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Prepair 1000+ v1.9 AGL Marta Cifuentes Ochoa commented on gene: AGL: Current Treatment high-fat, high-protein and low-carbohydrate diet with cornstarch supplementation
Bleeding and Platelet Disorders v1.43 PROC Jane Lin gene: PROC was added
gene: PROC was added to Bleeding and Platelet Disorders. Sources: Expert list
Mode of inheritance for gene: PROC was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: PROC were set to PMID: 2437584; PMID: 7670104; PMID: 10942114; PMID: 28265398
Phenotypes for gene: PROC were set to THROMBOPHILIA DUE TO PROTEIN C DEFICIENCY, AUTOSOMAL DOMINANT # 176860; THROMBOPHILIA DUE TO PROTEIN C DEFICIENCY, AUTOSOMAL RECESSIVE, # 612304
Review for gene: PROC was set to GREEN
gene: PROC was marked as current diagnostic
Added comment: Has well established gene-disease association with thrombosis. Biallelic inheritance is rare and there is evidence it is more severe but data is complicated by findings that some patients also have changes in Factor V Leiden so have not selected the option where biallelic inheritance is more severe.
Sources: Expert list
Bleeding and Platelet Disorders v1.43 PIGA Jane Lin gene: PIGA was added
gene: PIGA was added to Bleeding and Platelet Disorders. Sources: Expert list
Mode of inheritance for gene: PIGA was set to Unknown
Publications for gene: PIGA were set to PMID: 9019395; PMID: 28516949
Phenotypes for gene: PIGA were set to PAROXYSMAL NOCTURNAL HEMOGLOBINURIA 1 OMIM# 300818
Review for gene: PIGA was set to RED
gene: PIGA was marked as current diagnostic
Added comment: PIGA variants linked to Paroxysmal nocturnal hemoglobinuria (PNH), clinical features which include thrombosis, but as somatic changes.
Sources: Expert list
Prepair 1000+ v1.9 ATRX Andrew Coventry reviewed gene: ATRX: Rating: GREEN; Mode of pathogenicity: None; Publications: 16813605, 16955409, 15350606, 23681356; Phenotypes: Alpha thalassemia X-linked intellectual disability syndrome MONDO:0010519; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.9 AARS2 Clare Hunt reviewed gene: AARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Combined oxidative phosphorylation deficiency 8, 614096 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 IL7R Lauren Rogers reviewed gene: IL7R: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Severe combined immunodeficiency 104 MIM# 608971; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 ASAH1 Lucy Spencer reviewed gene: ASAH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinal muscular atrophy with progressive myoclonic epilepsy, MIM#159950, Farber lipogranulomatosis, MIM#; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 IL2RG Lauren Rogers reviewed gene: IL2RG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Severe combined immunodeficiency, X-linked MIM# 300400; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.9 IL1RN Lauren Rogers reviewed gene: IL1RN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Interleukin 1 receptor antagonist deficiency, MIM# 612852, Chronic recurrent multifocal osteomyelitis 2, with periostitis and pustulosis, MIM# 61285; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 CRB1 Lauren Rogers reviewed gene: CRB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11231775, 11389483, 16543197; Phenotypes: Leber congenital amaurosis 8 MIM#613835; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 AP4S1 Lucy Spencer reviewed gene: AP4S1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 52, autosomal recessive, MIM#614067; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 HSD17B4 Lauren Rogers reviewed gene: HSD17B4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: D-bifunctional protein deficiency, AR (MIM#261515); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 HPSE2 Lauren Rogers reviewed gene: HPSE2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25145936, 23313374, 33558177; Phenotypes: Urofacial syndrome 1 MIM#236730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 AP4M1 Lucy Spencer reviewed gene: AP4M1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 50, autosomal recessive (MIM#612936); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 ANTXR1 Lucy Spencer reviewed gene: ANTXR1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: GAPO syndrome (MIM#230740); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 HPGD Lauren Rogers reviewed gene: HPGD: Rating: GREEN; Mode of pathogenicity: None; Publications: 20406614, 32282352, 31878983, 29282707; Phenotypes: Hypertrophic osteoarthropathy, primary, autosomal recessive 1 MIM#259100, Cranioosteoarthropathy MIM#259100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 ALOXE3 Lucy Spencer reviewed gene: ALOXE3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Ichthyosis, congenital, autosomal recessive 3 (MIM#606545); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 ALDH3A2 Lucy Spencer reviewed gene: ALDH3A2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Sjogren-Larsson syndrome (MIM#270200); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 ACADVL Lucy Spencer reviewed gene: ACADVL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: VLCAD deficiency (MIM#201475); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 GFM1 Lauren Rogers reviewed gene: GFM1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Combined oxidative phosphorylation deficiency 1, MIM#609060; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 CD81 Lauren Rogers reviewed gene: CD81: Rating: AMBER; Mode of pathogenicity: None; Publications: 20237408, 35849269; Phenotypes: Immunodeficiency, common variable, 6, OMIM:613496; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1891 CRNKL1 Zornitza Stark Marked gene: CRNKL1 as ready
Mendeliome v1.1891 CRNKL1 Zornitza Stark Gene: crnkl1 has been classified as Green List (High Evidence).
Mendeliome v1.1891 CRNKL1 Zornitza Stark Classified gene: CRNKL1 as Green List (high evidence)
Mendeliome v1.1891 CRNKL1 Zornitza Stark Gene: crnkl1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.9 C1QA Lauren Rogers reviewed gene: C1QA: Rating: GREEN; Mode of pathogenicity: None; Publications: 21654842, 9225968, 9590289; Phenotypes: C1q deficiency, MIM# 613652; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1890 DCC Zornitza Stark Publications for gene: DCC were set to 20431009; 31697046; 21242494; 28250454; 28250456; 25763452
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.
Skeletal dysplasia v0.285 DCC Zornitza Stark Marked gene: DCC as ready
Skeletal dysplasia v0.285 DCC Zornitza Stark Gene: dcc has been classified as Green List (High Evidence).
Skeletal dysplasia v0.285 DCC Zornitza Stark Phenotypes for gene: DCC were changed from Gaze palsy, familial horizontal, with progressive scoliosis, 2, MIM# 617542 to Gaze palsy, familial horizontal, with progressive scoliosis, 2, MIM# 617542
Skeletal dysplasia v0.284 DCC Zornitza Stark Phenotypes for gene: DCC were changed from Gaze palsy, familial horizontal, with progressive scoliosis, 2 617542; Gaze palsy, familial horizontal, with progressive scoliosis, 2 617542 to Gaze palsy, familial horizontal, with progressive scoliosis, 2, MIM# 617542
Skeletal dysplasia v0.283 DCC Zornitza Stark Publications for gene: DCC were set to 28250456
Skeletal dysplasia v0.282 DCC Zornitza Stark Classified gene: DCC as Green List (high evidence)
Skeletal dysplasia v0.282 DCC Zornitza Stark Gene: dcc has been classified as Green List (High Evidence).
Mendeliome v1.1889 SLC7A5 Zornitza Stark Marked gene: SLC7A5 as ready
Mendeliome v1.1889 SLC7A5 Zornitza Stark Gene: slc7a5 has been classified as Red List (Low Evidence).
Mendeliome v1.1889 SLC7A5 Zornitza Stark Classified gene: SLC7A5 as Red List (low evidence)
Mendeliome v1.1889 SLC7A5 Zornitza Stark Gene: slc7a5 has been classified as Red List (Low Evidence).
Aminoacidopathy v1.128 SLC6A20 Zornitza Stark Marked gene: SLC6A20 as ready
Aminoacidopathy v1.128 SLC6A20 Zornitza Stark Gene: slc6a20 has been classified as Red List (Low Evidence).
Aminoacidopathy v1.128 SLC6A20 Zornitza Stark Classified gene: SLC6A20 as Red List (low evidence)
Aminoacidopathy v1.128 SLC6A20 Zornitza Stark Gene: slc6a20 has been classified as Red List (Low Evidence).
Aminoacidopathy v1.127 SLC25A22 Zornitza Stark Marked gene: SLC25A22 as ready
Aminoacidopathy v1.127 SLC25A22 Zornitza Stark Gene: slc25a22 has been classified as Green List (High Evidence).
Aminoacidopathy v1.127 SLC25A22 Zornitza Stark Classified gene: SLC25A22 as Green List (high evidence)
Aminoacidopathy v1.127 SLC25A22 Zornitza Stark Gene: slc25a22 has been classified as Green List (High Evidence).
Aminoacidopathy v1.126 SLC25A13 Zornitza Stark Marked gene: SLC25A13 as ready
Aminoacidopathy v1.126 SLC25A13 Zornitza Stark Gene: slc25a13 has been classified as Green List (High Evidence).
Aminoacidopathy v1.126 SLC25A13 Zornitza Stark Classified gene: SLC25A13 as Green List (high evidence)
Aminoacidopathy v1.126 SLC25A13 Zornitza Stark Gene: slc25a13 has been classified as Green List (High Evidence).
Aminoacidopathy v1.125 SLC7A5 Zornitza Stark Marked gene: SLC7A5 as ready
Aminoacidopathy v1.125 SLC7A5 Zornitza Stark Gene: slc7a5 has been classified as Red List (Low Evidence).
Aminoacidopathy v1.125 SLC7A5 Zornitza Stark Classified gene: SLC7A5 as Red List (low evidence)
Aminoacidopathy v1.125 SLC7A5 Zornitza Stark Gene: slc7a5 has been classified as Red List (Low Evidence).
Aminoacidopathy v1.124 XPNPEP3 Zornitza Stark Marked gene: XPNPEP3 as ready
Aminoacidopathy v1.124 XPNPEP3 Zornitza Stark Gene: xpnpep3 has been classified as Green List (High Evidence).
Aminoacidopathy v1.124 XPNPEP3 Zornitza Stark Classified gene: XPNPEP3 as Green List (high evidence)
Aminoacidopathy v1.124 XPNPEP3 Zornitza Stark Gene: xpnpep3 has been classified as Green List (High Evidence).
Aminoacidopathy v1.123 SLC1A4 Zornitza Stark Marked gene: SLC1A4 as ready
Aminoacidopathy v1.123 SLC1A4 Zornitza Stark Gene: slc1a4 has been classified as Green List (High Evidence).
Aminoacidopathy v1.123 SLC1A4 Zornitza Stark Classified gene: SLC1A4 as Green List (high evidence)
Aminoacidopathy v1.123 SLC1A4 Zornitza Stark Gene: slc1a4 has been classified as Green List (High Evidence).
Aminoacidopathy v1.122 PYCR2 Zornitza Stark Marked gene: PYCR2 as ready
Aminoacidopathy v1.122 PYCR2 Zornitza Stark Gene: pycr2 has been classified as Green List (High Evidence).
Aminoacidopathy v1.122 PYCR2 Zornitza Stark Classified gene: PYCR2 as Green List (high evidence)
Aminoacidopathy v1.122 PYCR2 Zornitza Stark Gene: pycr2 has been classified as Green List (High Evidence).
Aminoacidopathy v1.121 PEPD Zornitza Stark Marked gene: PEPD as ready
Aminoacidopathy v1.121 PEPD Zornitza Stark Gene: pepd has been classified as Green List (High Evidence).
Aminoacidopathy v1.121 PEPD Zornitza Stark Classified gene: PEPD as Green List (high evidence)
Aminoacidopathy v1.121 PEPD Zornitza Stark Gene: pepd has been classified as Green List (High Evidence).
Aminoacidopathy v1.120 OPLAH Zornitza Stark Marked gene: OPLAH as ready
Aminoacidopathy v1.120 OPLAH Zornitza Stark Gene: oplah has been classified as Red List (Low Evidence).
Aminoacidopathy v1.120 OPLAH Zornitza Stark Classified gene: OPLAH as Red List (low evidence)
Aminoacidopathy v1.120 OPLAH Zornitza Stark Gene: oplah has been classified as Red List (Low Evidence).
Aminoacidopathy v1.119 NFE2L2 Zornitza Stark Marked gene: NFE2L2 as ready
Aminoacidopathy v1.119 NFE2L2 Zornitza Stark Gene: nfe2l2 has been classified as Green List (High Evidence).
Aminoacidopathy v1.119 NFE2L2 Zornitza Stark Classified gene: NFE2L2 as Green List (high evidence)
Aminoacidopathy v1.119 NFE2L2 Zornitza Stark Gene: nfe2l2 has been classified as Green List (High Evidence).
Aminoacidopathy v1.118 GSR Zornitza Stark Marked gene: GSR as ready
Aminoacidopathy v1.118 GSR Zornitza Stark Gene: gsr has been classified as Amber List (Moderate Evidence).
Aminoacidopathy v1.118 GSR Zornitza Stark Classified gene: GSR as Amber List (moderate evidence)
Aminoacidopathy v1.118 GSR Zornitza Stark Gene: gsr has been classified as Amber List (Moderate Evidence).
Aminoacidopathy v1.117 GRHPR Zornitza Stark Marked gene: GRHPR as ready
Aminoacidopathy v1.117 GRHPR Zornitza Stark Gene: grhpr has been classified as Green List (High Evidence).
Aminoacidopathy v1.117 GRHPR Zornitza Stark Classified gene: GRHPR as Green List (high evidence)
Aminoacidopathy v1.117 GRHPR Zornitza Stark Gene: grhpr has been classified as Green List (High Evidence).
Aminoacidopathy v1.116 GPX4 Zornitza Stark Marked gene: GPX4 as ready
Aminoacidopathy v1.116 GPX4 Zornitza Stark Gene: gpx4 has been classified as Green List (High Evidence).
Aminoacidopathy v1.116 GPX4 Zornitza Stark Classified gene: GPX4 as Green List (high evidence)
Aminoacidopathy v1.116 GPX4 Zornitza Stark Gene: gpx4 has been classified as Green List (High Evidence).
Aminoacidopathy v1.115 GCLC Zornitza Stark Marked gene: GCLC as ready
Aminoacidopathy v1.115 GCLC Zornitza Stark Gene: gclc has been classified as Green List (High Evidence).
Aminoacidopathy v1.115 GCLC Zornitza Stark Classified gene: GCLC as Green List (high evidence)
Aminoacidopathy v1.115 GCLC Zornitza Stark Gene: gclc has been classified as Green List (High Evidence).
Aminoacidopathy v1.114 GRM6 Zornitza Stark Marked gene: GRM6 as ready
Aminoacidopathy v1.114 GRM6 Zornitza Stark Gene: grm6 has been classified as Green List (High Evidence).
Aminoacidopathy v1.114 GRM6 Zornitza Stark Classified gene: GRM6 as Green List (high evidence)
Aminoacidopathy v1.114 GRM6 Zornitza Stark Gene: grm6 has been classified as Green List (High Evidence).
Prepair 1000+ v1.9 ABHD5 Lauren Thomas reviewed gene: ABHD5: Rating: GREEN; Mode of pathogenicity: None; Publications: 30795549; Phenotypes: Chanarin-Dorfman syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Aminoacidopathy v1.113 GRM6 Sangavi Sivagnanasundram gene: GRM6 was added
gene: GRM6 was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: GRM6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GRM6 were set to 22008250
Phenotypes for gene: GRM6 were set to GRM6-related retinopathy MONDO:0800397
Review for gene: GRM6 was set to GREEN
Added comment: GRM6-related retinopathy is a glutamate neurotransmitter disorders affecting the ON-centre of the retinal ganglion cells.

>5 unrelated families with a night blindness phenotype due to a defective signal transmission at the ON-centre.
Sources: Other
Aminoacidopathy v1.113 SLC25A22 Sangavi Sivagnanasundram gene: SLC25A22 was added
gene: SLC25A22 was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: SLC25A22 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A22 were set to 15592994; 19780765; 24596948
Phenotypes for gene: SLC25A22 were set to Developmental and epileptic encephalopathy MONDO:0100062
Review for gene: SLC25A22 was set to GREEN
Added comment: Established gene-disease association with reported individuals having impaired mitochondrial glutamate transport.
Three unrelated families reported with three different rare missense variants.
Sources: Other
Aminoacidopathy v1.113 XPNPEP3 Sangavi Sivagnanasundram gene: XPNPEP3 was added
gene: XPNPEP3 was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: XPNPEP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: XPNPEP3 were set to 32660933; 20179356
Phenotypes for gene: XPNPEP3 were set to Nephronophthisis-like nephropathy 1 MONDO:0013163
Review for gene: XPNPEP3 was set to GREEN
Added comment: XPNPEP3 is member of the X-pro-aminopeptidases family.

A total of 3 unrelated families (with different variants) reported with abnormal renal function due to an inborn error of peptide metabolism

32660933 - individual case with a rare frameshift variant p.Q241Tfs*13 who also had evidence of an inborn error of peptide metabolism.
Sources: Other
Aminoacidopathy v1.113 PEPD Sangavi Sivagnanasundram gene: PEPD was added
gene: PEPD was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: PEPD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PEPD were set to 2365824; 19308961; 16470701
Phenotypes for gene: PEPD were set to Prolidase deficiency MONDO:0008221
Review for gene: PEPD was set to GREEN
Added comment: Well established gene-disease association with >10 individuals reported with variants in PEPD and a clinical phenotype associated with prolidase deficiency.
Prolidase deficiency is a classified inborn error of amino acid metabolism.
LoF appears to be the mechanism of disease (https://search.clinicalgenome.org/CCID:007640)
Sources: Other
Aminoacidopathy v1.113 PYCR2 Sangavi Sivagnanasundram edited their review of gene: PYCR2: Changed rating: GREEN
Aminoacidopathy v1.113 PYCR2 Sangavi Sivagnanasundram changed review comment from: Has been reported in 10 consanguineous families with different variants (frameshift, missense, splice). The affected individuals all had neurological clinical presentation however upon biochemical assessment, plasma proline levels were normal (showed no depletion). There is not enough evidence to indicate that these individuals have a phenotype consistent with an inborn error of amino acid metabolism.
Sources: Other; to: Has been reported in 10 consanguineous families with different variants (frameshift, missense, splice). The affected individuals all had neurological clinical presentation along with other phenotypes including failure to thrive.

Sources: Other
Aminoacidopathy v1.113 PYCR2 Sangavi Sivagnanasundram gene: PYCR2 was added
gene: PYCR2 was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: PYCR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PYCR2 were set to 25865492; 27130255
Phenotypes for gene: PYCR2 were set to Hypomyelinating leukodystrophy 10 MONDO:0014632; Disorders of ornithine, proline and hydroxyproline metabolism
Review for gene: PYCR2 was set to RED
Added comment: Has been reported in 10 consanguineous families with different variants (frameshift, missense, splice). The affected individuals all had neurological clinical presentation however upon biochemical assessment, plasma proline levels were normal (showed no depletion). There is not enough evidence to indicate that these individuals have a phenotype consistent with an inborn error of amino acid metabolism.
Sources: Other
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
Aminoacidopathy v1.113 SLC7A5 Sangavi Sivagnanasundram gene: SLC7A5 was added
gene: SLC7A5 was added to Aminoacidopathy. 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
Aminoacidopathy v1.113 SLC6A20 Sangavi Sivagnanasundram gene: SLC6A20 was added
gene: SLC6A20 was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: SLC6A20 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC6A20 were set to 36820062; 19033659; 24816252
Phenotypes for gene: SLC6A20 were set to Hyperglycinuria MONDO:0007677
Review for gene: SLC6A20 was set to RED
Added comment: Only one family reported with a rare missense variant and a clinical phenotype consistent with an inborn error of amino acid metabolism.

Cases have been reported in 19033659 and 24816252 however the variant is too common for a mendelian disease.

No other new publications have been released supporting the gene-disease association with relation to evidence of a biochemical abnormality.
Sources: Other
Skeletal dysplasia v0.281 DCC Achchuthan Shanmugasundram reviewed gene: DCC: Rating: GREEN; Mode of pathogenicity: None; Publications: 33141514; Phenotypes: Gaze palsy, familial horizontal, with progressive scoliosis, 2, OMIM:617542; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Speech apraxia v1.0 KDM5C Thomas Scerri changed review comment from: First reported CAS case with a de novo HNRNPK frameshift variant (Kaspi et al., 2022; PMID: 36117209).

Leonardi et al. (2023; PMID: 36434256) report 30 individuals with HNRNPK variants, of which 16 have reported speech delay (including all males with records, and several females). No mention of speech/verbal apraxia or dyspraxia though.

Note: Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type (MIM# 300534) is recorded as autosomal recessive, however female heterozygotes can have milder phenotypes.
Sources: Expert list, Expert Review; to: First reported CAS case with a de novo KDM5C frameshift variant (Kaspi et al., 2022; PMID: 36117209).

Leonardi et al. (2023; PMID: 36434256) report 30 individuals with KDM5C variants, of which 16 have reported speech delay (including all males with records, and several females). No mention of speech/verbal apraxia or dyspraxia though.

Note: Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type (MIM# 300534) is recorded as autosomal recessive, however female heterozygotes can have milder phenotypes.
Sources: Expert list, Expert Review
Aminoacidopathy v1.113 NFE2L2 Sangavi Sivagnanasundram gene: NFE2L2 was added
gene: NFE2L2 was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: NFE2L2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NFE2L2 were set to 29018201
Phenotypes for gene: NFE2L2 were set to Immunodeficiency, developmental delay, and hypohomocysteinemia MONDO:0060591; Disorders of glutathione metabolism
Review for gene: NFE2L2 was set to GREEN
Added comment: 4 unrelated patients with de novo missense variants affected with a multisystem disorder with failure to thrive, immunodeficiency and neurological symptoms including an inborn error of amino acid metabolism.
Sources: Other
Aminoacidopathy v1.113 GPX4 Sangavi Sivagnanasundram gene: GPX4 was added
gene: GPX4 was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: GPX4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GPX4 were set to 24706940; 32827718
Phenotypes for gene: GPX4 were set to Spondylometaphyseal dysplasia, Sedaghatian type MONDO:0009593; Disorders of glutathione metabolism
Review for gene: GPX4 was set to GREEN
Added comment: SSMD is an inborn error of gluthathione metabolism. Reports of four children (two were siblings from a consanguineous family) with SSMD. Parents were unaffected carriers.
LoF is the mechanism of disease.
Sources: Other
Aminoacidopathy v1.113 GSR Sangavi Sivagnanasundram gene: GSR was added
gene: GSR was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: GSR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GSR were set to 17185460; 31122244
Phenotypes for gene: GSR were set to Hemolytic anemia due to glutathione reductase deficiency MONDO:0019531; Disorders of glutathione metabolism
Review for gene: GSR was set to AMBER
Added comment: Not an established gene-disease association however there have been reports of two families reported with GR deficiency and there has been a report of functional evidence as well. More concrete evidence of biochemical abnormalities is required to promote the gene to green.
Sources: Other
Aminoacidopathy v1.113 OPLAH Sangavi Sivagnanasundram gene: OPLAH was added
gene: OPLAH was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: OPLAH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OPLAH were set to 27477828; 27604308
Phenotypes for gene: OPLAH were set to 5-oxoprolinase deficiency MONDO:0009825; Disorders of glutathione metabolism
Review for gene: OPLAH was set to RED
Added comment: Variants have been reported in individuals however it appears that this inborn error of glutathione metabolism appears to be of benign nature.
Sources: Other
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
Aminoacidopathy v1.113 GCLC Sangavi Sivagnanasundram gene: GCLC was added
gene: GCLC was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: GCLC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GCLC were set to 28571779; 10515893; 18024385
Phenotypes for gene: GCLC were set to Gamma-glutamylcysteine synthetase deficiency MONDO:0009259; Disorders of glutathione metabolism
Review for gene: GCLC was set to GREEN
Added comment: Established gene-disease association with >3 unrelated probands reported with GCLC deficiency which is an inborn error of amino acid metabolism.
Sources: Other
Aminoacidopathy v1.113 SLC25A15 Zornitza Stark Marked gene: SLC25A15 as ready
Aminoacidopathy v1.113 SLC25A15 Zornitza Stark Gene: slc25a15 has been classified as Green List (High Evidence).
Aminoacidopathy v1.113 SLC25A15 Zornitza Stark Classified gene: SLC25A15 as Green List (high evidence)
Aminoacidopathy v1.113 SLC25A15 Zornitza Stark Gene: slc25a15 has been classified as Green List (High Evidence).
Aminoacidopathy v1.112 SLC36A2 Zornitza Stark Marked gene: SLC36A2 as ready
Aminoacidopathy v1.112 SLC36A2 Zornitza Stark Gene: slc36a2 has been classified as Red List (Low Evidence).
Aminoacidopathy v1.112 SLC36A2 Zornitza Stark Classified gene: SLC36A2 as Red List (low evidence)
Aminoacidopathy v1.112 SLC36A2 Zornitza Stark Gene: slc36a2 has been classified as Red List (Low Evidence).
Aminoacidopathy v1.111 SLC38A8 Zornitza Stark Marked gene: SLC38A8 as ready
Aminoacidopathy v1.111 SLC38A8 Zornitza Stark Gene: slc38a8 has been classified as Green List (High Evidence).
Aminoacidopathy v1.111 SLC38A8 Zornitza Stark Classified gene: SLC38A8 as Green List (high evidence)
Aminoacidopathy v1.111 SLC38A8 Zornitza Stark Gene: slc38a8 has been classified as Green List (High Evidence).
Aminoacidopathy v1.110 SLC3A1 Zornitza Stark Marked gene: SLC3A1 as ready
Aminoacidopathy v1.110 SLC3A1 Zornitza Stark Gene: slc3a1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.110 SLC3A1 Zornitza Stark Classified gene: SLC3A1 as Green List (high evidence)
Aminoacidopathy v1.110 SLC3A1 Zornitza Stark Gene: slc3a1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.109 SLC6A19 Zornitza Stark Marked gene: SLC6A19 as ready
Aminoacidopathy v1.109 SLC6A19 Zornitza Stark Gene: slc6a19 has been classified as Green List (High Evidence).
Aminoacidopathy v1.109 SLC6A19 Zornitza Stark Classified gene: SLC6A19 as Green List (high evidence)
Aminoacidopathy v1.109 SLC6A19 Zornitza Stark Gene: slc6a19 has been classified as Green List (High Evidence).
Aminoacidopathy v1.108 SLC6A6 Zornitza Stark Marked gene: SLC6A6 as ready
Aminoacidopathy v1.108 SLC6A6 Zornitza Stark Gene: slc6a6 has been classified as Amber List (Moderate Evidence).
Aminoacidopathy v1.108 SLC6A6 Zornitza Stark Classified gene: SLC6A6 as Amber List (moderate evidence)
Aminoacidopathy v1.108 SLC6A6 Zornitza Stark Gene: slc6a6 has been classified as Amber List (Moderate Evidence).
Aminoacidopathy v1.107 SLC6A8 Zornitza Stark Marked gene: SLC6A8 as ready
Aminoacidopathy v1.107 SLC6A8 Zornitza Stark Gene: slc6a8 has been classified as Green List (High Evidence).
Aminoacidopathy v1.107 SLC6A8 Zornitza Stark Classified gene: SLC6A8 as Green List (high evidence)
Aminoacidopathy v1.107 SLC6A8 Zornitza Stark Gene: slc6a8 has been classified as Green List (High Evidence).
Aminoacidopathy v1.106 SLC7A7 Zornitza Stark Marked gene: SLC7A7 as ready
Aminoacidopathy v1.106 SLC7A7 Zornitza Stark Gene: slc7a7 has been classified as Green List (High Evidence).
Aminoacidopathy v1.106 SLC7A7 Zornitza Stark Classified gene: SLC7A7 as Green List (high evidence)
Aminoacidopathy v1.106 SLC7A7 Zornitza Stark Gene: slc7a7 has been classified as Green List (High Evidence).
Aminoacidopathy v1.105 SLC7A9 Zornitza Stark Marked gene: SLC7A9 as ready
Aminoacidopathy v1.105 SLC7A9 Zornitza Stark Gene: slc7a9 has been classified as Green List (High Evidence).
Aminoacidopathy v1.105 SLC7A9 Zornitza Stark Classified gene: SLC7A9 as Green List (high evidence)
Aminoacidopathy v1.105 SLC7A9 Zornitza Stark Gene: slc7a9 has been classified as Green List (High Evidence).
Aminoacidopathy v1.104 SPR Zornitza Stark Marked gene: SPR as ready
Aminoacidopathy v1.104 SPR Zornitza Stark Gene: spr has been classified as Green List (High Evidence).
Aminoacidopathy v1.104 SPR Zornitza Stark Classified gene: SPR as Green List (high evidence)
Aminoacidopathy v1.104 SPR Zornitza Stark Gene: spr has been classified as Green List (High Evidence).
Aminoacidopathy v1.103 SUGCT Zornitza Stark Marked gene: SUGCT as ready
Aminoacidopathy v1.103 SUGCT Zornitza Stark Gene: sugct has been classified as Amber List (Moderate Evidence).
Aminoacidopathy v1.103 SUGCT Zornitza Stark Classified gene: SUGCT as Amber List (moderate evidence)
Aminoacidopathy v1.103 SUGCT Zornitza Stark Gene: sugct has been classified as Amber List (Moderate Evidence).
Aminoacidopathy v1.102 SUOX Zornitza Stark Marked gene: SUOX as ready
Aminoacidopathy v1.102 SUOX Zornitza Stark Gene: suox has been classified as Green List (High Evidence).
Aminoacidopathy v1.102 SUOX Zornitza Stark Classified gene: SUOX as Green List (high evidence)
Aminoacidopathy v1.102 SUOX Zornitza Stark Gene: suox has been classified as Green List (High Evidence).
Aminoacidopathy v1.101 TAT Zornitza Stark Marked gene: TAT as ready
Aminoacidopathy v1.101 TAT Zornitza Stark Gene: tat has been classified as Green List (High Evidence).
Aminoacidopathy v1.101 TAT Zornitza Stark Classified gene: TAT as Green List (high evidence)
Aminoacidopathy v1.101 TAT Zornitza Stark Gene: tat has been classified as Green List (High Evidence).
Aminoacidopathy v1.100 TDO2 Zornitza Stark Marked gene: TDO2 as ready
Aminoacidopathy v1.100 TDO2 Zornitza Stark Gene: tdo2 has been classified as Red List (Low Evidence).
Aminoacidopathy v1.100 TDO2 Zornitza Stark Classified gene: TDO2 as Red List (low evidence)
Aminoacidopathy v1.100 TDO2 Zornitza Stark Gene: tdo2 has been classified as Red List (Low Evidence).
Aminoacidopathy v1.99 TH Zornitza Stark Marked gene: TH as ready
Aminoacidopathy v1.99 TH Zornitza Stark Gene: th has been classified as Green List (High Evidence).
Aminoacidopathy v1.99 TH Zornitza Stark Classified gene: TH as Green List (high evidence)
Aminoacidopathy v1.99 TH Zornitza Stark Gene: th has been classified as Green List (High Evidence).
Aminoacidopathy v1.98 TYR Zornitza Stark Marked gene: TYR as ready
Aminoacidopathy v1.98 TYR Zornitza Stark Gene: tyr has been classified as Green List (High Evidence).
Aminoacidopathy v1.98 TYR Zornitza Stark Classified gene: TYR as Green List (high evidence)
Aminoacidopathy v1.98 TYR Zornitza Stark Gene: tyr has been classified as Green List (High Evidence).
Aminoacidopathy v1.97 GRHPR Sangavi Sivagnanasundram gene: GRHPR was added
gene: GRHPR was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: GRHPR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GRHPR were set to 24116921
Phenotypes for gene: GRHPR were set to primary hyperoxaluria type 2 MONDO:0009824; Disorders of glyoxylate and oxalate metabolism
Review for gene: GRHPR was set to GREEN
Added comment: Well established gene - disease association with reported individuals having abnormal biochemical function.
Sources: Other
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.328 ZNF483 Zornitza Stark Marked gene: ZNF483 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.328 ZNF483 Zornitza Stark Gene: znf483 has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.328 ZNF483 Zornitza Stark Mode of inheritance for gene: ZNF483 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.327 ZNF483 Zornitza Stark Classified gene: ZNF483 as Amber List (moderate evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.327 ZNF483 Zornitza Stark Gene: znf483 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1888 ZNF483 Zornitza Stark Marked gene: ZNF483 as ready
Mendeliome v1.1888 ZNF483 Zornitza Stark Gene: znf483 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1888 ZNF483 Zornitza Stark Mode of inheritance for gene: ZNF483 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1887 ZNF483 Zornitza Stark Classified gene: ZNF483 as Amber List (moderate evidence)
Mendeliome v1.1887 ZNF483 Zornitza Stark Gene: znf483 has been classified as Amber List (Moderate Evidence).
Aminoacidopathy v1.97 UROC1 Zornitza Stark Marked gene: UROC1 as ready
Aminoacidopathy v1.97 UROC1 Zornitza Stark Gene: uroc1 has been classified as Amber List (Moderate Evidence).
Aminoacidopathy v1.97 UROC1 Zornitza Stark Classified gene: UROC1 as Amber List (moderate evidence)
Aminoacidopathy v1.97 UROC1 Zornitza Stark Gene: uroc1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6063 CRNKL1 Zornitza Stark Marked gene: CRNKL1 as ready
Intellectual disability syndromic and non-syndromic v0.6063 CRNKL1 Zornitza Stark Gene: crnkl1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6063 CRNKL1 Zornitza Stark Classified gene: CRNKL1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6063 CRNKL1 Zornitza Stark Gene: crnkl1 has been classified as Green List (High Evidence).
Microcephaly v1.269 CRNKL1 Zornitza Stark Marked gene: CRNKL1 as ready
Microcephaly v1.269 CRNKL1 Zornitza Stark Gene: crnkl1 has been classified as Green List (High Evidence).
Microcephaly v1.269 CRNKL1 Zornitza Stark Classified gene: CRNKL1 as Green List (high evidence)
Microcephaly v1.269 CRNKL1 Zornitza Stark Gene: crnkl1 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v1.65 CRNKL1 Zornitza Stark Marked gene: CRNKL1 as ready
Cerebellar and Pontocerebellar Hypoplasia v1.65 CRNKL1 Zornitza Stark Gene: crnkl1 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v1.65 CRNKL1 Zornitza Stark Classified gene: CRNKL1 as Green List (high evidence)
Cerebellar and Pontocerebellar Hypoplasia v1.65 CRNKL1 Zornitza Stark Gene: crnkl1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.96 HOGA1 Zornitza Stark Marked gene: HOGA1 as ready
Aminoacidopathy v1.96 HOGA1 Zornitza Stark Gene: hoga1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.96 HOGA1 Zornitza Stark Classified gene: HOGA1 as Green List (high evidence)
Aminoacidopathy v1.96 HOGA1 Zornitza Stark Gene: hoga1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.95 HOGA1 Sangavi Sivagnanasundram gene: HOGA1 was added
gene: HOGA1 was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: HOGA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HOGA1 were set to 26401545; 21896830; 20797690
Phenotypes for gene: HOGA1 were set to primary hyperoxaluria type 3 MONDO:0013327; Disorders of ornithine, proline and hydroxyproline metabolism
Review for gene: HOGA1 was set to GREEN
Added comment: Established gene-disease association with >4 unrelated individuals having evidence of abnormal biochemical function.
Sources: Other
Cerebellar and Pontocerebellar Hypoplasia v1.64 CRNKL1 Mark Cleghorn gene: CRNKL1 was added
gene: CRNKL1 was added to Cerebellar and Pontocerebellar Hypoplasia. 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
RNQ seq on affected zebrafish embryos - transcriptome strongly disrupted
Splicing analysis in progress

CRKNL1 supports U6 structure in spliceosome
Sources: Other
Microcephaly v1.268 CRNKL1 Mark Cleghorn gene: CRNKL1 was added
gene: CRNKL1 was added to Microcephaly. 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
RNQ seq on affected zebrafish embryos - transcriptome strongly disrupted
Splicing analysis in progress

CRKNL1 supports U6 structure in spliceosome
Sources: Other
Intellectual disability syndromic and non-syndromic v0.6062 CRNKL1 Mark Cleghorn gene: CRNKL1 was added
gene: CRNKL1 was added to Intellectual disability syndromic and non-syndromic. 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
Penetrance for gene: CRNKL1 were set to Complete
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
RNQ seq on affected zebrafish embryos - transcriptome strongly disrupted
Splicing analysis in progress

CRKNL1 supports U6 structure in spliceosome
Sources: Other
Aminoacidopathy v1.95 UROC1 Sangavi Sivagnanasundram gene: UROC1 was added
gene: UROC1 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: UROC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UROC1 were set to 19304569; 30619714; 32439973; 27391121
Phenotypes for gene: UROC1 were set to urocanic aciduria MONDO:0010167
Review for gene: UROC1 was set to AMBER
Added comment: The relationship between the phenotypes and evidence of biochemical abnormality remains unclear for this gene-disease association.

Variants have been reported in 4 unrelated individuals however one individual was reported to be phenotypically asymptomatic except for evidence of urocanase deficiency in a biochemical assay (PMID: 30619714).

Classified Moderate by Aminoacidopathy GCEP on 26/04/2024 - https://search.clinicalgenome.org/CCID:006504
Sources: ClinGen
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
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.326 ZNF483 Mark Cleghorn gene: ZNF483 was added
gene: ZNF483 was added to Primary Ovarian Insufficiency_Premature Ovarian Failure. 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
Penetrance for gene: ZNF483 were set to unknown
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
Aminoacidopathy v1.95 TYR Sangavi Sivagnanasundram gene: TYR was added
gene: TYR was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: TYR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TYR were set to 2511845; 32411182; 31199599; 29052256
Phenotypes for gene: TYR were set to oculocutaneous albinism type 1 MONDO:0018135
Review for gene: TYR was set to GREEN
Added comment: TYR encodes tyrosinase which vital in melanin synthesis. Reported individuals have an error in tyrosinase metabolism thus affecting melanin synthesis. >5 probands have been reported with errors in tyrosinase metabolism.

Classified Definitive by Aminoacidopathy GCEP on 28/08/2020 - https://search.clinicalgenome.org/CCID:006490
Sources: ClinGen
Aminoacidopathy v1.95 TH Sangavi Sivagnanasundram gene: TH was added
gene: TH was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: TH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TH were set to 30383639; 29225908; 22264700; 12891655
Phenotypes for gene: TH were set to tyrosine hydroxylase deficiency MONDO:0100064
Review for gene: TH was set to GREEN
Added comment: >10 unrelated probands reported with an inborn error in tyrosine metabolism.

Classified Definitive by Aminoacidopathy GCEP on 22/03/2019 - https://search.clinicalgenome.org/CCID:006363
Sources: ClinGen
Aminoacidopathy v1.95 TDO2 Sangavi Sivagnanasundram gene: TDO2 was added
gene: TDO2 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: TDO2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TDO2 were set to 28285122
Phenotypes for gene: TDO2 were set to familial hypertryptophanemia MONDO:0010907
Review for gene: TDO2 was set to RED
Added comment: Reported in one individual to date however there is evidence that this is a benign biochemical variant with no clinical significance.

Classified Limitied by Aminoacidopathy GCEP on 17/11/2023 - https://search.clinicalgenome.org/CCID:006345
Sources: ClinGen
Aminoacidopathy v1.95 TAT Sangavi Sivagnanasundram gene: TAT was added
gene: TAT was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: TAT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TAT were set to 9544843; 16917729
Phenotypes for gene: TAT were set to tyrosinemia type II MONDO:0010160
Review for gene: TAT was set to GREEN
Added comment: Well reported gene-disease association with affected individuals having reports of a deficiency in hepatic tyrosine aminotransferase (TAT).

Classified Definitive by Aminoacidopathy GCEP on 29/06/2020 - https://search.clinicalgenome.org/CCID:006320
Sources: ClinGen
Aminoacidopathy v1.95 SUOX Sangavi Sivagnanasundram gene: SUOX was added
gene: SUOX was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SUOX was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUOX were set to 28980090
Phenotypes for gene: SUOX were set to isolated sulfite oxidase deficiency MONDO:0010089
Review for gene: SUOX was set to GREEN
Added comment: Well established gene-disease association (reported in >40 patients).

Classified Definitive by Aminoacidopathy GCEP on 22/03/2019 - https://search.clinicalgenome.org/CCID:006301
Sources: ClinGen
Aminoacidopathy v1.95 SUGCT Sangavi Sivagnanasundram gene: SUGCT was added
gene: SUGCT was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SUGCT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUGCT were set to 18926513; 28766179; 29421601
Phenotypes for gene: SUGCT were set to glutaric acidemia type 3 MONDO:0009283
Review for gene: SUGCT was set to AMBER
Added comment: There is uncertain clinical relevance for this gene-disease association - reports of different clinical phenotypes between affected individuals and potentially a benign condition. Variants have been reported in >3 unrelated affected probands however their clinical presentations vary.

Classified Moderate by Aminoacidopathy GCEP on 12/12/2022- https://search.clinicalgenome.org/CCID:006299
Sources: ClinGen
Aminoacidopathy v1.95 SPR Sangavi Sivagnanasundram gene: SPR was added
gene: SPR was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SPR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPR were set to 33903016
Phenotypes for gene: SPR were set to dopa-responsive dystonia due to sepiapterin reductase deficiency MONDO:0012994
Review for gene: SPR was set to GREEN
Added comment: Well-established gene-disease association with reported individuals having an inborn error of amino acid metabolism.

Classified Definitive by Aminoacidopathy GCEP on 04/06/2021- https://search.clinicalgenome.org/CCID:006266
Sources: ClinGen
Aminoacidopathy v1.95 SLC7A9 Sangavi Sivagnanasundram gene: SLC7A9 was added
gene: SLC7A9 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SLC7A9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC7A9 were set to 23532419; 16609684; 25296721; 11157794; 10471498
Phenotypes for gene: SLC7A9 were set to cystinuria MONDO:0009067
Review for gene: SLC7A9 was set to GREEN
Added comment: Established gene-disease association with reported individuals having errors in amino acid transport and metabolism.

Classified Definitive by Aminoacidopathy GCEP on 29/06/2020 - https://search.clinicalgenome.org/CCID:006202
Sources: ClinGen
Aminoacidopathy v1.95 SLC7A7 Sangavi Sivagnanasundram gene: SLC7A7 was added
gene: SLC7A7 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SLC7A7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC7A7 were set to 10080182; 10080183; 15776247
Phenotypes for gene: SLC7A7 were set to lysinuric protein intolerance MONDO:0009109
Review for gene: SLC7A7 was set to GREEN
Added comment: Reported in at least 8 probands all having an error in amino acid transport. LoF is the mechanism of disease.

Classified Definitive by Aminoacidopathy GCEP on 08/11/2019 - https://search.clinicalgenome.org/CCID:006201
Sources: ClinGen
Aminoacidopathy v1.95 SLC6A8 Sangavi Sivagnanasundram gene: SLC6A8 was added
gene: SLC6A8 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SLC6A8 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SLC6A8 were set to 27604308; 16738945
Phenotypes for gene: SLC6A8 were set to creatine transporter deficiency MONDO:0010305
Review for gene: SLC6A8 was set to GREEN
Added comment: Well-established gene disease association with reported individuals having error in creatine transport.

Classified Definitive by Aminoacidopathy GCEP on 10/02/2020 - https://search.clinicalgenome.org/CCID:006200
Sources: ClinGen
Aminoacidopathy v1.95 SLC6A6 Sangavi Sivagnanasundram gene: SLC6A6 was added
gene: SLC6A6 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SLC6A6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC6A6 were set to 31903486; 31345061
Phenotypes for gene: SLC6A6 were set to hypotaurinemic retinal degeneration and cardiomyopathy MONDO:0007777
Review for gene: SLC6A6 was set to AMBER
Added comment: 4 individuals reported with retinal degeneration while 2 (who are siblings) also reported cardiomyopathy. The proband (one of the siblings) was given oral taurine supplementation that reversed their phenotype (cardiomyopathy was reversed and the retinal degeneration was halted) (PMID: 31903486).

Classified Limited by Aminoacidopathy GCEP on 10/03/2023 - https://search.clinicalgenome.org/CCID:006199
Sources: ClinGen
Prepair 1000+ v1.9 ETFDH Lilian Downie Marked gene: ETFDH as ready
Prepair 1000+ v1.9 ETFDH Lilian Downie Gene: etfdh has been classified as Green List (High Evidence).
Prepair 1000+ v1.9 ETFDH Lilian Downie Publications for gene: ETFDH were set to 31904027
Prepair 1000+ v1.8 ETFDH Lilian Downie Publications for gene: ETFDH were set to
Aminoacidopathy v1.95 SLC6A19 Sangavi Sivagnanasundram gene: SLC6A19 was added
gene: SLC6A19 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SLC6A19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC6A19 were set to 15286787; 15286788; 18484095
Phenotypes for gene: SLC6A19 were set to Hartnup disease MONDO:0009324
Review for gene: SLC6A19 was set to GREEN
Added comment: Established gene-disease association with >10 probands reported with clinical symptoms assocation with Hartnup disease. Mechanism of disease is LoF with affected individuals having a defect in amino acid transportation.

Classified Definitive by Aminoacidopathy GCEP on 07/05/2020 - https://search.clinicalgenome.org/CCID:006196
Sources: ClinGen
Aminoacidopathy v1.95 SLC3A1 Sangavi Sivagnanasundram gene: SLC3A1 was added
gene: SLC3A1 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SLC3A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC3A1 were set to 8054986; 16374432; 8486766
Phenotypes for gene: SLC3A1 were set to cystinuria MONDO:0009067
Review for gene: SLC3A1 was set to GREEN
Added comment: Established gene-disease association with reported individuals having biochemical abnormalities affecting cystine transportation.

Classified Definitive by Aminoacidopathy GCEP on 29/06/2020 - https://search.clinicalgenome.org/CCID:006188
Sources: ClinGen
Aminoacidopathy v1.95 SLC38A8 Sangavi Sivagnanasundram gene: SLC38A8 was added
gene: SLC38A8 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SLC38A8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC38A8 were set to 32744312; 24290379; 24045842; 25451601; 24290379
Phenotypes for gene: SLC38A8 were set to foveal hypoplasia - optic nerve decussation defect - anterior segment dysgenesis syndrome MONDO:0012216
Review for gene: SLC38A8 was set to GREEN
Added comment: Reported in >5 unrelated probands with reported errors in glutamate/glutamine transport.

Classified Definitive by Aminoacidopathy GCEP on 10/02/2023 - https://search.clinicalgenome.org/CCID:006184
Sources: ClinGen
Aminoacidopathy v1.95 SLC36A2 Sangavi Sivagnanasundram gene: SLC36A2 was added
gene: SLC36A2 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SLC36A2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SLC36A2 were set to 19033659; 26141664
Phenotypes for gene: SLC36A2 were set to iminoglycinuria MONDO:0009448
Review for gene: SLC36A2 was set to RED
Added comment: IG phenotype is due to excess urinary excretion of proline, hydroxyproline and glycine which is thought to be benign. Variants have been reported in individuals with varying phenotypes - One homozygous individual reported with an IG phenotype while some heterozygous individuals reported to have hyperglycinuria. Biochemical abnormalities result in an IG phenotype is not a common clinical feature in the reported individuals.

Classified Limitied by Aminoacidopathy GCEP on 11/04/2024 - https://search.clinicalgenome.org/CCID:006183
Sources: ClinGen
Aminoacidopathy v1.95 SLC25A15 Sangavi Sivagnanasundram gene: SLC25A15 was added
gene: SLC25A15 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SLC25A15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A15 were set to 25874378
Phenotypes for gene: SLC25A15 were set to ornithine translocase deficiency MONDO:0009393 (HHH Syndrome)
Review for gene: SLC25A15 was set to GREEN
Added comment: Well established gene-disease association with reported individuals presenting with a biochemical triad of abnormalities - hyperornithinemia, hyperammonemia, and homocitrullinuria (severity of the clinical symptoms can vary).

Common variants in individuals with HHH syndrome
p.Phe188del
French Canadian Founder - NFE GrpMax AF - 0.004% (reported in 62 hets globally)

p.Arg179X
Commonly seen in Japanese patients - EAS GrpMax AF - 0.017% (reported in 26 hets globally)

Classified Definitive by Aminoacidopathy GCEP on 04/12/2019 -https://search.clinicalgenome.org/CCID:006162
Sources: ClinGen
Aminoacidopathy v1.95 SLC25A13 Sangavi Sivagnanasundram gene: SLC25A13 was added
gene: SLC25A13 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SLC25A13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A13 were set to 18367750; 10369257; 19036621; 18392553; 11343053; 31607264
Phenotypes for gene: SLC25A13 were set to citrin deficiency MONDO:0016602
Review for gene: SLC25A13 was set to GREEN
Added comment: Established gene-disease association with variants reported in >10 probands with reported biochemical abnormalities. Variants in this gene have been reported in both adult onset citrullinemia type 2 but also in individuals with neonatal intrahepatic cholestasis.

Mechanism of disease is biallelic loss of function - significantly reduced or absent glutamate transport in and aspartate transport out of mitochondria depriving argininosuccinate synthetase leading to the accumulation of citrulline and ammonia.

Classified Definitive by Aminoacidopathy GCEP on 23/07/2021 - https://search.clinicalgenome.org/CCID:006161
Sources: ClinGen
Aminoacidopathy v1.95 SLC1A4 Sangavi Sivagnanasundram gene: SLC1A4 was added
gene: SLC1A4 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SLC1A4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC1A4 were set to 25930971, 27711071, 29989513, 29652076, 26041762, 27193218, 30125339
Phenotypes for gene: SLC1A4 were set to spastic tetraplegia-thin corpus callosum-progressive postnatal microcephaly syndrome MONDO:0014725
Review for gene: SLC1A4 was set to GREEN
Added comment: Reported in at least 9 individuals with reported biochemical abnormalities involving the L-serine transporter.

Classified Definitive by Aminoacidopathy GCEP on 14/05/2021 - https://search.clinicalgenome.org/CCID:006155
Sources: ClinGen
Intellectual disability syndromic and non-syndromic v0.6062 B9D1 Achchuthan Shanmugasundram reviewed gene: B9D1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: 32622957; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v1.44 DDOST Achchuthan Shanmugasundram changed review comment from: PMID:34462534 reported the identification of homozygous DDOST variant (c.1187G>A) in a Chinese patient who presented with feeding difficulty, lactose intolerance, facial dysmorphism, failure to thrive, strabismus, high myopia, astigmatism, hypotonia, developmental delay and situs inversus totalis. Serum transferrin isoelectrofocusing demonstrated defective glycosylation in the patient. T; to: PMID:34462534 reported the identification of homozygous DDOST variant (c.1187G>A) in a Chinese patient who presented with feeding difficulty, lactose intolerance, facial dysmorphism, failure to thrive, strabismus, high myopia, astigmatism, hypotonia, developmental delay and situs inversus totalis. Serum transferrin isoelectrofocusing demonstrated defective glycosylation in the patient.
Congenital Disorders of Glycosylation v1.44 DDOST Achchuthan Shanmugasundram reviewed gene: DDOST: Rating: GREEN; Mode of pathogenicity: None; Publications: 34462534; Phenotypes: Congenital disorder of glycosylation, type Ir, OMIM:614507; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1886 DDOST Achchuthan Shanmugasundram reviewed gene: DDOST: Rating: GREEN; Mode of pathogenicity: None; Publications: 34462534; Phenotypes: Congenital disorder of glycosylation, type Ir, OMIM:614507; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 ETFDH Lauren Rogers reviewed gene: ETFDH: Rating: GREEN; Mode of pathogenicity: None; Publications: 31904027; Phenotypes: Glutaric acidemia IIC, MIM# 231680; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 ECHS1 Lauren Rogers reviewed gene: ECHS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32642440; Phenotypes: Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency MIM# 616277; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 DIS3L2 Lauren Rogers reviewed gene: DIS3L2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22306653, 28328139, 29950491; Phenotypes: Perlman syndrome MIM# 267000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 DBT Lauren Rogers reviewed gene: DBT: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Maple syrup urine disease, type II (MIM#248600); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 ATP7B Andrew Coventry reviewed gene: ATP7B: Rating: GREEN; Mode of pathogenicity: None; Publications: 35042319 8298639 9554743 10790207 7626145 16133174 28433102; Phenotypes: Wilson disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 ALG3 Andrew Coventry reviewed gene: ALG3: Rating: GREEN; Mode of pathogenicity: None; Publications: 31067009, 10581255, 15840742; Phenotypes: Congenital disorder of glycosylation, type Id; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Speech apraxia v1.0 SETD1A Thomas Scerri edited their review of gene: SETD1A: Changed rating: GREEN; Changed publications: 29463886, 32346159, 36117209
Speech apraxia v1.0 SETD1A Thomas Scerri changed review comment from: First reported CAS case with a de novo SETD1A frameshift variant (Eising et al., 2019; PMID: 29463886)

Fifteen further independent probands with loss-of-function SETD1A variants were investigated (Kummeling et al., 2021; PMID: 32346159) and "global DD was reported in 14/15 individuals, including delayed speech and language development (14/14) and motor development (13/14)". However, only one proband was explicitly recorded with speech apraxia (proband 14; supplementary Table 1).

Sources: Expert list, Expert Review; to: First reported CAS case with a de novo SETD1A frameshift variant (Eising et al., 2019; PMID: 29463886)

Kaspi et al. (2022; PMID: 36117209) report a CAS proband with a de novo SETD1A splice acceptor variant.

An independent (unpublished) in-house CAS proband has a de novo SETD1A frameshift variant.

Fifteen further independent probands with loss-of-function SETD1A variants were investigated (Kummeling et al., 2021; PMID: 32346159) and "global DD was reported in 14/15 individuals, including delayed speech and language development (14/14) and motor development (13/14)". However, only one proband was explicitly recorded with speech apraxia (proband 14; supplementary Table 1).

Sources: Expert list, Expert Review
Predominantly Antibody Deficiency v0.135 FNIP1 Zornitza Stark Marked gene: FNIP1 as ready
Predominantly Antibody Deficiency v0.135 FNIP1 Zornitza Stark Gene: fnip1 has been classified as Green List (High Evidence).
Predominantly Antibody Deficiency v0.135 FNIP1 Zornitza Stark Classified gene: FNIP1 as Green List (high evidence)
Predominantly Antibody Deficiency v0.135 FNIP1 Zornitza Stark Gene: fnip1 has been classified as Green List (High Evidence).
Predominantly Antibody Deficiency v0.134 SENP7 Zornitza Stark Marked gene: SENP7 as ready
Predominantly Antibody Deficiency v0.134 SENP7 Zornitza Stark Gene: senp7 has been classified as Green List (High Evidence).
Predominantly Antibody Deficiency v0.134 SENP7 Zornitza Stark Classified gene: SENP7 as Green List (high evidence)
Predominantly Antibody Deficiency v0.134 SENP7 Zornitza Stark Gene: senp7 has been classified as Green List (High Evidence).
Predominantly Antibody Deficiency v0.133 SENP7 Zornitza Stark gene: SENP7 was added
gene: SENP7 was added to Predominantly Antibody Deficiency. Sources: Literature
Mode of inheritance for gene: SENP7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SENP7 were set to 38972567
Phenotypes for gene: SENP7 were set to Arthrogryposis multiplex congenita, MONDO:0015168, SENP7-related
Review for gene: SENP7 was set to GREEN
Added comment: 4 individuals from three unrelated families reported with biallelic variants and neurodevelopmental abnormalities, dysmorphism, and immunodeficiency, including hypogammaglobulinaemia.
Sources: Literature
Mendeliome v1.1886 SENP7 Zornitza Stark Publications for gene: SENP7 were set to PMID: 37460201
Mendeliome v1.1885 SENP7 Zornitza Stark Classified gene: SENP7 as Green List (high evidence)
Mendeliome v1.1885 SENP7 Zornitza Stark Gene: senp7 has been classified as Green List (High Evidence).
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
Phagocyte Defects v1.29 SENP7 Zornitza Stark Publications for gene: SENP7 were set to PMID: 37460201; 38972567
Phagocyte Defects v1.28 SENP7 Zornitza Stark Publications for gene: SENP7 were set to PMID: 37460201
Phagocyte Defects v1.27 SENP7 Zornitza Stark Classified gene: SENP7 as Green List (high evidence)
Phagocyte Defects v1.27 SENP7 Zornitza Stark Gene: senp7 has been classified as Green List (High Evidence).
Phagocyte Defects v1.26 SENP7 Zornitza Stark reviewed gene: SENP7: Rating: GREEN; Mode of pathogenicity: None; Publications: 38972567; 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
Dilated Cardiomyopathy v1.33 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
Mendeliome v1.1884 MYZAP Zornitza Stark Marked gene: MYZAP as ready
Mendeliome v1.1884 MYZAP Zornitza Stark Gene: myzap has been classified as Green List (High Evidence).
Mendeliome v1.1884 MYZAP Zornitza Stark Classified gene: MYZAP as Green List (high evidence)
Mendeliome v1.1884 MYZAP Zornitza Stark Gene: myzap has been classified as Green List (High Evidence).
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
Dilated Cardiomyopathy v1.33 MYZAP Zornitza Stark Marked gene: MYZAP as ready
Dilated Cardiomyopathy v1.33 MYZAP Zornitza Stark Gene: myzap has been classified as Green List (High Evidence).
Dilated Cardiomyopathy v1.33 MYZAP Zornitza Stark Classified gene: MYZAP as Green List (high evidence)
Dilated Cardiomyopathy v1.33 MYZAP Zornitza Stark Gene: myzap has been classified as Green List (High Evidence).
Dilated Cardiomyopathy v1.32 MYZAP Zornitza Stark gene: MYZAP was added
gene: MYZAP was added to Dilated Cardiomyopathy. 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
Prepair 1000+ v1.7 AFF2 Lauren Rogers reviewed gene: AFF2: Rating: AMBER; Mode of pathogenicity: None; Publications: 35431806, 8334699, 21739600, 22773736; Phenotypes: Intellectual disability, X-linked, FRAXE type 309548; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.7 ALDH7A1 Andrew Coventry reviewed gene: ALDH7A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 16491085, 17068770, 32969477, 33200442, 17721876, 19142996, 22784480, 29053735; Phenotypes: Epilepsy, early-onset, 4, vitamin B6-dependent MIM #266100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 AK2 Andrew Coventry reviewed gene: AK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 19043416, 19043417; Phenotypes: Reticular dysgenesis MIM# 267500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 AGXT Andrew Coventry reviewed gene: AGXT: Rating: GREEN; Mode of pathogenicity: None; Publications: 2039493, 19479957, 33789010; Phenotypes: Hyperoxaluria, primary, type 1 MIM #259900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Aminoacidopathy v1.94 PCBD1 Zornitza Stark Marked gene: PCBD1 as ready
Aminoacidopathy v1.94 PCBD1 Zornitza Stark Gene: pcbd1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.94 PCBD1 Zornitza Stark Classified gene: PCBD1 as Green List (high evidence)
Aminoacidopathy v1.94 PCBD1 Zornitza Stark Gene: pcbd1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.93 PAH Zornitza Stark Marked gene: PAH as ready
Aminoacidopathy v1.93 PAH Zornitza Stark Gene: pah has been classified as Green List (High Evidence).
Aminoacidopathy v1.93 PAH Zornitza Stark Classified gene: PAH as Green List (high evidence)
Aminoacidopathy v1.93 PAH Zornitza Stark Gene: pah has been classified as Green List (High Evidence).
Aminoacidopathy v1.92 OTC Zornitza Stark Marked gene: OTC as ready
Aminoacidopathy v1.92 OTC Zornitza Stark Gene: otc has been classified as Green List (High Evidence).
Aminoacidopathy v1.92 OTC Zornitza Stark Classified gene: OTC as Green List (high evidence)
Aminoacidopathy v1.92 OTC Zornitza Stark Gene: otc has been classified as Green List (High Evidence).
Aminoacidopathy v1.91 OAT Zornitza Stark Marked gene: OAT as ready
Aminoacidopathy v1.91 OAT Zornitza Stark Gene: oat has been classified as Green List (High Evidence).
Aminoacidopathy v1.91 OAT Zornitza Stark Classified gene: OAT as Green List (high evidence)
Aminoacidopathy v1.91 OAT Zornitza Stark Gene: oat has been classified as Green List (High Evidence).
Aminoacidopathy v1.90 NAT8L Zornitza Stark Marked gene: NAT8L as ready
Aminoacidopathy v1.90 NAT8L Zornitza Stark Gene: nat8l has been classified as Red List (Low Evidence).
Aminoacidopathy v1.90 NAT8L Zornitza Stark Classified gene: NAT8L as Red List (low evidence)
Aminoacidopathy v1.90 NAT8L Zornitza Stark Gene: nat8l has been classified as Red List (Low Evidence).
Aminoacidopathy v1.89 NAGS Zornitza Stark Marked gene: NAGS as ready
Aminoacidopathy v1.89 NAGS Zornitza Stark Gene: nags has been classified as Green List (High Evidence).
Aminoacidopathy v1.89 NAGS Zornitza Stark Classified gene: NAGS as Green List (high evidence)
Aminoacidopathy v1.89 NAGS Zornitza Stark Gene: nags has been classified as Green List (High Evidence).
Aminoacidopathy v1.88 MTRR Zornitza Stark Marked gene: MTRR as ready
Aminoacidopathy v1.88 MTRR Zornitza Stark Gene: mtrr has been classified as Green List (High Evidence).
Aminoacidopathy v1.88 MTRR Zornitza Stark Classified gene: MTRR as Green List (high evidence)
Aminoacidopathy v1.88 MTRR Zornitza Stark Gene: mtrr has been classified as Green List (High Evidence).
Aminoacidopathy v1.87 MTR Zornitza Stark Marked gene: MTR as ready
Aminoacidopathy v1.87 MTR Zornitza Stark Gene: mtr has been classified as Green List (High Evidence).
Aminoacidopathy v1.87 MTR Zornitza Stark Classified gene: MTR as Green List (high evidence)
Aminoacidopathy v1.87 MTR Zornitza Stark Gene: mtr has been classified as Green List (High Evidence).
Aminoacidopathy v1.86 MTHFR Zornitza Stark Marked gene: MTHFR as ready
Aminoacidopathy v1.86 MTHFR Zornitza Stark Gene: mthfr has been classified as Green List (High Evidence).
Aminoacidopathy v1.86 MTHFR Zornitza Stark Classified gene: MTHFR as Green List (high evidence)
Aminoacidopathy v1.86 MTHFR Zornitza Stark Gene: mthfr has been classified as Green List (High Evidence).
Aminoacidopathy v1.85 MPST Zornitza Stark Marked gene: MPST as ready
Aminoacidopathy v1.85 MPST Zornitza Stark Gene: mpst has been classified as Red List (Low Evidence).
Aminoacidopathy v1.85 MPST Zornitza Stark Classified gene: MPST as Red List (low evidence)
Aminoacidopathy v1.85 MPST Zornitza Stark Gene: mpst has been classified as Red List (Low Evidence).
Aminoacidopathy v1.84 MMACHC Zornitza Stark Marked gene: MMACHC as ready
Aminoacidopathy v1.84 MMACHC Zornitza Stark Gene: mmachc has been classified as Green List (High Evidence).
Aminoacidopathy v1.84 MMACHC Zornitza Stark Classified gene: MMACHC as Green List (high evidence)
Aminoacidopathy v1.84 MMACHC Zornitza Stark Gene: mmachc has been classified as Green List (High Evidence).
Aminoacidopathy v1.83 MCEE Zornitza Stark Marked gene: MCEE as ready
Aminoacidopathy v1.83 MCEE Zornitza Stark Gene: mcee has been classified as Green List (High Evidence).
Aminoacidopathy v1.83 MCEE Zornitza Stark Classified gene: MCEE as Green List (high evidence)
Aminoacidopathy v1.83 MCEE Zornitza Stark Gene: mcee has been classified as Green List (High Evidence).
Aminoacidopathy v1.82 MAT1A Zornitza Stark Marked gene: MAT1A as ready
Aminoacidopathy v1.82 MAT1A Zornitza Stark Gene: mat1a has been classified as Green List (High Evidence).
Aminoacidopathy v1.82 MAT1A Zornitza Stark Classified gene: MAT1A as Green List (high evidence)
Aminoacidopathy v1.82 MAT1A Zornitza Stark Gene: mat1a has been classified as Green List (High Evidence).
Ataxia - adult onset v1.16 PNPT1 Zornitza Stark Publications for gene: PNPT1 were set to 35411967
Prepair 1000+ v1.7 CTSD Lauren Rogers reviewed gene: CTSD: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ceroid lipofuscinosis, neuronal, 10, MIM# 610127; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 ABCB7 Andrew Coventry reviewed gene: ABCB7: Rating: GREEN; Mode of pathogenicity: None; Publications: 10196363, 33157103, 31772327, 31511561, 26242992, 34354969, 22398176; Phenotypes: Anaemia, sideroblastic, with ataxia MIM# 301310; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.7 ABCB7 Andrew Coventry Deleted their review
Prepair 1000+ v1.7 ABCB7 Andrew Coventry changed review comment from: HGNC approved symbol/name: ABCB7
Reported cases of ataxia are typically childhood onset and progressive, anaemia reported to be mostly mild.; to: HGNC approved symbol/name: ABCB7
Reported cases of ataxia are typically childhood onset and progressive, anaemia reported to be mostly mild.
Prepair 1000+ v1.7 COQ4 Lauren Rogers reviewed gene: COQ4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Coenzyme Q10 deficiency, primary, 7, MIM# 616276; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 ABCB7 Andrew Coventry reviewed gene: ABCB7: Rating: ; Mode of pathogenicity: None; Publications: 10196363, 33157103, 31772327, 31511561, 26242992, 34354969, 22398176; Phenotypes: Anaemia, sideroblastic, with ataxia MIM# 301310; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Ataxia - adult onset v1.15 PNPT1 Chris Ciotta reviewed gene: PNPT1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 37935417; Phenotypes: Spinocerebellar ataxia 25 (MIM#608703); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Prepair 1000+ v1.7 AGL Marta Cifuentes Ochoa reviewed gene: AGL: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 26885414, 20301788, 35834487, 27106217; Phenotypes: Glycogen storage disease IIIa and IIIb, MIM#232400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 ACY1 Marta Cifuentes Ochoa reviewed gene: ACY1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 16274666, 16465618, 17562838, 24117009, 37523070, 29653693, 26686503; Phenotypes: Aminoacylase 1 deficiency, MIM# 609924; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.7 AIFM1 Karina Sandoval reviewed gene: AIFM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20362274, 22019070, 26173962, 31523922, 31783324, 28299359, 25934856, 28842795, 28842795; Phenotypes: Combined oxidative phosphorylation deficiency 6, 300816, Cowchock syndrome, 310490, Deafness, X-linked 5, 300614, Spondyloepimetaphyseal dysplasia, X-linked, with hypomyelinating leukodystrophy, 300232; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cerebral vascular malformations v0.39 BRCC3 Zornitza Stark Marked gene: BRCC3 as ready
Cerebral vascular malformations v0.39 BRCC3 Zornitza Stark Gene: brcc3 has been classified as Red List (Low Evidence).
Cerebral vascular malformations v0.39 BRCC3 Zornitza Stark Publications for gene: BRCC3 were set to 21596366
Cerebral vascular malformations v0.38 BRCC3 Zornitza Stark changed review comment from: PMID 21596366: three unrelated families with multiple affected males segregating a deletion involving MTCP1 and BRCC3. Positional approach used. Supportive zebrafish model, knockdown of BRCC3; angiogenesis affected.

