RNF139 | Belinda Chong reviewed gene: RNF139: Rating: RED; Mode of pathogenicity: None; Publications: 9689122; Phenotypes: Renal cell carcinoma MIM#144700; Mode of inheritance: Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14223 | FUT8 | Bryony Thompson Marked gene: FUT8 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14220 | FUT1 | Bryony Thompson Marked gene: FUT1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14219 | FUT1 | Bryony Thompson Added comment: Comment on list classification: Biallelic loss of function variants produce the Bombay blood group, which is a recessive H-deficient red blood cell phenotype. Bombay and para-Bombay individuals display no apparent deleterious phenotype except in circumstances requiring blood transfusion. No evidence for Mendelian disease associated with this gene. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14217 | FUT1 | Bryony Thompson Added comment: Comment on list classification: Biallelic loss of function variants cause Bombay phenotype, which is a recessive H-deficient red blood cell phenotype. Bombay and para-Bombay individuals display no apparent deleterious phenotype except in circumstances requiring blood transfusion. No evidence for Mendelian disease associated with this gene. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14215 | FSHR | Bryony Thompson Marked gene: FSHR as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14215 | FTO | Bryony Thompson Marked gene: FTO as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14214 | FTO | Bryony Thompson Phenotypes for gene: FTO were changed from to Growth retardation, developmental delay, facial dysmorphism MIM#612938 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14212 | FTO | Bryony Thompson reviewed gene: FTO: Rating: GREEN; Mode of pathogenicity: None; Publications: 19234441, 19559399, 26378117, 26697951, 26378117, 26740239; Phenotypes: Growth retardation, developmental delay, facial dysmorphism MIM#612938; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14212 | RIMS1 | Zornitza Stark Marked gene: RIMS1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14209 | RHEB | Zornitza Stark Marked gene: RHEB as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14209 | FSHR | Bryony Thompson Phenotypes for gene: FSHR were changed from to Ovarian dysgenesis 1 MONDO:0024463; Ovarian hyperstimulation syndrome MONDO:0011972 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14203 | FSHR | Bryony Thompson reviewed gene: FSHR: Rating: GREEN; Mode of pathogenicity: None; Publications: 16630814, 7553856, 9020851, 9769327, 20087398, 9854118, 12930928, 12930927, 17721928, 26911863; Phenotypes: Ovarian dysgenesis 1 MONDO:0024463, Ovarian hyperstimulation syndrome MONDO:0011972; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14203 | RHCE | Zornitza Stark Marked gene: RHCE as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14200 | RGS9BP | Zornitza Stark Marked gene: RGS9BP as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14197 | RGS9 | Zornitza Stark Marked gene: RGS9 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14194 | RFX6 | Zornitza Stark Marked gene: RFX6 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14191 | FXYD6 | Bryony Thompson Marked gene: FXYD6 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14188 | FZD2 | Bryony Thompson Marked gene: FZD2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14186 | FBP2 | Zornitza Stark Marked gene: FBP2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14185 | FBP2 |
Zornitza Stark gene: FBP2 was added gene: FBP2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: FBP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: FBP2 were set to 33977262 Phenotypes for gene: FBP2 were set to Leukodystrophy, childhood-onset, remitting, MIM# 619864 Review for gene: FBP2 was set to AMBER Added comment: 8 individuals from 3 generations in a single family reported with a variant in this gene. The children presented with episode of regression and leukodystrophy in early childhood, from which they made a slow recovery. The adults had a broad range of neurobehavioural phenotypes but also had leukodystrophy on imaging. Some functional data presented (in vitro). Sources: Expert list |
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| Mendeliome v0.14181 | MOV10L1 | Zornitza Stark Marked gene: MOV10L1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14178 | RFC2 | Zornitza Stark Marked gene: RFC2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14177 | REST | Zornitza Stark Marked gene: REST as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14174 | REEP6 | Zornitza Stark Marked gene: REEP6 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14171 | RCBTB1 | Zornitza Stark Marked gene: RCBTB1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14171 | RCBTB1 | Zornitza Stark Phenotypes for gene: RCBTB1 were changed from to Retinal dystrophy with or without extraocular anomalies, MIM# 617175 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14168 | RCBTB1 | Zornitza Stark reviewed gene: RCBTB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27486781, 35057699, 33624564, 33104391; Phenotypes: Retinal dystrophy with or without extraocular anomalies, MIM# 617175; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14167 | FSHB | Bryony Thompson Marked gene: FSHB as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14164 | FRZB | Bryony Thompson Marked gene: FRZB as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14164 | FRZB | Bryony Thompson Phenotypes for gene: FRZB were changed from to {Osteoarthritis susceptibility 1} MIM#165720 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14163 | FRRS1L | Bryony Thompson Marked gene: FRRS1L as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14158 | FRZB | Bryony Thompson reviewed gene: FRZB: Rating: RED; Mode of pathogenicity: None; Publications: 15210948; Phenotypes: {Osteoarthritis susceptibility 1} MIM#165720; Mode of inheritance: Unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14158 | FOXN1 | Bryony Thompson Marked gene: FOXN1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14158 | RBPJ | Zornitza Stark Marked gene: RBPJ as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14152 | FOXI1 | Bryony Thompson Marked gene: FOXI1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14152 | FOXI1 | Bryony Thompson Phenotypes for gene: FOXI1 were changed from to autosomal recessive distal renal tubular acidosis MONDO:0018440 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14149 | FOXI1 | Bryony Thompson reviewed gene: FOXI1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9843211, 12642503, 29242249, 17503324, 30268946, 27997596, 22285650, 23965030, 24860705, 32447495, 19204907; Phenotypes: autosomal recessive distal renal tubular acidosis MONDO:0018440; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14149 | FOXD3 | Bryony Thompson Marked gene: FOXD3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14146 | FMR1 | Bryony Thompson Marked gene: FMR1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14145 | RBP3 | Zornitza Stark Marked gene: RBP3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14142 | RBM28 | Zornitza Stark Marked gene: RBM28 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14138 | RASGRP2 | Zornitza Stark Marked gene: RASGRP2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14135 | SCN2A | Zornitza Stark Marked gene: SCN2A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14131 | SCN9A | Zornitza Stark Marked gene: SCN9A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14131 | SCN9A | Zornitza Stark Phenotypes for gene: SCN9A were changed from to Erythermalgia, primary, MIM# 133020; Insensitivity to pain, congenital, MIM# 243000; Neuropathy, hereditary sensory and autonomic, type IID, MIM# 243000; Paroxysmal extreme pain disorder, MIM# 167400; Small fiber neuropathy,MIM# 133020 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14129 | SLC22A5 | Zornitza Stark Marked gene: SLC22A5 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14129 | SLC22A5 | Zornitza Stark Phenotypes for gene: SLC22A5 were changed from to Carnitine deficiency, systemic primary, MIM# 212140, MONDO:0008919 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14126 | SLC22A12 | Zornitza Stark Marked gene: SLC22A12 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14123 | SLC1A2 | Zornitza Stark Marked gene: SLC1A2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14119 | SLC1A1 | Zornitza Stark Marked gene: SLC1A1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14119 | SLC1A1 | Zornitza Stark Phenotypes for gene: SLC1A1 were changed from to Dicarboxylic aminoaciduria, MIM# 222730 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14115 | SLC1A1 | Zornitza Stark reviewed gene: SLC1A1: Rating: AMBER; Mode of pathogenicity: None; Publications: 21123949; Phenotypes: Dicarboxylic aminoaciduria, MIM# 222730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14115 | SLC19A3 | Zornitza Stark Marked gene: SLC19A3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14112 | SLC17A8 | Zornitza Stark Marked gene: SLC17A8 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14109 | SLC17A3 | Zornitza Stark Marked gene: SLC17A3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14105 | SLC16A1 | Zornitza Stark Marked gene: SLC16A1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14105 | SLC16A1 | Zornitza Stark Phenotypes for gene: SLC16A1 were changed from to Erythrocyte lactate transporter defect, MIM# 245340; Hyperinsulinemic hypoglycaemia, familial, 7, MIM# 610021; Monocarboxylate transporter 1 deficiency, MIM# 616095 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14102 | SLC16A1 | Zornitza Stark reviewed gene: SLC16A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25390740, 32170320; Phenotypes: Erythrocyte lactate transporter defect, MIM# 245340, Hyperinsulinemic hypoglycaemia, familial, 7, MIM# 610021, Monocarboxylate transporter 1 deficiency, MIM# 616095; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14102 | SLC11A2 | Zornitza Stark Marked gene: SLC11A2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14099 | SH2D1A | Zornitza Stark Marked gene: SH2D1A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14096 | SGCG | Zornitza Stark Marked gene: SGCG as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14096 | SGCG | Zornitza Stark Phenotypes for gene: SGCG were changed from to Muscular dystrophy, limb-girdle, autosomal recessive 5 MIM#253700; autosomal recessive limb-girdle muscular dystrophy MONDO:0015152 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14092 | FLVCR1 | Bryony Thompson Marked gene: FLVCR1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14091 | FLNC | Bryony Thompson Marked gene: FLNC as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14088 | FLNC | Bryony Thompson Phenotypes for gene: FLNC were changed from to Myofibrillar myopathy MONDO:0018943; Dilated cardiomyopathy MONDO:0005021; distal myopathy with posterior leg and anterior hand involvement MONDO:0013550 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14085 | FLNC | Bryony Thompson reviewed gene: FLNC: Rating: GREEN; Mode of pathogenicity: None; Publications: 15929027, 32112656; Phenotypes: Myofibrillar myopathy MONDO:0018943, Dilated cardiomyopathy MONDO:0005021, distal myopathy with posterior leg and anterior hand involvement MONDO:0013550; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14085 | FLNB | Bryony Thompson edited their review of gene: FLNB: Changed phenotypes: spondylocarpotarsal synostosis syndrome MONDO:0010094, filamin-related bone disorder MONDO:0019690 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14085 | FLNB | Bryony Thompson Phenotypes for gene: FLNB were changed from spondylocarpotarsal synostosis syndrome MONDO:0010094; osteochondrodysplasia MONDO:0005516 to spondylocarpotarsal synostosis syndrome MONDO:0010094; filamin-related bone disorder MONDO:0019690 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14084 | FLNB | Bryony Thompson Marked gene: FLNB as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14084 | FLNB | Bryony Thompson Phenotypes for gene: FLNB were changed from to spondylocarpotarsal synostosis syndrome MONDO:0010094; osteochondrodysplasia MONDO:0005516 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14081 | FLNB | Bryony Thompson reviewed gene: FLNB: Rating: GREEN; Mode of pathogenicity: None; Publications: 14991055, 17360453, 20301736, 29566257, 16801345, 22190451; Phenotypes: spondylocarpotarsal synostosis syndrome MONDO:0010094, osteochondrodysplasia MONDO:0005516; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14081 | FLI1 | Bryony Thompson Marked gene: FLI1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14078 | FLG | Bryony Thompson Marked gene: FLG as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14078 | ASS1 | Elena Savva Marked gene: ASS1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14078 | FLG | Bryony Thompson Phenotypes for gene: FLG were changed from to Ichthyosis vulgaris MONDO:0024304 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14074 | ASTN1 | Elena Savva Marked gene: ASTN1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14072 | FLG | Bryony Thompson reviewed gene: FLG: Rating: GREEN; Mode of pathogenicity: None; Publications: 16444271, 19349982, 34608691; Phenotypes: Ichthyosis vulgaris MONDO:0024304; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14070 | FKTN | Bryony Thompson Marked gene: FKTN as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14070 | FKTN | Bryony Thompson Phenotypes for gene: FKTN were changed from to Muscular dystrophy-dystroglycanopathy MONDO:0018276 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14067 | FKTN | Bryony Thompson reviewed gene: FKTN: Rating: GREEN; Mode of pathogenicity: None; Publications: 9690476, 19017726, 20301385, 28680109; Phenotypes: Muscular dystrophy-dystroglycanopathy MONDO:0018276; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14067 | GSN | Zornitza Stark Marked gene: GSN as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14064 | GSN |
Zornitza Stark changed review comment from: The Finnish type of systemic amyloidosis is characterized clinically by a unique constellation of features including lattice corneal dystrophy, and cranial neuropathy, bulbar signs, and skin changes. Some patients may develop peripheral neuropathy and renal failure. The disorder is usually inherited in an autosomal dominant pattern; however, homozygotes with a more severe phenotype have also been reported. Multiple families with same founder variant.; to: The Finnish type of systemic amyloidosis is characterized clinically by a unique constellation of features including lattice corneal dystrophy, and cranial neuropathy, bulbar signs, and skin changes. Some patients may develop peripheral neuropathy and renal failure. The disorder is usually inherited in an autosomal dominant pattern; however, homozygotes with a more severe phenotype have also been reported. Multiple families with same founder variant, p.Asp187Asn, though other variants also reported. |
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| Mendeliome v0.14064 | GSS | Zornitza Stark Marked gene: GSS as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14061 | GTF3C3 | Zornitza Stark Marked gene: GTF3C3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14058 | GUCA1A | Zornitza Stark Marked gene: GUCA1A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14054 | ASB10 | Elena Savva Marked gene: ASB10 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14053 | FKRP | Bryony Thompson Marked gene: FKRP as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14053 | FKRP | Bryony Thompson Phenotypes for gene: FKRP were changed from to Muscular dystrophy-dystroglycanopathy MONDO:0018276 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14050 | ART4 | Elena Savva Phenotypes for gene: ART4 were changed from {Macular degeneration, age-related, 8} MIM#613778 to {Macular degeneration, age-related, 8} MIM#613778 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14050 | ART4 | Elena Savva Mode of inheritance for gene: ART4 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14049 | FKRP | Bryony Thompson reviewed gene: FKRP: Rating: GREEN; Mode of pathogenicity: None; Publications: 11592034, 11741828, 14647208, 19299310, 19155270; Phenotypes: Muscular dystrophy-dystroglycanopathy MONDO:0018276; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14049 | ART4 | Elena Savva Phenotypes for gene: ART4 were changed from to {Macular degeneration, age-related, 8} MIM#613778 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14048 | ART4 | Elena Savva Mode of inheritance for gene: ART4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14048 | ART4 | Elena Savva Marked gene: ART4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14048 | ART4 | Elena Savva Gene: art4 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14048 | ART4 | Elena Savva Publications for gene: ART4 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14048 | ART4 | Elena Savva Classified gene: ART4 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14048 | ART4 | Elena Savva Gene: art4 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14047 | ART4 | Elena Savva reviewed gene: ART4: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 33675039, 33206405; Phenotypes: {Macular degeneration, age-related, 8} MIM#613778; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14047 | FHL1 | Bryony Thompson Marked gene: FHL1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14047 | FHL1 | Bryony Thompson Phenotypes for gene: FHL1 were changed from to Reducing body myopathy MONDO:0019948; X-linked Emery-Dreifuss muscular dystrophy MONDO:0010680 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14045 | ASPA | Elena Savva Marked gene: ASPA as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14044 | ARMS2 | Elena Savva Phenotypes for gene: ARMS2 were changed from {Macular degeneration, age-related, 8} MIM#613778 to {Macular degeneration, age-related, 8} MIM#613778 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14041 | ASH1L | Elena Savva Phenotypes for gene: ASH1L were changed from Mental retardation, autosomal dominant 52, MIM#617796 to Mental retardation, autosomal dominant 52, MIM#617796 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14040 | ARMS2 | Elena Savva Phenotypes for gene: ARMS2 were changed from to {Macular degeneration, age-related, 8} MIM#613778 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14040 | ARMS2 | Elena Savva Classified gene: ARMS2 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14040 | ARMS2 | Elena Savva Gene: arms2 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14039 | ARMS2 | Elena Savva Marked gene: ARMS2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14039 | ARMS2 | Elena Savva Gene: arms2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14039 | FHL1 | Bryony Thompson reviewed gene: FHL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19716112, 20186852, 20301609, 18179901, 25274776, 34366191, 18274675, 19181672; Phenotypes: Reducing body myopathy MONDO:0019948, X-linked Emery-Dreifuss muscular dystrophy MONDO:0010680; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males); Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14039 | ASH1L | Elena Savva Phenotypes for gene: ASH1L were changed from to Mental retardation, autosomal dominant 52, MIM#617796 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14038 | ASH1L | Elena Savva Marked gene: ASH1L as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14037 | ARMS2 | Elena Savva reviewed gene: ARMS2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Macular degeneration, age-related, 8} MIM#613778; Mode of inheritance: Unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14037 | ARL2BP | Elena Savva Publications for gene: ARL2BP were set to PMID: 23849777; 27790702; 29718757 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14036 | ARL2BP | Elena Savva Publications for gene: ARL2BP were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14035 | ARL2BP | Elena Savva Marked gene: ARL2BP as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14035 | ARL2BP | Elena Savva Gene: arl2bp has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14035 | ARL2BP | Elena Savva Phenotypes for gene: ARL2BP were changed from to Retinitis pigmentosa with or without situs inversus MIM#615434 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14035 | ARL2BP | Elena Savva Mode of inheritance for gene: ARL2BP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14034 | ARL2BP | Elena Savva reviewed gene: ARL2BP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Retinitis pigmentosa with or without situs inversus MIM#615434; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14034 | FH | Bryony Thompson Marked gene: FH as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14034 | FH | Bryony Thompson Phenotypes for gene: FH were changed from to hereditary leiomyomatosis and renal cell cancer MONDO:0007888; fumaric aciduria MONDO:0011730 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14031 | FH | Bryony Thompson changed review comment from: Well established gene-disease associations. Loss of function is the mechanism of disease. Monoallelic variants associated with decreased fumarate hydratase enzyme activity cause FH tumour predisposition syndrome (also known as HLRCC; PMID: 11865300, 28300276). FH deficiency (also known as fumarase deficiency or fumaric aciduria) caused by biallelic variants results in severe neonatal and early infantile encephalopathy (PMID: 8200987, 20549362, 31746132). FH encodes for both mitochondrial and cytosolic FH enzyme isoforms, which catalyze hydration of fumarate to malate.; to: Well established gene-disease associations. Loss of function is the mechanism of disease. Monoallelic variants associated with decreased fumarate hydratase enzyme activity cause FH tumour predisposition syndrome (also known as HLRCC; PMID: 11865300, 28300276, 20301430). FH deficiency (also known as fumarase deficiency or fumaric aciduria) caused by biallelic variants results in severe neonatal and early infantile encephalopathy (PMID: 8200987, 20549362, 31746132, 20301679). FH encodes for both mitochondrial and cytosolic FH enzyme isoforms, which catalyze hydration of fumarate to malate. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14031 | FH | Bryony Thompson reviewed gene: FH: Rating: GREEN; Mode of pathogenicity: None; Publications: 11865300, 28300276, 8200987, 20549362, 31746132; Phenotypes: hereditary leiomyomatosis and renal cell cancer MONDO:0007888, fumaric aciduria MONDO:0011730; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14031 | ARID1B | Elena Savva Phenotypes for gene: ARID1B were changed from to Coffin-Siris syndrome 1 MIM#135900 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14030 | ARID1B | Elena Savva Marked gene: ARID1B as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14030 | ARID1B | Elena Savva Gene: arid1b has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14030 | ARID1B | Elena Savva Mode of inheritance for gene: ARID1B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14029 | ARID1B | Elena Savva reviewed gene: ARID1B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Coffin-Siris syndrome 1 MIM#135900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14029 | FGG | Bryony Thompson Marked gene: FGG as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14027 | ARHGDIA | Elena Savva Phenotypes for gene: ARHGDIA were changed from Nephrotic syndrome, type 8 MIM#615244 to Nephrotic syndrome, type 8 MIM#615244 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14026 | ARHGDIA | Elena Savva Publications for gene: ARHGDIA were set to PMID: 23867502; 35060086 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14026 | ARHGDIA | Elena Savva Mode of inheritance for gene: ARHGDIA was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14025 | ARHGEF18 | Elena Savva Marked gene: ARHGEF18 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14025 | ARHGEF18 | Elena Savva Gene: arhgef18 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14024 | FGFR3 | Bryony Thompson Phenotypes for gene: FGFR3 were changed from achondroplasia MONDO:0007037; Thanatophoric dysplasia type 1 MONDO:0008546; Thanatophoric dysplasia type 2 MONDO:0008547; hypochondroplasia MONDO:0007793; Muenke syndrome MONDO:0011274; FGFR3-related chondrodysplasia MONDO:0019685; severe achondroplasia-developmental delay-acanthosis nigricans syndrome MONDO:0014658; camptodactyly-tall stature-scoliosis-hearing loss syndrome MONDO:0012504; Crouzon syndrome-acanthosis nigricans syndrome MONDO:0012833 to achondroplasia MONDO:0007037; Thanatophoric dysplasia type 1 MONDO:0008546; Thanatophoric dysplasia type 2 MONDO:0008547; hypochondroplasia MONDO:0007793; Muenke syndrome MONDO:0011274; FGFR3-related chondrodysplasia MONDO:0019685; severe achondroplasia-developmental delay-acanthosis nigricans syndrome MONDO:0014658; Crouzon syndrome-acanthosis nigricans syndrome MONDO:0012833; camptodactyly-tall stature-scoliosis-hearing loss syndrome MONDO:0012504 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14020 | FGFR3 |