PMID 33868155, additional report of affected male, with similar deletion.; to: PMID 21596366: three unrelated families with multiple affected males segregating a deletion involving MTCP1 and BRCC3. Positional approach used. Supportive zebrafish model, knockdown of BRCC3; angiogenesis affected.

PMID 33868155, additional report of affected male, with similar deletion.

No reports of SNVs identified, including in ClinVar.
Cerebral vascular malformations v0.38 BRCC3 Zornitza Stark edited their review of gene: BRCC3: Changed rating: RED
Cerebral vascular malformations v0.38 BRCC3 Zornitza Stark reviewed gene: BRCC3: Rating: ; Mode of pathogenicity: None; Publications: 21596366, 33868155; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Deafness_IsolatedAndComplex v1.194 RAF1 Chirag Patel Classified gene: RAF1 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.194 RAF1 Chirag Patel Gene: raf1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.195 MAP2K1 Chirag Patel Classified gene: MAP2K1 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.195 MAP2K1 Chirag Patel Gene: map2k1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.194 BRAF Chirag Patel Classified gene: BRAF as Green List (high evidence)
Deafness_IsolatedAndComplex v1.194 BRAF Chirag Patel Gene: braf has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.194 RAF1 Chirag Patel Classified gene: RAF1 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.194 RAF1 Chirag Patel Gene: raf1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.194 RAF1 Chirag Patel Classified gene: RAF1 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.194 RAF1 Chirag Patel Gene: raf1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.193 PTPN11 Chirag Patel Classified gene: PTPN11 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.193 PTPN11 Chirag Patel Gene: ptpn11 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.193 MAP2K1 Chirag Patel gene: MAP2K1 was added
gene: MAP2K1 was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: MAP2K1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAP2K1 were set to PMID: 20301557
Phenotypes for gene: MAP2K1 were set to Noonan Syndrome with Multiple Lentigines, OMIM # 615279
Review for gene: MAP2K1 was set to GREEN
gene: MAP2K1 was marked as current diagnostic
Added comment: Established gene-disease association.
Sensorineural hearing loss is present in ~20% of 'Noonan Syndrome with Multiple Lentigines'
Sources: Literature
Deafness_IsolatedAndComplex v1.192 RAF1 Chirag Patel gene: RAF1 was added
gene: RAF1 was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: RAF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAF1 were set to PMID: 20301557
Phenotypes for gene: RAF1 were set to Noonan Syndrome with Multiple Lentigines, OMIM # 611554
Review for gene: RAF1 was set to GREEN
gene: RAF1 was marked as current diagnostic
Added comment: Established gene-disease association.
Sensorineural hearing loss is present in ~20% of 'Noonan Syndrome with Multiple Lentigines'
Sources: Literature
Deafness_IsolatedAndComplex v1.191 PTPN11 Chirag Patel gene: PTPN11 was added
gene: PTPN11 was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: PTPN11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTPN11 were set to PMID: 20301557, 32737134
Phenotypes for gene: PTPN11 were set to Noonan Syndrome with Multiple Lentigines, OMIM # 151100
Review for gene: PTPN11 was set to GREEN
gene: PTPN11 was marked as current diagnostic
Added comment: Established gene-disease association.
Sensorineural hearing loss is present in ~20% of 'Noonan Syndrome with Multiple Lentigines'
Sources: Literature
Deafness_IsolatedAndComplex v1.191 BRAF Chirag Patel gene: BRAF was added
gene: BRAF was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: BRAF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BRAF were set to PMID: 20301557
Phenotypes for gene: BRAF were set to Noonan Syndrome with Multiple Lentigines, OMIM # 613707
Review for gene: BRAF was set to GREEN
gene: BRAF was marked as current diagnostic
Added comment: Established gene-disease association.
Sensorineural hearing loss is present in ~20% of 'Noonan Syndrome with Multiple Lentigines'
Sources: Literature
Aminoacidopathy v1.81 PHGDH Zornitza Stark Classified gene: PHGDH as Green List (high evidence)
Aminoacidopathy v1.81 PHGDH Zornitza Stark Gene: phgdh has been classified as Green List (High Evidence).
Aminoacidopathy v1.80 PHYKPL Zornitza Stark Marked gene: PHYKPL as ready
Aminoacidopathy v1.80 PHYKPL Zornitza Stark Gene: phykpl has been classified as Red List (Low Evidence).
Aminoacidopathy v1.80 PHYKPL Zornitza Stark Classified gene: PHYKPL as Red List (low evidence)
Aminoacidopathy v1.80 PHYKPL Zornitza Stark Gene: phykpl has been classified as Red List (Low Evidence).
Aminoacidopathy v1.79 PRODH Zornitza Stark Marked gene: PRODH as ready
Aminoacidopathy v1.79 PRODH Zornitza Stark Gene: prodh has been classified as Green List (High Evidence).
Aminoacidopathy v1.79 PRODH Zornitza Stark Classified gene: PRODH as Green List (high evidence)
Aminoacidopathy v1.79 PRODH Zornitza Stark Gene: prodh has been classified as Green List (High Evidence).
Aminoacidopathy v1.78 PRODH2 Zornitza Stark Marked gene: PRODH2 as ready
Aminoacidopathy v1.78 PRODH2 Zornitza Stark Gene: prodh2 has been classified as Red List (Low Evidence).
Aminoacidopathy v1.78 PRODH2 Zornitza Stark Classified gene: PRODH2 as Red List (low evidence)
Aminoacidopathy v1.78 PRODH2 Zornitza Stark Gene: prodh2 has been classified as Red List (Low Evidence).
Mendeliome v1.1882 PRODH2 Zornitza Stark Marked gene: PRODH2 as ready
Mendeliome v1.1882 PRODH2 Zornitza Stark Gene: prodh2 has been classified as Red List (Low Evidence).
Mendeliome v1.1882 PRODH2 Zornitza Stark Classified gene: PRODH2 as Red List (low evidence)
Mendeliome v1.1882 PRODH2 Zornitza Stark Gene: prodh2 has been classified as Red List (Low Evidence).
Aminoacidopathy v1.77 PSAT1 Zornitza Stark Marked gene: PSAT1 as ready
Aminoacidopathy v1.77 PSAT1 Zornitza Stark Gene: psat1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.77 PSAT1 Zornitza Stark Classified gene: PSAT1 as Green List (high evidence)
Aminoacidopathy v1.77 PSAT1 Zornitza Stark Gene: psat1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.76 PSPH Zornitza Stark Marked gene: PSPH as ready
Aminoacidopathy v1.76 PSPH Zornitza Stark Gene: psph has been classified as Green List (High Evidence).
Aminoacidopathy v1.76 PSPH Zornitza Stark Classified gene: PSPH as Green List (high evidence)
Aminoacidopathy v1.76 PSPH Zornitza Stark Gene: psph has been classified as Green List (High Evidence).
Aminoacidopathy v1.75 PTS Zornitza Stark Marked gene: PTS as ready
Aminoacidopathy v1.75 PTS Zornitza Stark Gene: pts has been classified as Green List (High Evidence).
Aminoacidopathy v1.75 PTS Zornitza Stark Classified gene: PTS as Green List (high evidence)
Aminoacidopathy v1.75 PTS Zornitza Stark Gene: pts has been classified as Green List (High Evidence).
Aminoacidopathy v1.74 PYCR1 Zornitza Stark Marked gene: PYCR1 as ready
Aminoacidopathy v1.74 PYCR1 Zornitza Stark Gene: pycr1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.74 PYCR1 Zornitza Stark Classified gene: PYCR1 as Green List (high evidence)
Aminoacidopathy v1.74 PYCR1 Zornitza Stark Gene: pycr1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.73 QDPR Zornitza Stark Marked gene: QDPR as ready
Aminoacidopathy v1.73 QDPR Zornitza Stark Gene: qdpr has been classified as Green List (High Evidence).
Aminoacidopathy v1.73 QDPR Zornitza Stark Classified gene: QDPR as Green List (high evidence)
Aminoacidopathy v1.73 QDPR Zornitza Stark Gene: qdpr has been classified as Green List (High Evidence).
Aminoacidopathy v1.72 SARDH Zornitza Stark Marked gene: SARDH as ready
Aminoacidopathy v1.72 SARDH Zornitza Stark Gene: sardh has been classified as Red List (Low Evidence).
Aminoacidopathy v1.72 SARDH Zornitza Stark Classified gene: SARDH as Red List (low evidence)
Aminoacidopathy v1.72 SARDH Zornitza Stark Gene: sardh has been classified as Red List (Low Evidence).
Aminoacidopathy v1.71 SELENBP1 Zornitza Stark Marked gene: SELENBP1 as ready
Aminoacidopathy v1.71 SELENBP1 Zornitza Stark Gene: selenbp1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.71 SELENBP1 Zornitza Stark Classified gene: SELENBP1 as Green List (high evidence)
Aminoacidopathy v1.71 SELENBP1 Zornitza Stark Gene: selenbp1 has been classified as Green List (High Evidence).
Mendeliome v1.1881 SELENBP1 Zornitza Stark Marked gene: SELENBP1 as ready
Mendeliome v1.1881 SELENBP1 Zornitza Stark Gene: selenbp1 has been classified as Green List (High Evidence).
Mendeliome v1.1881 SELENBP1 Zornitza Stark Classified gene: SELENBP1 as Green List (high evidence)
Mendeliome v1.1881 SELENBP1 Zornitza Stark Gene: selenbp1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.70 SHMT2 Zornitza Stark Marked gene: SHMT2 as ready
Aminoacidopathy v1.70 SHMT2 Zornitza Stark Gene: shmt2 has been classified as Green List (High Evidence).
Aminoacidopathy v1.70 SHMT2 Zornitza Stark Classified gene: SHMT2 as Green List (high evidence)
Aminoacidopathy v1.70 SHMT2 Zornitza Stark Gene: shmt2 has been classified as Green List (High Evidence).
Aminoacidopathy v1.69 SLC1A1 Zornitza Stark Marked gene: SLC1A1 as ready
Aminoacidopathy v1.69 SLC1A1 Zornitza Stark Gene: slc1a1 has been classified as Amber List (Moderate Evidence).
Aminoacidopathy v1.69 SLC1A1 Zornitza Stark Classified gene: SLC1A1 as Amber List (moderate evidence)
Aminoacidopathy v1.69 SLC1A1 Zornitza Stark Gene: slc1a1 has been classified as Amber List (Moderate Evidence).
Aminoacidopathy v1.68 SLC1A2 Zornitza Stark Marked gene: SLC1A2 as ready
Aminoacidopathy v1.68 SLC1A2 Zornitza Stark Gene: slc1a2 has been classified as Green List (High Evidence).
Aminoacidopathy v1.68 SLC1A2 Zornitza Stark Classified gene: SLC1A2 as Green List (high evidence)
Aminoacidopathy v1.68 SLC1A2 Zornitza Stark Gene: slc1a2 has been classified as Green List (High Evidence).
Aminoacidopathy v1.67 SLC1A3 Zornitza Stark Marked gene: SLC1A3 as ready
Aminoacidopathy v1.67 SLC1A3 Zornitza Stark Gene: slc1a3 has been classified as Green List (High Evidence).
Aminoacidopathy v1.67 SLC1A3 Zornitza Stark Classified gene: SLC1A3 as Green List (high evidence)
Aminoacidopathy v1.67 SLC1A3 Zornitza Stark Gene: slc1a3 has been classified as Green List (High Evidence).
Mendeliome v1.1880 RNU4-2 Zornitza Stark Publications for gene: RNU4-2 were set to 38645094
Mendeliome v1.1879 RNU4-2 Zornitza Stark edited their review of gene: RNU4-2: Changed publications: 38991538
Intellectual disability syndromic and non-syndromic v0.6062 RNU4-2 Zornitza Stark Publications for gene: RNU4-2 were set to 38645094
Intellectual disability syndromic and non-syndromic v0.6061 RNU4-2 Zornitza Stark edited their review of gene: RNU4-2: Changed publications: 38991538
Ataxia - adult onset v1.15 FDXR Zornitza Stark Marked gene: FDXR as ready
Ataxia - adult onset v1.15 FDXR Zornitza Stark Gene: fdxr has been classified as Amber List (Moderate Evidence).
Ataxia - paediatric v1.26 FDXR Zornitza Stark Marked gene: FDXR as ready
Ataxia - paediatric v1.26 FDXR Zornitza Stark Gene: fdxr has been classified as Green List (High Evidence).
Ataxia - paediatric v1.26 FDXR Zornitza Stark Classified gene: FDXR as Green List (high evidence)
Ataxia - paediatric v1.26 FDXR Zornitza Stark Gene: fdxr has been classified as Green List (High Evidence).
Ataxia - paediatric v1.25 FDXR Zornitza Stark gene: FDXR was added
gene: FDXR was added to Ataxia - paediatric. Sources: Literature
Mode of inheritance for gene: FDXR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FDXR were set to 30250212; 28965846; 29040572; 33348459; 37046037; 37481223
Phenotypes for gene: FDXR were set to Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887
Review for gene: FDXR was set to GREEN
Added comment: Multiple reports of individuals with extra-ocular features, including ID and regression; microcephaly. Ataxia reported in multiple individuals, largely paediatric.
Sources: Literature
Ataxia - adult onset v1.15 FDXR Zornitza Stark Phenotypes for gene: FDXR were changed from Auditory neuropathy and optic atrophy, 617717 to Auditory neuropathy and optic atrophy, 617717; Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887
Ataxia - adult onset v1.14 FDXR Zornitza Stark Publications for gene: FDXR were set to
Ataxia - adult onset v1.13 FDXR Zornitza Stark Classified gene: FDXR as Amber List (moderate evidence)
Ataxia - adult onset v1.13 FDXR Zornitza Stark Gene: fdxr has been classified as Amber List (Moderate Evidence).
Ataxia - adult onset v1.12 FDXR Zornitza Stark changed review comment from: Multiple reports of individuals with extra-ocular features, including ID and regression; microcephaly. Ataxia reported in multiple individuals.; to: Multiple reports of individuals with extra-ocular features, including ID and regression; microcephaly. Ataxia reported in multiple individuals, though largely paediatric.
Ataxia - adult onset v1.12 FDXR Zornitza Stark edited their review of gene: FDXR: Added comment: Multiple reports of individuals with extra-ocular features, including ID and regression; microcephaly. Ataxia reported in multiple individuals.; Changed rating: AMBER; 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
Regression v0.556 FDXR Zornitza Stark Publications for gene: FDXR were set to 30250212
Regression v0.555 FDXR Zornitza Stark Classified gene: FDXR as Green List (high evidence)
Regression v0.555 FDXR Zornitza Stark Gene: fdxr has been classified as Green List (High Evidence).
Regression v0.554 FDXR Zornitza Stark edited their review of gene: FDXR: Added comment: Multiple reports of individuals with extra-ocular features, including ID and regression; microcephaly.; Changed rating: GREEN; 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
Mitochondrial disease v0.927 FDXR Zornitza Stark Marked gene: FDXR as ready
Mitochondrial disease v0.927 FDXR Zornitza Stark Gene: fdxr has been classified as Green List (High Evidence).
Mitochondrial disease v0.927 FDXR Zornitza Stark Phenotypes for gene: FDXR were changed from to Auditory neuropathy and optic atrophy, MIM#617717; Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887
Mitochondrial disease v0.926 FDXR Zornitza Stark Publications for gene: FDXR were set to
Mitochondrial disease v0.925 FDXR Zornitza Stark Mode of inheritance for gene: FDXR was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.924 FDXR Zornitza Stark Mode of inheritance for gene: FDXR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.923 FDXR Zornitza Stark edited their review of gene: FDXR: Added comment: Multiple reports of individuals with extra-ocular features, including ID and regression; microcephaly. Leigh-like presentation at the severe end of the spectrum.; 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
Microcephaly v1.268 FDXR Zornitza Stark Phenotypes for gene: FDXR were changed from Auditory neuropathy and optic atrophy, MIM# 617717 to Auditory neuropathy and optic atrophy, MIM# 617717; Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887
Microcephaly v1.267 FDXR Zornitza Stark Publications for gene: FDXR were set to 30250212
Microcephaly v1.266 FDXR Zornitza Stark Classified gene: FDXR as Green List (high evidence)
Microcephaly v1.266 FDXR Zornitza Stark Gene: fdxr has been classified as Green List (High Evidence).
Microcephaly v1.265 FDXR Zornitza Stark edited their review of gene: FDXR: Added comment: Multiple reports of individuals with extra-ocular features, including ID and regression; microcephaly.; Changed rating: GREEN; 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 v1.1879 FDXR Zornitza Stark Phenotypes for gene: FDXR were changed from Auditory neuropathy and optic atrophy, MIM#617717 to Auditory neuropathy and optic atrophy, MIM#617717; Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887
Mendeliome v1.1878 FDXR Zornitza Stark Publications for gene: FDXR were set to 30250212; 28965846
Intellectual disability syndromic and non-syndromic v0.6061 FDXR Zornitza Stark Publications for gene: FDXR were set to 30250212
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
Intellectual disability syndromic and non-syndromic v0.6060 FDXR Zornitza Stark Phenotypes for gene: FDXR were changed from Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887; Auditory neuropathy and optic atrophy, MIM# 617717 to Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887; Auditory neuropathy and optic atrophy, MIM# 617717
Intellectual disability syndromic and non-syndromic v0.6059 FDXR Zornitza Stark Phenotypes for gene: FDXR were changed from Auditory neuropathy and optic atrophy, MIM# 617717 to Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887; Auditory neuropathy and optic atrophy, MIM# 617717
Intellectual disability syndromic and non-syndromic v0.6058 FDXR Zornitza Stark Classified gene: FDXR as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6058 FDXR Zornitza Stark Gene: fdxr has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6057 FDXR Zornitza Stark edited their review of gene: FDXR: Added comment: Multiple reports of individuals with extra-ocular features, including ID and regression.; Changed rating: GREEN; Changed publications: 30250212, 29040572, 33348459, 37046037, 37481223; Changed phenotypes: Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887, Auditory neuropathy and optic atrophy, MIM# 617717
Prepair 1000+ v1.7 CLN5 Lauren Rogers reviewed gene: CLN5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ceroid lipofuscinosis, neuronal, 5, MIM# 256731, MONDO:0009745; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 CD40 Lauren Rogers reviewed gene: CD40: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency with hyper-IgM, type 3, MIM# 606843; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 CD3D Lauren Rogers reviewed gene: CD3D: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency 19, severe combined MIM# 615617; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 BBS12 Lauren Rogers reviewed gene: BBS12: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Bardet-Biedl syndrome 12, MIM# 615989; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 BBS1 Lauren Rogers reviewed gene: BBS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20177705, 15637713; Phenotypes: Bardet-Biedl syndrome 1, MIM# 209900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 ATP6V1B1 Lauren Rogers reviewed gene: ATP6V1B1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Distal renal tubular acidosis 2 with progressive sensorineural hearing loss, MIM# 267300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 ARL6 Lauren Rogers reviewed gene: ARL6: Rating: ; Mode of pathogenicity: None; Publications: 15258860, 32361989, 31888296, 25402481, 31736247, 19858128; Phenotypes: Bardet-Biedl syndrome 3, MIM# 600151; Mode of inheritance: None
Prepair 1000+ v1.7 ANTXR2 Lauren Rogers reviewed gene: ANTXR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 12973667, 14508707; Phenotypes: Hyaline fibromatosis syndrome, MIM# 228600, MONDO:0009229; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 ALOX12B Lauren Rogers reviewed gene: ALOX12B: Rating: GREEN; Mode of pathogenicity: None; Publications: 16116617, 11773004; Phenotypes: Ichthyosis, congenital, autosomal recessive 2, MIM# 242100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 ADPRHL2 Karina Sandoval reviewed gene: ADPRHL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30100084, 30401461, 35664652; Phenotypes: Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures (MIM#618170); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 ALMS1 Lauren Rogers reviewed gene: ALMS1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Alstrom syndrome, MIM# 203800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 AAAS Lauren Rogers reviewed gene: AAAS: Rating: GREEN; Mode of pathogenicity: None; Publications: 29255950; Phenotypes: Achalasia-addisonianism-alacrimia syndrome, MIM#231550; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 ACAD9 Karina Sandoval reviewed gene: ACAD9: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:30025539, 26475292; Phenotypes: Mitochondrial complex I deficiency, nuclear type 20 (MIM#611126); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 ABCA12 Karina Sandoval reviewed gene: ABCA12: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31168818, 19664001, 31489029; Phenotypes: Ichthyosis, congenital, autosomal recessive 4A (MIM#601277), Ichthyosis, congenital, autosomal recessive 4B (harlequin) (MIM#242500); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rhabdomyolysis and Metabolic Myopathy v1.6 SLC25A32 Bryony Thompson Marked gene: SLC25A32 as ready
Rhabdomyolysis and Metabolic Myopathy v1.6 SLC25A32 Bryony Thompson Gene: slc25a32 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v1.6 SLC25A32 Bryony Thompson Classified gene: SLC25A32 as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v1.6 SLC25A32 Bryony Thompson Gene: slc25a32 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v1.5 SLC25A32 Bryony Thompson gene: SLC25A32 was added
gene: SLC25A32 was added to Rhabdomyolysis and Metabolic Myopathy. Sources: Literature
Mode of inheritance for gene: SLC25A32 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A32 were set to 26933868; 35727412; 34764427; 28443623
Phenotypes for gene: SLC25A32 were set to Exercise intolerance, riboflavin-responsive MONDO:0014795
Review for gene: SLC25A32 was set to GREEN
Added comment: 5 cases with MADD from 4 unrelated families (4 homozygotes & 1 chet) and a supporting mouse model. At least 2 cases and the mouse model had exercise intolerance.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6057 RNU4-2 Zornitza Stark Phenotypes for gene: RNU4-2 were changed from Neurodevelopmental disorder, MONDO:0700092, RNU4-2 related to Neurodevelopmental disorder with hypotonia, brain anomalies, distinctive facies, and absent language, MIM# 620851
Intellectual disability syndromic and non-syndromic v0.6056 RNU4-2 Zornitza Stark edited their review of gene: RNU4-2: Changed phenotypes: Neurodevelopmental disorder with hypotonia, brain anomalies, distinctive facies, and absent language, MIM# 620851
Mendeliome v1.1877 RNU4-2 Zornitza Stark Phenotypes for gene: RNU4-2 were changed from Neurodevelopmental disorder, MONDO:0700092, RNU4-2 related to Neurodevelopmental disorder with hypotonia, brain anomalies, distinctive facies, and absent language, MIM# 620851
Mendeliome v1.1876 RNU4-2 Zornitza Stark edited their review of gene: RNU4-2: Changed phenotypes: Neurodevelopmental disorder with hypotonia, brain anomalies, distinctive facies, and absent language, MIM# 620851
Speech apraxia v1.0 Zornitza Stark promoted panel to version 1.0
Aminoacidopathy v1.66 SLC1A3 Sangavi Sivagnanasundram gene: SLC1A3 was added
gene: SLC1A3 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SLC1A3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC1A3 were set to 27829685, 16116111, 29062094, 19139306, 29208948, 29066757, 32754645, 25497598
Phenotypes for gene: SLC1A3 were set to episodic ataxia type 6 MONDO:0012982
Mode of pathogenicity for gene: SLC1A3 was set to Other
Review for gene: SLC1A3 was set to GREEN
Added comment: Variants reported in 8 unrelated probands with reported errors in glutamate metabolism. Mechanism of disease varies depending on the mutation. The most severe variants (p.M128R, p.P290R, and p.T318A) appear to have gain of function mechanism.

Classified as Definitive by ClinGen Aminoacidopathy GCEP on 09/10/2020
https://search.clinicalgenome.org/CCID:006154
Sources: ClinGen
Aminoacidopathy v1.66 SLC1A2 Sangavi Sivagnanasundram gene: SLC1A2 was added
gene: SLC1A2 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SLC1A2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC1A2 were set to 23934111; 27476654; 28777935; 30937933
Phenotypes for gene: SLC1A2 were set to developmental and epileptic encephalopathy, 41 MONDO:0014916
Review for gene: SLC1A2 was set to GREEN
Added comment: Reported variants in 6 unrelated probands. The mechanism of disease is heterozygous dominant negative.

Classified as Definitive by ClinGen Aminoacidopathy GCEP on 29/10/2020
https://search.clinicalgenome.org/CCID:006153
Sources: ClinGen
Aminoacidopathy v1.66 SLC1A1 Sangavi Sivagnanasundram gene: SLC1A1 was added
gene: SLC1A1 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SLC1A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC1A1 were set to 21123949
Phenotypes for gene: SLC1A1 were set to dicarboxylic aminoaciduria MONDO:0009110
Review for gene: SLC1A1 was set to AMBER
Added comment: Reported in 2 unrelated probands along with a mouse knockout model recapitulating human phenotype.

Classified as Limited by ClinGen Aminoacidopathy GCEP on 12/12/2022
https://search.clinicalgenome.org/CCID:006152
Sources: ClinGen
Aminoacidopathy v1.66 SHMT2 Sangavi Sivagnanasundram gene: SHMT2 was added
gene: SHMT2 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SHMT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SHMT2 were set to 33015733; 35398349; 29323231
Phenotypes for gene: SHMT2 were set to neurodevelopmental disorder with cardiomyopathy, spasticity, and brain abnormalities MONDO:0030866
Review for gene: SHMT2 was set to GREEN
Added comment: Reported in 5 unrelated probands with abnormal biochemical function.

Classified as Moderate by ClinGen Aminoacidopathy GCEP on 11/11/2022
https://search.clinicalgenome.org/CCID:006136
Sources: ClinGen
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
Aminoacidopathy v1.66 SELENBP1 Sangavi Sivagnanasundram gene: SELENBP1 was added
gene: SELENBP1 was added to Aminoacidopathy. 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
Aminoacidopathy v1.66 SARDH Sangavi Sivagnanasundram gene: SARDH was added
gene: SARDH was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SARDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SARDH were set to 22825317
Phenotypes for gene: SARDH were set to sarcosinemia MONDO:0010008
Review for gene: SARDH was set to RED
Added comment: The clinical phenotypes vary and sarcosinemia is considered a benign condition.

Classified as Limited by ClinGen Aminoacidopathy GCEP on 12/12/2022
https://search.clinicalgenome.org/CCID:006052
Sources: ClinGen
Aminoacidopathy v1.66 QDPR Sangavi Sivagnanasundram gene: QDPR was added
gene: QDPR was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: QDPR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: QDPR were set to 14114862; 3033643; 11153907; 9341885; 19099731
Phenotypes for gene: QDPR were set to dihydropteridine reductase deficiency MONDO:0009862
Review for gene: QDPR was set to GREEN
Added comment: Well established gene disease association. LoF is a mechanism of disease.

Classified as Definitive by ClinGen Aminoacidopathy GCEP on 18/06/2018
https://search.clinicalgenome.org/CCID:005939
Sources: ClinGen
Aminoacidopathy v1.66 PYCR1 Sangavi Sivagnanasundram gene: PYCR1 was added
gene: PYCR1 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: PYCR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PYCR1 were set to 19576563; 19648921
Phenotypes for gene: PYCR1 were set to autosomal recessive cutis laxa type 2B MONDO:0013051
Review for gene: PYCR1 was set to GREEN
Added comment: Established gene disease association with reported individuals having an inborn error of proline metabolism.

Classified as Definitive by ClinGen Aminoacidopathy GCEP on 21/05/2020
https://search.clinicalgenome.org/CCID:005936
Sources: ClinGen
Aminoacidopathy v1.66 PTS Sangavi Sivagnanasundram gene: PTS was added
gene: PTS was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: PTS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTS were set to 22729819; 21542064; 20059486
Phenotypes for gene: PTS were set to BH4-deficient hyperphenylalaninemia A MONDO:0009863
Review for gene: PTS was set to GREEN
Added comment: Well established gene-disease association. >5 unrelated individuals reported with a biochemical phenotype. LoF is the mechanism of disease.

Classified as Definitive by ClinGen Aminoacidopathy GCEP on 22/12/2017
https://search.clinicalgenome.org/CCID:005931
Sources: ClinGen
Aminoacidopathy v1.66 PSPH Sangavi Sivagnanasundram gene: PSPH was added
gene: PSPH was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: PSPH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSPH were set to 26589312, 25080166, 14673469; 27604308; 26888760; 25152457
Phenotypes for gene: PSPH were set to neurometabolic disorder due to serine deficiency MONDO:0018162
Review for gene: PSPH was set to GREEN
Added comment: Established gene disease assocation. Reported in >5 unrelated individuals with biochemical phenotypes.
Classified as Moderate by ClinGen Aminoacidopathy GCEP on 12/12/2022
https://search.clinicalgenome.org/CCID:005917
Sources: ClinGen
Aminoacidopathy v1.66 PSAT1 Sangavi Sivagnanasundram gene: PSAT1 was added
gene: PSAT1 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: PSAT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSAT1 were set to 26610677; 12633500; 27626380; 32077105
Phenotypes for gene: PSAT1 were set to neurometabolic disorder due to serine deficiency MONDO:0018162
Review for gene: PSAT1 was set to GREEN
Added comment: Well established gene disease association with reported individuals having errors in serine deficiency. Severity of the condition depends on the residual enzyme activity.

Classified as Definitive by ClinGen Aminoacidopathy GCEP on 29/06/2020
https://search.clinicalgenome.org/CCID:005912
Sources: ClinGen
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
Aminoacidopathy v1.66 PRODH2 Sangavi Sivagnanasundram gene: PRODH2 was added
gene: PRODH2 was added to Aminoacidopathy. 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
Aminoacidopathy v1.66 PRODH Sangavi Sivagnanasundram gene: PRODH was added
gene: PRODH was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: PRODH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRODH were set to 12217952
Phenotypes for gene: PRODH were set to hyperprolinemia type 1 MONDO:0009400
Review for gene: PRODH was set to GREEN
Added comment: Well established gene disease association with reported individuals having an inborn error of proline metabolism.
Reported affected individuals have reported 2-10 times the normal plasma proline level.

Classified as Moderate by ClinGen Aminoacidopathy GCEP on 27/04/2021
https://search.clinicalgenome.org/CCID:005892
Sources: ClinGen
Aminoacidopathy v1.66 PHYKPL Sangavi Sivagnanasundram gene: PHYKPL was added
gene: PHYKPL was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: PHYKPL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PHYKPL were set to 23242558
Phenotypes for gene: PHYKPL were set to phosphohydroxylysinuria MONDO:0014008
Review for gene: PHYKPL was set to RED
Added comment: Chet individual reported with variants in this gene and a phenotype similar to EDS. This individual was not reported to any metabolic phenotype. No other reports published at this stage to support gene-disease association.

Classified as Limitied by ClinGen Aminoacidopathy GCEP on 17/11/2023
https://search.clinicalgenome.org/CCID:005792
Sources: ClinGen
Aminoacidopathy v1.66 PHGDH Sangavi Sivagnanasundram gene: PHGDH was added
gene: PHGDH was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: PHGDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PHGDH were set to 37347880; 19235232; 24836451; 28440900; 22393170; 25913727
Phenotypes for gene: PHGDH were set to neurometabolic disorder due to serine deficiency MONDO:0018162
Review for gene: PHGDH was set to GREEN
Added comment: Established gene-disease association. >10 unrelated probands reported with an inborn error of serine deficiency. LoF is the mechanism of disease (PMID: 37347880).

Classified as Definitive by ClinGen Aminoacidopathy GCEP on 29/06/2020
https://search.clinicalgenome.org/CCID:005786
Sources: ClinGen
Aminoacidopathy v1.66 PCBD1 Sangavi Sivagnanasundram gene: PCBD1 was added
gene: PCBD1 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: PCBD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCBD1 were set to 19234759
Phenotypes for gene: PCBD1 were set to pterin-4 alpha-carbinolamine dehydratase 1 deficiency MONDO:0009908
Review for gene: PCBD1 was set to GREEN
Added comment: Well established gene disease association with affected individuals having a transient hyperphenylalaninemia phenotype.

Mechanism of disease appears to be a defect in BH4 regeneration leading to an excess build up of phenylalanine and primapterim levels in blood, urine and tissues (PMID: 19234759)

Classified as Definitive by ClinGen Aminoacidopathy GCEP on 27/07/2021
https://search.clinicalgenome.org/CCID:005739
Sources: ClinGen
Aminoacidopathy v1.66 PAH Sangavi Sivagnanasundram gene: PAH was added
gene: PAH was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: PAH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PAH were set to 1301187, 13138177
Phenotypes for gene: PAH were set to phenylketonuria MONDO:0009861
Review for gene: PAH was set to GREEN
Added comment: Well-established gene-disease association. Affected individuals reported to have an inborn error of phenylalanine metabolism. LoF is the established mechanism of disease (PMID:1301187).

Classified as Definitive by ClinGen Aminoacidopathy GCEP on 24/04/2020
https://search.clinicalgenome.org/CCID:005722
Sources: ClinGen
Aminoacidopathy v1.66 OTC Sangavi Sivagnanasundram gene: OTC was added
gene: OTC was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: OTC 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: OTC were set to 26059767
Phenotypes for gene: OTC were set to ornithine carbamoyltransferase deficiency MONDO:0010703
Review for gene: OTC was set to GREEN
Added comment: Well established gene-disease association where affected individuals have a deficiency in carbamoyltransferase which affects the urea cycle.

Classified as Definitive by ClinGen Aminoacidopathy GCEP on 29/10/2019
https://search.clinicalgenome.org/CCID:005712
Sources: Other
Pulmonary Fibrosis_Interstitial Lung Disease v0.57 COPA Zornitza Stark Marked gene: COPA as ready
Pulmonary Fibrosis_Interstitial Lung Disease v0.57 COPA Zornitza Stark Gene: copa has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.57 COPA Zornitza Stark Phenotypes for gene: COPA were changed from COPA syndrome - autoimmune disorder associated with childhood interstitial lung disease and pulmonary haemorrhage, arthritis, and kidney disease to Autoimmune interstitial lung, joint, and kidney disease, MIM# 616414
Mendeliome v1.1876 GAS2 Zornitza Stark Marked gene: GAS2 as ready
Mendeliome v1.1876 GAS2 Zornitza Stark Gene: gas2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1876 GAS2 Zornitza Stark Classified gene: GAS2 as Amber List (moderate evidence)
Mendeliome v1.1876 GAS2 Zornitza Stark Gene: gas2 has been classified as Amber List (Moderate Evidence).
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
Deafness_IsolatedAndComplex v1.190 GAS2 Zornitza Stark Marked gene: GAS2 as ready
Deafness_IsolatedAndComplex v1.190 GAS2 Zornitza Stark Gene: gas2 has been classified as Amber List (Moderate Evidence).
Deafness_IsolatedAndComplex v1.190 GAS2 Zornitza Stark Classified gene: GAS2 as Amber List (moderate evidence)
Deafness_IsolatedAndComplex v1.190 GAS2 Zornitza Stark Gene: gas2 has been classified as Amber List (Moderate Evidence).
Deafness_IsolatedAndComplex v1.189 GAS2 Zornitza Stark gene: GAS2 was added
gene: GAS2 was added to Deafness_IsolatedAndComplex. 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
Deafness_Isolated v1.63 GAS2 Zornitza Stark Marked gene: GAS2 as ready
Deafness_Isolated v1.63 GAS2 Zornitza Stark Gene: gas2 has been classified as Amber List (Moderate Evidence).
Deafness_Isolated v1.63 GAS2 Zornitza Stark Classified gene: GAS2 as Amber List (moderate evidence)
Deafness_Isolated v1.63 GAS2 Zornitza Stark Gene: gas2 has been classified as Amber List (Moderate Evidence).
Deafness_Isolated v1.62 GAS2 Zornitza Stark gene: GAS2 was added
gene: GAS2 was added to Deafness_Isolated. 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
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
Hereditary Spastic Paraplegia - adult onset v1.11 KIF1A Zornitza Stark Phenotypes for gene: KIF1A were changed from Spastic paraplegia 30, autosomal recessive, 610357 to Spastic paraplegia 30, autosomal dominant MIM# 610357; Spastic paraplegia 30, autosomal recessive 620607
Hereditary Spastic Paraplegia - adult onset v1.10 KIF1A Zornitza Stark edited their review of gene: KIF1A: Changed phenotypes: Spastic paraplegia 30, autosomal dominant MIM# 610357, Spastic paraplegia 30, autosomal recessive 620607
Hereditary Spastic Paraplegia - paediatric v1.76 KIF1A Zornitza Stark Phenotypes for gene: KIF1A were changed from Spastic paraplegia 30, MIM# 610357 to Spastic paraplegia 30, autosomal dominant MIM# 610357; Spastic paraplegia 30, autosomal recessive 620607
Hereditary Spastic Paraplegia - paediatric v1.75 KIF1A Zornitza Stark edited their review of gene: KIF1A: Changed phenotypes: Spastic paraplegia 30, autosomal dominant MIM# 610357, Spastic paraplegia 30, autosomal recessive 620607
Pulmonary Fibrosis_Interstitial Lung Disease v0.56 COPA Chirag Patel Classified gene: COPA as Green List (high evidence)
Pulmonary Fibrosis_Interstitial Lung Disease v0.56 COPA Chirag Patel Gene: copa has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.55 COPA Chirag Patel gene: COPA was added
gene: COPA was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Expert list
Mode of inheritance for gene: COPA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COPA were set to PMID: 27048656, 30385646, 30804679, 29977900
Phenotypes for gene: COPA were set to COPA syndrome - autoimmune disorder associated with childhood interstitial lung disease and pulmonary haemorrhage, arthritis, and kidney disease
Review for gene: COPA was set to GREEN
gene: COPA was marked as current diagnostic
Added comment: Over 10 unrelated families reported.
Well-established gene-disease association.
Sources: Expert list
Ichthyosis v1.11 SREBF2 Zornitza Stark Marked gene: SREBF2 as ready
Ichthyosis v1.11 SREBF2 Zornitza Stark Gene: srebf2 has been classified as Amber List (Moderate Evidence).
Ichthyosis v1.11 SREBF2 Zornitza Stark Classified gene: SREBF2 as Amber List (moderate evidence)
Ichthyosis v1.11 SREBF2 Zornitza Stark Gene: srebf2 has been classified as Amber List (Moderate Evidence).
Ichthyosis v1.10 SREBF2 Zornitza Stark gene: SREBF2 was added
gene: SREBF2 was added to Ichthyosis. 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
Intellectual disability syndromic and non-syndromic v0.6056 SREBF2 Zornitza Stark Marked gene: SREBF2 as ready
Intellectual disability syndromic and non-syndromic v0.6056 SREBF2 Zornitza Stark Gene: srebf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6056 SREBF2 Zornitza Stark Classified gene: SREBF2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.6056 SREBF2 Zornitza Stark Gene: srebf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6055 SREBF2 Zornitza Stark gene: SREBF2 was added
gene: SREBF2 was added to Intellectual disability syndromic and non-syndromic. 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
Mendeliome v1.1873 SREBF2 Zornitza Stark Marked gene: SREBF2 as ready
Mendeliome v1.1873 SREBF2 Zornitza Stark Gene: srebf2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1873 SREBF2 Zornitza Stark Classified gene: SREBF2 as Amber List (moderate evidence)
Mendeliome v1.1873 SREBF2 Zornitza Stark Gene: srebf2 has been classified as Amber List (Moderate Evidence).
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
Genetic Epilepsy v1.33 USP25 Zornitza Stark Classified gene: USP25 as Green List (high evidence)
Genetic Epilepsy v1.33 USP25 Zornitza Stark Gene: usp25 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.32 USP25 Zornitza Stark gene: USP25 was added
gene: USP25 was added to Genetic Epilepsy. Sources: Literature
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 Epilepsy, idiopathic generalized, MONDO:0005579, USP25-related
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: Literature
Mendeliome v1.1871 USP25 Zornitza Stark Marked gene: USP25 as ready
Mendeliome v1.1871 USP25 Zornitza Stark Gene: usp25 has been classified as Green List (High Evidence).
Mendeliome v1.1871 USP25 Zornitza Stark Classified gene: USP25 as Green List (high evidence)
Mendeliome v1.1871 USP25 Zornitza Stark Gene: usp25 has been classified as Green List (High Evidence).
Familial Generalised Epilepsy v0.14 USP25 Zornitza Stark Marked gene: USP25 as ready
Familial Generalised Epilepsy v0.14 USP25 Zornitza Stark Gene: usp25 has been classified as Green List (High Evidence).
Familial Generalised Epilepsy v0.14 USP25 Zornitza Stark Classified gene: USP25 as Green List (high evidence)
Familial Generalised Epilepsy v0.14 USP25 Zornitza Stark Gene: usp25 has been classified as Green List (High Evidence).
Mendeliome v1.1870 C10orf71 Zornitza Stark Marked gene: C10orf71 as ready
Mendeliome v1.1870 C10orf71 Zornitza Stark Gene: c10orf71 has been classified as Green List (High Evidence).
Mendeliome v1.1870 C10orf71 Zornitza Stark Classified gene: C10orf71 as Green List (high evidence)
Mendeliome v1.1870 C10orf71 Zornitza Stark Gene: c10orf71 has been classified as Green List (High Evidence).
Dilated Cardiomyopathy v1.31 C10orf71 Zornitza Stark Marked gene: C10orf71 as ready
Dilated Cardiomyopathy v1.31 C10orf71 Zornitza Stark Gene: c10orf71 has been classified as Green List (High Evidence).
Dilated Cardiomyopathy v1.31 C10orf71 Zornitza Stark Classified gene: C10orf71 as Green List (high evidence)
Dilated Cardiomyopathy v1.31 C10orf71 Zornitza Stark Gene: c10orf71 has been classified as Green List (High Evidence).
Mendeliome v1.1869 PSMC5 Zornitza Stark Phenotypes for gene: PSMC5 were changed from Developmental disorders to Neurodevelopmental disorder (MONDO#0700092), PSMC5-related
Mendeliome v1.1868 PSMC5 Zornitza Stark Publications for gene: PSMC5 were set to 33057194
Mendeliome v1.1867 PSMC5 Zornitza Stark Classified gene: PSMC5 as Green List (high evidence)
Mendeliome v1.1867 PSMC5 Zornitza Stark Gene: psmc5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6054 PSMC5 Zornitza Stark Phenotypes for gene: PSMC5 were changed from Developmental disorders to Neurodevelopmental disorder (MONDO#0700092), PSMC5-related
Intellectual disability syndromic and non-syndromic v0.6053 PSMC5 Zornitza Stark Classified gene: PSMC5 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6053 PSMC5 Zornitza Stark Gene: psmc5 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v2.3 PSMF1 Zornitza Stark Marked gene: PSMF1 as ready
Early-onset Parkinson disease v2.3 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v2.3 PSMF1 Zornitza Stark Classified gene: PSMF1 as Green List (high evidence)
Early-onset Parkinson disease v2.3 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v2.2 PSMF1 Zornitza Stark gene: PSMF1 was added
gene: PSMF1 was added to Early-onset Parkinson disease. 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
Fetal anomalies v1.255 PSMF1 Zornitza Stark Marked gene: PSMF1 as ready
Fetal anomalies v1.255 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Green List (High Evidence).
Fetal anomalies v1.255 PSMF1 Zornitza Stark Classified gene: PSMF1 as Green List (high evidence)
Fetal anomalies v1.255 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Green List (High Evidence).
Fetal anomalies v1.254 PSMF1 Zornitza Stark gene: PSMF1 was added
gene: PSMF1 was added to Fetal anomalies. 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
Arthrogryposis v0.411 PSMF1 Zornitza Stark Marked gene: PSMF1 as ready
Arthrogryposis v0.411 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Green List (High Evidence).
Arthrogryposis v0.411 PSMF1 Zornitza Stark Classified gene: PSMF1 as Green List (high evidence)
Arthrogryposis v0.411 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Green List (High Evidence).
Arthrogryposis v0.410 PSMF1 Zornitza Stark gene: PSMF1 was added
gene: PSMF1 was added to Arthrogryposis. Sources: Expert list
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: Expert list
Mendeliome v1.1866 PSMF1 Zornitza Stark Marked gene: PSMF1 as ready
Mendeliome v1.1866 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Green List (High Evidence).
Mendeliome v1.1866 PSMF1 Zornitza Stark Classified gene: PSMF1 as Green List (high evidence)
Mendeliome v1.1866 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Green List (High Evidence).
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
Intellectual disability syndromic and non-syndromic v0.6052 PSMF1 Zornitza Stark Marked gene: PSMF1 as ready
Intellectual disability syndromic and non-syndromic v0.6052 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6052 PSMF1 Zornitza Stark Classified gene: PSMF1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6052 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6051 PSMF1 Zornitza Stark gene: PSMF1 was added
gene: PSMF1 was added to Intellectual disability syndromic and non-syndromic. 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
Regression v0.554 PSMF1 Zornitza Stark Classified gene: PSMF1 as Green List (high evidence)
Regression v0.554 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Green List (High Evidence).
Regression v0.553 PSMF1 Zornitza Stark Classified gene: PSMF1 as Green List (high evidence)
Regression v0.553 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Green List (High Evidence).
Regression v0.552 PSMF1 Zornitza Stark Marked gene: PSMF1 as ready
Regression v0.552 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Red List (Low Evidence).
Regression v0.552 PSMF1 Zornitza Stark gene: PSMF1 was added
gene: PSMF1 was added to Regression. 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
Severe Combined Immunodeficiency (absent T present B cells) v1.6 POLD3 Zornitza Stark Phenotypes for gene: POLD3 were changed from Severe combined immunodeficiency MONDO:0015974 to Immunodeficiency 122, MIM# 620869
Severe Combined Immunodeficiency (absent T present B cells) v1.5 POLD3 Zornitza Stark Publications for gene: POLD3 were set to 37030525; 36395985; 27524497
Severe Combined Immunodeficiency (absent T present B cells) v1.4 POLD3 Zornitza Stark Classified gene: POLD3 as Green List (high evidence)
Severe Combined Immunodeficiency (absent T present B cells) v1.4 POLD3 Zornitza Stark Gene: pold3 has been classified as Green List (High Evidence).
Severe Combined Immunodeficiency (absent T present B cells) v1.3 POLD3 Zornitza Stark reviewed gene: POLD3: Rating: GREEN; Mode of pathogenicity: None; Publications: 38099988; Phenotypes: Immunodeficiency 122, MIM# 620869; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1864 POLD3 Zornitza Stark Phenotypes for gene: POLD3 were changed from Severe combined immunodeficiency MONDO:0015974 to Immunodeficiency 122, MIM# 620869
Mendeliome v1.1863 POLD3 Zornitza Stark Publications for gene: POLD3 were set to 37030525; 36395985; 27524497
Mendeliome v1.1862 POLD3 Zornitza Stark Classified gene: POLD3 as Green List (high evidence)
Mendeliome v1.1862 POLD3 Zornitza Stark Gene: pold3 has been classified as Green List (High Evidence).
Mendeliome v1.1861 POLD3 Zornitza Stark reviewed gene: POLD3: Rating: GREEN; Mode of pathogenicity: None; Publications: 38099988; Phenotypes: Immunodeficiency 122, MIM# 620869; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.418 ALDH1A2 Gina Ravenscroft commented on gene: ALDH1A2
Calcium and Phosphate disorders v1.24 SGK3 Bryony Thompson Marked gene: SGK3 as ready
Calcium and Phosphate disorders v1.24 SGK3 Bryony Thompson Gene: sgk3 has been classified as Red List (Low Evidence).
Calcium and Phosphate disorders v1.24 SGK3 Bryony Thompson gene: SGK3 was added
gene: SGK3 was added to Calcium and Phosphate disorders. Sources: Literature
Mode of inheritance for gene: SGK3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SGK3 were set to 31821448; 21451460
Phenotypes for gene: SGK3 were set to Hypophosphatemic rickets
Review for gene: SGK3 was set to RED
Added comment: SGK3 c.979-96T>A reported to segregate in the single family is more common in gnomAD v4.1 than expected for a dominant disease: global allele frequency of 0.004729 (0.5%, 5,882/1,243,870 alleles, 27 homozygotes in gnomAD v4.1).
A knockout mouse model had decreased bone density and increased phosphaturia.
Sources: Literature
Mendeliome v1.1861 TUBA4A Bryony Thompson Classified gene: TUBA4A as Green List (high evidence)
Mendeliome v1.1861 TUBA4A Bryony Thompson Gene: tuba4a has been classified as Green List (High Evidence).
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
Motor Neurone Disease v1.24 TUBA4A Bryony Thompson Publications for gene: TUBA4A were set to 25374358; 25893256; 28069311; 38463699; 38884572; 26675813
Motor Neurone Disease v1.23 TUBA4A Bryony Thompson Publications for gene: TUBA4A were set to 28069311; 25374358; 26675813
Motor Neurone Disease v1.22 TUBA4A Bryony Thompson Classified gene: TUBA4A as Green List (high evidence)
Motor Neurone Disease v1.22 TUBA4A Bryony Thompson Gene: tuba4a has been classified as Green List (High Evidence).
Motor Neurone Disease v1.21 TUBA4A Bryony Thompson edited their review of gene: TUBA4A: Added comment: At least 13 probands reported with ALS or phenotype including motor neurone involvement. Limited segregation evidence and mechanism of disease not established - toxic gain of function, dominant negative, or loss of function suggested
PMID: 25374358 - 7 rare TUBA4A variants OR = 36 [95% CI: 10–210], p = 4.3 × 10−7, Pcorrected = 4.2 × 10−3 in an FALS cohort. Included 1 nonsense (W407X in last exon) and 6 missense variants. FALS cases n=635, controls n=5,510. T145P variant segregated with disease within the family, while K430N was not detected in an affected first cousin of the sequenced proband (?phenocopy). Functional analyses revealed that TUBA4A mutants destabilize the microtubule network, diminishing its repolymerization capability - suggesting a dominant negative mechanism of disease.
PMID: 25893256 - 4 Italian sporadic ALS cases with rare TUBA4A variants (3 missense & 1 splice variant). Minigene assay demonstrates c.226+4A>G causes exon 2 skipping which is expected to a frameshift and NMD. Loss of function is not an established mechanism of ALS in relation to TUBA4A.
PMID: 28069311 - rare missense (Thr381Met) detected in 2 siblings with ALS, but both had the C9orf72 expansion
PMID: 38463699 - reduced TUBA4A protein expression in familial and sporadic ALS brain tissue. Knockout zebrafish has a motor axonopathy and motor behavior defects reflecting a motor neuron disease phenotype
PMID: 38884572 - Multicentre cohort of 12 patients from 11 unrelated families presenting with ataxia age of onset 2-60 yrs (9 different missense variants). Amyotrophy or upper limb muscular weakness in 2/12, 16.6%.; Changed rating: GREEN; Changed publications: 25374358, 25893256, 28069311, 38463699, 38884572; Changed phenotypes: amyotrophic lateral sclerosis type 22 MONDO:0014531; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v1.24 TUBA4A Bryony Thompson Publications for gene: TUBA4A were set to 28069311; 25374358; 26675813
Early-onset Dementia v1.23 TUBA4A Bryony Thompson edited their review of gene: TUBA4A: Changed phenotypes: Inherited neurodegenerative disorder MONDO:0024237, TUBA4A-related
Early-onset Dementia v1.23 TUBA4A Bryony Thompson Classified gene: TUBA4A as Green List (high evidence)
Early-onset Dementia v1.23 TUBA4A Bryony Thompson Gene: tuba4a has been classified as Green List (High Evidence).
Early-onset Dementia v1.22 TUBA4A Bryony Thompson reviewed gene: TUBA4A: Rating: GREEN; Mode of pathogenicity: None; Publications: 25374358, 28069311, 35327632, 34169147, 38884572, 33760283; Phenotypes: amyotrophic lateral sclerosis type 22 MONDO:0014531; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Speech apraxia v0.39 KAT6A Thomas Scerri changed review comment from: First reported CAS case with a KAT6A splice acceptor variant (Eising et al., 2019; PMID: 29463886).

Kennedy et al. (2019; PMID: 30245513) examined 76 cases (including 52 new cases) with KAT6A variants and found speech delay was a core feature, and report 1 case diagnosed with oromotor dyspraxia.

St John et al. (2022; PMID: 35892268) examined 49 cases with KAT6A variants and found "Verbal participants (13/49) displayed complex and co-occurring speech diagnoses regarding the perception/production of speech sounds, including phonological impairment (i.e., linguistic deficits) and speech apraxia (i.e., motor planning/programming deficits), which significantly impacted intelligibility. Receptive/expressive language and adaptive functioning were also severely impaired." In detail, "Across the 13 verbal participants, speech profiles, and intelligibility were varied (Table 2). 10/13 verbal participants were female (77%). 11/13 had delayed speech milestones, some not achieving first words until >18 months and others not combining words until >8 years of age. Verbal participants had a range of speech disorder subtypes, and most had at least two diagnoses (Figure 1c). Phonological delay was most common (8/13, 63%), followed by phonological disorder (7/13, 54%) and CAS (7/13, 54%), but all three conditions always co-occurred with at least one other speech diagnosis. "


Sources: Expert list, Expert Review; to: First reported CAS case with a KAT6A splice acceptor variant (Eising et al., 2019; PMID: 29463886).

Kennedy et al. (2019; PMID: 30245513) examined 76 cases (including 52 new cases) with KAT6A variants and found speech delay was a core feature.

St John et al. (2022; PMID: 35892268) examined 49 cases with KAT6A variants and found "Verbal participants (13/49) displayed complex and co-occurring speech diagnoses regarding the perception/production of speech sounds, including phonological impairment (i.e., linguistic deficits) and speech apraxia (i.e., motor planning/programming deficits), which significantly impacted intelligibility. Receptive/expressive language and adaptive functioning were also severely impaired." In detail, "Across the 13 verbal participants, speech profiles, and intelligibility were varied (Table 2). 10/13 verbal participants were female (77%). 11/13 had delayed speech milestones, some not achieving first words until >18 months and others not combining words until >8 years of age. Verbal participants had a range of speech disorder subtypes, and most had at least two diagnoses (Figure 1c). Phonological delay was most common (8/13, 63%), followed by phonological disorder (7/13, 54%) and CAS (7/13, 54%), but all three conditions always co-occurred with at least one other speech diagnosis. "


Sources: Expert list, Expert Review
Hereditary Spastic Paraplegia - paediatric v1.75 TUBA4A Bryony Thompson Marked gene: TUBA4A as ready
Hereditary Spastic Paraplegia - paediatric v1.75 TUBA4A Bryony Thompson Gene: tuba4a has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v1.75 TUBA4A Bryony Thompson Classified gene: TUBA4A as Green List (high evidence)
Hereditary Spastic Paraplegia - paediatric v1.75 TUBA4A Bryony Thompson Gene: tuba4a has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v1.74 TUBA4A Bryony Thompson gene: TUBA4A was added
gene: TUBA4A was added to Hereditary Spastic Paraplegia - paediatric. Sources: Literature
Mode of inheritance for gene: TUBA4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBA4A were set to 38884572; 37418012
Phenotypes for gene: TUBA4A were set to Hereditary ataxia MONDO:0100309, TUBA4A-related
Mode of pathogenicity for gene: TUBA4A was set to Other
Review for gene: TUBA4A was set to GREEN
Added comment: PMID: 38884572 - Multicentre cohort of 12 patients from 11 unrelated families presenting with ataxia age of onset 2-60 yrs (9 different missense variants). Spasticity was present in 7/12, 58.3%, cognitive decline in 4/12, 33,3%, and amyotrophy or upper limb muscular weakness in 2/12, 16.6%. 2 patients with p.Pro173Arg also had learning disabilities. 5 cases were confirmed de novo for the variants. Enrichment of rare missense in an ataxia cohort from UK 100k genomes - 6/1103 cases vs 2/20,904 controls, OR = 57.0847 [10.2- 576.7], p = 4.02e-7. Cultured fibroblasts from 3 patients harbouring distinct TUBA4A missense showed significant alterations in microtubule organisation and dynamics, suggestive of a dominant negative mechanism of disease.

PMID: 37418012 - 2 Italian spastic ataxia families with p.Glu415Lys, one family segregating the variant in 11 affected individuals and one de novo.
Sources: Literature
Hereditary Spastic Paraplegia - adult onset v1.10 TUBA4A Bryony Thompson Marked gene: TUBA4A as ready
Hereditary Spastic Paraplegia - adult onset v1.10 TUBA4A Bryony Thompson Gene: tuba4a has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - adult onset v1.10 TUBA4A Bryony Thompson Classified gene: TUBA4A as Green List (high evidence)
Hereditary Spastic Paraplegia - adult onset v1.10 TUBA4A Bryony Thompson Gene: tuba4a has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - adult onset v1.9 TUBA4A Bryony Thompson gene: TUBA4A was added
gene: TUBA4A was added to Hereditary Spastic Paraplegia - adult onset. Sources: Literature
Mode of inheritance for gene: TUBA4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBA4A were set to 38884572; 37418012
Phenotypes for gene: TUBA4A were set to Hereditary ataxia MONDO:0100309, TUBA4A-related
Mode of pathogenicity for gene: TUBA4A was set to Other
Review for gene: TUBA4A was set to GREEN
Added comment: PMID: 38884572 - Multicentre cohort of 12 patients from 11 unrelated families presenting with ataxia age of onset 2-60 yrs (9 different missense variants). Spasticity was present in 7/12, 58.3%, cognitive decline in 4/12, 33,3%, and amyotrophy or upper limb muscular weakness in 2/12, 16.6%. 2 patients with p.Pro173Arg also had learning disabilities. 5 cases were confirmed de novo for the variants. Enrichment of rare missense in an ataxia cohort from UK 100k genomes - 6/1103 cases vs 2/20,904 controls, OR = 57.0847 [10.2- 576.7], p = 4.02e-7. Cultured fibroblasts from 3 patients harbouring distinct TUBA4A missense showed significant alterations in microtubule organisation and dynamics, suggestive of a dominant negative mechanism of disease.

PMID: 37418012 - 2 Italian spastic ataxia families with p.Glu415Lys, one family segregating the variant in 11 affected individuals and one de novo.
Sources: Literature
Ataxia - paediatric v1.24 TUBA4A Bryony Thompson Marked gene: TUBA4A as ready
Ataxia - paediatric v1.24 TUBA4A Bryony Thompson Gene: tuba4a has been classified as Green List (High Evidence).
Ataxia - paediatric v1.24 TUBA4A Bryony Thompson Classified gene: TUBA4A as Green List (high evidence)
Ataxia - paediatric v1.24 TUBA4A Bryony Thompson Gene: tuba4a has been classified as Green List (High Evidence).
Ataxia - paediatric v1.23 TUBA4A Bryony Thompson gene: TUBA4A was added
gene: TUBA4A was added to Ataxia - paediatric. Sources: Literature
Mode of inheritance for gene: TUBA4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBA4A were set to 38884572; 37418012
Phenotypes for gene: TUBA4A were set to Hereditary ataxia MONDO:0100309, TUBA4A-related
Mode of pathogenicity for gene: TUBA4A was set to Other
Review for gene: TUBA4A was set to GREEN
Added comment: PMID: 38884572 - Multicentre cohort of 12 patients from 11 unrelated families presenting with ataxia age of onset 2-60 yrs (9 different missense variants). Spasticity was present in 7/12, 58.3%, cognitive decline in 4/12, 33,3%, and amyotrophy or upper limb muscular weakness in 2/12, 16.6%. 2 patients with p.Pro173Arg also had learning disabilities. 5 cases were confirmed de novo for the variants. Enrichment of rare missense in an ataxia cohort from UK 100k genomes - 6/1103 cases vs 2/20,904 controls, OR = 57.0847 [10.2- 576.7], p = 4.02e-7. Cultured fibroblasts from 3 patients harbouring distinct TUBA4A missense showed significant alterations in microtubule organisation and dynamics, suggestive of a dominant negative mechanism of disease.

PMID: 37418012 - 2 Italian spastic ataxia families with p.Glu415Lys, one family segregating the variant in 11 affected individuals and one de novo.
Sources: Literature
Ataxia - adult onset v1.12 TUBA4A Bryony Thompson edited their review of gene: TUBA4A: Changed mode of pathogenicity: Other
Ataxia - adult onset v1.12 TUBA4A Bryony Thompson Marked gene: TUBA4A as ready
Ataxia - adult onset v1.12 TUBA4A Bryony Thompson Gene: tuba4a has been classified as Green List (High Evidence).
Ataxia - adult onset v1.12 TUBA4A Bryony Thompson Classified gene: TUBA4A as Green List (high evidence)
Ataxia - adult onset v1.12 TUBA4A Bryony Thompson Gene: tuba4a has been classified as Green List (High Evidence).
Ataxia - adult onset v1.11 TUBA4A Bryony Thompson gene: TUBA4A was added
gene: TUBA4A was added to Ataxia - adult onset. Sources: Literature
Mode of inheritance for gene: TUBA4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBA4A were set to 38884572; 37418012
Phenotypes for gene: TUBA4A were set to Hereditary ataxia MONDO:0100309, TUBA4A-related
Review for gene: TUBA4A was set to GREEN
Added comment: PMID: 38884572 - Multicentre cohort of 12 patients from 11 unrelated families presenting with ataxia age of onset 2-60 yrs (9 different missense variants). Spasticity was present in 7/12, 58.3%, cognitive decline in 4/12, 33,3%, and amyotrophy or upper limb muscular weakness in 2/12, 16.6%. 2 patients with p.Pro173Arg also had learning disabilities. 5 cases were confirmed de novo for the variants. Enrichment of rare missense in an ataxia cohort from UK 100k genomes - 6/1103 cases vs 2/20,904 controls, OR = 57.0847 [10.2- 576.7], p = 4.02e-7. Cultured fibroblasts from 3 patients harbouring distinct TUBA4A missense showed significant alterations in microtubule organisation and dynamics, suggestive of a dominant negative mechanism of disease.

PMID: 37418012 - 2 Italian spastic ataxia families with p.Glu415Lys, one family segregating the variant in 11 affected individuals and one de novo.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6050 PSMC5 Rylee Peters reviewed gene: PSMC5: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38776958, 38293138; Phenotypes: Neurodevelopmental disorder (MONDO#0700092), PSMC5-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1860 PSMC5 Rylee Peters reviewed gene: PSMC5: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38776958, 38293138; Phenotypes: Neurodevelopmental disorder (MONDO#0700092), PSMC5-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.253 VPS50 Ain Roesley Publications for gene: VPS50 were set to PMID: 34037727
Fetal anomalies v1.252 VPS50 Ain Roesley reviewed gene: VPS50: Rating: AMBER; Mode of pathogenicity: None; Publications: 38876772; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Genetic Epilepsy v1.31 VPS50 Ain Roesley Publications for gene: VPS50 were set to 34037727; 38876772
Genetic Epilepsy v1.30 VPS50 Ain Roesley Publications for gene: VPS50 were set to 34037727; 38876772
Intellectual disability syndromic and non-syndromic v0.6050 VPS50 Ain Roesley Classified gene: VPS50 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6050 VPS50 Ain Roesley Gene: vps50 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.30 VPS50 Ain Roesley Classified gene: VPS50 as Green List (high evidence)
Genetic Epilepsy v1.30 VPS50 Ain Roesley Gene: vps50 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6050 VPS50 Ain Roesley Publications for gene: VPS50 were set to 34037727
Genetic Epilepsy v1.30 VPS50 Ain Roesley Publications for gene: VPS50 were set to 34037727
Genetic Epilepsy v1.30 VPS50 Ain Roesley Classified gene: VPS50 as Green List (high evidence)
Genetic Epilepsy v1.30 VPS50 Ain Roesley Gene: vps50 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6049 VPS50 Ain Roesley reviewed gene: VPS50: Rating: GREEN; Mode of pathogenicity: None; Publications: 38876772; Phenotypes: Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis MIM#619685; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Genetic Epilepsy v1.29 VPS50 Ain Roesley commented on gene: VPS50: 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
Genetic Epilepsy v1.29 VPS50 Ain Roesley reviewed gene: VPS50: Rating: GREEN; Mode of pathogenicity: None; Publications: 38876772; Phenotypes: Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis MIM#619685; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Cholestasis v0.240 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
Microcephaly v1.265 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
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
Fetal anomalies v1.252 SERPINA11 Ain Roesley Marked gene: SERPINA11 as ready
Fetal anomalies v1.252 SERPINA11 Ain Roesley Gene: serpina11 has been classified as Red List (Low Evidence).
Mendeliome v1.1860 SERPINA11 Ain Roesley Marked gene: SERPINA11 as ready
Mendeliome v1.1860 SERPINA11 Ain Roesley Gene: serpina11 has been classified as Red List (Low Evidence).
Fetal anomalies v1.252 SERPINA11 Ain Roesley gene: SERPINA11 was added
gene: SERPINA11 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: SERPINA11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SERPINA11 were set to 38831697
Phenotypes for gene: SERPINA11 were set to pericardial effusion; pleural effusion
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
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
Intellectual disability syndromic and non-syndromic v0.6049 PSMD11 Bryony Thompson Marked gene: PSMD11 as ready
Intellectual disability syndromic and non-syndromic v0.6049 PSMD11 Bryony Thompson Gene: psmd11 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6049 PSMD11 Bryony Thompson Classified gene: PSMD11 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6049 PSMD11 Bryony Thompson Gene: psmd11 has been classified as Green List (High Evidence).
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
Intellectual disability syndromic and non-syndromic v0.6048 PSMD11 Bryony Thompson gene: PSMD11 was added
gene: PSMD11 was added to Intellectual disability syndromic and non-syndromic. 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
Mendeliome v1.1858 PSMD11 Bryony Thompson Marked gene: PSMD11 as ready
Mendeliome v1.1858 PSMD11 Bryony Thompson Gene: psmd11 has been classified as Green List (High Evidence).
Mendeliome v1.1858 PSMD11 Bryony Thompson Classified gene: PSMD11 as Green List (high evidence)
Mendeliome v1.1858 PSMD11 Bryony Thompson Gene: psmd11 has been classified as Green List (High Evidence).
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
Microcephaly v1.265 VPS50 Ain Roesley Classified gene: VPS50 as Green List (high evidence)
Microcephaly v1.265 VPS50 Ain Roesley Gene: vps50 has been classified as Green List (High Evidence).
Cholestasis v0.240 VPS50 Ain Roesley Classified gene: VPS50 as Green List (high evidence)
Cholestasis v0.240 VPS50 Ain Roesley Gene: vps50 has been classified as Green List (High Evidence).
Mendeliome v1.1856 VPS50 Ain Roesley Classified gene: VPS50 as Green List (high evidence)
Mendeliome v1.1856 VPS50 Ain Roesley Gene: vps50 has been classified as Green List (High Evidence).
Microcephaly v1.264 VPS50 Ain Roesley reviewed gene: VPS50: Rating: GREEN; Mode of pathogenicity: None; Publications: 38876772; Phenotypes: Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis MIM#619685; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
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
Cholestasis v0.239 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
Cholestasis v0.239 VPS50 Ain Roesley reviewed gene: VPS50: Rating: GREEN; Mode of pathogenicity: None; Publications: 38876772; Phenotypes: Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis MIM#619685; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v1.1855 VPS50 Ain Roesley reviewed gene: VPS50: Rating: GREEN; Mode of pathogenicity: None; Publications: 38876772; Phenotypes: Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis MIM#619685; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6047 PAK2 Ain Roesley Marked gene: PAK2 as ready
Intellectual disability syndromic and non-syndromic v0.6047 PAK2 Ain Roesley Gene: pak2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6047 PAK2 Ain Roesley Classified gene: PAK2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6047 PAK2 Ain Roesley Gene: pak2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6046 PAK2 Ain Roesley gene: PAK2 was added
gene: PAK2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PAK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PAK2 were set to 33693784; 38894571; 38712026
Phenotypes for gene: PAK2 were set to Knobloch 2 syndrome MIM#618458
Review for gene: PAK2 was set to GREEN
gene: PAK2 was marked as current diagnostic
Added comment: total of 3 families including 2 siblings with intra-familial variability

Siblings' phenotypes:
Both had retinal detachment and interstitial parenchymal pulmonary changes on chest X-rays, but only one child had additional significant features such as cataract, posterior encephalocele, severe DD/ID with ASD, and epilepsy.

Other 2 pro bands:
GDD, delayed motor (but normal verbal) skills, hypotonia

Missense variants with in vitro functional demonstrating reduction in PAK2 auto phosphorylation
Sources: Literature
Genetic Epilepsy v1.29 PAK2 Ain Roesley Publications for gene: PAK2 were set to 33693784
Genetic Epilepsy v1.29 PAK2 Ain Roesley Classified gene: PAK2 as Amber List (moderate evidence)
Genetic Epilepsy v1.29 PAK2 Ain Roesley Gene: pak2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v1.28 PAK2 Ain Roesley reviewed gene: PAK2: Rating: AMBER; Mode of pathogenicity: None; Publications: 38894571, 38712026; Phenotypes: Knobloch syndrome 2 MIM#618458; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Dilated Cardiomyopathy v1.30 C10orf71 Sangavi Sivagnanasundram gene: C10orf71 was added
gene: C10orf71 was added to Dilated Cardiomyopathy. 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
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
Mendeliome v1.1855 PAK2 Ain Roesley Publications for gene: PAK2 were set to 33693784
Mendeliome v1.1854 PAK2 Ain Roesley Classified gene: PAK2 as Green List (high evidence)
Mendeliome v1.1854 PAK2 Ain Roesley Gene: pak2 has been classified as Green List (High Evidence).
Mendeliome v1.1853 PAK2 Ain Roesley reviewed gene: PAK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 38894571, 38712026; Phenotypes: Knobloch syndrome 2 MIM#618458; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Prepair 500+ v1.1 IQSEC2 Ain Roesley Phenotypes for gene: IQSEC2 were changed from Mental retardation, X-linked 1, 309530 (3) to Intellectual developmental disorder, X-linked 1 MIM#309530
Prepair 1000+ v1.7 IQSEC2 Ain Roesley Phenotypes for gene: IQSEC2 were changed from Mental retardation, X-linked 1, 309530 (3) to Intellectual developmental disorder, X-linked 1 MIM#309530
Familial Generalised Epilepsy v0.13 USP25 Sangavi Sivagnanasundram gene: USP25 was added
gene: USP25 was added to Familial Generalised Epilepsy. 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 and/or febrile seizures.

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
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
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
Hereditary Neuropathy_CMT - isolated v1.48 RTN2 Zornitza Stark Phenotypes for gene: RTN2 were changed from distal hereditary motor neuropathy, MONDO:0018894, RTN2-related to Neuronopathy, distal hereditary motor, autosomal recessive 11, with spasticity, MIM# 620854
Hereditary Neuropathy_CMT - isolated v1.47 RTN2 Zornitza Stark edited their review of gene: RTN2: Changed phenotypes: Neuronopathy, distal hereditary motor, autosomal recessive 11, with spasticity, MIM# 620854
Speech apraxia v0.39 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Rare Disease
Speech apraxia v0.38 FOXP2 Thomas Scerri changed review comment from: Additional phenotypes: Cognition ranges from average to mild ID, feeding difficulties in infancy, fine & gross motor impairment, ASD, language impairment, anxiety, depression, sleep disturbance (PMID: 38366112).; to: Lai et al. (2001; PMID: 11586359) reported a 3-generation family with speech apraxia carrying a missense FOXP2 variant and also an independent case with a translocation affecting FOXP2.

Morison et al. (2023; PMID 36328423) "phenotyped 28 individuals from 17 families with pathogenic FOXP2-only variants (12 loss-of-function, five missense variants; 14 males; aged 2 to 62 years)" and found "speech disorders were prevalent (23/25, 92%) and CAS was most common (22/25, 88%)".
Speech apraxia v0.38 KDM5C Thomas Scerri changed review comment from: First reported CAS case with a de novo HNRNPK frameshift variant (Kaspi et al., 2022; PMID: 36117209).

Leonardi et al. (2023; PMID: 36434256) report 30 individuals with HNRNPK variants, of which 16 have reported speech delay (including all males with records, and several females). No mention of apraxia or dyspraxia though.

Note: Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type (MIM# 300534) is recorded as autosomal recessive, however female heterozygotes can have milder phenotypes.
Sources: Expert list, Expert Review; to: First reported CAS case with a de novo HNRNPK frameshift variant (Kaspi et al., 2022; PMID: 36117209).

Leonardi et al. (2023; PMID: 36434256) report 30 individuals with HNRNPK variants, of which 16 have reported speech delay (including all males with records, and several females). No mention of speech/verbal apraxia or dyspraxia though.

Note: Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type (MIM# 300534) is recorded as autosomal recessive, however female heterozygotes can have milder phenotypes.
Sources: Expert list, Expert Review
Speech apraxia v0.38 ZBTB18 Thomas Scerri changed review comment from: First reported CAS case with an de novo nonsense ZBTB18 variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review; to: First reported CAS case with an de novo ZBTB18 nonsense variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review
Speech apraxia v0.38 TAOK2 Thomas Scerri changed review comment from: First reported CAS case with an de novo missense TAOK2 variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review; to: First reported CAS case with an de novo TAOK2 missense variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review
Speech apraxia v0.38 SPAST Thomas Scerri changed review comment from: First reported CAS case with an de novo missense SPAST variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review; to: First reported CAS case with an de novo SPAST missense variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review
Speech apraxia v0.38 PURA Thomas Scerri changed review comment from: First reported CAS case with an inherited PURA missense variant (Kaspi et al., 2022; PMID: 36117209). Both proband and parent affected.
Sources: Expert list, Expert Review; to: First reported CAS case with an inherited PURA missense variant (Kaspi et al., 2022; PMID: 36117209). Both proband and parent affected.

Also several cases of "absence of speech" in the literature.

Sources: Expert list, Expert Review
Speech apraxia v0.38 PURA Thomas Scerri changed review comment from: First reported CAS case with an inherited missense PURA variant (Kaspi et al., 2022; PMID: 36117209). Both proband and parent affected.
Sources: Expert list, Expert Review; to: First reported CAS case with an inherited PURA missense variant (Kaspi et al., 2022; PMID: 36117209). Both proband and parent affected.
Sources: Expert list, Expert Review
Speech apraxia v0.38 PHF21A Thomas Scerri changed review comment from: First reported CAS case with a de novo frameshift PHF21A variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review; to: First reported CAS case with a de novo PHF21A frameshift variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review
Speech apraxia v0.38 KDM5C Thomas Scerri changed review comment from: First reported CAS case with a de novo frameshift HNRNPK variant (Kaspi et al., 2022; PMID: 36117209).

Leonardi et al. (2023; PMID: 36434256) report 30 individuals with HNRNPK variants, of which 16 have reported speech delay (including all males with records, and several females). No mention of apraxia or dyspraxia though.

Note: Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type (MIM# 300534) is recorded as autosomal recessive, however female heterozygotes can have milder phenotypes.
Sources: Expert list, Expert Review; to: First reported CAS case with a de novo HNRNPK frameshift variant (Kaspi et al., 2022; PMID: 36117209).

Leonardi et al. (2023; PMID: 36434256) report 30 individuals with HNRNPK variants, of which 16 have reported speech delay (including all males with records, and several females). No mention of apraxia or dyspraxia though.

Note: Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type (MIM# 300534) is recorded as autosomal recessive, however female heterozygotes can have milder phenotypes.
Sources: Expert list, Expert Review
Speech apraxia v0.38 SHANK3 Thomas Scerri changed review comment from: First reported CAS case with an de novo frameshift SHANK3 variant (Kaspi et al., 2022; PMID: 36117209).

Brignell et al. (2021; PMID: 33293697) report 2 cases of CAS in a cohort of individuals with Phelan-McDermid/22q13 deletion syndrome, caused by heterozygous loss of function of SHANK3.
Sources: Expert list, Expert Review; to: First reported CAS case with a de novo SHANK3 frameshift variant (Kaspi et al., 2022; PMID: 36117209).

Brignell et al. (2021; PMID: 33293697) report 2 cases of CAS in a cohort of individuals with Phelan-McDermid/22q13 deletion syndrome, caused by heterozygous loss of function of SHANK3.
Sources: Expert list, Expert Review
Speech apraxia v0.38 CHD3 Thomas Scerri changed review comment from: First reported CAS case with a de novo missense CHD3 variant (Eising et al., 2019; PMID: 29463886).

Snijders Blok et al. (2018; PMID: 30397230) examined 35 cases with CHD3 variants. The index case was diagnosed with severe speech apraxia.

Van der Spek et al. (2022; PMID: 35346573) examined 21 families with CHD3 variants and found at least 2 independent cases with speech dyspraxia.; to: First reported CAS case with a de novo CHD3 missense variant (Eising et al., 2019; PMID: 29463886).

Snijders Blok et al. (2018; PMID: 30397230) examined 35 cases with CHD3 variants. The index case was diagnosed with severe speech apraxia.

Van der Spek et al. (2022; PMID: 35346573) examined 21 families with CHD3 variants and found at least 2 independent cases with speech dyspraxia.
Speech apraxia v0.38 TNRC6B Thomas Scerri edited their review of gene: TNRC6B: Changed rating: RED
Speech apraxia v0.38 TNRC6B Thomas Scerri changed review comment from: First reported CAS case with a TNRC6B nonsense variant (Eising et al., 2019; PMID: 29463886)

These additional supporting studies are for speech delay rather than speech apraxia per se:

Granadillo et al., (2020; PMID: 32152250) studied seventeen further probands with LoF TNRC6B variants and found "speech delay in 94% (16/17), fine motor delay in 82% (14/17) and gross motor delay in 71% (12/17)".

Yahia et al. (2024; PMID: 38300321) looked at a Swedish cohort with severe developmental language disorder and find another case with a LoF variant in TNRC6B.

Yang et al. (2024; PMID: 38404251) report two independent cases with speech delay/abnormalities carrying LoF variants in TNRC6B.

Sources: Expert list, Expert Review; to: First reported CAS case with a TNRC6B nonsense variant (Eising et al., 2019; PMID: 29463886)

These additional supporting studies are for speech delay rather than speech apraxia per se:

Granadillo et al., (2020; PMID: 32152250) studied seventeen further probands with LoF TNRC6B variants and found "speech delay in 94% (16/17), fine motor delay in 82% (14/17) and gross motor delay in 71% (12/17)".

Yahia et al. (2024; PMID: 38300321) looked at a Swedish cohort with severe developmental language disorder and find another case with a loss-of-function variant in TNRC6B.

Yang et al. (2024; PMID: 38404251) report two independent cases with speech delay/abnormalities carrying loss-of-function variants in TNRC6B.

Sources: Expert list, Expert Review
Speech apraxia v0.38 MKL2 Thomas Scerri edited their review of gene: MKL2: Changed rating: RED
Speech apraxia v0.38 GNAO1 Thomas Scerri edited their review of gene: GNAO1: Changed rating: RED
Speech apraxia v0.38 ERF Thomas Scerri edited their review of gene: ERF: Changed rating: RED
Speech apraxia v0.38 SHANK3 Thomas Scerri edited their review of gene: SHANK3: Changed rating: AMBER
Speech apraxia v0.38 ZNF142 Thomas Scerri changed review comment from: A reported CAS proband with compound heterozygous missenses ZNF142 variants (Hildebrand et al., 2020; PMID: 32345733).

Khan et al. (2019, PMID: 31036918) report 7 cases with compound heterozygous or else homozygous LoF or missense ZNF142 variants for which the cases have a range of speech deficits including speech apraxia in one case.

Kameyama et al. (2020, PMID: 34531528) report two brothers with biallelic LoF ZNF142 variants for which the cases have speech deficits.

Christensen et al. (2022; PMID: 35616059) report a further 26 individuals with biallelic ZNF142 variants for which the cases have a range of speech deficits.
Sources: Expert list, Expert Review; to: First reported CAS proband with compound heterozygous ZNF142 missenses variants (Hildebrand et al., 2020; PMID: 32345733).

Khan et al. (2019, PMID: 31036918) report 7 cases with compound heterozygous or else homozygous loss-of-function or missense ZNF142 variants for which the cases have a range of speech deficits, including speech apraxia in one case.

Kameyama et al. (2020, PMID: 34531528) report two brothers with biallelic loss-of-function ZNF142 variants for which the cases have speech deficits.

Christensen et al. (2022; PMID: 35616059) report a further 26 individuals with biallelic ZNF142 variants for which the cases have a range of speech deficits.

Sources: Expert list, Expert Review
Speech apraxia v0.38 UPF2 Thomas Scerri changed review comment from: A CAS proband with a de novo LoF UPF2 variant (Hildebrand et al., 2020; PMID: 32345733).

Johnson et al. (2019; PMID: 31585809) report 3 independent cases with LoF UPF2 variants and a range of speech deficits, including speech apraxia in one of the cases (although the speech disorder had resolved to a mild phonological disorder at later testing).
Sources: Expert list, Expert Review; to: First reported CAS proband with a de novo UPF2 frameshift variant (Hildebrand et al., 2020; PMID: 32345733).

Johnson et al. (2019; PMID: 31585809) report 3 independent cases with loss-of-function UPF2 variants and a range of speech deficits, including speech apraxia in one of the cases (although the speech disorder had resolved to a mild phonological disorder at later testing).

Sources: Expert list, Expert Review
Speech apraxia v0.38 POGZ Thomas Scerri changed review comment from: Only reported CAS proband with a de novo missense POGZ variant (Hildebrand et al., 2020; PMID: 32345733).

Nagy et al. (2022; PMID: 35052493) reported 117 cases from a meta-analysis and found that "the most common symptoms were speech delay in 88%". This is not strong enough evidence to be supporting evidence for speech apraxia per se.
Sources: Expert list, Expert Review; to: First reported CAS proband with a de novo POGZ missense variant (Hildebrand et al., 2020; PMID: 32345733).

Nagy et al. (2022; PMID: 35052493) reported 117 cases from a meta-analysis and found that "the most common symptoms were speech delay in 88%". This is not strong enough evidence to be supporting evidence for speech apraxia per se.
Sources: Expert list, Expert Review
Speech apraxia v0.38 MEIS2 Thomas Scerri changed review comment from: First reported CAS proband with a LoF MEI2 variant (Hildebrand et al., 2020; PMID: 32345733).

Douglas et al. (2018; PMID: 30055086) report 3 new cases with de novo missense variants and 2 previously published deletion and nonsense variants. All cases have a range of differently worded speech problems, and one has verbal apraxia.
Sources: Expert Review, Expert list; to: First reported CAS proband with a MEI2 frameshift variant (Hildebrand et al., 2020; PMID: 32345733).

Douglas et al. (2018; PMID: 30055086) report 3 new cases with de novo missense variants and 2 previously published deletion and nonsense variants. All cases have a range of differently worded speech problems, and one has verbal apraxia.
Sources: Expert Review, Expert list
Speech apraxia v0.38 GNB1 Thomas Scerri changed review comment from: Only reported CAS proband with a de novo nonsense GNB1 variant (Hildebrand et al., 2020; PMID: 32345733).
Sources: Expert list, Expert Review; to: First reported CAS proband with a de novo GNB1 nonsense variant (Hildebrand et al., 2020; PMID: 32345733).

Sources: Expert list, Expert Review
Speech apraxia v0.38 GNAO1 Thomas Scerri changed review comment from: First reported CAS proband with a de novo missense GNAO1 variant (Hildebrand et al., 2020; PMID: 32345733).

These additional cases are less clear for speech apraxia:

Wirth et al. (2020; PMID: 35722775) reported twenty-four independent cases with a range of de novo and inherited variants, including missense and nonsense, for which a speech disorder (dysarthria) was reported for 19 individuals.

Lasa-Aranzasti et al. (2024; PMID: 38881224) report eighteen independent cases and find "all patients developed some type of nonverbal communication, but only four acquired verbal language."
Sources: Expert list, Expert Review; to: First reported CAS proband with a de novo GNAO1 missense variant (Hildebrand et al., 2020; PMID: 32345733).

These additional cases are less clear for speech apraxia:

Wirth et al. (2020; PMID: 35722775) reported twenty-four independent cases with a range of de novo and inherited variants, including missense and nonsense, for which a speech disorder (dysarthria) was reported for 19 individuals.

Lasa-Aranzasti et al. (2024; PMID: 38881224) report eighteen independent cases and find "all patients developed some type of nonverbal communication, but only four acquired verbal language."
Sources: Expert list, Expert Review
Speech apraxia v0.38 EBF3 Thomas Scerri changed review comment from: First reported CAS case with a de novo EBF3 nonsense variant (Hildebrand et al., 2020; PMID: 32345733).

Chao et al. (2017; PMID: 28017372) report three independent cases with de novo missense variants (all three curiously substituting the same amino acid). All three cases have "expressive speech disorder (3/3)" and one specifically had apraxia.

Deisseroth et al. (2022; PMID: 35340043) report a total of 83 individuals with missense or protein-truncating variants for EBF3 from a meta-analysis and find 10% have speech apraxia. Specifically, of these ten cases, carried de novo EBF3 variants and were reported as having speech apraxia (supplementary tables).

Sources: Expert list, Expert Review; to: First reported CAS case with a de novo EBF3 nonsense variant (Hildebrand et al., 2020; PMID: 32345733).

Chao et al. (2017; PMID: 28017372) report three independent cases with de novo missense variants (all three curiously substituting the same amino acid). All three cases had "expressive speech disorder (3/3)" and one was reported with apraxia.

Deisseroth et al. (2022; PMID: 35340043) report a total of 83 individuals with missense or protein-truncating variants for EBF3 from a meta-analysis and find 10% have speech apraxia. Specifically, of these ten cases, carried de novo EBF3 variants and were reported as having speech apraxia (supplementary tables).

Sources: Expert list, Expert Review
Speech apraxia v0.38 EBF3 Thomas Scerri changed review comment from: First reported CAS case with a de novo EBF3 nonsense variant (Hildebrand et al., 2020; PMID: 32345733).

Chao et al. (2017; PMID: 28017372) report three independent cases with de novo missense variants (all three curiously substituting the same amino acid). All three cases have "expressive speech disorder (3/3)" and one specifically has apraxia.

Deisseroth et al. (2022; PMID: 35340043) report a total of 83 individuals with missense or protein-truncating variants for EBF3 from a meta-analysis and find 10% have speech apraxia. Specifically, of these ten cases, carried de novo EBF3 variants and were reported as having speech apraxia (supplementary tables).

Sources: Expert list, Expert Review; to: First reported CAS case with a de novo EBF3 nonsense variant (Hildebrand et al., 2020; PMID: 32345733).

Chao et al. (2017; PMID: 28017372) report three independent cases with de novo missense variants (all three curiously substituting the same amino acid). All three cases have "expressive speech disorder (3/3)" and one specifically had apraxia.

Deisseroth et al. (2022; PMID: 35340043) report a total of 83 individuals with missense or protein-truncating variants for EBF3 from a meta-analysis and find 10% have speech apraxia. Specifically, of these ten cases, carried de novo EBF3 variants and were reported as having speech apraxia (supplementary tables).

Sources: Expert list, Expert Review
Speech apraxia v0.38 EBF3 Thomas Scerri changed review comment from: First reported CAS case with a de novo EBF3 nonsense variant (Hildebrand et al., 2020; PMID: 32345733).

Chao et al. (2017; PMID: 28017372) report three independent cases with de novo missense variants (all three curiously substituting the same amino acid). All three cases have "expressive speech disorder (3/3)" and a range of dysarthria and apraxia.

Deisseroth et al. (2022; PMID: 35340043) report a total of 83 individuals with missense or protein-truncating variants for EBF3 from a meta-analysis and find 10% have speech apraxia. Specifically, of these ten cases, carried de novo EBF3 variants and were reported as having speech apraxia (supplementary tables).

Sources: Expert list, Expert Review; to: First reported CAS case with a de novo EBF3 nonsense variant (Hildebrand et al., 2020; PMID: 32345733).

Chao et al. (2017; PMID: 28017372) report three independent cases with de novo missense variants (all three curiously substituting the same amino acid). All three cases have "expressive speech disorder (3/3)" and one specifically has apraxia.

Deisseroth et al. (2022; PMID: 35340043) report a total of 83 individuals with missense or protein-truncating variants for EBF3 from a meta-analysis and find 10% have speech apraxia. Specifically, of these ten cases, carried de novo EBF3 variants and were reported as having speech apraxia (supplementary tables).

Sources: Expert list, Expert Review
Speech apraxia v0.38 EBF3 Thomas Scerri edited their review of gene: EBF3: Changed publications: 32345733, 28017372, 35340043
Speech apraxia v0.38 EBF3 Thomas Scerri changed review comment from: First proband with a de novo nonsense EBF3 variant reported for CAS (Hildebrand et al., 2020; PMID: 32345733).

Chao et al. (2017; PMID: 28017372) report three independent cases with de novo missense variants (all three curiously substituting the same amino acid). All three cases have "expressive speech disorder (3/3)" and a range of dysarthria and apraxia.

Deisseroth et al. (2022; PMID: 35340043) report a total of 83 individuals with missense or protein-truncating variants for EBF3 from a meta-analysis and find 10% have speech apraxia. Of these ten cases carried de novo EBF3 variants and were reported as having speech apraxia (supplementary tables).

Sources: Expert list, Expert Review; to: First reported CAS case with a de novo EBF3 nonsense variant (Hildebrand et al., 2020; PMID: 32345733).

Chao et al. (2017; PMID: 28017372) report three independent cases with de novo missense variants (all three curiously substituting the same amino acid). All three cases have "expressive speech disorder (3/3)" and a range of dysarthria and apraxia.

Deisseroth et al. (2022; PMID: 35340043) report a total of 83 individuals with missense or protein-truncating variants for EBF3 from a meta-analysis and find 10% have speech apraxia. Specifically, of these ten cases, carried de novo EBF3 variants and were reported as having speech apraxia (supplementary tables).

Sources: Expert list, Expert Review
Speech apraxia v0.38 DDX3X Thomas Scerri changed review comment from: First reported CAS proband with a de novo LoF DDX3X variant (Hildebrand et al., 2020; PMID: 32345733).

Second reported CAS proband with a de novo LoF DDX3X variant (Kaspi et al., 2022; PMID: 36117209)

Third in-house CAS proband with a de novo LoF DDX3X variant (not published).

Parra et al. (2024; PMID: 37904618) report thirty-four independent probands with DDX3X mutations for which "the most frequent clinical features (>70%) identified in these patients included speech dyspraxia (88.2%)".
Sources: Expert list, Expert Review; to: Hildebrand et al. (2020; PMID: 32345733) report the first CAS case has a de novo DDX3X frameshift variant.

Kaspi et al. (2022; PMID: 36117209) report a case with dysarthria and a de novo DDX3X nonsense variant.

An independent (unpublished) in-house CAS proband has a de novo DDX3X nonsense variant.

Parra et al. (2024; PMID: 37904618) report thirty-four independent probands with DDX3X mutations for which "the most frequent clinical features (>70%) identified in these patients included speech dyspraxia (88.2%; 30/34)".
Sources: Expert list, Expert Review
Speech apraxia v0.38 CDK13 Thomas Scerri changed review comment from: First proband with a de novo missense CDK13 variant reported for CAS (Hildebrand et al., 2020; PMID: 32345733).

Morison et al. (2023; PMID: 36599938) report 41 cases (with 33 novel variants) and find "most participants used augmentative and alternative communication (AAC) in early childhood (24/41). CAS was common (14/22)."
Sources: Expert list, Expert Review; to: First reported CAS case with a de novo CDK13 missense variant (Hildebrand et al., 2020; PMID: 32345733).

Morison et al. (2023; PMID: 36599938) report 41 cases (with 33 novel variants) and find "most participants used augmentative and alternative communication (AAC) in early childhood (24/41). CAS was common (14/22)."
Sources: Expert list, Expert Review
Speech apraxia v0.38 ERF Thomas Scerri changed review comment from: First two reported CAS cases with a ERF nonsense variant (Kaspi et al., 2022; PMID: 36117209) inherited from mother to proband.

Care et al. (2022; PMID: 35761471) report 5 cases with ERF variants, and of these 3 have speech disorder.

Moddemann et al. (PMID: 35852485) conduct a meta-analysis of 79 independent samples with ERF variants and find 60% have speech delay/impairments.
Sources: Expert list, Expert Review; to: First two reported CAS cases with a ERF nonsense variant (Kaspi et al., 2022; PMID: 36117209) inherited from mother to proband.

Care et al. (2022; PMID: 35761471) report 5 cases with ERF variants, and of these 3 have speech disorder.

Moddemann et al. (2022; PMID: 35852485) conduct a meta-analysis of 79 independent samples with ERF variants and find 60% have speech delay/impairments.
Sources: Expert list, Expert Review
Speech apraxia v0.38 ERF Thomas Scerri changed review comment from: First two reported CAS cases with a nonsense ERF variant (Kaspi et al., 2022; PMID: 36117209) inherited from mother to proband.

Care et al. (2022; PMID: 35761471) report 5 cases with ERF variants, and of these 3 have speech disorder.

Moddemann et al. (PMID: 35852485) conduct a meta-analysis of 79 independent samples with ERF variants and find 60% have speech delay/impairments.
Sources: Expert list, Expert Review; to: First two reported CAS cases with a ERF nonsense variant (Kaspi et al., 2022; PMID: 36117209) inherited from mother to proband.

Care et al. (2022; PMID: 35761471) report 5 cases with ERF variants, and of these 3 have speech disorder.

Moddemann et al. (PMID: 35852485) conduct a meta-analysis of 79 independent samples with ERF variants and find 60% have speech delay/impairments.
Sources: Expert list, Expert Review
Speech apraxia v0.38 DIP2C Thomas Scerri changed review comment from: First reported CAS proband with a de novo splice DIP2C variant (Kaspi et al., 2022; PMID: 36117209).

Ha et al. (2024; PMID: 38421105) report 23 cases with various DIP2C variants, including the one published by Kaspi et al. (2022; PMID: 36117209). All 23 cases have various speech deficits and two (including the Kaspi et al. (2022) case) are reported having speech apraxia.
Sources: Expert list, Expert Review; to: First reported CAS proband with a de novo DIP2C splice acceptor variant (Kaspi et al., 2022; PMID: 36117209).

Ha et al. (2024; PMID: 38421105) report 23 cases with various DIP2C variants, including the one published by Kaspi et al. (2022; PMID: 36117209). All 23 cases have various speech deficits and two (including the Kaspi et al. (2022) case) are reported having speech apraxia.
Sources: Expert list, Expert Review
Speech apraxia v0.38 BRPF1 Thomas Scerri changed review comment from: First reported CAS proband with a de novo missense BRPF1 variant (Kaspi et al., 2022; PMID: 36117209).

Yan et al. (2017; PMID: 27939640) reported 10 independent cases with de novo or inherited BRPF1 variants and with a range of speech and language deficits, including one proband with speech apraxia (proband 4, Table S1).

Morison et al. (2024; PMID: 38346666) report 15 new cases with mostly de novo BRPF1 variants and a range of speech deficits, including 3 specifically with speech apraxia.
Sources: Expert list, Expert Review; to: First reported CAS case with a de novo BRPF1 missense variant (Kaspi et al., 2022; PMID: 36117209).

Yan et al. (2017; PMID: 27939640) reported 10 independent cases with de novo or inherited BRPF1 variants and with a range of speech and language deficits, including one proband with speech apraxia (proband 4, Table S1).

Morison et al. (2024; PMID: 38346666) report 15 new cases with mostly de novo BRPF1 variants and a range of speech deficits, including 3 specifically with speech apraxia.
Sources: Expert list, Expert Review
Speech apraxia v0.38 ARHGEF9 Thomas Scerri changed review comment from: Only reported CAS proband with a de novo nonsense ARHGEF9 variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review; to: First reported CAS case with a de novo ARHGEF9 nonsense variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review
Speech apraxia v0.38 ZFHX4 Thomas Scerri changed review comment from: First proband with splice acceptor ZFHX4 variant reported for CAS (Eising et al., 2019; PMID: 29463886).

Fontana et al. (2021; PMID: 34461323) report a similar splice region variant in ZFHX4 for a proband with a neuropsychological phenotype, and summarise other probands with deletions or point mutations and associated phenotypes. Only one of these has a recorded speech phenotype. Overall this paper doesn't add strong evidence for a link between speech apraxia and ZFHX4.
Sources: Expert list, Expert Review; to: First reported CAS case with a ZFHX4 splice acceptor variant (Eising et al., 2019; PMID: 29463886)

Fontana et al. (2021; PMID: 34461323) report a similar splice region variant in ZFHX4 for a proband with a neuropsychological phenotype, and summarise other probands with deletions or point mutations and associated phenotypes. Only one of these has a recorded speech phenotype. Overall this paper doesn't add strong evidence for a link between speech apraxia and ZFHX4.
Sources: Expert list, Expert Review
Speech apraxia v0.38 WDR5 Thomas Scerri changed review comment from: First reported CAS case with a de novo WDR5 missense variant (Eising et al., 2019; PMID: 29463886)

Blok et al. (2022; PMID: 36408368) studied "11 unrelated individuals with six different rare de novo germline missense variants in WDR5; one identical variant was found in five individuals and another variant in two individuals. All individuals had neurodevelopmental disorders including speech/language delays (n = 11). Speech delays were reported in all individuals, including nasal speech, developmental language disorders, verbal dyspraxia, and persistent stuttering." However, only 1 was diagnosed with speech dyspraxia.

Sources: Expert list, Expert Review; to: First reported CAS case with a de novo WDR5 missense variant (Eising et al., 2019; PMID: 29463886)

Snijders Blok et al. (2022; PMID: 36408368) studied "11 unrelated individuals with six different rare de novo germline missense variants in WDR5; one identical variant was found in five individuals and another variant in two individuals. All individuals had neurodevelopmental disorders including speech/language delays (n = 11). Speech delays were reported in all individuals, including nasal speech, developmental language disorders, verbal dyspraxia, and persistent stuttering." However, only 1 was diagnosed with speech dyspraxia.

Sources: Expert list, Expert Review
Speech apraxia v0.38 WDR5 Thomas Scerri edited their review of gene: WDR5: Changed rating: AMBER
Speech apraxia v0.38 WDR5 Thomas Scerri changed review comment from: First reported CAS case with a de novo WDR5 missense variant (Eising et al., 2019; PMID: 29463886)

Blok et al. (2022; PMID: 36408368) studied "11 unrelated individuals with six different rare de novo germline missense variants in WDR5; one identical variant was found in five individuals and another variant in two individuals. All individuals had neurodevelopmental disorders including speech/language delays (n = 11). Speech delays were reported in all individuals, including nasal speech, developmental language disorders, verbal dyspraxia, and persistent stuttering."
Sources: Expert list, Expert Review; to: First reported CAS case with a de novo WDR5 missense variant (Eising et al., 2019; PMID: 29463886)

Blok et al. (2022; PMID: 36408368) studied "11 unrelated individuals with six different rare de novo germline missense variants in WDR5; one identical variant was found in five individuals and another variant in two individuals. All individuals had neurodevelopmental disorders including speech/language delays (n = 11). Speech delays were reported in all individuals, including nasal speech, developmental language disorders, verbal dyspraxia, and persistent stuttering." However, only 1 was diagnosed with speech dyspraxia.

Sources: Expert list, Expert Review
Speech apraxia v0.38 TNRC6B Thomas Scerri changed review comment from: First reported CAS case with a TNRC6B nonsense variant (Eising et al., 2019; PMID: 29463886)

These additional supporting studies are for speech delay rather than speech apraxia per se:

Granadillo et al., (2020; PMID: 32152250) studied seventeen further probands with LoF TNRC6B variants and found "speech delay in 94% (16/17), fine motor delay in 82% (14/17) and gross motor delay in 71% (12/17)".

Yahia et al. (2024; PMID: 38300321) looked at a Swedish cohort with severe developmental language disorder and find another case with a LoF variant in TNRC6B.

Yang et al., (2024; PMID: 38404251) report two independent cases with speech delay/abnormalities carrying LoF variants in TNRC6B.

Sources: Expert list, Expert Review; to: First reported CAS case with a TNRC6B nonsense variant (Eising et al., 2019; PMID: 29463886)

These additional supporting studies are for speech delay rather than speech apraxia per se:

Granadillo et al., (2020; PMID: 32152250) studied seventeen further probands with LoF TNRC6B variants and found "speech delay in 94% (16/17), fine motor delay in 82% (14/17) and gross motor delay in 71% (12/17)".

Yahia et al. (2024; PMID: 38300321) looked at a Swedish cohort with severe developmental language disorder and find another case with a LoF variant in TNRC6B.

Yang et al. (2024; PMID: 38404251) report two independent cases with speech delay/abnormalities carrying LoF variants in TNRC6B.

Sources: Expert list, Expert Review
Speech apraxia v0.38 TNRC6B Thomas Scerri changed review comment from: First reported CAS case with a TNRC6B nonsense variant (Eising et al., 2019; PMID: 29463886)

These additional supporting studies are for speech delay rather than speech apraxia per se:

Granadillo et al., (2020; PMID: 32152250) studied seventeen further probands with LoF TNRC6B variants and found "speech delay in 94% (16/17), fine motor delay in 82% (14/17) and gross motor delay in 71% (12/17)".

Yahia et al., (2024; PMID: 38300321) looked at a Swedish cohort with severe developmental language disorder and find another case with a LoF variant in TNRC6B.

Yang et al., (2024; PMID: 38404251) report two independent cases with speech delay/abnormalities carrying LoF variants in TNRC6B.

Sources: Expert list, Expert Review; to: First reported CAS case with a TNRC6B nonsense variant (Eising et al., 2019; PMID: 29463886)

These additional supporting studies are for speech delay rather than speech apraxia per se:

Granadillo et al., (2020; PMID: 32152250) studied seventeen further probands with LoF TNRC6B variants and found "speech delay in 94% (16/17), fine motor delay in 82% (14/17) and gross motor delay in 71% (12/17)".

Yahia et al. (2024; PMID: 38300321) looked at a Swedish cohort with severe developmental language disorder and find another case with a LoF variant in TNRC6B.

Yang et al., (2024; PMID: 38404251) report two independent cases with speech delay/abnormalities carrying LoF variants in TNRC6B.

Sources: Expert list, Expert Review
Speech apraxia v0.38 WDR5 Thomas Scerri changed review comment from: First proband with a de novo missense WDR5 variant reported for CAS (Eising et al., 2019; PMID: 29463886).

Blok et al. (2022; PMID: 36408368) studied "11 unrelated individuals with six different rare de novo germline missense variants in WDR5; one identical variant was found in five individuals and another variant in two individuals. All individuals had neurodevelopmental disorders including speech/language delays (n = 11). Speech delays were reported in all individuals, including nasal speech, developmental language disorders, verbal dyspraxia, and persistent stuttering."
Sources: Expert list, Expert Review; to: First reported CAS case with a de novo WDR5 missense variant (Eising et al., 2019; PMID: 29463886)

Blok et al. (2022; PMID: 36408368) studied "11 unrelated individuals with six different rare de novo germline missense variants in WDR5; one identical variant was found in five individuals and another variant in two individuals. All individuals had neurodevelopmental disorders including speech/language delays (n = 11). Speech delays were reported in all individuals, including nasal speech, developmental language disorders, verbal dyspraxia, and persistent stuttering."
Sources: Expert list, Expert Review
Speech apraxia v0.38 TNRC6B Thomas Scerri changed review comment from: First proband with a LoF TNRC6B variant reported for CAS (Eising et al., 2019; PMID: 29463886).

These additional supporting studies are for speech delay rather than speech apraxia per se:

Granadillo et al., (2020; PMID: 32152250) studied seventeen further probands with LoF TNRC6B variants and found "speech delay in 94% (16/17), fine motor delay in 82% (14/17) and gross motor delay in 71% (12/17)".

Yahia et al., (2024; PMID: 38300321) looked at a Swedish cohort with severe developmental language disorder and find another case with a LoF variant in TNRC6B.

Yang et al., (2024; PMID: 38404251) report two independent cases with speech delay/abnormalities carrying LoF variants in TNRC6B.
Sources: Expert list, Expert Review; to: First reported CAS case with a TNRC6B nonsense variant (Eising et al., 2019; PMID: 29463886)

These additional supporting studies are for speech delay rather than speech apraxia per se:

Granadillo et al., (2020; PMID: 32152250) studied seventeen further probands with LoF TNRC6B variants and found "speech delay in 94% (16/17), fine motor delay in 82% (14/17) and gross motor delay in 71% (12/17)".

Yahia et al., (2024; PMID: 38300321) looked at a Swedish cohort with severe developmental language disorder and find another case with a LoF variant in TNRC6B.

Yang et al., (2024; PMID: 38404251) report two independent cases with speech delay/abnormalities carrying LoF variants in TNRC6B.

Sources: Expert list, Expert Review
Speech apraxia v0.38 SETD1A Thomas Scerri changed review comment from: First proband with a LoF SETD1A variant reported for CAS (Eising et al., 2019; PMID: 29463886).

Fifteen further independent probands with LoF SETD1A variants were investigated (Kummeling et al., 2021; PMID: 32346159) and "global DD was reported in 14/15 individuals, including delayed speech and language development (14/14) and motor development (13/14)". However, only one proband was explicitly recorded with speech apraxia (proband 14; supplementary Table 1).

Sources: Expert list, Expert Review; to: First reported CAS case with a de novo SETD1A frameshift variant (Eising et al., 2019; PMID: 29463886)

Fifteen further independent probands with loss-of-function SETD1A variants were investigated (Kummeling et al., 2021; PMID: 32346159) and "global DD was reported in 14/15 individuals, including delayed speech and language development (14/14) and motor development (13/14)". However, only one proband was explicitly recorded with speech apraxia (proband 14; supplementary Table 1).

Sources: Expert list, Expert Review
Speech apraxia v0.38 SETD1B Thomas Scerri changed review comment from: First reported CAS case with a de novo missense SETD1B variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review; to: First reported CAS case with a de novo SETD1B missense variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review
Speech apraxia v0.38 SETBP1 Thomas Scerri changed review comment from: First proband with LoF SETBP1 variant reported for CAS (Eising et al., 2019; PMID: 29463886)

Thirty one further probands with LoF SETBP1 variants studied (Morgan et al., 2019; PMID: 33907317) revealing that "Protracted and aberrant speech development was consistently seen, regardless of motor or intellectual ability. We expand the linguistic phenotype associated with SETBP1 LoF syndrome (SETBP1 haploinsufficiency disorder), revealing a striking speech presentation that implicates both motor (CAS, dysarthria) and language (phonological errors) systems, with CAS (80%) being the most common diagnosis.".
Sources: Expert list, Expert Review; to: First reported CAS case with a SETBP1 frameshift variant reported for CAS (Eising et al., 2019; PMID: 29463886)

Thirty one further probands with loss-of-function SETBP1 variants studied (Morgan et al., 2019; PMID: 33907317) revealing that "Protracted and aberrant speech development was consistently seen, regardless of motor or intellectual ability. We expand the linguistic phenotype associated with SETBP1 LoF syndrome (SETBP1 haploinsufficiency disorder), revealing a striking speech presentation that implicates both motor (CAS, dysarthria) and language (phonological errors) systems, with CAS (80%; 25/31) being the most common diagnosis.".
Sources: Expert list, Expert Review
Cerebral Palsy v1.356 ZDHHC9 Zornitza Stark Publications for gene: ZDHHC9 were set to PMID: 33528536; PMID: 38693247
Cerebral Palsy v1.355 ZIC2 Zornitza Stark Marked gene: ZIC2 as ready
Cerebral Palsy v1.355 ZIC2 Zornitza Stark Gene: zic2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.355 ZIC2 Zornitza Stark Classified gene: ZIC2 as Red List (low evidence)
Cerebral Palsy v1.355 ZIC2 Zornitza Stark Gene: zic2 has been classified as Red List (Low Evidence).
Speech apraxia v0.38 ZBTB18 Zornitza Stark Marked gene: ZBTB18 as ready
Speech apraxia v0.38 ZBTB18 Zornitza Stark Gene: zbtb18 has been classified as Red List (Low Evidence).
Speech apraxia v0.38 ZBTB18 Zornitza Stark Classified gene: ZBTB18 as Red List (low evidence)
Speech apraxia v0.38 ZBTB18 Zornitza Stark Gene: zbtb18 has been classified as Red List (Low Evidence).
Speech apraxia v0.37 TRIP12 Zornitza Stark Marked gene: TRIP12 as ready
Speech apraxia v0.37 TRIP12 Zornitza Stark Gene: trip12 has been classified as Red List (Low Evidence).
Speech apraxia v0.37 TRIP12 Zornitza Stark Classified gene: TRIP12 as Red List (low evidence)
Speech apraxia v0.37 TRIP12 Zornitza Stark Gene: trip12 has been classified as Red List (Low Evidence).
Speech apraxia v0.36 TAOK2 Zornitza Stark Marked gene: TAOK2 as ready
Speech apraxia v0.36 TAOK2 Zornitza Stark Gene: taok2 has been classified as Red List (Low Evidence).
Speech apraxia v0.36 TAOK2 Zornitza Stark Classified gene: TAOK2 as Red List (low evidence)
Speech apraxia v0.36 TAOK2 Zornitza Stark Gene: taok2 has been classified as Red List (Low Evidence).
Speech apraxia v0.35 SPAST Zornitza Stark Marked gene: SPAST as ready
Speech apraxia v0.35 SPAST Zornitza Stark Gene: spast has been classified as Red List (Low Evidence).
Speech apraxia v0.35 SPAST Zornitza Stark Classified gene: SPAST as Red List (low evidence)
Speech apraxia v0.35 SPAST Zornitza Stark Gene: spast has been classified as Red List (Low Evidence).
Speech apraxia v0.34 SHANK3 Zornitza Stark Marked gene: SHANK3 as ready
Speech apraxia v0.34 SHANK3 Zornitza Stark Gene: shank3 has been classified as Green List (High Evidence).
Speech apraxia v0.34 SHANK3 Zornitza Stark Classified gene: SHANK3 as Green List (high evidence)
Speech apraxia v0.34 SHANK3 Zornitza Stark Gene: shank3 has been classified as Green List (High Evidence).
Speech apraxia v0.33 SETD1B Zornitza Stark Marked gene: SETD1B as ready
Speech apraxia v0.33 SETD1B Zornitza Stark Gene: setd1b has been classified as Red List (Low Evidence).
Speech apraxia v0.33 SETD1B Zornitza Stark Classified gene: SETD1B as Red List (low evidence)
Speech apraxia v0.33 SETD1B Zornitza Stark Gene: setd1b has been classified as Red List (Low Evidence).
Mendeliome v1.1852 RBFOX3 Zornitza Stark Marked gene: RBFOX3 as ready
Mendeliome v1.1852 RBFOX3 Zornitza Stark Gene: rbfox3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1852 RBFOX3 Zornitza Stark Classified gene: RBFOX3 as Amber List (moderate evidence)
Mendeliome v1.1852 RBFOX3 Zornitza Stark Gene: rbfox3 has been classified as Amber List (Moderate Evidence).
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
Genetic Epilepsy v1.28 RBFOX3 Zornitza Stark Marked gene: RBFOX3 as ready
Genetic Epilepsy v1.28 RBFOX3 Zornitza Stark Gene: rbfox3 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v1.28 RBFOX3 Zornitza Stark Classified gene: RBFOX3 as Amber List (moderate evidence)
Genetic Epilepsy v1.28 RBFOX3 Zornitza Stark Gene: rbfox3 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v1.27 RBFOX3 Zornitza Stark gene: RBFOX3 was added
gene: RBFOX3 was added to Genetic Epilepsy. 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
Speech apraxia v0.32 RBFOX3 Zornitza Stark Marked gene: RBFOX3 as ready
Speech apraxia v0.32 RBFOX3 Zornitza Stark Gene: rbfox3 has been classified as Amber List (Moderate Evidence).
Speech apraxia v0.32 RBFOX3 Zornitza Stark Classified gene: RBFOX3 as Amber List (moderate evidence)
Speech apraxia v0.32 RBFOX3 Zornitza Stark Gene: rbfox3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1850 GRXCR2 Zornitza Stark Publications for gene: GRXCR2 were set to 24619944
Mendeliome v1.1849 GRXCR2 Zornitza Stark Mode of inheritance for gene: GRXCR2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1848 GRXCR2 Zornitza Stark Classified gene: GRXCR2 as Green List (high evidence)
Mendeliome v1.1848 GRXCR2 Zornitza Stark Gene: grxcr2 has been classified as Green List (High Evidence).
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
Deafness_Isolated v1.61 GRXCR2 Zornitza Stark Publications for gene: GRXCR2 were set to 24619944
Deafness_Isolated v1.60 GRXCR2 Zornitza Stark Classified gene: GRXCR2 as Green List (high evidence)
Deafness_Isolated v1.60 GRXCR2 Zornitza Stark Gene: grxcr2 has been classified as Green List (High Evidence).
Deafness_Isolated v1.59 GRXCR2 Zornitza Stark reviewed gene: GRXCR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33528103; Phenotypes: Deafness, autosomal recessive 101, MIM# 615837; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.188 GRXCR2 Zornitza Stark Publications for gene: GRXCR2 were set to 24619944
Deafness_IsolatedAndComplex v1.187 GRXCR2 Zornitza Stark Classified gene: GRXCR2 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.187 GRXCR2 Zornitza Stark Gene: grxcr2 has been classified as Green List (High Evidence).
Speech apraxia v0.31 MKL2 Thomas Scerri changed review comment from: p.R104G and p.A91P reported as a gain of function (JC Andrews et al., 2023).

Additional phenotypes: ID, GDD, CAS, mild dysmorphic features, impulse control issues (PMID: 38366112).
Sources: Expert list, Expert Review; to: First reported CAS case with a MKL2 splice acceptor variant (Eising et al., 2019; PMID: 29463886). However, it is only predicted to be likely pathogenic and is observed 500+ times in gnomad v4 and has a low variant quality score.

Andrews et al. (2023; PMID: 37013900) identify two cases with de novo MKL2 missense variants (p.R104G and p.A91P) with reported gain of function. One case is reported with apraxia and the other with speech apraxia (Table 1).

Additional phenotypes: ID, GDD, CAS, mild dysmorphic features, impulse control issues (PMID: 38366112).
Sources: Expert list, Expert Review
Speech apraxia v0.31 KAT6A Thomas Scerri changed review comment from: First reported CAS case with a de novo missense CHD3 variant (Eising et al., 2019; PMID: 29463886).

Kennedy et al. (2019; PMID: 30245513) examined 76 cases (including 52 new cases) with CHD3 variants and found speech delay was a core feature, and report 1 case diagnosed with oromotor dyspraxia.

St John et al. (2022; PMID: 35892268) examined 49 cases and found "Verbal participants (13/49) displayed complex and co-occurring speech diagnoses regarding the perception/production of speech sounds, including phonological impairment (i.e., linguistic deficits) and speech apraxia (i.e., motor planning/programming deficits), which significantly impacted intelligibility. Receptive/expressive language and adaptive functioning were also severely impaired." In detail, "Across the 13 verbal participants, speech profiles, and intelligibility were varied (Table 2). 10/13 verbal participants were female (77%). 11/13 had delayed speech milestones, some not achieving first words until >18 months and others not combining words until >8 years of age. Verbal participants had a range of speech disorder subtypes, and most had at least two diagnoses (Figure 1c). Phonological delay was most common (8/13, 63%), followed by phonological disorder (7/13, 54%) and CAS (7/13, 54%), but all three conditions always co-occurred with at least one other speech diagnosis. "


Sources: Expert list, Expert Review; to: First reported CAS case with a KAT6A splice acceptor variant (Eising et al., 2019; PMID: 29463886).

Kennedy et al. (2019; PMID: 30245513) examined 76 cases (including 52 new cases) with KAT6A variants and found speech delay was a core feature, and report 1 case diagnosed with oromotor dyspraxia.

St John et al. (2022; PMID: 35892268) examined 49 cases with KAT6A variants and found "Verbal participants (13/49) displayed complex and co-occurring speech diagnoses regarding the perception/production of speech sounds, including phonological impairment (i.e., linguistic deficits) and speech apraxia (i.e., motor planning/programming deficits), which significantly impacted intelligibility. Receptive/expressive language and adaptive functioning were also severely impaired." In detail, "Across the 13 verbal participants, speech profiles, and intelligibility were varied (Table 2). 10/13 verbal participants were female (77%). 11/13 had delayed speech milestones, some not achieving first words until >18 months and others not combining words until >8 years of age. Verbal participants had a range of speech disorder subtypes, and most had at least two diagnoses (Figure 1c). Phonological delay was most common (8/13, 63%), followed by phonological disorder (7/13, 54%) and CAS (7/13, 54%), but all three conditions always co-occurred with at least one other speech diagnosis. "


Sources: Expert list, Expert Review
Speech apraxia v0.31 KAT6A Thomas Scerri changed review comment from: Additional phenotypes: ID, vision impairment, GI dysfunction, sleep disturbance, ASD, majority minimally verbal & rely on alternate communication. Rates of epilepsy, ADHD, CP higher than typical population (PMID: 38366112).
Sources: Expert list, Expert Review; to: First reported CAS case with a de novo missense CHD3 variant (Eising et al., 2019; PMID: 29463886).

Kennedy et al. (2019; PMID: 30245513) examined 76 cases (including 52 new cases) with CHD3 variants and found speech delay was a core feature, and report 1 case diagnosed with oromotor dyspraxia.

St John et al. (2022; PMID: 35892268) examined 49 cases and found "Verbal participants (13/49) displayed complex and co-occurring speech diagnoses regarding the perception/production of speech sounds, including phonological impairment (i.e., linguistic deficits) and speech apraxia (i.e., motor planning/programming deficits), which significantly impacted intelligibility. Receptive/expressive language and adaptive functioning were also severely impaired." In detail, "Across the 13 verbal participants, speech profiles, and intelligibility were varied (Table 2). 10/13 verbal participants were female (77%). 11/13 had delayed speech milestones, some not achieving first words until >18 months and others not combining words until >8 years of age. Verbal participants had a range of speech disorder subtypes, and most had at least two diagnoses (Figure 1c). Phonological delay was most common (8/13, 63%), followed by phonological disorder (7/13, 54%) and CAS (7/13, 54%), but all three conditions always co-occurred with at least one other speech diagnosis. "


Sources: Expert list, Expert Review
Speech apraxia v0.31 CHD3 Thomas Scerri changed review comment from: Additional phenotypes: ID/DD, macrocephaly, prominent forehead, hypertelorism, hypotonia, joint laxity, severity of neurologic deficits & presence of non-neurologic features are variable. Autistic features are commonly reported (PMID: 38366112).; to: First reported CAS case with a de novo missense CHD3 variant (Eising et al., 2019; PMID: 29463886).

Snijders Blok et al. (2018; PMID: 30397230) examined 35 cases with CHD3 variants. The index case was diagnosed with severe speech apraxia.

Van der Spek et al. (2022; PMID: 35346573) examined 21 families with CHD3 variants and found at least 2 independent cases with speech dyspraxia.
Cerebral Palsy v1.354 ZIC2 Clare van Eyk gene: ZIC2 was added
gene: ZIC2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ZIC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZIC2 were set to PMID: 38553553
Phenotypes for gene: ZIC2 were set to Holoprosencephaly, MIM#609637
Review for gene: ZIC2 was set to RED
Added comment: Single individual with de novo frameshift deletion described in WGS study of clinically confirmed CP (PMID: 38553553).
Sources: Literature
Cerebral Palsy v1.354 ZDHHC9 Clare van Eyk edited their review of gene: ZDHHC9: Added comment: Additional hemizygous male (maternally inherited) with splice variant described in WGS study of clinically confirmed CP (PMID: 38553553).; Changed publications: PMID: 33528536, PMID: 38693247, PMID: 38553553
Speech apraxia v0.31 ZBTB18 Thomas Scerri gene: ZBTB18 was added
gene: ZBTB18 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: ZBTB18 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZBTB18 were set to 36117209
Phenotypes for gene: ZBTB18 were set to Intellectual developmental disorder, autosomal dominant 22, MIM# 612337
Review for gene: ZBTB18 was set to RED
Added comment: First reported CAS case with an de novo nonsense ZBTB18 variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review
Speech apraxia v0.31 TRIP12 Thomas Scerri gene: TRIP12 was added
gene: TRIP12 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: TRIP12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRIP12 were set to 36117209
Phenotypes for gene: TRIP12 were set to Intellectual developmental disorder, autosomal dominant 49, MIM# 617752
Review for gene: TRIP12 was set to RED
Added comment: First reported CAS case with a de novo exon duplication of TRIP12 (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review
Speech apraxia v0.31 TAOK2 Thomas Scerri gene: TAOK2 was added
gene: TAOK2 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: TAOK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TAOK2 were set to 36117209
Phenotypes for gene: TAOK2 were set to Neurodevelopmental disorder (MONDO:0700092), TAOK2-related
Review for gene: TAOK2 was set to RED
Added comment: First reported CAS case with an de novo missense TAOK2 variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review
Speech apraxia v0.31 SPAST Thomas Scerri gene: SPAST was added
gene: SPAST was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: SPAST was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPAST were set to 36117209
Phenotypes for gene: SPAST were set to Spastic paraplegia 4, autosomal dominant, MIM# 182601
Review for gene: SPAST was set to RED
Added comment: First reported CAS case with an de novo missense SPAST variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review
Speech apraxia v0.31 SHANK3 Thomas Scerri gene: SHANK3 was added
gene: SHANK3 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: SHANK3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SHANK3 were set to 36117209; 33293697
Phenotypes for gene: SHANK3 were set to Phelan-McDermid syndrome, MIM# 606232
Review for gene: SHANK3 was set to GREEN
Added comment: First reported CAS case with an de novo frameshift SHANK3 variant (Kaspi et al., 2022; PMID: 36117209).

Brignell et al. (2021; PMID: 33293697) report 2 cases of CAS in a cohort of individuals with Phelan-McDermid/22q13 deletion syndrome, caused by heterozygous loss of function of SHANK3.
Sources: Expert list, Expert Review
Speech apraxia v0.31 SETD1B Thomas Scerri gene: SETD1B was added
gene: SETD1B was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: SETD1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SETD1B were set to 36117209
Phenotypes for gene: SETD1B were set to Intellectual developmental disorder with seizures and language delay, MIM# 619000
Review for gene: SETD1B was set to RED
Added comment: First reported CAS case with a de novo missense SETD1B variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review
Speech apraxia v0.31 RBFOX3 Thomas Scerri gene: RBFOX3 was added
gene: RBFOX3 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: RBFOX3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RBFOX3 were set to 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: First reported CAS case with a paternally inherited nonsense RBFOX3 variant (Kaspi et al., 2022; PMID: 36117209). The carrier father was also affected.