Bryony Thompson changed review comment from: FGFR3 has many well-established gene-disease associations with various skeletal dysplasia phenotypes. Gain-of-function is the main mechanism of disease for these disorders, except camptodactyly-tall stature-scoliosis-hearing loss syndrome where bialellic loss-of-function is the expected mechanism of disease. Specific monoallelic variants cause different phenotypes: >99% achondroplasia is caused by variants leading to the missense change p.Gly380Arg; Cysteine substitutions and stop-loss protein elongation variants are highly specific for Thanatophoric dysplasia (TD) type 1; p.Lys650Glu is associated with TD type 2; p.Ala391Glu causes Crouzon syndrome with acanthosis nigricans; and p.Pro250Arg causes Muenke syndrome.; to: FGFR3 has many well-established gene-disease associations with various skeletal dysplasia phenotypes. Gain-of-function is the main mechanism of disease for these disorders, except camptodactyly-tall stature-scoliosis-hearing loss syndrome (CATSHL syndrome, see separate curation below). Specific monoallelic variants cause different phenotypes: >99% achondroplasia is caused by variants leading to the missense change p.Gly380Arg; Cysteine substitutions and stop-loss protein elongation variants are highly specific for Thanatophoric dysplasia (TD) type 1; p.Lys650Glu is associated with TD type 2; p.Ala391Glu causes Crouzon syndrome with acanthosis nigricans; and p.Pro250Arg causes Muenke syndrome. Moderate evidence for CATSHL syndrome, AD & AR: PMID: 8630492, 17033969, 27139183, 24864036, 32641982 - 2 apparently unrelated families segregating the same missense, p.Arg621His. One consanguineous family with 2 affected brothers with homozygous p.Thr546Lys. Heterozygous individuals in the family were unaffected. No functional assays were conducted for either missense to demonstrate loss of function. Null mouse and zebrafish models are similar to the human CATSHL syndrome phenotype. |
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| Mendeliome v0.14020 | GUCA1B |
Zornitza Stark changed review comment from: Single founder variant identified in several Japanese individuals.; to: Single founder variant identified in several Japanese individuals. No other P/LP variants in ClinVar. |
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| Mendeliome v0.14020 | GUCA1B | Zornitza Stark Marked gene: GUCA1B as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14016 | FGFR3 | Bryony Thompson edited their review of gene: FGFR3: Changed mode of pathogenicity: Other; Changed publications: 8630492, 32641982, 27139183, 24864036, 17033969, 20301331, 20301540, 20301650, 20301628; Changed phenotypes: achondroplasia MONDO:0007037, Thanatophoric dysplasia type 1 MONDO:0008546, Thanatophoric dysplasia type 2 MONDO:0008547, hypochondroplasia MONDO:0007793, Muenke syndrome MONDO:0011274, FGFR3-related chondrodysplasia MONDO:0019685, severe achondroplasia-developmental delay-acanthosis nigricans syndrome MONDO:0014658, Crouzon syndrome-acanthosis nigricans syndrome MONDO:0012833, camptodactyly-tall stature-scoliosis-hearing loss syndrome MONDO:0012504; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14016 | GUCY1A3 | Zornitza Stark Marked gene: GUCY1A3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14013 | GYG1 | Zornitza Stark Marked gene: GYG1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14010 | GUCY2D | Zornitza Stark Marked gene: GUCY2D as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14010 | GUCY2D | Zornitza Stark Phenotypes for gene: GUCY2D were changed from to Cone-rod dystrophy 6, MIM# 601777; Leber congenital amaurosis 1, MIM# 204000; Night blindness, congenital stationary, type 1I, MIM# 618555 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14007 | GUCY2D | Zornitza Stark reviewed gene: GUCY2D: Rating: GREEN; Mode of pathogenicity: None; Publications: 35314386, 35205358; Phenotypes: Cone-rod dystrophy 6, MIM# 601777, Leber congenital amaurosis 1, MIM# 204000, Night blindness, congenital stationary, type 1I, MIM# 618555; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14007 | HPRT1 | Zornitza Stark Marked gene: HPRT1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14006 | ARHGEF18 | Elena Savva Phenotypes for gene: ARHGEF18 were changed from to Retinitis pigmentosa 78 MIM#617433 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14005 | ARHGEF18 | Elena Savva Publications for gene: ARHGEF18 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14005 | ARHGEF18 | Elena Savva Mode of inheritance for gene: ARHGEF18 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14004 | ARHGEF18 | Elena Savva reviewed gene: ARHGEF18: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28132693; Phenotypes: Retinitis pigmentosa 78 MIM#617433; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14004 | ARHGDIA | Elena Savva Publications for gene: ARHGDIA were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14004 | ARHGDIA | Elena Savva Phenotypes for gene: ARHGDIA were changed from to Nephrotic syndrome, type 8 MIM#615244 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14004 | ARHGDIA | Elena Savva Mode of inheritance for gene: ARHGDIA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14003 | ARHGDIA | Elena Savva Marked gene: ARHGDIA as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14003 | ARHGDIA | Elena Savva Gene: arhgdia has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14003 | ARHGDIA | Elena Savva reviewed gene: ARHGDIA: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 23867502, 35060086; Phenotypes: Nephrotic syndrome, type 8 MIM#615244; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14003 | ARHGAP31 | Elena Savva Marked gene: ARHGAP31 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14003 | ARHGAP31 | Elena Savva Gene: arhgap31 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14003 | ARHGAP31 | Elena Savva Phenotypes for gene: ARHGAP31 were changed from to Adams-Oliver syndrome 1, MIM#100300 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14002 | ARHGAP31 | Elena Savva Publications for gene: ARHGAP31 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14001 | ARHGAP31 | Elena Savva Mode of inheritance for gene: ARHGAP31 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14000 | ARHGAP31 | Elena Savva reviewed gene: ARHGAP31: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33655927, 29924900; Phenotypes: Adams-Oliver syndrome 1, MIM#100300; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14000 | ANXA5 | Elena Savva Marked gene: ANXA5 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13997 | AR | Elena Savva Marked gene: AR as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13997 | AR | Elena Savva Gene: ar has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13997 | GYPA | Zornitza Stark Marked gene: GYPA as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13994 | GYPB | Zornitza Stark Marked gene: GYPB as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13991 | HAAO | Zornitza Stark reviewed gene: HAAO: Rating: GREEN; Mode of pathogenicity: None; Publications: 33942433; Phenotypes: Vertebral, cardiac, renal, and limb defects syndrome 1 MIM#617660; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13991 | LZTS1 | Alison Yeung Marked gene: LZTS1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13991 | LZTS1 | Alison Yeung Phenotypes for gene: LZTS1 were changed from to Esophageal squamous cell carcinoma, somatic, MIM# 133239 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13989 | LZTS1 | Alison Yeung reviewed gene: LZTS1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Esophageal squamous cell carcinoma, somatic, MIM# 133239; Mode of inheritance: Unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13989 | LYZ | Alison Yeung Marked gene: LYZ as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13986 | LYST | Alison Yeung Marked gene: LYST as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13984 | LYRM7 | Alison Yeung Marked gene: LYRM7 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13984 | LYRM7 | Alison Yeung Phenotypes for gene: LYRM7 were changed from to Mitochondrial complex III deficiency, nuclear type 8, MIM#615838 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13982 | LYN | Alison Yeung Marked gene: LYN as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13982 | LYN | Alison Yeung Added comment: Comment when marking as ready: No human disease association published. Mouse models suggest role in auto inflammatory pathways. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13981 | LTC4S | Alison Yeung Marked gene: LTC4S as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13978 | LTA | Alison Yeung Marked gene: LTA as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13978 | LTA | Alison Yeung Added comment: Comment when marking as ready: Not associated with Mendelian disease | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13978 | LTA | Alison Yeung Phenotypes for gene: LTA were changed from to Myocardial infarction, susceptibility to, MIM# 608446 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13975 | LTA | Alison Yeung reviewed gene: LTA: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Myocardial infarction, susceptibility to, MIM# 608446; Mode of inheritance: Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13975 | LRP6 | Alison Yeung Marked gene: LRP6 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13973 | LRP5 | Alison Yeung Marked gene: LRP5 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13971 | LRP2 | Alison Yeung Marked gene: LRP2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13971 | LRP2 | Alison Yeung Phenotypes for gene: LRP2 were changed from to Donnai-Barrow syndrome, MIM# 222448 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13970 | LRIG2 | Alison Yeung Marked gene: LRIG2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13967 | FGFR3 | Bryony Thompson Marked gene: FGFR3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13967 | FGFR3 | Bryony Thompson Phenotypes for gene: FGFR3 were changed from to achondroplasia MONDO:0007037; Thanatophoric dysplasia type 1 MONDO:0008546; Thanatophoric dysplasia type 2 MONDO:0008547; hypochondroplasia MONDO:0007793; Muenke syndrome MONDO:0011274; FGFR3-related chondrodysplasia MONDO:0019685; severe achondroplasia-developmental delay-acanthosis nigricans syndrome MONDO:0014658; camptodactyly-tall stature-scoliosis-hearing loss syndrome MONDO:0012504; Crouzon syndrome-acanthosis nigricans syndrome MONDO:0012833 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13964 | FGFR3 | Bryony Thompson reviewed gene: FGFR3: Rating: GREEN; Mode of pathogenicity: None; Publications: 26740388, 20301331, 20301540, 20301650, 20301628, 24864036, 17033969; Phenotypes: achondroplasia MONDO:0007037, Thanatophoric dysplasia type 1 MONDO:0008546, Thanatophoric dysplasia type 2 MONDO:0008547, hypochondroplasia MONDO:0007793, Muenke syndrome MONDO:0011274, FGFR3-related chondrodysplasia MONDO:0019685, severe achondroplasia-developmental delay-acanthosis nigricans syndrome MONDO:0014658, camptodactyly-tall stature-scoliosis-hearing loss syndrome MONDO:0012504, Crouzon syndrome-acanthosis nigricans syndrome MONDO:0012833; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13964 | DNAJB6 | Ain Roesley Marked gene: DNAJB6 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13964 | DNAJB6 | Ain Roesley Phenotypes for gene: DNAJB6 were changed from to Muscular dystrophy, limb-girdle, autosomal dominant 1 MIM#603511 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13962 | DNAJB6 | Ain Roesley reviewed gene: DNAJB6: Rating: GREEN; Mode of pathogenicity: None; Publications: 26847086, 26338452, 24170373; Phenotypes: Muscular dystrophy, limb-girdle, autosomal dominant 1 MIM#603511; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13962 | DNAH1 | Ain Roesley Phenotypes for gene: DNAH1 were changed from Spermatogenic failure 18 MIM#617576 to primary ciliary dyskinesia,37 MIM#617577; Spermatogenic failure 18 MIM#617576 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13961 | DNAH1 | Ain Roesley Marked gene: DNAH1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13958 | DNAH1 | Ain Roesley reviewed gene: DNAH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31507630, 31765523, 25927852, 24360805, 33577779; Phenotypes: primary ciliary dyskinesia,37 MIM#617577, Spermatogenic failure 18 MIM#617576; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13958 | DNA2 | Ain Roesley Marked gene: DNA2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13956 | DMP1 | Ain Roesley Marked gene: DMP1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13954 | AQP3 | Elena Savva Marked gene: AQP3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13954 | DMD | Ain Roesley Marked gene: DMD as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13954 | DMD | Ain Roesley Phenotypes for gene: DMD were changed from to Becker muscular dystrophy MIM@300376 XLR; Cardiomyopathy, dilated, 3B MIM#302045 XL; Duchenne muscular dystrophy MIM#310200 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13952 | DMD | Ain Roesley reviewed gene: DMD: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301298; Phenotypes: Becker muscular dystrophy MIM@300376 XLR, Cardiomyopathy, dilated, 3B MIM#302045 XL, Duchenne muscular dystrophy MIM#310200; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males); Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13952 | DLX3 | Ain Roesley Marked gene: DLX3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13951 | DLAT | Ain Roesley Marked gene: DLAT as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13949 | DISC1 | Ain Roesley Marked gene: DISC1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13948 | LPL | Alison Yeung Marked gene: LPL as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13946 | DHTKD1 | Ain Roesley Marked gene: DHTKD1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13946 | DHTKD1 | Ain Roesley Added comment: Comment when marking as ready: green for AR, amber for AD | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13945 | DHTKD1 | Ain Roesley Phenotypes for gene: DHTKD1 were changed from to Alpha-aminoadipic and alpha-ketoadipic aciduria MIM#204750, AR; Charcot-Marie-Tooth disease, axonal, type 2Q, MIM#615025 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13943 | LPAR6 | Alison Yeung Marked gene: LPAR6 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13943 | LPAR6 | Alison Yeung Gene: lpar6 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13943 | LPAR6 | Alison Yeung Phenotypes for gene: LPAR6 were changed from to Woolly hair, autosomal recessive 1, with or without hypotrichosis, MIM# 609239 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13942 | LPAR6 | Alison Yeung Mode of inheritance for gene: LPAR6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13941 | LPAR6 | Alison Yeung reviewed gene: LPAR6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Woolly hair, autosomal recessive 1, with or without hypotrichosis, MIM# 609239; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13941 | DHH | Ain Roesley Marked gene: DHH as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13941 | DHH | Ain Roesley Phenotypes for gene: DHH were changed from 46XY partial gonadal dysgenesis, with minifascicular neuropathy, MIM# 607080 to 46XY gonadal dysgenesis with minifascicular neuropathy MIM#607080; 46XY sex reversal 7 MIM#233420 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13940 | LOXL1 | Alison Yeung Marked gene: LOXL1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13937 | LMF1 | Alison Yeung Marked gene: LMF1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13935 | LMBRD1 | Alison Yeung Marked gene: LMBRD1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13932 | LMBR1 | Alison Yeung Marked gene: LMBR1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13930 | SLC22A5 | Manny Jacobs reviewed gene: SLC22A5: Rating: GREEN; Mode of pathogenicity: None; Publications: 9916797, 10072434, 10051646, 10425211, 10480371, 10679939, 9837751, 23379544, 31399326; Phenotypes: Carnitine deficiency, systemic primary, MIM# 212140, MONDO:0008919; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13930 | CYP27B1 | Ain Roesley Marked gene: CYP27B1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13928 | CYP51A1 | Ain Roesley Marked gene: CYP51A1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13928 | CYP51A1 | Ain Roesley Phenotypes for gene: CYP51A1 were changed from to congenital cataract-severe neonatal hepatopathy-global developmental delay syndrome MONDO#0033853 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13926 | CYP4V2 | Ain Roesley Marked gene: CYP4V2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13924 | CYP2R1 | Ain Roesley Marked gene: CYP2R1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13922 | CYP2D6 | Ain Roesley Marked gene: CYP2D6 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13919 | CYP2C19 |
Ain Roesley changed review comment from: Voriconazole: Improved time to target concentration with genotype directed dosing (PMID 26616742), reduced underexposure (PMID: 31549389) (PMID 31549386) (PMID:27981572) Voriconazole, moderate strength. Poor metabolizer: "Higher dose-adjusted trough concentrations of voriconazole and may increase probability of adverse events." Ultrarapid metabolizer: "probability of attainment of therapeutic voriconazole concentrations is small with standard dosing."; to: Pharmacogenomics gene Voriconazole: Improved time to target concentration with genotype directed dosing (PMID 26616742), reduced underexposure (PMID: 31549389) (PMID 31549386) (PMID:27981572) Voriconazole, moderate strength. Poor metabolizer: "Higher dose-adjusted trough concentrations of voriconazole and may increase probability of adverse events." Ultrarapid metabolizer: "probability of attainment of therapeutic voriconazole concentrations is small with standard dosing." |
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| Mendeliome v0.13919 | DGUOK | Zornitza Stark Marked gene: DGUOK as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13916 | DGKE | Zornitza Stark Marked gene: DGKE as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13913 | DES | Zornitza Stark Marked gene: DES as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13913 | DES | Zornitza Stark Phenotypes for gene: DES were changed from to Cardiomyopathy, dilated, 1I, MIM# 604765; Myopathy, myofibrillar, 1 , MIM#601419; Arrhythmogenic right ventricular cardiomyopathy | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13911 | DES | Zornitza Stark reviewed gene: DES: Rating: GREEN; Mode of pathogenicity: None; Publications: 20718792, 19879535, 20423733, 24200904, 22395865, 29212896, 23168288, 20829228, 10430757, 11728149, 17325244, 23300193, 31514951, 26724190, 23349452, 25557463, 33947203; Phenotypes: Cardiomyopathy, dilated, 1I, MIM# 604765, Myopathy, myofibrillar, 1 , MIM#601419, Arrhythmogenic right ventricular cardiomyopathy; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13911 | DEPDC5 | Zornitza Stark Marked gene: DEPDC5 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13911 | DEPDC5 | Zornitza Stark Phenotypes for gene: DEPDC5 were changed from to Epilepsy, familial focal, with variable foci 1, MIM#604364 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13908 | DEPDC5 | Zornitza Stark reviewed gene: DEPDC5: Rating: GREEN; Mode of pathogenicity: None; Publications: 31444548, 23542697, 23542701; Phenotypes: Epilepsy, familial focal, with variable foci 1 MIM#604364; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13908 | DECR1 | Zornitza Stark Marked gene: DECR1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13907 | DDIT3 | Zornitza Stark Marked gene: DDIT3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13906 | DDHD2 | Zornitza Stark Marked gene: DDHD2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13906 | DDHD2 | Zornitza Stark Phenotypes for gene: DDHD2 were changed from to Spastic paraplegia 54, autosomal recessive, MIM# 615033 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13903 | DDHD2 | Zornitza Stark reviewed gene: DDHD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23486545, 24482476, 23176823, 31302745; Phenotypes: Spastic paraplegia 54, autosomal recessive, MIM# 615033; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13903 | DDC | Zornitza Stark Marked gene: DDC as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13903 | DDC | Zornitza Stark Phenotypes for gene: DDC were changed from to Aromatic L-amino acid decarboxylase deficiency, MIM# 608643 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13900 | DDC | Zornitza Stark reviewed gene: DDC: Rating: GREEN; Mode of pathogenicity: None; Publications: 20505134, 30952622; Phenotypes: Aromatic L-amino acid decarboxylase deficiency, MIM# 608643; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13900 | DDB2 | Zornitza Stark Marked gene: DDB2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13895 | DCTN1 | Zornitza Stark Marked gene: DCTN1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13895 | DCTN1 | Zornitza Stark Phenotypes for gene: DCTN1 were changed from to Neuronopathy, distal hereditary motor, type VIIB, MIM# 607641; MONDO:0011879; Perry syndrome, MIM# 168605 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13892 | DCTN1 | Zornitza Stark edited their review of gene: DCTN1: Changed phenotypes: Neuronopathy, distal hereditary motor, type VIIB, MIM# 607641, MONDO:0011879, Perry syndrome, MIM# 168605 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13892 | AQP5 | Elena Savva Phenotypes for gene: AQP5 were changed from Palmoplantar keratoderma, Bothnian type MIM#600231 to Palmoplantar keratoderma, Bothnian type MIM#600231 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13892 | AQP5 | Elena Savva Phenotypes for gene: AQP5 were changed from to Palmoplantar keratoderma, Bothnian type MIM#600231 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13891 | AQP5 | Elena Savva Marked gene: AQP5 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13890 | AQP5 | Elena Savva reviewed gene: AQP5: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35014096, 23830519; Phenotypes: Palmoplantar keratoderma, Bothnian type MIM#600231; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13890 | AR | Elena Savva Phenotypes for gene: AR were changed from to Hypospadias 1, X-linked MIM#30063; Androgen insensitivity MIM#300068; Androgen insensitivity, partial, with or without breast cancer MIM#312300; Spinal and bulbar muscular atrophy of Kennedy MIM#313200 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13890 | AR | Elena Savva Publications for gene: AR were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13889 | AR | Elena Savva Mode of inheritance for gene: AR was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13888 | AR | Elena Savva reviewed gene: AR: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 22334387; Phenotypes: Hypospadias 1, X-linked MIM#30063, Androgen insensitivity MIM#300068, Androgen insensitivity, partial, with or without breast cancer MIM#312300, Spinal and bulbar muscular atrophy of Kennedy MIM#313200; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13888 | DCLRE1C | Zornitza Stark Marked gene: DCLRE1C as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13885 | ARCN1 | Elena Savva Marked gene: ARCN1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13885 | ARCN1 | Elena Savva Gene: arcn1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13884 | DCHS1 | Zornitza Stark Marked gene: DCHS1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13879 | APPL1 | Elena Savva Marked gene: APPL1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13879 | AQP1 | Elena Savva Phenotypes for gene: AQP1 were changed from Pulmonary arterial hypertension to Pulmonary arterial hypertension | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13878 | APRT | Elena Savva Marked gene: APRT as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13878 | AQP1 | Elena Savva Phenotypes for gene: AQP1 were changed from to Pulmonary arterial hypertension | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13877 | AQP1 | Elena Savva Marked gene: AQP1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13875 | AQP1 | Elena Savva reviewed gene: AQP1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:22683574, 29650961; Phenotypes: Pulmonary arterial hypertension; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13873 | APOC4-APOC2 | Elena Savva Marked gene: APOC4-APOC2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13870 | APOC2 | Elena Savva Marked gene: APOC2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13868 | APOC3 | Elena Savva Marked gene: APOC3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13864 | ACTL6B | Zornitza Stark edited their review of gene: ACTL6B: Changed phenotypes: Epileptic encephalopathy, early infantile, 76, MIM# 618468, Intellectual developmental disorder with severe speech and ambulation defects, MIM# 618470; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13862 | MAPKAPK5 | Zornitza Stark Phenotypes for gene: MAPKAPK5 were changed from Developmental delay, variable brain anomalies, congenital heart defects, dysmorphic to Neurocardiofaciodigital syndrome, MIM# 619869 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13861 | MAPKAPK5 | Zornitza Stark edited their review of gene: MAPKAPK5: Changed phenotypes: Neurocardiofaciodigital syndrome, MIM# 619869 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13860 | DCAF17 | Zornitza Stark Marked gene: DCAF17 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13857 | CYP2C19 | Ain Roesley Marked gene: CYP2C19 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13856 | CYP2B6 | Ain Roesley Marked gene: CYP2B6 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13854 | DAZ4 | Zornitza Stark Marked gene: DAZ4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13853 | DAZ3 | Zornitza Stark Marked gene: DAZ3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13852 | CYP2A6 | Ain Roesley Marked gene: CYP2A6 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13852 | CYP2A6 | Ain Roesley Phenotypes for gene: CYP2A6 were changed from to Coumarin resistance MIM#122700 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13851 | CYP2A6 | Ain Roesley reviewed gene: CYP2A6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Coumarin resistance MIM#122700; Mode of inheritance: None; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13851 | DAZ2 | Zornitza Stark Marked gene: DAZ2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13850 | DAZ1 | Zornitza Stark Marked gene: DAZ1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13848 | CYP27A1 | Ain Roesley Marked gene: CYP27A1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13846 | DARS2 | Zornitza Stark Marked gene: DARS2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13846 | DARS2 | Zornitza Stark Gene: dars2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13846 | DARS2 | Zornitza Stark Phenotypes for gene: DARS2 were changed from to Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, MIM# 611105 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13845 | CYP26C1 | Ain Roesley Marked gene: CYP26C1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13845 | DARS2 | Zornitza Stark Publications for gene: DARS2 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13844 | DARS2 | Zornitza Stark Mode of inheritance for gene: DARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13843 | DARS2 | Zornitza Stark changed review comment from: Slowly progressive disorder with variable age of onset, multiple families reported.; to: Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is defined on the basis of a highly characteristic constellation of abnormalities observed by magnetic resonance imaging and spectroscopy (Scheper et al., 2007). Affected individuals develop slowly progressive cerebellar ataxia, spasticity, and dorsal column dysfunction, sometimes with a mild cognitive deficit or decline. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13842 | DARS2 | Zornitza Stark reviewed gene: DARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 17384640, 15002045, 16788019; Phenotypes: Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, MIM# 611105; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13842 | D2HGDH | Zornitza Stark Marked gene: D2HGDH as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13842 | D2HGDH | Zornitza Stark Phenotypes for gene: D2HGDH were changed from to D-2-hydroxyglutaric aciduria MIM#600721 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13839 | D2HGDH | Zornitza Stark reviewed gene: D2HGDH: Rating: GREEN; Mode of pathogenicity: None; Publications: 25778941, 31349060, 15609246, 20020533; Phenotypes: D-2-hydroxyglutaric aciduria MIM#600721; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13839 | CYP7B1 | Zornitza Stark Marked gene: CYP7B1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13839 | CYP7B1 | Zornitza Stark Phenotypes for gene: CYP7B1 were changed from to Bile acid synthesis defect, congenital, 3 MIM#613812; Spastic paraplegia 5A, autosomal recessive MIM#270800; Disorders of bile acid biosynthesis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13836 | CYP1A2 | Ain Roesley Marked gene: CYP1A2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13835 | KLF4 | Zornitza Stark Marked gene: KLF4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13834 | CYP19A1 | Ain Roesley Marked gene: CYP19A1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13834 | CYP19A1 | Ain Roesley Phenotypes for gene: CYP19A1 were changed from to Aromatase deficiency (MIM#613546), AR; Aromatase excess syndrome (MIM#139300), AD | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13832 | CYP19A1 | Ain Roesley reviewed gene: CYP19A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 17164303, 25264451; Phenotypes: Aromatase deficiency (MIM#613546), AR, Aromatase excess syndrome (MIM#139300), AD; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13832 | CYCS | Ain Roesley Marked gene: CYCS as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13828 | CYC1 | Ain Roesley Marked gene: CYC1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13828 | CYC1 | Ain Roesley Phenotypes for gene: CYC1 were changed from to Mitochondrial complex III deficiency, nuclear type 6 MIM#615453 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13826 | CYC1 | Ain Roesley reviewed gene: CYC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23910460, 34252606; Phenotypes: Mitochondrial complex III deficiency, nuclear type 6 MIM#615453; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13825 | HNRNPA2B1 | Zornitza Stark Phenotypes for gene: HNRNPA2B1 were changed from Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2 MIM#615422 to oculopharyngeal muscular dystrophy, MONDO:0008116; Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2 MIM#615422 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13820 | KCNH5 | Zornitza Stark Marked gene: KCNH5 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13820 | CREB1 | Zornitza Stark Phenotypes for gene: CREB1 were changed from corpus callosum agenesis; thyroid follicular hypoplasia to Agenesis of corpus callosum, MONDO:0009022 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13819 | SLC16A12 | Zornitza Stark Marked gene: SLC16A12 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13819 | SLC16A12 | Zornitza Stark Phenotypes for gene: SLC16A12 were changed from to Cataract 47, juvenile, with microcornea, MIM# 612018 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13816 | SLC14A1 | Zornitza Stark Marked gene: SLC14A1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13812 | SLC12A5 | Zornitza Stark Marked gene: SLC12A5 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13809 | CORIN | Zornitza Stark Marked gene: CORIN as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13809 | DUSP6 | Zornitza Stark Marked gene: DUSP6 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13805 | DYRK1B | Zornitza Stark Marked gene: DYRK1B as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13798 | KLF4 |
Elena Savva gene: KLF4 was added gene: KLF4 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KLF4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: KLF4 were set to PMID: 35168889; 10431239 Phenotypes for gene: KLF4 were set to Hereditary palmoplantar keratoderma MONDO:0019272, KFL4-related Review for gene: KLF4 was set to GREEN Added comment: PMID: 35168889 - 3 patients from 2 unrelated families with palmoplantar keratoderma. Two variants found, fs and a missense. Functional studies on patient skin biopsy shows "slightly but significantly decreased" protein expression in both children. Gene was shown to bind the DSG1 promoter and regulate expression. Transfected cells showed reduced DSG1 expression. PMID: 10431239 - mouse K/O died shortly after birth due to loss of skin barrier function gnomAD: single het fs in the population Sources: Literature |
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| Mendeliome v0.13797 | CTR9 | Zornitza Stark Marked gene: CTR9 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13797 | HNRNPA2B1 | Naomi Baker reviewed gene: HNRNPA2B1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:35484142; Phenotypes: oculopharyngeal muscular dystrophy, MONDO:0008116; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13796 | P3H2 | Daniel Flanagan reviewed gene: P3H2: Rating: GREEN; Mode of pathogenicity: None; Publications: 35499085; Phenotypes: Myopia, high, with cataract and vitreoretinal degeneration (MIM# 614292); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13796 | CDH4 | Ain Roesley Marked gene: CDH4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13796 | DNAH14 | Zornitza Stark Marked gene: DNAH14 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13796 | CDH4 |
Ain Roesley gene: CDH4 was added gene: CDH4 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CDH4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CDH4 were set to 35034853 Phenotypes for gene: CDH4 were set to coloboma MONDO#0001476, CDH4-related Review for gene: CDH4 was set to RED gene: CDH4 was marked as current diagnostic Added comment: 1x family with AD coloboma Also presented with ID and post natal microcephaly zebrafish KO model Sources: Literature |
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| Mendeliome v0.13793 | CD164 | Alison Yeung Marked gene: CD164 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13792 | CD164 |
Alison Yeung gene: CD164 was added gene: CD164 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CD164 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CD164 were set to 26197441; 35254497; 26197441 Phenotypes for gene: CD164 were set to Deafness, autosomal dominant 66, MIM# 616969 Review for gene: CD164 was set to GREEN Added comment: p.(Arg192Ter), a truncating variant that results in loss of 6 amino acids, was detected in two families (one Polish and one Korean) with hearing loss. Four affected (heterozygous) and two unaffected (neg) were tested, however 14 members had been diagnosed with HL in a large multi generational family (gene panel 237 genes). The second family (WES) had two affected heterozygous and no unaffected were tested. This same variant had previously been reported in a Danish family (12 affected heterozygous and 13 unaffected negative, but one younger member unaffected are heterozygous) with hearing loss (PMID: 26197441), for which functional studies in HEK cells demonstrated that the truncated protein was almost completely retained on the plasma cell membrane in contrast to the wild-type protein, which targeted primarily to the endo-lysosomal compartments. The YHTL motif, deleted by the c.574C>T nonsense mutation, is a canonical sorting motif known to be recognized by specific adaptor proteins in the cytosol, leading to subcellular trafficking of the transmembrane protein to endosomes and lysosomes. Sources: Literature |
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| Mendeliome v0.13791 | CTR9 |
Dean Phelan gene: CTR9 was added gene: CTR9 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CTR9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CTR9 were set to PMID: 35499524 Phenotypes for gene: CTR9 were set to Neurodevelopmental disorder (MONDO:0700092), CTR9 related; Intellectual disability (MONDO:0001071); hypotonia (HP:0001252); joint hyperlaxity (HP:0001388); speech delay; coordination problems; tremor (HP:0001337); autism spectrum disorder (MONDO:0005258) Review for gene: CTR9 was set to GREEN Added comment: PMID: 35499524 - Thirteen individuals with variables degrees of intellectual disability, hypotonia, joint hyperlaxity, speech delay, coordination problems, tremor, autism spectrum disorder. Mild dysmorphism and cardiac anomalies were less frequent. Eleven of the variants were shown to be de novo. Sources: Literature |
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| Mendeliome v0.13791 | TULP3 | Zornitza Stark Marked gene: TULP3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13789 | DNAH14 |
Chern Lim gene: DNAH14 was added gene: DNAH14 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: DNAH14 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DNAH14 were set to PMID: 35438214 Phenotypes for gene: DNAH14 were set to Neurodevelopmental disorder, DNAH14-related (MONDO#0700092) Review for gene: DNAH14 was set to GREEN gene: DNAH14 was marked as current diagnostic Added comment: PMID: 35438214: - Three previously unreported patients with compound heterozygous DNAH14 variants, including one nonsense, one frameshift, and four missense variants. A spectrum of neurological and developmental phenotypes was observed, including seizures, global developmental delay, microcephaly, and hypotonia. Sources: Literature |
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| Mendeliome v0.13789 | ANK3 | Ain Roesley Phenotypes for gene: ANK3 were changed from Mental retardation, autosomal recessive, 37 615493; Intellectual disability, autosomal dominant; coloboma MONDO#0001476, ANK3-related to Mental retardation, autosomal recessive, 37 615493; Intellectual disability, autosomal dominant; coloboma MONDO#0001476, ANK3-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13788 | PRDM13 | Zornitza Stark Phenotypes for gene: PRDM13 were changed from Retinal dystrophy; Chorioretinal atrophy, progressive bifocal, MIM# 600790; intellectual disability, MONDO:0001071, PRDM13-associated; ataxia with cerebellar hypoplasia, MONDO:0016054, PRDM13-associated; congenital hypogonadotropic hypogonadism, MONDO:0015770 to Retinal dystrophy; Chorioretinal atrophy, progressive bifocal, MIM# 600790; intellectual disability, MONDO:0001071, PRDM13-associated; ataxia with cerebellar hypoplasia, MONDO:0016054, PRDM13-associated; congenital hypogonadotropic hypogonadism, MONDO:0015770 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13788 | ANK3 | Ain Roesley Phenotypes for gene: ANK3 were changed from Mental retardation, autosomal recessive, 37 615493; Intellectual disability, autosomal dominant to Mental retardation, autosomal recessive, 37 615493; Intellectual disability, autosomal dominant; coloboma MONDO#0001476, ANK3-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13787 | TULP3 |
Anna Ritchie gene: TULP3 was added gene: TULP3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TULP3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TULP3 were set to PMID: 35397207 Phenotypes for gene: TULP3 were set to progressive degenerative liver fibrosis with variable fibrocystic kidney disease; hypertrophic cardiomyopathy MONDO:0005045 Review for gene: TULP3 was set to GREEN Added comment: 15 individuals from eight unrelated families with bi-allelic variants in TULP3 were detected. The affected individuals reported are mostly adults, in the 3rd through 7th decades of life, and presented with progressive degenerative liver fibrosis with variable fibrocystic kidney disease and hypertrophic cardiomyopathy. The human phenotype was ecapitulated in adult zebrafish and confirmed disruption of critical ciliary cargo composition in several primary cell lines derived from affected individuals Sources: Literature |
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| Mendeliome v0.13786 | DROSHA | Zornitza Stark Marked gene: DROSHA as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13784 | PRDM13 | Dean Phelan reviewed gene: PRDM13: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35390279; Phenotypes: Pontocerebellar hypoplasia (MONDO:0020135), PRDM13 related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13784 | DROSHA |
Lucy Spencer gene: DROSHA was added gene: DROSHA was added to Mendeliome. Sources: Literature Mode of inheritance for gene: DROSHA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: DROSHA were set to 35405010 Phenotypes for gene: DROSHA were set to Neurodevelopmental disorder (MONDO#0700092), DROSHA-related Review for gene: DROSHA was set to AMBER Added comment: 2 individuals with profound intellectual disability, epilepsy, white matter atrophy, microcephaly, and dysmorphic features, who carry damaging de novo heterozygous variants in DROSHA. Both variants are missense, absent from gnomad. Both individuals noted to have Rett-like features. Functional studies in patient fibroblasts showed one of the missense altered the expression of mature miRNA. Fruit fly models with homozygous LOF variants die during larval stages. introduction of the missense seen in the patients was able to partially rescue this phenotype suggesting LOF is not the mechanism. Sources: Literature |
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| Mendeliome v0.13784 | KCNH5 |
Elena Savva gene: KCNH5 was added gene: KCNH5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KCNH5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: KCNH5 were set to https://www.medrxiv.org/content/10.1101/2022.04.26.22274147v1 Phenotypes for gene: KCNH5 were set to Neurodevelopmental disorders Mode of pathogenicity for gene: KCNH5 was set to Other Review for gene: KCNH5 was set to GREEN Added comment: Happ (2022), preprint: Screen of 893 patients with DEE found 17 patients with missense variants (16/17 de novo, 1/17 inherited). GOF mechanism suggested. Patient phenotypes included focal/generalized seizures, Cognitive outcome for the ten individuals >5 years ranged from normal (3/10) to mild (3/10), moderate (2/10), severe (1/10) and profound (1/10) intellectual disability (ID) p.Arg327His (7 probands), p.Arg333His (4 probands) were recurring Sources: Literature |
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| Mendeliome v0.13783 | PPFIBP1 | Zornitza Stark Marked gene: PPFIBP1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13783 | STX1A | Ain Roesley Marked gene: STX1A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13782 | STX1A |
Ain Roesley changed review comment from: Preprint: 8 individuals - 2x hom (related) and 6x hets (all de novo except 1x unknown) 7 unrelated since the 2 siblings share similar features: 7/7 ID, 7/7 motor delay, 4/7 epilepsy, 5/7 neonatal hypotonia 2/7 regression, 2/7 ASD excluding 1 with features but did not meet criteria Sources: Literature; to: Preprint: https://www.medrxiv.org/content/10.1101/2022.04.20.22274073v1 8 individuals - 2x hom (related) and 6x hets (all de novo except 1x unknown) 7 unrelated since the 2 siblings share similar features: 7/7 ID, 7/7 motor delay, 4/7 epilepsy, 5/7 neonatal hypotonia 2/7 regression, 2/7 ASD excluding 1 with features but did not meet criteria Sources: Literature |
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| Mendeliome v0.13781 | PPFIBP1 |
Zornitza Stark gene: PPFIBP1 was added gene: PPFIBP1 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: PPFIBP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PPFIBP1 were set to https://www.medrxiv.org/content/10.1101/2022.04.04.22273309v1 Phenotypes for gene: PPFIBP1 were set to Neurodevelopmental disorder, MONDO:0700092 Review for gene: PPFIBP1 was set to GREEN Added comment: 16 individuals from 10 unrelated families reported with moderate to profound developmental delay, often refractory early-onset epilepsy and progressive microcephaly. Drosophila model. Sources: Expert Review |
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| Mendeliome v0.13778 | STX1A |
Ain Roesley gene: STX1A was added gene: STX1A was added to Mendeliome. Sources: Literature Mode of inheritance for gene: STX1A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Review for gene: STX1A was set to GREEN gene: STX1A was marked as current diagnostic Added comment: Preprint: 8 individuals - 2x hom (related) and 6x hets (all de novo except 1x unknown) 7 unrelated since the 2 siblings share similar features: 7/7 ID, 7/7 motor delay, 4/7 epilepsy, 5/7 neonatal hypotonia 2/7 regression, 2/7 ASD excluding 1 with features but did not meet criteria Sources: Literature |
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| Mendeliome v0.13777 | HYDIN | Zornitza Stark Marked gene: HYDIN as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13777 | HYDIN | Zornitza Stark Phenotypes for gene: HYDIN were changed from to Ciliary dyskinesia, primary, 5 (MIM#608647) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13774 | HYDIN | Zornitza Stark reviewed gene: HYDIN: Rating: GREEN; Mode of pathogenicity: None; Publications: 23022101, 23849777, 28441829, 31116566; Phenotypes: Ciliary dyskinesia, primary, 5 (MIM#608647); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13774 | HTRA2 | Zornitza Stark Marked gene: HTRA2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13771 | HTR1A | Zornitza Stark Marked gene: HTR1A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13767 | HSPD1 | Zornitza Stark Marked gene: HSPD1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13767 | HSPD1 | Zornitza Stark Phenotypes for gene: HSPD1 were changed from to Leukodystrophy, hypomyelinating, 4, MIM# 612233; Spastic paraplegia 13, autosomal dominant, MIM# 605280 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13764 | HSPD1 | Zornitza Stark reviewed gene: HSPD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18571143, 27405012, 32532876, 28377887, 27405012, 11898127, 17420924; Phenotypes: Leukodystrophy, hypomyelinating, 4, MIM# 612233, Spastic paraplegia 13, autosomal dominant, MIM# 605280; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13764 | HSD3B7 | Zornitza Stark Marked gene: HSD3B7 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13761 | HSD3B2 | Zornitza Stark Marked gene: HSD3B2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13758 | CPN1 | Ain Roesley changed review comment from: only 1 probed reported thus far; to: only 1 proband reported thus far | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13758 | CUBN | Ain Roesley Marked gene: CUBN as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13758 | CUBN | Ain Roesley Phenotypes for gene: CUBN were changed from to Imerslund-Grasbeck syndrome 1 MIM#261100 AR; [Proteinuria, chronic benign] MIM#618884 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13755 | CUBN | Ain Roesley reviewed gene: CUBN: Rating: GREEN; Mode of pathogenicity: None; Publications: 31613795, 21903995, 31497480; Phenotypes: Imerslund-Grasbeck syndrome 1 MIM#261100 AR, [Proteinuria, chronic benign] MIM#618884; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13755 | CTSF | Ain Roesley Marked gene: CTSF as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13753 | CTSC | Ain Roesley Marked gene: CTSC as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13750 | CTNS | Ain Roesley Marked gene: CTNS as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13750 | CTNS | Ain Roesley Phenotypes for gene: CTNS were changed from to Cystinosis, atypical nephropathic MIM#219800; Cystinosis, late-onset juvenile or adolescent nephropathic MIM#219900; Cystinosis, nephropathic MIM#219800; Cystinosis, ocular nonnephropathic MIM#219750 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13747 | CTNS | Ain Roesley reviewed gene: CTNS: Rating: ; Mode of pathogenicity: None; Publications: 20301574, 9537412, 31068690; Phenotypes: Cystinosis, atypical nephropathic MIM#219800, Cystinosis, late-onset juvenile or adolescent nephropathic MIM#219900, Cystinosis, nephropathic MIM#219800, Cystinosis, ocular nonnephropathic MIM#219750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13747 | CTNNA1 | Ain Roesley Marked gene: CTNNA1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13747 | CTNNA1 | Ain Roesley Phenotypes for gene: CTNNA1 were changed from to Macular dystrophy, butterfly-shaped pigmentary, 2, MIM# 608970; Familial exudative vitreoretinopathy MONDO#0019516, CTNNA1-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13745 | CTNNA1 | Ain Roesley reviewed gene: CTNNA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26691986, 33497368; Phenotypes: Macular dystrophy, butterfly-shaped pigmentary, 2, MIM# 608970, Familial exudative vitreoretinopathy MONDO#0019516, CTNNA1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13745 | CTHRC1 | Ain Roesley Marked gene: CTHRC1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13745 | CTHRC1 | Ain Roesley Phenotypes for gene: CTHRC1 were changed from to Barrett esophagus/esophageal adenocarcinoma MIM#614266 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13743 | CTHRC1 | Ain Roesley reviewed gene: CTHRC1: Rating: RED; Mode of pathogenicity: None; Publications: 21791690; Phenotypes: Barrett esophagus/esophageal adenocarcinoma MIM#614266; Mode of inheritance: None; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13743 | CSRP3 | Ain Roesley Marked gene: CSRP3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13743 | CSRP3 | Ain Roesley Phenotypes for gene: CSRP3 were changed from to hypertrophic cardiomyopathy12 MIM#612124; dilated cardiomyopathy 1M MIM#607482 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13741 | CSRP3 | Ain Roesley reviewed gene: CSRP3: Rating: GREEN; Mode of pathogenicity: None; Publications: 18505755, 30681346, 12507422, 14567970, 19412328; Phenotypes: hypertrophic cardiomyopathy12 MIM#612124, dilated cardiomyopathy 1M MIM#607482; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13741 | CRYGS | Ain Roesley Marked gene: CRYGS as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13741 | CRYGS | Ain Roesley Phenotypes for gene: CRYGS were changed from to Cataract 20, multiple types MIM#116100 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13739 | CRYGS | Ain Roesley reviewed gene: CRYGS: Rating: GREEN; Mode of pathogenicity: None; Publications: 34014271, 16141006, 18587492, 19262743; Phenotypes: Cataract 20, multiple types MIM#116100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13739 | CRYGB | Ain Roesley Marked gene: CRYGB as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13739 | CRYGB | Ain Roesley Phenotypes for gene: CRYGB were changed from to Cataract 39, multiple types, autosomal dominant MIM#615188 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13737 | CRYGB | Ain Roesley reviewed gene: CRYGB: Rating: RED; Mode of pathogenicity: None; Publications: 23288985; Phenotypes: Cataract 39, multiple types, autosomal dominant MIM#615188; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13737 | CRYAB | Ain Roesley Marked gene: CRYAB as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13737 | CRYAB | Ain Roesley Phenotypes for gene: CRYAB were changed from to Cataract 16, multiple types MIM#613763 AD, AR; Myopathy, myofibrillar, 2 MIM#608810 AD; Myopathy, myofibrillar, fatal infantile hypertonic, alpha-B crystallin-related MIM#613869 AR | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13735 | CRYAB | Ain Roesley reviewed gene: CRYAB: Rating: GREEN; Mode of pathogenicity: None; Publications: 31215171, 21337604, 21130652, 32420686, 33272090; Phenotypes: Cataract 16, multiple types MIM#613763 AD, AR, Myopathy, myofibrillar, 2 MIM#608810 AD, Myopathy, myofibrillar, fatal infantile hypertonic, alpha-B crystallin-related MIM#613869 AR; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13735 | CRX | Ain Roesley Marked gene: CRX as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13732 | CREB1 | Ain Roesley Marked gene: CREB1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13732 | CREB1 | Ain Roesley Phenotypes for gene: CREB1 were changed from to corpus callosum agenesis; thyroid follicular hypoplasia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13729 | CREB1 | Ain Roesley reviewed gene: CREB1: Rating: RED; Mode of pathogenicity: None; Publications: 22267179; Phenotypes: corpus callosum agenesis, thyroid follicular hypoplasia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13729 | SLC16A12 | Samantha Ayres reviewed gene: SLC16A12: Rating: GREEN; Mode of pathogenicity: None; Publications: 20181839, 21778275, 18304496, 29088427, 34126080; Phenotypes: Cataract 47, juvenile, with microcornea, MIM# 612018; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13729 | CRBN | Ain Roesley Marked gene: CRBN as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13727 | CRB1 | Ain Roesley Marked gene: CRB1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13727 | CRB1 | Ain Roesley Phenotypes for gene: CRB1 were changed from to Leber congenital amaurosis 8 MIM#613835; Pigmented paravenous chorioretinal atrophy MIM#172870; Retinitis pigmentosa-12 MIM#600105 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13725 | CRB1 | Ain Roesley reviewed gene: CRB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30285347, 32922261, 31884620, 15459956; Phenotypes: Leber congenital amaurosis 8 MIM#613835, Pigmented paravenous chorioretinal atrophy MIM#172870, Retinitis pigmentosa-12 MIM#600105; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13725 | CPT1A | Ain Roesley Marked gene: CPT1A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13723 | CPS1 | Ain Roesley Marked gene: CPS1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13722 | CPS1 | Ain Roesley reviewed gene: CPS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 8486760, 17310273, 21120950, 31268178; Phenotypes: Carbamoylphosphate synthetase I deficiency MIM#237300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13722 | CPOX | Ain Roesley Marked gene: CPOX as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13722 | CPOX | Ain Roesley Phenotypes for gene: CPOX were changed from to Coproporphyria, MIM#121300; Harderoporphyria, MIM#121300 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13720 | CPOX | Ain Roesley reviewed gene: CPOX: Rating: GREEN; Mode of pathogenicity: None; Publications: 30828546, 28349448, 23582006, 24156084; Phenotypes: Coproporphyria, MIM#121300, Harderoporphyria, MIM#121300; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13720 | CPN1 | Ain Roesley Marked gene: CPN1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13720 | CPN1 | Ain Roesley Phenotypes for gene: CPN1 were changed from to Carboxypeptidase N deficiency MIM#212070 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13717 | CPN1 | Ain Roesley reviewed gene: CPN1: Rating: RED; Mode of pathogenicity: None; Publications: 12560874, 7437116; Phenotypes: Carboxypeptidase N deficiency MIM#212070; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13717 | COMP | Ain Roesley Marked gene: COMP as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13717 | HSD11B1 | Zornitza Stark Marked gene: HSD11B1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13713 | HRG | Zornitza Stark Marked gene: HRG as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13710 | HP | Zornitza Stark Marked gene: HP as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13708 | HOXD13 | Zornitza Stark Marked gene: HOXD13 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13705 | HOXA13 | Zornitza Stark Marked gene: HOXA13 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13702 | HOXA1 | Zornitza Stark Marked gene: HOXA1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13699 | HOXA1 |
Zornitza Stark changed review comment from: At least 10 families reported. 175-176insG is known as the Saudi Arabian variant, while 76C>T is known as the Native American variant. Features include: Conotruncal heart defects, Abnormalities of the internal carotid artery and other cerebral arteries, Abnormal skull base Biallelic variants in this gene cause a syndrome affecting hindbrain development, with BSAS and ABDS allelic disorders.; to: Biallelic variants in this gene cause a syndrome affecting hindbrain development, with BSAS and ABDS allelic disorders. At least 10 families reported. 175-176insG is known as the Saudi Arabian variant, while 76C>T is known as the Native American variant. Features include: Conotruncal heart defects, Abnormalities of the internal carotid artery and other cerebral arteries, Abnormal skull base |
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| Mendeliome v0.13699 | HNRNPA1 | Zornitza Stark Marked gene: HNRNPA1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13696 | HNF4A | Zornitza Stark Marked gene: HNF4A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13696 | HNF4A | Zornitza Stark Phenotypes for gene: HNF4A were changed from to Fanconi renotubular syndrome 4, with maturity-onset diabetes of the young, OMIM #616026; MODY, type I, OMIM # 125850 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13693 | HNF4A | Zornitza Stark reviewed gene: HNF4A: Rating: GREEN; Mode of pathogenicity: None; Publications: 31875549, 24285859, 22802087, 30005691, 28458902; Phenotypes: Fanconi renotubular syndrome 4, with maturity-onset diabetes of the young, OMIM #616026, MODY, type I, OMIM # 125850; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13693 | HNF1A | Zornitza Stark Marked gene: HNF1A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13690 | HMX1 | Zornitza Stark Marked gene: HMX1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13690 | HMX1 | Zornitza Stark Phenotypes for gene: HMX1 were changed from to Oculoauricular syndrome, MIM#612109 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13687 | HMX1 |
Zornitza Stark changed review comment from: Oculoauricular syndrome (OCACS) is characterized by complex ocular anomalies, including congenital cataract, anterior segment dysgenesis, iris coloboma, and early-onset retinal dystrophy, and dysplastic ears with abnormal external ear cartilage. At least two families and two animal models. Also evidence that duplication of long-range enhancer causes microbial.; to: Oculoauricular syndrome (OCACS) is characterized by complex ocular anomalies, including congenital cataract, anterior segment dysgenesis, iris coloboma, and early-onset retinal dystrophy, and dysplastic ears with abnormal external ear cartilage. At least two families and two animal models. Also evidence that duplication of long-range enhancer causes microtia. |
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| Mendeliome v0.13687 | HMX1 | Zornitza Stark reviewed gene: HMX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18423520, 25574057, 33465110, 32552830, 31691317; Phenotypes: Oculoauricular syndrome, MIM#612109; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13687 | COL9A1 | Ain Roesley Marked gene: COL9A1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13683 | DUSP6 |
Krithika Murali changed review comment from: PMID: 23643382 Miraoui et al 2013 - - candidate gene study for genes in the FGFR1 pathway that may be associated with CHH, either as causative genes or disease modifiers. A cohort of 386 CHH individuals and 155 unaffected controls of European descent. A number of affected individuals included in this cohort already had known causative variants in CHH-associated genes. The coding exons and proximal introns (≥15 bp from splice sites) of FGF17, FGF18, IL17RD, DUSP6, SPRY2, SPRY4, and FLRT3 were amplified by PCR and determined by direct sequencing. Summary of DUSP6 variants identified in this study c.229 T>A p.(Phe77Ile) - absent gnomAD v2 and v3 c.545C>T p.(Ser182Phe) - 203 hets gnomad v2, 137 hets and 1 hom - v3 - identified in conjunction with FGFR1 variant in this individual c.566A>G p.Asn189Ser - v2 57 hets, v3 29 hets (another individual identified with this variant and an SPRY4 variant) c.1037C>T p.Thr346Met - 81 hets v2, 27 hets and 1 hom v3 (identified in conjunction with SPRY4 variant No segregation information provided. PMID: 23643382 - Dusp6 null mouse model reportedly has craniofacial defects and hearing defects, but no mention of hypogonadotropic hypogonadism. In 5 unrelated individuals with congenital hypogonadotropic hypogonadism 4 heterozygous missense were identified. In 3 of the probands, the DUSP6 mutation was accompanied by a heterozygous missense mutation in another HH-associated gene. 3 of the 4 variants have subpopulation allele frequencies in gnomAD v2.1 that are higher than expected for a dominant condition: p.Thr346Met (AJ AF 0.002797), p.Ser182Phe (NFE AF 0.001396), p.Asn189Ser (NFE AF 0.0003641). No functional assays were conducted. PMID: 32389901 - 6 unrelated male Chinese Kallman syndrome cases with 4 DUSP6 missense variants. 2 of 4 variants have East Asian allele frequencies in gnomAD v2.1 that are higher than expected for a dominant condition: p.Pro188Leu (EAS AF 0.001203), p.Arg83Gln (EAS AF 0.001129). No functional assays conducted.; to: PMID: 23643382 Miraoui et al 2013 - - candidate gene study for genes in the FGFR1 pathway that may be associated with CHH, either as causative genes or disease modifiers. A cohort of 386 CHH individuals and 155 unaffected controls of European descent. A number of affected individuals included in this cohort already had known causative variants in CHH-associated genes. The coding exons and proximal introns (≥15 bp from splice sites) of FGF17, FGF18, IL17RD, DUSP6, SPRY2, SPRY4, and FLRT3 were amplified by PCR and determined by direct sequencing. Summary of DUSP6 variants identified in this study c.229 T>A p.(Phe77Ile) - absent gnomAD v2 and v3 c.545C>T p.(Ser182Phe) - 203 hets gnomad v2, 137 hets and 1 hom - v3 - identified in conjunction with FGFR1 variant in this individual c.566A>G p.Asn189Ser - v2 57 hets, v3 29 hets (another individual identified with this variant and an SPRY4 variant) c.1037C>T p.Thr346Met - 81 hets v2, 27 hets and 1 hom v3 (identified in conjunction with SPRY4 variant No segregation information provided. Dusp6 null mouse model reportedly has craniofacial defects and hearing defects, but no mention of hypogonadotropic hypogonadism. PMID: 32389901 - 6 unrelated male Chinese Kallman syndrome cases with 4 DUSP6 missense variants. 2 of 4 variants have East Asian allele frequencies in gnomAD v2.1 that are higher than expected for a dominant condition: p.Pro188Leu (EAS AF 0.001203), p.Arg83Gln (EAS AF 0.001129). No functional assays conducted. |
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| Mendeliome v0.13683 | DUSP6 |
Krithika Murali changed review comment from: 1 study cited by OMIM (Miraoui et al 2013) - heterozygous variants in 5 unrelated individuals with congenital hypogonadotrophic hypogonadism (CHH). 4/5 variants highly prevalent in healthy population and/or in conjunction with variants in other genes either known to be associated with CHH or possibly associated. No additional studies published since this paper. PMID: 23643382 Miraoui et al 2013 - - candidate gene study for genes in the FGFR1 pathway that may be associated with CHH, either as causative genes or disease modifiers. A cohort of 386 CHH individuals and 155 unaffected controls of European descent. A number of affected individuals included in this cohort already had known causative variants in CHH-associated genes. The coding exons and proximal introns (≥15 bp from splice sites) of FGF17, FGF18, IL17RD, DUSP6, SPRY2, SPRY4, and FLRT3 were amplified by PCR and determined by direct sequencing. Summary of DUSP6 variants identified in this study c.229 T>A p.(Phe77Ile) - absent gnomAD v2 and v3 c.545C>T p.(Ser182Phe) - 203 hets gnomad v2, 137 hets and 1 hom - v3 - identified in conjunction with FGFR1 variant in this individual c.566A>G p.Asn189Ser - v2 57 hets, v3 29 hets (another individual identified with this variant and an SPRY4 variant) c.1037C>T p.Thr346Met - 81 hets v2, 27 hets and 1 hom v3 (identified in conjunction with SPRY4 variant No segregation information provided.; to: PMID: 23643382 Miraoui et al 2013 - - candidate gene study for genes in the FGFR1 pathway that may be associated with CHH, either as causative genes or disease modifiers. A cohort of 386 CHH individuals and 155 unaffected controls of European descent. A number of affected individuals included in this cohort already had known causative variants in CHH-associated genes. The coding exons and proximal introns (≥15 bp from splice sites) of FGF17, FGF18, IL17RD, DUSP6, SPRY2, SPRY4, and FLRT3 were amplified by PCR and determined by direct sequencing. Summary of DUSP6 variants identified in this study c.229 T>A p.(Phe77Ile) - absent gnomAD v2 and v3 c.545C>T p.(Ser182Phe) - 203 hets gnomad v2, 137 hets and 1 hom - v3 - identified in conjunction with FGFR1 variant in this individual c.566A>G p.Asn189Ser - v2 57 hets, v3 29 hets (another individual identified with this variant and an SPRY4 variant) c.1037C>T p.Thr346Met - 81 hets v2, 27 hets and 1 hom v3 (identified in conjunction with SPRY4 variant No segregation information provided. PMID: 23643382 - Dusp6 null mouse model reportedly has craniofacial defects and hearing defects, but no mention of hypogonadotropic hypogonadism. In 5 unrelated individuals with congenital hypogonadotropic hypogonadism 4 heterozygous missense were identified. In 3 of the probands, the DUSP6 mutation was accompanied by a heterozygous missense mutation in another HH-associated gene. 3 of the 4 variants have subpopulation allele frequencies in gnomAD v2.1 that are higher than expected for a dominant condition: p.Thr346Met (AJ AF 0.002797), p.Ser182Phe (NFE AF 0.001396), p.Asn189Ser (NFE AF 0.0003641). No functional assays were conducted. PMID: 32389901 - 6 unrelated male Chinese Kallman syndrome cases with 4 DUSP6 missense variants. 2 of 4 variants have East Asian allele frequencies in gnomAD v2.1 that are higher than expected for a dominant condition: p.Pro188Leu (EAS AF 0.001203), p.Arg83Gln (EAS AF 0.001129). No functional assays conducted. |
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| Mendeliome v0.13683 | COQ9 | Ain Roesley Marked gene: COQ9 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13683 | COQ9 | Ain Roesley Phenotypes for gene: COQ9 were changed from to Coenzyme Q10 deficiency, primary, 5, MIM#614654 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13681 | COQ9 | Ain Roesley reviewed gene: COQ9: Rating: GREEN; Mode of pathogenicity: None; Publications: 19375058, 26081641, 23255162, 31821167; Phenotypes: Coenzyme Q10 deficiency, primary, 5, MIM#614654; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13681 | COQ8B | Ain Roesley Marked gene: COQ8B as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13680 | COQ8A | Ain Roesley Marked gene: COQ8A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13680 | COQ8A | Ain Roesley Phenotypes for gene: COQ8A were changed from to Coenzyme Q10 deficiency, primary, 4 MIM#612016 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13679 | COQ8A | Ain Roesley reviewed gene: COQ8A: Rating: GREEN; Mode of pathogenicity: None; Publications: 32337771; Phenotypes: Coenzyme Q10 deficiency, primary, 4 MIM#612016; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13679 | COQ7 | Ain Roesley Marked gene: COQ7 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13679 | COQ7 | Ain Roesley Phenotypes for gene: COQ7 were changed from to Coenzyme Q10 deficiency, primary, 8 MIM#616733 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13678 | COQ7 | Ain Roesley reviewed gene: COQ7: Rating: GREEN; Mode of pathogenicity: None; Publications: 26084283, 31240163, 33215859, 28409910; Phenotypes: Coenzyme Q10 deficiency, primary, 8 MIM#616733; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13678 | COQ6 | Ain Roesley Marked gene: COQ6 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13678 | COQ6 | Ain Roesley Phenotypes for gene: COQ6 were changed from to Coenzyme Q10 deficiency, primary, 6 MIM#614650 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13677 | COQ6 | Ain Roesley reviewed gene: COQ6: Rating: GREEN; Mode of pathogenicity: None; Publications: 28125198; Phenotypes: Coenzyme Q10 deficiency, primary, 6 MIM#614650; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13675 | COL9A2 | Ain Roesley Marked gene: COL9A2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13674 | COL6A3 | Ain Roesley Marked gene: COL6A3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13674 | COL6A3 | Ain Roesley Phenotypes for gene: COL6A3 were changed from to Bethlem myopathy 1 MIM#158810; Dystonia 27 MIM#616411; Ullrich congenital muscular dystrophy 1 MIM#254090 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13673 | COL6A3 | Ain Roesley reviewed gene: COL6A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301676; Phenotypes: Bethlem myopathy 1 MIM#158810, Dystonia 27 MIM#616411, Ullrich congenital muscular dystrophy 1 MIM#254090; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13673 | COL6A2 |
Ain Roesley changed review comment from: GeneReviews PMID:20301676 AD variants typically occur near the N terminal of the triple helical (TH) domain, which contains a critical region of 10 to 15 Gly-X-Y triplets; in-frame exon-skipping variants and glycine substitutions in this region tend to result in more severe phenotypes AR variants are usually nonsense or fs, or biallelic variants located near the C-terminal end of the TH domain, where they will be excluded from assembly COL621 accounts for 44-46% of Collagen VI-Related Dystrophies cases; to: GeneReviews PMID:20301676 AD variants typically occur near the N terminal of the triple helical (TH) domain, which contains a critical region of 10 to 15 Gly-X-Y triplets; in-frame exon-skipping variants and glycine substitutions in this region tend to result in more severe phenotypes AR variants are usually nonsense or fs, or biallelic variants located near the C-terminal end of the TH domain, where they will be excluded from assembly COL6A2 accounts for 44-46% of Collagen VI-Related Dystrophies cases |
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| Mendeliome v0.13673 | COL6A2 | Ain Roesley Marked gene: COL6A2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13673 | COL6A2 | Ain Roesley Phenotypes for gene: COL6A2 were changed from to Bethlem myopathy 1 MIM#158810; Ullrich congenital muscular dystrophy 1 MIM#254090 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13671 | COL6A2 | Ain Roesley reviewed gene: COL6A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301676; Phenotypes: Bethlem myopathy 1 MIM#158810, Ullrich congenital muscular dystrophy 1 MIM#254090; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13671 | COL6A1 |
Ain Roesley changed review comment from: Well established association Genereviews PMID:20301676 AD variants typically occur near the N terminal of the triple helical (TH) domain, which contains a critical region of 10 to 15 Gly-X-Y triplets; in-frame exon-skipping variants and glycine substitutions in this region tend to result in more severe phenotypes AR variants are usually nonsense or fs, or biallelic variants located near the C-terminal end of the TH domain, where they will be excluded from assembly; to: Well established association Genereviews PMID:20301676 AD variants typically occur near the N terminal of the triple helical (TH) domain, which contains a critical region of 10 to 15 Gly-X-Y triplets; in-frame exon-skipping variants and glycine substitutions in this region tend to result in more severe phenotypes AR variants are usually nonsense or fs, or biallelic variants located near the C-terminal end of the TH domain, where they will be excluded from assembly COL6A1 accounts for 35-38% of Collagen VI-Related Dystrophies cases |
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| Mendeliome v0.13671 | COL6A1 | Ain Roesley Marked gene: COL6A1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13671 | COL6A1 | Ain Roesley Phenotypes for gene: COL6A1 were changed from to Bethlem myopathy MIM#158810; Ullrich congenital muscular dystrophy MIM#254090 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13669 | COL6A1 |
Ain Roesley changed review comment from: Well established association Both loss-of-function and dominant negative mechanism has been reported for this gene. Mutations result in a spectrum of disease, ranging from the milder Bethlem myopathy (monoallelic) to the more severe Ullrich congenital muscular dystrophy (biallelic) (PMID: 29277723; 24443028). Sources: Literature; to: Well established association Genereviews PMID:20301676 AD variants typically occur near the N terminal of the triple helical (TH) domain, which contains a critical region of 10 to 15 Gly-X-Y triplets; in-frame exon-skipping variants and glycine substitutions in this region tend to result in more severe phenotypes AR variants are usually nonsense or fs, or biallelic variants located near the C-terminal end of the TH domain, where they will be excluded from assembly |
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| Mendeliome v0.13669 | COL6A1 | Ain Roesley reviewed gene: COL6A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25535305, 15955946, 23738969, 29277723, 24443028; Phenotypes: Bethlem myopathy MIM#158810, Ullrich congenital muscular dystrophy MIM#254090; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13669 | COL5A2 | Ain Roesley Marked gene: COL5A2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13668 | COL4A4 | Ain Roesley Marked gene: COL4A4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13666 | COL4A3 | Ain Roesley Marked gene: COL4A3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13665 | COL4A2 | Ain Roesley Marked gene: COL4A2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13664 | COL4A1 | Ain Roesley Marked gene: COL4A1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13664 | COL4A1 | Ain Roesley Phenotypes for gene: COL4A1 were changed from to Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps MIM#611773; Brain small vessel disease with or without ocular anomalies MIM#175780; Microangiopathy and leukoencephalopathy, pontine, autosomal dominant MIM#618564 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13662 | COL4A1 | Ain Roesley reviewed gene: COL4A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24628545, 25719457, 21625620, 23225343, 23065703, 20818663, 20301768; Phenotypes: Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps MIM#611773, Brain small vessel disease with or without ocular anomalies MIM#175780, Microangiopathy and leukoencephalopathy, pontine, autosomal dominant MIM#618564; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13662 | HMOX1 | Zornitza Stark Marked gene: HMOX1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13658 | COL27A1 | Ain Roesley Marked gene: COL27A1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13656 | COL1A2 | Ain Roesley edited their review of gene: COL1A2: Changed phenotypes: Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2, MIM# 619120, Ehlers-Danlos syndrome, arthrochalasia type, 2, MIM# 617821, Ehlers-Danlos syndrome, cardiac valvular type, MIM# 225320, Osteogenesis imperfecta, type II, MIM# 166210, Osteogenesis imperfecta, type III, MIM# 259420, Osteogenesis imperfecta, type IV, MIM# 166220 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13656 | COL1A2 | Ain Roesley Marked gene: COL1A2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13656 | COL1A2 | Ain Roesley Phenotypes for gene: COL1A2 were changed from to Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2, MIM# 619120; Ehlers-Danlos syndrome, arthrochalasia type, 2, MIM# 617821; Ehlers-Danlos syndrome, cardiac valvular type, MIM# 225320; Osteogenesis imperfecta, type II, MIM# 166210; Osteogenesis imperfecta, type III, MIM# 259420; Osteogenesis imperfecta, type IV, MIM# 166220 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13653 | COL1A2 | Ain Roesley reviewed gene: COL1A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 28306229, 32091183, 2993307, 30821104; Phenotypes: Ehlers-Danlos syndrome, arthrochalasia type, 2 MIM#617821, Ehlers-Danlos syndrome, cardiac valvular type MIM#225320; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13653 | COL1A1 |
Ain Roesley changed review comment from: COL1A1 is mostly associated with osteogenesis imperfecta however, substitutions of arginine by cysteine in the triple helical domain) have been reported in individuals w/classic EDS & aneurysm & dissection of large vessels (PMID: 20301422;20301667) The mild forms are usually caused by haploinsufficiency and result in a reduced amount of normal type I collagen, the severe and lethal forms result from dominant negative variants which produce structural defects in the collagen molecule (PMID:12362985).; to: COL1A1 is mostly associated with osteogenesis imperfecta however, substitutions of arginine by cysteine in the triple helical domain) have been reported in individuals w/classic EDS & aneurysm & dissection of large vessels (PMID: 20301422;20301667) For skeletal phenotypes: The mild forms are usually caused by haploinsufficiency and result in a reduced amount of normal type I collagen, the severe and lethal forms result from dominant negative variants which produce structural defects in the collagen molecule (PMID:12362985). |