Lal et al. (2013; PMID: 24039908) report two cases with nonsense RBFOX3 variants, both with initial speech or language delay, and one of which with "Moderate developmetal delay, delayed speech development, mild oral dyspraxia".
Sources: Expert list, Expert Review
Cerebral Palsy v1.354 PDE10A Zornitza Stark Marked gene: PDE10A as ready
Cerebral Palsy v1.354 PDE10A Zornitza Stark Gene: pde10a has been classified as Red List (Low Evidence).
Cerebral Palsy v1.354 PDE10A Zornitza Stark Classified gene: PDE10A as Red List (low evidence)
Cerebral Palsy v1.354 PDE10A Zornitza Stark Gene: pde10a has been classified as Red List (Low Evidence).
Cerebral Palsy v1.353 PHIP Zornitza Stark Classified gene: PHIP as Green List (high evidence)
Cerebral Palsy v1.353 PHIP Zornitza Stark Gene: phip has been classified as Green List (High Evidence).
Cerebral Palsy v1.352 PHKA2 Zornitza Stark Marked gene: PHKA2 as ready
Cerebral Palsy v1.352 PHKA2 Zornitza Stark Gene: phka2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.352 PHKA2 Zornitza Stark Classified gene: PHKA2 as Red List (low evidence)
Cerebral Palsy v1.352 PHKA2 Zornitza Stark Gene: phka2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.351 PIK3R2 Zornitza Stark Marked gene: PIK3R2 as ready
Cerebral Palsy v1.351 PIK3R2 Zornitza Stark Gene: pik3r2 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.351 PIK3R2 Zornitza Stark Classified gene: PIK3R2 as Amber List (moderate evidence)
Cerebral Palsy v1.351 PIK3R2 Zornitza Stark Gene: pik3r2 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.350 SOX2 Zornitza Stark Marked gene: SOX2 as ready
Cerebral Palsy v1.350 SOX2 Zornitza Stark Gene: sox2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.350 SOX2 Zornitza Stark Classified gene: SOX2 as Red List (low evidence)
Cerebral Palsy v1.350 SOX2 Zornitza Stark Gene: sox2 has been classified as Red List (Low Evidence).
Speech apraxia v0.31 HNRNPK Zornitza Stark Marked gene: HNRNPK as ready
Speech apraxia v0.31 HNRNPK Zornitza Stark Gene: hnrnpk has been classified as Red List (Low Evidence).
Speech apraxia v0.31 HNRNPK Zornitza Stark Classified gene: HNRNPK as Red List (low evidence)
Speech apraxia v0.31 HNRNPK Zornitza Stark Gene: hnrnpk has been classified as Red List (Low Evidence).
Speech apraxia v0.30 KDM5C Zornitza Stark Marked gene: KDM5C as ready
Speech apraxia v0.30 KDM5C Zornitza Stark Gene: kdm5c has been classified as Red List (Low Evidence).
Speech apraxia v0.30 KDM5C Zornitza Stark Classified gene: KDM5C as Red List (low evidence)
Speech apraxia v0.30 KDM5C Zornitza Stark Gene: kdm5c has been classified as Red List (Low Evidence).
Speech apraxia v0.29 PHF21A Zornitza Stark Marked gene: PHF21A as ready
Speech apraxia v0.29 PHF21A Zornitza Stark Gene: phf21a has been classified as Red List (Low Evidence).
Speech apraxia v0.29 PHF21A Zornitza Stark Classified gene: PHF21A as Red List (low evidence)
Speech apraxia v0.29 PHF21A Zornitza Stark Gene: phf21a has been classified as Red List (Low Evidence).
Speech apraxia v0.28 PURA Zornitza Stark Marked gene: PURA as ready
Speech apraxia v0.28 PURA Zornitza Stark Gene: pura has been classified as Red List (Low Evidence).
Speech apraxia v0.28 PURA Zornitza Stark Classified gene: PURA as Red List (low evidence)
Speech apraxia v0.28 PURA Zornitza Stark Gene: pura has been classified as Red List (Low Evidence).
Bone Marrow Failure v1.93 ERG Zornitza Stark Classified gene: ERG as Green List (high evidence)
Bone Marrow Failure v1.93 ERG Zornitza Stark Gene: erg has been classified as Green List (High Evidence).
Cerebral Palsy v1.349 TRIP12 Zornitza Stark Marked gene: TRIP12 as ready
Cerebral Palsy v1.349 TRIP12 Zornitza Stark Gene: trip12 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.349 TRIP12 Zornitza Stark Classified gene: TRIP12 as Red List (low evidence)
Cerebral Palsy v1.349 TRIP12 Zornitza Stark Gene: trip12 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.348 TRIP12 Clare van Eyk gene: TRIP12 was added
gene: TRIP12 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TRIP12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRIP12 were set to PMID: 36747006
Phenotypes for gene: TRIP12 were set to Intellectual developmental disorder, autosomal dominant 49, MIM#617752
Review for gene: TRIP12 was set to RED
Added comment: Single individual with de novo splice variant described in WGS study of clinically confirmed CP (PMID: 38553553). Motor delays are reported to be common in TRIP12 syndrome.
Sources: Literature
Bone Marrow Failure v1.92 ERG Hamish Scott reviewed gene: ERG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: cytopenia, Thrombocytopenia, MDS, Lymphedema; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Early-onset Dementia v1.22 GBA Lauren Rogers reviewed gene: GBA: Rating: AMBER; Mode of pathogenicity: None; Publications: 36084847; Phenotypes: {Lewy body dementia, susceptibility to} (MIM# 127750); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Speech apraxia v0.27 PURA Thomas Scerri edited their review of gene: PURA: Changed rating: RED
Speech apraxia v0.27 PURA Thomas Scerri gene: PURA was added
gene: PURA was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: PURA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PURA were set to 36117209
Phenotypes for gene: PURA were set to Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties, MIM# 616158
Added comment: First reported CAS case with an inherited missense PURA variant (Kaspi et al., 2022; PMID: 36117209). Both proband and parent affected.
Sources: Expert list, Expert Review
Speech apraxia v0.27 PHF21A Thomas Scerri gene: PHF21A was added
gene: PHF21A was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: PHF21A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PHF21A were set to 36117209
Phenotypes for gene: PHF21A were set to Intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures, MIM# 618725
Review for gene: PHF21A was set to RED
Added comment: First reported CAS case with a de novo frameshift PHF21A variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review
Speech apraxia v0.27 KDM5C Thomas Scerri gene: KDM5C was added
gene: KDM5C was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: KDM5C 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: KDM5C were set to 36117209; 36434256
Phenotypes for gene: KDM5C were set to Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type, MIM# 300534
Review for gene: KDM5C was set to RED
Added comment: First reported CAS case with a de novo frameshift HNRNPK variant (Kaspi et al., 2022; PMID: 36117209).

Leonardi et al. (2023; PMID: 36434256) report 30 individuals with HNRNPK variants, of which 16 have reported speech delay (including all males with records, and several females). No mention of apraxia or dyspraxia though.

Note: Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type (MIM# 300534) is recorded as autosomal recessive, however female heterozygotes can have milder phenotypes.
Sources: Expert list, Expert Review
Speech apraxia v0.27 HNRNPK Thomas Scerri gene: HNRNPK was added
gene: HNRNPK was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: HNRNPK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HNRNPK were set to 36117209
Phenotypes for gene: HNRNPK were set to Au-Kline syndrome, MIM# 616580
Review for gene: HNRNPK was set to RED
Added comment: First reported CAS case with a de novo nonsense HNRNPK variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review
Cerebral Palsy v1.348 SOX2 Clare van Eyk gene: SOX2 was added
gene: SOX2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SOX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOX2 were set to PMID: 38553553
Phenotypes for gene: SOX2 were set to Microphthalmia, syndromic 3; Optic nerve hypoplasia and abnormalities of the central nervous system, MIM#206900
Review for gene: SOX2 was set to RED
Added comment: Single individual with de novo frameshift deletion described in WGS study of clinically confirmed CP (PMID: 38553553). SOX2 disorders are associated with a spectrum of phenotypes which frequently include psychomotor delay, hypotonia, dystonia (including status dystonicus), spastic diplegia/quadriplegia.
Sources: Literature
Cerebral Palsy v1.348 PIK3R2 Clare van Eyk gene: PIK3R2 was added
gene: PIK3R2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PIK3R2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PIK3R2 were set to PMID: 38553553
Phenotypes for gene: PIK3R2 were set to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1, MIM#603387
Mode of pathogenicity for gene: PIK3R2 was set to Other
Review for gene: PIK3R2 was set to AMBER
Added comment: Single individual with de novo heterozygous p.G373R variant described in WGS study of clinically confirmed CP (PMID: 38553553). This variant is reported multiple times in ClinVar and literature as a recurrent pathogenic activating mutation. Additional case in literature with same variant and spastic hemiplegia (PMID: 26860062). Constitutional and mosaic mutations in PIK3R2 are associated with a range of developmental brain disorders.
Sources: Literature
Cerebral Palsy v1.348 PHKA2 Clare van Eyk gene: PHKA2 was added
gene: PHKA2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PHKA2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PHKA2 were set to PMID: 38553553
Phenotypes for gene: PHKA2 were set to Glycogen storage disease, type IXa, 306000
Review for gene: PHKA2 was set to RED
Added comment: Single individual with de novo hemizygous variant described in WGS study of clinically confirmed CP (PMID: 38553553). Variant has multiple entries in ClinVar - pathogenic/likely pathogenic. GSD9A is primarily associated with liver dysfunction, however dysregulation of glucose metabolism can cause damage to the CNS.
Sources: Literature
Cerebral Palsy v1.348 PHIP Clare van Eyk edited their review of gene: PHIP: Added comment: Additional individual with a pathogenic de novo frameshift insertion described in WGS study of clinically confirmed CP (PMID: 38553553).; Changed rating: GREEN; Changed publications: PMID: 38693247, PMID:33528536, PMID: 38553553
Cerebral Palsy v1.348 PDE10A Clare van Eyk gene: PDE10A was added
gene: PDE10A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PDE10A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: PDE10A were set to PMID: 38553553
Phenotypes for gene: PDE10A were set to Dyskinesia, limb and orofacial, infantile-onset, autosomal recessive, MIM#616921; Striatal degeneration, autosomal dominant, MIM#616922
Review for gene: PDE10A was set to RED
Added comment: Single individual with de novo frameshift deletion described in WGS study of clinically confirmed CP (PMID: 38553553).

Biallelic variants have been reported to cause a hyperkinetic movement disorder with onset in infancy (PMID: 27058446).
Sources: Literature
Cerebral Palsy v1.348 MEF2C Clare van Eyk reviewed gene: MEF2C: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38553553; Phenotypes: Neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language MIM#613443; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.348 KDM3B Clare van Eyk gene: KDM3B was added
gene: KDM3B was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: KDM3B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KDM3B were set to PMID: 38553553
Phenotypes for gene: KDM3B were set to Diets-Jongmans syndrome, MIM#618846
Review for gene: KDM3B was set to RED
Added comment: Single individual with de novo likely pathogenic variant described in WGS study of clinically confirmed CP (PMID: 38553553).
Sources: Literature
Cerebral Palsy v1.348 GATAD2B Clare van Eyk edited their review of gene: GATAD2B: Added comment: Additional case with de novo heterozygous LP variant described in WGS study of clinically confirmed CP (PMID: 38553553). Same variant previously reported pathogenic from clinical testing in ClinVar, but no phenotypic data.; Changed publications: PMID: 38693247, PMID: 38553553
Cerebral Palsy v1.348 ERLIN2 Clare van Eyk gene: ERLIN2 was added
gene: ERLIN2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ERLIN2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ERLIN2 were set to PMID: 38553553
Phenotypes for gene: ERLIN2 were set to Spastic paraplegia 18A, autosomal dominant, MIM#620512; Spastic paraplegia 18B, autosomal recessive, MIM#611225
Review for gene: ERLIN2 was set to RED
Added comment: Single individual with homozygous frameshift insertion in ERLIN2 described in WGS study of clinically confirmed CP (PMID: 38553553). Both monoallelic and biallelic variants have been reported to cause hereditary spastic paraplegia.
Sources: Literature
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
Aortopathy_Connective Tissue Disorders v1.85 THBS2 Zornitza Stark Phenotypes for gene: THBS2 were changed from connective tissue disorder MONDO:0003900, THBS2-related to Ehlers-Danlos syndrome, classic type, 3, MIM# 620865
Aortopathy_Connective Tissue Disorders v1.84 THBS2 Zornitza Stark reviewed gene: THBS2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Ehlers-Danlos syndrome, classic type, 3, MIM# 620865; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v1.186 GRXCR2 Achchuthan Shanmugasundram reviewed gene: GRXCR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33528103; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.348 LZTR1 Zornitza Stark Marked gene: LZTR1 as ready
Cerebral Palsy v1.348 LZTR1 Zornitza Stark Gene: lztr1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.348 LZTR1 Zornitza Stark Classified gene: LZTR1 as Red List (low evidence)
Cerebral Palsy v1.348 LZTR1 Zornitza Stark Gene: lztr1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.347 MCCC2 Zornitza Stark Marked gene: MCCC2 as ready
Cerebral Palsy v1.347 MCCC2 Zornitza Stark Gene: mccc2 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.347 MCCC2 Zornitza Stark Classified gene: MCCC2 as Amber List (moderate evidence)
Cerebral Palsy v1.347 MCCC2 Zornitza Stark Gene: mccc2 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.346 MED12 Zornitza Stark Marked gene: MED12 as ready
Cerebral Palsy v1.346 MED12 Zornitza Stark Gene: med12 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.346 MED12 Zornitza Stark Publications for gene: MED12 were set to PMID: 38693247
Cerebral Palsy v1.345 MED12 Zornitza Stark Classified gene: MED12 as Amber List (moderate evidence)
Cerebral Palsy v1.345 MED12 Zornitza Stark Gene: med12 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.344 MMACHC Zornitza Stark Marked gene: MMACHC as ready
Cerebral Palsy v1.344 MMACHC Zornitza Stark Gene: mmachc has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.344 MMACHC Zornitza Stark Classified gene: MMACHC as Amber List (moderate evidence)
Cerebral Palsy v1.344 MMACHC Zornitza Stark Gene: mmachc has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.343 MUT Zornitza Stark Marked gene: MUT as ready
Cerebral Palsy v1.343 MUT Zornitza Stark Gene: mut has been classified as Red List (Low Evidence).
Cerebral Palsy v1.343 MUT Zornitza Stark Classified gene: MUT as Red List (low evidence)
Cerebral Palsy v1.343 MUT Zornitza Stark Gene: mut has been classified as Red List (Low Evidence).
Cerebral Palsy v1.342 MYO9A Zornitza Stark Marked gene: MYO9A as ready
Cerebral Palsy v1.342 MYO9A Zornitza Stark Gene: myo9a has been classified as Red List (Low Evidence).
Cerebral Palsy v1.342 MYO9A Zornitza Stark Classified gene: MYO9A as Red List (low evidence)
Cerebral Palsy v1.342 MYO9A Zornitza Stark Gene: myo9a has been classified as Red List (Low Evidence).
Cerebral Palsy v1.341 PCLO Zornitza Stark Marked gene: PCLO as ready
Cerebral Palsy v1.341 PCLO Zornitza Stark Gene: pclo has been classified as Red List (Low Evidence).
Cerebral Palsy v1.341 PCLO Zornitza Stark Classified gene: PCLO as Red List (low evidence)
Cerebral Palsy v1.341 PCLO Zornitza Stark Gene: pclo has been classified as Red List (Low Evidence).
Cerebral Palsy v1.340 PIDD1 Zornitza Stark Marked gene: PIDD1 as ready
Cerebral Palsy v1.340 PIDD1 Zornitza Stark Gene: pidd1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.340 PIDD1 Zornitza Stark Classified gene: PIDD1 as Red List (low evidence)
Cerebral Palsy v1.340 PIDD1 Zornitza Stark Gene: pidd1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.339 LRP2 Zornitza Stark Marked gene: LRP2 as ready
Cerebral Palsy v1.339 LRP2 Zornitza Stark Gene: lrp2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.339 LRP2 Zornitza Stark Classified gene: LRP2 as Red List (low evidence)
Cerebral Palsy v1.339 LRP2 Zornitza Stark Gene: lrp2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.338 LAMA1 Zornitza Stark Marked gene: LAMA1 as ready
Cerebral Palsy v1.338 LAMA1 Zornitza Stark Gene: lama1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.338 LAMA1 Zornitza Stark Classified gene: LAMA1 as Red List (low evidence)
Cerebral Palsy v1.338 LAMA1 Zornitza Stark Gene: lama1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.337 HCFC1 Zornitza Stark Marked gene: HCFC1 as ready
Cerebral Palsy v1.337 HCFC1 Zornitza Stark Gene: hcfc1 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.337 HCFC1 Zornitza Stark Classified gene: HCFC1 as Amber List (moderate evidence)
Cerebral Palsy v1.337 HCFC1 Zornitza Stark Gene: hcfc1 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.336 FGD1 Zornitza Stark Marked gene: FGD1 as ready
Cerebral Palsy v1.336 FGD1 Zornitza Stark Gene: fgd1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.336 FGD1 Zornitza Stark Classified gene: FGD1 as Red List (low evidence)
Cerebral Palsy v1.336 FGD1 Zornitza Stark Gene: fgd1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.335 EBP Zornitza Stark Marked gene: EBP as ready
Cerebral Palsy v1.335 EBP Zornitza Stark Gene: ebp has been classified as Red List (Low Evidence).
Cerebral Palsy v1.335 EBP Zornitza Stark Classified gene: EBP as Red List (low evidence)
Cerebral Palsy v1.335 EBP Zornitza Stark Gene: ebp has been classified as Red List (Low Evidence).
Cerebral Palsy v1.334 CCDC22 Zornitza Stark Marked gene: CCDC22 as ready
Cerebral Palsy v1.334 CCDC22 Zornitza Stark Gene: ccdc22 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.334 CCDC22 Zornitza Stark Classified gene: CCDC22 as Red List (low evidence)
Cerebral Palsy v1.334 CCDC22 Zornitza Stark Gene: ccdc22 has been classified as Red List (Low Evidence).
Speech apraxia v0.27 ERF Zornitza Stark Marked gene: ERF as ready
Speech apraxia v0.27 ERF Zornitza Stark Gene: erf has been classified as Amber List (Moderate Evidence).
Speech apraxia v0.27 ERF Zornitza Stark Classified gene: ERF as Amber List (moderate evidence)
Speech apraxia v0.27 ERF Zornitza Stark Gene: erf has been classified as Amber List (Moderate Evidence).
Speech apraxia v0.26 ZNF142 Zornitza Stark Marked gene: ZNF142 as ready
Speech apraxia v0.26 ZNF142 Zornitza Stark Gene: znf142 has been classified as Amber List (Moderate Evidence).
Speech apraxia v0.26 ZNF142 Zornitza Stark Classified gene: ZNF142 as Amber List (moderate evidence)
Speech apraxia v0.26 ZNF142 Zornitza Stark Gene: znf142 has been classified as Amber List (Moderate Evidence).
Speech apraxia v0.25 ZFHX4 Zornitza Stark Marked gene: ZFHX4 as ready
Speech apraxia v0.25 ZFHX4 Zornitza Stark Gene: zfhx4 has been classified as Red List (Low Evidence).
Speech apraxia v0.25 ZFHX4 Zornitza Stark Classified gene: ZFHX4 as Red List (low evidence)
Speech apraxia v0.25 ZFHX4 Zornitza Stark Gene: zfhx4 has been classified as Red List (Low Evidence).
Speech apraxia v0.24 WDR5 Zornitza Stark Marked gene: WDR5 as ready
Speech apraxia v0.24 WDR5 Zornitza Stark Gene: wdr5 has been classified as Green List (High Evidence).
Speech apraxia v0.24 WDR5 Zornitza Stark Classified gene: WDR5 as Green List (high evidence)
Speech apraxia v0.24 WDR5 Zornitza Stark Gene: wdr5 has been classified as Green List (High Evidence).
Speech apraxia v0.23 UPF2 Zornitza Stark Marked gene: UPF2 as ready
Speech apraxia v0.23 UPF2 Zornitza Stark Gene: upf2 has been classified as Red List (Low Evidence).
Speech apraxia v0.23 UPF2 Zornitza Stark Classified gene: UPF2 as Red List (low evidence)
Speech apraxia v0.23 UPF2 Zornitza Stark Gene: upf2 has been classified as Red List (Low Evidence).
Speech apraxia v0.22 TNRC6B Zornitza Stark Marked gene: TNRC6B as ready
Speech apraxia v0.22 TNRC6B Zornitza Stark Gene: tnrc6b has been classified as Amber List (Moderate Evidence).
Speech apraxia v0.22 TNRC6B Zornitza Stark Classified gene: TNRC6B as Amber List (moderate evidence)
Speech apraxia v0.22 TNRC6B Zornitza Stark Gene: tnrc6b has been classified as Amber List (Moderate Evidence).
Speech apraxia v0.21 SETD1A Zornitza Stark Marked gene: SETD1A as ready
Speech apraxia v0.21 SETD1A Zornitza Stark Gene: setd1a has been classified as Amber List (Moderate Evidence).
Speech apraxia v0.21 SETD1A Zornitza Stark Classified gene: SETD1A as Amber List (moderate evidence)
Speech apraxia v0.21 SETD1A Zornitza Stark Gene: setd1a has been classified as Amber List (Moderate Evidence).
Speech apraxia v0.20 SETBP1 Zornitza Stark Marked gene: SETBP1 as ready
Speech apraxia v0.20 SETBP1 Zornitza Stark Gene: setbp1 has been classified as Green List (High Evidence).
Speech apraxia v0.20 SETBP1 Zornitza Stark Classified gene: SETBP1 as Green List (high evidence)
Speech apraxia v0.20 SETBP1 Zornitza Stark Gene: setbp1 has been classified as Green List (High Evidence).
Speech apraxia v0.19 POGZ Zornitza Stark Marked gene: POGZ as ready
Speech apraxia v0.19 POGZ Zornitza Stark Gene: pogz has been classified as Red List (Low Evidence).
Speech apraxia v0.19 POGZ Zornitza Stark Classified gene: POGZ as Red List (low evidence)
Speech apraxia v0.19 POGZ Zornitza Stark Gene: pogz has been classified as Red List (Low Evidence).
Speech apraxia v0.18 MEIS2 Zornitza Stark Marked gene: MEIS2 as ready
Speech apraxia v0.18 MEIS2 Zornitza Stark Gene: meis2 has been classified as Amber List (Moderate Evidence).
Speech apraxia v0.18 MEIS2 Zornitza Stark Classified gene: MEIS2 as Amber List (moderate evidence)
Speech apraxia v0.18 MEIS2 Zornitza Stark Gene: meis2 has been classified as Amber List (Moderate Evidence).
Speech apraxia v0.17 GNB1 Zornitza Stark Marked gene: GNB1 as ready
Speech apraxia v0.17 GNB1 Zornitza Stark Gene: gnb1 has been classified as Red List (Low Evidence).
Speech apraxia v0.17 GNB1 Zornitza Stark Classified gene: GNB1 as Red List (low evidence)
Speech apraxia v0.17 GNB1 Zornitza Stark Gene: gnb1 has been classified as Red List (Low Evidence).
Speech apraxia v0.16 GNAO1 Zornitza Stark Marked gene: GNAO1 as ready
Speech apraxia v0.16 GNAO1 Zornitza Stark Gene: gnao1 has been classified as Amber List (Moderate Evidence).
Speech apraxia v0.16 GNAO1 Zornitza Stark Classified gene: GNAO1 as Amber List (moderate evidence)
Speech apraxia v0.16 GNAO1 Zornitza Stark Gene: gnao1 has been classified as Amber List (Moderate Evidence).
Speech apraxia v0.15 EBF3 Zornitza Stark Marked gene: EBF3 as ready
Speech apraxia v0.15 EBF3 Zornitza Stark Gene: ebf3 has been classified as Green List (High Evidence).
Speech apraxia v0.15 EBF3 Zornitza Stark Classified gene: EBF3 as Green List (high evidence)
Speech apraxia v0.15 EBF3 Zornitza Stark Gene: ebf3 has been classified as Green List (High Evidence).
Speech apraxia v0.14 DIP2C Zornitza Stark Marked gene: DIP2C as ready
Speech apraxia v0.14 DIP2C Zornitza Stark Gene: dip2c has been classified as Green List (High Evidence).
Speech apraxia v0.14 DIP2C Zornitza Stark Classified gene: DIP2C as Green List (high evidence)
Speech apraxia v0.14 DIP2C Zornitza Stark Gene: dip2c has been classified as Green List (High Evidence).
Speech apraxia v0.13 DDX3X Zornitza Stark Marked gene: DDX3X as ready
Speech apraxia v0.13 DDX3X Zornitza Stark Gene: ddx3x has been classified as Green List (High Evidence).
Speech apraxia v0.13 DDX3X Zornitza Stark Classified gene: DDX3X as Green List (high evidence)
Speech apraxia v0.13 DDX3X Zornitza Stark Gene: ddx3x has been classified as Green List (High Evidence).
Speech apraxia v0.12 CDK13 Zornitza Stark Marked gene: CDK13 as ready
Speech apraxia v0.12 CDK13 Zornitza Stark Gene: cdk13 has been classified as Green List (High Evidence).
Speech apraxia v0.12 CDK13 Zornitza Stark Classified gene: CDK13 as Green List (high evidence)
Speech apraxia v0.12 CDK13 Zornitza Stark Gene: cdk13 has been classified as Green List (High Evidence).
Speech apraxia v0.11 BRPF1 Zornitza Stark Marked gene: BRPF1 as ready
Speech apraxia v0.11 BRPF1 Zornitza Stark Gene: brpf1 has been classified as Green List (High Evidence).
Speech apraxia v0.11 BRPF1 Zornitza Stark Classified gene: BRPF1 as Green List (high evidence)
Speech apraxia v0.11 BRPF1 Zornitza Stark Gene: brpf1 has been classified as Green List (High Evidence).
Speech apraxia v0.10 ARHGEF9 Zornitza Stark Marked gene: ARHGEF9 as ready
Speech apraxia v0.10 ARHGEF9 Zornitza Stark Gene: arhgef9 has been classified as Red List (Low Evidence).
Speech apraxia v0.10 ARHGEF9 Zornitza Stark Mode of inheritance for gene: ARHGEF9 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Speech apraxia v0.9 ARHGEF9 Zornitza Stark Classified gene: ARHGEF9 as Red List (low evidence)
Speech apraxia v0.9 ARHGEF9 Zornitza Stark Gene: arhgef9 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.333 OPHN1 Zornitza Stark Marked gene: OPHN1 as ready
Cerebral Palsy v1.333 OPHN1 Zornitza Stark Gene: ophn1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.333 OPHN1 Zornitza Stark Classified gene: OPHN1 as Red List (low evidence)
Cerebral Palsy v1.333 OPHN1 Zornitza Stark Gene: ophn1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.332 PIGA Zornitza Stark Publications for gene: PIGA were set to 33528536; 24706016
Cerebral Palsy v1.331 PLP1 Zornitza Stark Publications for gene: PLP1 were set to 33528536; 25280894; 34816117
Cerebral Palsy v1.330 PHF6 Zornitza Stark Marked gene: PHF6 as ready
Cerebral Palsy v1.330 PHF6 Zornitza Stark Gene: phf6 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.330 PHF6 Zornitza Stark Classified gene: PHF6 as Red List (low evidence)
Cerebral Palsy v1.330 PHF6 Zornitza Stark Gene: phf6 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.329 POLA1 Zornitza Stark Marked gene: POLA1 as ready
Cerebral Palsy v1.329 POLA1 Zornitza Stark Gene: pola1 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.329 POLA1 Zornitza Stark Classified gene: POLA1 as Amber List (moderate evidence)
Cerebral Palsy v1.329 POLA1 Zornitza Stark Gene: pola1 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.328 PQBP1 Zornitza Stark Marked gene: PQBP1 as ready
Cerebral Palsy v1.328 PQBP1 Zornitza Stark Gene: pqbp1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.328 PQBP1 Zornitza Stark Classified gene: PQBP1 as Red List (low evidence)
Cerebral Palsy v1.328 PQBP1 Zornitza Stark Gene: pqbp1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.327 TAF1 Zornitza Stark Publications for gene: TAF1 were set to 26637982; 33528536; 17273961
Cerebral Palsy v1.326 THOC2 Zornitza Stark Marked gene: THOC2 as ready
Cerebral Palsy v1.326 THOC2 Zornitza Stark Added comment: Comment when marking as ready: Amber rating due to lack of phenotypic data in the large cohort study.
Cerebral Palsy v1.326 THOC2 Zornitza Stark Gene: thoc2 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.326 THOC2 Zornitza Stark Classified gene: THOC2 as Amber List (moderate evidence)
Cerebral Palsy v1.326 THOC2 Zornitza Stark Gene: thoc2 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.325 ZDHHC9 Zornitza Stark Marked gene: ZDHHC9 as ready
Cerebral Palsy v1.325 ZDHHC9 Zornitza Stark Gene: zdhhc9 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.325 ZDHHC9 Zornitza Stark Classified gene: ZDHHC9 as Amber List (moderate evidence)
Cerebral Palsy v1.325 ZDHHC9 Zornitza Stark Gene: zdhhc9 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.324 B4GALNT1 Zornitza Stark Classified gene: B4GALNT1 as Amber List (moderate evidence)
Cerebral Palsy v1.324 B4GALNT1 Zornitza Stark Gene: b4galnt1 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.323 RARB Zornitza Stark Marked gene: RARB as ready
Cerebral Palsy v1.323 RARB Zornitza Stark Gene: rarb has been classified as Red List (Low Evidence).
Cerebral Palsy v1.323 RARB Zornitza Stark Classified gene: RARB as Red List (low evidence)
Cerebral Palsy v1.323 RARB Zornitza Stark Gene: rarb has been classified as Red List (Low Evidence).
Cerebral Palsy v1.322 MAPK8IP3 Zornitza Stark Marked gene: MAPK8IP3 as ready
Cerebral Palsy v1.322 MAPK8IP3 Zornitza Stark Gene: mapk8ip3 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.322 MAPK8IP3 Zornitza Stark Classified gene: MAPK8IP3 as Amber List (moderate evidence)
Cerebral Palsy v1.322 MAPK8IP3 Zornitza Stark Gene: mapk8ip3 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.321 POLR2A Zornitza Stark Marked gene: POLR2A as ready
Cerebral Palsy v1.321 POLR2A Zornitza Stark Gene: polr2a has been classified as Red List (Low Evidence).
Cerebral Palsy v1.321 POLR2A Zornitza Stark Classified gene: POLR2A as Red List (low evidence)
Cerebral Palsy v1.321 POLR2A Zornitza Stark Gene: polr2a has been classified as Red List (Low Evidence).
Cerebral Palsy v1.320 KCNB1 Zornitza Stark Publications for gene: KCNB1 were set to 33528536; 34788679
Cerebral Palsy v1.319 KCNB1 Zornitza Stark Classified gene: KCNB1 as Green List (high evidence)
Cerebral Palsy v1.319 KCNB1 Zornitza Stark Gene: kcnb1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.318 CHD3 Zornitza Stark Marked gene: CHD3 as ready
Cerebral Palsy v1.318 CHD3 Zornitza Stark Gene: chd3 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.318 CHD3 Zornitza Stark Classified gene: CHD3 as Red List (low evidence)
Cerebral Palsy v1.318 CHD3 Zornitza Stark Gene: chd3 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.317 ABHD16A Zornitza Stark Marked gene: ABHD16A as ready
Cerebral Palsy v1.317 ABHD16A Zornitza Stark Gene: abhd16a has been classified as Red List (Low Evidence).
Cerebral Palsy v1.317 ABHD16A Zornitza Stark Classified gene: ABHD16A as Red List (low evidence)
Cerebral Palsy v1.317 ABHD16A Zornitza Stark Gene: abhd16a has been classified as Red List (Low Evidence).
Cerebral Palsy v1.316 ZMYM2 Zornitza Stark Marked gene: ZMYM2 as ready
Cerebral Palsy v1.316 ZMYM2 Zornitza Stark Gene: zmym2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.316 ZMYM2 Zornitza Stark Classified gene: ZMYM2 as Red List (low evidence)
Cerebral Palsy v1.316 ZMYM2 Zornitza Stark Gene: zmym2 has been classified as Red List (Low Evidence).
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.
Mendeliome v1.1846 ERBB4 Zornitza Stark edited their review of gene: ERBB4: Changed rating: AMBER
Cerebral Palsy v1.315 ZMYM2 Clare van Eyk gene: ZMYM2 was added
gene: ZMYM2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ZMYM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZMYM2 were set to PMID: 38168508
Phenotypes for gene: ZMYM2 were set to Neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities, MIM#619522
Review for gene: ZMYM2 was set to RED
Added comment: Single case with de novo pathogenic variant in ZMYM2, diagnosed with spastic quadriplegic cerebral palsy originally attributed to other causes (PMID: 38168508).
Sources: Literature
Cerebral Palsy v1.315 ABHD16A Clare van Eyk gene: ABHD16A was added
gene: ABHD16A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ABHD16A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABHD16A were set to PMID: 38168508
Phenotypes for gene: ABHD16A were set to Spastic paraplegia 86, autosomal recessive, MIM#619735
Review for gene: ABHD16A was set to RED
Added comment: Single case with homozygous LP variant in ABHD16A, diagnosed with hypotonic-ataxic cerebral palsy with unclear cause (PMID: 38168508). SPG86 is associated with global developmental delay/intellectual disability, progressive spasticity affecting the upper and lower limbs, and corpus callosum and white matter anomalies.
Sources: Literature
Cerebral Palsy v1.315 CHD3 Clare van Eyk gene: CHD3 was added
gene: CHD3 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CHD3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHD3 were set to PMID: 38168508
Phenotypes for gene: CHD3 were set to Snijders Blok-Campeau syndrome, MIM#618205
Review for gene: CHD3 was set to RED
Added comment: Single case with de novo LP variant in CHD3, diagnosed with spastic hemiplegic cerebral palsy with unclear cause (PMID: 38168508). Causal link not established.
Sources: Literature
Cerebral Palsy v1.315 KCNB1 Clare van Eyk edited their review of gene: KCNB1: Added comment: Additional case with de novo likely pathogenic variant, diagnosed with spastic diplegic cerebral palsy with unclear cause (PMID: 38168508).; Changed rating: GREEN; Changed publications: PMID: 38693247, 38168508
Cerebral Palsy v1.315 POLR2A Clare van Eyk gene: POLR2A was added
gene: POLR2A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: POLR2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POLR2A were set to PMID: 38168508
Phenotypes for gene: POLR2A were set to Neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities, MIM#618603
Review for gene: POLR2A was set to RED
Added comment: Single case with de novo LP variant in POLR2A, diagnosed with hypotonic-ataxic cerebral palsy with unclear cause (PMID: 38168508).
Sources: Literature
Cerebral Palsy v1.315 MAPK8IP3 Clare van Eyk gene: MAPK8IP3 was added
gene: MAPK8IP3 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MAPK8IP3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAPK8IP3 were set to PMID: 38168508
Phenotypes for gene: MAPK8IP3 were set to Neurodevelopmental disorder with or without variable brain abnormalities, MIM#618443
Review for gene: MAPK8IP3 was set to AMBER
Added comment: Single case with pathogenic MAPK8IP3 variant, inheritance not confirmed, diagnosed with spastic diplegic cerebral palsy with unclear cause (PMID: 38168508).

Additional cases series reported two recurrent de novo missense variants in MAPK8IP3 in 5 individuals from four families with a core set of neurodevelopmental symptoms, including spastic diplegia, intellectual disability, and corpus callosum hypoplasia (PMID: 30945334).
Sources: Literature
Cerebral Palsy v1.315 RARB Clare van Eyk gene: RARB was added
gene: RARB was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: RARB was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: RARB were set to PMID: 38168508
Phenotypes for gene: RARB were set to Microphthalmia, syndromic 12, MIM#615524
Mode of pathogenicity for gene: RARB was set to Other
Review for gene: RARB was set to RED
Added comment: 1 individual reported with phenotype mimicking CP and recurrent p.Leu213Pro GOF variant in RARB. GOF variants in RARB are associated with severe global developmental delay with progressive motor impairment due to spasticity and/or dystonia (with or without chorea). Biallelic truncating variants also reported to cause microphthalmia and diaphragmatic hernia.
Sources: Literature
Cerebral Palsy v1.315 B4GALNT1 Clare van Eyk edited their review of gene: B4GALNT1: Added comment: Additional case with compound heterozygous variants in B4GALNT1, diagnosed with spastic diplegic cerebral palsy with unclear cause (PMID: 38168508).; Changed rating: AMBER; Changed publications: PMID: 38693247, PMID: 38168508
Cerebral Palsy v1.315 ZDHHC9 Clare van Eyk gene: ZDHHC9 was added
gene: ZDHHC9 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ZDHHC9 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ZDHHC9 were set to PMID: 33528536; PMID: 38693247
Phenotypes for gene: ZDHHC9 were set to Intellectual developmental disorder, X-linked syndromic, Raymond type, MIM#300799
Review for gene: ZDHHC9 was set to AMBER
Added comment: Single males hemizygous for P/LP variants reported in each of 2 large CP sequencing studies (PMID: 33528536; PMID: 38693247). Detailed clinical information not supplied for either. Genome-wide significant burden of rare variants in ZDHHC9 reported in panel resequencing study of CP cohort (PMID: 31700678).
Sources: Literature
Cerebral Palsy v1.315 THOC2 Clare van Eyk gene: THOC2 was added
gene: THOC2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: THOC2 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: THOC2 were set to PMID: 38168508; PMID: 38693247; PMID: 32116545
Phenotypes for gene: THOC2 were set to Intellectual developmental disorder, X-linked 12, MIM#300957
Review for gene: THOC2 was set to GREEN
Added comment: 3 hemizygous males with pathogenic/likely pathogenic variants reported in large-scale CP exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.

Additional female with cryptogenic spastic quadriplegic CP also reported with heterozygous de novo pathogenic THOC2 variant (PMID: 38168508). Some females reported in literature previously. Dyskinesia, dystonia and spasticity are reported as clinical features in several additional cases in a series (PMID: 32116545).
Sources: Literature
Cerebral Palsy v1.315 TAF1 Clare van Eyk reviewed gene: TAF1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Intellectual developmental disorder, X-linked syndromic 33, OMIM #300966, Dystonia-Parkinsonism, X-linked, OMIM #314250; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cerebral Palsy v1.315 PQBP1 Clare van Eyk gene: PQBP1 was added
gene: PQBP1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PQBP1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PQBP1 were set to PMID: 38693247
Phenotypes for gene: PQBP1 were set to Renpenning syndrome, MIM#309500
Review for gene: PQBP1 was set to RED
Added comment: 1 hemizygous male reported with splice variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Spastic diplegia is a common feature in individuals with Renpenning syndrome.
Sources: Literature
Cerebral Palsy v1.315 POLA1 Clare van Eyk gene: POLA1 was added
gene: POLA1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: POLA1 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: POLA1 were set to PMID: 38693247
Phenotypes for gene: POLA1 were set to Van Esch-O'Driscoll syndrome, MIM#301030
Review for gene: POLA1 was set to AMBER
Added comment: 3 males with hemizygous LOF variants reported in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Spasticity has been reported as a rare feature of VEODS.
Sources: Literature
Cerebral Palsy v1.315 PHF6 Clare van Eyk gene: PHF6 was added
gene: PHF6 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PHF6 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: PHF6 were set to PMID: 38693247
Phenotypes for gene: PHF6 were set to Borjeson-Forssman-Lehmann syndrome, MIM#301900
Review for gene: PHF6 was set to RED
Added comment: Single male proband with hemizygous variant impacting splicing of the first non-coding exon reported in large-scale exome sequencing study (PMID: 38693247). In silico prediction is strong, but functional impact not assessed. Detailed clinical information not supplied. BFLS is characterized by short stature, obesity, hypogonadism, hypotonia, intellectual disability, distinctive facial features, fleshy ears, and finger and toe abnormalities.
Sources: Literature
Cerebral Palsy v1.315 PLP1 Clare van Eyk reviewed gene: PLP1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Pelizaeus-Merzbacher disease MIM#312080, Spastic paraplegia 2, X-linked MIM#312920; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral Palsy v1.315 PIGA Clare van Eyk reviewed gene: PIGA: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Multiple congenital anomalies-hypotonia-seizures syndrome 2 MIM#300868, Neurodevelopmental disorder with epilepsy and hemochromatosis MIM#301072, Paroxysmal nocturnal hemoglobinuria, somatic MIM#300818; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cerebral Palsy v1.315 OPHN1 Clare van Eyk gene: OPHN1 was added
gene: OPHN1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: OPHN1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: OPHN1 were set to PMID: 38693247
Phenotypes for gene: OPHN1 were set to Intellectual developmental disorder, X-linked syndromic, Billuart type, MIM#300486
Review for gene: OPHN1 was set to RED
Added comment: 1 male with hemizygous variant reported in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. MRXSBL is associated with generalized hypotonia and delayed psychomotor development from infancy, with some individuals developing ataxia associated with cerebellar hypoplasia.
Sources: Literature
Speech apraxia v0.8 ERF Thomas Scerri gene: ERF was added
gene: ERF was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: ERF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ERF were set to 36117209; 35761471; 35852485
Phenotypes for gene: ERF were set to Craniosynostosis 4, MIM# 600775
Review for gene: ERF was set to AMBER
Added comment: First two reported CAS cases with a nonsense ERF variant (Kaspi et al., 2022; PMID: 36117209) inherited from mother to proband.

Care et al. (2022; PMID: 35761471) report 5 cases with ERF variants, and of these 3 have speech disorder.

Moddemann et al. (PMID: 35852485) conduct a meta-analysis of 79 independent samples with ERF variants and find 60% have speech delay/impairments.
Sources: Expert list, Expert Review
Speech apraxia v0.8 DIP2C Thomas Scerri gene: DIP2C was added
gene: DIP2C was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: DIP2C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DIP2C were set to 36117209; 38421105
Phenotypes for gene: DIP2C were set to Neurodevelopmental disorder (MONDO:0700092), DIP2C-related
Review for gene: DIP2C was set to AMBER
Added comment: First reported CAS proband with a de novo splice DIP2C variant (Kaspi et al., 2022; PMID: 36117209).

Ha et al. (2024; PMID: 38421105) report 23 cases with various DIP2C variants, including the one published by Kaspi et al. (2022; PMID: 36117209). All 23 cases have various speech deficits and two (including the Kaspi et al. (2022) case) are reported having speech apraxia.
Sources: Expert list, Expert Review
Speech apraxia v0.8 BRPF1 Thomas Scerri gene: BRPF1 was added
gene: BRPF1 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: BRPF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BRPF1 were set to 36117209; 27939640; 38346666
Phenotypes for gene: BRPF1 were set to Intellectual developmental disorder with dysmorphic facies and ptosis, MIM# 617333
Review for gene: BRPF1 was set to GREEN
Added comment: First reported CAS proband with a de novo missense BRPF1 variant (Kaspi et al., 2022; PMID: 36117209).

Yan et al. (2017; PMID: 27939640) reported 10 independent cases with de novo or inherited BRPF1 variants and with a range of speech and language deficits, including one proband with speech apraxia (proband 4, Table S1).

Morison et al. (2024; PMID: 38346666) report 15 new cases with mostly de novo BRPF1 variants and a range of speech deficits, including 3 specifically with speech apraxia.
Sources: Expert list, Expert Review
Speech apraxia v0.8 ARHGEF9 Thomas Scerri gene: ARHGEF9 was added
gene: ARHGEF9 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: ARHGEF9 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: ARHGEF9 were set to 36117209
Phenotypes for gene: ARHGEF9 were set to Developmental and epileptic encephalopathy 8, MIM# 300607
Review for gene: ARHGEF9 was set to RED
Added comment: Only reported CAS proband with a de novo nonsense ARHGEF9 variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review
Speech apraxia v0.8 ZNF142 Thomas Scerri gene: ZNF142 was added
gene: ZNF142 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: ZNF142 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNF142 were set to 32345733; 31036918; 34531528; 35616059
Phenotypes for gene: ZNF142 were set to Neurodevelopmental disorder with impaired speech and hyperkinetic movements, MIM# 618425
Review for gene: ZNF142 was set to AMBER
Added comment: A reported CAS proband with compound heterozygous missenses ZNF142 variants (Hildebrand et al., 2020; PMID: 32345733).

Khan et al. (2019, PMID: 31036918) report 7 cases with compound heterozygous or else homozygous LoF or missense ZNF142 variants for which the cases have a range of speech deficits including speech apraxia in one case.

Kameyama et al. (2020, PMID: 34531528) report two brothers with biallelic LoF ZNF142 variants for which the cases have speech deficits.

Christensen et al. (2022; PMID: 35616059) report a further 26 individuals with biallelic ZNF142 variants for which the cases have a range of speech deficits.
Sources: Expert list, Expert Review
Speech apraxia v0.8 UPF2 Thomas Scerri gene: UPF2 was added
gene: UPF2 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: UPF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: UPF2 were set to 32345733; 31585809
Phenotypes for gene: UPF2 were set to Neurodevelopmental disorder (MONDO:0700092), UPF2-related
Review for gene: UPF2 was set to RED
Added comment: A CAS proband with a de novo LoF UPF2 variant (Hildebrand et al., 2020; PMID: 32345733).

Johnson et al. (2019; PMID: 31585809) report 3 independent cases with LoF UPF2 variants and a range of speech deficits, including speech apraxia in one of the cases (although the speech disorder had resolved to a mild phonological disorder at later testing).
Sources: Expert list, Expert Review
Speech apraxia v0.8 POGZ Thomas Scerri gene: POGZ was added
gene: POGZ was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: POGZ was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POGZ were set to 32345733; 35052493
Phenotypes for gene: POGZ were set to White-Sutton syndrome, MIM# 616364
Review for gene: POGZ was set to RED
Added comment: Only reported CAS proband with a de novo missense POGZ variant (Hildebrand et al., 2020; PMID: 32345733).

Nagy et al. (2022; PMID: 35052493) reported 117 cases from a meta-analysis and found that "the most common symptoms were speech delay in 88%". This is not strong enough evidence to be supporting evidence for speech apraxia per se.
Sources: Expert list, Expert Review
Speech apraxia v0.8 MEIS2 Thomas Scerri gene: MEIS2 was added
gene: MEIS2 was added to Speech apraxia. Sources: Expert Review,Expert list
Mode of inheritance for gene: MEIS2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MEIS2 were set to 32345733; 30055086
Phenotypes for gene: MEIS2 were set to Cleft palate, cardiac defects, and impaired intellectual development, MIM# 600987
Review for gene: MEIS2 was set to AMBER
Added comment: First reported CAS proband with a LoF MEI2 variant (Hildebrand et al., 2020; PMID: 32345733).

Douglas et al. (2018; PMID: 30055086) report 3 new cases with de novo missense variants and 2 previously published deletion and nonsense variants. All cases have a range of differently worded speech problems, and one has verbal apraxia.
Sources: Expert Review, Expert list
Speech apraxia v0.8 GNB1 Thomas Scerri gene: GNB1 was added
gene: GNB1 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: GNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GNB1 were set to 32345733
Phenotypes for gene: GNB1 were set to Intellectual developmental disorder, autosomal dominant 42, MIM# 616973
Review for gene: GNB1 was set to RED
Added comment: Only reported CAS proband with a de novo nonsense GNB1 variant (Hildebrand et al., 2020; PMID: 32345733).
Sources: Expert list, Expert Review
Speech apraxia v0.8 GNAO1 Thomas Scerri gene: GNAO1 was added
gene: GNAO1 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: GNAO1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GNAO1 were set to 32345733; 35722775; 38881224
Phenotypes for gene: GNAO1 were set to Developmental and epileptic encephalopathy 17, MIM# 615473; Neurodevelopmental disorder with involuntary movements, MIM# 617493
Review for gene: GNAO1 was set to AMBER
Added comment: First reported CAS proband with a de novo missense GNAO1 variant (Hildebrand et al., 2020; PMID: 32345733).

These additional cases are less clear for speech apraxia:

Wirth et al. (2020; PMID: 35722775) reported twenty-four independent cases with a range of de novo and inherited variants, including missense and nonsense, for which a speech disorder (dysarthria) was reported for 19 individuals.

Lasa-Aranzasti et al. (2024; PMID: 38881224) report eighteen independent cases and find "all patients developed some type of nonverbal communication, but only four acquired verbal language."
Sources: Expert list, Expert Review
Speech apraxia v0.8 EBF3 Thomas Scerri changed review comment from: First proband with a de novo nonsense EBF3 variant reported for CAS (Hildebrand et al., 2020; PMID: 32345733).

Chao et al. (2017; PMID: 28017372) report three independent cases with de novo missense variants (all three curiously substituting the same amino acid). All three cases have "expressive speech disorder (3/3)" and a range of dysarthria and apraxia.

Deisseroth et al. (2022; PMID: 35340043) report a total of 83 individuals with missense or protein-truncating variants for EBF3 from a meta-analysis and find 10% have speech apraxia. Ten cases carried de novo EBF3 variants and were reported as having speech apraxia (supplementary tables).

Sources: Expert list, Expert Review; to: First proband with a de novo nonsense EBF3 variant reported for CAS (Hildebrand et al., 2020; PMID: 32345733).

Chao et al. (2017; PMID: 28017372) report three independent cases with de novo missense variants (all three curiously substituting the same amino acid). All three cases have "expressive speech disorder (3/3)" and a range of dysarthria and apraxia.

Deisseroth et al. (2022; PMID: 35340043) report a total of 83 individuals with missense or protein-truncating variants for EBF3 from a meta-analysis and find 10% have speech apraxia. Of these ten cases carried de novo EBF3 variants and were reported as having speech apraxia (supplementary tables).

Sources: Expert list, Expert Review
Speech apraxia v0.8 EBF3 Thomas Scerri changed review comment from: First proband with a de novo nonsense EBF3 variant reported for CAS (Hildebrand et al., 2020; PMID: 32345733).

Chao et al., (2017; PMID: 28017372) report three independent cases with de novo missense variants (all three curiously substituting the same amino acid). All three cases have "expressive speech disorder (3/3)" and a range of dysarthria and apraxia.
Sources: Expert list, Expert Review; to: First proband with a de novo nonsense EBF3 variant reported for CAS (Hildebrand et al., 2020; PMID: 32345733).

Chao et al. (2017; PMID: 28017372) report three independent cases with de novo missense variants (all three curiously substituting the same amino acid). All three cases have "expressive speech disorder (3/3)" and a range of dysarthria and apraxia.

Deisseroth et al. (2022; PMID: 35340043) report a total of 83 individuals with missense or protein-truncating variants for EBF3 from a meta-analysis and find 10% have speech apraxia. Ten cases carried de novo EBF3 variants and were reported as having speech apraxia (supplementary tables).

Sources: Expert list, Expert Review
Speech apraxia v0.8 DDX3X Thomas Scerri changed review comment from: First proband with a de novo LoF DDX3X variant reported for CAS (Hildebrand et al., 2020; PMID: 32345733).

Second proband with a de novo LoF DDX3X variant reported for CAS (Kaspi et al., 2022; PMID: 36117209)

Parra et al. (2024; PMID: 37904618) report thirty-four independent probands with DDX3X mutations for which "the most frequent clinical features (>70%) identified in these patients included speech dyspraxia (88.2%)".
Sources: Expert list, Expert Review; to: First reported CAS proband with a de novo LoF DDX3X variant (Hildebrand et al., 2020; PMID: 32345733).

Second reported CAS proband with a de novo LoF DDX3X variant (Kaspi et al., 2022; PMID: 36117209)

Third in-house CAS proband with a de novo LoF DDX3X variant (not published).

Parra et al. (2024; PMID: 37904618) report thirty-four independent probands with DDX3X mutations for which "the most frequent clinical features (>70%) identified in these patients included speech dyspraxia (88.2%)".
Sources: Expert list, Expert Review
Speech apraxia v0.8 TNRC6B Thomas Scerri edited their review of gene: TNRC6B: Changed rating: AMBER
Speech apraxia v0.8 TNRC6B Thomas Scerri changed review comment from: First proband with a LoF TNRC6B variant reported for CAS (Eising et al., 2019; PMID: 29463886).

Granadillo et al., (2020; PMID: 32152250) studied seventeen further probands with LoF TNRC6B variants and found "speech delay in 94% (16/17), fine motor delay in 82% (14/17) and gross motor delay in 71% (12/17)".

Yahia et al., (2024; PMID: 38300321) looked at a Swedish cohort with severe developmental language disorder and find another case with a LoF variant in TNRC6B.

Yang et al., (2024; PMID: 38404251) report two independent cases with speech delay/abnormalities carrying LoF variants in TNRC6B.
Sources: Expert list, Expert Review; to: First proband with a LoF TNRC6B variant reported for CAS (Eising et al., 2019; PMID: 29463886).

These additional supporting studies are for speech delay rather than speech apraxia per se:

Granadillo et al., (2020; PMID: 32152250) studied seventeen further probands with LoF TNRC6B variants and found "speech delay in 94% (16/17), fine motor delay in 82% (14/17) and gross motor delay in 71% (12/17)".

Yahia et al., (2024; PMID: 38300321) looked at a Swedish cohort with severe developmental language disorder and find another case with a LoF variant in TNRC6B.

Yang et al., (2024; PMID: 38404251) report two independent cases with speech delay/abnormalities carrying LoF variants in TNRC6B.
Sources: Expert list, Expert Review
Cerebral Palsy v1.315 MED12 Clare van Eyk changed review comment from: 3 individuals reported with hemizygous variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Two variants lack in silico support for pathogenicity.

1 additional female with a de novo heterozygous variant reported in large retrospective cohort study of patients with cerebral palsy (PMID 33528536); to: 3 individuals reported with hemizygous variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Two variants lack in silico support for pathogenicity.

1 additional female with a de novo likely pathogenic heterozygous variant reported in large retrospective cohort study of patients with cerebral palsy (PMID 33528536)
Cerebral Palsy v1.315 MED12 Clare van Eyk reviewed gene: MED12: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 38693247, PMID 33528536; Phenotypes: Opitz-Kaveggia syndrome, MIM#305450; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral Palsy v1.315 MED12 Clare van Eyk Deleted their review
Cerebral Palsy v1.315 MED12 Clare van Eyk changed review comment from: 3 individuals reported with hemizygous variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Two variants lack in silico support for pathogenicity.
Sources: Literature; to: 3 individuals reported with hemizygous variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Two variants lack in silico support for pathogenicity.

1 additional female with a de novo heterozygous variant reported in large retrospective cohort study of patients with cerebral palsy (PMID 33528536)
Sources: Literature
Cerebral Palsy v1.315 MED12 Clare van Eyk gene: MED12 was added
gene: MED12 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MED12 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: MED12 were set to PMID: 38693247
Phenotypes for gene: MED12 were set to Opitz-Kaveggia syndrome, MIM#305450
Review for gene: MED12 was set to RED
Added comment: 3 individuals reported with hemizygous variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Two variants lack in silico support for pathogenicity.
Sources: Literature
Cerebral Palsy v1.315 L1CAM Clare van Eyk reviewed gene: L1CAM: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247, PMID 33528536; Phenotypes: CRASH syndrome, MIM# 303350; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cerebral Palsy v1.315 KDM5C Clare van Eyk reviewed gene: KDM5C: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Mental retardation, X-linked, syndromic, Claes-Jensen type, MIM# 300534, MONDO:0010355; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral Palsy v1.315 HPRT1 Clare van Eyk reviewed gene: HPRT1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Hyperuricemia, HRPT-related MIM#300323, Lesch-Nyhan syndrome MIM#300322; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cerebral Palsy v1.315 HCFC1 Clare van Eyk gene: HCFC1 was added
gene: HCFC1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: HCFC1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: HCFC1 were set to PMID: 38693247
Phenotypes for gene: HCFC1 were set to Methylmalonic aciduria and homocysteinemia, cblX type, MIM#309541
Review for gene: HCFC1 was set to AMBER
Added comment: 2 males reported with hemizygous LOF variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. MAHCX is characterized by severely delayed psychomotor development apparent in infancy.
Sources: Literature
Speech apraxia v0.8 SETD1A Thomas Scerri edited their review of gene: SETD1A: Changed rating: AMBER
Speech apraxia v0.8 SETD1A Thomas Scerri edited their review of gene: SETD1A: Changed rating: RED
Speech apraxia v0.8 SETD1A Thomas Scerri changed review comment from: First proband with a LoF SETD1A variant reported for CAS (Eising et al., 2019; PMID: 29463886).

Fifteen further independent probands with LoF SETD1A variants were investigated (Kummeling et al., 2021; PMID: 32346159) and "global DD was reported in 14/15 individuals, including delayed speech and language development (14/14) and motor development (13/14)".
Sources: Expert list, Expert Review; to: First proband with a LoF SETD1A variant reported for CAS (Eising et al., 2019; PMID: 29463886).

Fifteen further independent probands with LoF SETD1A variants were investigated (Kummeling et al., 2021; PMID: 32346159) and "global DD was reported in 14/15 individuals, including delayed speech and language development (14/14) and motor development (13/14)". However, only one proband was explicitly recorded with speech apraxia (proband 14; supplementary Table 1).

Sources: Expert list, Expert Review
Cerebral Palsy v1.315 CCDC22 Clare van Eyk changed review comment from: 1 individual reported with hemizygous LOF variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Mutations in RTSC2 cause syndromic ID, with hypotonia and delayed psychomotor development reported in some individuals.
Sources: Literature; to: 1 individual reported with hemizygous LOF variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Mutations in CCDC22 cause syndromic ID, with hypotonia and delayed psychomotor development reported in some individuals.
Sources: Literature
Cerebral Palsy v1.315 FGD1 Clare van Eyk gene: FGD1 was added
gene: FGD1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: FGD1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: FGD1 were set to PMID: 38693247; PMID:33528536
Phenotypes for gene: FGD1 were set to Aarskog-Scott syndrome; Intellectual developmental disorder, X-linked syndromic 16, MIM#305400
Review for gene: FGD1 was set to RED
Added comment: 1 individual reported with hemizygous likely pathogenic missense variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Additional male with de novo hemizygous pathogenic variant reported in a clinical laboratory referral cohort (PMID:33528536). No clear phenotypic overlap with CP.
Sources: Literature
Cerebral Palsy v1.315 EBP Clare van Eyk gene: EBP was added
gene: EBP was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: EBP was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: EBP were set to PMID: 38693247
Phenotypes for gene: EBP were set to MEND syndrome, MIM#300960
Review for gene: EBP was set to RED
Added comment: 1 individual reported with hemizygous likely pathogenic missense variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. MEND syndrome is associated with severe neurological involvement (e.g. intellectual disability, delayed psychomotor development, seizures, hydrocephalus, cerebellar/corpus callosum hypoplasia, Dandy-Walker malformation, hypotonia).
Sources: Literature
Speech apraxia v0.8 EBF3 Thomas Scerri gene: EBF3 was added
gene: EBF3 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: EBF3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EBF3 were set to 32345733; 28017372
Phenotypes for gene: EBF3 were set to Hypotonia, ataxia, and delayed development syndrome, MIM# 617330
Review for gene: EBF3 was set to GREEN
Added comment: First proband with a de novo nonsense EBF3 variant reported for CAS (Hildebrand et al., 2020; PMID: 32345733).

Chao et al., (2017; PMID: 28017372) report three independent cases with de novo missense variants (all three curiously substituting the same amino acid). All three cases have "expressive speech disorder (3/3)" and a range of dysarthria and apraxia.
Sources: Expert list, Expert Review
Speech apraxia v0.8 DDX3X Thomas Scerri gene: DDX3X was added
gene: DDX3X was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: DDX3X 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: DDX3X were set to 32345733; 36117209; 37904618
Phenotypes for gene: DDX3X were set to Intellectual developmental disorder, X-linked syndromic, Snijders Blok type, MIM# 300958
Review for gene: DDX3X was set to GREEN
Added comment: First proband with a de novo LoF DDX3X variant reported for CAS (Hildebrand et al., 2020; PMID: 32345733).

Second proband with a de novo LoF DDX3X variant reported for CAS (Kaspi et al., 2022; PMID: 36117209)

Parra et al. (2024; PMID: 37904618) report thirty-four independent probands with DDX3X mutations for which "the most frequent clinical features (>70%) identified in these patients included speech dyspraxia (88.2%)".
Sources: Expert list, Expert Review
Cerebral Palsy v1.315 CLCN4 Clare van Eyk reviewed gene: CLCN4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247, PMID: 37789889; Phenotypes: Raynaud-Claes syndrome MIM#300114; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral Palsy v1.315 CCDC22 Clare van Eyk gene: CCDC22 was added
gene: CCDC22 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CCDC22 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: CCDC22 were set to PMID: 38693247
Phenotypes for gene: CCDC22 were set to Ritscher-Schinzel syndrome 2, MIM#300963
Review for gene: CCDC22 was set to RED
Added comment: 1 individual reported with hemizygous LOF variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Mutations in RTSC2 cause syndromic ID, with hypotonia and delayed psychomotor development reported in some individuals.
Sources: Literature
Microcephaly v1.264 MTSS1L Ain Roesley Phenotypes for gene: MTSS1L were changed from Intellectual developmental disorder with ocular anomalies and distinctive facial features MIM#620086 to Intellectual developmental disorder with ocular anomalies and distinctive facial features MIM#620086
Deafness_IsolatedAndComplex v1.186 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
Microcephaly v1.263 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
Intellectual disability syndromic and non-syndromic v0.6045 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
Congenital nystagmus v1.21 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
Intellectual disability syndromic and non-syndromic v0.6044 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 v1.1846 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
Congenital nystagmus v1.20 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
Deafness_IsolatedAndComplex v1.185 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
Microcephaly v1.262 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 v1.1845 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
Ataxia - paediatric v1.22 MTCL1 Zornitza Stark Mode of inheritance for gene: MTCL1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Ataxia - adult onset v1.10 MTCL1 Zornitza Stark Mode of inheritance for gene: MTCL1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1844 MTCL1 Zornitza Stark Mode of inheritance for gene: MTCL1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6043 ZNF292 Ain Roesley Phenotypes for gene: ZNF292 were changed from Intellectual developmental disorder, autosomal dominant 63, MIM# 619188; Intellectual disability; autism; ADHD to Intellectual developmental disorder, autosomal dominant 64 MIM#619188
Mendeliome v1.1843 ZNF292 Ain Roesley Phenotypes for gene: ZNF292 were changed from Intellectual developmental disorder, autosomal dominant 63, MIM# 619188; Intellectual disability; Autism; ADHD to Intellectual developmental disorder, autosomal dominant 64 MIM#619188
Speech apraxia v0.8 CDK13 Thomas Scerri gene: CDK13 was added
gene: CDK13 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: CDK13 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDK13 were set to 32345733; 36599938
Phenotypes for gene: CDK13 were set to Congenital heart defects, dysmorphic facial features, and intellectual developmental disorder, MIM# 617360
Review for gene: CDK13 was set to GREEN
Added comment: First proband with a de novo missense CDK13 variant reported for CAS (Hildebrand et al., 2020; PMID: 32345733).

Morison et al. (2023; PMID: 36599938) report 41 cases (with 33 novel variants) and find "most participants used augmentative and alternative communication (AAC) in early childhood (24/41). CAS was common (14/22)."
Sources: Expert list, Expert Review
Speech apraxia v0.8 ZFHX4 Thomas Scerri gene: ZFHX4 was added
gene: ZFHX4 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: ZFHX4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZFHX4 were set to 29463886; 34461323
Phenotypes for gene: ZFHX4 were set to Neurodevelopmental disorder (MONDO:0700092), ZFHX4-related
Review for gene: ZFHX4 was set to RED
Added comment: First proband with splice acceptor ZFHX4 variant reported for CAS (Eising et al., 2019; PMID: 29463886).

Fontana et al. (2021; PMID: 34461323) report a similar splice region variant in ZFHX4 for a proband with a neuropsychological phenotype, and summarise other probands with deletions or point mutations and associated phenotypes. Only one of these has a recorded speech phenotype. Overall this paper doesn't add strong evidence for a link between speech apraxia and ZFHX4.
Sources: Expert list, Expert Review
Speech apraxia v0.8 WDR5 Thomas Scerri gene: WDR5 was added
gene: WDR5 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: WDR5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WDR5 were set to 29463886; 36408368
Phenotypes for gene: WDR5 were set to Neurodevelopmental disorder (MONDO:0700092), WDR5-related
Review for gene: WDR5 was set to GREEN
Added comment: First proband with a de novo missense WDR5 variant reported for CAS (Eising et al., 2019; PMID: 29463886).

Blok et al. (2022; PMID: 36408368) studied "11 unrelated individuals with six different rare de novo germline missense variants in WDR5; one identical variant was found in five individuals and another variant in two individuals. All individuals had neurodevelopmental disorders including speech/language delays (n = 11). Speech delays were reported in all individuals, including nasal speech, developmental language disorders, verbal dyspraxia, and persistent stuttering."
Sources: Expert list, Expert Review
Speech apraxia v0.8 TNRC6B Thomas Scerri gene: TNRC6B was added
gene: TNRC6B was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: TNRC6B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TNRC6B were set to 29463886; 32152250; 38300321; 38404251
Phenotypes for gene: TNRC6B were set to Global developmental delay with speech and behavioral abnormalities, MIM# 619243
Review for gene: TNRC6B was set to GREEN
Added comment: First proband with a LoF TNRC6B variant reported for CAS (Eising et al., 2019; PMID: 29463886).

Granadillo et al., (2020; PMID: 32152250) studied seventeen further probands with LoF TNRC6B variants and found "speech delay in 94% (16/17), fine motor delay in 82% (14/17) and gross motor delay in 71% (12/17)".

Yahia et al., (2024; PMID: 38300321) looked at a Swedish cohort with severe developmental language disorder and find another case with a LoF variant in TNRC6B.

Yang et al., (2024; PMID: 38404251) report two independent cases with speech delay/abnormalities carrying LoF variants in TNRC6B.
Sources: Expert list, Expert Review
Speech apraxia v0.8 SETD1A Thomas Scerri gene: SETD1A was added
gene: SETD1A was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: SETD1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SETD1A were set to 29463886; 32346159
Phenotypes for gene: SETD1A were set to Neurodevelopmental disorder with speech impairment and dysmorphic facies, MIM# 619056
Review for gene: SETD1A was set to GREEN
Added comment: First proband with a LoF SETD1A variant reported for CAS (Eising et al., 2019; PMID: 29463886).

Fifteen further independent probands with LoF SETD1A variants were investigated (Kummeling et al., 2021; PMID: 32346159) and "global DD was reported in 14/15 individuals, including delayed speech and language development (14/14) and motor development (13/14)".
Sources: Expert list, Expert Review
Speech apraxia v0.8 SETBP1 Thomas Scerri gene: SETBP1 was added
gene: SETBP1 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: SETBP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SETBP1 were set to 29463886; 33907317
Phenotypes for gene: SETBP1 were set to Intellectual developmental disorder, autosomal dominant 29, MIM# 616078
Review for gene: SETBP1 was set to GREEN
Added comment: First proband with LoF SETBP1 variant reported for CAS (Eising et al., 2019; PMID: 29463886)

Thirty one further probands with LoF SETBP1 variants studied (Morgan et al., 2019; PMID: 33907317) revealing that "Protracted and aberrant speech development was consistently seen, regardless of motor or intellectual ability. We expand the linguistic phenotype associated with SETBP1 LoF syndrome (SETBP1 haploinsufficiency disorder), revealing a striking speech presentation that implicates both motor (CAS, dysarthria) and language (phonological errors) systems, with CAS (80%) being the most common diagnosis.".
Sources: Expert list, Expert Review
Cerebral Palsy v1.315 ROGDI Zornitza Stark Marked gene: ROGDI as ready
Cerebral Palsy v1.315 ROGDI Zornitza Stark Gene: rogdi has been classified as Red List (Low Evidence).
Cerebral Palsy v1.315 ROGDI Zornitza Stark Classified gene: ROGDI as Red List (low evidence)
Cerebral Palsy v1.315 ROGDI Zornitza Stark Gene: rogdi has been classified as Red List (Low Evidence).
Cerebral Palsy v1.314 RTTN Zornitza Stark Marked gene: RTTN as ready
Cerebral Palsy v1.314 RTTN Zornitza Stark Gene: rttn has been classified as Red List (Low Evidence).
Cerebral Palsy v1.314 RTTN Zornitza Stark Classified gene: RTTN as Red List (low evidence)
Cerebral Palsy v1.314 RTTN Zornitza Stark Gene: rttn has been classified as Red List (Low Evidence).
Cerebral Palsy v1.313 SLC25A12 Zornitza Stark Marked gene: SLC25A12 as ready
Cerebral Palsy v1.313 SLC25A12 Zornitza Stark Gene: slc25a12 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.313 SLC25A12 Zornitza Stark Classified gene: SLC25A12 as Red List (low evidence)
Cerebral Palsy v1.313 SLC25A12 Zornitza Stark Gene: slc25a12 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.312 SYNE1 Zornitza Stark Phenotypes for gene: SYNE1 were changed from Arthrogryposis multiplex congenita 3, myogenic type MIM#618484; Emery-Dreifuss muscular dystrophy 4, autosomal dominant MIM#612998; Spinocerebellar ataxia, autosomal recessive 8 MIM#610743 to Spinocerebellar ataxia, autosomal recessive 8 MIM#610743
Cerebral Palsy v1.311 SYNE1 Zornitza Stark Publications for gene: SYNE1 were set to 34321325; 34816117
Cerebral Palsy v1.310 TH Zornitza Stark Publications for gene: TH were set to 34788679
Cerebral Palsy v1.309 TH Zornitza Stark Classified gene: TH as Green List (high evidence)
Cerebral Palsy v1.309 TH Zornitza Stark Gene: th has been classified as Green List (High Evidence).
Cerebral Palsy v1.308 VPS13B Zornitza Stark Marked gene: VPS13B as ready
Cerebral Palsy v1.308 VPS13B Zornitza Stark Gene: vps13b has been classified as Red List (Low Evidence).
Cerebral Palsy v1.308 VPS13B Zornitza Stark Classified gene: VPS13B as Red List (low evidence)
Cerebral Palsy v1.308 VPS13B Zornitza Stark Gene: vps13b has been classified as Red List (Low Evidence).
Cerebral Palsy v1.307 VPS53 Zornitza Stark Marked gene: VPS53 as ready
Cerebral Palsy v1.307 VPS53 Zornitza Stark Gene: vps53 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.307 VPS53 Zornitza Stark Classified gene: VPS53 as Red List (low evidence)
Cerebral Palsy v1.307 VPS53 Zornitza Stark Gene: vps53 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.306 WDR62 Zornitza Stark Marked gene: WDR62 as ready
Cerebral Palsy v1.306 WDR62 Zornitza Stark Gene: wdr62 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.306 WDR62 Zornitza Stark Classified gene: WDR62 as Red List (low evidence)
Cerebral Palsy v1.306 WDR62 Zornitza Stark Gene: wdr62 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.305 CDKL5 Zornitza Stark Publications for gene: CDKL5 were set to 33528536; 34788679
Cerebral Palsy v1.304 HUWE1 Zornitza Stark Publications for gene: HUWE1 were set to 31700678
Cerebral Palsy v1.303 HUWE1 Zornitza Stark Classified gene: HUWE1 as Amber List (moderate evidence)
Cerebral Palsy v1.303 HUWE1 Zornitza Stark Gene: huwe1 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.302 IQSEC2 Zornitza Stark 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 MIM#309530
Cerebral Palsy v1.301 IQSEC2 Zornitza Stark Publications for gene: IQSEC2 were set to 33368194; 20473311; 23674175; 33528536
Cerebral Palsy v1.300 MECP2 Zornitza Stark Publications for gene: MECP2 were set to 30542205; 33528536
Cerebral Palsy v1.299 PDHA1 Zornitza Stark Publications for gene: PDHA1 were set to 33528536; 10486093
Cerebral Palsy v1.298 SLC35A2 Zornitza Stark Marked gene: SLC35A2 as ready
Cerebral Palsy v1.298 SLC35A2 Zornitza Stark Gene: slc35a2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.298 SLC35A2 Zornitza Stark Classified gene: SLC35A2 as Red List (low evidence)
Cerebral Palsy v1.298 SLC35A2 Zornitza Stark Gene: slc35a2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.297 SMC1A Zornitza Stark Marked gene: SMC1A as ready
Cerebral Palsy v1.297 SMC1A Zornitza Stark Gene: smc1a has been classified as Red List (Low Evidence).
Cerebral Palsy v1.297 SMC1A Zornitza Stark Classified gene: SMC1A as Red List (low evidence)
Cerebral Palsy v1.297 SMC1A Zornitza Stark Gene: smc1a has been classified as Red List (Low Evidence).
Cerebral Palsy v1.296 ABCD1 Zornitza Stark Marked gene: ABCD1 as ready
Cerebral Palsy v1.296 ABCD1 Zornitza Stark Gene: abcd1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.296 ABCD1 Zornitza Stark Classified gene: ABCD1 as Red List (low evidence)
Cerebral Palsy v1.296 ABCD1 Zornitza Stark Gene: abcd1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.295 ARHGEF9 Zornitza Stark Marked gene: ARHGEF9 as ready
Cerebral Palsy v1.295 ARHGEF9 Zornitza Stark Gene: arhgef9 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.295 ARHGEF9 Zornitza Stark Classified gene: ARHGEF9 as Red List (low evidence)
Cerebral Palsy v1.295 ARHGEF9 Zornitza Stark Gene: arhgef9 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.294 ARHGEF9 Clare van Eyk gene: ARHGEF9 was added
gene: ARHGEF9 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ARHGEF9 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ARHGEF9 were set to PMID: 38693247
Phenotypes for gene: ARHGEF9 were set to Developmental and epileptic encephalopathy 8, MIM#300607
Review for gene: ARHGEF9 was set to RED
Added comment: 1 individual reported with hemizygous pathogenic variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Impaired psychomotor development is a feature of DEE8.
Sources: Literature
Cerebral Palsy v1.294 ABCD1 Clare van Eyk gene: ABCD1 was added
gene: ABCD1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ABCD1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ABCD1 were set to PMID: 38693247
Phenotypes for gene: ABCD1 were set to Adrenoleukodystrophy, MIM#300100
Review for gene: ABCD1 was set to RED
Added comment: 1 male with hemizygous pathogenic missense variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.

Variable age of onset, even within same family. Heterozygous females may develop spastic paraparesis with bowel and bladder difficulties.
Sources: Literature
Cerebral Palsy v1.294 SMC1A Clare van Eyk gene: SMC1A was added
gene: SMC1A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SMC1A 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: SMC1A were set to PMID: 38693247; 26358754
Phenotypes for gene: SMC1A were set to Developmental and epileptic encephalopathy 85, with or without midline brain defects, MIM#301044
Review for gene: SMC1A was set to RED
Added comment: 1 male reported with apparently hemizygous LOF variant in large-scale exome sequencing study (PMID: 38693247). LOF variants thought to be male-lethal. Detailed clinical information not supplied.

1 female in literature with a heterozygous de novo splice site mutation in SMC1A and severe encephalopathy with early-onset epilepsy who developed spastic tetraparesis (PMID: 26358754)
Sources: Literature
Cerebral Palsy v1.294 SLC35A2 Clare van Eyk gene: SLC35A2 was added
gene: SLC35A2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SLC35A2 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: SLC35A2 were set to PMID: 38693247
Phenotypes for gene: SLC35A2 were set to Congenital disorder of glycosylation, type IIm, MIM#300896
Review for gene: SLC35A2 was set to RED
Added comment: 1 individual reported with hemizygous stopgain variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Variants cause an epileptic encephalopathy which has been associated with ataxia and hypotonia.
Sources: Literature
Cerebral Palsy v1.294 PDHA1 Clare van Eyk reviewed gene: PDHA1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Pyruvate dehydrogenase E1-alpha deficiency MIM#312170; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral Palsy v1.294 PCDH19 Clare van Eyk changed review comment from: Variants in PCDH19 cause an X-linked disorder which affects heterozygous females, with hemizygous males largely unaffected. 1 female with heterozygous likely pathogenic missense variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.; to: 1 female with heterozygous likely pathogenic missense variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Cerebral Palsy v1.294 PCDH19 Clare van Eyk commented on gene: PCDH19: Variants in PCDH19 cause an X-linked disorder which affects heterozygous females, with hemizygous males largely unaffected. 1 female with heterozygous likely pathogenic missense variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Cerebral Palsy v1.294 MECP2 Clare van Eyk reviewed gene: MECP2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Encephalopathy, neonatal severe - 300673, Intellectual developmental disorder, X-linked syndromic, Lubs type - 300260, Intellectual developmental disorder, X-linked, syndromic 13 - 300055, Rett syndrome - 312750; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral Palsy v1.294 IQSEC2 Clare van Eyk reviewed gene: IQSEC2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Intellectual developmental disorder MIM#309530; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral Palsy v1.294 HUWE1 Clare van Eyk reviewed gene: HUWE1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Intellectual developmental disorder, X-linked syndromic, Turner type, MIM#309590; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral Palsy v1.294 CDKL5 Clare van Eyk reviewed gene: CDKL5: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Developmental and epileptic encephalopathy 2, MIM#300672; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral Palsy v1.294 WDR62 Clare van Eyk gene: WDR62 was added
gene: WDR62 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: WDR62 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR62 were set to PMID: 38693247
Phenotypes for gene: WDR62 were set to Microcephaly 2, primary, autosomal recessive, with or without cortical malformations, MIM#604317
Review for gene: WDR62 was set to RED
Added comment: 1 individual reported with biallelic pathogenic variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.

MCPH2 is associated with primary microcephaly with variable other neurodevelopmental features. Spastic quadriplegia, hemiplegia, hypertonia are reported.
Sources: Literature
Cerebral Palsy v1.294 VPS53 Clare van Eyk gene: VPS53 was added
gene: VPS53 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: VPS53 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS53 were set to PMID: 38693247
Phenotypes for gene: VPS53 were set to Pontocerebellar hypoplasia, type 2E, MIM#615851
Review for gene: VPS53 was set to RED
Added comment: 1 individual reported with biallelic LOF variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Pontocerebellar hypoplasia type 2E is an autosomal recessive neurodegenerative disorder characterized by profound intellectual disability, progressive microcephaly, spasticity, and early-onset epilepsy. 1 family reported with complex hereditary spastic paraparesis phenotype (PMID: 31418091).
Sources: Literature
Cerebral Palsy v1.294 VPS13B Clare van Eyk gene: VPS13B was added
gene: VPS13B was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: VPS13B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS13B were set to PMID: 38693247
Phenotypes for gene: VPS13B were set to Cohen syndrome, MIM#216550
Review for gene: VPS13B was set to RED
Added comment: 2 individuals with biallelic LOF variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.294 TH Clare van Eyk reviewed gene: TH: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247, PMID: 28904579; Phenotypes: Segawa syndrome, recessive, MIM#605407; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.294 SYNE1 Clare van Eyk reviewed gene: SYNE1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 38693247, PMID: 30275942; Phenotypes: Spinocerebellar ataxia, autosomal recessive 8 MIM#610743; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.294 SLC25A12 Clare van Eyk gene: SLC25A12 was added
gene: SLC25A12 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SLC25A12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A12 were set to PMID: 31403263; PMID: 38693247
Phenotypes for gene: SLC25A12 were set to Developmental and epileptic encephalopathy 39, MIM#612949
Review for gene: SLC25A12 was set to RED
Added comment: 1 patient with novel compound heterozygous variants reported with spastic quadriplegic cerebral palsy (PMID: 31403263). Additional individual reported with homozygous missense variant in large-scale exome sequencing study (PMID: 38693247), however detailed clinical information and functional support for pathogenicity were not supplied.
Sources: Literature
Cerebral Palsy v1.294 RTTN Clare van Eyk gene: RTTN was added
gene: RTTN was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: RTTN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RTTN were set to PMID: 38693247
Phenotypes for gene: RTTN were set to Microcephaly, short stature, and polymicrogyria with seizures, MIM#614833
Review for gene: RTTN was set to RED
Added comment: 1 individual reported with biallelic LOF variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Hypotonia and spasticity have been reported in MSSP.
Sources: Literature
Cerebral Palsy v1.294 ROGDI Clare van Eyk gene: ROGDI was added
gene: ROGDI was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ROGDI was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ROGDI were set to PMID: 38693247
Phenotypes for gene: ROGDI were set to Kohlschutter-Tonz syndrome, MIM#226750
Review for gene: ROGDI was set to RED
Added comment: 1 individual reported with biallelic pathogenic LOF variants (1 stopgain,1 splice) in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.

Kohlschutter-Tonz syndrome is characterized by a consistent phenotype of severe global developmental delay, early-onset intractable seizures, progressive spasticity, and amelogenesis imperfecta causing discoloration of both primary and secondary teeth.
Sources: Literature
Speech apraxia v0.8 MKL2 Zornitza Stark changed review comment from: Only two individuals reported.; to: Only two individuals reported with GoF variants.

The variant reported in a third individual in PMID 29463886 is present in >500 individuals in gnomAD v4, and is marked as LCLoF.
Speech apraxia v0.8 MKL2 Zornitza Stark edited their review of gene: MKL2: Changed publications: 29463886
Speech apraxia v0.8 CHD3 Zornitza Stark Marked gene: CHD3 as ready
Speech apraxia v0.8 CHD3 Zornitza Stark Gene: chd3 has been classified as Green List (High Evidence).
Speech apraxia v0.8 CHD3 Zornitza Stark Phenotypes for gene: CHD3 were changed from to Snijders Blok-Campeau syndrome MIM#618205
Speech apraxia v0.7 CHD3 Zornitza Stark Classified gene: CHD3 as Green List (high evidence)
Speech apraxia v0.7 CHD3 Zornitza Stark Gene: chd3 has been classified as Green List (High Evidence).
Speech apraxia v0.6 CHD3 Zornitza Stark reviewed gene: CHD3: Rating: GREEN; Mode of pathogenicity: None; Publications: 30397230; Phenotypes: Snijders Blok-Campeau syndrome MIM#618205; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Speech apraxia v0.6 KAT6A Zornitza Stark Marked gene: KAT6A as ready
Speech apraxia v0.6 KAT6A Zornitza Stark Gene: kat6a has been classified as Green List (High Evidence).
Speech apraxia v0.6 KAT6A Zornitza Stark Phenotypes for gene: KAT6A were changed from Childhood apraxia of speech; see comments. to Arboleda-Tham syndrome, MIM# 616268
Speech apraxia v0.5 KAT6A Zornitza Stark Classified gene: KAT6A as Green List (high evidence)
Speech apraxia v0.5 KAT6A Zornitza Stark Gene: kat6a has been classified as Green List (High Evidence).
Speech apraxia v0.4 KAT6A Zornitza Stark reviewed gene: KAT6A: Rating: GREEN; Mode of pathogenicity: None; Publications: 35892268; Phenotypes: Arboleda-Tham syndrome, MIM# 616268; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Speech apraxia v0.4 MKL2 Zornitza Stark Marked gene: MKL2 as ready
Speech apraxia v0.4 MKL2 Zornitza Stark Gene: mkl2 has been classified as Amber List (Moderate Evidence).
Speech apraxia v0.4 MKL2 Zornitza Stark Phenotypes for gene: MKL2 were changed from Childhood apraxia of speech; see comments. to Neurodevelopmental disorder (MONDO:0700092), MKL2-related
Speech apraxia v0.3 MKL2 Zornitza Stark Classified gene: MKL2 as Amber List (moderate evidence)
Speech apraxia v0.3 MKL2 Zornitza Stark Gene: mkl2 has been classified as Amber List (Moderate Evidence).
Speech apraxia v0.2 MKL2 Zornitza Stark reviewed gene: MKL2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder (MONDO:0700092), MKL2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Speech apraxia v0.2 FOXP2 Zornitza Stark Marked gene: FOXP2 as ready
Speech apraxia v0.2 FOXP2 Zornitza Stark Gene: foxp2 has been classified as Green List (High Evidence).
Speech apraxia v0.2 FOXP2 Zornitza Stark Phenotypes for gene: FOXP2 were changed from Childhood apraxia of speech to Speech-language disorder-1, MIM# 602081
Speech apraxia v0.1 FOXP2 Zornitza Stark Classified gene: FOXP2 as Green List (high evidence)
Speech apraxia v0.1 FOXP2 Zornitza Stark Gene: foxp2 has been classified as Green List (High Evidence).
Speech apraxia v0.0 FOXP2 Zornitza Stark reviewed gene: FOXP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Speech-language disorder-1, MIM# 602081; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.294 PIGN Zornitza Stark Publications for gene: PIGN were set to PMID: 33528536
Cerebral Palsy v1.293 PLA2G6 Zornitza Stark Publications for gene: PLA2G6 were set to 33528536; 34540776; 34788679
Cerebral Palsy v1.292 POLG Zornitza Stark Marked gene: POLG as ready
Cerebral Palsy v1.292 POLG Zornitza Stark Gene: polg has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.292 POLG Zornitza Stark Classified gene: POLG as Amber List (moderate evidence)
Cerebral Palsy v1.292 POLG Zornitza Stark Gene: polg has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.251 MYH10 Zornitza Stark Phenotypes for gene: MYH10 were changed from MYH10-related Multiple congenital anomalies; Bilateral ventriculomegaly; aqueductal stenosis; Microcephaly; Hip dysplasia to AD complex neurodevelopmental disorder with or without congenital anomalies (MONDO:0100465)
Intellectual disability syndromic and non-syndromic v0.6042 MYH10 Zornitza Stark Phenotypes for gene: MYH10 were changed from Microcephaly; Intellectual Disability to AD complex neurodevelopmental disorder with or without congenital anomalies (MONDO:0100465)
Microcephaly v1.261 MYH10 Zornitza Stark Phenotypes for gene: MYH10 were changed from Microcephaly; Intellectual Disability to AD complex neurodevelopmental disorder with or without congenital anomalies (MONDO:0100465)
Mendeliome v1.1842 MYH10 Zornitza Stark Phenotypes for gene: MYH10 were changed from Microcephaly; Intellectual Disability to AD complex neurodevelopmental disorder with or without congenital anomalies (MONDO:0100465)
Cerebral Palsy v1.291 POLG Clare van Eyk gene: POLG was added
gene: POLG was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: POLG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLG were set to PMID: 33528536; PMID: 38693247
Phenotypes for gene: POLG were set to Mitochondrial DNA depletion syndrome 4a, MIM#203700, Mitochondrial DNA Depletion Syndrome 4B, MIM#613662, Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE), MIM#607459
Review for gene: POLG was set to AMBER
Added comment: 1 individual reported with biallelic P/LP missense variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Additional individual reported in clinical referral cohort (PMID: 33528536). Mutations in POLG are associated with a wide range of clinical features including lactic acidosis, seizures, ataxia, peripheral neuropathy, developmental delay, myopathy, chronic progressive external ophthalmoplegia, and hepatopathy.
Sources: Literature
Cerebral Palsy v1.291 PLA2G6 Clare van Eyk reviewed gene: PLA2G6: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.291 PIGN Clare van Eyk edited their review of gene: PIGN: Added comment: An additional individual reported with biallelic stopgain variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.; Changed publications: PMID: 33528536, PMID: 34540776, PMID: 38693247
Cerebral Palsy v1.291 PIDD1 Clare van Eyk gene: PIDD1 was added
gene: PIDD1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PIDD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIDD1 were set to PMID: 38693247
Phenotypes for gene: PIDD1 were set to Intellectual developmental disorder, autosomal recessive 75, with neuropsychiatric features and variant lissencephaly, MIM#619827
Review for gene: PIDD1 was set to RED
Added comment: 1 individual reported with biallelic LOF variants reported in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. PIDD1 is associated with an intellectual developmental disorder with variant lissencephaly.
Sources: Literature
Aminoacidopathy v1.66 OAT Sangavi Sivagnanasundram gene: OAT was added
gene: OAT was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: OAT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OAT were set to 609808; 23076989; 24429551; 25264521
Phenotypes for gene: OAT were set to ornithine aminotransferase deficiency MONDO:0009796
Review for gene: OAT was set to GREEN
Added comment: Established gene disease association with mouse model recapitulating human phenotype.

Classified DEFINITIVE by ClinGen Aminoacidopathy GCEP on 10/07/2019 - https://search.clinicalgenome.org/CCID:005692
Sources: ClinGen
Aminoacidopathy v1.66 NAT8L Sangavi Sivagnanasundram gene: NAT8L was added
gene: NAT8L was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: NAT8L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAT8L were set to 19807691
Phenotypes for gene: NAT8L were set to N-acetylaspartate deficiency MONDO:0013549
Review for gene: NAT8L was set to RED
Added comment: Reported in one individual with N-acetylaspartate deficiency but also has other severe neurological features however the gene-disease association in this individual is unclear.

Classified LIMITED by ClinGen Aminoacidopathy GCEP on 29/03/2024 - https://search.clinicalgenome.org/CCID:005565
Sources: ClinGen
Aminoacidopathy v1.66 NAGS Sangavi Sivagnanasundram gene: NAGS was added
gene: NAGS was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: NAGS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAGS were set to 15714518; 27037498; 22503289
Phenotypes for gene: NAGS were set to hyperammonemia due to N-acetylglutamate synthase deficiency MONDO:0009377
Review for gene: NAGS was set to GREEN
Added comment: Established gene-disease with reported individuals having an urea cycle disorder.

Classified DEFINITIVE by ClinGen Aminoacidopathy GCEP on 26/07/2019 - https://search.clinicalgenome.org/CCID:005562
Sources: ClinGen
Aminoacidopathy v1.66 MTRR Sangavi Sivagnanasundram gene: MTRR was added
gene: MTRR was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: MTRR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTRR were set to 10484769; 12555939; 15714522; 17369066
Phenotypes for gene: MTRR were set to methylcobalamin deficiency type cblE MONDO:0009354
Review for gene: MTRR was set to GREEN
Added comment: Well established gene-disease association with reported individuals having errors in cobalamin metabolism.

Classified DEFINITIVE by ClinGen Aminoacidopathy GCEP on 02/7/2021 - https://search.clinicalgenome.org/CCID:005505
Sources: ClinGen
Aminoacidopathy v1.66 MTR Sangavi Sivagnanasundram gene: MTR was added
gene: MTR was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: MTR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTR were set to 12068375; 30651581; 31951343
Phenotypes for gene: MTR were set to methylcobalamin deficiency type cblG MONDO:0009609
Review for gene: MTR was set to GREEN
Added comment: Well established gene-disease association with reported individuals having a deficiency methionine synthase.

Classified as DEFINITIVE by ClinGen Aminoacidopathy GCEP on 02/7/2021 - https://search.clinicalgenome.org/CCID:005503
Sources: ClinGen
Fetal anomalies v1.250 FUZ Zornitza Stark Mode of inheritance for gene: FUZ was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1841 FUZ Zornitza Stark Mode of inheritance for gene: FUZ was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Aminoacidopathy v1.66 MTHFR Sangavi Sivagnanasundram gene: MTHFR was added
gene: MTHFR was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: MTHFR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTHFR were set to 26872964
Phenotypes for gene: MTHFR were set to homocystinuria due to methylene tetrahydrofolate reductase deficiency MONDO:0009353
Review for gene: MTHFR was set to GREEN
Added comment: Established gene-disease association with reported individuals having reported elevated homocysteine and decreased methionine.

Classified as DEFINITIVE by ClinGen Aminoacidopathy GCEP on 18/06/2019 - https://search.clinicalgenome.org/CCID:005497
Sources: ClinGen
Aminoacidopathy v1.66 MPST Sangavi Sivagnanasundram gene: MPST was added
gene: MPST was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: MPST was set to Unknown
Phenotypes for gene: MPST were set to encephalopathy due to beta-mercaptolactate-cysteine disulfiduria MONDO:0009585
Review for gene: MPST was set to RED
Added comment: No reported individuals with deficiency in MPST enzymatic activity.

No known disease relationship classification given by ClinGen Aminoacidopathy GCEP on
28/04/2023 - https://search.clinicalgenome.org/CCID:005413
Sources: ClinGen
Aminoacidopathy v1.66 MMACHC Sangavi Sivagnanasundram gene: MMACHC was added
gene: MMACHC was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: MMACHC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MMACHC were set to 26149271; 28693988; 18164228; 16963011; 30157807; 16311595; 23580368
Phenotypes for gene: MMACHC were set to methylmalonic aciduria and homocystinuria type cblC MONDO:0010184
Review for gene: MMACHC was set to GREEN
Added comment: Well established gene disease association with reported individuals having errors in biochemical function.

Classified as DEFINITIVE by ClinGen Aminoacidopathy GCEP on 29/06/2020 - https://search.clinicalgenome.org/CCID:005397
Sources: ClinGen
Aminoacidopathy v1.66 MCEE Sangavi Sivagnanasundram gene: MCEE was added
gene: MCEE was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: MCEE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCEE were set to 16697227; 17823972; 27699154; 29104221; 30682498; 31146325
Phenotypes for gene: MCEE were set to methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency MONDO:0009615
Review for gene: MCEE was set to GREEN
Added comment: Established gene-disease association with >10 probands reported with variants in this gene.

Classified as DEFINITIVE by ClinGen Aminoacidopathy GCEP on 09/07/2020 - https://search.clinicalgenome.org/CCID:005348
Sources: ClinGen
Aminoacidopathy v1.66 MAT1A Sangavi Sivagnanasundram gene: MAT1A was added
gene: MAT1A was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: MAT1A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAT1A were set to 9042912; 11320206
Phenotypes for gene: MAT1A were set to methionine adenosyltransferase deficiency MONDO:0009607
Mode of pathogenicity for gene: MAT1A was set to Other
Review for gene: MAT1A was set to GREEN
Added comment: Well established gene-disease association. Dominant negative appears to be the mechanism of disease.

Classified as DEFINITIVE by ClinGen Aminoacidopathy GCEP on 13/09/2019 - https://search.clinicalgenome.org/CCID:005340
Sources: ClinGen
Speech apraxia v0.0 MKL2 Thomas Scerri changed review comment from: p.R104G and p.A91P reported as a gain of function (JC Andrews et al., 2023).

Additional phenotypes: ID, GDD, CAS, mild dysmorphic features, impulse control issues (PMID: 38366112).
Sources: Expert list, Expert Review; to: p.R104G and p.A91P reported as a gain of function (JC Andrews et al., 2023).

Additional phenotypes: ID, GDD, CAS, mild dysmorphic features, impulse control issues (PMID: 38366112).
Sources: Expert list, Expert Review
Speech apraxia v0.0 KAT6A Thomas Scerri changed review comment from: ID, vision impairment, GI dysfunction, sleep disturbance, ASD, majority minimally verbal & rely on alternate communication. Rates of epilepsy, ADHD, CP higher than typical population (PMID: 38366112).
Sources: Expert list, Expert Review; to: Additional phenotypes: ID, vision impairment, GI dysfunction, sleep disturbance, ASD, majority minimally verbal & rely on alternate communication. Rates of epilepsy, ADHD, CP higher than typical population (PMID: 38366112).
Sources: Expert list, Expert Review
Speech apraxia v0.0 FOXP2 Thomas Scerri changed review comment from: Cognition ranges from average to mild ID, feeding difficulties in infancy, fine & gross motor impairment, ASD, language impairment, anxiety, depression, sleep disturbance (PMID: 38366112).; to: Additional phenotypes: Cognition ranges from average to mild ID, feeding difficulties in infancy, fine & gross motor impairment, ASD, language impairment, anxiety, depression, sleep disturbance (PMID: 38366112).
Speech apraxia v0.0 CHD3 Thomas Scerri changed review comment from: ID/DD, macrocephaly, prominent forehead, hypertelorism, hypotonia, joint laxity, severity of neurologic deficits & presence of non-neurologic features are variable. Autistic features are commonly reported (PMID: 38366112).; to: Additional phenotypes: ID/DD, macrocephaly, prominent forehead, hypertelorism, hypotonia, joint laxity, severity of neurologic deficits & presence of non-neurologic features are variable. Autistic features are commonly reported (PMID: 38366112).
Speech apraxia v0.0 FOXP2 Thomas Scerri edited their review of gene: FOXP2: Changed publications: 11586359, 36328423, 38366112
Speech apraxia v0.0 CHD3 Thomas Scerri edited their review of gene: CHD3: Changed publications: 30397230, 38366112, 35346573
Speech apraxia v0.0 MKL2 Thomas Scerri edited their review of gene: MKL2: Changed rating: GREEN
Speech apraxia v0.0 MKL2 Thomas Scerri changed review comment from: p.R104G and p.A91P reported as a gain of function (JC Andrews et al., 2023).

Additional phenotypes: ID, GDD, CAS, mild dysmorphic features, impulse control issues. AT Morgan et al., (2024).
Sources: Expert list, Expert Review; to: p.R104G and p.A91P reported as a gain of function (JC Andrews et al., 2023).

Additional phenotypes: ID, GDD, CAS, mild dysmorphic features, impulse control issues (PMID: 38366112).
Sources: Expert list, Expert Review
Speech apraxia v0.0 KAT6A Thomas Scerri changed review comment from: ID, vision impairment, GI dysfunction, sleep disturbance, ASD, majority minimally verbal & rely on alternate communication. Rates of epilepsy, ADHD, CP higher than typical population. (PMID: 38366112).
Sources: Expert list, Expert Review; to: ID, vision impairment, GI dysfunction, sleep disturbance, ASD, majority minimally verbal & rely on alternate communication. Rates of epilepsy, ADHD, CP higher than typical population (PMID: 38366112).
Sources: Expert list, Expert Review
Speech apraxia v0.0 FOXP2 Thomas Scerri changed review comment from: Cognition ranges from average to mild ID, feeding difficulties in infancy, fine & gross motor impairment, ASD, language impairment, anxiety, depression, sleep disturbance. (PMID: 38366112).; to: Cognition ranges from average to mild ID, feeding difficulties in infancy, fine & gross motor impairment, ASD, language impairment, anxiety, depression, sleep disturbance (PMID: 38366112).
Speech apraxia v0.0 CHD3 Thomas Scerri changed review comment from: ID/DD, macrocephaly, prominent forehead, hypertelorism, hypotonia, joint laxity, severity of neurologic deficits & presence of non-neurologic features are variable. Autistic features are commonly reported. (PMID: 38366112).; to: ID/DD, macrocephaly, prominent forehead, hypertelorism, hypotonia, joint laxity, severity of neurologic deficits & presence of non-neurologic features are variable. Autistic features are commonly reported (PMID: 38366112).
Cerebral Palsy v1.291 PCLO Clare van Eyk gene: PCLO was added
gene: PCLO was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PCLO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCLO were set to PMID: 38693247
Phenotypes for gene: PCLO were set to Pontocerebellar hypoplasia, type 3, MIM#608027
Review for gene: PCLO was set to RED
Added comment: 1 individual reported with homozygous stopgain variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Speech apraxia v0.0 KAT6A Thomas Scerri changed review comment from: ID, vision impairment, GI dysfunction, sleep disturbance, ASD, majority minimally verbal & rely on alternate communication. Rates of epilepsy, ADHD, CP higher than typical population. AT Morgan et al., (2024).
Sources: Expert list, Expert Review; to: ID, vision impairment, GI dysfunction, sleep disturbance, ASD, majority minimally verbal & rely on alternate communication. Rates of epilepsy, ADHD, CP higher than typical population. (PMID: 38366112).
Sources: Expert list, Expert Review
Speech apraxia v0.0 FOXP2 Thomas Scerri changed review comment from: Cognition ranges from average to mild ID, feeding difficulties in infancy, fine & gross motor impairment, ASD, language impairment, anxiety, depression, sleep disturbance. AT Morgan et al., (2024).; to: Cognition ranges from average to mild ID, feeding difficulties in infancy, fine & gross motor impairment, ASD, language impairment, anxiety, depression, sleep disturbance. (PMID: 38366112).
Speech apraxia v0.0 CHD3 Thomas Scerri changed review comment from: ID/DD, macrocephaly, prominent forehead, hypertelorism, hypotonia, joint laxity, severity of neurologic deficits & presence of non-neurologic features are variable. Autistic features are commonly reported. AT Morgan et al., (2024).; to: ID/DD, macrocephaly, prominent forehead, hypertelorism, hypotonia, joint laxity, severity of neurologic deficits & presence of non-neurologic features are variable. Autistic features are commonly reported. (PMID: 38366112).
Speech apraxia v0.0 CHD3 Thomas Scerri changed review comment from: ID/DD, macrocephaly, prominent forehead, hypertelorism, hypotonia, joint laxity, severity of neurologic deficits & presence of non-neurologic features are variable. Autistic features are commonly reported. AT Morgan et al. (2024).; to: ID/DD, macrocephaly, prominent forehead, hypertelorism, hypotonia, joint laxity, severity of neurologic deficits & presence of non-neurologic features are variable. Autistic features are commonly reported. AT Morgan et al., (2024).
Speech apraxia v0.0 KAT6A Thomas Scerri changed review comment from: ID, vision impairment, GI dysfunction, sleep disturbance, ASD, majority minimally verbal & rely on alternate communication. Rates of epilepsy, ADHD, CP higher than typical population. AT Morgan et al. (2024).
Sources: Expert list, Expert Review; to: ID, vision impairment, GI dysfunction, sleep disturbance, ASD, majority minimally verbal & rely on alternate communication. Rates of epilepsy, ADHD, CP higher than typical population. AT Morgan et al., (2024).
Sources: Expert list, Expert Review
Speech apraxia v0.0 MKL2 Thomas Scerri gene: MKL2 was added
gene: MKL2 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: MKL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MKL2 were set to 29463886; 37013900; 38366112
Phenotypes for gene: MKL2 were set to Childhood apraxia of speech; see comments.
Penetrance for gene: MKL2 were set to Complete
Added comment: p.R104G and p.A91P reported as a gain of function (JC Andrews et al., 2023).

Additional phenotypes: ID, GDD, CAS, mild dysmorphic features, impulse control issues. AT Morgan et al., (2024).
Sources: Expert list, Expert Review
Cerebral Palsy v1.291 MYO9A Clare van Eyk gene: MYO9A was added
gene: MYO9A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MYO9A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYO9A were set to PMID: 38693247
Phenotypes for gene: MYO9A were set to Myasthenic syndrome, congenital, 24, presynaptic, MIM#618198
Review for gene: MYO9A was set to RED
Added comment: 2 individuals reported with biallelic P/LP variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.291 PCDH12 Clare van Eyk commented on gene: PCDH12: 2 additional individuals reported with biallelic LOF variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Cerebral Palsy v1.291 MUT Clare van Eyk gene: MUT was added
gene: MUT was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MUT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MUT were set to PMID: 38693247
Phenotypes for gene: MUT were set to Methylmalonic aciduria, MIM#251000
Review for gene: MUT was set to AMBER
Added comment: 1 individual reported with homozygous pathogenic missense variant in large-scale exome sequencing study (PMID: 38693247). Methylmalonic aciduria has a broad clinical spectrum, with neurologic manifestations, such as seizure, encephalopathy, and stroke, frequently reported.
Sources: Literature
Speech apraxia v0.0 KAT6A Thomas Scerri gene: KAT6A was added
gene: KAT6A was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: KAT6A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KAT6A were set to 35892268; 38366112; 30245513
Phenotypes for gene: KAT6A were set to Childhood apraxia of speech; see comments.
Penetrance for gene: KAT6A were set to Complete
Review for gene: KAT6A was set to GREEN
Added comment: ID, vision impairment, GI dysfunction, sleep disturbance, ASD, majority minimally verbal & rely on alternate communication. Rates of epilepsy, ADHD, CP higher than typical population. AT Morgan et al. (2024).
Sources: Expert list, Expert Review
Speech apraxia v0.0 CHD3 Thomas Scerri edited their review of gene: CHD3: Added comment: ID/DD, macrocephaly, prominent forehead, hypertelorism, hypotonia, joint laxity, severity of neurologic deficits & presence of non-neurologic features are variable. Autistic features are commonly reported. AT Morgan et al. (2024).; Changed phenotypes: Childhood apraxia of speech, see comments.
Speech apraxia v0.0 FOXP2 Thomas Scerri edited their review of gene: FOXP2: Added comment: Cognition ranges from average to mild ID, feeding difficulties in infancy, fine & gross motor impairment, ASD, language impairment, anxiety, depression, sleep disturbance. AT Morgan et al., (2024).; Changed phenotypes: Childhood apraxia of speech, see comments.
Cerebral Palsy v1.291 MOCS1 Clare van Eyk reviewed gene: MOCS1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Molybdenum cofactor deficiency A MIM#252150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.291 MMACHC Clare van Eyk gene: MMACHC was added
gene: MMACHC was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MMACHC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MMACHC were set to PMID: 38693247
Phenotypes for gene: MMACHC were set to Methylmalonic aciduria and homocystinuria, cblC type, MIM#277400
Review for gene: MMACHC was set to AMBER
Added comment: 3 individuals reported with biallelic LOF variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Variable age at onset with frequent neurological and cardiovascular sequelae.
Sources: Literature
Cerebral Palsy v1.291 MCCC2 Clare van Eyk gene: MCCC2 was added
gene: MCCC2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MCCC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCCC2 were set to PMID: 38693247
Phenotypes for gene: MCCC2 were set to 3-Methylcrotonyl-CoA carboxylase 2 deficiency, MIM#210210
Review for gene: MCCC2 was set to AMBER
Added comment: 1 individual reported with homozygous likely pathogenic missense variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. MCC2D is an autosomal recessive disorder of leucine catabolism. Highly variable clinical phenotype ranging from neonatal onset with severe neurologic involvement to asymptomatic adults. Additional individuals with a clinical diagnosis of CP or overlapping clinical presentation can be found in the literature (e.g. PMID: 9187484, PMID: 10485305)
Sources: Literature
Cerebral Palsy v1.291 LZTR1 Clare van Eyk gene: LZTR1 was added
gene: LZTR1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: LZTR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LZTR1 were set to PMID: 38693247
Phenotypes for gene: LZTR1 were set to Noonan syndrome 2, MIM#605275
Review for gene: LZTR1 was set to RED
Added comment: 1 individual reported with homozygous pathogenic missense variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.291 LRP2 Clare van Eyk gene: LRP2 was added
gene: LRP2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: LRP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRP2 were set to PMID: 38693247
Phenotypes for gene: LRP2 were set to Donnai-Barrow syndrome, MIM#222448
Review for gene: LRP2 was set to RED
Added comment: 1 individual reported with compound heterozygous predicted LOF variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. DBS is associated with multiple congenital anomalies.
Sources: Literature
Cerebral Palsy v1.291 LAMA1 Clare van Eyk gene: LAMA1 was added
gene: LAMA1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: LAMA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LAMA1 were set to PMID: 38693247
Phenotypes for gene: LAMA1 were set to Poretti-Boltshauser syndrome, MIM#615960
Review for gene: LAMA1 was set to RED
Added comment: 1 individual reported with biallelic pathogenic LOF variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Cerebellar cysts and periventricular white matter abnormalities are common imaging findings in Poretti-Boltshauser syndrome.
Sources: Literature
Mendeliome v1.1840 THRB Achchuthan Shanmugasundram reviewed gene: THRB: Rating: AMBER; Mode of pathogenicity: None; Publications: 37547476; Phenotypes: inherited retinal dystrophy, MONDO:0019118; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
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.
Mendeliome v1.1840 SUMF1 Achchuthan Shanmugasundram reviewed gene: SUMF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 38863195; Phenotypes: inherited retinal dystrophy, MONDO:0019118; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Speech apraxia v0.0 CHD3 Thomas Scerri edited their review of gene: CHD3: Changed phenotypes: Childhood apraxia of speech
Speech apraxia v0.0 CHD3 Thomas Scerri gene: CHD3 was added
gene: CHD3 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: CHD3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHD3 were set to PMID: 30397230; 38366112; 35346573
Penetrance for gene: CHD3 were set to Complete
Review for gene: CHD3 was set to GREEN
Added comment: Variant p.Leu915Phe yielded increased activity (PMID: 30397230).
Evidence of reduced penetrance and variable expressivity (PMID: 35346573).
Sources: Expert list, Expert Review
Speech apraxia v0.0 FOXP2 Thomas Scerri gene: FOXP2 was added
gene: FOXP2 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: FOXP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOXP2 were set to PMID: 11586359; 36328423; 38366112
Phenotypes for gene: FOXP2 were set to Childhood apraxia of speech
Penetrance for gene: FOXP2 were set to Complete
Review for gene: FOXP2 was set to GREEN
Added comment: Sources: Expert list, Expert Review
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.
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.
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.
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).
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).
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)
Mendeliome v1.1840 PRRX1 Melanie Marty reviewed gene: PRRX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 37154149, 28366454, 34376651; Phenotypes: Craniosynostosis (MONDO:0015469), PRRX1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6041 AFF2 Zornitza Stark Phenotypes for gene: AFF2 were changed from Mental retardation, X-linked, FRAXE type 309548 to Intellectual disability, X-linked, FRAXE type 309548
Intellectual disability syndromic and non-syndromic v0.6040 AFF2 Zornitza Stark Mode of inheritance for gene: AFF2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.6039 AFF2 Zornitza Stark Mode of inheritance for gene: AFF2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.6038 AFF2 Zornitza Stark edited their review of gene: AFF2: Changed phenotypes: Intellectual disability, X-linked, FRAXE type 309548; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
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 v1.1839 AFF2 Zornitza Stark Mode of inheritance for gene: AFF2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.1838 AFF2 Zornitza Stark edited their review of gene: AFF2: Changed phenotypes: Intellectual disability, X-linked, FRAXE type 309548; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cerebral Palsy v1.291 KIF14 Zornitza Stark Marked gene: KIF14 as ready
Cerebral Palsy v1.291 KIF14 Zornitza Stark Gene: kif14 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.291 KIF14 Zornitza Stark Classified gene: KIF14 as Red List (low evidence)
Cerebral Palsy v1.291 KIF14 Zornitza Stark Gene: kif14 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.290 KIF14 Clare van Eyk gene: KIF14 was added
gene: KIF14 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: KIF14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF14 were set to PMID: 38693247
Phenotypes for gene: KIF14 were set to Microcephaly 20, primary, MIM#617914
Review for gene: KIF14 was set to RED
Added comment: 1 individual reported with biallelic variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.290 GCDH Zornitza Stark Phenotypes for gene: GCDH were changed from Glutaricaciduria, type I MIM#231670 to Glutaric aciduria, type I MIM#231670
Cerebral Palsy v1.289 GCDH Zornitza Stark Publications for gene: GCDH were set to 30542205; 26593172
Cerebral Palsy v1.288 GCDH Zornitza Stark Classified gene: GCDH as Green List (high evidence)
Cerebral Palsy v1.288 GCDH Zornitza Stark Gene: gcdh has been classified as Green List (High Evidence).
Mendeliome v1.1838 RDH14 Zornitza Stark Marked gene: RDH14 as ready
Mendeliome v1.1838 RDH14 Zornitza Stark Gene: rdh14 has been classified as Red List (Low Evidence).
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
Intellectual disability syndromic and non-syndromic v0.6038 RDH14 Zornitza Stark Marked gene: RDH14 as ready
Intellectual disability syndromic and non-syndromic v0.6038 RDH14 Zornitza Stark Gene: rdh14 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.6038 RDH14 Zornitza Stark gene: RDH14 was added
gene: RDH14 was added to Intellectual disability syndromic and non-syndromic. 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
Brain Calcification v1.96 Zornitza Stark removed gene:GBA from the panel
Cerebral Palsy v1.287 HSPD1 Zornitza Stark Marked gene: HSPD1 as ready
Cerebral Palsy v1.287 HSPD1 Zornitza Stark Gene: hspd1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.287 HSPD1 Zornitza Stark Classified gene: HSPD1 as Red List (low evidence)
Cerebral Palsy v1.287 HSPD1 Zornitza Stark Gene: hspd1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.286 GBA Zornitza Stark Marked gene: GBA as ready
Cerebral Palsy v1.286 GBA Zornitza Stark Gene: gba has been classified as Red List (Low Evidence).
Cerebral Palsy v1.286 GBA Zornitza Stark Classified gene: GBA as Red List (low evidence)
Cerebral Palsy v1.286 GBA Zornitza Stark Gene: gba has been classified as Red List (Low Evidence).
Cerebral Palsy v1.285 GALC Zornitza Stark Marked gene: GALC as ready
Cerebral Palsy v1.285 GALC Zornitza Stark Gene: galc has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.285 GALC Zornitza Stark Classified gene: GALC as Amber List (moderate evidence)
Cerebral Palsy v1.285 GALC Zornitza Stark Gene: galc has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.284 Zornitza Stark removed gene:AGA from the panel
Cerebral Palsy v1.283 HSPD1 Clare van Eyk gene: HSPD1 was added
gene: HSPD1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: HSPD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HSPD1 were set to PMID: 38693247
Phenotypes for gene: HSPD1 were set to Leukodystrophy, hypomyelinating, 4, MIM#612233
Review for gene: HSPD1 was set to RED
Added comment: 1 individual reported with homozygous likely pathogenic missense variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. HLD4 has been reported to show rapidly progressive prominent spasticity and developmental regression.
Sources: Literature
Cerebral Palsy v1.283 GCDH Clare van Eyk reviewed gene: GCDH: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Glutaricaciduria, type I MIM#231670; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.283 GBA Clare van Eyk gene: GBA was added
gene: GBA was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: GBA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GBA were set to PMID: 38693247
Phenotypes for gene: GBA were set to Gaucher disease, MIM#231000
Review for gene: GBA was set to RED
Added comment: 1 individual reported with homozygous pathogenic missense variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Gaucher disease can be associated with ataxia, dystonia and spasticity with variable age of onset.
Sources: Literature
Sources: Literature
Brain Calcification v1.95 GBA Clare van Eyk Deleted their review
Brain Calcification v1.95 GBA Clare van Eyk gene: GBA was added
gene: GBA was added to Brain Calcification. Sources: Literature
Mode of inheritance for gene: GBA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GBA were set to PMID: 38693247
Phenotypes for gene: GBA were set to Gaucher disease, MIM#231000
Review for gene: GBA was set to RED
Added comment: 1 individual reported with homozygous pathogenic missense variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Gaucher disease can be associated with ataxia, dystonia and spasticity with variable age of onset.
Sources: Literature
Cerebral Palsy v1.283 FAM20C Zornitza Stark Marked gene: FAM20C as ready
Cerebral Palsy v1.283 FAM20C Zornitza Stark Gene: fam20c has been classified as Red List (Low Evidence).
Cerebral Palsy v1.283 FAM20C Zornitza Stark Classified gene: FAM20C as Red List (low evidence)
Cerebral Palsy v1.283 FAM20C Zornitza Stark Gene: fam20c has been classified as Red List (Low Evidence).
Cerebral Palsy v1.282 GAMT Zornitza Stark Marked gene: GAMT as ready
Cerebral Palsy v1.282 GAMT Zornitza Stark Gene: gamt has been classified as Red List (Low Evidence).
Cerebral Palsy v1.282 GAMT Zornitza Stark Classified gene: GAMT as Red List (low evidence)
Cerebral Palsy v1.282 GAMT Zornitza Stark Gene: gamt has been classified as Red List (Low Evidence).
Cerebral Palsy v1.281 GAMT Clare van Eyk gene: GAMT was added
gene: GAMT was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: GAMT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GAMT were set to PMID: 38693247
Phenotypes for gene: GAMT were set to Cerebral creatine deficiency syndrome 2, MIM#612736
Review for gene: GAMT was set to AMBER
Added comment: 1 individual reported with CP and biallelic variants (missense and stopgain) in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Cerebral creatine deficiency syndrome 2 is associated with prominent movement disturbances and can be initially diagnosed as CP (PMID: 31380813).
Sources: Literature
Cerebral Palsy v1.281 FAM20C Clare van Eyk gene: FAM20C was added
gene: FAM20C was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: FAM20C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAM20C were set to PMID: 38693247
Phenotypes for gene: FAM20C were set to Raine syndrome, MIM#259775
Review for gene: FAM20C was set to RED
Added comment: 1 individual reported with biallelic variants (1 stopgain, 1 frameshift) in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Raine syndrome was originally described as a neonatal osteosclerotic bone dysplasia of early and aggressive onset usually resulting in death within the first few weeks of life, however more recently non-lethal cases with a variable spectrum of features including neurological have been described (PMID: 32299476).
Sources: Literature
Aminoacidopathy v1.66 HGD Zornitza Stark Marked gene: HGD as ready
Aminoacidopathy v1.66 HGD Zornitza Stark Gene: hgd has been classified as Green List (High Evidence).
Aminoacidopathy v1.66 HGD Zornitza Stark Classified gene: HGD as Green List (high evidence)
Aminoacidopathy v1.66 HGD Zornitza Stark Gene: hgd has been classified as Green List (High Evidence).
Aminoacidopathy v1.65 HIBADH Zornitza Stark Marked gene: HIBADH as ready
Aminoacidopathy v1.65 HIBADH Zornitza Stark Gene: hibadh has been classified as Red List (Low Evidence).
Aminoacidopathy v1.65 HIBADH Zornitza Stark Classified gene: HIBADH as Red List (low evidence)
Aminoacidopathy v1.65 HIBADH Zornitza Stark Gene: hibadh has been classified as Red List (Low Evidence).
Aminoacidopathy v1.64 HPD Zornitza Stark Marked gene: HPD as ready
Aminoacidopathy v1.64 HPD Zornitza Stark Gene: hpd has been classified as Green List (High Evidence).
Aminoacidopathy v1.64 HPD Zornitza Stark Classified gene: HPD as Green List (high evidence)
Aminoacidopathy v1.64 HPD Zornitza Stark Gene: hpd has been classified as Green List (High Evidence).
Mendeliome v1.1837 HYKK Zornitza Stark Marked gene: HYKK as ready
Mendeliome v1.1837 HYKK Zornitza Stark Gene: hykk has been classified as Red List (Low Evidence).
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
Cerebral Palsy v1.281 GALC Clare van Eyk gene: GALC was added
gene: GALC was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: GALC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GALC were set to PMID: 38693247
Phenotypes for gene: GALC were set to Krabbe disease, MIM#245200
Review for gene: GALC was set to AMBER
Added comment: 2 individuals reported with biallelic P/LP variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Krabbe disease is associated with progressive spasticity with variable at age at onset. Later onset can be associated with a slower progression and can mimic CP.
Sources: Literature
Aminoacidopathy v1.63 HYKK Zornitza Stark Marked gene: HYKK as ready
Aminoacidopathy v1.63 HYKK Zornitza Stark Gene: hykk has been classified as Red List (Low Evidence).
Aminoacidopathy v1.63 HYKK Zornitza Stark Classified gene: HYKK as Red List (low evidence)
Aminoacidopathy v1.63 HYKK Zornitza Stark Gene: hykk has been classified as Red List (Low Evidence).
Mendeliome v1.1836 KMO Zornitza Stark Marked gene: KMO as ready
Mendeliome v1.1836 KMO Zornitza Stark Gene: kmo has been classified as Red List (Low Evidence).
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
Aminoacidopathy v1.62 KMO Zornitza Stark Marked gene: KMO as ready
Aminoacidopathy v1.62 KMO Zornitza Stark Gene: kmo has been classified as Red List (Low Evidence).
Aminoacidopathy v1.62 KMO Zornitza Stark Classified gene: KMO as Red List (low evidence)
Aminoacidopathy v1.62 KMO Zornitza Stark Gene: kmo has been classified as Red List (Low Evidence).
Vitamin metabolism disorders v1.6 MCEE Zornitza Stark Marked gene: MCEE as ready
Vitamin metabolism disorders v1.6 MCEE Zornitza Stark Gene: mcee has been classified as Green List (High Evidence).
Cerebral Palsy v1.281 DDX59 Zornitza Stark Marked gene: DDX59 as ready
Cerebral Palsy v1.281 DDX59 Zornitza Stark Gene: ddx59 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.281 DDX59 Zornitza Stark Classified gene: DDX59 as Red List (low evidence)
Cerebral Palsy v1.281 DDX59 Zornitza Stark Gene: ddx59 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.280 DHCR7 Zornitza Stark Marked gene: DHCR7 as ready
Cerebral Palsy v1.280 DHCR7 Zornitza Stark Gene: dhcr7 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.280 DHCR7 Zornitza Stark Classified gene: DHCR7 as Red List (low evidence)
Cerebral Palsy v1.280 DHCR7 Zornitza Stark Gene: dhcr7 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.279 DIAPH1 Zornitza Stark Marked gene: DIAPH1 as ready
Cerebral Palsy v1.279 DIAPH1 Zornitza Stark Gene: diaph1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.279 DIAPH1 Zornitza Stark Classified gene: DIAPH1 as Red List (low evidence)
Cerebral Palsy v1.279 DIAPH1 Zornitza Stark Gene: diaph1 has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v1.184 LMNA Zornitza Stark Marked gene: LMNA as ready
Deafness_IsolatedAndComplex v1.184 LMNA Zornitza Stark Gene: lmna has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.184 LMNA Zornitza Stark Classified gene: LMNA as Green List (high evidence)
Deafness_IsolatedAndComplex v1.184 LMNA Zornitza Stark Gene: lmna has been classified as Green List (High Evidence).
Cerebral Palsy v1.278 DUOX2 Zornitza Stark Marked gene: DUOX2 as ready
Cerebral Palsy v1.278 DUOX2 Zornitza Stark Gene: duox2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.278 DUOX2 Zornitza Stark Classified gene: DUOX2 as Red List (low evidence)
Cerebral Palsy v1.278 DUOX2 Zornitza Stark Gene: duox2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.277 EPG5 Zornitza Stark Marked gene: EPG5 as ready
Cerebral Palsy v1.277 EPG5 Zornitza Stark Gene: epg5 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.277 EPG5 Zornitza Stark Classified gene: EPG5 as Red List (low evidence)
Cerebral Palsy v1.277 EPG5 Zornitza Stark Gene: epg5 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.276 ERCC8 Zornitza Stark Publications for gene: ERCC8 were set to 33528536; 30279719
Cerebral Palsy v1.275 ERCC8 Clare van Eyk reviewed gene: ERCC8: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Cockayne syndrome MIM#216400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.275 EPG5 Clare van Eyk gene: EPG5 was added
gene: EPG5 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: EPG5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EPG5 were set to PMID: 38693247
Phenotypes for gene: EPG5 were set to Vici syndrome, MIM#242840
Review for gene: EPG5 was set to RED
Added comment: 1 individual reported with a homozygous stopgain variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Vici syndrome is a neurodevelopmental and immunological disorder affecting multiple systems. Structural abnormalities of the brain along with profound psychomotor retardation have been reported.
Sources: Literature
Cerebral Palsy v1.275 DUOX2 Clare van Eyk gene: DUOX2 was added
gene: DUOX2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: DUOX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DUOX2 were set to PMID: 38693247
Phenotypes for gene: DUOX2 were set to Thyroid dyshormonogenesis 6, MIM#607200
Review for gene: DUOX2 was set to RED
Added comment: 1 individual reported with biallelic variants (1 missense, 1 stopgain) in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Congenital hypothyroidism is associated with increased risk of cerebral palsy if untreated, amongst other developmental sequelae.
Sources: Literature
Deafness_IsolatedAndComplex v1.183 LMNA Rylee Peters gene: LMNA was added
gene: LMNA was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: LMNA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LMNA were set to PMID: 32913962
Phenotypes for gene: LMNA were set to Laminopathy (MONDO#0021106), LMNA-related
Review for gene: LMNA was set to GREEN
Added comment: PMID: 32913962; Total of 13 individuals heterozygous for the R349W variant. Recurrent phenotypes in these individuals include partial lipodystrophy, proteinuric nephropathy, cardiopathies and sensorineural hearing impairment.
Hearing impairment was identified in 66% of the patients (6/9 individuals, 4 were not reported) and ranged from reduction or complete sensorineural deafness.
Sources: Literature
Cerebral Palsy v1.275 DIAPH1 Clare van Eyk gene: DIAPH1 was added
gene: DIAPH1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: DIAPH1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: DIAPH1 were set to PMID: 38693247; 34125151
Phenotypes for gene: DIAPH1 were set to Seizures, cortical blindness, and microcephaly syndrome, MIM#616632
Review for gene: DIAPH1 was set to AMBER
Added comment: 1 individual reported with biallelic LOF variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.

De novo and rare, transmitted damaging variants in DIAPH1 have been reported as a risk factor for Moyamoya disease resulting in ischemic stroke, however CP was not reported as a sequelae in this case series (PMID:34125151).
Sources: Literature
Cerebral Palsy v1.275 DHCR7 Clare van Eyk gene: DHCR7 was added
gene: DHCR7 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: DHCR7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DHCR7 were set to PMID: 38693247
Phenotypes for gene: DHCR7 were set to Smith-Lemli-Opitz syndrome, MIM#270400
Review for gene: DHCR7 was set to RED
Added comment: 1 individual reported with biallelic P/LP variants (1 missense, 1 frameshift) in a large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Hypotonia in infancy followed by later hypertonia are described, usually presenting with multiple congenital anomalies.
Sources: Literature
Cerebral Palsy v1.275 DDX59 Clare van Eyk edited their review of gene: DDX59: Changed rating: RED
Cerebral Palsy v1.275 DDX59 Clare van Eyk gene: DDX59 was added
gene: DDX59 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: DDX59 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DDX59 were set to PMID: 38693247
Phenotypes for gene: DDX59 were set to Orofaciodigital syndrome V, MIM#174300
Added comment: 1 individual reported with biallelic variants (1 missense, 1 frameshift) in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. OFD5 has not been previously associated with CP, however white matter abnormalities on MRI have been reported.
Sources: Literature
Vitamin metabolism disorders v1.6 MCEE Bryony Thompson changed review comment from: Involved in the metabolism of cobalamin (vitamin B12). Serum B12 levels are measures as part of the diagnosis of this condition.
Sources: Expert list; to: It is not directly involved in cobalamin (vitamin B12) metabolism, but serum B12 levels are measured in diagnosing this condition. Included as a differential diagnosis.
Sources: Expert list
Vitamin metabolism disorders v1.6 MUT Bryony Thompson changed review comment from: Involved in cobalamin (vitamin B12) metabolism. Serum B12 levels are measured in the diagnosis of this condition.
Sources: Expert list; to: It is not directly involved in cobalamin (vitamin B12) metabolism, but serum B12 levels are measured in diagnosing this condition. Included as a differential diagnosis.
Sources: Expert list
Aminoacidopathy v1.61 KYNU Zornitza Stark Marked gene: KYNU as ready
Aminoacidopathy v1.61 KYNU Zornitza Stark Gene: kynu has been classified as Green List (High Evidence).
Aminoacidopathy v1.61 KYNU Zornitza Stark Classified gene: KYNU as Green List (high evidence)
Aminoacidopathy v1.61 KYNU Zornitza Stark Gene: kynu has been classified as Green List (High Evidence).
Aminoacidopathy v1.60 LMBRD1 Zornitza Stark Marked gene: LMBRD1 as ready
Aminoacidopathy v1.60 LMBRD1 Zornitza Stark Gene: lmbrd1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.60 LMBRD1 Zornitza Stark Classified gene: LMBRD1 as Green List (high evidence)
Aminoacidopathy v1.60 LMBRD1 Zornitza Stark Gene: lmbrd1 has been classified as Green List (High Evidence).
Vitamin metabolism disorders v1.6 MCEE Bryony Thompson Classified gene: MCEE as Green List (high evidence)
Vitamin metabolism disorders v1.6 MCEE Bryony Thompson Gene: mcee has been classified as Green List (High Evidence).
Vitamin metabolism disorders v1.5 MCEE Bryony Thompson gene: MCEE was added
gene: MCEE was added to Vitamin metabolism disorders. Sources: Expert list
Mode of inheritance for gene: MCEE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCEE were set to 20301409
Phenotypes for gene: MCEE were set to methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency MONDO:0009615
Review for gene: MCEE was set to GREEN
gene: MCEE was marked as current diagnostic
Added comment: Involved in the metabolism of cobalamin (vitamin B12). Serum B12 levels are measures as part of the diagnosis of this condition.
Sources: Expert list
Vitamin metabolism disorders v1.4 MUT Bryony Thompson Marked gene: MUT as ready
Vitamin metabolism disorders v1.4 MUT Bryony Thompson Gene: mut has been classified as Green List (High Evidence).
Vitamin metabolism disorders v1.4 MUT Bryony Thompson Classified gene: MUT as Green List (high evidence)
Vitamin metabolism disorders v1.4 MUT Bryony Thompson Gene: mut has been classified as Green List (High Evidence).
Vitamin metabolism disorders v1.3 MUT Bryony Thompson gene: MUT was added
gene: MUT was added to Vitamin metabolism disorders. Sources: Expert list
Mode of inheritance for gene: MUT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MUT were set to 20301409
Phenotypes for gene: MUT were set to methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency MONDO:0009612
Review for gene: MUT was set to GREEN
gene: MUT was marked as current diagnostic
Added comment: Involved in cobalamin (vitamin B12) metabolism. Serum B12 levels are measured in the diagnosis of this condition.
Sources: Expert list
Aminoacidopathy v1.59 LMBRD1 Sangavi Sivagnanasundram gene: LMBRD1 was added
gene: LMBRD1 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: LMBRD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LMBRD1 were set to 20301503; 19136951; 32875039; 20127417; 21303734
Phenotypes for gene: LMBRD1 were set to methylmalonic aciduria and homocystinuria type cblF MONDO:0010183
Review for gene: LMBRD1 was set to GREEN
Added comment: Classified Definitive by ClinGen Aminoacidopathy GCEP on 26/03/2021 - https://search.clinicalgenome.org/CCID:005290

Reported in multiple individuals with evidence of defective cobalamin metabolism.
Mechanism of disease appears to be loss of function leading to a defective release of cobalamin from lysosomes.
Sources: ClinGen
Aminoacidopathy v1.59 KYNU Sangavi Sivagnanasundram edited their review of gene: KYNU: Changed publications: 37499065, 28792876, 33942433, 31923704, 17334708, 34200361
Aminoacidopathy v1.59 KYNU Sangavi Sivagnanasundram gene: KYNU was added
gene: KYNU was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: KYNU was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KYNU were set to 37499065, 28792876, 33942433, 31923704, 17334708, 34200361
Phenotypes for gene: KYNU were set to vertebral, cardiac, renal, and limb defects syndrome 2 MONDO:0060555
Review for gene: KYNU was set to GREEN
Added comment: Classified Definitive by ClinGen Aminoacidopathy GCEP on 12/05/2023 - https://search.clinicalgenome.org/CCID:005259

Reported in >5 unrelated probands with an error in synthesis of NAD from tryptophan. Mouse model recapitulates human phenotype while on a NAD-restricted diet.
Sources: ClinGen
Aminoacidopathy v1.59 KMO Sangavi Sivagnanasundram gene: KMO was added
gene: KMO was added to Aminoacidopathy. Sources: ClinGen
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: ClinGen
Aminoacidopathy v1.59 HYKK Sangavi Sivagnanasundram gene: HYKK was added
gene: HYKK was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: HYKK was set to Unknown
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: ClinGen
Aminoacidopathy v1.59 HPD Sangavi Sivagnanasundram gene: HPD was added
gene: HPD was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: HPD was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: HPD were set to 10942115, 11073718, 28649543, 11073718, 31342835
Phenotypes for gene: HPD were set to tyrosinemia type III MONDO:0010162; hawkinsinuria MONDO:0007700
Review for gene: HPD was set to GREEN
Added comment: Tyrosinemia type III - AR and Hawkinsinuria - AD

ClinGen classified limited evidence for the AD gene-disease association on 17/11/2023 and definitive for AR gene-disease association on 29/06/2020.