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| Mendeliome v0.13653 | COL1A1 |
Ain Roesley changed review comment from: COL1A1 is mostly associated with osteogenesis imperfecta however, substitutions of arginine by cysteine in the triple helical domain) have been reported in individuals w/classic EDS & aneurysm & dissection of large vessels (PMID: 20301422;20301667); to: COL1A1 is mostly associated with osteogenesis imperfecta however, substitutions of arginine by cysteine in the triple helical domain) have been reported in individuals w/classic EDS & aneurysm & dissection of large vessels (PMID: 20301422;20301667) The mild forms are usually caused by haploinsufficiency and result in a reduced amount of normal type I collagen, the severe and lethal forms result from dominant negative variants which produce structural defects in the collagen molecule (PMID:12362985). |
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| Mendeliome v0.13653 | COL1A1 | Ain Roesley Marked gene: COL1A1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13653 | COL1A1 | Ain Roesley Phenotypes for gene: COL1A1 were changed from to Caffey disease MIM#114000; Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 1 MIM#619115; Ehlers-Danlos syndrome, arthrochalasia type, 1 MIM#130060; Osteogenesis imperfecta, type I MIM#166200; Osteogenesis imperfecta, type II MIM#166210; Osteogenesis imperfecta, type III MIM#259420; Osteogenesis imperfecta, type IV MIM#166220 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13652 | COL1A1 | Ain Roesley reviewed gene: COL1A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301422, 20301667, 30071989, 28981071, 12362985, 28956891; Phenotypes: Caffey disease MIM#114000, Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 1 MIM#619115, Ehlers-Danlos syndrome, arthrochalasia type, 1 MIM#130060, Osteogenesis imperfecta, type I MIM#166200, Osteogenesis imperfecta, type II MIM#166210, Osteogenesis imperfecta, type III MIM#259420, Osteogenesis imperfecta, type IV MIM#166220; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13652 | COL18A1 | Ain Roesley Marked gene: COL18A1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13650 | COL17A1 | Ain Roesley Marked gene: COL17A1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13649 | COL17A1 |
Ain Roesley commented on gene: COL17A1: For Epithelial recurrent erosion dystrophy, AD: Multiple families reported, c.3156C>T is recurrent. For EB, AR: well established association (GeneReviews PMID:20301304) |
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| Mendeliome v0.13649 | COL12A1 | Ain Roesley Marked gene: COL12A1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13648 | COL12A1 | Ain Roesley Phenotypes for gene: COL12A1 were changed from to Myopathic EDS; Bethlem myopathy 2 MIM#616471; Ullrich congenital muscular dystrophy 2 MIM#616470 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13647 | COL12A1 | Ain Roesley reviewed gene: COL12A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28306229, 31273343, 24334604; Phenotypes: Myopathic EDS, Bethlem myopathy 2 MIM#616471, Ullrich congenital muscular dystrophy 2 MIM#616470; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13647 | COL11A2 | Ain Roesley Marked gene: COL11A2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13645 | COG7 | Ain Roesley Marked gene: COG7 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13643 | COASY | Ain Roesley Marked gene: COASY as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13643 | COASY | Ain Roesley Phenotypes for gene: COASY were changed from to Neurodegeneration with brain iron accumulation 6 MIM#615643; Pontocerebellar hypoplasia, type 12 MIM#v618266 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13642 | COASY |
Ain Roesley changed review comment from: Green for both NBIA and PCH; to: Green for both NBIA and PCH only 2 variants reported for PCH - a fs (c.1549_1550delAG) and c.1486-3C>G (Recurrent) |
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| Mendeliome v0.13642 | COASY | Ain Roesley reviewed gene: COASY: Rating: GREEN; Mode of pathogenicity: None; Publications: 30089828, 28489334, 24360804, 35499143; Phenotypes: Neurodegeneration with brain iron accumulation 6 MIM#615643, Pontocerebellar hypoplasia, type 12 MIM#v618266; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13642 | HMBS | Zornitza Stark Marked gene: HMBS as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13642 | HMBS | Zornitza Stark Phenotypes for gene: HMBS were changed from to Porphyria, acute intermittent, MIM#176000; Porphyria, acute intermittent, non-erythroid variant, MIM#176000 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13640 | HMBS | Zornitza Stark reviewed gene: HMBS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Porphyria, acute intermittent, MIM#176000, Porphyria, acute intermittent, non-erythroid variant, MIM#176000; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13640 | HK1 | Zornitza Stark Marked gene: HK1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13640 | HK1 | Zornitza Stark Phenotypes for gene: HK1 were changed from to Neuropathy, hereditary motor and sensory, Russe type , MIM#605285; Haemolytic anaemia due to hexokinase deficiency, MIM# 235700; Neurodevelopmental disorder with visual defects and brain anomalies, MIM# 618547; Retinitis pigmentosa 79, MIM# 617460 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13637 | HK1 |
Zornitza Stark changed review comment from: HMSNR is an autosomal recessive progressive complex peripheral neuropathy characterized by onset in the first decade of distal lower limb weakness and muscle atrophy resulting in walking difficulties. Distal impairment of the upper limbs usually occurs later, as does proximal lower limb weakness. There is distal sensory impairment, with pes cavus and areflexia. Laboratory studies suggest that it is a myelinopathy resulting in reduced nerve conduction velocities in the demyelinating range as well as a length-dependent axonopathy. Founder variant in the Roma, -3818-195G-C, AltT2 EXON in 5'UTR identified in multiple families. Note gene is associated with other phenotypes.; to: Bi-allelic variants and neuropathy: HMSNR is an autosomal recessive progressive complex peripheral neuropathy characterized by onset in the first decade of distal lower limb weakness and muscle atrophy resulting in walking difficulties. Distal impairment of the upper limbs usually occurs later, as does proximal lower limb weakness. There is distal sensory impairment, with pes cavus and areflexia. Laboratory studies suggest that it is a myelinopathy resulting in reduced nerve conduction velocities in the demyelinating range as well as a length-dependent axonopathy. Founder variant in the Roma, -3818-195G-C, AltT2 EXON in 5'UTR identified in multiple families. Note gene is associated with other phenotypes. |
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| Mendeliome v0.13637 | HK1 |
Zornitza Stark edited their review of gene: HK1: Added comment: Mono-allelic variants and ID: PMID30778173, 7 patients from 6 unrelated families with denovo missense variants in the N-terminal half of HK1 Mono-allelic variants and RP: Seven families reported with the same heterozygous missense variant, p.Glu847Lys and RP from different ethnicities. Some supportive evidence. Variant is present in 3 hets in gnomad. Bi-allelic variants and haemolytic anaemia: more than 10 families reported.; Changed publications: 19536174, 30778173, 25316723, 25190649, 31621442, 32814480, 7655856, 12393545, 33361148, 31119733, 27282571; Changed phenotypes: Neuropathy, hereditary motor and sensory, Russe type , MIM#605285, Haemolytic anaemia due to hexokinase deficiency, MIM# 235700, Neurodevelopmental disorder with visual defects and brain anomalies, MIM# 618547, Retinitis pigmentosa 79, MIM# 617460; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal |
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| Mendeliome v0.13636 | RPE65 | Zornitza Stark Marked gene: RPE65 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13633 | SLC24A1 | Zornitza Stark Marked gene: SLC24A1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13633 | SLC24A1 | Zornitza Stark Phenotypes for gene: SLC24A1 were changed from to Night blindness, congenital stationary (complete), 1D, autosomal recessive, MIM#613830, MONDO:0013450 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13630 | SLC25A1 | Zornitza Stark Marked gene: SLC25A1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13630 | SLC25A1 | Zornitza Stark Phenotypes for gene: SLC25A1 were changed from to Combined D-2- and L-2-hydroxyglutaric aciduria MIM#: 615182, MONDO:0014072; Myasthenic syndrome, congenital, 23, presynaptic, MIM#618197, MONDO:0032596 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13627 | RRAS | Zornitza Stark Marked gene: RRAS as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13623 | SLC11A1 | Zornitza Stark Marked gene: SLC11A1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13619 | SIL1 | Zornitza Stark Marked gene: SIL1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13619 | SIL1 | Zornitza Stark Phenotypes for gene: SIL1 were changed from to Marinesco-Sjogren syndrome, MIM#248800; MONDO#0009567 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13616 | SLC24A1 | Manny Jacobs reviewed gene: SLC24A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35486108, 35446361, 20850105, 26822852; Phenotypes: Night blindness, congenital stationary (complete), 1D, autosomal recessive, MIM#613830, MONDO:0013450; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13616 | SIK1 | Zornitza Stark Marked gene: SIK1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13613 | SLC25A1 | Manny Jacobs reviewed gene: SLC25A1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 26870663, 31527857, 31808147, 23561848, 23393310; Phenotypes: Combined D-2- and L-2-hydroxyglutaric aciduria MIM#: 615182, MONDO:0014072, Myasthenic syndrome, congenital, 23, presynaptic, MIM#618197, MONDO:0032596; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13613 | RRAS |
Belinda Chong changed review comment from: Catts et al (2021) identified a 7-year-old boy with a history of craniosynostosis, congenital heart defect, and mild dysmorphic features who was incidentally found to have pediatric MDS with monosomy 7 in the context of previously unrecognized germline RRAS mutation. A heterozygous c.116_118dup (NM_006270.5) variant resulting in p.G39dup was identified and excluded in an unaffected sibling, and both parents. Two individuals reported. One de novo variant, the inheritance of the other variant uncertain. Some supportive functional data. Rated as LIMITED by ClinGen (reviewed 27/04/2018).; to: Catts et al (2021) identified a 7-year-old boy with a history of craniosynostosis, congenital heart defect, and mild dysmorphic features who was incidentally found to have pediatric MDS with monosomy 7 in the context of previously unrecognized germline RRAS mutation. A heterozygous c.116_118dup (NM_006270.5) variant resulting in p.G39dup was identified and excluded in an unaffected sibling, and both parents. Two individuals reported. One de novo variant, the inheritance of the other variant uncertain. Some supportive functional data. Rated as LIMITED by ClinGen (reviewed 27/04/2018). |
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| Mendeliome v0.13613 | HIBCH | Zornitza Stark Marked gene: HIBCH as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13610 | HGF | Zornitza Stark Marked gene: HGF as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13607 | HGD | Zornitza Stark Marked gene: HGD as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13604 | HFE | Zornitza Stark Marked gene: HFE as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13602 | HESX1 | Zornitza Stark Marked gene: HESX1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13602 | HESX1 | Zornitza Stark Phenotypes for gene: HESX1 were changed from to Growth hormone deficiency with pituitary anomalies, MIM#182230; Pituitary hormone deficiency, combined, 5, MIM#182230; Septooptic dysplasia, MIM#182230 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13600 | HESX1 | Zornitza Stark reviewed gene: HESX1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Growth hormone deficiency with pituitary anomalies, MIM#182230, Pituitary hormone deficiency, combined, 5, MIM#182230, Septooptic dysplasia, MIM#182230; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13599 | HERC1 | Zornitza Stark Marked gene: HERC1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13599 | HERC1 | Zornitza Stark Phenotypes for gene: HERC1 were changed from to Macrocephaly, dysmorphic facies, and psychomotor retardation, MIM# 617011 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13596 | HERC1 | Zornitza Stark reviewed gene: HERC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28323226, 27108999, 26153217, 26138117, 20041218; Phenotypes: Macrocephaly, dysmorphic facies, and psychomotor retardation, MIM# 617011; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13596 | HEPACAM | Zornitza Stark Marked gene: HEPACAM as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13596 | HEPACAM | Zornitza Stark Phenotypes for gene: HEPACAM were changed from to Megalencephalic leukoencephalopathy with subcortical cysts 2A, MIM# 613925; Megalencephalic leukoencephalopathy with subcortical cysts 2B, remitting, with or without mental retardation, MIM# 613926 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13593 | HEPACAM | Zornitza Stark reviewed gene: HEPACAM: Rating: GREEN; Mode of pathogenicity: None; Publications: 21419380, 21419380; Phenotypes: Megalencephalic leukoencephalopathy with subcortical cysts 2A, MIM# 613925, Megalencephalic leukoencephalopathy with subcortical cysts 2B, remitting, with or without mental retardation, MIM# 613926; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13593 | LIPT2 | Alison Yeung Marked gene: LIPT2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13592 | SIL1 | Samantha Ayres reviewed gene: SIL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24176978, 16282977, 20301371; Phenotypes: Marinesco-Sjogren syndrome, MIM#248800, MONDO#0009567; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13592 | DNASE2 | Zornitza Stark Phenotypes for gene: DNASE2 were changed from Auto-inflammatory disorder; splenomegaly; glomerulonephritis; liver fibrosis; arthritis; HLH to Autoinflammatory-pancytopaenia syndrome, MIM# 619858 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13589 | LIPH | Alison Yeung Marked gene: LIPH as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13587 | LIPC | Alison Yeung Marked gene: LIPC as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13585 | LIPC |
Alison Yeung Added comment: Comment on mode of inheritance: PMID: 1671786, 12777476, 1883393, 22798447 - 7 cases from 3 unrelated families with hepatic lipase deficiency and biallelic variants. PMID: 26423094 - null mouse had dyslipidemia on a high cholesterol and fat diet PMID: 23219720, 22464213 - 2 cases with hyperalphalipoproteinemia and heterozygous variants, with supporting in vitro funcitonal assays |
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| Mendeliome v0.13583 | LINS1 | Alison Yeung Marked gene: LINS1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13581 | HCRT | Zornitza Stark Marked gene: HCRT as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13581 | HCRT | Zornitza Stark Phenotypes for gene: HCRT were changed from to Narcolepsy 1 , MIM# 161400 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13577 | LIM2 | Alison Yeung Marked gene: LIM2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13577 | HCRT | Zornitza Stark reviewed gene: HCRT: Rating: RED; Mode of pathogenicity: None; Publications: 10973318, 11148249, 11723284; Phenotypes: Narcolepsy 1 , MIM# 161400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13577 | LIM2 | Alison Yeung Phenotypes for gene: LIM2 were changed from to Cataract 19, multiple types, MIM# 615277 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13574 | LIM2 | Alison Yeung reviewed gene: LIM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 27814360, 11917274, 18596884, 33708862, 32202185, 21617753; Phenotypes: Cataract 19, multiple types, MIM# 615277; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13574 | HCN1 | Zornitza Stark Marked gene: HCN1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13571 | HCCS | Zornitza Stark Marked gene: HCCS as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13571 | HCCS | Zornitza Stark Phenotypes for gene: HCCS were changed from to Linear skin defects with multiple congenital anomalies 1, MIM# 309801 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13568 | HCCS | Zornitza Stark reviewed gene: HCCS: Rating: GREEN; Mode of pathogenicity: None; Publications: 17033964, 30068298, 24735900; Phenotypes: Linear skin defects with multiple congenital anomalies 1, MIM# 309801; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13568 | HBA2 | Zornitza Stark Marked gene: HBA2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13565 | HBA1 | Zornitza Stark Marked gene: HBA1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13563 | HAO1 | Zornitza Stark Marked gene: HAO1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13562 | HAMP | Zornitza Stark Marked gene: HAMP as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13559 | HADHB | Zornitza Stark Marked gene: HADHB as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13556 | HADHA | Zornitza Stark Marked gene: HADHA as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13554 | HADH | Zornitza Stark Marked gene: HADH as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13552 | HACD1 | Zornitza Stark Marked gene: HACD1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13549 | HAAO | Zornitza Stark Marked gene: HAAO as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13549 | HAAO | Zornitza Stark Phenotypes for gene: HAAO were changed from to Vertebral, cardiac, renal, and limb defects syndrome 1 MIM#617660; NAD deficiency | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13546 | H6PD | Zornitza Stark Marked gene: H6PD as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13543 | BUD23 | Zornitza Stark Marked gene: BUD23 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13542 | BTNL2 | Zornitza Stark Marked gene: BTNL2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13542 | BTNL2 | Zornitza Stark Phenotypes for gene: BTNL2 were changed from to {Sarcoidosis, susceptibility to, 2} 612387 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13539 | BTNL2 | Zornitza Stark reviewed gene: BTNL2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Sarcoidosis, susceptibility to, 2} 612387; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13539 | BTK | Zornitza Stark Marked gene: BTK as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13536 | BRIP1 | Zornitza Stark Marked gene: BRIP1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13533 | BRAF | Zornitza Stark Marked gene: BRAF as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13533 | BRAF | Zornitza Stark Phenotypes for gene: BRAF were changed from to Noonan syndrome 7, MIM# 613706; Cardiofaciocutaneous syndrome, MIM# 115150 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13531 | BRAF | Zornitza Stark Mode of pathogenicity for gene: BRAF was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13529 | BRAF | Zornitza Stark reviewed gene: BRAF: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 19206169, 18042262; Phenotypes: Noonan syndrome 7, MIM# 613706, Cardiofaciocutaneous syndrome, MIM# 115150; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13529 | BPGM | Zornitza Stark Marked gene: BPGM as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13525 | BMPR1A | Zornitza Stark Marked gene: BMPR1A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13522 | BLVRA | Zornitza Stark Marked gene: BLVRA as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13518 | BLK | Zornitza Stark Marked gene: BLK as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13518 | BLK | Zornitza Stark Phenotypes for gene: BLK were changed from to Common variable immunodeficiency, MONDO:0015517 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13514 | BLK | Zornitza Stark reviewed gene: BLK: Rating: AMBER; Mode of pathogenicity: None; Publications: 25926555; Phenotypes: Common variable immunodeficiency, MONDO:0015517; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13514 | BHLHE41 | Zornitza Stark Marked gene: BHLHE41 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13511 | BFSP1 | Zornitza Stark Marked gene: BFSP1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13511 | BFSP1 | Zornitza Stark Phenotypes for gene: BFSP1 were changed from to Cataract 33, multiple types, MIM# 611391 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13508 | BFSP1 | Zornitza Stark reviewed gene: BFSP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 17225135, 26694549, 24379646, 28450710, 31842807, 26694549; Phenotypes: Cataract 33, multiple types, MIM# 611391; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13508 | BCL2 | Zornitza Stark Marked gene: BCL2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13507 | BCKDK | Zornitza Stark Marked gene: BCKDK as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13504 | BCL10 | Zornitza Stark Marked gene: BCL10 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13501 | BCHE | Zornitza Stark Marked gene: BCHE as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13499 | BBS2 | Zornitza Stark Marked gene: BBS2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13499 | BBS2 | Zornitza Stark Phenotypes for gene: BBS2 were changed from to Bardet-Biedl syndrome 2, MIM# 615981; Retinitis pigmentosa 74, MIM# 616562 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13496 | BBS12 | Zornitza Stark Marked gene: BBS12 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13496 | BBS12 | Zornitza Stark Phenotypes for gene: BBS12 were changed from to Bardet-Biedl syndrome 12, MIM# 615989 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13493 | BBS10 | Zornitza Stark Marked gene: BBS10 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13493 | BBS10 | Zornitza Stark Phenotypes for gene: BBS10 were changed from to Bardet-Biedl syndrome 10, MIM# 615987 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13490 | BBS1 | Zornitza Stark Marked gene: BBS1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13490 | BBS1 | Zornitza Stark Phenotypes for gene: BBS1 were changed from to Bardet-Biedl syndrome 1, MIM# 209900 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13487 | BAG3 | Zornitza Stark Marked gene: BAG3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13487 | BAG3 | Zornitza Stark Phenotypes for gene: BAG3 were changed from to Cardiomyopathy, dilated, 1HH, MIM# 613881; Myopathy, myofibrillar, 6, MIM# 612954 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13484 | BAG3 | Zornitza Stark reviewed gene: BAG3: Rating: GREEN; Mode of pathogenicity: None; Publications: 21353195, 25008357, 25448463, 24623017, 27391596, 28211974, 30442290, 31983221, 28737513, 29323723, 33947203, 25208129, 32453099, 22734908; Phenotypes: Cardiomyopathy, dilated, 1HH, MIM# 613881, Myopathy, myofibrillar, 6, MIM# 612954; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13484 | BACH2 | Zornitza Stark Marked gene: BACH2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13481 | B4GALT1 | Zornitza Stark Marked gene: B4GALT1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13478 | B4GALT1 |
Zornitza Stark changed review comment from: Intellectual disability is part of CDG, although non-neurological forms of this CDG have been described. Sources: Expert list; to: At least 3 unrelated families. Sources: Expert list |