Established gene-disease association. Reported individuals reported with inborn errors of amino acid metabolism.
Sources: ClinGen
Aminoacidopathy v1.59 HIBADH Sangavi Sivagnanasundram gene: HIBADH was added
gene: HIBADH was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: HIBADH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HIBADH were set to 34176136; 35174513
Phenotypes for gene: HIBADH were set to 3-hydroxyisobutyric aciduria MONDO:0009371
Review for gene: HIBADH was set to RED
Added comment: Classified Limited by ClinGen Aminoacidopathy GCEP on 24/03/2023 - https://search.clinicalgenome.org/CCID:005058

Reported in 3 probands however there is lack of clinical evidence to show that hydroxyisobutyrate dehydrogenase deficiency leads to their clinical phenotype.
Sources: ClinGen
Aminoacidopathy v1.59 HGD Sangavi Sivagnanasundram gene: HGD was added
gene: HGD was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: HGD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HGD were set to 8782815; 9529363; 9154114; 9674916
Phenotypes for gene: HGD were set to alkaptonuria MONDO:0008753
Review for gene: HGD was set to GREEN
Added comment: Classified Definitive by ClinGen Aminoacidopathy GCEP on 29/06/2020 - https://search.clinicalgenome.org/CCID:005055

Well established gene-disease association with reported individuals showing evidence of abnormal biochemical function.
Sources: ClinGen
Hydrops fetalis v0.313 RAPSN Zornitza Stark Publications for gene: RAPSN were set to 18252226
Hydrops fetalis v0.312 RAPSN Zornitza Stark Classified gene: RAPSN as Green List (high evidence)
Hydrops fetalis v0.312 RAPSN Zornitza Stark Gene: rapsn has been classified as Green List (High Evidence).
Aminoacidopathy v1.59 HAL Zornitza Stark Marked gene: HAL as ready
Aminoacidopathy v1.59 HAL Zornitza Stark Gene: hal has been classified as Red List (Low Evidence).
Aminoacidopathy v1.59 HAL Zornitza Stark Classified gene: HAL as Red List (low evidence)
Aminoacidopathy v1.59 HAL Zornitza Stark Gene: hal has been classified as Red List (Low Evidence).
Aminoacidopathy v1.58 HAAO Zornitza Stark Marked gene: HAAO as ready
Aminoacidopathy v1.58 HAAO Zornitza Stark Gene: haao has been classified as Green List (High Evidence).
Aminoacidopathy v1.58 HAAO Zornitza Stark Classified gene: HAAO as Green List (high evidence)
Aminoacidopathy v1.58 HAAO Zornitza Stark Gene: haao has been classified as Green List (High Evidence).
Aminoacidopathy v1.57 GSTZ1 Zornitza Stark Marked gene: GSTZ1 as ready
Aminoacidopathy v1.57 GSTZ1 Zornitza Stark Gene: gstz1 has been classified as Red List (Low Evidence).
Aminoacidopathy v1.57 GSTZ1 Zornitza Stark Classified gene: GSTZ1 as Red List (low evidence)
Aminoacidopathy v1.57 GSTZ1 Zornitza Stark Gene: gstz1 has been classified as Red List (Low Evidence).
Aminoacidopathy v1.56 GSS Zornitza Stark Marked gene: GSS as ready
Aminoacidopathy v1.56 GSS Zornitza Stark Gene: gss has been classified as Green List (High Evidence).
Aminoacidopathy v1.56 GSS Zornitza Stark Classified gene: GSS as Green List (high evidence)
Aminoacidopathy v1.56 GSS Zornitza Stark Gene: gss has been classified as Green List (High Evidence).
Aminoacidopathy v1.55 GNMT Zornitza Stark Marked gene: GNMT as ready
Aminoacidopathy v1.55 GNMT Zornitza Stark Gene: gnmt has been classified as Red List (Low Evidence).
Aminoacidopathy v1.55 GNMT Zornitza Stark Classified gene: GNMT as Red List (low evidence)
Aminoacidopathy v1.55 GNMT Zornitza Stark Gene: gnmt has been classified as Red List (Low Evidence).
Aminoacidopathy v1.54 GLUL Zornitza Stark Marked gene: GLUL as ready
Aminoacidopathy v1.54 GLUL Zornitza Stark Gene: glul has been classified as Green List (High Evidence).
Aminoacidopathy v1.54 GLUL Zornitza Stark Classified gene: GLUL as Green List (high evidence)
Aminoacidopathy v1.54 GLUL Zornitza Stark Gene: glul has been classified as Green List (High Evidence).
Aminoacidopathy v1.53 GLUD1 Zornitza Stark Marked gene: GLUD1 as ready
Aminoacidopathy v1.53 GLUD1 Zornitza Stark Gene: glud1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.53 GLUD1 Zornitza Stark Classified gene: GLUD1 as Green List (high evidence)
Aminoacidopathy v1.53 GLUD1 Zornitza Stark Gene: glud1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.52 GLS Zornitza Stark Marked gene: GLS as ready
Aminoacidopathy v1.52 GLS Zornitza Stark Gene: gls has been classified as Green List (High Evidence).
Aminoacidopathy v1.52 GLS Zornitza Stark Classified gene: GLS as Green List (high evidence)
Aminoacidopathy v1.52 GLS Zornitza Stark Gene: gls has been classified as Green List (High Evidence).
Aminoacidopathy v1.51 GLDC Zornitza Stark Marked gene: GLDC as ready
Aminoacidopathy v1.51 GLDC Zornitza Stark Gene: gldc has been classified as Green List (High Evidence).
Aminoacidopathy v1.51 GLDC Zornitza Stark Classified gene: GLDC as Green List (high evidence)
Aminoacidopathy v1.51 GLDC Zornitza Stark Gene: gldc has been classified as Green List (High Evidence).
Aminoacidopathy v1.50 GCSH Zornitza Stark Marked gene: GCSH as ready
Aminoacidopathy v1.50 GCSH Zornitza Stark Gene: gcsh has been classified as Green List (High Evidence).
Aminoacidopathy v1.50 GCSH Zornitza Stark Classified gene: GCSH as Green List (high evidence)
Aminoacidopathy v1.50 GCSH Zornitza Stark Gene: gcsh has been classified as Green List (High Evidence).
Aminoacidopathy v1.49 GCH1 Zornitza Stark Marked gene: GCH1 as ready
Aminoacidopathy v1.49 GCH1 Zornitza Stark Gene: gch1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.49 GCH1 Zornitza Stark Classified gene: GCH1 as Green List (high evidence)
Aminoacidopathy v1.49 GCH1 Zornitza Stark Gene: gch1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.48 GCDH Zornitza Stark Marked gene: GCDH as ready
Aminoacidopathy v1.48 GCDH Zornitza Stark Gene: gcdh has been classified as Green List (High Evidence).
Aminoacidopathy v1.48 GCDH Zornitza Stark Classified gene: GCDH as Green List (high evidence)
Aminoacidopathy v1.48 GCDH Zornitza Stark Gene: gcdh has been classified as Green List (High Evidence).
Skeletal dysplasia v0.281 FUZ Zornitza Stark Marked gene: FUZ as ready
Skeletal dysplasia v0.281 FUZ Zornitza Stark Gene: fuz has been classified as Green List (High Evidence).
Fetal anomalies v1.249 FUZ Zornitza Stark Phenotypes for gene: FUZ were changed from Neural tube defects 182940 to Neural tube defects 182940; Ciliopathy_MONDO_0005308, FUZ-related; skeletal ciliopathy
Fetal anomalies v1.248 FUZ Zornitza Stark Publications for gene: FUZ were set to 21840926
Fetal anomalies v1.247 FUZ Zornitza Stark Mode of inheritance for gene: FUZ was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v0.281 FUZ Zornitza Stark Phenotypes for gene: FUZ were changed from Ciliopathy_MONDO_0005308; skeletal ciliopathy to Ciliopathy_MONDO_0005308, FUZ-related; skeletal ciliopathy
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v1.15 FUZ Zornitza Stark Marked gene: FUZ as ready
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v1.15 FUZ Zornitza Stark Gene: fuz has been classified as Green List (High Evidence).
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v1.15 FUZ Zornitza Stark Phenotypes for gene: FUZ were changed from Ciliopathy_MONDO_0005308; skeletal ciliopathy to Ciliopathy_MONDO_0005308, FUZ-related; skeletal ciliopathy
Mendeliome v1.1835 FUZ Zornitza Stark Phenotypes for gene: FUZ were changed from {Neural tube defects, susceptibility to} MIM#182940; craniosynostosis, FUZ-related MONDO#0015469 to {Neural tube defects, susceptibility to} MIM#182940; craniosynostosis, FUZ-related MONDO#0015469; Ciliopathy_MONDO_0005308, FUZ-related; skeletal ciliopathy
Mendeliome v1.1834 FUZ Zornitza Stark Publications for gene: FUZ were set to 21840926
Ciliopathies v1.54 FUZ Zornitza Stark Marked gene: FUZ as ready
Ciliopathies v1.54 FUZ Zornitza Stark Gene: fuz has been classified as Green List (High Evidence).
Ciliopathies v1.54 FUZ Zornitza Stark Phenotypes for gene: FUZ were changed from Ciliopathy_MONDO_0005308; skeletal ciliopathy to Ciliopathy_MONDO_0005308, FUZ-related; skeletal ciliopathy
Skeletal Dysplasia_Fetal v0.223 FUZ Zornitza Stark Phenotypes for gene: FUZ were changed from Ciliopathy_MONDO_0005308; skeletal ciliopathy to Ciliopathy_MONDO_0005308, FUZ-related; skeletal ciliopathy
Intellectual disability syndromic and non-syndromic v0.6037 ATXN7L3 Zornitza Stark Marked gene: ATXN7L3 as ready
Intellectual disability syndromic and non-syndromic v0.6037 ATXN7L3 Zornitza Stark Gene: atxn7l3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6037 ATXN7L3 Zornitza Stark Phenotypes for gene: ATXN7L3 were changed from Neurodevelopmental disorder, MONDO_0100500 to Neurodevelopmental disorder, MONDO_0100500, ATXN7L3-related
Mendeliome v1.1833 ATXN7L3 Zornitza Stark Marked gene: ATXN7L3 as ready
Mendeliome v1.1833 ATXN7L3 Zornitza Stark Gene: atxn7l3 has been classified as Green List (High Evidence).
Mendeliome v1.1833 ATXN7L3 Zornitza Stark Phenotypes for gene: ATXN7L3 were changed from Neurodevelopmental disorder, MONDO_0100500 to Neurodevelopmental disorder, MONDO_0100500, ATXN7L3-related
Mendeliome v1.1832 STK33 Zornitza Stark Marked gene: STK33 as ready
Mendeliome v1.1832 STK33 Zornitza Stark Gene: stk33 has been classified as Red List (Low Evidence).
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
Mendeliome v1.1831 NAT6 Zornitza Stark Marked gene: NAT6 as ready
Mendeliome v1.1831 NAT6 Zornitza Stark Gene: nat6 has been classified as Red List (Low Evidence).
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
Deafness_IsolatedAndComplex v1.183 NAT6 Zornitza Stark changed review comment from: Case report of two brothers with homozygous missense variant and deafness, periodic hypotonia and dental anomalies.
Sources: Literature; to: Case report of two brothers with homozygous missense variant and deafness, periodic hypotonia and dental anomalies.

HGNC approved name is NAA80.

Sources: Literature
Deafness_IsolatedAndComplex v1.183 NAT6 Zornitza Stark Marked gene: NAT6 as ready
Deafness_IsolatedAndComplex v1.183 NAT6 Zornitza Stark Gene: nat6 has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v1.183 NAT6 Zornitza Stark gene: NAT6 was added
gene: NAT6 was added to Deafness_IsolatedAndComplex. 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.
Sources: Literature
Aminoacidopathy v1.47 HAL Sangavi Sivagnanasundram gene: HAL was added
gene: HAL was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: HAL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HAL were set to 15806399
Phenotypes for gene: HAL were set to histidinemia MONDO:0009345
Review for gene: HAL was set to RED
Added comment: Classified Limited by ClinGen Aminoacidopathy GCEP on 17/11/2023 - https://search.clinicalgenome.org/CCID:005031

Metabolic disorder appears to be benign in most reported affected individuals.
Sources: ClinGen
Aminoacidopathy v1.47 HAAO Sangavi Sivagnanasundram gene: HAAO was added
gene: HAAO was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: HAAO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HAAO were set to 37499065; 28792876; 33942433
Phenotypes for gene: HAAO were set to vertebral, cardiac, renal, and limb defects syndrome 1 MONDO:0060554
Review for gene: HAAO was set to GREEN
Added comment: Classified Definitive by ClinGen Aminoacidopathy GCEP on 24/06/2022 - https://search.clinicalgenome.org/CCID:005026

Reported in >3 unrelated probands with biochemical abnormalities. LoF appears to be the mechanism of disease.
Sources: ClinGen
Aminoacidopathy v1.47 GSTZ1 Sangavi Sivagnanasundram gene: GSTZ1 was added
gene: GSTZ1 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: GSTZ1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GSTZ1 were set to 27876694
Phenotypes for gene: GSTZ1 were set to maleylacetoacetate isomerase deficiency MONDO:0060527
Review for gene: GSTZ1 was set to RED
Added comment: Classified Moderate by ClinGen Aminoacidopathy GCEP on 09/09/2022 -https://search.clinicalgenome.org/CCID:005017

6 probands have been reported with mild hypersuccinylacetonaemia (MHSA). The reported individuals remained well without receiving any treatment or change in diet.
Sources: ClinGen
Intellectual disability syndromic and non-syndromic v0.6036 PTEN Ain Roesley Phenotypes for gene: PTEN were changed from Cowden syndrome 1 MIM#158350; Macrocephaly/autism syndrome MIM#605309 to Cowden syndrome 1 MIM#158350; Macrocephaly/autism syndrome MIM#605309; PTEN hamartoma tumor syndrome MONDO:0017623
Overgrowth v1.12 PTEN Ain Roesley Phenotypes for gene: PTEN were changed from Cowden syndrome 1, MIM# 158350; Macrocephaly/autism syndrome, MIM# 605309 to Cowden syndrome 1, MIM# 158350; Macrocephaly/autism syndrome, MIM# 605309; PTEN hamartoma tumor syndrome MONDO:0017623
Aminoacidopathy v1.47 GSS Sangavi Sivagnanasundram gene: GSS was added
gene: GSS was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: GSS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GSS were set to 17397529
Phenotypes for gene: GSS were set to inherited glutathione synthetase deficiency MONDO:0017909
Review for gene: GSS was set to GREEN
Added comment: Classified Definitive by ClinGen Aminoacidopathy GCEP on 26/04/2019 -https://search.clinicalgenome.org/CCID:005016

Well established gene-disease association with reported individuals having errors in glutathione metabolism.
Sources: ClinGen
Aminoacidopathy v1.47 GNMT Sangavi Sivagnanasundram gene: GNMT was added
gene: GNMT was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: GNMT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GNMT were set to 11810299; 14739680
Phenotypes for gene: GNMT were set to glycine N-methyltransferase deficiency MONDO:0011698
Review for gene: GNMT was set to RED
Added comment: Classified Limited by ClinGen Aminoacidopathy GCEP on 12/12/2022 -https://search.clinicalgenome.org/CCID:004979
Sources: ClinGen
Aminoacidopathy v1.47 GLUL Sangavi Sivagnanasundram gene: GLUL was added
gene: GLUL was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: GLUL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GLUL were set to 25870278; 20140959; 30053506
Phenotypes for gene: GLUL were set to congenital brain dysgenesis due to glutamine synthetase deficiency MONDO:0012393
Review for gene: GLUL was set to GREEN
Added comment: Classified Moderate by ClinGen Aminoacidopathy GCEP on 12/12/2022 - https://search.clinicalgenome.org/CCID:004969

At least 5 probands from 4 unrelated families reported with glutamine deficiency.
Sources: ClinGen
Aminoacidopathy v1.47 GLUD1 Sangavi Sivagnanasundram gene: GLUD1 was added
gene: GLUD1 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: GLUD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GLUD1 were set to 9571255; 11214910; 26759084
Phenotypes for gene: GLUD1 were set to hyperinsulinism-hyperammonemia syndrome MONDO:0011717
Review for gene: GLUD1 was set to GREEN
Added comment: Classified Definitive by ClinGen Aminoacidopathy GCEP on 13/11/2020 - https://search.clinicalgenome.org/CCID:004968

Well-established gene disease association with reported individuals having a metabolic abnormality.
Sources: ClinGen
Mendeliome v1.1830 FAM177A1 Zornitza Stark Marked gene: FAM177A1 as ready
Mendeliome v1.1830 FAM177A1 Zornitza Stark Gene: fam177a1 has been classified as Green List (High Evidence).
Mendeliome v1.1830 FAM177A1 Zornitza Stark Phenotypes for gene: FAM177A1 were changed from Neurodevelopmental disorder, MONDO_0100500 to Neurodevelopmental disorder, MONDO_0100500, FAM177A1-related
Intellectual disability syndromic and non-syndromic v0.6035 FAM177A1 Zornitza Stark Marked gene: FAM177A1 as ready
Intellectual disability syndromic and non-syndromic v0.6035 FAM177A1 Zornitza Stark Gene: fam177a1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6035 FAM177A1 Zornitza Stark Phenotypes for gene: FAM177A1 were changed from Neurodevelopmental disorder, MONDO_0100500 to Neurodevelopmental disorder, MONDO_0100500, FAM177a1-related
Skeletal dysplasia v0.280 PISD Zornitza Stark Phenotypes for gene: PISD were changed from Liberfarb syndrome MIM# 618889; Spondylometaphyseal dysplasia with large epiphyses to Liberfarb syndrome MIM# 618889; Spondylometaphyseal dysplasia with large epiphyses, MONDO:0100510
Skeletal dysplasia v0.279 PISD Zornitza Stark Phenotypes for gene: PISD were changed from Spondylometaphyseal dysplasia with large epiphyses to Liberfarb syndrome MIM# 618889; Spondylometaphyseal dysplasia with large epiphyses
Skeletal dysplasia v0.278 PISD Zornitza Stark Classified gene: PISD as Green List (high evidence)
Skeletal dysplasia v0.278 PISD Zornitza Stark Gene: pisd has been classified as Green List (High Evidence).
Mendeliome v1.1829 ERF Zornitza Stark Phenotypes for gene: ERF were changed from Craniosynostosis 4, MIM# 600775; Chitayat syndrome, MIM# 617180 to Craniosynostosis 4, MIM# 600775; Chitayat syndrome, MIM# 617180; Noonan syndrome-like, MONDO:0018997, with or without craniosynostosis, ERF-related
Mendeliome v1.1828 ERF Zornitza Stark edited their review of gene: ERF: Changed phenotypes: Craniosynostosis 4, MIM# 600775, Chitayat syndrome, MIM# 617180, Noonan syndrome-like, MONDO:0018997, with or without craniosynostosis, ERF-related
Rasopathy v0.105 ERF Zornitza Stark Marked gene: ERF as ready
Rasopathy v0.105 ERF Zornitza Stark Gene: erf has been classified as Green List (High Evidence).
Rasopathy v0.105 ERF Zornitza Stark Phenotypes for gene: ERF were changed from Noonan syndrome-like with or without craniosynostosis to Noonan syndrome-like, MONDO:0018997, with or without craniosynostosis, ERF-related
Rasopathy v0.104 ERF Zornitza Stark reviewed gene: ERF: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Noonan syndrome-like, MONDO:0018997, with or without craniosynostosis, ERF-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v1.26 ANO4 Zornitza Stark Marked gene: ANO4 as ready
Genetic Epilepsy v1.26 ANO4 Zornitza Stark Gene: ano4 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.26 ANO4 Zornitza Stark Classified gene: ANO4 as Green List (high evidence)
Genetic Epilepsy v1.26 ANO4 Zornitza Stark Gene: ano4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6034 SLC6A1 Zornitza Stark Publications for gene: SLC6A1 were set to 29315614
Intellectual disability syndromic and non-syndromic v0.6033 SLC6A1 Zornitza Stark edited their review of gene: SLC6A1: Added comment: Haploinsufficiency established as the mechanism.; Changed publications: 29315614, 38781976
Intellectual disability syndromic and non-syndromic v0.6033 MSL2 Zornitza Stark Phenotypes for gene: MSL2 were changed from Developmental disorders; autism to Neurodevelopmental disorder, MONDO:0700092, MSL2-related
Mendeliome v1.1828 MSL2 Zornitza Stark Phenotypes for gene: MSL2 were changed from Developmental disorders; autism to Neurodevelopmental disorder, MONDO:0700092, MSL2-related
Mendeliome v1.1827 MSL2 Zornitza Stark Publications for gene: MSL2 were set to 31332282; 33057194
Mendeliome v1.1826 MSL2 Zornitza Stark Classified gene: MSL2 as Green List (high evidence)
Mendeliome v1.1826 MSL2 Zornitza Stark Gene: msl2 has been classified as Green List (High Evidence).
Mendeliome v1.1825 HGF Zornitza Stark Phenotypes for gene: HGF were changed from Deafness, autosomal recessive 39, MIM# 608265 to Deafness, autosomal recessive 39, MIM# 608265; Lymphoedema, MONDO:0019297, HGF-related
Mendeliome v1.1824 HGF Zornitza Stark Publications for gene: HGF were set to 19576567
Mendeliome v1.1823 HGF Zornitza Stark Mode of inheritance for gene: HGF was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1822 HGF Zornitza Stark edited their review of gene: HGF: Added comment: More than 10 families reported with childhood- to late-onset lymphoedema.; Changed publications: 19576567, 38676400, 38791500; Changed phenotypes: Deafness, autosomal recessive 39, MIM# 608265, Lymphoedema, MONDO:0019297, HGF-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Lymphoedema_nonsyndromic v0.39 HGF Zornitza Stark Marked gene: HGF as ready
Lymphoedema_nonsyndromic v0.39 HGF Zornitza Stark Gene: hgf has been classified as Green List (High Evidence).
Lymphoedema_nonsyndromic v0.39 HGF Zornitza Stark Classified gene: HGF as Green List (high evidence)
Lymphoedema_nonsyndromic v0.39 HGF Zornitza Stark Gene: hgf has been classified as Green List (High Evidence).
Lymphoedema_nonsyndromic v0.38 HGF Zornitza Stark gene: HGF was added
gene: HGF was added to Lymphoedema_nonsyndromic. Sources: Literature
Mode of inheritance for gene: HGF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HGF were set to 38676400; 38791500
Phenotypes for gene: HGF were set to Lymphoedema, MONDO:0019297, HGF-related
Review for gene: HGF was set to GREEN
Added comment: More than 10 families reported with childhood- to late-onset lymphoedema.
Sources: Literature
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
Combined Immunodeficiency v1.66 TKFC Zornitza Stark changed review comment from: Single individual reported with homozygous variant.
Sources: Literature; to: Single individual reported with homozygous variant.

Note relationship with syndromic ID also postulated.
Sources: Literature
Combined Immunodeficiency v1.66 TKFC Zornitza Stark Marked gene: TKFC as ready
Combined Immunodeficiency v1.66 TKFC Zornitza Stark Gene: tkfc has been classified as Red List (Low Evidence).
Combined Immunodeficiency v1.66 TKFC Zornitza Stark gene: TKFC was added
gene: TKFC was added to Combined Immunodeficiency. Sources: Literature
Mode of inheritance for gene: TKFC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TKFC were set to 38697782
Phenotypes for gene: TKFC were set to Inborn error of immunity, MONDO:0003778, TKFC-related
Review for gene: TKFC was set to RED
Added comment: Single individual reported with homozygous variant.
Sources: Literature
Mendeliome v1.1821 CYLC1 Zornitza Stark Marked gene: CYLC1 as ready
Mendeliome v1.1821 CYLC1 Zornitza Stark Gene: cylc1 has been classified as Green List (High Evidence).
Mendeliome v1.1821 CYLC1 Zornitza Stark Classified gene: CYLC1 as Green List (high evidence)
Mendeliome v1.1821 CYLC1 Zornitza Stark Gene: cylc1 has been classified as Green List (High Evidence).
Mendeliome v1.1820 CYLC1 Zornitza Stark gene: CYLC1 was added
gene: CYLC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CYLC1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: CYLC1 were set to Spermatogenic failure, X-linked, 8, MIM# 301119
Review for gene: CYLC1 was set to GREEN
Added comment: 19 individuals and a mouse model reported.
Sources: Literature
Aminoacidopathy v1.47 GLS Sangavi Sivagnanasundram gene: GLS was added
gene: GLS was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: GLS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GLS were set to 29468182, 30575854, 30970188; 16641247
Phenotypes for gene: GLS were set to glutaminase deficiency MONDO:0600001
Review for gene: GLS was set to GREEN
Added comment: Classified Definitive by ClinGen Aminoacidopathy GCEP on 09/07/2021 - https://search.clinicalgenome.org/CCID:004965

6 probands have been reported with glutaminase deficiency. Nonsense, framshift and missense variants have been reported. 5’UTR repeat expansion (680-1500 repeats; normal range 8-16 repeats) has also been reported.
Mouse model was also conducted that recapitulates the human phenotype (PMID: 16641247).
Sources: ClinGen
Aminoacidopathy v1.47 GLDC Sangavi Sivagnanasundram gene: GLDC was added
gene: GLDC was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: GLDC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GLDC were set to 25736695; 27362913; 26179960; 24407464
Phenotypes for gene: GLDC were set to glycine encephalopathy MONDO:0011612
Review for gene: GLDC was set to GREEN
Added comment: Classified Definitive by ClinGen Aminoacidopathy GCEP on 06/02/2019 - https://search.clinicalgenome.org/CCID:004962

Well reported gene-disease association with reported individuals present with glycine encephalopathy.
Sources: ClinGen
Skeletal Dysplasia_Fetal v0.222 FUZ Zornitza Stark Marked gene: FUZ as ready
Skeletal Dysplasia_Fetal v0.222 FUZ Zornitza Stark Gene: fuz has been classified as Green List (High Evidence).
Skeletal Dysplasia_Fetal v0.222 FUZ Zornitza Stark Classified gene: FUZ as Green List (high evidence)
Skeletal Dysplasia_Fetal v0.222 FUZ Zornitza Stark Gene: fuz has been classified as Green List (High Evidence).
Bone Marrow Failure v1.92 FLT3LG Ain Roesley Marked gene: FLT3LG as ready
Bone Marrow Failure v1.92 FLT3LG Ain Roesley Gene: flt3lg has been classified as Red List (Low Evidence).
Mendeliome v1.1819 FLT3LG Ain Roesley Marked gene: FLT3LG as ready
Mendeliome v1.1819 FLT3LG Ain Roesley Gene: flt3lg has been classified as Red List (Low Evidence).
Bone Marrow Failure v1.92 FLT3LG Ain Roesley gene: FLT3LG was added
gene: FLT3LG was added to Bone Marrow Failure. 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
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
Lymphoedema_nonsyndromic v0.37 TIE1 Ain Roesley Publications for gene: TIE1 were set to 32947856; 24764452; 38820174
Lymphoedema_nonsyndromic v0.36 TIE1 Ain Roesley Publications for gene: TIE1 were set to 32947856; 24764452; 38820174
Lymphoedema_nonsyndromic v0.36 TIE1 Ain Roesley Publications for gene: TIE1 were set to 32947856; 24764452
Lymphoedema_nonsyndromic v0.36 TIE1 Ain Roesley Classified gene: TIE1 as Green List (high evidence)
Lymphoedema_nonsyndromic v0.36 TIE1 Ain Roesley Gene: tie1 has been classified as Green List (High Evidence).
Lymphoedema_nonsyndromic v0.35 TIE1 Ain Roesley edited their review of gene: TIE1: Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Lymphoedema_nonsyndromic v0.35 TIE1 Ain Roesley reviewed gene: TIE1: Rating: ; Mode of pathogenicity: None; Publications: 38820174; Phenotypes: Lymphatic malformation 11, MIM# 619401; Mode of inheritance: None; Current diagnostic: yes
Mendeliome v1.1818 TIE1 Ain Roesley Classified gene: TIE1 as Green List (high evidence)
Mendeliome v1.1818 TIE1 Ain Roesley Gene: tie1 has been classified as Green List (High Evidence).
Mendeliome v1.1818 TIE1 Ain Roesley Publications for gene: TIE1 were set to 32947856; 24764452
Mendeliome v1.1817 TIE1 Ain Roesley reviewed gene: TIE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 38820174; Phenotypes: Lymphatic malformation 11, MIM# 619401; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v1.1817 MSL2 Sangavi Sivagnanasundram reviewed gene: MSL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 38815585, 38702431; Phenotypes: MSL2-Related Developmental Disorder; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6032 MSL2 Sangavi Sivagnanasundram reviewed gene: MSL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 38815585, 38702431; Phenotypes: MSL2-Related Developmental Disorder; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
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
Skeletal dysplasia v0.277 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 v1.1817 ATXN7L3 Chirag Patel Classified gene: ATXN7L3 as Green List (high evidence)
Mendeliome v1.1817 ATXN7L3 Chirag Patel Gene: atxn7l3 has been classified as Green List (High Evidence).
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
Mendeliome v1.1815 FAM177A1 Chirag Patel Classified gene: FAM177A1 as Green List (high evidence)
Mendeliome v1.1815 FAM177A1 Chirag Patel Gene: fam177a1 has been classified as Green List (High Evidence).
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
Mendeliome v1.1813 ERF Chirag Patel reviewed gene: ERF: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38824261; Phenotypes: Noonan syndrome-like with or without craniosynostosis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v1.1813 SLC6A1 Sangavi Sivagnanasundram reviewed gene: SLC6A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 38781976; Phenotypes: myoclonic-atonic epilepsy MONDO:0014633; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v0.277 FUZ Chirag Patel Classified gene: FUZ as Green List (high evidence)
Skeletal dysplasia v0.277 FUZ Chirag Patel Gene: fuz has been classified as Green List (High Evidence).
Skeletal dysplasia v0.276 FUZ Chirag Patel Classified gene: FUZ as Green List (high evidence)
Skeletal dysplasia v0.276 FUZ Chirag Patel Gene: fuz has been classified as Green List (High Evidence).
Skeletal Dysplasia_Fetal v0.220 FUZ Chirag Patel gene: FUZ was added
gene: FUZ was added to Skeletal Dysplasia_Fetal. Sources: Literature
Mode of inheritance for gene: FUZ was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FUZ were set to PMID: 38702430, 29068549, 34719684
Phenotypes for gene: FUZ were set to Ciliopathy_MONDO_0005308; skeletal ciliopathy
Review for gene: FUZ was set to GREEN
gene: FUZ was marked as current diagnostic
Added comment: FUZ is crucial for the transport of components to the primary cilium and potentially promotes protein complex assembly necessary for downstream cilium formation and function. Previous studies have shown complete knockout of Fuz in a mouse model leads to prenatal lethality, coronal craniosynostosis, micrognathia, facial malformations, eye, and heart defects. Suggested as a skeletal ciliopathy disorder gene.

PMID: 38702430
1 individual (from family with 2 affecteds) with orofaciodigital syndrome like phenotype (dysmorphism, bilateral foot preaxial polysyndactyly, right foot postaxial polysyndactyly, broad thumbs, bilateral 5th finger clinodactyly narrow chest, partial AVSD). They found a homozygous missense variant in FUZ [p.(Glu201Lys)]. Parents were heterozygous carriers. A sibling died at 18mths and had complete AVSD, bilateral cleft lip and palate, right 5th finger clinodactyly, and medially deviated/broad great toes.

1 fetus with orofaciodigital syndrome like phenotype (right cleft lip, 4 limb polydactyly, bilateral duplicated hallux, and AVSD). They found compound heterozygous variants in FUZ [p.(Val209_Leu212del) and p.(Glu201Lys)].

PMID: 29068549
1 fetus with lethal short-rib polydactyly syndrome II-like phenotype and a homozygous variant (c.98_111+9del) in FUZ.
1 individual with asphyxiating thoracic dystrophy (ATD) with polydactyly and a (unclear if homozygous) missense variant [p.(Arg284Leu)] in FUZ.

PMID: 34719684
Monozygotic twins with craniosynostosis (1 x metopic, 1 x metopic/coronal) and a homozygous missense variant in FUZ [p.(Arg284Pro)]. They cultured primary osteoblasts and mouse embryonic fibroblasts from Fuz mutant mice. Loss of Fuz resulted in increased osteoblastic mineralisation, suggesting that the FUZ protein normally acts as a negative regulator of osteogenesis.
Sources: Literature
Skeletal dysplasia v0.276 FUZ Chirag Patel Classified gene: FUZ as Green List (high evidence)
Skeletal dysplasia v0.276 FUZ Chirag Patel Gene: fuz has been classified as Green List (High Evidence).
Skeletal Dysplasia_Fetal v0.220 FUZ Chirag Patel gene: FUZ was added
gene: FUZ was added to Skeletal Dysplasia_Fetal. Sources: Literature
Mode of inheritance for gene: FUZ was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FUZ were set to PMID: 38702430, 29068549, 34719684
Phenotypes for gene: FUZ were set to Ciliopathy_MONDO_0005308; skeletal ciliopathy
Review for gene: FUZ was set to GREEN
gene: FUZ was marked as current diagnostic
Added comment: FUZ is crucial for the transport of components to the primary cilium and potentially promotes protein complex assembly necessary for downstream cilium formation and function. Previous studies have shown complete knockout of Fuz in a mouse model leads to prenatal lethality, coronal craniosynostosis, micrognathia, facial malformations, eye, and heart defects. Suggested as a skeletal ciliopathy disorder gene.

PMID: 38702430
1 individual (from family with 2 affecteds) with orofaciodigital syndrome like phenotype (dysmorphism, bilateral foot preaxial polysyndactyly, right foot postaxial polysyndactyly, broad thumbs, bilateral 5th finger clinodactyly narrow chest, partial AVSD). They found a homozygous missense variant in FUZ [p.(Glu201Lys)]. Parents were heterozygous carriers. A sibling died at 18mths and had complete AVSD, bilateral cleft lip and palate, right 5th finger clinodactyly, and medially deviated/broad great toes.

1 fetus with orofaciodigital syndrome like phenotype (right cleft lip, 4 limb polydactyly, bilateral duplicated hallux, and AVSD). They found compound heterozygous variants in FUZ [p.(Val209_Leu212del) and p.(Glu201Lys)].

PMID: 29068549
1 fetus with lethal short-rib polydactyly syndrome II-like phenotype and a homozygous variant (c.98_111+9del) in FUZ.
1 individual with asphyxiating thoracic dystrophy (ATD) with polydactyly and a (unclear if homozygous) missense variant [p.(Arg284Leu)] in FUZ.

PMID: 34719684
Monozygotic twins with craniosynostosis (1 x metopic, 1 x metopic/coronal) and a homozygous missense variant in FUZ [p.(Arg284Pro)]. They cultured primary osteoblasts and mouse embryonic fibroblasts from Fuz mutant mice. Loss of Fuz resulted in increased osteoblastic mineralisation, suggesting that the FUZ protein normally acts as a negative regulator of osteogenesis.
Sources: Literature
Skeletal dysplasia v0.276 FUZ Chirag Patel Classified gene: FUZ as Green List (high evidence)
Skeletal dysplasia v0.276 FUZ Chirag Patel Gene: fuz has been classified as Green List (High Evidence).
Skeletal Dysplasia_Fetal v0.220 FUZ Chirag Patel gene: FUZ was added
gene: FUZ was added to Skeletal Dysplasia_Fetal. Sources: Literature
Mode of inheritance for gene: FUZ was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FUZ were set to PMID: 38702430, 29068549, 34719684
Phenotypes for gene: FUZ were set to Ciliopathy_MONDO_0005308; skeletal ciliopathy
Review for gene: FUZ was set to GREEN
gene: FUZ was marked as current diagnostic
Added comment: FUZ is crucial for the transport of components to the primary cilium and potentially promotes protein complex assembly necessary for downstream cilium formation and function. Previous studies have shown complete knockout of Fuz in a mouse model leads to prenatal lethality, coronal craniosynostosis, micrognathia, facial malformations, eye, and heart defects. Suggested as a skeletal ciliopathy disorder gene.

PMID: 38702430
1 individual (from family with 2 affecteds) with orofaciodigital syndrome like phenotype (dysmorphism, bilateral foot preaxial polysyndactyly, right foot postaxial polysyndactyly, broad thumbs, bilateral 5th finger clinodactyly narrow chest, partial AVSD). They found a homozygous missense variant in FUZ [p.(Glu201Lys)]. Parents were heterozygous carriers. A sibling died at 18mths and had complete AVSD, bilateral cleft lip and palate, right 5th finger clinodactyly, and medially deviated/broad great toes.

1 fetus with orofaciodigital syndrome like phenotype (right cleft lip, 4 limb polydactyly, bilateral duplicated hallux, and AVSD). They found compound heterozygous variants in FUZ [p.(Val209_Leu212del) and p.(Glu201Lys)].

PMID: 29068549
1 fetus with lethal short-rib polydactyly syndrome II-like phenotype and a homozygous variant (c.98_111+9del) in FUZ.
1 individual with asphyxiating thoracic dystrophy (ATD) with polydactyly and a (unclear if homozygous) missense variant [p.(Arg284Leu)] in FUZ.

PMID: 34719684
Monozygotic twins with craniosynostosis (1 x metopic, 1 x metopic/coronal) and a homozygous missense variant in FUZ [p.(Arg284Pro)]. They cultured primary osteoblasts and mouse embryonic fibroblasts from Fuz mutant mice. Loss of Fuz resulted in increased osteoblastic mineralisation, suggesting that the FUZ protein normally acts as a negative regulator of osteogenesis.
Sources: Literature
Skeletal dysplasia v0.275 FUZ Chirag Patel gene: FUZ was added
gene: FUZ was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: FUZ was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FUZ were set to PMID: 38702430, 29068549, 34719684
Phenotypes for gene: FUZ were set to Ciliopathy_MONDO_0005308; skeletal ciliopathy
Review for gene: FUZ was set to GREEN
gene: FUZ was marked as current diagnostic
Added comment: FUZ is crucial for the transport of components to the primary cilium and potentially promotes protein complex assembly necessary for downstream cilium formation and function. Previous studies have shown complete knockout of Fuz in a mouse model leads to prenatal lethality, coronal craniosynostosis, micrognathia, facial malformations, eye, and heart defects. Suggested as a skeletal ciliopathy disorder gene.

PMID: 38702430
1 individual (from family with 2 affecteds) with orofaciodigital syndrome like phenotype (dysmorphism, bilateral foot preaxial polysyndactyly, right foot postaxial polysyndactyly, broad thumbs, bilateral 5th finger clinodactyly narrow chest, partial AVSD). They found a homozygous missense variant in FUZ [p.(Glu201Lys)]. Parents were heterozygous carriers. A sibling died at 18mths and had complete AVSD, bilateral cleft lip and palate, right 5th finger clinodactyly, and medially deviated/broad great toes.

1 fetus with orofaciodigital syndrome like phenotype (right cleft lip, 4 limb polydactyly, bilateral duplicated hallux, and AVSD). They found compound heterozygous variants in FUZ [p.(Val209_Leu212del) and p.(Glu201Lys)].

PMID: 29068549
1 fetus with lethal short-rib polydactyly syndrome II-like phenotype and a homozygous variant (c.98_111+9del) in FUZ.
1 individual with asphyxiating thoracic dystrophy (ATD) with polydactyly and a (unclear if homozygous) missense variant [p.(Arg284Leu)] in FUZ.

PMID: 34719684
Monozygotic twins with craniosynostosis (1 x metopic, 1 x metopic/coronal) and a homozygous missense variant in FUZ [p.(Arg284Pro)]. They cultured primary osteoblasts and mouse embryonic fibroblasts from Fuz mutant mice. Loss of Fuz resulted in increased osteoblastic mineralisation, suggesting that the FUZ protein normally acts as a negative regulator of osteogenesis.
Sources: Literature
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v1.14 FUZ Chirag Patel Classified gene: FUZ as Green List (high evidence)
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v1.14 FUZ Chirag Patel Gene: fuz has been classified as Green List (High Evidence).
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v1.13 FUZ Chirag Patel gene: FUZ was added
gene: FUZ was added to Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy. Sources: Literature
Mode of inheritance for gene: FUZ was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FUZ were set to PMID: 38702430, 29068549, 34719684
Phenotypes for gene: FUZ were set to Ciliopathy_MONDO_0005308; skeletal ciliopathy
Review for gene: FUZ was set to GREEN
gene: FUZ was marked as current diagnostic
Added comment: FUZ is crucial for the transport of components to the primary cilium and potentially promotes protein complex assembly necessary for downstream cilium formation and function. Previous studies have shown complete knockout of Fuz in a mouse model leads to prenatal lethality, coronal craniosynostosis, micrognathia, facial malformations, eye, and heart defects. Suggested as a skeletal ciliopathy disorder gene.

PMID: 38702430
1 individual (from family with 2 affecteds) with orofaciodigital syndrome like phenotype (dysmorphism, bilateral foot preaxial polysyndactyly, right foot postaxial polysyndactyly, broad thumbs, bilateral 5th finger clinodactyly narrow chest, partial AVSD). They found a homozygous missense variant in FUZ [p.(Glu201Lys)]. Parents were heterozygous carriers. A sibling died at 18mths and had complete AVSD, bilateral cleft lip and palate, right 5th finger clinodactyly, and medially deviated/broad great toes.

1 fetus with orofaciodigital syndrome like phenotype (right cleft lip, 4 limb polydactyly, bilateral duplicated hallux, and AVSD). They found compound heterozygous variants in FUZ [p.(Val209_Leu212del) and p.(Glu201Lys)].

PMID: 29068549
1 fetus with lethal short-rib polydactyly syndrome II-like phenotype and a homozygous variant (c.98_111+9del) in FUZ.
1 individual with asphyxiating thoracic dystrophy (ATD) with polydactyly and a (unclear if homozygous) missense variant [p.(Arg284Leu)] in FUZ.

PMID: 34719684
Monozygotic twins with craniosynostosis (1 x metopic, 1 x metopic/coronal) and a homozygous missense variant in FUZ [p.(Arg284Pro)]. They cultured primary osteoblasts and mouse embryonic fibroblasts from Fuz mutant mice. Loss of Fuz resulted in increased osteoblastic mineralisation, suggesting that the FUZ protein normally acts as a negative regulator of osteogenesis.
Sources: Literature
Ciliopathies v1.53 FUZ Chirag Patel Classified gene: FUZ as Green List (high evidence)
Ciliopathies v1.53 FUZ Chirag Patel Gene: fuz has been classified as Green List (High Evidence).
Fetal anomalies v1.246 FUZ Chirag Patel Classified gene: FUZ as Green List (high evidence)
Fetal anomalies v1.246 FUZ Chirag Patel Gene: fuz has been classified as Green List (High Evidence).
Genetic Epilepsy v1.11 ANO4 Ain Roesley gene: ANO4 was added
gene: ANO4 was added to Genetic Epilepsy. 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
Fetal anomalies v1.245 FUZ Chirag Patel reviewed gene: FUZ: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38702430, 29068549, 34719684; Phenotypes: Ciliopathy_MONDO_0005308, skeletal ciliopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6032 ANO4 Ain Roesley Classified gene: ANO4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6032 ANO4 Ain Roesley Gene: ano4 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.11 ANO4 Ain Roesley gene: ANO4 was added
gene: ANO4 was added to Genetic Epilepsy. 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
Ciliopathies v1.52 FUZ Chirag Patel gene: FUZ was added
gene: FUZ was added to Ciliopathies. Sources: Literature
Mode of inheritance for gene: FUZ was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FUZ were set to PMID: 38702430, 29068549, 34719684
Phenotypes for gene: FUZ were set to Ciliopathy_MONDO_0005308; skeletal ciliopathy
Review for gene: FUZ was set to GREEN
gene: FUZ was marked as current diagnostic
Added comment: FUZ is crucial for the transport of components to the primary cilium and potentially promotes protein complex assembly necessary for downstream cilium formation and function. Previous studies have shown complete knockout of Fuz in a mouse model leads to prenatal lethality, coronal craniosynostosis, micrognathia, facial malformations, eye, and heart defects. Suggested as a skeletal ciliopathy disorder gene.

PMID: 38702430
1 individual (from family with 2 affecteds) with orofaciodigital syndrome like phenotype (dysmorphism, bilateral foot preaxial polysyndactyly, right foot postaxial polysyndactyly, broad thumbs, bilateral 5th finger clinodactyly narrow chest, partial AVSD). They found a homozygous missense variant in FUZ [p.(Glu201Lys)]. Parents were heterozygous carriers. A sibling died at 18mths and had complete AVSD, bilateral cleft lip and palate, right 5th finger clinodactyly, and medially deviated/broad great toes.

1 fetus with orofaciodigital syndrome like phenotype (right cleft lip, 4 limb polydactyly, bilateral duplicated hallux, and AVSD). They found compound heterozygous variants in FUZ [p.(Val209_Leu212del) and p.(Glu201Lys)].

PMID: 29068549
1 fetus with lethal short-rib polydactyly syndrome II-like phenotype and a homozygous variant (c.98_111+9del) in FUZ.
1 individual with asphyxiating thoracic dystrophy (ATD) with polydactyly and a (unclear if homozygous) missense variant [p.(Arg284Leu)] in FUZ.

PMID: 34719684
Monozygotic twins with craniosynostosis (1 x metopic, 1 x metopic/coronal) and a homozygous missense variant in FUZ [p.(Arg284Pro)]. They cultured primary osteoblasts and mouse embryonic fibroblasts from Fuz mutant mice. Loss of Fuz resulted in increased osteoblastic mineralisation, suggesting that the FUZ protein normally acts as a negative regulator of osteogenesis.
Sources: Literature
Genetic Epilepsy v1.11 ANO4 Ain Roesley gene: ANO4 was added
gene: ANO4 was added to Genetic Epilepsy. 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
Intellectual disability syndromic and non-syndromic v0.6031 ANO4 Ain Roesley Classified gene: ANO4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6031 ANO4 Ain Roesley Gene: ano4 has been classified as Green List (High Evidence).
Mendeliome v1.1813 FUZ Chirag Patel Classified gene: FUZ as Green List (high evidence)
Mendeliome v1.1813 FUZ Chirag Patel Gene: fuz has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6031 ANO4 Ain Roesley Marked gene: ANO4 as ready
Intellectual disability syndromic and non-syndromic v0.6031 ANO4 Ain Roesley Gene: ano4 has been classified as Green List (High Evidence).
Mendeliome v1.1812 ANO4 Ain Roesley Marked gene: ANO4 as ready
Mendeliome v1.1812 ANO4 Ain Roesley Gene: ano4 has been classified as Green List (High Evidence).
Mendeliome v1.1812 ANO4 Ain Roesley Classified gene: ANO4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6031 ANO4 Ain Roesley Classified gene: ANO4 as Green List (high evidence)
Mendeliome v1.1812 ANO4 Ain Roesley Gene: ano4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6031 ANO4 Ain Roesley Gene: ano4 has been classified as Green List (High Evidence).
Mendeliome v1.1811 FUZ Chirag Patel reviewed gene: FUZ: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38702430, 29068549, 34719684; Phenotypes: Ciliopathy_MONDO_0005308, skeletal ciliopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v1.1811 ANO4 Ain Roesley Classified gene: ANO4 as Green List (high evidence)
Mendeliome v1.1811 ANO4 Ain Roesley Gene: ano4 has been classified as Green List (High Evidence).
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
Intellectual disability syndromic and non-syndromic v0.6030 ANO4 Ain Roesley gene: ANO4 was added
gene: ANO4 was added to Intellectual disability syndromic and non-syndromic. 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
Genetic Epilepsy v1.10 KCND1 Ain Roesley Marked gene: KCND1 as ready
Genetic Epilepsy v1.10 KCND1 Ain Roesley Gene: kcnd1 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.10 KCND1 Ain Roesley Classified gene: KCND1 as Green List (high evidence)
Genetic Epilepsy v1.10 KCND1 Ain Roesley Gene: kcnd1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6029 KCND1 Ain Roesley Classified gene: KCND1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6029 KCND1 Ain Roesley Gene: kcnd1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6028 KCND1 Ain Roesley Marked gene: KCND1 as ready
Intellectual disability syndromic and non-syndromic v0.6028 KCND1 Ain Roesley Gene: kcnd1 has been classified as Green List (High Evidence).
Mendeliome v1.1809 KCND1 Ain Roesley Marked gene: KCND1 as ready
Mendeliome v1.1809 KCND1 Ain Roesley Gene: kcnd1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6028 KCND1 Ain Roesley Classified gene: KCND1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6028 KCND1 Ain Roesley Gene: kcnd1 has been classified as Green List (High Evidence).
Mendeliome v1.1809 KCND1 Ain Roesley Classified gene: KCND1 as Green List (high evidence)
Mendeliome v1.1809 KCND1 Ain Roesley Gene: kcnd1 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.9 KCND1 Ain Roesley gene: KCND1 was added
gene: KCND1 was added to Genetic Epilepsy. 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
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
Intellectual disability syndromic and non-syndromic v0.6027 KCND1 Ain Roesley gene: KCND1 was added
gene: KCND1 was added to Intellectual disability syndromic and non-syndromic. 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
Intellectual disability syndromic and non-syndromic v0.6026 ATXN7L3 Chirag Patel Classified gene: ATXN7L3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6026 ATXN7L3 Chirag Patel Gene: atxn7l3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6025 ATXN7L3 Chirag Patel gene: ATXN7L3 was added
gene: ATXN7L3 was added to Intellectual disability syndromic and non-syndromic. 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
Intellectual disability syndromic and non-syndromic v0.6024 FAM177A1 Chirag Patel Classified gene: FAM177A1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6024 FAM177A1 Chirag Patel Gene: fam177a1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6023 FAM177A1 Chirag Patel Classified gene: FAM177A1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6023 FAM177A1 Chirag Patel Gene: fam177a1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6022 FAM177A1 Chirag Patel gene: FAM177A1 was added
gene: FAM177A1 was added to Intellectual disability syndromic and non-syndromic. 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
Intellectual disability syndromic and non-syndromic v0.6021 ERF Chirag Patel Classified gene: ERF as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6021 ERF Chirag Patel Gene: erf has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6020 ERF Chirag Patel reviewed gene: ERF: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38824261; Phenotypes: Noonan syndrome-like with or without craniosynostosis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Rasopathy v0.104 ERF Chirag Patel Classified gene: ERF as Green List (high evidence)
Rasopathy v0.104 ERF Chirag Patel Gene: erf has been classified as Green List (High Evidence).
Rasopathy v0.103 ERF Chirag Patel gene: ERF was added
gene: ERF was added to Rasopathy. Sources: Literature
Mode of inheritance for gene: ERF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ERF were set to PMID: 38824261
Phenotypes for gene: ERF were set to Noonan syndrome-like with or without craniosynostosis
Review for gene: ERF was set to GREEN
gene: ERF was marked as current diagnostic
Added comment: ERF gene encodes a transcriptional regulator negatively controlling RAS-MAPK signalling. It has been associated with syndromic craniosynostosis involving various cranial sutures and Chitayat syndrome (respiratory distress, skeletal anomalies, and facial dysmorphism).

This paper describes 26 individuals from 15 unrelated families with Noonan-syndrome (NS) like phenotype and heterozygous nonsense and frameshift variants in ERF (most cases were familial). The clinical features included: variable global developmental and/or language delay, absolute/relative macrocephaly, short stature (<3rd centile), and dysmorphism (high forehead, hypertelorism, ptosis, wide nasal bridge, and low-set/posteriorly angulated ears). There were no individuals with typical NS cardiac involvement. Craniosynostosis was only seen in 3/26 unrelated individuals.

These findings provide evidence that heterozygous loss-of-function variants in ERF cause a "RASopathy" resembling NS with or without craniosynostosis.
Sources: Literature
Hydrops fetalis v0.311 RAPSN Lilian Downie reviewed gene: RAPSN: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34302381, PMID: 33897756, PMID: 28495245; Phenotypes: Fetal akinesia deformation sequence 2 MIM#618388; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6020 PPFIA3 Zornitza Stark Publications for gene: PPFIA3 were set to 37034625
Intellectual disability syndromic and non-syndromic v0.6019 PPFIA3 Zornitza Stark edited their review of gene: PPFIA3: Changed publications: 38723631
Mendeliome v1.1807 PPFIA3 Zornitza Stark Publications for gene: PPFIA3 were set to 37034625
Mendeliome v1.1806 PPFIA3 Zornitza Stark edited their review of gene: PPFIA3: Changed publications: 38723631
Genetic Epilepsy v1.8 PPFIA3 Zornitza Stark Publications for gene: PPFIA3 were set to 38723631
Genetic Epilepsy v1.7 PPFIA3 Zornitza Stark Publications for gene: PPFIA3 were set to 37034625
Genetic Epilepsy v1.6 PPFIA3 Zornitza Stark edited their review of gene: PPFIA3: Changed publications: 38723631
Mendeliome v1.1806 LRRC23 Zornitza Stark Phenotypes for gene: LRRC23 were changed from Non-syndromic male infertility due to sperm motility disorder, (MONDO:0017173), LRRC23-related to Spermatogenic failure 92, MIM# 620848
Mendeliome v1.1805 LRRC23 Zornitza Stark Publications for gene: LRRC23 were set to 37804054
Mendeliome v1.1804 LRRC23 Zornitza Stark Classified gene: LRRC23 as Amber List (moderate evidence)
Mendeliome v1.1804 LRRC23 Zornitza Stark Gene: lrrc23 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1803 LRRC23 Zornitza Stark reviewed gene: LRRC23: Rating: AMBER; Mode of pathogenicity: None; Publications: 38091523; Phenotypes: Spermatogenic failure 92, MIM# 620848; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Aminoacidopathy v1.47 GCSH Sangavi Sivagnanasundram gene: GCSH was added
gene: GCSH was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: GCSH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GCSH were set to 33890291; 36190515; 33569080
Phenotypes for gene: GCSH were set to glycine encephalopathy MONDO:0011612
Review for gene: GCSH was set to GREEN
Added comment: Classified Strong by ClinGen Aminoacidopathy GCEP on 10/02/2023 - https://search.clinicalgenome.org/CCID:004937

Reported in 7 individuals with abnormal biochemical metabolism.
Sources: ClinGen
Aminoacidopathy v1.47 GCDH Sangavi Sivagnanasundram edited their review of gene: GCDH: Changed rating: GREEN
Aminoacidopathy v1.47 GCH1 Sangavi Sivagnanasundram gene: GCH1 was added
gene: GCH1 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: GCH1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: GCH1 were set to 20301681, 9749603, 10582612, 11026444, 15303002
Phenotypes for gene: GCH1 were set to GTP cyclohydrolase I deficiency MONDO:0100184
Review for gene: GCH1 was set to GREEN
Added comment: Classified Definitive by ClinGen Aminoacidopathy GCEP on 11/12/2020 - https://search.clinicalgenome.org/CCID:004935

AD individuals have less than 50% GTPCH activity suggesting a dominant negative mechanism of disease.