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| Mendeliome v0.13478 | B4GALNT1 | Zornitza Stark Marked gene: B4GALNT1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13478 | B4GALNT1 | Zornitza Stark Phenotypes for gene: B4GALNT1 were changed from to Spastic paraplegia 26, autosomal recessive (MIM #609195) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13474 | B4GALNT1 | Zornitza Stark reviewed gene: B4GALNT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23746551 24103911; Phenotypes: Spastic paraplegia 26, autosomal recessive (MIM #609195); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13474 | B3GLCT | Zornitza Stark Marked gene: B3GLCT as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13471 | APOA5 | Zornitza Stark Marked gene: APOA5 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13471 | AP1S2 | Zornitza Stark Phenotypes for gene: AP1S2 were changed from Mental retardation, X-linked syndromic 5, MIM#304340 to Pettigrew syndrome, MIM# 304340 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13469 | APCDD1 | Zornitza Stark Marked gene: APCDD1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13466 | ANO10 | Zornitza Stark Phenotypes for gene: ANO10 were changed from Spinocerebellar ataxia, autosomal recessive 10 MIM#613728 to Spinocerebellar ataxia, autosomal recessive 10, MIM#613728 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13464 | ANO10 | Zornitza Stark reviewed gene: ANO10: Rating: GREEN; Mode of pathogenicity: None; Publications: 21092923, 25182700; Phenotypes: Spinocerebellar ataxia, autosomal recessive 10, MIM#613728; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13464 | PHOX2B | Zornitza Stark Marked gene: PHOX2B as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13461 | PEX26 | Zornitza Stark Marked gene: PEX26 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13458 | PEX2 | Zornitza Stark Marked gene: PEX2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13455 | PEX19 | Zornitza Stark Marked gene: PEX19 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13454 | PEX16 | Zornitza Stark Marked gene: PEX16 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13451 | PEX14 | Zornitza Stark Marked gene: PEX14 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13448 | PEX13 | Zornitza Stark Marked gene: PEX13 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13446 | PEX12 | Zornitza Stark Marked gene: PEX12 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13443 | ENTPD1 | Zornitza Stark commented on gene: ENTPD1: PMID 35471564: 27 individuals from 17 families published, expanding the phenotype to a complex neurodevelopmental disorder characterised by ID, white matter abnormalities and spastic paraplegia. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13443 | RSPH1 | Zornitza Stark Marked gene: RSPH1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13443 | RSPH1 | Zornitza Stark Phenotypes for gene: RSPH1 were changed from to Ciliary dyskinesia, primary, 24 MIM#615481 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13437 | APOA2 | Elena Savva Marked gene: APOA2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13435 | APOA1 | Elena Savva Marked gene: APOA1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13435 | APOA1 | Elena Savva Phenotypes for gene: APOA1 were changed from to Amyloidosis, 3 or more types MIM#105200; Hypoalphalipoproteinemia, primary, 2 MIM#618463; Hypoalphalipoproteinemia, primary, 2, intermediate MIM#619836 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13434 | APOA1 | Elena Savva reviewed gene: APOA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Amyloidosis, 3 or more types MIM#105200, Hypoalphalipoproteinemia, primary, 2 MIM#618463, Hypoalphalipoproteinemia, primary, 2, intermediate MIM#619836; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13434 | AP1S2 | Elena Savva Marked gene: AP1S2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13434 | AP1S2 | Elena Savva Phenotypes for gene: AP1S2 were changed from to Mental retardation, X-linked syndromic 5, MIM#304340 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13432 | ANO10 | Elena Savva Phenotypes for gene: ANO10 were changed from Spinocerebellar ataxia, autosomal recessive 10 MIM#613728 to Spinocerebellar ataxia, autosomal recessive 10 MIM#613728 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13430 | ANO10 | Elena Savva Phenotypes for gene: ANO10 were changed from to Spinocerebellar ataxia, autosomal recessive 10 MIM#613728 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13430 | ANO10 | Elena Savva Marked gene: ANO10 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13429 | DIO1 | Zornitza Stark Marked gene: DIO1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13422 | TUBA8 | Zornitza Stark changed review comment from: Two families reported initially (PMID 19896110). However, note that mouse model does not have a brain phenotype and WES in the original families identified homozygous, previously reported as pathogenic, LoF variant in SNAP29, which is much more likely to be causative (28388629).; to: Bi-allelic variants and cortical dysplasia: Two families reported initially (PMID 19896110). However, note that mouse model does not have a brain phenotype and WES in the original families identified homozygous, previously reported as pathogenic, LoF variant in SNAP29, which is much more likely to be causative (28388629). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13422 | TUBA8 | Zornitza Stark edited their review of gene: TUBA8: Added comment: Mono-allelic variants and macrothrombocytopaenia: 6 unrelated individuals with missense variants found in a large cohort of blood donors, some functional data. Individuals were generally asymptomatic.; Changed rating: AMBER; Changed publications: 34704371; Changed phenotypes: Macrothrombocytopaenia, isolated, 2, autosomal dominant, MIM# 619840; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13422 | NRCAM | Zornitza Stark Phenotypes for gene: NRCAM were changed from neurodevelopmental disorder, NRCAM-related, MONDO:0700092 to Neurodevelopmental disorder with neuromuscular and skeletal abnormalities, MIM# 619833 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13421 | NRCAM | Zornitza Stark reviewed gene: NRCAM: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with neuromuscular and skeletal abnormalities, MIM# 619833; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13420 | PEX3 | Zornitza Stark Marked gene: PEX3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13417 | PEX5 | Zornitza Stark Marked gene: PEX5 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13414 | PEX7 | Zornitza Stark Marked gene: PEX7 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13411 | PFKM | Zornitza Stark Marked gene: PFKM as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13408 | PGAM2 | Zornitza Stark Marked gene: PGAM2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13405 | PHF11 | Zornitza Stark Marked gene: PHF11 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13404 | PHIP | Zornitza Stark Marked gene: PHIP as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13401 | PHIP |
Zornitza Stark changed review comment from: Chung-Jansen syndrome (CHUJANS) is characterized by global developmental delay apparent from infancy, impaired intellectual development or learning difficulties, behavioral abnormalities, dysmorphic features, and obesity. More than 20 individuals reported.; to: Chung-Jansen syndrome (CHUJANS) is characterized by global developmental delay apparent from infancy, impaired intellectual development or learning difficulties, behavioural abnormalities, dysmorphic features, and obesity. More than 20 individuals reported. |
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| Mendeliome v0.13401 | PHKA2 | Zornitza Stark Marked gene: PHKA2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13398 | PIK3CA | Zornitza Stark Marked gene: PIK3CA as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13398 | PIK3CA | Zornitza Stark Phenotypes for gene: PIK3CA were changed from to Megalencephaly-capillary malformation (MCAP) syndrome , MIM#602501; CLAPO syndrome, somatic, MIM# 613089; CLOVE syndrome, somatic, MIM# 612918 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13396 | PIK3CA | Zornitza Stark reviewed gene: PIK3CA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Megalencephaly-capillary malformation (MCAP) syndrome , MIM#602501, CLAPO syndrome, somatic, MIM# 613089, CLOVE syndrome, somatic, MIM# 612918; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13396 | PISD | Zornitza Stark Phenotypes for gene: PISD were changed from to Liberfarb syndrome, MIM# 618889; Intellectual disability; cataracts; retinal degeneration; microcephaly; deafness; short stature; white matter abnormalities | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13393 | PISD | Zornitza Stark edited their review of gene: PISD: Changed phenotypes: Liberfarb syndrome, MIM# 618889, Intellectual disability, cataracts, retinal degeneration, microcephaly, deafness, short stature, white matter abnormalities | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13393 | PHYH | Zornitza Stark Marked gene: PHYH as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13390 | PHYH |
Zornitza Stark edited their review of gene: PHYH: Added comment: Refsum disease is an autosomal recessive inborn error of lipid metabolism classically characterized by a tetrad of clinical abnormalities: retinitis pigmentosa, peripheral neuropathy, cerebellar ataxia, and elevated protein levels in the cerebrospinal fluid (CSF) without an increase in the number of cells. Well established gene-disease association.; Changed publications: 9326939, 9326940 |
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| Mendeliome v0.13390 | PIEZO2 | Zornitza Stark Marked gene: PIEZO2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13390 | PIEZO2 | Zornitza Stark Phenotypes for gene: PIEZO2 were changed from to Marden-Walker syndrome (MIM#248700); Arthrogryposis, distal, type 3 (MIM#114300); Arthrogryposis, distal, type 5 (MIM#108145); Arthrogryposis, distal, with impaired proprioception and touch, MIM# 617146 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13387 | PIEZO2 |
Zornitza Stark changed review comment from: Bi-allelic variants: more than 5 unrelated families reported. Mono-allelic variants: DA5, more than 20 families reported. DA3, more than 10 families reported, R2686H is recurrent.; to: Bi-allelic variants: more than 5 unrelated families reported. Mono-allelic variants: DA5, more than 20 families reported. DA3, more than 10 families reported, R2686H is recurrent. Marden-Walker: 2 families reported. |
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| Mendeliome v0.13387 | PIEZO2 | Zornitza Stark edited their review of gene: PIEZO2: Changed phenotypes: Marden-Walker syndrome (MIM#248700), Arthrogryposis, distal, type 3 (MIM#114300), Arthrogryposis, distal, type 5 (MIM#108145), Arthrogryposis, distal, with impaired proprioception and touch, MIM# 617146 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13387 | PIEZO2 |
Zornitza Stark changed review comment from: Bi-allelic variants: more than 5 unrelated families reported. Mono-allelic variants: DA5, more than 20 families reported.; to: Bi-allelic variants: more than 5 unrelated families reported. Mono-allelic variants: DA5, more than 20 families reported. DA3, more than 10 families reported, R2686H is recurrent. |
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| Mendeliome v0.13387 | PIEZO2 |
Zornitza Stark changed review comment from: Bi-allelic variants: more than 5 unrelated families reported. Mono-allelic variants: DA3, more than 20 families reported.; to: Bi-allelic variants: more than 5 unrelated families reported. Mono-allelic variants: DA5, more than 20 families reported. |
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| Mendeliome v0.13387 | PIEZO2 |
Zornitza Stark changed review comment from: Bi-allelic variants: more than 5 unrelated families reported.; to: Bi-allelic variants: more than 5 unrelated families reported. Mono-allelic variants: DA3, more than 20 families reported. |
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| Mendeliome v0.13387 | RSPH1 | Belinda Chong reviewed gene: RSPH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23993197; Phenotypes: Ciliary dyskinesia, primary, 24 MIM#615481; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13387 | PIEZO2 | Zornitza Stark reviewed gene: PIEZO2: Rating: GREEN; Mode of pathogenicity: None; Publications: 27653382, 27607563, 27843126, 27974811; Phenotypes: Marden-Walker syndrome (MIM#248700), Arthrogryposis, distal, type 3 (MIM#114300), Arthrogryposis, distal, type 5 (MIM#108145); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13387 | BSCL2 | Zornitza Stark Marked gene: BSCL2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13387 | BSCL2 | Zornitza Stark Phenotypes for gene: BSCL2 were changed from to Neuropathy, distal hereditary motor, type VC, MIM# 619112; Encephalopathy, progressive, with or without lipodystrophy, MIM#615924; Lipodystrophy, congenital generalized, type 2, MIM# 269700; Silver spastic paraplegia syndrome, MIM# 270685; Developmental and epileptic encephalopathy, BSCL2-related, dominant, MONDO:0100062 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13384 | BSCL2 |
Zornitza Stark edited their review of gene: BSCL2: Added comment: Multiple families reported with bi-allelic variants and isolated or syndromic lipodystrophy. Mono-allelic variants and DEE: Two families reported with de novo variants in PMIDs 31369919 and 35290466. We are aware of further three individuals identified as a result of clinical testing, so a total of 4 with a change at position p.Pro149; Changed publications: 14981520, 15732094, 11479539, 15181077, 15126564, 23564749, 31369919, 35290466 |
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| Mendeliome v0.13384 | BSCL2 | Zornitza Stark edited their review of gene: BSCL2: Changed phenotypes: Neuropathy, distal hereditary motor, type VC, MIM# 619112, Encephalopathy, progressive, with or without lipodystrophy, MIM#615924, Lipodystrophy, congenital generalized, type 2, MIM# 269700, Silver spastic paraplegia syndrome, MIM# 270685, Developmental and epileptic encephalopathy, BSCL2-related, dominant, MONDO:0100062; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13384 | CNNM2 | Ain Roesley Marked gene: CNNM2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13384 | CNNM2 | Ain Roesley Phenotypes for gene: CNNM2 were changed from to Hypomagnesemia 6, renal MIM#613882; Hypomagnesemia, seizures, and mental retardation MIM#616418 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13382 | CNNM2 | Ain Roesley reviewed gene: CNNM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34604137, 35170241; Phenotypes: Hypomagnesemia 6, renal MIM#613882, Hypomagnesemia, seizures, and mental retardation MIM#616418; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13382 | PIGC | Zornitza Stark Marked gene: PIGC as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13379 | CNGB1 | Ain Roesley Marked gene: CNGB1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13377 | CNGA1 | Ain Roesley Marked gene: CNGA1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13375 | CLN8 | Ain Roesley Marked gene: CLN8 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13375 | CLN8 | Ain Roesley Phenotypes for gene: CLN8 were changed from to Ceroid lipofuscinosis, neuronal, 8, MIM# 600143; Ceroid lipofuscinosis, neuronal, 8, Northern epilepsy variant, MIM# 610003 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13374 | CLN8 | Ain Roesley reviewed gene: CLN8: Rating: GREEN; Mode of pathogenicity: None; Publications: 10508524, 15024724, 16570191; Phenotypes: Ceroid lipofuscinosis, neuronal, 8, MIM# 600143, Ceroid lipofuscinosis, neuronal, 8, Northern epilepsy variant, MIM# 610003; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13374 | CLN6 | Ain Roesley Marked gene: CLN6 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13372 | CLEC7A | Ain Roesley Marked gene: CLEC7A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13370 | PIGW | Zornitza Stark Marked gene: PIGW as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13367 | PIK3R2 | Zornitza Stark Marked gene: PIK3R2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13364 | PITX2 | Zornitza Stark Marked gene: PITX2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13361 | PITX3 | Zornitza Stark Marked gene: PITX3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13361 | PITX3 | Zornitza Stark Phenotypes for gene: PITX3 were changed from Anterior segment dysgenesis 1, multiple subtypes, MIM# 107250; Cataract 11, multiple types, MIM# 610623; Microphthalmia to Anterior segment dysgenesis 1, multiple subtypes, MIM# 107250; Cataract 11, multiple types, MIM# 610623; Microphthalmia MONDO:0021129 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13360 | PITX3 | Zornitza Stark Phenotypes for gene: PITX3 were changed from to Anterior segment dysgenesis 1, multiple subtypes, MIM# 107250; Cataract 11, multiple types, MIM# 610623; Microphthalmia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13357 | PITX3 | Zornitza Stark reviewed gene: PITX3: Rating: GREEN; Mode of pathogenicity: None; Publications: 29405783; Phenotypes: Anterior segment dysgenesis 1, multiple subtypes, MIM# 107250, Cataract 11, multiple types, MIM# 610623, Microphthalmia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13357 | CLDN19 | Zornitza Stark Phenotypes for gene: CLDN19 were changed from Hypomagnesemia 5, renal, with ocular involvement, MIM#248190 to Hypomagnesaemia 5, renal, with ocular involvement, MIM#248190 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13356 | PEX11B | Zornitza Stark Marked gene: PEX11B as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13356 | PEX11B | Zornitza Stark Added comment: Comment when marking as ready: Two published families and one International. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13353 | PER2 | Zornitza Stark Marked gene: PER2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13349 | PDZD7 | Zornitza Stark Marked gene: PDZD7 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13346 | PDYN | Zornitza Stark Marked gene: PDYN as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13346 | PDYN | Zornitza Stark Added comment: Comment when marking as ready: The presence of some of these variants in the population is concerning. However, functional data also supports gene-disease association. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13346 | PDYN | Zornitza Stark Phenotypes for gene: PDYN were changed from to Spinocerebellar ataxia 23 - MIM#610245 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13343 | PDGFRA | Zornitza Stark Marked gene: PDGFRA as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13340 | RSPH3 | Zornitza Stark Marked gene: RSPH3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13340 | RSPH3 | Zornitza Stark Phenotypes for gene: RSPH3 were changed from to Ciliary dyskinesia, primary, 32 MIM#616481 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13337 | RSPH4A | Zornitza Stark Marked gene: RSPH4A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13337 | RSPH4A | Zornitza Stark Phenotypes for gene: RSPH4A were changed from to Ciliary dyskinesia, primary, 11, OMIM#612649 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13334 | RSPH9 | Zornitza Stark Marked gene: RSPH9 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13334 | RSPH9 | Zornitza Stark Phenotypes for gene: RSPH9 were changed from to Ciliary dyskinesia, primary, 12, MIM#612650 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13331 | BVES | Zornitza Stark Marked gene: BVES as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13331 | BVES | Zornitza Stark Phenotypes for gene: BVES were changed from to Muscular dystrophy, limb-girdle, autosomal recessive 25, MIM# 616812 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13327 | BVES |
Zornitza Stark changed review comment from: PMID: 26642364 - 1 family (3 affecteds) with cardiac arrhythmia and limb-girdle muscular dystrophy. Supported by functional studies. The proband showed lower limb girdle weakness at ~40 years old with muscle biopsy proving dystrophic changes. His 2 affected grandchildren had onset in teenage years. PMID: 32528171 - 1 patient with limb girdle weakness. PMID: 31119192 - 3 families (4 affecteds) with limb-girdle muscular weakness and cardiac abnormalities/arrhythmia. All had onset in adulthood, with exercise intolerance or proximal weakness.; to: PMID: 26642364 - 1 family (3 affecteds) with cardiac arrhythmia and limb-girdle muscular dystrophy. Supported by functional studies: zebrafish model. The proband showed lower limb girdle weakness at ~40 years old with muscle biopsy proving dystrophic changes. His 2 affected grandchildren had onset in teenage years. PMID: 32528171 - 1 patient with limb girdle weakness. PMID: 31119192 - 3 families (4 affecteds) with limb-girdle muscular weakness and cardiac abnormalities/arrhythmia. All had onset in adulthood, with exercise intolerance or proximal weakness. |
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| Mendeliome v0.13327 | BVES | Zornitza Stark reviewed gene: BVES: Rating: GREEN; Mode of pathogenicity: None; Publications: 26642364, 32528171, 31119192; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 25, MIM# 616812; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13327 | FLII | Bryony Thompson Phenotypes for gene: FLII were changed from Dilated cardiomyopathy to Dilated cardiomyopathy MONDO:0005021 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13326 | CLDN19 | Ain Roesley Marked gene: CLDN19 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13326 | CLDN19 | Ain Roesley Phenotypes for gene: CLDN19 were changed from to Hypomagnesemia 5, renal, with ocular involvement, MIM#248190 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13324 | CLDN19 | Ain Roesley reviewed gene: CLDN19: Rating: GREEN; Mode of pathogenicity: None; Publications: 17033971, 22422540, 27530400]; Phenotypes: Hypomagnesemia 5, renal, with ocular involvement, MIM#248190; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13324 | CLDN16 | Ain Roesley Marked gene: CLDN16 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13323 | CLDN1 | Ain Roesley Marked gene: CLDN1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13322 | CLCNKB | Ain Roesley Marked gene: CLCNKB as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13322 | CLCNKB | Ain Roesley Phenotypes for gene: CLCNKB were changed from to Bartter syndrome, type 3, MIM# 607364; Bartter syndrome, type 4b, digenic, MIM# 613090 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13320 | CLCNKB | Ain Roesley reviewed gene: CLCNKB: Rating: GREEN; Mode of pathogenicity: None; Publications: 9326936, 15044642, 18310267; Phenotypes: Bartter syndrome, type 3, MIM# 607364, Bartter syndrome, type 4b, digenic, MIM# 613090; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13320 | CLCF1 | Ain Roesley Marked gene: CLCF1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13318 | CIT | Ain Roesley Marked gene: CIT as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13317 | CIT | Ain Roesley Phenotypes for gene: CIT were changed from Microcephaly 17, primary, autosomal recessive (MIM#617090) to Microcephaly 17, primary, autosomal recessive (MIM#617090) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13317 | CIT | Ain Roesley Phenotypes for gene: CIT were changed from to Microcephaly 17, primary, autosomal recessive (MIM#617090) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13315 | CIT | Ain Roesley reviewed gene: CIT: Rating: GREEN; Mode of pathogenicity: None; Publications: 27453578, 27503289, 27453579; Phenotypes: Microcephaly 17, primary, autosomal recessive (MIM#617090); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13315 | CISH | Ain Roesley Marked gene: CISH as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13314 | CISD2 | Ain Roesley Marked gene: CISD2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13313 | CILP | Ain Roesley Marked gene: CILP as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13312 | PDYN | Krithika Murali reviewed gene: PDYN: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301317, 23471613, 23108490, 22243190, 22287014; Phenotypes: Spinocerebellar ataxia 23 - MIM#610245; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13312 | CIC | Ain Roesley Marked gene: CIC as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13310 | CHST14 | Ain Roesley Marked gene: CHST14 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13308 | CHRNA2 | Ain Roesley Marked gene: CHRNA2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13306 | CHRM2 | Ain Roesley Marked gene: CHRM2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13306 | CHRM2 | Ain Roesley Phenotypes for gene: CHRM2 were changed from to Familial Dilated Cardiomyopathy MONDO#0016333, CHRM2-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13304 | CHRM2 | Ain Roesley reviewed gene: CHRM2: Rating: RED; Mode of pathogenicity: None; Publications: 23743182, 18451336; Phenotypes: Familial Dilated Cardiomyopathy MONDO#0016333, CHRM2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13304 | CHN1 | Ain Roesley Marked gene: CHN1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13302 | CHN1 | Ain Roesley Mode of pathogenicity for gene: CHN1 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13301 | CHN1 | Ain Roesley reviewed gene: CHN1: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 20301369; Phenotypes: Duane retraction syndrome 2,MIM#604356; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13301 | CHMP4B | Ain Roesley Marked gene: CHMP4B as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13301 | CHMP4B | Ain Roesley Phenotypes for gene: CHMP4B were changed from to Cataract 31, multiple types MIM#605387 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13299 | CHMP4B | Ain Roesley reviewed gene: CHMP4B: Rating: GREEN; Mode of pathogenicity: None; Publications: 34722561, 17701905, 10682967, 30078984; Phenotypes: Cataract 31, multiple types MIM#605387; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13299 | CHM | Ain Roesley Marked gene: CHM as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13297 | CHIT1 | Ain Roesley Marked gene: CHIT1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13297 | PDGFRA |