AR individuals are shown to have severe deficiency of GTPCH activity resulting in hhyperphenylalaninemia due to secondary PAH deficiency which can be detected on NBS.
Sources: ClinGen
Aminoacidopathy v1.47 GCDH Sangavi Sivagnanasundram gene: GCDH was added
gene: GCDH was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: GCDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GCDH were set to 31536184, 7795610, 27476540, 31062211
Phenotypes for gene: GCDH were set to glutaryl-CoA dehydrogenase deficiency MONDO:0009281
Added comment: Classified Definitive by ClinGen Aminoacidopathy GCEP on 08/11/2019 - https://search.clinicalgenome.org/CCID:004934

Well established gene-disease association.
Affected individuals present with abnormal glutaric acid, 3-hydroxy-glutaric acid, glutaconic acid and glutarylcarnitine.
c.91+5G>T has been reported to segregate closely within closely related Native American kindreds.
Sources: ClinGen
Combined Immunodeficiency v1.65 POLD1 Zornitza Stark Phenotypes for gene: POLD1 were changed from Combined immunodeficiency, MONDO:0015131, POLD1-related; Low CD4 T cells; Low B cells, normal maturation; recurrent respiratory tract infections, skin infections, warts and molluscum; short stature; intellectual disability to Immunodeficiency 120, MIM# 620836; Low CD4 T cells; Low B cells, normal maturation; recurrent respiratory tract infections, skin infections, warts and molluscum; short stature; intellectual disability
Combined Immunodeficiency v1.64 POLD1 Zornitza Stark edited their review of gene: POLD1: Changed phenotypes: Immunodeficiency 120, MIM# 620836, Low CD4 T cells, Low B cells, normal maturation, recurrent respiratory tract infections, skin infections, warts and molluscum, short stature, intellectual disability
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
Common Variable Immunodeficiency v1.12 ICOSLG Zornitza Stark edited their review of gene: ICOSLG: Changed phenotypes: Immunodeficiency 119, MIM# 620825, Combined immunodeficiency, recurrent bacterial and viral infections, neutropaenia
Combined Immunodeficiency v1.64 ICOSLG Zornitza Stark Phenotypes for gene: ICOSLG were changed from Combined immunodeficiency; recurrent bacterial and viral infections; neutropaenia to Immunodeficiency 119, MIM# 620825; Combined immunodeficiency; recurrent bacterial and viral infections; neutropaenia
Combined Immunodeficiency v1.63 ICOSLG Zornitza Stark edited their review of gene: ICOSLG: Changed phenotypes: Immunodeficiency 119, MIM# 620825, Combined immunodeficiency, recurrent bacterial and viral infections, neutropaenia
Mendeliome v1.1802 ICOSLG Zornitza Stark Phenotypes for gene: ICOSLG were changed from Combined immunodeficiency; recurrent bacterial and viral infections; neutropaenia to Immunodeficiency 119, MIM# 620825; Combined immunodeficiency; recurrent bacterial and viral infections; neutropaenia
Mendeliome v1.1801 ICOSLG Zornitza Stark edited their review of gene: ICOSLG: Changed phenotypes: Immunodeficiency 119, MIM# 620825, Combined immunodeficiency, recurrent bacterial and viral infections, neutropaenia
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.326 SYCP2L Zornitza Stark Phenotypes for gene: SYCP2L were changed from Premature ovarian insufficiency to Premature ovarian failure 24, MIM# 620840
Mendeliome v1.1801 SYCP2L Zornitza Stark Phenotypes for gene: SYCP2L were changed from Premature ovarian insufficiency to Premature ovarian failure 24, MIM# 620840
Cerebral Palsy v1.275 DLG4 Zornitza Stark Marked gene: DLG4 as ready
Cerebral Palsy v1.275 DLG4 Zornitza Stark Gene: dlg4 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.275 DLG4 Zornitza Stark Classified gene: DLG4 as Red List (low evidence)
Cerebral Palsy v1.275 DLG4 Zornitza Stark Gene: dlg4 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.274 DLG4 Zornitza Stark Classified gene: DLG4 as Red List (low evidence)
Cerebral Palsy v1.274 DLG4 Zornitza Stark Gene: dlg4 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.273 DCC Zornitza Stark Marked gene: DCC as ready
Cerebral Palsy v1.273 DCC Zornitza Stark Gene: dcc has been classified as Red List (Low Evidence).
Cerebral Palsy v1.273 DCC Zornitza Stark Classified gene: DCC as Red List (low evidence)
Cerebral Palsy v1.273 DCC Zornitza Stark Gene: dcc has been classified as Red List (Low Evidence).
Cerebral Palsy v1.272 CUL3 Zornitza Stark Marked gene: CUL3 as ready
Cerebral Palsy v1.272 CUL3 Zornitza Stark Gene: cul3 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.272 CUL3 Zornitza Stark Classified gene: CUL3 as Red List (low evidence)
Cerebral Palsy v1.272 CUL3 Zornitza Stark Gene: cul3 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.271 DNMT3A Zornitza Stark Marked gene: DNMT3A as ready
Cerebral Palsy v1.271 DNMT3A Zornitza Stark Gene: dnmt3a has been classified as Red List (Low Evidence).
Cerebral Palsy v1.271 DNMT3A Zornitza Stark Classified gene: DNMT3A as Red List (low evidence)
Cerebral Palsy v1.271 DNMT3A Zornitza Stark Gene: dnmt3a has been classified as Red List (Low Evidence).
Cerebral Palsy v1.270 EHMT1 Zornitza Stark Marked gene: EHMT1 as ready
Cerebral Palsy v1.270 EHMT1 Zornitza Stark Gene: ehmt1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.270 EHMT1 Zornitza Stark Classified gene: EHMT1 as Red List (low evidence)
Cerebral Palsy v1.270 EHMT1 Zornitza Stark Gene: ehmt1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.269 EZH2 Zornitza Stark Marked gene: EZH2 as ready
Cerebral Palsy v1.269 EZH2 Zornitza Stark Gene: ezh2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.269 EZH2 Zornitza Stark Classified gene: EZH2 as Red List (low evidence)
Cerebral Palsy v1.269 EZH2 Zornitza Stark Gene: ezh2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.268 FGFR1 Zornitza Stark Marked gene: FGFR1 as ready
Cerebral Palsy v1.268 FGFR1 Zornitza Stark Gene: fgfr1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.268 FGFR1 Zornitza Stark Classified gene: FGFR1 as Red List (low evidence)
Cerebral Palsy v1.268 FGFR1 Zornitza Stark Gene: fgfr1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.267 FUS Zornitza Stark Marked gene: FUS as ready
Cerebral Palsy v1.267 FUS Zornitza Stark Gene: fus has been classified as Red List (Low Evidence).
Cerebral Palsy v1.267 FUS Zornitza Stark Classified gene: FUS as Red List (low evidence)
Cerebral Palsy v1.267 FUS Zornitza Stark Gene: fus has been classified as Red List (Low Evidence).
Cerebral Palsy v1.266 GABBR2 Zornitza Stark Marked gene: GABBR2 as ready
Cerebral Palsy v1.266 GABBR2 Zornitza Stark Gene: gabbr2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.266 GABBR2 Zornitza Stark Classified gene: GABBR2 as Red List (low evidence)
Cerebral Palsy v1.266 GABBR2 Zornitza Stark Gene: gabbr2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.265 GATAD2B Zornitza Stark Marked gene: GATAD2B as ready
Cerebral Palsy v1.265 GATAD2B Zornitza Stark Gene: gatad2b has been classified as Red List (Low Evidence).
Cerebral Palsy v1.265 GATAD2B Zornitza Stark Classified gene: GATAD2B as Red List (low evidence)
Cerebral Palsy v1.265 GATAD2B Zornitza Stark Gene: gatad2b has been classified as Red List (Low Evidence).
Cerebral Palsy v1.264 GRIN2A Zornitza Stark Marked gene: GRIN2A as ready
Cerebral Palsy v1.264 GRIN2A Zornitza Stark Gene: grin2a has been classified as Red List (Low Evidence).
Cerebral Palsy v1.264 GRIN2A Zornitza Stark Classified gene: GRIN2A as Red List (low evidence)
Cerebral Palsy v1.264 GRIN2A Zornitza Stark Gene: grin2a has been classified as Red List (Low Evidence).
Cerebral Palsy v1.263 HIVEP2 Zornitza Stark Marked gene: HIVEP2 as ready
Cerebral Palsy v1.263 HIVEP2 Zornitza Stark Gene: hivep2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.263 HIVEP2 Zornitza Stark Classified gene: HIVEP2 as Red List (low evidence)
Cerebral Palsy v1.263 HIVEP2 Zornitza Stark Gene: hivep2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.262 KAT6B Zornitza Stark Marked gene: KAT6B as ready
Cerebral Palsy v1.262 KAT6B Zornitza Stark Gene: kat6b has been classified as Red List (Low Evidence).
Cerebral Palsy v1.262 KAT6B Zornitza Stark Classified gene: KAT6B as Red List (low evidence)
Cerebral Palsy v1.262 KAT6B Zornitza Stark Gene: kat6b has been classified as Red List (Low Evidence).
Cerebral Palsy v1.261 KCNH1 Zornitza Stark Marked gene: KCNH1 as ready
Cerebral Palsy v1.261 KCNH1 Zornitza Stark Gene: kcnh1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.261 KCNH1 Zornitza Stark Classified gene: KCNH1 as Red List (low evidence)
Cerebral Palsy v1.261 KCNH1 Zornitza Stark Gene: kcnh1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.260 KCNQ3 Zornitza Stark Marked gene: KCNQ3 as ready
Cerebral Palsy v1.260 KCNQ3 Zornitza Stark Gene: kcnq3 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.260 KCNQ3 Zornitza Stark Classified gene: KCNQ3 as Red List (low evidence)
Cerebral Palsy v1.260 KCNQ3 Zornitza Stark Gene: kcnq3 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.259 KCNQ5 Zornitza Stark Marked gene: KCNQ5 as ready
Cerebral Palsy v1.259 KCNQ5 Zornitza Stark Gene: kcnq5 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.259 KCNQ5 Zornitza Stark Classified gene: KCNQ5 as Red List (low evidence)
Cerebral Palsy v1.259 KCNQ5 Zornitza Stark Gene: kcnq5 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.258 KMT2D Zornitza Stark Marked gene: KMT2D as ready
Cerebral Palsy v1.258 KMT2D Zornitza Stark Gene: kmt2d has been classified as Red List (Low Evidence).
Cerebral Palsy v1.258 KMT2D Zornitza Stark Classified gene: KMT2D as Red List (low evidence)
Cerebral Palsy v1.258 KMT2D Zornitza Stark Gene: kmt2d has been classified as Red List (Low Evidence).
Cerebral Palsy v1.257 MACF1 Zornitza Stark Marked gene: MACF1 as ready
Cerebral Palsy v1.257 MACF1 Zornitza Stark Gene: macf1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.257 MACF1 Zornitza Stark Classified gene: MACF1 as Red List (low evidence)
Cerebral Palsy v1.257 MACF1 Zornitza Stark Gene: macf1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.256 MBD5 Zornitza Stark Marked gene: MBD5 as ready
Cerebral Palsy v1.256 MBD5 Zornitza Stark Gene: mbd5 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.256 MBD5 Zornitza Stark Classified gene: MBD5 as Red List (low evidence)
Cerebral Palsy v1.256 MBD5 Zornitza Stark Gene: mbd5 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.255 MED13L Zornitza Stark Marked gene: MED13L as ready
Cerebral Palsy v1.255 MED13L Zornitza Stark Gene: med13l has been classified as Red List (Low Evidence).
Cerebral Palsy v1.255 MED13L Zornitza Stark Classified gene: MED13L as Red List (low evidence)
Cerebral Palsy v1.255 MED13L Zornitza Stark Gene: med13l has been classified as Red List (Low Evidence).
Cerebral Palsy v1.254 MYH2 Zornitza Stark Marked gene: MYH2 as ready
Cerebral Palsy v1.254 MYH2 Zornitza Stark Gene: myh2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.254 MYH2 Zornitza Stark Classified gene: MYH2 as Red List (low evidence)
Cerebral Palsy v1.254 MYH2 Zornitza Stark Gene: myh2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.253 NEFL Zornitza Stark Marked gene: NEFL as ready
Cerebral Palsy v1.253 NEFL Zornitza Stark Gene: nefl has been classified as Red List (Low Evidence).
Cerebral Palsy v1.253 NEFL Zornitza Stark Classified gene: NEFL as Red List (low evidence)
Cerebral Palsy v1.253 NEFL Zornitza Stark Gene: nefl has been classified as Red List (Low Evidence).
Cerebral Palsy v1.252 NFE2L2 Zornitza Stark Marked gene: NFE2L2 as ready
Cerebral Palsy v1.252 NFE2L2 Zornitza Stark Gene: nfe2l2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.252 NFE2L2 Zornitza Stark Classified gene: NFE2L2 as Red List (low evidence)
Cerebral Palsy v1.252 NFE2L2 Zornitza Stark Gene: nfe2l2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.251 NFIB Zornitza Stark Marked gene: NFIB as ready
Cerebral Palsy v1.251 NFIB Zornitza Stark Gene: nfib has been classified as Red List (Low Evidence).
Cerebral Palsy v1.251 NFIB Zornitza Stark Classified gene: NFIB as Red List (low evidence)
Cerebral Palsy v1.251 NFIB Zornitza Stark Gene: nfib has been classified as Red List (Low Evidence).
Cerebral Palsy v1.250 NOTCH1 Zornitza Stark Marked gene: NOTCH1 as ready
Cerebral Palsy v1.250 NOTCH1 Zornitza Stark Gene: notch1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.250 NOTCH1 Zornitza Stark Classified gene: NOTCH1 as Red List (low evidence)
Cerebral Palsy v1.250 NOTCH1 Zornitza Stark Gene: notch1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.249 NR2F1 Zornitza Stark Marked gene: NR2F1 as ready
Cerebral Palsy v1.249 NR2F1 Zornitza Stark Gene: nr2f1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.249 NR2F1 Zornitza Stark Classified gene: NR2F1 as Red List (low evidence)
Cerebral Palsy v1.249 NR2F1 Zornitza Stark Gene: nr2f1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.248 NSD1 Zornitza Stark Marked gene: NSD1 as ready
Cerebral Palsy v1.248 NSD1 Zornitza Stark Gene: nsd1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.248 NSD1 Zornitza Stark Classified gene: NSD1 as Red List (low evidence)
Cerebral Palsy v1.248 NSD1 Zornitza Stark Gene: nsd1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.247 NSD2 Zornitza Stark Marked gene: NSD2 as ready
Cerebral Palsy v1.247 NSD2 Zornitza Stark Gene: nsd2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.247 NSD2 Zornitza Stark Classified gene: NSD2 as Red List (low evidence)
Cerebral Palsy v1.247 NSD2 Zornitza Stark Gene: nsd2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.246 PACS1 Zornitza Stark Marked gene: PACS1 as ready
Cerebral Palsy v1.246 PACS1 Zornitza Stark Gene: pacs1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.246 PACS1 Zornitza Stark Classified gene: PACS1 as Red List (low evidence)
Cerebral Palsy v1.246 PACS1 Zornitza Stark Gene: pacs1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.245 PHIP Zornitza Stark Marked gene: PHIP as ready
Cerebral Palsy v1.245 PHIP Zornitza Stark Gene: phip has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.245 PHIP Zornitza Stark Classified gene: PHIP as Amber List (moderate evidence)
Cerebral Palsy v1.245 PHIP Zornitza Stark Gene: phip has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.244 PPM1D Zornitza Stark Marked gene: PPM1D as ready
Cerebral Palsy v1.244 PPM1D Zornitza Stark Gene: ppm1d has been classified as Red List (Low Evidence).
Cerebral Palsy v1.244 PPM1D Zornitza Stark Classified gene: PPM1D as Red List (low evidence)
Cerebral Palsy v1.244 PPM1D Zornitza Stark Gene: ppm1d has been classified as Red List (Low Evidence).
Cerebral Palsy v1.243 SETBP1 Zornitza Stark Marked gene: SETBP1 as ready
Cerebral Palsy v1.243 SETBP1 Zornitza Stark Gene: setbp1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.243 SETBP1 Zornitza Stark Classified gene: SETBP1 as Red List (low evidence)
Cerebral Palsy v1.243 SETBP1 Zornitza Stark Gene: setbp1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.242 SETD2 Zornitza Stark Marked gene: SETD2 as ready
Cerebral Palsy v1.242 SETD2 Zornitza Stark Gene: setd2 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.242 SETD2 Zornitza Stark Classified gene: SETD2 as Amber List (moderate evidence)
Cerebral Palsy v1.242 SETD2 Zornitza Stark Gene: setd2 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.241 SGCE Zornitza Stark Marked gene: SGCE as ready
Cerebral Palsy v1.241 SGCE Zornitza Stark Gene: sgce has been classified as Red List (Low Evidence).
Cerebral Palsy v1.241 SGCE Zornitza Stark Classified gene: SGCE as Red List (low evidence)
Cerebral Palsy v1.241 SGCE Zornitza Stark Gene: sgce has been classified as Red List (Low Evidence).
Cerebral Palsy v1.240 SIK1 Zornitza Stark Marked gene: SIK1 as ready
Cerebral Palsy v1.240 SIK1 Zornitza Stark Gene: sik1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.240 SIK1 Zornitza Stark Classified gene: SIK1 as Red List (low evidence)
Cerebral Palsy v1.240 SIK1 Zornitza Stark Gene: sik1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.239 SLC1A2 Zornitza Stark Marked gene: SLC1A2 as ready
Cerebral Palsy v1.239 SLC1A2 Zornitza Stark Gene: slc1a2 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.239 SLC1A2 Zornitza Stark Classified gene: SLC1A2 as Amber List (moderate evidence)
Cerebral Palsy v1.239 SLC1A2 Zornitza Stark Gene: slc1a2 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.238 SLC6A5 Zornitza Stark Marked gene: SLC6A5 as ready
Cerebral Palsy v1.238 SLC6A5 Zornitza Stark Gene: slc6a5 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.238 SLC6A5 Zornitza Stark Classified gene: SLC6A5 as Red List (low evidence)
Cerebral Palsy v1.238 SLC6A5 Zornitza Stark Gene: slc6a5 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.237 SMARCA2 Zornitza Stark Marked gene: SMARCA2 as ready
Cerebral Palsy v1.237 SMARCA2 Zornitza Stark Gene: smarca2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.237 SMARCA2 Zornitza Stark Classified gene: SMARCA2 as Red List (low evidence)
Cerebral Palsy v1.237 SMARCA2 Zornitza Stark Gene: smarca2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.236 SMARCA4 Zornitza Stark Marked gene: SMARCA4 as ready
Cerebral Palsy v1.236 SMARCA4 Zornitza Stark Gene: smarca4 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.236 SMARCA4 Zornitza Stark Classified gene: SMARCA4 as Red List (low evidence)
Cerebral Palsy v1.236 SMARCA4 Zornitza Stark Gene: smarca4 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.235 SMC3 Zornitza Stark Marked gene: SMC3 as ready
Cerebral Palsy v1.235 SMC3 Zornitza Stark Gene: smc3 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.235 SMC3 Zornitza Stark Classified gene: SMC3 as Red List (low evidence)
Cerebral Palsy v1.235 SMC3 Zornitza Stark Gene: smc3 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.234 SOX10 Zornitza Stark Marked gene: SOX10 as ready
Cerebral Palsy v1.234 SOX10 Zornitza Stark Gene: sox10 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.234 SOX10 Zornitza Stark Classified gene: SOX10 as Red List (low evidence)
Cerebral Palsy v1.234 SOX10 Zornitza Stark Gene: sox10 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.233 TANC2 Zornitza Stark Marked gene: TANC2 as ready
Cerebral Palsy v1.233 TANC2 Zornitza Stark Gene: tanc2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.233 TANC2 Zornitza Stark Classified gene: TANC2 as Red List (low evidence)
Cerebral Palsy v1.233 TANC2 Zornitza Stark Gene: tanc2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.232 TBR1 Zornitza Stark Marked gene: TBR1 as ready
Cerebral Palsy v1.232 TBR1 Zornitza Stark Gene: tbr1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.232 TBR1 Zornitza Stark Classified gene: TBR1 as Red List (low evidence)
Cerebral Palsy v1.232 TBR1 Zornitza Stark Gene: tbr1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.231 TBX6 Zornitza Stark Marked gene: TBX6 as ready
Cerebral Palsy v1.231 TBX6 Zornitza Stark Gene: tbx6 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.231 TBX6 Zornitza Stark Classified gene: TBX6 as Red List (low evidence)
Cerebral Palsy v1.231 TBX6 Zornitza Stark Gene: tbx6 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.230 TGM6 Zornitza Stark Marked gene: TGM6 as ready
Cerebral Palsy v1.230 TGM6 Zornitza Stark Gene: tgm6 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.230 TGM6 Zornitza Stark Classified gene: TGM6 as Red List (low evidence)
Cerebral Palsy v1.230 TGM6 Zornitza Stark Gene: tgm6 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.229 TOR1A Zornitza Stark Marked gene: TOR1A as ready
Cerebral Palsy v1.229 TOR1A Zornitza Stark Gene: tor1a has been classified as Red List (Low Evidence).
Cerebral Palsy v1.229 TOR1A Zornitza Stark Classified gene: TOR1A as Red List (low evidence)
Cerebral Palsy v1.229 TOR1A Zornitza Stark Gene: tor1a has been classified as Red List (Low Evidence).
Cerebral Palsy v1.228 TSC2 Zornitza Stark Marked gene: TSC2 as ready
Cerebral Palsy v1.228 TSC2 Zornitza Stark Gene: tsc2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.228 TSC2 Zornitza Stark Classified gene: TSC2 as Red List (low evidence)
Cerebral Palsy v1.228 TSC2 Zornitza Stark Gene: tsc2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.227 TSHR Zornitza Stark Marked gene: TSHR as ready
Cerebral Palsy v1.227 TSHR Zornitza Stark Gene: tshr has been classified as Red List (Low Evidence).
Cerebral Palsy v1.227 TSHR Zornitza Stark Classified gene: TSHR as Red List (low evidence)
Cerebral Palsy v1.227 TSHR Zornitza Stark Gene: tshr has been classified as Red List (Low Evidence).
Prepair 1000+ v1.6 AAAS Zornitza Stark edited their review of gene: AAAS: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.6 AAAS Zornitza Stark edited their review of gene: AAAS: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Prepair 1000+ v1.6 AAAS Zornitza Stark reviewed gene: AAAS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Achalasia-addisonianism-alacrimia syndrome, MIM# 231550; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6019 SSR4 Zornitza Stark Marked gene: SSR4 as ready
Intellectual disability syndromic and non-syndromic v0.6019 SSR4 Zornitza Stark Gene: ssr4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6019 SSR4 Zornitza Stark Phenotypes for gene: SSR4 were changed from to Congenital disorder of glycosylation, type Iy, MIM# 300934
Intellectual disability syndromic and non-syndromic v0.6018 SSR4 Zornitza Stark Publications for gene: SSR4 were set to
Intellectual disability syndromic and non-syndromic v0.6017 SSR4 Zornitza Stark Mode of inheritance for gene: SSR4 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.6016 SSR4 Zornitza Stark reviewed gene: SSR4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type Iy, MIM# 300934; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.6016 RELN Zornitza Stark Marked gene: RELN as ready
Intellectual disability syndromic and non-syndromic v0.6016 RELN Zornitza Stark Gene: reln has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6016 RELN Zornitza Stark Publications for gene: RELN were set to
Intellectual disability syndromic and non-syndromic v0.6015 RELN Zornitza Stark reviewed gene: RELN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Lissencephaly 2 (Norman-Roberts type), MIM# 257320; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6015 RELN Zornitza Stark Phenotypes for gene: RELN were changed from to Lissencephaly 2 (Norman-Roberts type), MIM# 257320
Intellectual disability syndromic and non-syndromic v0.6014 RELN Zornitza Stark Mode of inheritance for gene: RELN was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6013 SLC35A1 Anissa Johnson Deleted their review
Intellectual disability syndromic and non-syndromic v0.6013 RELN Tashunka Taylor-Miller changed review comment from: 7 individuals from 4 families with biallelic variants, and 13 individuals from 7 families with monoallelic (heterozygous) variants of RELN and frontotemporal or temporal-predominant lissencephaly variant. Associated features: intellectual disability (16/20), seizures (5/20), unprovoked aggression (6/20), sleep disturbance (7/20)
Variant spectrum includes: loss of function, missense, splice-site variants.

MRI features include: anterior-predominant “thin”lisencephaly pachygyria with cerebellar hypoplasia
Biallelic variants are associated with a severe phenotype that includes cerebellar hypoplasia.
Monoallelic variants are associated with incomplete penetrance and variable expressivity (eg: one adult with abnormal MRI but normal intelligence and neurological profile).; to: 7 individuals from 4 families with biallelic variants, and 13 individuals from 7 families with monoallelic (heterozygous) variants of RELN and frontotemporal or temporal-predominant lissencephaly variant. Associated features: intellectual disability (16/20), seizures (5/20), unprovoked aggression (6/20), sleep disturbance (7/20)
Variant spectrum includes: loss of function, missense, splice-site variants.

MRI features include: anterior-predominant “thin” lisencephaly pachygyria with cerebellar hypoplasia.
Biallelic variants are associated with a severe phenotype that includes cerebellar hypoplasia.
Monoallelic variants are associated with incomplete penetrance and variable expressivity (eg: one adult with abnormal MRI but normal intelligence and neurological profile).
Intellectual disability syndromic and non-syndromic v0.6013 RELN Tashunka Taylor-Miller edited their review of gene: RELN: Changed publications: PMID: 35769015, PMID: 29671837
Intellectual disability syndromic and non-syndromic v0.6013 RELN Tashunka Taylor-Miller reviewed gene: RELN: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35769015, 29671837; Phenotypes: OMIM *600514, HP:0001339, DOID:0070338; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cerebral Palsy v1.226 CTCF Zornitza Stark Marked gene: CTCF as ready
Cerebral Palsy v1.226 CTCF Zornitza Stark Gene: ctcf has been classified as Red List (Low Evidence).
Cerebral Palsy v1.226 CTCF Zornitza Stark Classified gene: CTCF as Red List (low evidence)
Cerebral Palsy v1.226 CTCF Zornitza Stark Gene: ctcf has been classified as Red List (Low Evidence).
Cerebral Palsy v1.225 CLCN7 Zornitza Stark Marked gene: CLCN7 as ready
Cerebral Palsy v1.225 CLCN7 Zornitza Stark Gene: clcn7 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.225 CLCN7 Zornitza Stark Classified gene: CLCN7 as Red List (low evidence)
Cerebral Palsy v1.225 CLCN7 Zornitza Stark Gene: clcn7 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.224 CHD7 Zornitza Stark Marked gene: CHD7 as ready
Cerebral Palsy v1.224 CHD7 Zornitza Stark Gene: chd7 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.224 CHD7 Zornitza Stark Classified gene: CHD7 as Amber List (moderate evidence)
Cerebral Palsy v1.224 CHD7 Zornitza Stark Gene: chd7 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.223 CHD4 Zornitza Stark Marked gene: CHD4 as ready
Cerebral Palsy v1.223 CHD4 Zornitza Stark Gene: chd4 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.223 CHD4 Zornitza Stark Classified gene: CHD4 as Red List (low evidence)
Cerebral Palsy v1.223 CHD4 Zornitza Stark Gene: chd4 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.222 CHCHD10 Zornitza Stark Marked gene: CHCHD10 as ready
Cerebral Palsy v1.222 CHCHD10 Zornitza Stark Gene: chchd10 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.222 CHCHD10 Zornitza Stark Classified gene: CHCHD10 as Red List (low evidence)
Cerebral Palsy v1.222 CHCHD10 Zornitza Stark Gene: chchd10 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.221 CAMK2G Zornitza Stark Marked gene: CAMK2G as ready
Cerebral Palsy v1.221 CAMK2G Zornitza Stark Gene: camk2g has been classified as Red List (Low Evidence).
Cerebral Palsy v1.221 CAMK2G Zornitza Stark Classified gene: CAMK2G as Red List (low evidence)
Cerebral Palsy v1.221 CAMK2G Zornitza Stark Gene: camk2g has been classified as Red List (Low Evidence).
Cerebral Palsy v1.220 CAMK2B Zornitza Stark Marked gene: CAMK2B as ready
Cerebral Palsy v1.220 CAMK2B Zornitza Stark Gene: camk2b has been classified as Red List (Low Evidence).
Cerebral Palsy v1.220 CAMK2B Zornitza Stark Classified gene: CAMK2B as Red List (low evidence)
Cerebral Palsy v1.220 CAMK2B Zornitza Stark Gene: camk2b has been classified as Red List (Low Evidence).
Cerebral Palsy v1.219 CACNA1G Zornitza Stark Marked gene: CACNA1G as ready
Cerebral Palsy v1.219 CACNA1G Zornitza Stark Gene: cacna1g has been classified as Green List (High Evidence).
Cerebral Palsy v1.219 CACNA1G Zornitza Stark Classified gene: CACNA1G as Green List (high evidence)
Cerebral Palsy v1.219 CACNA1G Zornitza Stark Gene: cacna1g has been classified as Green List (High Evidence).
Cerebral Palsy v1.218 CACNA1D Zornitza Stark Marked gene: CACNA1D as ready
Cerebral Palsy v1.218 CACNA1D Zornitza Stark Gene: cacna1d has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.218 CACNA1D Zornitza Stark Classified gene: CACNA1D as Amber List (moderate evidence)
Cerebral Palsy v1.218 CACNA1D Zornitza Stark Gene: cacna1d has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.217 ATP6V1A Zornitza Stark Marked gene: ATP6V1A as ready
Cerebral Palsy v1.217 ATP6V1A Zornitza Stark Gene: atp6v1a has been classified as Red List (Low Evidence).
Cerebral Palsy v1.217 ATP6V1A Zornitza Stark Classified gene: ATP6V1A as Red List (low evidence)
Cerebral Palsy v1.217 ATP6V1A Zornitza Stark Gene: atp6v1a has been classified as Red List (Low Evidence).
Cerebral Palsy v1.216 ATP1A2 Zornitza Stark Marked gene: ATP1A2 as ready
Cerebral Palsy v1.216 ATP1A2 Zornitza Stark Gene: atp1a2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.216 ATP1A2 Zornitza Stark Classified gene: ATP1A2 as Red List (low evidence)
Cerebral Palsy v1.216 ATP1A2 Zornitza Stark Gene: atp1a2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.215 ARID1B Zornitza Stark Marked gene: ARID1B as ready
Cerebral Palsy v1.215 ARID1B Zornitza Stark Gene: arid1b has been classified as Red List (Low Evidence).
Cerebral Palsy v1.215 ARID1B Zornitza Stark Classified gene: ARID1B as Red List (low evidence)
Cerebral Palsy v1.215 ARID1B Zornitza Stark Gene: arid1b has been classified as Red List (Low Evidence).
Cerebral Palsy v1.214 DNM2 Zornitza Stark Marked gene: DNM2 as ready
Cerebral Palsy v1.214 DNM2 Zornitza Stark Gene: dnm2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.214 DNM2 Zornitza Stark Classified gene: DNM2 as Red List (low evidence)
Cerebral Palsy v1.214 DNM2 Zornitza Stark Gene: dnm2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.213 TUBB4A Zornitza Stark Publications for gene: TUBB4A were set to 34531397; 33528536
Cerebral Palsy v1.212 TUBG1 Zornitza Stark Marked gene: TUBG1 as ready
Cerebral Palsy v1.212 TUBG1 Zornitza Stark Gene: tubg1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.212 TUBG1 Zornitza Stark Classified gene: TUBG1 as Red List (low evidence)
Cerebral Palsy v1.212 TUBG1 Zornitza Stark Gene: tubg1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.211 UBE3A Zornitza Stark Publications for gene: UBE3A were set to PMID: 33528536
Cerebral Palsy v1.210 ZBTB18 Zornitza Stark Marked gene: ZBTB18 as ready
Cerebral Palsy v1.210 ZBTB18 Zornitza Stark Gene: zbtb18 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.210 ZBTB18 Zornitza Stark Classified gene: ZBTB18 as Red List (low evidence)
Cerebral Palsy v1.210 ZBTB18 Zornitza Stark Gene: zbtb18 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.209 ZEB2 Zornitza Stark Publications for gene: ZEB2 were set to 33528536; 33098801
Cerebral Palsy v1.208 ITPR1 Zornitza Stark Publications for gene: ITPR1 were set to 28826917; 25981959; 22986007
Cerebral Palsy v1.207 SPTBN2 Zornitza Stark Publications for gene: SPTBN2 were set to 31066025; 25981959; 31721007
Cerebral Palsy v1.206 AP4M1 Zornitza Stark Publications for gene: AP4M1 were set to 19559397; 24065543; 25496299
Cerebral Palsy v1.205 ACAD9 Zornitza Stark Marked gene: ACAD9 as ready
Cerebral Palsy v1.205 ACAD9 Zornitza Stark Gene: acad9 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.205 ACAD9 Zornitza Stark Classified gene: ACAD9 as Red List (low evidence)
Cerebral Palsy v1.205 ACAD9 Zornitza Stark Gene: acad9 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.204 ARMC9 Zornitza Stark Marked gene: ARMC9 as ready
Cerebral Palsy v1.204 ARMC9 Zornitza Stark Gene: armc9 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.204 ARMC9 Zornitza Stark Classified gene: ARMC9 as Red List (low evidence)
Cerebral Palsy v1.204 ARMC9 Zornitza Stark Gene: armc9 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.203 ARSA Zornitza Stark Marked gene: ARSA as ready
Cerebral Palsy v1.203 ARSA Zornitza Stark Gene: arsa has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.203 ARSA Zornitza Stark Classified gene: ARSA as Amber List (moderate evidence)
Cerebral Palsy v1.203 ARSA Zornitza Stark Gene: arsa has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.202 ASL Zornitza Stark Marked gene: ASL as ready
Cerebral Palsy v1.202 ASL Zornitza Stark Gene: asl has been classified as Red List (Low Evidence).
Cerebral Palsy v1.202 ASL Zornitza Stark Classified gene: ASL as Red List (low evidence)
Cerebral Palsy v1.202 ASL Zornitza Stark Gene: asl has been classified as Red List (Low Evidence).
Cerebral Palsy v1.201 ASPA Zornitza Stark Marked gene: ASPA as ready
Cerebral Palsy v1.201 ASPA Zornitza Stark Gene: aspa has been classified as Red List (Low Evidence).
Cerebral Palsy v1.201 ASPA Zornitza Stark Classified gene: ASPA as Red List (low evidence)
Cerebral Palsy v1.201 ASPA Zornitza Stark Gene: aspa has been classified as Red List (Low Evidence).
Cerebral Palsy v1.200 ATR Zornitza Stark Marked gene: ATR as ready
Cerebral Palsy v1.200 ATR Zornitza Stark Gene: atr has been classified as Red List (Low Evidence).
Cerebral Palsy v1.200 ATR Zornitza Stark Classified gene: ATR as Red List (low evidence)
Cerebral Palsy v1.200 ATR Zornitza Stark Gene: atr has been classified as Red List (Low Evidence).
Cerebral Palsy v1.199 B4GALNT1 Zornitza Stark Marked gene: B4GALNT1 as ready
Cerebral Palsy v1.199 B4GALNT1 Zornitza Stark Gene: b4galnt1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.199 B4GALNT1 Zornitza Stark Classified gene: B4GALNT1 as Red List (low evidence)
Cerebral Palsy v1.199 B4GALNT1 Zornitza Stark Gene: b4galnt1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.198 CACNA1B Zornitza Stark Marked gene: CACNA1B as ready
Cerebral Palsy v1.198 CACNA1B Zornitza Stark Gene: cacna1b has been classified as Red List (Low Evidence).
Cerebral Palsy v1.198 CACNA1B Zornitza Stark Classified gene: CACNA1B as Red List (low evidence)
Cerebral Palsy v1.198 CACNA1B Zornitza Stark Gene: cacna1b has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.6013 DPYD Zornitza Stark Marked gene: DPYD as ready
Intellectual disability syndromic and non-syndromic v0.6013 DPYD Zornitza Stark Gene: dpyd has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6013 DPYD Zornitza Stark Phenotypes for gene: DPYD were changed from to Dihydropyrimidine dehydrogenase deficiency (MIM#274270)
Intellectual disability syndromic and non-syndromic v0.6012 DPYD Zornitza Stark Publications for gene: DPYD were set to
Intellectual disability syndromic and non-syndromic v0.6011 DPYD Zornitza Stark Mode of inheritance for gene: DPYD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6010 DPYD Zornitza Stark Classified gene: DPYD as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.6010 DPYD Zornitza Stark Gene: dpyd has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6009 DMD Zornitza Stark Marked gene: DMD as ready
Intellectual disability syndromic and non-syndromic v0.6009 DMD Zornitza Stark Gene: dmd has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6009 DMD Zornitza Stark Phenotypes for gene: DMD were changed from to Duchenne muscular dystrophy MIM#310200
Intellectual disability syndromic and non-syndromic v0.6008 DMD Zornitza Stark Mode of inheritance for gene: DMD was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.6007 DMD Zornitza Stark Tag SV/CNV tag was added to gene: DMD.
Intellectual disability syndromic and non-syndromic v0.6007 DMD Zornitza Stark reviewed gene: DMD: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Duchenne muscular dystrophy MIM#310200; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.6007 SSR4 Katie Thompson changed review comment from: Decipher - only disorder of glycosolation (XLR)
ORPHA:370927
OMIM: 300934. 2 good quality papers, one with 4 unrelated families, two with mendelian inheritance. Evidence of less severe phenotype in heterozygote females
Western blot showed complete loss of protein; to: Decipher - disorder of glycosolation (XLR), strong evidence
ORPHA:370927 GenCC strong. Not in gene2phenotype.
OMIM: 300934. 2 good quality papers, one with 4 unrelated families, two with mendelian inheritance. Evidence of less severe phenotype in heterozygote females
Western blot showed complete loss of protein. All variants caused loss of function mainly from premature termination.
Intellectual disability syndromic and non-syndromic v0.6007 COG7 Zornitza Stark Marked gene: COG7 as ready
Intellectual disability syndromic and non-syndromic v0.6007 COG7 Zornitza Stark Gene: cog7 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6007 COG7 Zornitza Stark Phenotypes for gene: COG7 were changed from to Congenital disorder of glycosylation, type IIe , MIM#608779
Intellectual disability syndromic and non-syndromic v0.6006 COG7 Zornitza Stark Publications for gene: COG7 were set to
Intellectual disability syndromic and non-syndromic v0.6005 COG7 Zornitza Stark Mode of inheritance for gene: COG7 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6005 COG7 Zornitza Stark Mode of inheritance for gene: COG7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6004 COG7 Zornitza Stark reviewed gene: COG7: Rating: GREEN; Mode of pathogenicity: None; Publications: 15107842, 17356545, 28883096; Phenotypes: Congenital disorder of glycosylation, type IIe , MIM#608779; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6004 SSR4 Katie Thompson changed review comment from: PMID: 24218363; 26264460
SSR4
Decipher - only disorder of glycosolation (XLR)
ORPHA:370927
OMIM: 300934. 2 good quality papers, one with 4 unrelated families, two with mendelian inheritance. Evidence of less severe phenotype in heterozygote females; to: Decipher - only disorder of glycosolation (XLR)
ORPHA:370927
OMIM: 300934. 2 good quality papers, one with 4 unrelated families, two with mendelian inheritance. Evidence of less severe phenotype in heterozygote females
Western blot showed complete loss of protein
Intellectual disability syndromic and non-syndromic v0.6004 COG1 Zornitza Stark Marked gene: COG1 as ready
Intellectual disability syndromic and non-syndromic v0.6004 COG1 Zornitza Stark Gene: cog1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6004 COG1 Zornitza Stark Phenotypes for gene: COG1 were changed from to Congenital disorder of glycosylation, type IIg, MIM# 611209
Intellectual disability syndromic and non-syndromic v0.6003 COG1 Zornitza Stark Publications for gene: COG1 were set to
Intellectual disability syndromic and non-syndromic v0.6002 COG1 Zornitza Stark Mode of inheritance for gene: COG1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6001 SSR4 Katie Thompson reviewed gene: SSR4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 24218363, 26264460; Phenotypes: intellectual disabilities, hypotonia, microcephaly, seizures, Feeding problems, Facial dysmorphism, Gastrointestinal abnormalities, Failure to thrive, strabismus; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.6001 COG1 Zornitza Stark reviewed gene: COG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 16537452, 19008299, 17904886, 11980916; Phenotypes: Congenital disorder of glycosylation, type IIg, MIM# 611209; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6001 COL4A1 Zornitza Stark Marked gene: COL4A1 as ready
Intellectual disability syndromic and non-syndromic v0.6001 COL4A1 Zornitza Stark Gene: col4a1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6001 COL4A1 Zornitza Stark Phenotypes for gene: COL4A1 were changed from to COL4A1-related disorder MONDO:0800461
Intellectual disability syndromic and non-syndromic v0.6000 COL4A1 Zornitza Stark Publications for gene: COL4A1 were set to
Intellectual disability syndromic and non-syndromic v0.5999 COL4A1 Zornitza Stark Mode of inheritance for gene: COL4A1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5998 SNAP29 Zornitza Stark Marked gene: SNAP29 as ready
Intellectual disability syndromic and non-syndromic v0.5998 SNAP29 Zornitza Stark Gene: snap29 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5998 SNAP29 Zornitza Stark Phenotypes for gene: SNAP29 were changed from to Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome (MIM#609528)
Intellectual disability syndromic and non-syndromic v0.5997 SNAP29 Zornitza Stark Publications for gene: SNAP29 were set to
Intellectual disability syndromic and non-syndromic v0.5997 SNAP29 Zornitza Stark Mode of inheritance for gene: SNAP29 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5996 SNAP29 Zornitza Stark Mode of inheritance for gene: SNAP29 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5995 SNAP29 Zornitza Stark reviewed gene: SNAP29: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome (MIM#609528); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v1.6 GABRA4 Zornitza Stark Phenotypes for gene: GABRA4 were changed from Neurodevelopmental disorder MONDO:0700092, GABRA4-related to Neurodevelopmental disorder MONDO:0700092, GABRA4-related
Genetic Epilepsy v1.5 GABRA4 Zornitza Stark Phenotypes for gene: GABRA4 were changed from Developmental and epileptic encephalopathy MONDO:0100062, GABRA4-related to Neurodevelopmental disorder MONDO:0700092, GABRA4-related
Genetic Epilepsy v1.4 GABRA4 Zornitza Stark Classified gene: GABRA4 as Green List (high evidence)
Genetic Epilepsy v1.4 GABRA4 Zornitza Stark Gene: gabra4 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.3 GABRA4 Zornitza Stark Classified gene: GABRA4 as Green List (high evidence)
Genetic Epilepsy v1.3 GABRA4 Zornitza Stark Gene: gabra4 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.2 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 phenotypes: Neurodevelopmental disorder MONDO:0700092, GABRA4-related
Mendeliome v1.1800 GABRA4 Zornitza Stark Phenotypes for gene: GABRA4 were changed from Developmental and epileptic encephalopathy MONDO:0100062, GABRA4-related to Neurodevelopmental disorder MONDO:0700092, GABRA4-related
Mendeliome v1.1799 GABRA4 Zornitza Stark Publications for gene: GABRA4 were set to 35152403
Mendeliome v1.1798 GABRA4 Zornitza Stark Classified gene: GABRA4 as Green List (high evidence)
Mendeliome v1.1798 GABRA4 Zornitza Stark Gene: gabra4 has been classified as Green List (High Evidence).
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
Intellectual disability syndromic and non-syndromic v0.5995 GABRA4 Zornitza Stark Marked gene: GABRA4 as ready
Intellectual disability syndromic and non-syndromic v0.5995 GABRA4 Zornitza Stark Gene: gabra4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5995 GABRA4 Zornitza Stark Phenotypes for gene: GABRA4 were changed from Developmental delay; Intellectual disability; Epileptic seizures to Neurodevelopmental disorder MONDO:0700092, GABRA4-related
Intellectual disability syndromic and non-syndromic v0.5994 GABRA4 Zornitza Stark Classified gene: GABRA4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5994 GABRA4 Zornitza Stark Gene: gabra4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5993 GABRA4 Zornitza Stark reviewed gene: GABRA4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder MONDO:0700092, GABRA4-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5993 SNAP29 Gunjan Garg reviewed gene: SNAP29: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33977139, 30793783, 29051910; Phenotypes: cerebral dysgenesis, 609528, Global developmental delay, schizencephaly, polymicrogyria, intellectual disability, neurodevelopment delay; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.197 CEP290 Zornitza Stark Marked gene: CEP290 as ready
Cerebral Palsy v1.197 CEP290 Zornitza Stark Gene: cep290 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.197 CEP290 Zornitza Stark Classified gene: CEP290 as Red List (low evidence)
Cerebral Palsy v1.197 CEP290 Zornitza Stark Gene: cep290 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.196 COL6A3 Zornitza Stark Marked gene: COL6A3 as ready
Cerebral Palsy v1.196 COL6A3 Zornitza Stark Gene: col6a3 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.196 COL6A3 Zornitza Stark Classified gene: COL6A3 as Red List (low evidence)
Cerebral Palsy v1.196 COL6A3 Zornitza Stark Gene: col6a3 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.195 CYP2U1 Zornitza Stark Publications for gene: CYP2U1 were set to 33528536; 29761117; 23176821
Cerebral Palsy v1.194 CYP2U1 Clare van Eyk reviewed gene: CYP2U1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Spastic paraplegia 56, autosomal recessive, MIM#615030; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.194 COL6A3 Clare van Eyk gene: COL6A3 was added
gene: COL6A3 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: COL6A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COL6A3 were set to PMID: 38693247
Phenotypes for gene: COL6A3 were set to Dystonia 27, MIM#616411
Review for gene: COL6A3 was set to RED
Added comment: 2 individuals reported with biallelic variants in large-scale CP exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.194 CEP290 Clare van Eyk gene: CEP290 was added
gene: CEP290 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CEP290 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP290 were set to PMID: 38693247
Phenotypes for gene: CEP290 were set to Joubert syndrome 5, MIM#610188
Review for gene: CEP290 was set to RED
Added comment: 1 individual reported with biallelic variants (1 frameshift insertion, 1 splice) in large-scale CP exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.194 CACNA1B Clare van Eyk gene: CACNA1B was added
gene: CACNA1B was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CACNA1B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CACNA1B were set to PMID: 38693247
Phenotypes for gene: CACNA1B were set to Neurodevelopmental disorder with seizures and nonepileptic hyperkinetic movements, MIM#618497
Review for gene: CACNA1B was set to RED
Added comment: 1 individual reported with biallelic variants (1 missense, 1 splice) in large-scale CP exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.194 B4GALNT1 Clare van Eyk gene: B4GALNT1 was added
gene: B4GALNT1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: B4GALNT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: B4GALNT1 were set to PMID: 38693247
Phenotypes for gene: B4GALNT1 were set to Spastic paraplegia 26, autosomal recessive, MIM#609195
Review for gene: B4GALNT1 was set to RED
Added comment: 1 individual reported with homozygous frameshift variant in large-scale CP exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.194 ATR Clare van Eyk gene: ATR was added
gene: ATR was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ATR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATR were set to PMID: 38693247
Phenotypes for gene: ATR were set to Seckel syndrome, MIM#210600
Review for gene: ATR was set to RED
Added comment: 1 individual reported with biallelic splice variants in large-scale CP exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.194 ASPA Clare van Eyk gene: ASPA was added
gene: ASPA was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ASPA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ASPA were set to PMID: 38693247
Phenotypes for gene: ASPA were set to Canavan disease, MIM#271900
Review for gene: ASPA was set to RED
Added comment: 1 individual reported with biallelic P/LP variants (1 missense and 1 stopgain) in large-scale CP exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.194 AGA Clare van Eyk Deleted their review
Cerebral Palsy v1.194 AGA Clare van Eyk gene: AGA was added
gene: AGA was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: AGA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AGA were set to PMID: 38693247
Phenotypes for gene: AGA were set to Canavan disease, MIM#271900
Review for gene: AGA was set to RED
Added comment: Single individual with biallelic variants (1 missense, 1 stopgain) reported in large-scale CP exome sequencing study (PMID: 38693247). No detailed clinical information provided. Rapid progression typically observed.
Sources: Literature
Cerebral Palsy v1.194 ASL Clare van Eyk gene: ASL was added
gene: ASL was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ASL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ASL were set to PMID: 38693247
Phenotypes for gene: ASL were set to Argininosuccinic aciduria, MIM#207900
Review for gene: ASL was set to RED
Added comment: 1 individual with biallelic P variants reported in large-scale CP exome sequencing study (PMID: 38693247). No detailed clinical information provided.
Sources: Literature
Cerebral Palsy v1.194 ARSA Clare van Eyk gene: ARSA was added
gene: ARSA was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ARSA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARSA were set to PMID: 38693247
Phenotypes for gene: ARSA were set to Metachromatic leukodystrophy, MIM#250100
Review for gene: ARSA was set to AMBER
Added comment: 3 individuals with biallelic P/LP variants reported in large-scale CP exome sequencing study (PMID: 38693247). No detailed clinical information provided. MLD is associated with progressive neurologic dysfunction, however variable rate of progression.
Sources: Literature
Cerebral Palsy v1.194 ARMC9 Clare van Eyk gene: ARMC9 was added
gene: ARMC9 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ARMC9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARMC9 were set to PMID: 38693247
Phenotypes for gene: ARMC9 were set to Joubert syndrome 30, MIM#617622
Review for gene: ARMC9 was set to RED
Added comment: 1 individual with biallelic variants (1 stopgain, 1 missense) reported in large-scale exome sequencing study (PMID: 38693247).
Sources: Literature
Cerebral Palsy v1.194 ACAD9 Clare van Eyk gene: ACAD9 was added
gene: ACAD9 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ACAD9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACAD9 were set to PMID: 38693247
Phenotypes for gene: ACAD9 were set to Mitochondrial complex I deficiency, nuclear type 20, MIM#611126
Review for gene: ACAD9 was set to RED
Added comment: 1 individual with biallelic splice variants reported in large-scale exome sequencing study (PMID: 38693247). No functional assessement reported. No detailed clinical information provided.
Sources: Literature
Cerebral Palsy v1.194 AP4M1 Clare van Eyk reviewed gene: AP4M1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Spastic paraplegia 50, autosomal recessive, MIM# 612936; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.194 SPTBN2 Clare van Eyk reviewed gene: SPTBN2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Spinocerebellar ataxia 5 MIM#600224, Spinocerebellar ataxia, autosomal recessive 14 MIM#615386; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Cerebral Palsy v1.194 ITPR1 Clare van Eyk reviewed gene: ITPR1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Spinocerebellar ataxia 29, congenital nonprogressive MIM#117360; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.194 ZEB2 Clare van Eyk reviewed gene: ZEB2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Mowat-Wilson syndrome, MIM # 235730; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.194 ZBTB18 Clare van Eyk gene: ZBTB18 was added
gene: ZBTB18 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ZBTB18 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZBTB18 were set to PMID: 38693247
Phenotypes for gene: ZBTB18 were set to Intellectual developmental disorder, autosomal dominant 22, MIM#612337
Review for gene: ZBTB18 was set to AMBER
Added comment: 1 individual with mono-allelic missense variant reported in large-scale exome sequencing study (PMID: 38693247). No detailed clinical information provided. Spasticity, ataxia, hypotonia are reported features, but not diagnosed CP (PMID: 27598823).
Sources: Literature
Renal Tubulopathies and related disorders v1.14 MUT Zornitza Stark changed review comment from: Well established gene-disease association.; to: Well established gene-disease association. Associated with interstitial nephritis and chronic kidney failure.
Renal Tubulopathies and related disorders v1.14 MUT Zornitza Stark Marked gene: MUT as ready
Renal Tubulopathies and related disorders v1.14 MUT Zornitza Stark Gene: mut has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5993 COL4A1 Hali Van Niel reviewed gene: COL4A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30413629, 33912663, 36786861, 32042920; Phenotypes: COL4A1-related disorder MONDO:0800461, brain small vessel disease 1 with or without ocular anomalies MONDO:0008289, microangiopathy and leukoencephalopathy, pontine, autosomal dominant MONDO:0032814; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cerebral Palsy v1.194 UBE3A Clare van Eyk reviewed gene: UBE3A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Angelman syndrome, MIM #105830; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.194 TUBG1 Clare van Eyk gene: TUBG1 was added
gene: TUBG1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TUBG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBG1 were set to PMID: 38693247
Phenotypes for gene: TUBG1 were set to Cortical dysplasia, complex, with other brain malformations 4, MIM#615412
Review for gene: TUBG1 was set to RED
Added comment: 1 individual with a LP missense variant reported in large-scale exome sequencing study (PMID: 38693247).
Sources: Literature
Cerebral Palsy v1.194 TUBB4A Clare van Eyk reviewed gene: TUBB4A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Dystonia 4, torsion, autosomal dominant, MIM#128101, Leukodystrophy, hypomyelinating, 6, MIM#612438; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.194 TUBB2B Clare van Eyk reviewed gene: TUBB2B: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Cortical dysplasia, complex, with other brain malformations 7, MIM#610031; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.194 TSHR Clare van Eyk gene: TSHR was added
gene: TSHR was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TSHR was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TSHR were set to PMID: 38693247
Phenotypes for gene: TSHR were set to Hyperthyroidism, nonautoimmune, MIM#609152
Review for gene: TSHR was set to RED
Added comment: 2 individuals with LP variants reported in large-scale exome sequencing study (PMID: 38693247).
Sources: Literature
Cerebral Palsy v1.194 TSC2 Clare van Eyk gene: TSC2 was added
gene: TSC2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TSC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TSC2 were set to PMID: 38693247
Phenotypes for gene: TSC2 were set to Tuberous sclerosis-2, MIM#613254
Review for gene: TSC2 was set to RED
Added comment: 1 individual with splice variant reported in large-scale exome sequencing study (PMID: 38693247).
Sources: Literature
Cerebral Palsy v1.194 TOR1A Clare van Eyk gene: TOR1A was added
gene: TOR1A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TOR1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TOR1A were set to PMID: 38693247
Phenotypes for gene: TOR1A were set to Dystonia-1, torsion, MIM#128100
Review for gene: TOR1A was set to RED
Added comment: 1 individual with heterozygous in-frame deletion reported in large-scale exome sequencing study (PMID: 38693247).
Sources: Literature
Cerebral Palsy v1.194 TGM6 Clare van Eyk gene: TGM6 was added
gene: TGM6 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TGM6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TGM6 were set to PMID: 38693247
Phenotypes for gene: TGM6 were set to Spinocerebellar ataxia 35, MIM#613908
Review for gene: TGM6 was set to AMBER
Added comment: 2 individuals with LP/P variants reported in large-scale exome sequencing study (PMID: 38693247). No additional clinical information provided.

Age of onset of SCA35 is reported to be teenage-adult years.
Sources: Literature
Cerebral Palsy v1.194 TCF4 Clare van Eyk reviewed gene: TCF4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Pitt-Hopkins syndrome, MIM# 610954; Mode of inheritance: None
Cerebral Palsy v1.194 TBX6 Clare van Eyk gene: TBX6 was added
gene: TBX6 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TBX6 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TBX6 were set to PMID: 38693247
Phenotypes for gene: TBX6 were set to Spondylocostal dysostosis 5, MIM#122600
Review for gene: TBX6 was set to RED
Added comment: 1 individual with likely pathogenic missense variant reported in large-scale exome sequencing study (PMID: 38693247). No additional clinical information provided.
Sources: Literature
Cerebral Palsy v1.194 TBR1 Clare van Eyk gene: TBR1 was added
gene: TBR1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TBR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TBR1 were set to PMID: 38693247
Phenotypes for gene: TBR1 were set to Intellectual developmental disorder with autism and speech delay, MIM#606053
Review for gene: TBR1 was set to RED
Added comment: 1 individual with mono-allelic LOF (frameshift deletion) reported in large-scale exome sequencing study (PMID: 38693247). No additional clinical information provided.
Sources: Literature
Cerebral Palsy v1.194 TANC2 Clare van Eyk gene: TANC2 was added
gene: TANC2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TANC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TANC2 were set to PMID: 38693247
Phenotypes for gene: TANC2 were set to Intellectual developmental disorder with autistic features and language delay, with or without seizures, MIM#618906
Review for gene: TANC2 was set to RED
Added comment: 1 individual with mono-allelic splice variant reported in large-scale exome sequencing study (PMID: 38693247).
Sources: Literature
Cerebral Palsy v1.194 SYNGAP1 Clare van Eyk reviewed gene: SYNGAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Intellectual developmental disorder, autosomal dominant 5, MIM#612621; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.194 SPAST Clare van Eyk reviewed gene: SPAST: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.194 SOX10 Clare van Eyk gene: SOX10 was added
gene: SOX10 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SOX10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOX10 were set to PMID: 38693247
Phenotypes for gene: SOX10 were set to PCWH syndrome, MIM#609136; Waardenburg syndrome, type 2E, with or without neurologic involvement, MIM#611584
Review for gene: SOX10 was set to RED
Added comment: 1 individual with mono-allelic LOF (stopgain variant) reported in large-scale exome sequencing study (PMID: 38693247).
Sources: Literature
Cerebral Palsy v1.194 SON Clare van Eyk reviewed gene: SON: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 38693247, PMID: 37168776; Phenotypes: ZTTK syndrome MIM#617140; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.194 SMC3 Clare van Eyk gene: SMC3 was added
gene: SMC3 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SMC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMC3 were set to PMID: 38693247
Phenotypes for gene: SMC3 were set to Cornelia de Lange syndrome 3, MIM#610759
Review for gene: SMC3 was set to RED
Added comment: 1 individual with mono-allelic LOF (frameshift deletion) reported in large-scale exome sequencing study (PMID: 38693247).
Sources: Literature
Cerebral Palsy v1.194 SMARCA4 Clare van Eyk gene: SMARCA4 was added
gene: SMARCA4 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SMARCA4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMARCA4 were set to PMID: 38693247
Phenotypes for gene: SMARCA4 were set to Coffin-Siris syndrome 4, MIM#614609
Review for gene: SMARCA4 was set to RED
Added comment: 1 individual with mono-allelic splice variant reported in large-scale exome sequencing study (PMID: 38693247). No detailed clinical information provided.
Sources: Literature
Cerebral Palsy v1.194 SMARCA2 Clare van Eyk gene: SMARCA2 was added
gene: SMARCA2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SMARCA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMARCA2 were set to PMID: 38693247
Phenotypes for gene: SMARCA2 were set to Blepharophimosis-impaired intellectual development syndrome, MIM#619293; Nicolaides-Baraitser syndrome, MIM#601358
Review for gene: SMARCA2 was set to RED
Added comment: 1 individual with mono-allelic missense variant reported in large-scale exome sequencing study (PMID: 38693247).
Sources: Literature
Cerebral Palsy v1.194 SLC6A5 Clare van Eyk gene: SLC6A5 was added
gene: SLC6A5 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SLC6A5 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SLC6A5 were set to PMID: 38693247
Phenotypes for gene: SLC6A5 were set to Hyperekplexia 3, MIM#614618
Review for gene: SLC6A5 was set to AMBER
Added comment: 2 individuals with mono-allelic pathogenic stopgain variants reported in large-scale exome sequencing study (PMID: 38693247).
Sources: Literature
Cerebral Palsy v1.194 SLC1A2 Clare van Eyk gene: SLC1A2 was added
gene: SLC1A2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SLC1A2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC1A2 were set to PMID: 38693247; PMID:33528536
Phenotypes for gene: SLC1A2 were set to Developmental and epileptic encephalopathy 41, MIM#617105
Review for gene: SLC1A2 was set to AMBER
Added comment: 1 individual with mono-allelic stopgain variant reported in large-scale exome sequencing study (PMID: 38693247). 1 individual with mono-allelic de novo missense variant reported in large retrospective analysis of WES data from a clinical laboratory referral cohort and healthcare cohort (PMID:33528536).
Sources: Literature
Cerebral Palsy v1.194 SIK1 Clare van Eyk gene: SIK1 was added
gene: SIK1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SIK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SIK1 were set to PMID: 38693247
Phenotypes for gene: SIK1 were set to Developmental and epileptic encephalopathy 30, MIM#616341
Review for gene: SIK1 was set to RED
Added comment: 1 individual with mono-allelic missense variant reported in large-scale exome sequencing study (PMID: 38693247).
Sources: Literature
Cerebral Palsy v1.194 SGCE Clare van Eyk gene: SGCE was added
gene: SGCE was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SGCE was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SGCE were set to PMID: 38693247
Phenotypes for gene: SGCE were set to Dystonia-11, myoclonic, MIM#159900
Review for gene: SGCE was set to RED
Added comment: 1 individual with mono-allelic LOF (frameshift deletion) reported in large-scale exome sequencing study (PMID: 38693247).
Sources: Literature
Cerebral Palsy v1.194 PHIP Clare van Eyk edited their review of gene: PHIP: Added comment: 2 individuals reported with cerebral palsy and P/LP splice variants in PHIP in a large retrospective analysis of WES data from a clinical laboratory referral cohort and healthcare cohort (PMID:33528536).; Changed rating: AMBER; Changed publications: PMID: 38693247, PMID:33528536
Cerebral Palsy v1.194 SETD2 Clare van Eyk gene: SETD2 was added
gene: SETD2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SETD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SETD2 were set to PMID: 38693247; 33528536
Phenotypes for gene: SETD2 were set to Intellectual developmental disorder, autosomal dominant 70, MIM#620157; Luscan-Lumish syndrome, MIM#61683; Rabin-Pappas syndrome, MIM#620155
Review for gene: SETD2 was set to AMBER
Added comment: 1 individual with mono-allelic LOF (frameshift deletion) reported in large-scale exome sequencing study (PMID: 38693247). No detailed clinical information provided.

1 individual reported with cerebral palsy and maternally inherited pathogenic stopgain variant in a large retrospective analysis of WES data from a clinical laboratory referral cohort and healthcare cohort (PMID:33528536).
Sources: Literature
Cerebral Palsy v1.194 SETBP1 Clare van Eyk gene: SETBP1 was added
gene: SETBP1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SETBP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SETBP1 were set to PMID: 38693247
Phenotypes for gene: SETBP1 were set to Intellectual developmental disorder, autosomal dominant 29, MIM#616078; Schinzel-Giedion midface retraction syndrome, MIM#269150
Review for gene: SETBP1 was set to RED
Added comment: 1 individual with mono-allelic stopgain variant reported in large-scale exome sequencing study (PMID: 38693247).
Sources: Literature
Cerebral Palsy v1.194 SCN8A Clare van Eyk reviewed gene: SCN8A: Rating: GREEN; Mode of pathogenicity: None; Publications: 38693247; Phenotypes: Epileptic encephalopathy 13 MIM# 614558, Cognitive impairment with or without cerebellar ataxia MIM# 614306; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.194 SCN2A Clare van Eyk edited their review of gene: SCN2A: Added comment: 3 additional individuals with mono-allelic P/LP variants (2 missense, 1 stopgain) reported in large-scale exome sequencing study (PMID: 38693247).; Changed publications: 33528536, 29761117, 34114234, 38693247
Cerebral Palsy v1.194 SCN1A Clare van Eyk commented on gene: SCN1A: 1 additional individual with LP missense variant reported in large-scale exome sequencing study (PMID: 38693247).
Cerebral Palsy v1.194 PPM1D Clare van Eyk gene: PPM1D was added
gene: PPM1D was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PPM1D was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPM1D were set to PMID: 38693247
Phenotypes for gene: PPM1D were set to Jansen-de Vries syndrome, MIM#617450
Review for gene: PPM1D was set to RED
Added comment: 1 individual with mono-allelic splice variant reported in large-scale exome sequencing study (PMID: 38693247).
Sources: Literature
Cerebral Palsy v1.194 PHIP Clare van Eyk gene: PHIP was added
gene: PHIP was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PHIP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PHIP were set to PMID: 38693247
Phenotypes for gene: PHIP were set to Chung-Jansen syndrome, MIM#617991
Review for gene: PHIP was set to RED
Added comment: 1 individual with monoallelic LOF (frameshift deletion) reported in large-scale exome sequencing study (PMID: 38693247). No detailed clinical information provided.