Krithika Murali changed review comment from: ?Suitability for Incidentalome versus Mendeliome based on adult age of diagnosis in reported cases. --- Six unrelated families reported with heterozygous germline variants associated with familial GIST and/or inflammatory fibroid polyps - IFP (benign lesions caused by excessive tissue proliferation and inflammatory cell infiltration into the lumen of the GI tract). Note that reported individuals diagnosed as adults. One individual reported with diagnosis of gastric mass/polyps age 22 (in 1977) raising the possibility of pre-symptomatic disease onset in adolescence. Green PanelApp England in the following panels: tumour predisposition - childhood onset; inherited predisposition to GIST; sarcoma cancer susceptibility. --- PMID 34107389 Hodan et al 2021 - report a 35 yo F with jejunal IFP and a heterozygous germline missense PDGFRA variant (c.1664A>G p.Y555C) . The variant segregated with 3 relatives with confirmed IFPs. Two obligate carriers were reported to have had a similar phenotype while at least one obligate male carrier had no reported history of IFPs. This variant was also reported in an unrelated family with multiple IFPs in 2006. PMID 29486293 Manley et al 2018 - proband is a 50 yo M with multiple ileal intusussceptions and IFPs and GIST. Heterozygous D846V germline variant identified. Variant identified in daughter and 2 siblings. Coarser face, coarser skin, broader hands and feet, unexplained premature loss of teeth requiring dentures in their 40s described in relatives with the variant, no polyps or tumour identified in screened family members. Pdgfra +/K mutant mice recapitulated the human phenotype. Mice with the constitutively activated mutant PDGFRA shown to have diffuse expansion of the gastrointestinal submucosa, which exhibits an increased number of spindled fibroblast-like cells and marked collagen deposition. Mutant mice also develop intestinal polyps morphologically similar to IFPs. The Pdgfra +/K mice also exhibit thickened skin due to excess collagen deposition within the dermis and subcutaneous tissues. PMID 25975287 Ricci et al 2015 - report a family with het germline P653L PDGFRA missense variant. The proband was a 67 yo M with multiple intra-abdominal GIST and gastric/colonic inflammatory fibroid polyps. Multiple adult relatives (youngest age 31) were diagnosed with IFPs/fibrous tumours with the variant segregating with disease. PMID: 18670346 Carney et al 2008 and PMID: 17566086 Pasini et al 2007 - heterozygous germline PDGFRA mutation (V561D) in an individual with GIST and multiple polyps, diagnosed initially aged 22 with multiple GIST/polyps. No other relatives available for genotyping and no other significant family history reported. PMID: 17087943 de Raedt et al 2006 - heterozygous PDGFRA(Y555C) variant reported in a family with multiple relatives affected by IFP, including one death from secondary bowel obstruction age 35. PMID: 14699510 Chompret et al 2004 - Heterozygous c.2675G>T D846Y germline variant detected in a French family with 5 relatives developing adult-onset GIST, variant segregated with disease. -- Gain of function somatic variants associated with sporadic GIST. Somatic chromosomal rearrangements resulting in PDGFRA and FIP1L1 gene fusion associated with idiopathic hypereosinophilic syndrome.; to: Six unrelated families reported with heterozygous germline variants associated with familial GIST and/or inflammatory fibroid polyps - IFP (benign lesions caused by excessive tissue proliferation and inflammatory cell infiltration into the lumen of the GI tract). Note that reported individuals diagnosed as adults. One individual reported with diagnosis of gastric mass/polyps age 22 (in 1977) raising the possibility of pre-symptomatic disease onset in adolescence. Green PanelApp England in the following panels: tumour predisposition - childhood onset; inherited predisposition to GIST; sarcoma cancer susceptibility. --- PMID 34107389 Hodan et al 2021 - report a 35 yo F with jejunal IFP and a heterozygous germline missense PDGFRA variant (c.1664A>G p.Y555C) . The variant segregated with 3 relatives with confirmed IFPs. Two obligate carriers were reported to have had a similar phenotype while at least one obligate male carrier had no reported history of IFPs. This variant was also reported in an unrelated family with multiple IFPs in 2006. PMID 29486293 Manley et al 2018 - proband is a 50 yo M with multiple ileal intusussceptions and IFPs and GIST. Heterozygous D846V germline variant identified. Variant identified in daughter and 2 siblings. Coarser face, coarser skin, broader hands and feet, unexplained premature loss of teeth requiring dentures in their 40s described in relatives with the variant, no polyps or tumour identified in screened family members. Pdgfra +/K mutant mice recapitulated the human phenotype. Mice with the constitutively activated mutant PDGFRA shown to have diffuse expansion of the gastrointestinal submucosa, which exhibits an increased number of spindled fibroblast-like cells and marked collagen deposition. Mutant mice also develop intestinal polyps morphologically similar to IFPs. The Pdgfra +/K mice also exhibit thickened skin due to excess collagen deposition within the dermis and subcutaneous tissues. PMID 25975287 Ricci et al 2015 - report a family with het germline P653L PDGFRA missense variant. The proband was a 67 yo M with multiple intra-abdominal GIST and gastric/colonic inflammatory fibroid polyps. Multiple adult relatives (youngest age 31) were diagnosed with IFPs/fibrous tumours with the variant segregating with disease. PMID: 18670346 Carney et al 2008 and PMID: 17566086 Pasini et al 2007 - heterozygous germline PDGFRA mutation (V561D) in an individual with GIST and multiple polyps, diagnosed initially aged 22 with multiple GIST/polyps. No other relatives available for genotyping and no other significant family history reported. PMID: 17087943 de Raedt et al 2006 - heterozygous PDGFRA(Y555C) variant reported in a family with multiple relatives affected by IFP, including one death from secondary bowel obstruction age 35. PMID: 14699510 Chompret et al 2004 - Heterozygous c.2675G>T D846Y germline variant detected in a French family with 5 relatives developing adult-onset GIST, variant segregated with disease. -- Gain of function somatic variants associated with sporadic GIST. Somatic chromosomal rearrangements resulting in PDGFRA and FIP1L1 gene fusion associated with idiopathic hypereosinophilic syndrome. |
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| Mendeliome v0.13296 | CHD1 | Ain Roesley Marked gene: CHD1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13296 | CHD1 | Ain Roesley Phenotypes for gene: CHD1 were changed from to Pilarowski-Bjornsson syndrome, MIM#617682 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13294 | CHD1 | Ain Roesley reviewed gene: CHD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28866611; Phenotypes: Pilarowski-Bjornsson syndrome, MIM#617682; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13294 | CFP | Ain Roesley Marked gene: CFP as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13292 | CFI | Ain Roesley Marked gene: CFI as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13292 | CFI | Ain Roesley Marked gene: CFI as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13289 | RSPH3 | Belinda Chong reviewed gene: RSPH3: Rating: GREEN; Mode of pathogenicity: None; Publications: 26073779; Phenotypes: Ciliary dyskinesia, primary, 32 MIM#616481; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13289 | HSPG2 |
Zornitza Stark changed review comment from: Allelic disorders with some phenotypic overlap. Schwartz-Jampel syndrome (SJS) is a rare autosomal recessive condition defined by the association of myotonia with chondrodysplasia; blepharophimosis is a key feature. More than 20 families reported. Silverman-Handmaker dyssegmental dysplasia (DDSH) is a lethal autosomal recessive skeletal dysplasia with anisospondyly and micromelia. Individuals with DDSH also have a flat face, micrognathia, cleft palate and reduced joint mobility, and frequently have an encephalocele. The endochondral growth plate is short, the calcospherites (spherical calcium-phosphorus crystals produced by hypertrophic chondrocytes) are unfused, and there is mucoid degeneration of the resting cartilage. Two families reported.; to: Allelic disorders with some phenotypic overlap. Schwartz-Jampel syndrome (SJS) is a rare autosomal recessive condition defined by the association of myotonia with chondrodysplasia; blepharophimosis is a key feature. More than 20 families reported. Silverman-Handmaker dyssegmental dysplasia (DDSH) is a lethal autosomal recessive skeletal dysplasia with anisospondyly and micromelia. Individuals with DDSH also have a flat face, micrognathia, cleft palate and reduced joint mobility, and frequently have an encephalocele. The endochondral growth plate is short, the calcospherites (spherical calcium-phosphorus crystals produced by hypertrophic chondrocytes) are unfused, and there is mucoid degeneration of the resting cartilage. Two families reported. Appears associated with null variants. |
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| Mendeliome v0.13289 | PKD1 | Zornitza Stark Marked gene: PKD1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13287 | PKD2 | Zornitza Stark Marked gene: PKD2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13285 | PKLR | Zornitza Stark Marked gene: PKLR as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13282 | PKP1 | Zornitza Stark Marked gene: PKP1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13279 | PLA2G5 | Zornitza Stark Marked gene: PLA2G5 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13276 | PLCE1 | Zornitza Stark Marked gene: PLCE1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13273 | PLCG2 | Zornitza Stark Marked gene: PLCG2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13273 | PLCG2 | Zornitza Stark Phenotypes for gene: PLCG2 were changed from to Common variable immunodeficiency; Autoinflammation, antibody deficiency, and immune dysregulation syndrome MIM#614878 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13266 | PLEKHM1 | Zornitza Stark changed review comment from: Three individuals reported with mono allelic variants, and one with bi-allelic. Animal model.; to: Three individuals reported with mono allelic variants, and two with bi-allelic. Animal models. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13266 | PLEKHM1 | Zornitza Stark Marked gene: PLEKHM1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13263 | RSPH4A |
Belinda Chong changed review comment from: Radial spokes are regularly spaced along cilia, sperm, and flagella axonemes and have a multisubunit 'stalk' and 'head' that form a signal transduction scaffold between the central microtubule pair and dynein arms. RSPH4A is predicted to be a component of the radial spoke head based on homology with proteins in the biflagellate alga Chlamydomonas reinhardtii and other ciliates (Castleman et al., 2009; PMID19200523) 9 families with primary ciliary dyskinesia without situs inversus (Kott et al. 2013 (PMID:23993197), Castleman et al., 2009 (PMID19200523) and Daniels et al. 2013; (PMID:23798057)): - In affected members of 4 Pakistani families with CILD11, Castleman et al. (2009) identified a homozygous mutation in the RSPH4A gene. - In affected members of a family of northern European descent with CILD11, Castleman et al. (2009) identified compound heterozygosity for 2 mutations in the RSPH4A gene - Kott et al. (2013) identified pathogenic mutations in the RSPH4A gene in 7 (14%) of 48 families with a specific CILD. Common founder mutation: - Daniels et al. (2013) identified a common founder mutation in the RSPH4A gene in 9 patients with CILD11, all of whom had Puerto Rican ancestry. Multiple individuals in ClinVar with primary ciliary dyskinesia; to: Radial spokes are regularly spaced along cilia, sperm, and flagella axonemes and have a multisubunit 'stalk' and 'head' that form a signal transduction scaffold between the central microtubule pair and dynein arms. RSPH4A is predicted to be a component of the radial spoke head based on homology with proteins in the biflagellate alga Chlamydomonas reinhardtii and other ciliates (Castleman et al., 2009; PMID19200523) 9 families with primary ciliary dyskinesia without situs inversus (Kott et al. 2013 (PMID:23993197), Castleman et al., 2009 (PMID19200523) and Daniels et al. 2013; (PMID:23798057)): - In affected members of 4 Pakistani families with CILD11, Castleman et al. (2009) identified a homozygous mutation in the RSPH4A gene. - In affected members of a family of northern European descent with CILD11, Castleman et al. (2009) identified compound heterozygosity for 2 mutations in the RSPH4A gene - Kott et al. (2013) identified pathogenic mutations in the RSPH4A gene in 7 (14%) of 48 families with a specific CILD. Common founder mutation: - Daniels et al. (2013) identified a common founder mutation in the RSPH4A gene in 9 patients with CILD11, all of whom had Puerto Rican ancestry. Multiple individuals in ClinVar with primary ciliary dyskinesia PMID: 25789548; Frommer 2015: 8 PCD families reported, only 4 different variants identified. Functional studies performed. PMID: 22448264; Ziętkiewicz 2012: 4 additional families/variants reported. |
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| Mendeliome v0.13263 | RSPH4A | Belinda Chong reviewed gene: RSPH4A: Rating: GREEN; Mode of pathogenicity: None; Publications: 23798057, 23798057, 23798057; Phenotypes: Ciliary dyskinesia, primary, 11 OMIM#612649; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13263 | RSPH9 | Belinda Chong reviewed gene: RSPH9: Rating: GREEN; Mode of pathogenicity: None; Publications: 25789548, 22384920, 23993197, 19200523, 27626380; Phenotypes: Ciliary dyskinesia, primary, 12 MIM#612650; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13263 | PLN | Zornitza Stark Marked gene: PLN as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13263 | PLN | Zornitza Stark Phenotypes for gene: PLN were changed from to Cardiomyopathy, dilated, 1P, MIM# 609909; Cardiomyopathy, hypertrophic, 18 (MIM #613874) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13260 | PLN | Zornitza Stark reviewed gene: PLN: Rating: GREEN; Mode of pathogenicity: None; Publications: 33947203; Phenotypes: Cardiomyopathy, dilated, 1P, MIM# 609909, Cardiomyopathy, hypertrophic, 18 (MIM #613874); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13260 | PLOD1 | Zornitza Stark Marked gene: PLOD1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13257 | PLOD2 | Zornitza Stark Marked gene: PLOD2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13254 | PMFBP1 | Zornitza Stark Marked gene: PMFBP1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13251 | PMPCA | Zornitza Stark Marked gene: PMPCA as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13251 | PMPCA | Zornitza Stark Phenotypes for gene: PMPCA were changed from to Spinocerebellar ataxia, autosomal recessive 2, MIM# 213200 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13248 | PMPCA | Zornitza Stark reviewed gene: PMPCA: Rating: GREEN; Mode of pathogenicity: None; Publications: 25808372, 26657514, 33272776, 30617178; Phenotypes: Spinocerebellar ataxia, autosomal recessive 2, MIM# 213200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13248 | PMPCB | Zornitza Stark Marked gene: PMPCB as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13245 | PNPO | Zornitza Stark Marked gene: PNPO as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13242 | PODXL | Zornitza Stark Marked gene: PODXL as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13239 | POFUT1 | Zornitza Stark Marked gene: POFUT1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13236 | POLG | Zornitza Stark Marked gene: POLG as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13233 | POMGNT1 | Zornitza Stark Marked gene: POMGNT1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13233 | POMGNT1 | Zornitza Stark Phenotypes for gene: POMGNT1 were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 8 MIM#614830; Muscular dystrophy-dystroglycanopathy (limb-girdle) type C, 8 MIM#618135; Retinitis pigmentosa 76 617123 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13230 | POMGNT1 | Zornitza Stark reviewed gene: POMGNT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27391550, 26908613, 30961548, 30937090; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 8 MIM#614830, Muscular dystrophy-dystroglycanopathy (limb-girdle) type C, 8 MIM#618135, Retinitis pigmentosa 76 617123; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13230 | POMGNT2 | Zornitza Stark Marked gene: POMGNT2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13230 | POMGNT2 | Zornitza Stark Phenotypes for gene: POMGNT2 were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 8, MIM# 614830; Muscular dystrophy-dystroglycanopathy (limb-girdle) type C, 8, MIM# 618135 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13227 | POMGNT2 | Zornitza Stark reviewed gene: POMGNT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34301702, 27066570, 26060116, 22958903; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 8, MIM# 614830, Muscular dystrophy-dystroglycanopathy (limb-girdle) type C, 8, MIM# 618135; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13227 | POMK | Zornitza Stark Marked gene: POMK as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13227 | POMK | Zornitza Stark Phenotypes for gene: POMK were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12, MIM# 615249; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 12, MIM# 616094 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13224 | POMK | Zornitza Stark reviewed gene: POMK: Rating: GREEN; Mode of pathogenicity: None; Publications: 32907597, 31833209, 29910097, 28109637, 24925318, 24556084; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12, MIM# 615249, Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 12, MIM# 616094; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13224 | RAX2 | Zornitza Stark Marked gene: RAX2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13221 | RASA1 | Zornitza Stark Marked gene: RASA1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13220 | PDX1 | Zornitza Stark Marked gene: PDX1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13220 | PDX1 | Zornitza Stark Phenotypes for gene: PDX1 were changed from to Pancreatic agenesis 1 - MIM#260370 (AR); MODY, type IV - MIM#606392(AD) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13215 | PDP1 | Zornitza Stark Marked gene: PDP1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13212 | PDHB | Zornitza Stark Marked gene: PDHB as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13210 | RSPO1 | Zornitza Stark Marked gene: RSPO1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13210 | RSPO1 | Zornitza Stark Phenotypes for gene: RSPO1 were changed from to Palmoplantar hyperkeratosis with squamous cell carcinoma of skin and sex reversal MIM#610644; Palmoplantar hyperkeratosis and true hermaphroditism MIM#610644 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13203 | PDHA1 | Zornitza Stark Marked gene: PDHA1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13200 | PDE6H | Zornitza Stark Marked gene: PDE6H as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13197 | PDE6G | Zornitza Stark Marked gene: PDE6G as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13193 | PDE6C | Zornitza Stark Marked gene: PDE6C as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13190 | PDE6B | Zornitza Stark Marked gene: PDE6B as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13190 | PDE6B | Zornitza Stark Phenotypes for gene: PDE6B were changed from to Night blindness, congenital stationary, autosomal dominant 2 - MIM#163500; Retinitis pigmentosa-40 - MIM#613801 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13187 | PDE6A | Zornitza Stark Marked gene: PDE6A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13184 | PDE4D | Zornitza Stark Marked gene: PDE4D as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13181 | PDE3A | Zornitza Stark Marked gene: PDE3A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13179 | PDE11A | Zornitza Stark Marked gene: PDE11A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13179 | PDE11A | Zornitza Stark Phenotypes for gene: PDE11A were changed from to Pigmented nodular adrenocortical disease, primary, 2 - MIM#610475 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13175 | SHH | Zornitza Stark Marked gene: SHH as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13175 | SHH | Zornitza Stark Added comment: Comment when marking as ready: DISPUTED association with schizencephaly | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13175 | SHH | Zornitza Stark Phenotypes for gene: SHH were changed from to Holoprosencephaly 3, MIM#142945; Microphthalmia with coloboma 5, MIM#611638; Single median maxillary central incisor, MIM#147250 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13172 | FAM111B | Zornitza Stark reviewed gene: FAM111B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: hereditary sclerosing poikiloderma with tendon and pulmonary involvement MONDO:0014310; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13172 | SH3BP2 | Zornitza Stark commented on gene: SH3BP2: Cherubism is characterized by a loss of bone, restricted to the jaws, and by the replacement of this bone with fibrous tissues, leading to facial swelling. Involvement of the infraorbital rim and the orbital floor leads to the upward tilting of the eyeballs and consequent exposure of the inferior part of the sclerae, giving a 'cherubic' appearance. Submandibular lymph node enlargement is often reported. Functional impairment includes mastication and speech problems, tooth alterations, and loss of normal vision. Onset of the disease is usually between 14 months and 4 years of age. The disease progresses through puberty, then stabilizes, and in some cases regresses without treatment. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13172 | SH3BP2 | Zornitza Stark Marked gene: SH3BP2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13170 | SH3BP2 | Zornitza Stark Mode of pathogenicity for gene: SH3BP2 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13168 | SH3BP2 | Zornitza Stark reviewed gene: SH3BP2: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: ; Phenotypes: Cherubism, MIM#118400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13167 | TLR8 | Zornitza Stark Phenotypes for gene: TLR8 were changed from Immunodeficiency; bone marrow failure; Autoinflammatory syndrome MONDO:0019751 to Immunodeficiency 98 with autoinflammation, X-linked, MIM# 301078 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13159 | CDKN1B | Zornitza Stark Marked gene: CDKN1B as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13158 | DNAJB11 | Elena Savva reviewed gene: DNAJB11: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34177435, 29706351, 29777155, 33129895; Phenotypes: Polycystic kidney disease 6 with or without polycystic liver disease, MIM#618061, Ivermark II syndrome, Prenatal Polycystic Kidney Disease; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13157 | SLC12A3 | Zornitza Stark Marked gene: SLC12A3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13153 | PIDD1 | Zornitza Stark Phenotypes for gene: PIDD1 were changed from Global developmental delay; Intellectual disability; Seizures; Autism; Behavioral abnormality; Psychosis; Pachygyria; Lissencephaly; Abnormality of the corpus callosum to Intellectual developmental disorder, autosomal recessive 75, with neuropsychiatric features and variant lissencephaly, MIM# 619827 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13152 | PIDD1 | Zornitza Stark edited their review of gene: PIDD1: Changed phenotypes: Intellectual developmental disorder, autosomal recessive 75, with neuropsychiatric features and variant lissencephaly, MIM# 619827 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13152 | SLC12A1 | Zornitza Stark Marked gene: SLC12A1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13152 | SLC12A1 | Zornitza Stark Phenotypes for gene: SLC12A1 were changed from to Bartter syndrome, type 1, MIM# 601678 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13149 | SLC12A1 | Zornitza Stark reviewed gene: SLC12A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 8640224, 9355073, 28095294; Phenotypes: Bartter syndrome, type 1, MIM# 601678; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13149 | FGF23 | Bryony Thompson Marked gene: FGF23 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13147 | PDX1 | Krithika Murali reviewed gene: PDX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9326926, 10545531, 10720084, 12970316, 20009086, 19496967; Phenotypes: Pancreatic agenesis 1 - MIM#260370 (AR), MODY, type IV - MIM#606392(AD); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13144 | FGF14 | Bryony Thompson Phenotypes for gene: FGF14 were changed from Spinocerebellar ataspinocerebellar ataxia type 27 MONDO:0012247; hereditary episodic ataxia MONDO:0016227xia 27 MIM#609307 to Spinocerebellar ataspinocerebellar ataxia type 27 MONDO:0012247; hereditary episodic ataxia MONDO:0016227 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13142 | FGF14 | Bryony Thompson Phenotypes for gene: FGF14 were changed from Spinocerebellar ataxia 27 MIM#609307 to Spinocerebellar ataspinocerebellar ataxia type 27 MONDO:0012247; hereditary episodic ataxia MONDO:0016227xia 27 MIM#609307 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13141 | FGF14 | Bryony Thompson edited their review of gene: FGF14: Added comment: 4 families with spinocerebellar ataxia and 7 families with episodic ataxia. Supporting animal models for both SCA and EA.; Changed publications: 12123606, 12489043, 15470364, 29253853, 30017992, 32112487, 32162847; Changed phenotypes: spinocerebellar ataxia type 27 MONDO:0012247, hereditary episodic ataxia MONDO:0016227; Set current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13141 | FGF10 | Bryony Thompson Marked gene: FGF10 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13141 | FGF10 | Bryony Thompson Phenotypes for gene: FGF10 were changed from to congenital alveolar dysplasia due to FGF10 MONDO:0100090; acinar dysplasia caused by mutation in FGF10 MONDO:0600017 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13138 | FGF10 | Bryony Thompson reviewed gene: FGF10: Rating: GREEN; Mode of pathogenicity: None; Publications: 9916808, 15654336, 16501574, 16630169, 17213838, 33967277, 30639323; Phenotypes: congenital alveolar dysplasia due to FGF10 MONDO:0100090, acinar dysplasia caused by mutation in FGF10 MONDO:0600017; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13138 | FFAR4 | Bryony Thompson Marked gene: FFAR4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13138 | FFAR4 | Bryony Thompson Gene: ffar4 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13138 | FFAR4 | Bryony Thompson Phenotypes for gene: FFAR4 were changed from to {Obesity, susceptibility to} MIM#607514 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13137 | FFAR4 | Bryony Thompson Publications for gene: FFAR4 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13136 | FFAR4 | Bryony Thompson Classified gene: FFAR4 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13136 | FFAR4 | Bryony Thompson Gene: ffar4 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13135 | FFAR4 | Bryony Thompson reviewed gene: FFAR4: Rating: RED; Mode of pathogenicity: None; Publications: 22343897, 34043793; Phenotypes: {Obesity, susceptibility to} MIM#607514; Mode of inheritance: Unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13135 | FDX2 | Bryony Thompson Marked gene: FDX2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13132 | FDFT1 | Bryony Thompson Marked gene: FDFT1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13129 | FBXO7 | Bryony Thompson Marked gene: FBXO7 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13129 | FBXO7 | Bryony Thompson Phenotypes for gene: FBXO7 were changed from to parkinsonian-pyramidal syndrome MONDO:0009830 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13125 | FBXO7 | Bryony Thompson reviewed gene: FBXO7: Rating: GREEN; Mode of pathogenicity: None; Publications: 18513678, 19038853, 34781237; Phenotypes: parkinsonian-pyramidal syndrome MONDO:0009830; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13125 | RSPO1 | Belinda Chong reviewed gene: RSPO1: Rating: GREEN; Mode of pathogenicity: None; Publications: 17041600, 18085567, 18250098, 18250097; Phenotypes: Palmoplantar hyperkeratosis with squamous cell carcinoma of skin and sex reversal MIM#610644, Palmoplantar hyperkeratosis and true hermaphroditism MIM#610644; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13125 | FBP1 | Bryony Thompson Marked gene: FBP1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13121 | FBP1 | Bryony Thompson changed review comment from: Well-established gene-disease association. Fructose-1,6-bisphosphatase (FBP1) deficiency is metabolic disorder characterised by episodic acute crises of lactic acidosis and ketotic hypoglycaemia, manifesting as hyperventilation, apneic spells, seizures, and/or coma. Both SNVs and CNVs have been reported.; to: Well-established gene-disease association. Fructose-1,6-bisphosphatase (FBP1) deficiency is a metabolic disorder characterised by episodic acute crises of lactic acidosis and ketotic hypoglycaemia, manifesting as hyperventilation, apneic spells, seizures, and/or coma. Both SNVs and CNVs have been reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13121 | CLPB | Zornitza Stark Phenotypes for gene: CLPB were changed from 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropaenia, MIM# 616271; Neutropenia, severe congenital, 9, autosomal dominant, MIM# 619813 to 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropaenia, MIM# 616271; 3-methylglutaconic aciduria, type VIIA, autosomal dominant, MIM# 619835; Neutropenia, severe congenital, 9, autosomal dominant, MIM# 619813 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13120 | CLPB | Zornitza Stark edited their review of gene: CLPB: Changed phenotypes: 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropaenia, MIM# 616271, 3-methylglutaconic aciduria, type VIIA, autosomal dominant, MIM# 619835, Neutropenia, severe congenital, 9, autosomal dominant, MIM# 619813 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13120 | GLRA2 | Zornitza Stark Marked gene: GLRA2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13119 | GLRA2 |
Zornitza Stark gene: GLRA2 was added gene: GLRA2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: GLRA2 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: GLRA2 were set to 26370147; 20479760; 35294868 Phenotypes for gene: GLRA2 were set to Intellectual developmental disorder, X-linked, syndromic, Pilorge type, MIM# 301076 Review for gene: GLRA2 was set to GREEN Added comment: More than 10 unrelated families reported. Both males and females affected, though some mothers are asymptomatic or mild. Zebrafish model. Sources: Expert list |
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| Mendeliome v0.13117 | FASTKD2 | Bryony Thompson Marked gene: FASTKD2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13115 | FASLG | Bryony Thompson Marked gene: FASLG as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13112 | FAS | Bryony Thompson Marked gene: FAS as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13109 | FARSB | Bryony Thompson Marked gene: FARSB as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13109 | FARSB | Bryony Thompson Gene: farsb has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13109 | FARSB | Bryony Thompson Phenotypes for gene: FARSB were changed from to Rajab interstitial lung disease with brain calcifications 1 MONDO:0100215 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13108 | FARSB | Bryony Thompson Publications for gene: FARSB were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13107 | FARSB | Bryony Thompson Mode of inheritance for gene: FARSB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13106 | FARSB | Bryony Thompson reviewed gene: FARSB: Rating: GREEN; Mode of pathogenicity: None; Publications: 29573043, 30014610, 29979980; Phenotypes: Rajab interstitial lung disease with brain calcifications 1 MONDO:0100215; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13106 | FARS2 | Bryony Thompson Marked gene: FARS2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13106 | FARS2 | Bryony Thompson Gene: fars2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13106 | FARS2 | Bryony Thompson Phenotypes for gene: FARS2 were changed from to combined oxidative phosphorylation defect type 14 MONDO:0013986; hereditary spastic paraplegia 77 MONDO:0014882 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13105 | FARS2 | Bryony Thompson Publications for gene: FARS2 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13104 | FARS2 | Bryony Thompson Mode of inheritance for gene: FARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13103 | FARS2 | Bryony Thompson reviewed gene: FARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30250868, 30177229, 29126765, 28043061; Phenotypes: combined oxidative phosphorylation defect type 14 MONDO:0013986, hereditary spastic paraplegia 77 MONDO:0014882; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13103 | FAM58A | Bryony Thompson Marked gene: FAM58A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13100 | PDE6B | Krithika Murali reviewed gene: PDE6B: Rating: GREEN; Mode of pathogenicity: None; Publications: 8394174, 8075643, 17044014, 7599633, 18854872; Phenotypes: Night blindness, congenital stationary, autosomal dominant 2 - MIM#163500, Retinitis pigmentosa-40 - MIM#613801; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13100 | FAM161A | Bryony Thompson Marked gene: FAM161A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13100 | PDE11A | Krithika Murali reviewed gene: PDE11A: Rating: RED; Mode of pathogenicity: None; Publications: 16767104, 18559625, 21047926, 17178847; Phenotypes: Pigmented nodular adrenocortical disease, primary, 2 - MIM#610475; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13097 | FAM126A | Bryony Thompson Marked gene: FAM126A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13096 | SHH | Samantha Ayres reviewed gene: SHH: Rating: GREEN; Mode of pathogenicity: None; Publications: 21976454, 12503095, 22791840, 19057928, 19533790; Phenotypes: Holoprosencephaly 3, MIM#142945, Microphthalmia with coloboma 5, MIM#611638, Schizencephaly, MIM#269160, Single median maxillary central incisor, MIM#147250; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13094 | FAM111B | Bryony Thompson Marked gene: FAM111B as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13094 | FAM111B | Bryony Thompson Phenotypes for gene: FAM111B were changed from to hereditary sclerosing poikiloderma with tendon and pulmonary involvement MONDO:0014310 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13090 | FAM111B | Bryony Thompson reviewed gene: FAM111B: Rating: ; Mode of pathogenicity: Other; Publications: 24268661, 26471370, 26495788, 27406236; Phenotypes: hereditary sclerosing poikiloderma with tendon and pulmonary involvement MONDO:0014310; Mode of inheritance: None; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13090 | FAM111A | Bryony Thompson Marked gene: FAM111A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13086 | FADD | Bryony Thompson Marked gene: FADD as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13085 | FAH | Bryony Thompson Marked gene: FAH as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13080 | F12 | Bryony Thompson Marked gene: F12 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13080 | F12 | Bryony Thompson Phenotypes for gene: F12 were changed from to Hereditary angioedema type 3 MONDO:0012526 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13078 | POMP | Zornitza Stark Marked gene: POMP as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13078 | POMP | Zornitza Stark Phenotypes for gene: POMP were changed from to Keratosis linearis with ichthyosis congenita and sclerosing keratoderma MIM#601952; Proteasome-associated autoinflammatory syndrome 2, MIM# 618048 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13075 | POMP | Zornitza Stark reviewed gene: POMP: Rating: GREEN; Mode of pathogenicity: None; Publications: 20226437, 27503413, 29805043; Phenotypes: Keratosis linearis with ichthyosis congenita and sclerosing keratoderma MIM#601952, Proteasome-associated autoinflammatory syndrome 2, MIM# 618048; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13075 | POMT1 | Zornitza Stark Marked gene: POMT1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13075 | POMT1 | Zornitza Stark Phenotypes for gene: POMT1 were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1 236670; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 1 613155; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 1 609308 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13073 | POMT1 | Zornitza Stark reviewed gene: POMT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1 236670, Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 1 613155, Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 1 609308; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13073 | POMT2 | Zornitza Stark Marked gene: POMT2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13073 | POMT2 | Zornitza Stark Phenotypes for gene: POMT2 were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 2 613150; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 2 613156; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 2 613158 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13071 | POMT2 | Zornitza Stark edited their review of gene: POMT2: Changed phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 2 613150, Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 2 613156, Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 2 613158 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13071 | POMT2 | Zornitza Stark reviewed gene: POMT2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 2 613150 Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 2 613156 Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 2 613158; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13071 | PPARA | Zornitza Stark Marked gene: PPARA as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13071 | PPARA | Zornitza Stark Gene: ppara has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13071 | PPARA | Zornitza Stark Phenotypes for gene: PPARA were changed from to {Hyperapobetalipoproteinemia, susceptibility to} | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13070 | PPARA | Zornitza Stark Mode of inheritance for gene: PPARA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13069 | PPARA | Zornitza Stark Classified gene: PPARA as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13069 | PPARA | Zornitza Stark Gene: ppara has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13068 | PPARA | Zornitza Stark reviewed gene: PPARA: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Hyperapobetalipoproteinemia, susceptibility to}; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13068 | PPM1K | Zornitza Stark Marked gene: PPM1K as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13068 | PPM1K | Zornitza Stark Phenotypes for gene: PPM1K were changed from to Maple syrup urine disease, mild variant, MIM#615135 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13064 | PPM1K | Zornitza Stark reviewed gene: PPM1K: Rating: RED; Mode of pathogenicity: None; Publications: 23086801; Phenotypes: Maple syrup urine disease, mild variant, MIM#615135; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13064 | PPOX | Zornitza Stark Marked gene: PPOX as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13064 | PPOX | Zornitza Stark Phenotypes for gene: PPOX were changed from to Porphyria variegata , MIM#176200 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13061 | PPOX | Zornitza Stark reviewed gene: PPOX: Rating: GREEN; Mode of pathogenicity: None; Publications: 12357337, 32247286, 23324528, 27982422; Phenotypes: Porphyria variegata , MIM#176200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13061 | PPP1R15B | Zornitza Stark Marked gene: PPP1R15B as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13061 | SGCG | Samantha Ayres reviewed gene: SGCG: Rating: GREEN; Mode of pathogenicity: None; Publications: 18285821, 8923014, 7481775, 8968757, 27708273; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 5 MIM#253700, autosomal recessive limb-girdle muscular dystrophy MONDO:0015152; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13061 | CFHR5 | Ain Roesley Marked gene: CFHR5 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13059 | CFH | Ain Roesley Marked gene: CFH as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13059 | CFH | Ain Roesley Phenotypes for gene: CFH were changed from to Basal laminar drusen MIM#126700; Complement factor H deficiency MIM#609814; {Hemolytic uremic syndrome, atypical, susceptibility to, 1} MIMI#235400 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13058 | CFH | Ain Roesley reviewed gene: CFH: Rating: GREEN; Mode of pathogenicity: None; Publications: 27572114, 25814826, 20301541, 9312129, 10803850, 29888403, 30905644; Phenotypes: Basal laminar drusen MIM#126700, Complement factor H deficiency MIM#609814, {Hemolytic uremic syndrome, atypical, susceptibility to, 1} MIMI#235400; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13054 | PPP1R3A | Zornitza Stark Marked gene: PPP1R3A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13050 | PRCD | Zornitza Stark Marked gene: PRCD as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13047 | PRDM16 | Zornitza Stark Marked gene: PRDM16 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13047 | PRDM16 | Zornitza Stark Phenotypes for gene: PRDM16 were changed from to Cardiomyopathy, dilated, 1LL MIM#615373; Left ventricular noncompaction 8 MIM#615373 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13043 | PRDM16 | Zornitza Stark reviewed gene: PRDM16: Rating: AMBER; Mode of pathogenicity: None; Publications: 23768516, 29367541, 34915728, 31965688, 29367541; Phenotypes: Cardiomyopathy, dilated, 1LL MIM#615373, Left ventricular noncompaction 8 MIM#615373; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13043 | CFD | Ain Roesley Marked gene: CFD as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13040 | CEP78 | Ain Roesley Marked gene: CEP78 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13040 | CEP78 | Ain Roesley Phenotypes for gene: CEP78 were changed from to Cone-rod dystrophy and hearing loss MIM#617236 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13038 | CEP78 | Ain Roesley reviewed gene: CEP78: Rating: GREEN; Mode of pathogenicity: None; Publications: 28005958, 27588451, 27588452, 27627988; Phenotypes: Cone-rod dystrophy and hearing loss MIM#617236; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13038 | CEBPA | Ain Roesley Marked gene: CEBPA as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13037 | CEACAM16 | Ain Roesley Marked gene: CEACAM16 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13036 | CDKN2A | Ain Roesley Marked gene: CDKN2A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13033 | CDK4 | Ain Roesley Marked gene: CDK4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13031 | CDK10 | Ain Roesley changed review comment from: >5 families; to: 6 families thus far | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13031 | CDK10 | Ain Roesley Marked gene: CDK10 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13030 | CDHR1 | Ain Roesley Marked gene: CDHR1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13028 | CDC73 | Ain Roesley Marked gene: CDC73 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13028 | CDC73 | Ain Roesley Phenotypes for gene: CDC73 were changed from to Hyperparathyroidism-jaw tumour syndrome, MIM# 145001; Hyperparathyroidism, familial primary, MIM# 145000 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13027 | CDC73 | Ain Roesley reviewed gene: CDC73: Rating: GREEN; Mode of pathogenicity: None; Publications: 12434154; Phenotypes: Hyperparathyroidism-jaw tumour syndrome, MIM# 145001, Hyperparathyroidism, familial primary, MIM# 145000; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13025 | CDC42 | Ain Roesley Marked gene: CDC42 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13024 | CDC14A | Ain Roesley Marked gene: CDC14A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13022 | CD79B | Ain Roesley Marked gene: CD79B as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13020 | PRDM5 | Zornitza Stark Marked gene: PRDM5 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13017 | PREPL | Zornitza Stark Marked gene: PREPL as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13014 | PRG4 | Zornitza Stark Marked gene: PRG4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13014 | PRG4 | Zornitza Stark Phenotypes for gene: PRG4 were changed from to Camptodactyly-arthropathy-coxa vara-pericarditis syndrome, MIM# 208250 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13011 | PRG4 | Zornitza Stark reviewed gene: PRG4: Rating: GREEN; Mode of pathogenicity: None; Publications: 10545950, 29397575; Phenotypes: Camptodactyly-arthropathy-coxa vara-pericarditis syndrome, MIM# 208250; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13010 | PRICKLE1 | Zornitza Stark Marked gene: PRICKLE1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13007 | PRKAR1A | Zornitza Stark Marked gene: PRKAR1A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13007 | PRKAR1A | Zornitza Stark Gene: prkar1a has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13007 | PRKAR1A | Zornitza Stark Phenotypes for gene: PRKAR1A were changed from to Acrodysostosis 1, with or without hormone resistance, MIM# 101800; Carney complex, type 1, MIM# 160980; Myxoma, intracardiac, MIM# 255960; Pigmented nodular adrenocortical disease, primary, 1, MIM# 610489 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13006 | PRKAR1A | Zornitza Stark Publications for gene: PRKAR1A were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13005 | PRKAR1A | Zornitza Stark Mode of inheritance for gene: PRKAR1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13004 | PRKAR1A | Zornitza Stark reviewed gene: PRKAR1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 10973256, 11115848, 12424709, 21651393; Phenotypes: Acrodysostosis 1, with or without hormone resistance, MIM# 101800, Carney complex, type 1, MIM# 160980, Myxoma, intracardiac, MIM# 255960, Pigmented nodular adrenocortical disease, primary, 1, MIM# 610489; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13004 | PRKCG | Zornitza Stark Marked gene: PRKCG as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13004 | PRKCG | Zornitza Stark Phenotypes for gene: PRKCG were changed from to Spinocerebellar ataxia 14, MIM# 605361 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13001 | PRKCG | Zornitza Stark reviewed gene: PRKCG: Rating: GREEN; Mode of pathogenicity: None; Publications: 12644968, 14676051, 14694043, 16193476, 33739604, 34292398; Phenotypes: Spinocerebellar ataxia 14, MIM# 605361; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13001 | PRKG1 | Zornitza Stark Marked gene: PRKG1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12998 | PRMT7 | Zornitza Stark Marked gene: PRMT7 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12995 | PRODH | Zornitza Stark Marked gene: PRODH as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12992 | PROK2 | Zornitza Stark Marked gene: PROK2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12989 | PROM1 | Zornitza Stark Marked gene: PROM1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12989 | PROM1 | Zornitza Stark Phenotypes for gene: PROM1 were changed from to Inherited retinal dystrophy, MONDO:0019118; Cone-rod dystrophy 12, MIM# 612657; Macular dystrophy, retinal, 2, MI# 608051; Retinitis pigmentosa 41, MIM# 612095; Stargardt disease 4, MIM# 603786 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12986 | PROM1 | Zornitza Stark reviewed gene: PROM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 10587575, 17605048, 18654668, 29416601, 31576780, 34664634, 32820593; Phenotypes: Inherited retinal dystrophy, MONDO:0019118, Cone-rod dystrophy 12, MIM# 612657, Macular dystrophy, retinal, 2, MI# 608051, Retinitis pigmentosa 41, MIM# 612095, Stargardt disease 4, MIM# 603786; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12986 | PROS1 | Zornitza Stark Marked gene: PROS1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12983 | PRPF3 | Zornitza Stark Marked gene: PRPF3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12980 | PRPF4 | Zornitza Stark Marked gene: PRPF4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12977 | PRPF6 | Zornitza Stark Marked gene: PRPF6 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12973 | PRPH | Zornitza Stark Marked gene: PRPH as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12969 | PRSS1 | Zornitza Stark Marked gene: PRSS1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12969 | PRSS1 | Zornitza Stark Phenotypes for gene: PRSS1 were changed from to Pancreatitis, hereditary, MIM# 167800 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12966 | PRSS1 | Zornitza Stark reviewed gene: PRSS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 8841182, 10204851, 10529393, 11097832, 11702203, 15776435, 16791840, 18461367, 17072318; Phenotypes: Pancreatitis, hereditary, MIM# 167800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12966 | PRSS12 | Zornitza Stark Marked gene: PRSS12 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12962 | PSMC2 | Zornitza Stark Marked gene: PSMC2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12961 | PSMC3IP | Zornitza Stark Marked gene: PSMC3IP as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12961 | PSMC3IP | Zornitza Stark Phenotypes for gene: PSMC3IP were changed from to Ovarian dysgenesis 3, MIM# 614324 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12958 | PSMC3IP | Zornitza Stark reviewed gene: PSMC3IP: Rating: GREEN; Mode of pathogenicity: None; Publications: 21963259, 35352317, 34878148, 30406445, 29240891; Phenotypes: Ovarian dysgenesis 3, MIM# 614324; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12958 | PSMD12 | Zornitza Stark Marked gene: PSMD12 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12955 | PSPH | Zornitza Stark Marked gene: PSPH as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12952 | PSTPIP1 | Zornitza Stark Marked gene: PSTPIP1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12952 | PSTPIP1 | Zornitza Stark Phenotypes for gene: PSTPIP1 were changed from to Pyogenic sterile arthritis, pyoderma gangrenosum, and acne, MIM# 604416; PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12949 | PSTPIP1 | Zornitza Stark reviewed gene: PSTPIP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11971877, 34938582, 34778321, 34745107, 34492165, 34047005; Phenotypes: Pyogenic sterile arthritis, pyoderma gangrenosum, and acne, MIM# 604416, PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12949 | PTGDR | Zornitza Stark Marked gene: PTGDR as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12946 | PTH | Zornitza Stark Marked gene: PTH as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12946 | PTH | Zornitza Stark Phenotypes for gene: PTH were changed from to Hypoparathyroidism, familial isolated 1, MIM# 146200 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12943 | PTH | Zornitza Stark reviewed gene: PTH: Rating: GREEN; Mode of pathogenicity: None; Publications: 2212001, 1302009, 10523031, 35165722, 32421798; Phenotypes: Hypoparathyroidism, familial isolated 1, MIM# 146200; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12943 | PTH1R | Zornitza Stark Marked gene: PTH1R as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||