LOF variants in PHIP are associated with developmental delay, intellectual disability, anxiety, hypotonia, poor balance, obesity, and dysmorphic features.
Sources: Literature
Cerebral Palsy v1.194 PACS1 Clare van Eyk gene: PACS1 was added
gene: PACS1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PACS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PACS1 were set to PMID: 38693247
Phenotypes for gene: PACS1 were set to Schuurs-Hoeijmakers syndrome, MIM#615009
Review for gene: PACS1 was set to AMBER
Added comment: 2 individuals with mono-allelic variants (1 missense, 1 splice) reported in large-scale exome sequencing study (PMID: 38693247). No detailed clinical information provided. PACS1 variants are associated with hypotonia starting in the new-born period which may persist throughout childhood.
Sources: Literature
Cerebral Palsy v1.194 NSD2 Clare van Eyk gene: NSD2 was added
gene: NSD2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: NSD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NSD2 were set to PMID: 38693247
Phenotypes for gene: NSD2 were set to Rauch-Steindl syndrome, MIM#619695
Review for gene: NSD2 was set to RED
Added comment: 1 individual with mono-allelic LOF variant (frameshift) reported in large-scale exome sequencing study (PMID: 38693247).
Sources: Literature
Cerebral Palsy v1.194 NSD1 Clare van Eyk gene: NSD1 was added
gene: NSD1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: NSD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NSD1 were set to PMID: 38693247
Phenotypes for gene: NSD1 were set to Sotos syndrome, MIM#117550
Review for gene: NSD1 was set to RED
Added comment: 2 individuals with mono-allelic LOF (1 stopgain, 1 frameshift deletion) reported in large-scale exome sequencing study (PMID: 38693247). No additional clinical information provided.
Sources: Literature
Cerebral Palsy v1.194 NR2F1 Clare van Eyk gene: NR2F1 was added
gene: NR2F1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: NR2F1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NR2F1 were set to PMID: 38693247
Phenotypes for gene: NR2F1 were set to Bosch-Boonstra-Schaaf optic atrophy syndrome, MIM#615722; NR2F1-related neurodevelopmental disorder
Review for gene: NR2F1 was set to RED
Added comment: 1 individual with mono-allelic missense variant reported in large-scale exome sequencing study (PMID: 38693247). No detailed clinical information provided.
Sources: Literature
Cerebral Palsy v1.194 NOTCH1 Clare van Eyk gene: NOTCH1 was added
gene: NOTCH1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: NOTCH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NOTCH1 were set to PMID: 38693247
Phenotypes for gene: NOTCH1 were set to Adams-Oliver syndrome 5, MIM#616028
Review for gene: NOTCH1 was set to AMBER
Added comment: 3 individuals with mono-allelic P/LP variants (1 splice, 1 stopgain, 1 missense) reported in large-scale exome sequencing study (PMID: 38693247). No detailed clinical information provided.
Sources: Literature
Cerebral Palsy v1.194 NFIB Clare van Eyk gene: NFIB was added
gene: NFIB was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: NFIB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NFIB were set to PMID: 38693247
Phenotypes for gene: NFIB were set to Macrocephaly, acquired, with impaired intellectual development, MIM#618286
Review for gene: NFIB was set to RED
Added comment: 1 individual with mono-allelic LOF (frameshift deletion) reported in large-scale exome sequencing study (PMID: 38693247).
Sources: Literature
Cerebral Palsy v1.194 NFE2L2 Clare van Eyk gene: NFE2L2 was added
gene: NFE2L2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: NFE2L2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NFE2L2 were set to PMID: 38693247
Phenotypes for gene: NFE2L2 were set to Immunodeficiency, developmental delay, and hypohomocysteinemia , MIM#617744
Review for gene: NFE2L2 was set to RED
Added comment: 1 individual with mono-allelic stopgain variant reported in large-scale exome sequencing study (PMID: 38693247). No detailed clinical information provided.
Sources: Literature
Cerebral Palsy v1.194 NEFL Clare van Eyk gene: NEFL was added
gene: NEFL was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: NEFL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: NEFL were set to Charcot-Marie-Tooth disease, dominant intermediate G, MIM#617882
Review for gene: NEFL was set to RED
Added comment: 1 individual with mono-allelic stopgain variant and cerebral palsy reported in large-scale exome sequencing study. Detailed clinical information not provided.
Sources: Literature
Cerebral Palsy v1.194 NALCN Clare van Eyk edited their review of gene: NALCN: Added comment: 1 additional individual with mono-allelic LP splice variant and cerebral palsy reported in large-scale exome sequencing study. Detailed clinical information not provided.; Changed publications: PMID:33528536, PMID:34364746, PMID: 38693247
Intellectual disability syndromic and non-syndromic v0.5993 CLN6 Zornitza Stark Marked gene: CLN6 as ready
Intellectual disability syndromic and non-syndromic v0.5993 CLN6 Zornitza Stark Gene: cln6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5993 CLN6 Zornitza Stark Phenotypes for gene: CLN6 were changed from to Ceroid lipofuscinosis, neuronal, 6, MIM# 601780
Intellectual disability syndromic and non-syndromic v0.5992 CLN6 Zornitza Stark Mode of inheritance for gene: CLN6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5991 CLN6 Zornitza Stark reviewed gene: CLN6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ceroid lipofuscinosis, neuronal, 6, MIM# 601780; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5991 CLN3 Zornitza Stark Marked gene: CLN3 as ready
Intellectual disability syndromic and non-syndromic v0.5991 CLN3 Zornitza Stark Gene: cln3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5991 CLN3 Zornitza Stark Phenotypes for gene: CLN3 were changed from to Ceroid lipofuscinosis, neuronal, 3 MIM#204200
Intellectual disability syndromic and non-syndromic v0.5990 CLN3 Zornitza Stark Mode of inheritance for gene: CLN3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5989 CLN3 Zornitza Stark reviewed gene: CLN3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ceroid lipofuscinosis, neuronal, 3 MIM#204200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5989 CHD7 Zornitza Stark Marked gene: CHD7 as ready
Intellectual disability syndromic and non-syndromic v0.5989 CHD7 Zornitza Stark Gene: chd7 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5989 CHD7 Zornitza Stark Phenotypes for gene: CHD7 were changed from to CHARGE syndrome, MIM# 214800
Intellectual disability syndromic and non-syndromic v0.5988 CHD7 Zornitza Stark Mode of inheritance for gene: CHD7 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5987 CHD7 Zornitza Stark reviewed gene: CHD7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: CHARGE syndrome, MIM# 214800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5987 CC2D2A Zornitza Stark Marked gene: CC2D2A as ready
Intellectual disability syndromic and non-syndromic v0.5987 CC2D2A Zornitza Stark Gene: cc2d2a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5987 CC2D2A Zornitza Stark Phenotypes for gene: CC2D2A were changed from to COACH syndrome 2, MIM# 619111; Joubert syndrome 9, MIM#612285; Meckel syndrome 6, MIM#612284
Intellectual disability syndromic and non-syndromic v0.5986 CC2D2A Zornitza Stark Mode of inheritance for gene: CC2D2A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5985 CC2D2A Zornitza Stark reviewed gene: CC2D2A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: COACH syndrome 2, MIM# 619111, Joubert syndrome 9, 612285, Meckel syndrome 6, 612284; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5985 CBL Zornitza Stark Marked gene: CBL as ready
Intellectual disability syndromic and non-syndromic v0.5985 CBL Zornitza Stark Gene: cbl has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5985 CBL Zornitza Stark Mode of pathogenicity for gene: CBL 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
Intellectual disability syndromic and non-syndromic v0.5985 CBL Zornitza Stark Phenotypes for gene: CBL were changed from to CBL-related disorder MONDO:0013308
Intellectual disability syndromic and non-syndromic v0.5984 CBL Zornitza Stark Publications for gene: CBL were set to
Intellectual disability syndromic and non-syndromic v0.5983 CBL Zornitza Stark Mode of inheritance for gene: CBL was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5982 CACNA1A Zornitza Stark Marked gene: CACNA1A as ready
Intellectual disability syndromic and non-syndromic v0.5982 CACNA1A Zornitza Stark Gene: cacna1a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5982 CACNA1A Zornitza Stark Phenotypes for gene: CACNA1A were changed from to developmental and epileptic encephalopathy, 42 MONDO:0014917
Intellectual disability syndromic and non-syndromic v0.5981 CACNA1A Zornitza Stark Publications for gene: CACNA1A were set to
Intellectual disability syndromic and non-syndromic v0.5980 CACNA1A Zornitza Stark Mode of inheritance for gene: CACNA1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5979 C12orf65 Zornitza Stark Marked gene: C12orf65 as ready
Intellectual disability syndromic and non-syndromic v0.5979 C12orf65 Zornitza Stark Gene: c12orf65 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5979 C12orf65 Zornitza Stark Phenotypes for gene: C12orf65 were changed from to hereditary spastic paraplegia 55 MONDO:0014020
Intellectual disability syndromic and non-syndromic v0.5978 C12orf65 Zornitza Stark Publications for gene: C12orf65 were set to
Intellectual disability syndromic and non-syndromic v0.5977 C12orf65 Zornitza Stark Mode of inheritance for gene: C12orf65 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5976 BTD Zornitza Stark Marked gene: BTD as ready
Intellectual disability syndromic and non-syndromic v0.5976 BTD Zornitza Stark Gene: btd has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5976 BTD Zornitza Stark Phenotypes for gene: BTD were changed from to biotinidase deficiency MONDO:0009665
Intellectual disability syndromic and non-syndromic v0.5975 BTD Zornitza Stark Publications for gene: BTD were set to
Intellectual disability syndromic and non-syndromic v0.5974 BTD Zornitza Stark Mode of inheritance for gene: BTD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.194 BSCL2 Zornitza Stark Marked gene: BSCL2 as ready
Cerebral Palsy v1.194 BSCL2 Zornitza Stark Gene: bscl2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.194 BSCL2 Zornitza Stark Classified gene: BSCL2 as Red List (low evidence)
Cerebral Palsy v1.194 BSCL2 Zornitza Stark Gene: bscl2 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5973 BSCL2 Zornitza Stark Marked gene: BSCL2 as ready
Intellectual disability syndromic and non-syndromic v0.5973 BSCL2 Zornitza Stark Gene: bscl2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5973 BSCL2 Zornitza Stark Phenotypes for gene: BSCL2 were changed from to congenital generalized lipodystrophy type 2 MONDO:0010020
Intellectual disability syndromic and non-syndromic v0.5972 BSCL2 Zornitza Stark Publications for gene: BSCL2 were set to
Intellectual disability syndromic and non-syndromic v0.5971 BSCL2 Zornitza Stark Mode of inheritance for gene: BSCL2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5970 BCS1L Zornitza Stark Marked gene: BCS1L as ready
Intellectual disability syndromic and non-syndromic v0.5970 BCS1L Zornitza Stark Gene: bcs1l has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5970 BCS1L Zornitza Stark Phenotypes for gene: BCS1L were changed from to Bjornstad syndrome MONDO:0009872
Intellectual disability syndromic and non-syndromic v0.5969 BCS1L Zornitza Stark Publications for gene: BCS1L were set to
Intellectual disability syndromic and non-syndromic v0.5968 BCS1L Zornitza Stark Mode of inheritance for gene: BCS1L was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5967 BCKDHB Zornitza Stark Marked gene: BCKDHB as ready
Intellectual disability syndromic and non-syndromic v0.5967 BCKDHB Zornitza Stark Gene: bckdhb has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5967 BCKDHB Zornitza Stark Phenotypes for gene: BCKDHB were changed from to maple syrup urine disease type 1B MONDO:0023692
Intellectual disability syndromic and non-syndromic v0.5966 BCKDHB Zornitza Stark Publications for gene: BCKDHB were set to
Intellectual disability syndromic and non-syndromic v0.5965 BCKDHB Zornitza Stark Mode of inheritance for gene: BCKDHB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5964 BCKDHA Zornitza Stark Marked gene: BCKDHA as ready
Intellectual disability syndromic and non-syndromic v0.5964 BCKDHA Zornitza Stark Gene: bckdha has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5964 BCKDHA Zornitza Stark Phenotypes for gene: BCKDHA were changed from to maple syrup urine disease type 1A MONDO:0023691
Intellectual disability syndromic and non-syndromic v0.5963 BCKDHA Zornitza Stark Publications for gene: BCKDHA were set to
Intellectual disability syndromic and non-syndromic v0.5962 BCKDHA Zornitza Stark Mode of inheritance for gene: BCKDHA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5961 BBS2 Zornitza Stark Marked gene: BBS2 as ready
Intellectual disability syndromic and non-syndromic v0.5961 BBS2 Zornitza Stark Gene: bbs2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5961 BBS2 Zornitza Stark Phenotypes for gene: BBS2 were changed from to Bardet-Biedl syndrome 2 MONDO:0014432
Intellectual disability syndromic and non-syndromic v0.5960 BBS2 Zornitza Stark Publications for gene: BBS2 were set to
Intellectual disability syndromic and non-syndromic v0.5959 BBS2 Zornitza Stark Mode of inheritance for gene: BBS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5958 BBS12 Zornitza Stark Marked gene: BBS12 as ready
Intellectual disability syndromic and non-syndromic v0.5958 BBS12 Zornitza Stark Gene: bbs12 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5958 BBS12 Zornitza Stark Phenotypes for gene: BBS12 were changed from to Bardet-Biedl syndrome 12 MONDO:0014440
Intellectual disability syndromic and non-syndromic v0.5957 BBS12 Zornitza Stark Publications for gene: BBS12 were set to
Intellectual disability syndromic and non-syndromic v0.5956 BBS12 Zornitza Stark Mode of inheritance for gene: BBS12 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5955 BBS10 Zornitza Stark Marked gene: BBS10 as ready
Intellectual disability syndromic and non-syndromic v0.5955 BBS10 Zornitza Stark Gene: bbs10 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5955 BBS10 Zornitza Stark Phenotypes for gene: BBS10 were changed from to Bardet-Biedl syndrome 10 MONDO:0014438
Intellectual disability syndromic and non-syndromic v0.5954 BBS10 Zornitza Stark Publications for gene: BBS10 were set to
Intellectual disability syndromic and non-syndromic v0.5953 BBS10 Zornitza Stark Mode of inheritance for gene: BBS10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5952 BBS1 Zornitza Stark Marked gene: BBS1 as ready
Intellectual disability syndromic and non-syndromic v0.5952 BBS1 Zornitza Stark Gene: bbs1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5952 BBS1 Zornitza Stark Phenotypes for gene: BBS1 were changed from to Bardet-Biedl syndrome 1 MONDO:0008854
Intellectual disability syndromic and non-syndromic v0.5951 BBS1 Zornitza Stark Publications for gene: BBS1 were set to
Intellectual disability syndromic and non-syndromic v0.5950 BBS1 Zornitza Stark Mode of inheritance for gene: BBS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5949 TBCE Zornitza Stark Marked gene: TBCE as ready
Intellectual disability syndromic and non-syndromic v0.5949 TBCE Zornitza Stark Gene: tbce has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5949 TBCE Zornitza Stark Phenotypes for gene: TBCE were changed from to Encephalopathy, progressive, with amyotrophy and optic atrophy MIM:617207; Hypoparathyroidism-retardation-dysmorphism syndrome MIM:241410
Intellectual disability syndromic and non-syndromic v0.5948 TBCE Zornitza Stark Publications for gene: TBCE were set to
Intellectual disability syndromic and non-syndromic v0.5947 TBCE Zornitza Stark Mode of inheritance for gene: TBCE was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5946 SLC25A1 Zornitza Stark Marked gene: SLC25A1 as ready
Intellectual disability syndromic and non-syndromic v0.5946 SLC25A1 Zornitza Stark Gene: slc25a1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5946 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
Intellectual disability syndromic and non-syndromic v0.5945 SLC25A1 Zornitza Stark Publications for gene: SLC25A1 were set to
Intellectual disability syndromic and non-syndromic v0.5944 SLC25A1 Zornitza Stark Mode of inheritance for gene: SLC25A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5943 SLC25A1 Zornitza Stark reviewed gene: SLC25A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; 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
Cerebral Palsy v1.193 MYH2 Clare van Eyk gene: MYH2 was added
gene: MYH2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MYH2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MYH2 were set to PMID: 38693247
Phenotypes for gene: MYH2 were set to Congenital myopathy 6 with ophthalmoplegia, MIM#605637
Review for gene: MYH2 was set to RED
Added comment: 1 individual with mono-allelic stopgain variant and cerebral palsy reported in large-scale exome sequencing study. Detailed clinical information not provided.
Sources: Literature
Cerebral Palsy v1.193 MFN2 Clare van Eyk reviewed gene: MFN2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Charcot-Marie-Tooth disease, axonal, type 2A2A MIM#609260, Hereditary motor and sensory neuropathy VIA MIM#601152; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.193 MED13L Clare van Eyk gene: MED13L was added
gene: MED13L was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MED13L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MED13L were set to PMID: 38693247
Phenotypes for gene: MED13L were set to Impaired intellectual development and distinctive facial features with or without cardiac defects, OMIM#616789
Review for gene: MED13L was set to AMBER
Added comment: 1 individual with mono-allelic stopgain variant and cerebral palsy reported in large-scale exome sequencing study. Detailed clinical information not provided.
Sources: Literature
Cerebral Palsy v1.193 MBD5 Clare van Eyk gene: MBD5 was added
gene: MBD5 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MBD5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MBD5 were set to PMID: 38693247
Phenotypes for gene: MBD5 were set to Intellectual developmental disorder, autosomal dominant 1, MIM#156200
Review for gene: MBD5 was set to AMBER
Added comment: 1 individuals with mono-allelic stopgain variants and cerebral palsy reported in large-scale exome sequencing study. Detailed clinical information not provided.
Sources: Literature
Cerebral Palsy v1.193 MACF1 Clare van Eyk gene: MACF1 was added
gene: MACF1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MACF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MACF1 were set to PMID: 38693247
Phenotypes for gene: MACF1 were set to Lissencephaly 9 with complex brainstem malformation, MIM#618325
Review for gene: MACF1 was set to AMBER
Added comment: 1 individual with mono-allelic LP missense variant and cerebral palsy reported in large-scale exome sequencing study. Detailed clinical information not provided. Spasticity and involuntary movements described in some cases.
Sources: Literature
Cerebral Palsy v1.193 KMT2D Clare van Eyk gene: KMT2D was added
gene: KMT2D was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: KMT2D was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KMT2D were set to PMID: 38693247
Phenotypes for gene: KMT2D were set to Kabuki syndrome 1, MIM#147920
Review for gene: KMT2D was set to AMBER
Added comment: 2 individuals with mono-allelic splice variants and cerebral palsy reported in large-scale exome sequencing study. Detailed clinical information not provided.
Sources: Literature
Cerebral Palsy v1.193 KMT2B Clare van Eyk reviewed gene: KMT2B: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Dystonia 28, childhood-onset MIM#617284, Intellectual developmental disorder, autosomal dominant MIM#619934; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.193 KMT2A Clare van Eyk reviewed gene: KMT2A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Wiedemann-Steiner syndrome - #605130; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.193 KIF1A Clare van Eyk reviewed gene: KIF1A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Spastic paraplegia 30, autosomal dominant, MIM# 610357; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.193 KIDINS220 Clare van Eyk reviewed gene: KIDINS220: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Spastic paraplegia, intellectual disability, nystagmus, and obesity - #617296; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.193 KCNT1 Clare van Eyk reviewed gene: KCNT1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Developmental and epileptic encephalopathy MIM#614959; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.193 KCNQ5 Clare van Eyk gene: KCNQ5 was added
gene: KCNQ5 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: KCNQ5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNQ5 were set to PMID: 38693247
Phenotypes for gene: KCNQ5 were set to Intellectual developmental disorder, autosomal dominant 46, MIM#617601
Review for gene: KCNQ5 was set to AMBER
Added comment: 1 individual with mono-allelic splice variant and cerebral palsy reported in large-scale exome sequencing study. Detailed clinical information not provided.

Additional individuals described have motor delays, mostly with hypotonia (PMID: 35583973).
Sources: Literature
Cerebral Palsy v1.193 KCNQ3 Clare van Eyk gene: KCNQ3 was added
gene: KCNQ3 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: KCNQ3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNQ3 were set to PMID: 38693247
Phenotypes for gene: KCNQ3 were set to Seizures, benign neonatal, 2, MIM#121201
Review for gene: KCNQ3 was set to RED
Added comment: 1 individual with mono-allelic frameshift deletion and cerebral palsy reported in large-scale exome sequencing study. Detailed clinical information not provided. No evidence for clinical overlap.
Sources: Literature
Cerebral Palsy v1.193 KCNH1 Clare van Eyk gene: KCNH1 was added
gene: KCNH1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: KCNH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNH1 were set to PMID: 38693247
Phenotypes for gene: KCNH1 were set to Temple-Baraitser syndrome, MIM#611816; Zimmermann-Laband syndrome 1, MIM#135500
Review for gene: KCNH1 was set to AMBER
Added comment: 4 individuals with mono-allelic LP missense variants and cerebral palsy reported in large-scale exome sequencing study. Detailed clinical information not provided.
Sources: Literature
Cerebral Palsy v1.193 KCNB1 Clare van Eyk reviewed gene: KCNB1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Developmental and epileptic encephalopathy 26, MIM#616056; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.193 KAT6B Clare van Eyk gene: KAT6B was added
gene: KAT6B was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: KAT6B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KAT6B were set to PMID: 38693247
Phenotypes for gene: KAT6B were set to SBBYSS syndrome, MIM#603736; Genitopatellar syndrome, MIM#606170
Review for gene: KAT6B was set to AMBER
Added comment: 1 individual with mono-allelic stopgain variant and cerebral palsy reported in large-scale exome sequencing study. Detailed clinical information not provided.
Sources: Literature
Cerebral Palsy v1.193 KAT6A Clare van Eyk reviewed gene: KAT6A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Arboleda-Tham syndrome MIM#616268; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.193 HIVEP2 Clare van Eyk gene: HIVEP2 was added
gene: HIVEP2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: HIVEP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HIVEP2 were set to PMID: 38693247
Phenotypes for gene: HIVEP2 were set to Intellectual developmental disorder, autosomal dominant 43, MIM#616977
Review for gene: HIVEP2 was set to RED
Added comment: 1 individual with mono-allelic stopgain variant and cerebral palsy reported in large-scale exome sequencing study. Detailed clinical information not provided.
Sources: Literature
Cerebral Palsy v1.193 HECW2 Clare van Eyk reviewed gene: HECW2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Neurodevelopmental disorder with hypotonia, seizures, and absent language, MIM#617268; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.193 GRIN2A Clare van Eyk gene: GRIN2A was added
gene: GRIN2A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: GRIN2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GRIN2A were set to PMID: 38693247
Phenotypes for gene: GRIN2A were set to Epilepsy, focal, with speech disorder and with or without impaired intellectual development, MIM#245570
Review for gene: GRIN2A was set to RED
Added comment: 1 individual with mono-allelic frameshift deletion and cerebral palsy reported in large-scale exome sequencing study. Detailed clinical information not provided.
Sources: Literature
Cerebral Palsy v1.193 GNB1 Clare van Eyk reviewed gene: GNB1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Intellectual developmental disorder, autosomal dominant 42 MIM# 616973; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.193 GNAO1 Clare van Eyk reviewed gene: GNAO1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.193 GATAD2B Clare van Eyk gene: GATAD2B was added
gene: GATAD2B was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: GATAD2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GATAD2B were set to PMID: 38693247
Phenotypes for gene: GATAD2B were set to GAND syndrome, MIM#615076
Review for gene: GATAD2B was set to AMBER
Added comment: 2 individuals with mono-allelic stopgain variants and cerebral palsy reported in large-scale exome sequencing study. Detailed clinical information not provided. Some clinical overlap with CP.
Sources: Literature
Cerebral Palsy v1.193 GABBR2 Clare van Eyk gene: GABBR2 was added
gene: GABBR2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: GABBR2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GABBR2 were set to PMID: 38693247
Phenotypes for gene: GABBR2 were set to Developmental and epileptic encephalopathy 59, MIM#617904; Neurodevelopmental disorder with poor language and loss of hand skills, MIM#617903
Review for gene: GABBR2 was set to AMBER
Added comment: 1 individual with mono-allelic LP missense variant and cerebral palsy reported in large-scale exome sequencing study. Detailed clinical information not provided.
Sources: Literature
Cerebral Palsy v1.193 FUS Clare van Eyk gene: FUS was added
gene: FUS was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: FUS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FUS were set to PMID: 38693247
Phenotypes for gene: FUS were set to Essential tremor, MIM#614782
Review for gene: FUS was set to RED
Added comment: 1 individual with mono-allelic splice variant and cerebral palsy reported in large-scale exome sequencing study. Detailed clinical information not provided.
Sources: Literature
Cerebral Palsy v1.193 FGFR1 Clare van Eyk gene: FGFR1 was added
gene: FGFR1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: FGFR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FGFR1 were set to PMID: 38693247
Phenotypes for gene: FGFR1 were set to Hartsfield syndrome, MIM#615465
Review for gene: FGFR1 was set to RED
Added comment: 1 individual reported with mono-allelic splice variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.193 EZH2 Clare van Eyk gene: EZH2 was added
gene: EZH2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: EZH2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EZH2 were set to PMID: 38693247
Phenotypes for gene: EZH2 were set to Weaver syndrome, MIM#277590
Review for gene: EZH2 was set to RED
Added comment: 1 individual reported with mono-allelic LP variant (frameshift deletion) in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.193 EHMT1 Clare van Eyk gene: EHMT1 was added
gene: EHMT1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: EHMT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EHMT1 were set to PMID: 38693247
Phenotypes for gene: EHMT1 were set to Kleefstra syndrome, MIM#610253
Review for gene: EHMT1 was set to RED
Added comment: Single individual reported with mono-allelic splice variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.193 EEF1A2 Clare van Eyk reviewed gene: EEF1A2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Developmental and epileptic encephalopathy MIM#616409; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.193 DYRK1A Clare van Eyk reviewed gene: DYRK1A: Rating: ; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Intellectual developmental disorder, MIM#614104; Mode of inheritance: None
Cerebral Palsy v1.193 DNMT3A Clare van Eyk gene: DNMT3A was added
gene: DNMT3A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: DNMT3A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DNMT3A were set to PMID: 38693247
Phenotypes for gene: DNMT3A were set to Heyn-Sproul-Jackson syndrome, MIM#618724; Tatton-Brown-Rahman syndrome, MIM#615879
Review for gene: DNMT3A was set to AMBER
Added comment: 2 individuals reported with mono-allelic frameshift deletions in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.193 DNM2 Clare van Eyk gene: DNM2 was added
gene: DNM2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: DNM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DNM2 were set to PMID: 38693247
Phenotypes for gene: DNM2 were set to Charcot-Marie-Tooth disease, axonal type 2M, MIM#606482
Review for gene: DNM2 was set to RED
Added comment: 1 individual reported with mono-allelic missense variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.193 DLG4 Clare van Eyk changed review comment from: 1 individual reported with mono-allelic stopgain variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature; to: 1 individual reported with mono-allelic stopgain variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.193 DLG4 Clare van Eyk gene: DLG4 was added
gene: DLG4 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: DLG4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DLG4 were set to PMID: 38693247
Phenotypes for gene: DLG4 were set to Intellectual developmental disorder, autosomal dominant 62, MIM#618793
Review for gene: DLG4 was set to AMBER
Added comment: 1 individual reported with mono-allelic stopgain variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.193 DCC Clare van Eyk gene: DCC was added
gene: DCC was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: DCC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DCC were set to PMID: 38693247
Phenotypes for gene: DCC were set to Mirror movements 1 and/or agenesis of the corpus callosum, MIM#157600
Review for gene: DCC was set to RED
Added comment: 1 individual reported with mono-allelic stopgain in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.193 CUL3 Clare van Eyk gene: CUL3 was added
gene: CUL3 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CUL3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CUL3 were set to PMID: 38693247
Phenotypes for gene: CUL3 were set to Neurodevelopmental disorder with or without autism or seizures, MIM#619239, Pseudohypoaldosteronism, type IIE, MIM#614496
Review for gene: CUL3 was set to AMBER
Added comment: 1 individual reported with mono-allelic splice variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Genetic Epilepsy v1.2 RAPGEF2 Zornitza Stark Marked gene: RAPGEF2 as ready
Genetic Epilepsy v1.2 RAPGEF2 Zornitza Stark Gene: rapgef2 has been removed from the panel.
Cerebral Palsy v1.193 CTNNB1 Clare van Eyk reviewed gene: CTNNB1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Neurodevelopmental disorder with spastic diplegia and visual defects, MIM#615075; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.193 CTCF Clare van Eyk gene: CTCF was added
gene: CTCF was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CTCF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CTCF were set to PMID: 38693247
Phenotypes for gene: CTCF were set to Intellectual developmental disorder, autosomal dominant 21, MIM#615502
Review for gene: CTCF was set to RED
Added comment: 1 individual reported with mono-allelic stopgain variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.193 CTBP1 Clare van Eyk reviewed gene: CTBP1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome MIM#617915; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.193 COL4A1 Clare van Eyk changed review comment from: Additional 2 individuals reproted with mono-allelic P/LP variants (1 frameshift deletion and 1 stopgain) in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.; to: Additional 2 individuals reported with mono-allelic P/LP variants (1 frameshift deletion and 1 stopgain) in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Cerebral Palsy v1.193 CREBBP Clare van Eyk reviewed gene: CREBBP: Rating: ; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Menke-Hennekam syndrome MIM#618332, Rubinstein-Taybi syndrome MIM#180849; Mode of inheritance: None
Cerebral Palsy v1.193 COL4A2 Clare van Eyk reviewed gene: COL4A2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Brain small vessel disease 2 MIM# 614483; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cerebral Palsy v1.193 COL4A1 Clare van Eyk reviewed gene: COL4A1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Brain small vessel disease MIM#614483; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.193 CLCN7 Clare van Eyk gene: CLCN7 was added
gene: CLCN7 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CLCN7 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: CLCN7 were set to PMID: 38693247
Phenotypes for gene: CLCN7 were set to Hypopigmentation, organomegaly, and delayed myelination and development, MIM#175780; Osteopetrosis, autosomal recessive 4; OPTB4, MIM#602727
Review for gene: CLCN7 was set to RED
Added comment: 1 individual with homozygous splice variant reported in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Bi-allelic variants have been reported to cause osteopetrosis.
Sources: Literature
Cerebral Palsy v1.193 CHD7 Clare van Eyk gene: CHD7 was added
gene: CHD7 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CHD7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHD7 were set to PMID: 38693247
Phenotypes for gene: CHD7 were set to CHARGE syndrome, MIM#608892
Review for gene: CHD7 was set to AMBER
Added comment: 2 individuals with mono-allelic LOF variants (1 stopgain, 1 splicing) reported in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.193 CHD4 Clare van Eyk gene: CHD4 was added
gene: CHD4 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CHD4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHD4 were set to PMID: 38693247
Phenotypes for gene: CHD4 were set to Sifrim-Hitz-Weiss syndrome, MIM#617159
Review for gene: CHD4 was set to AMBER
Added comment: 2 individuals with mono-allelic missense variants reported in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.193 CHCHD10 Clare van Eyk gene: CHCHD10 was added
gene: CHCHD10 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CHCHD10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHCHD10 were set to PMID: 38693247
Phenotypes for gene: CHCHD10 were set to Myopathy, isolated mitochondrial, MIM#616209
Review for gene: CHCHD10 was set to AMBER
Added comment: 1 individual with mono-allelic missense variant reported in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.193 CAMK2G Clare van Eyk gene: CAMK2G was added
gene: CAMK2G was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CAMK2G was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CAMK2G were set to PMID: 38693247
Phenotypes for gene: CAMK2G were set to Intellectual developmental disorder, autosomal dominant 59, MIM#618522
Review for gene: CAMK2G was set to AMBER
Added comment: 1 individual with mono-allelic missense variant reported in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.193 CAMK2B Clare van Eyk gene: CAMK2B was added
gene: CAMK2B was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CAMK2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CAMK2B were set to PMID: 38693247
Phenotypes for gene: CAMK2B were set to Intellectual developmental disorder, autosomal dominant 54, MIM#617799
Review for gene: CAMK2B was set to AMBER
Added comment: 1 individual with mono-allelic splice variant reported in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.193 CACNA1G Clare van Eyk gene: CACNA1G was added
gene: CACNA1G was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CACNA1G was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CACNA1G were set to PMID: 38693247
Phenotypes for gene: CACNA1G were set to Spinocerebellar ataxia 42, early-onset, severe, with neurodevelopmental deficits, MIM#618087
Review for gene: CACNA1G was set to GREEN
Added comment: 5 individuals with mono-allelic LP missense variants reported in large-scale exome sequencing study (PMID: 38693247). Ataxia, spasticity and dystonia are reported features of SCA42ND.
Sources: Literature
Cerebral Palsy v1.193 CACNA1D Clare van Eyk gene: CACNA1D was added
gene: CACNA1D was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CACNA1D was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CACNA1D were set to PMID: 38693247; 23913001
Phenotypes for gene: CACNA1D were set to Primary aldosteronism, seizures and neurologic abnormalities; PASNA, MIM#615474
Mode of pathogenicity for gene: CACNA1D was set to Other
Review for gene: CACNA1D was set to AMBER
Added comment: 1 individual with mono-allelic LP missense variant reported in large-scale exome sequencing study (PMID: 38693247). No detailed clincal data.

1 individual described previously with cerebral palsy and a de novo heterozygous gain-of-function missense mutation (PMID: 23913001).
Sources: Literature
Severe Combined Immunodeficiency (absent T absent B cells) v1.7 NUDCD3 Peter McNaughton gene: NUDCD3 was added
gene: NUDCD3 was added to Severe Combined Immunodeficiency (absent T absent B cells). Sources: Literature
Mode of inheritance for gene: NUDCD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUDCD3 were set to PMID: 38787962
Phenotypes for gene: NUDCD3 were set to Severe combined immunodeficiency; omenn syndrome
Review for gene: NUDCD3 was set to GREEN
Added comment: Multiple familial cases from 4 unrelated consanguineous kindreds of South Asian origin presenting with SCID or Omenn syndrome. Extensive functional validation including knock in mouse model demonstrating impaired VDJ recombination.
Sources: Literature
Cerebral Palsy v1.193 CACNA1A Clare van Eyk reviewed gene: CACNA1A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Developmental and epileptic encephalopathy MIM#617106, Episodic ataxia MIM#108500, familial hemiplegic Migraine MIM#141500 and MIM#141500, Spinocerebellar ataxia MIM#183086; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.193 BSCL2 Clare van Eyk gene: BSCL2 was added
gene: BSCL2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: BSCL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BSCL2 were set to PMID: 38693247
Phenotypes for gene: BSCL2 were set to Spastic paraplegia 17, MIM#270685
Review for gene: BSCL2 was set to AMBER
Added comment: Single individual reported with mono-allelic LP frameshift deletion reported in large-scale exome sequencing study (PMID: 38693247). No detailed clinical information provided.
Sources: Literature
Cerebral Palsy v1.193 AUTS2 Clare van Eyk reviewed gene: AUTS2: Rating: ; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Intellectual developmental disorder, autosomal dominant 26, MIM# 615834; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.193 ASXL3 Clare van Eyk reviewed gene: ASXL3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247, PMID:33528536, PMID: 35863334; Phenotypes: Bainbridge-Ropers syndrome, MIM#615485; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5943 ROR2 Zornitza Stark Marked gene: ROR2 as ready
Intellectual disability syndromic and non-syndromic v0.5943 ROR2 Zornitza Stark Gene: ror2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5943 ROR2 Zornitza Stark Phenotypes for gene: ROR2 were changed from to Robinow syndrome, autosomal recessive, MIM#268310
Intellectual disability syndromic and non-syndromic v0.5942 ROR2 Zornitza Stark Publications for gene: ROR2 were set to 33937263, 32954672, 32172608
Cerebral Palsy v1.193 ATP6V1A Clare van Eyk gene: ATP6V1A was added
gene: ATP6V1A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ATP6V1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP6V1A were set to PMID: 38693247
Phenotypes for gene: ATP6V1A were set to Developmental and epileptic encephalopathy 93, MIM#618012
Review for gene: ATP6V1A was set to AMBER
Added comment: 1 individual with mono-allelic LP missense variant reported in large-scale exome sequencing study (PMID: 38693247). Detailed clincal information not supplied. Spastic quadriparesis and dyskinesia are reported features of DEE93.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5941 ROR2 Zornitza Stark Publications for gene: ROR2 were set to
Cerebral Palsy v1.193 ATP1A3 Clare van Eyk edited their review of gene: ATP1A3: Added comment: Additional 5 individuals with mono-allelic LP missense variants reported in large-scale exome sequencing study (PMID: 38693247).; Changed publications: 33528536, 30542205, 38693247; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.193 ATP1A2 Clare van Eyk gene: ATP1A2 was added
gene: ATP1A2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ATP1A2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP1A2 were set to PMID: 38693247
Phenotypes for gene: ATP1A2 were set to Alternating hemiplegia of childhood 1, MIM#104290
Review for gene: ATP1A2 was set to AMBER
Added comment: 1 individual with monoallelic missense variant reported in large-scale exome sequencing study. Detailed clinical data not provided.
Sources: Literature
Cerebral Palsy v1.193 ATL1 Clare van Eyk edited their review of gene: ATL1: Added comment: Additional 3 individuals with mono-allelic LP missense variants reported in large-scale exome sequencing study (PMID: 38693247).; Changed publications: PMID: 33528536, PMID: 34321325, PMID: 38693247
Intellectual disability syndromic and non-syndromic v0.5940 ROR2 Zornitza Stark Mode of inheritance for gene: ROR2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5939 ROR2 Zornitza Stark reviewed gene: ROR2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Robinow syndrome, autosomal recessive, MIM#268310; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5939 SOX10 Zornitza Stark Marked gene: SOX10 as ready
Intellectual disability syndromic and non-syndromic v0.5939 SOX10 Zornitza Stark Gene: sox10 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5939 SOX10 Zornitza Stark Phenotypes for gene: SOX10 were changed from to Peripheral demyelinating neuropathy Central demyelination, Waardenburg and Hirschsprung disease, OMIM #609136; Waardenburg syndrome, type 2E, with or without neurologic involvement (OMIM #611584)
Intellectual disability syndromic and non-syndromic v0.5938 SOX10 Zornitza Stark Publications for gene: SOX10 were set to
Intellectual disability syndromic and non-syndromic v0.5937 SOX10 Zornitza Stark Mode of inheritance for gene: SOX10 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5936 SLC4A4 Zornitza Stark Marked gene: SLC4A4 as ready
Intellectual disability syndromic and non-syndromic v0.5936 SLC4A4 Zornitza Stark Gene: slc4a4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5936 SLC4A4 Zornitza Stark Mode of inheritance for gene: SLC4A4 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5935 SLC4A4 Zornitza Stark Mode of inheritance for gene: SLC4A4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5934 SLC4A4 Zornitza Stark Publications for gene: SLC4A4 were set to
Intellectual disability syndromic and non-syndromic v0.5933 SLC4A4 Zornitza Stark Phenotypes for gene: SLC4A4 were changed from to Renal tubular acidosis, proximal, with ocular abnormalities MIM#604278
Intellectual disability syndromic and non-syndromic v0.5932 SLX4 Zornitza Stark Marked gene: SLX4 as ready
Intellectual disability syndromic and non-syndromic v0.5932 SLX4 Zornitza Stark Gene: slx4 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5932 SLX4 Zornitza Stark Phenotypes for gene: SLX4 were changed from to Fanconi anaemia, complementation group P, MIM# 613951
Intellectual disability syndromic and non-syndromic v0.5931 SLX4 Zornitza Stark Publications for gene: SLX4 were set to
Intellectual disability syndromic and non-syndromic v0.5930 SLX4 Zornitza Stark Mode of inheritance for gene: SLX4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.193 ASXL3 Clare van Eyk Deleted their review
Intellectual disability syndromic and non-syndromic v0.5929 SLX4 Zornitza Stark Classified gene: SLX4 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.5929 SLX4 Zornitza Stark Gene: slx4 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.193 ASXL3 Clare van Eyk edited their review of gene: ASXL3: Added comment: 1 additional individual with mono-allelic LOF (frameshift insertion) reported in large-scale exome sequencing study.; Changed publications: PMID: 38693247
Intellectual disability syndromic and non-syndromic v0.5928 SLX4 Zornitza Stark reviewed gene: SLX4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Fanconi anemia, complementation group P, MIM# 613951; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5928 SCN8A Zornitza Stark Marked gene: SCN8A as ready
Intellectual disability syndromic and non-syndromic v0.5928 SCN8A Zornitza Stark Gene: scn8a has been classified as Green List (High Evidence).
Cerebral Palsy v1.193 ARID2 Clare van Eyk reviewed gene: ARID2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Coffin-Siris syndrome 6, MIM#617808; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5928 SCN8A Zornitza Stark Phenotypes for gene: SCN8A were changed from to Developmental and epileptic encephalopathy 13, MIM# 614558
Intellectual disability syndromic and non-syndromic v0.5927 SCN8A Zornitza Stark Publications for gene: SCN8A were set to
Intellectual disability syndromic and non-syndromic v0.5926 SCN8A Zornitza Stark Mode of inheritance for gene: SCN8A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.193 ARID1B Clare van Eyk gene: ARID1B was added
gene: ARID1B was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ARID1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARID1B were set to PMID: 38693247
Phenotypes for gene: ARID1B were set to Coffin-Siris syndrome 1, MIM#135900
Review for gene: ARID1B was set to AMBER
Added comment: 1 individual with mono-allelic frameshift deletion and cerebral palsy reported in large-scale exome sequencing study. Detailed clinical information not provided.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5925 THRA Zornitza Stark Marked gene: THRA as ready
Intellectual disability syndromic and non-syndromic v0.5925 THRA Zornitza Stark Gene: thra has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5925 THRA Zornitza Stark Phenotypes for gene: THRA were changed from to Hypothyroidism congenital nongoitrous 6 (MIM 614450)
Intellectual disability syndromic and non-syndromic v0.5924 THRA Zornitza Stark Publications for gene: THRA were set to
Cerebral Palsy v1.193 AHDC1 Clare van Eyk reviewed gene: AHDC1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Xia-Gibbs syndrome, MIM#615829; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5923 THRA Zornitza Stark Mode of inheritance for gene: THRA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5922 SIX3 Zornitza Stark Marked gene: SIX3 as ready
Intellectual disability syndromic and non-syndromic v0.5922 SIX3 Zornitza Stark Gene: six3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5922 SIX3 Zornitza Stark Phenotypes for gene: SIX3 were changed from to Holoprosencephaly 2, autosomal dominant, MIM#157170
Intellectual disability syndromic and non-syndromic v0.5921 SIX3 Zornitza Stark Publications for gene: SIX3 were set to
Intellectual disability syndromic and non-syndromic v0.5920 SIX3 Zornitza Stark Mode of inheritance for gene: SIX3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5919 SIX3 Zornitza Stark reviewed gene: SIX3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Holoprosencephaly 2, autosomal dominant, MIM#157170; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5919 SAMHD1 Zornitza Stark Marked gene: SAMHD1 as ready
Intellectual disability syndromic and non-syndromic v0.5919 SAMHD1 Zornitza Stark Gene: samhd1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5919 SAMHD1 Zornitza Stark Phenotypes for gene: SAMHD1 were changed from to Aicardi-Goutieres syndrome 5, MIM# 612952
Intellectual disability syndromic and non-syndromic v0.5918 SAMHD1 Zornitza Stark Publications for gene: SAMHD1 were set to
Intellectual disability syndromic and non-syndromic v0.5917 SAMHD1 Zornitza Stark Mode of inheritance for gene: SAMHD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5916 SCN2A Zornitza Stark Marked gene: SCN2A as ready
Intellectual disability syndromic and non-syndromic v0.5916 SCN2A Zornitza Stark Gene: scn2a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5916 SCN2A Zornitza Stark Publications for gene: SCN2A were set to
Intellectual disability syndromic and non-syndromic v0.5915 SCN2A Zornitza Stark Phenotypes for gene: SCN2A were changed from to Developmental and epileptic encephalopathy 11, MIM# 613721
Intellectual disability syndromic and non-syndromic v0.5914 SCN2A Zornitza Stark Mode of inheritance for gene: SCN2A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5913 SCN2A Zornitza Stark Mode of inheritance for gene: SCN2A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5912 BMP4 Zornitza Stark Phenotypes for gene: BMP4 were changed from Microphthalmia, syndromic 6, MIM# 607932 to Microphthalmia, syndromic 6, MIM# 607932
Intellectual disability syndromic and non-syndromic v0.5911 BMP4 Zornitza Stark Marked gene: BMP4 as ready
Intellectual disability syndromic and non-syndromic v0.5911 BMP4 Zornitza Stark Gene: bmp4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5911 BMP4 Zornitza Stark Phenotypes for gene: BMP4 were changed from to Microphthalmia, syndromic 6, MIM# 607932
Intellectual disability syndromic and non-syndromic v0.5910 BMP4 Zornitza Stark Publications for gene: BMP4 were set to
Intellectual disability syndromic and non-syndromic v0.5909 BMP4 Zornitza Stark Mode of inheritance for gene: BMP4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5908 BMP4 Zornitza Stark edited their review of gene: BMP4: Changed publications: 31053785
Intellectual disability syndromic and non-syndromic v0.5908 BMP4 Zornitza Stark reviewed gene: BMP4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Microphthalmia, syndromic 6, MIM# 607932; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1797 CCIN Zornitza Stark Phenotypes for gene: CCIN were changed from male infertility with teratozoospermia due to single gene mutation, MONDO:0018394 to Spermatogenic failure 91, MIM# 620838
Mendeliome v1.1796 CCIN Zornitza Stark reviewed gene: CCIN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spermatogenic failure 91, MIM# 620838; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5908 CDON Zornitza Stark Marked gene: CDON as ready
Intellectual disability syndromic and non-syndromic v0.5908 CDON Zornitza Stark Gene: cdon has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5908 CDON Zornitza Stark Phenotypes for gene: CDON were changed from to holoprosencephaly 11 MONDO:0013642
Intellectual disability syndromic and non-syndromic v0.5907 CDON Zornitza Stark Publications for gene: CDON were set to
Intellectual disability syndromic and non-syndromic v0.5906 CDON Zornitza Stark Mode of inheritance for gene: CDON was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aminoacidopathy v1.47 GAD1 Zornitza Stark Marked gene: GAD1 as ready
Aminoacidopathy v1.47 GAD1 Zornitza Stark Gene: gad1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.47 GAD1 Zornitza Stark Phenotypes for gene: GAD1 were changed from obsolete early infantile epileptic encephalopathy MONDO:0016021 to Developmental and epileptic encephalopathy 89, MIM# 619124
Aminoacidopathy v1.46 GAD1 Zornitza Stark Classified gene: GAD1 as Green List (high evidence)
Aminoacidopathy v1.46 GAD1 Zornitza Stark Gene: gad1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.45 FMO3 Zornitza Stark Marked gene: FMO3 as ready
Aminoacidopathy v1.45 FMO3 Zornitza Stark Gene: fmo3 has been classified as Green List (High Evidence).
Aminoacidopathy v1.45 FMO3 Zornitza Stark Classified gene: FMO3 as Green List (high evidence)
Aminoacidopathy v1.45 FMO3 Zornitza Stark Gene: fmo3 has been classified as Green List (High Evidence).
Aminoacidopathy v1.44 FAH Zornitza Stark Marked gene: FAH as ready
Aminoacidopathy v1.44 FAH Zornitza Stark Gene: fah has been classified as Green List (High Evidence).
Aminoacidopathy v1.44 FAH Zornitza Stark Classified gene: FAH as Green List (high evidence)
Aminoacidopathy v1.44 FAH Zornitza Stark Gene: fah has been classified as Green List (High Evidence).
Aminoacidopathy v1.43 DNAJC12 Zornitza Stark Marked gene: DNAJC12 as ready
Aminoacidopathy v1.43 DNAJC12 Zornitza Stark Gene: dnajc12 has been classified as Green List (High Evidence).
Aminoacidopathy v1.43 DNAJC12 Zornitza Stark Publications for gene: DNAJC12 were set to 28132689, 30179615, 28892570, 28794131, 30139987
Aminoacidopathy v1.42 DNAJC12 Zornitza Stark Classified gene: DNAJC12 as Green List (high evidence)
Aminoacidopathy v1.42 DNAJC12 Zornitza Stark Gene: dnajc12 has been classified as Green List (High Evidence).
Aminoacidopathy v1.41 DMGDH Zornitza Stark Marked gene: DMGDH as ready
Aminoacidopathy v1.41 DMGDH Zornitza Stark Gene: dmgdh has been classified as Red List (Low Evidence).
Aminoacidopathy v1.41 DMGDH Zornitza Stark Classified gene: DMGDH as Red List (low evidence)
Aminoacidopathy v1.41 DMGDH Zornitza Stark Gene: dmgdh has been classified as Red List (Low Evidence).
Aminoacidopathy v1.40 DHTKD1 Zornitza Stark Marked gene: DHTKD1 as ready
Aminoacidopathy v1.40 DHTKD1 Zornitza Stark Gene: dhtkd1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.40 DHTKD1 Zornitza Stark Publications for gene: DHTKD1 were set to 26141459, 25860818, 23141293
Aminoacidopathy v1.39 DHTKD1 Zornitza Stark Classified gene: DHTKD1 as Green List (high evidence)
Aminoacidopathy v1.39 DHTKD1 Zornitza Stark Gene: dhtkd1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.38 CTH Zornitza Stark Marked gene: CTH as ready
Aminoacidopathy v1.38 CTH Zornitza Stark Gene: cth has been classified as Green List (High Evidence).
Aminoacidopathy v1.38 CTH Zornitza Stark Classified gene: CTH as Green List (high evidence)
Aminoacidopathy v1.38 CTH Zornitza Stark Gene: cth has been classified as Green List (High Evidence).
Aminoacidopathy v1.37 CPS1 Zornitza Stark Marked gene: CPS1 as ready
Aminoacidopathy v1.37 CPS1 Zornitza Stark Gene: cps1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.37 CPS1 Zornitza Stark Classified gene: CPS1 as Green List (high evidence)
Aminoacidopathy v1.37 CPS1 Zornitza Stark Gene: cps1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.36 CBS Zornitza Stark Marked gene: CBS as ready
Aminoacidopathy v1.36 CBS Zornitza Stark Gene: cbs has been classified as Green List (High Evidence).
Aminoacidopathy v1.36 CBS Zornitza Stark Classified gene: CBS as Green List (high evidence)
Aminoacidopathy v1.36 CBS Zornitza Stark Gene: cbs has been classified as Green List (High Evidence).
Aminoacidopathy v1.35 CA5A Zornitza Stark Marked gene: CA5A as ready
Aminoacidopathy v1.35 CA5A Zornitza Stark Gene: ca5a has been classified as Green List (High Evidence).
Aminoacidopathy v1.35 CA5A Zornitza Stark Publications for gene: CA5A were set to 24530203, 26913920, 23589845
Aminoacidopathy v1.34 CA5A Zornitza Stark Classified gene: CA5A as Green List (high evidence)
Aminoacidopathy v1.34 CA5A Zornitza Stark Gene: ca5a has been classified as Green List (High Evidence).
Aminoacidopathy v1.33 ASS1 Zornitza Stark Marked gene: ASS1 as ready
Aminoacidopathy v1.33 ASS1 Zornitza Stark Gene: ass1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.33 ASS1 Zornitza Stark Classified gene: ASS1 as Green List (high evidence)
Aminoacidopathy v1.33 ASS1 Zornitza Stark Gene: ass1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.32 ALDH7A1 Zornitza Stark Marked gene: ALDH7A1 as ready
Aminoacidopathy v1.32 ALDH7A1 Zornitza Stark Gene: aldh7a1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.32 ALDH7A1 Zornitza Stark Publications for gene: ALDH7A1 were set to 19142996, 16491085, 22784480, 29053735
Aminoacidopathy v1.31 ALDH7A1 Zornitza Stark Classified gene: ALDH7A1 as Green List (high evidence)
Aminoacidopathy v1.31 ALDH7A1 Zornitza Stark Gene: aldh7a1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.30 ALDH4A1 Zornitza Stark Marked gene: ALDH4A1 as ready
Aminoacidopathy v1.30 ALDH4A1 Zornitza Stark Gene: aldh4a1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.30 ALDH4A1 Zornitza Stark Publications for gene: ALDH4A1 were set to 2624476, 13835167, 4369405, 8621661
Aminoacidopathy v1.29 ALDH4A1 Zornitza Stark Classified gene: ALDH4A1 as Green List (high evidence)
Aminoacidopathy v1.29 ALDH4A1 Zornitza Stark Gene: aldh4a1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.28 ALDH18A1 Zornitza Stark Marked gene: ALDH18A1 as ready
Aminoacidopathy v1.28 ALDH18A1 Zornitza Stark Gene: aldh18a1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.28 ALDH18A1 Zornitza Stark Publications for gene: ALDH18A1 were set to 32017139, 26026163, 26320891
Aminoacidopathy v1.27 ALDH18A1 Zornitza Stark Classified gene: ALDH18A1 as Green List (high evidence)
Aminoacidopathy v1.27 ALDH18A1 Zornitza Stark Gene: aldh18a1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.26 AHCY Zornitza Stark Marked gene: AHCY as ready
Aminoacidopathy v1.26 AHCY Zornitza Stark Gene: ahcy has been classified as Green List (High Evidence).
Aminoacidopathy v1.26 AHCY Zornitza Stark Publications for gene: AHCY were set to 13641268, 15024124, 16736098, 20852937, 22959829, 30121674, 26527160, 26095522, 27848944, 31957987, 35463910
Aminoacidopathy v1.25 AHCY Zornitza Stark Classified gene: AHCY as Green List (high evidence)
Aminoacidopathy v1.25 AHCY Zornitza Stark Gene: ahcy has been classified as Green List (High Evidence).
Aminoacidopathy v1.24 ADK Zornitza Stark Marked gene: ADK as ready
Aminoacidopathy v1.24 ADK Zornitza Stark Gene: adk has been classified as Green List (High Evidence).
Aminoacidopathy v1.24 ADK Zornitza Stark Publications for gene: ADK were set to 21963049, 26642971, 33309011, 27671891
Aminoacidopathy v1.23 ADK Zornitza Stark Classified gene: ADK as Green List (high evidence)
Aminoacidopathy v1.23 ADK Zornitza Stark Gene: adk has been classified as Green List (High Evidence).
Aminoacidopathy v1.22 ACY1 Zornitza Stark Marked gene: ACY1 as ready
Aminoacidopathy v1.22 ACY1 Zornitza Stark Gene: acy1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.22 ACY1 Zornitza Stark Publications for gene: ACY1 were set to 4997716, 24117009, 16465618, 17562838, 21414403, 16274666, 20480396
Aminoacidopathy v1.21 ACY1 Zornitza Stark Classified gene: ACY1 as Green List (high evidence)
Aminoacidopathy v1.21 ACY1 Zornitza Stark Gene: acy1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.20 GAMT Zornitza Stark Marked gene: GAMT as ready
Aminoacidopathy v1.20 GAMT Zornitza Stark Gene: gamt has been classified as Green List (High Evidence).
Aminoacidopathy v1.20 GAMT Zornitza Stark Classified gene: GAMT as Green List (high evidence)
Aminoacidopathy v1.20 GAMT Zornitza Stark Gene: gamt has been classified as Green List (High Evidence).
Aminoacidopathy v1.19 GATM Zornitza Stark Marked gene: GATM as ready
Aminoacidopathy v1.19 GATM Zornitza Stark Gene: gatm has been classified as Green List (High Evidence).
Aminoacidopathy v1.19 GATM Zornitza Stark Classified gene: GATM as Green List (high evidence)
Aminoacidopathy v1.19 GATM Zornitza Stark Gene: gatm has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5905 RBBP8 Zornitza Stark Marked gene: RBBP8 as ready
Intellectual disability syndromic and non-syndromic v0.5905 RBBP8 Zornitza Stark Gene: rbbp8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5905 RBBP8 Zornitza Stark Phenotypes for gene: RBBP8 were changed from to Jawad syndrome, MIM#251255; Seckel syndrome 2, MIM#606744
Intellectual disability syndromic and non-syndromic v0.5904 RBBP8 Zornitza Stark Publications for gene: RBBP8 were set to
Intellectual disability syndromic and non-syndromic v0.5903 RBBP8 Zornitza Stark Mode of inheritance for gene: RBBP8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5902 RBBP8 Zornitza Stark reviewed gene: RBBP8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Jawad syndrome, MIM#251255, Seckel syndrome 2, MIM#606744; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Aminoacidopathy v1.18 GATM Sangavi Sivagnanasundram gene: GATM was added
gene: GATM was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: GATM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GATM were set to 26490222; 23770102; 12468279; 27233232
Phenotypes for gene: GATM were set to AGAT deficiency MONDO:0012996
Review for gene: GATM was set to GREEN
Added comment: Classified Definitive by ClinGen Aminoacidopathy GCEP on 08/03/2019 - https://search.clinicalgenome.org/CCID:004930

AGAT deficiency is an inborn error of creatine metabolism.
Well established gene-disease association with evidence of segregation between affected individuals. LoF is the mechanism of disease
Sources: ClinGen
Mendeliome v1.1796 RBBP8 James The Deleted their review
Aminoacidopathy v1.18 GAMT Sangavi Sivagnanasundram gene: GAMT was added
gene: GAMT was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: GAMT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GAMT were set to 20301745; 17466557; 16293431; 12701824; 2441567
Phenotypes for gene: GAMT were set to guanidinoacetate methyltransferase deficiency MONDO:0012999
Review for gene: GAMT was set to GREEN
Added comment: Classified Definitive by ClinGen Aminoacidopathy GCEP on 25/01/2019 - https://search.clinicalgenome.org/CCID:004917

Well established gene-disease association.
Reported as an inborn error of creatine metabolism.
The two most commonly reported variants are p.Trp20Ser (c.59G>C) and c.327G>A (p.Lys109=). Both variants are pathogenic on ClinVar (>2 stars) and is classified pathogenic by the ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel (FDA recognised database).
Sources: ClinGen
Intellectual disability syndromic and non-syndromic v0.5902 RBBP8 James The reviewed gene: RBBP8: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:30561437, 34270086, 32379725; Phenotypes: 606744, 251255, 113705; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Aminoacidopathy v1.18 GAD1 Sangavi Sivagnanasundram changed review comment from: Classified Definitive by ClinGen Aminoacidopathy GCEP on 13/05/2021 - https://search.clinicalgenome.org/CCID:004907

Established gene-disease association with multiple reported individuals having a metabolic abnormality. Mouse models were performed that recaptulated the human phenotype.
Sources: ClinGen; to: Classified Definitive by ClinGen Aminoacidopathy GCEP on 13/05/2021 - https://search.clinicalgenome.org/CCID:004907

Established gene-disease association with multiple reported individuals having a metabolic abnormality. Mouse models were performed that recapitulated the human phenotype.
Sources: ClinGen
Aminoacidopathy v1.18 GAD1 Sangavi Sivagnanasundram gene: GAD1 was added
gene: GAD1 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: GAD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GAD1 were set to 28454995; 31144778; 32282878; 15571623; 32705143; 9177246; 9326630; 20333300
Phenotypes for gene: GAD1 were set to obsolete early infantile epileptic encephalopathy MONDO:0016021
Review for gene: GAD1 was set to GREEN
Added comment: Classified Definitive by ClinGen Aminoacidopathy GCEP on 13/05/2021 - https://search.clinicalgenome.org/CCID:004907

Established gene-disease association with multiple reported individuals having a metabolic abnormality. Mouse models were performed that recaptulated the human phenotype.
Sources: ClinGen
Aminoacidopathy v1.18 FMO3 Sangavi Sivagnanasundram gene: FMO3 was added
gene: FMO3 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: FMO3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FMO3 were set to 31317802; 28649550
Phenotypes for gene: FMO3 were set to trimethylaminuria MONDO:0011182
Review for gene: FMO3 was set to GREEN
Added comment: Classified Definitive by ClinGen Aminoacidopathy GCEP on 14/08/2020 - https://search.clinicalgenome.org/CCID:004868

Well established gene-disease assocation. Multiple reported individuals with an abnormality in trimethylamine metabolism.
Sources: ClinGen
Aminoacidopathy v1.18 FAH Sangavi Sivagnanasundram gene: FAH was added
gene: FAH was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: FAH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAH were set to 20301688; 8318997; 7550234; 7942842; 2378356; 9095403; 26829318
Phenotypes for gene: FAH were set to tyrosinemia type I MONDO:0010161
Review for gene: FAH was set to GREEN
Added comment: Classified Definitive by ClinGen Aminoacidopathy GCEP on 29/06/2020 - https://search.clinicalgenome.org/CCID:004804

Typically present in young infants with abnormal liver function as FAH is mainly expressed in the liver.
Well established gene-disease association with multiple reported individuals having abnormal biochemical function of FAH.
LoF is the mechanism of disease. Gene Reviews reports many founder variants in different population.
Sources: ClinGen
Aminoacidopathy v1.18 DNAJC12 Sangavi Sivagnanasundram gene: DNAJC12 was added
gene: DNAJC12 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: DNAJC12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAJC12 were set to 28132689, 30179615, 28892570, 28794131, 30139987
Phenotypes for gene: DNAJC12 were set to hyperphenylalaninemia due to DNAJC12 deficiency MONDO:0044304
Review for gene: DNAJC12 was set to GREEN
Added comment: Classified Definitive by ClinGen Aminoacidopathy GCEP on 11/01/2021 - https://search.clinicalgenome.org/CCID:004679

Biochemical abnormalities have been reported in at least 7 probands.
Sources: ClinGen
Aminoacidopathy v1.18 DMGDH Sangavi Sivagnanasundram gene: DMGDH was added
gene: DMGDH was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: DMGDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DMGDH were set to 11231903
Phenotypes for gene: DMGDH were set to dimethylglycine dehydrogenase deficiency MONDO:0011610
Review for gene: DMGDH was set to RED
Added comment: Classified Limited by ClinGen Aminoacidopathy GCEP on 12/12/2022 - https://search.clinicalgenome.org/CCID:004660

Reported in one individual with abnormal choline metabolism.
Sources: ClinGen
Aminoacidopathy v1.18 DHTKD1 Sangavi Sivagnanasundram gene: DHTKD1 was added
gene: DHTKD1 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: DHTKD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DHTKD1 were set to 26141459, 25860818, 23141293
Phenotypes for gene: DHTKD1 were set to 2-aminoadipic 2-oxoadipic aciduria MONDO:0008774
Review for gene: DHTKD1 was set to GREEN
Added comment: Classified Definitive by ClinGen Aminoacidopathy GCEP on 03/11/2020 - https://search.clinicalgenome.org/CCID:004644

Reported in >10 probands with biochemical abnormalities. Mouse models and functional assays have been conducted that confirm LoF mechanism of disease.
Sources: ClinGen
Schwannomatosis v0.16 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 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
Intellectual disability syndromic and non-syndromic v0.5902 CDON Hali Van Niel reviewed gene: CDON: Rating: GREEN; Mode of pathogenicity: None; Publications: 21802063, 26728615, 31502381, 32729136, 26529631; Phenotypes: holoprosencephaly 11 MONDO:0013642; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aminoacidopathy v1.18 CTH Sangavi Sivagnanasundram gene: CTH was added
gene: CTH was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: CTH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTH were set to 20584029; 19428278; 12574942
Phenotypes for gene: CTH were set to cystathioninuria MONDO:0009058
Review for gene: CTH was set to GREEN
Added comment: Classified Definitive by ClinGen Aminoacidopathy GCEP on 14/06/2019 - https://search.clinicalgenome.org/CCID:004594

Inborn error of cystathionine gamma-lyase metabolism and has been reported in >5 affected individuals.
Sources: ClinGen
Intellectual disability syndromic and non-syndromic v0.5902 SAMD9 Zornitza Stark Marked gene: SAMD9 as ready
Intellectual disability syndromic and non-syndromic v0.5902 SAMD9 Zornitza Stark Gene: samd9 has been classified as Green List (High Evidence).
Aminoacidopathy v1.18 CPS1 Sangavi Sivagnanasundram gene: CPS1 was added
gene: CPS1 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: CPS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CPS1 were set to 9862865; 29801986; 27834067; 27150549; 22173106
Phenotypes for gene: CPS1 were set to carbamoyl phosphate synthetase I deficiency disease MONDO:0009376
Review for gene: CPS1 was set to GREEN
Added comment: Classified Definitive by ClinGen Aminoacidopathy GCEP on 12/10/2018 - https://search.clinicalgenome.org/CCID:004568

Well established gene-disease association. Reported individuals are deficient in CPS which affects their urea cycle. Classified as an inborn error of metabolism of the urea cycle.
Sources: ClinGen
Intellectual disability syndromic and non-syndromic v0.5902 SAMD9 Zornitza Stark Phenotypes for gene: SAMD9 were changed from MIRAGE Syndrome, MIM#617053 to MIRAGE Syndrome, MIM#617053
Intellectual disability syndromic and non-syndromic v0.5901 SAMD9 Zornitza Stark Phenotypes for gene: SAMD9 were changed from to MIRAGE Syndrome, MIM#617053
Intellectual disability syndromic and non-syndromic v0.5900 SAMD9 Zornitza Stark Publications for gene: SAMD9 were set to
Intellectual disability syndromic and non-syndromic v0.5899 SAMD9 Zornitza Stark Mode of inheritance for gene: SAMD9 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5898 SAMD9 Zornitza Stark reviewed gene: SAMD9: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: MIRAGE Syndrome, MIM#617053; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5898 BMP4 Hali Van Niel reviewed gene: BMP4: Rating: AMBER; Mode of pathogenicity: None; Publications: 22581619, 31053785, 30568244, 18252212, 21340693, 34926457, 36140739, 37107605; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Inflammatory bowel disease v0.121 LIG4 Zornitza Stark Marked gene: LIG4 as ready
Inflammatory bowel disease v0.121 LIG4 Zornitza Stark Gene: lig4 has been classified as Green List (High Evidence).
Inflammatory bowel disease v0.121 LIG4 Zornitza Stark Publications for gene: LIG4 were set to
Inflammatory bowel disease v0.120 LIG4 Zornitza Stark Phenotypes for gene: LIG4 were changed from to LIG4 syndrome, MIM# 606593
Inflammatory bowel disease v0.119 LIG4 Zornitza Stark Mode of inheritance for gene: LIG4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Aminoacidopathy v1.18 CBS Sangavi Sivagnanasundram gene: CBS was added
gene: CBS was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: CBS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CBS were set to 20301697; 18987302; 29398487
Phenotypes for gene: CBS were set to classic homocystinuria MONDO:0009352
Review for gene: CBS was set to GREEN
Added comment: Classified Definitive by ClinGen Aminoacidopathy GCEP on 12/04/2019 - https://search.clinicalgenome.org/CCID:004360

Well established gene-disease association. Multiple reported individuals and mouse models recapitulating the clinical phenotype. Classic homocystinuria is an inborn error of amino acid metabolism.
Sources: ClinGen
Intellectual disability syndromic and non-syndromic v0.5898 LIG4 Zornitza Stark Marked gene: LIG4 as ready
Intellectual disability syndromic and non-syndromic v0.5898 LIG4 Zornitza Stark Gene: lig4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5898 LIG4 Zornitza Stark Publications for gene: LIG4 were set to
Intellectual disability syndromic and non-syndromic v0.5897 LIG4 Zornitza Stark Phenotypes for gene: LIG4 were changed from to LIG4 syndrome, MIM# 606593
Intellectual disability syndromic and non-syndromic v0.5896 LIG4 Zornitza Stark Mode of inheritance for gene: LIG4 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5895 LIG4 Zornitza Stark Mode of inheritance for gene: LIG4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
IBMDx study v0.25 LIG4 Zornitza Stark Marked gene: LIG4 as ready
IBMDx study v0.25 LIG4 Zornitza Stark Gene: lig4 has been classified as Green List (High Evidence).
IBMDx study v0.25 LIG4 Zornitza Stark Publications for gene: LIG4 were set to
IBMDx study v0.24 LIG4 Zornitza Stark Mode of inheritance for gene: LIG4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.113 LIG4 Zornitza Stark Publications for gene: LIG4 were set to 16088910; 9823897; 10911993; 15333585; 9809069, 12023982; 11040211; 15175260; 19451691; 17554302; 11779494
BabyScreen+ newborn screening v1.112 LIG4 Zornitza Stark Publications for gene: LIG4 were set to
Intellectual disability syndromic and non-syndromic v0.5894 SLC35A1 Zornitza Stark Marked gene: SLC35A1 as ready
Intellectual disability syndromic and non-syndromic v0.5894 SLC35A1 Zornitza Stark Gene: slc35a1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5894 SLC35A1 Zornitza Stark Phenotypes for gene: SLC35A1 were changed from to Congenital disorder of glycosylation, type IIf, MIM# 603585
Intellectual disability syndromic and non-syndromic v0.5893 SLC35A1 Zornitza Stark Publications for gene: SLC35A1 were set to
Intellectual disability syndromic and non-syndromic v0.5892 SLC35A1 Zornitza Stark Mode of inheritance for gene: SLC35A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5891 SLC35A1 Zornitza Stark Classified gene: SLC35A1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5891 SLC35A1 Zornitza Stark Gene: slc35a1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5890 SLC35A1 Zornitza Stark edited their review of gene: SLC35A1: Changed rating: AMBER
Intellectual disability syndromic and non-syndromic v0.5890 SLC35A1 Zornitza Stark changed review comment from: At least 3 families reported.; to: At least 3 families reported, neurological presentation in two.
Intellectual disability syndromic and non-syndromic v0.5890 SLC35A1 Zornitza Stark reviewed gene: SLC35A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28856833, 23873973, 11157507; Phenotypes: Congenital disorder of glycosylation, type IIf, MIM# 603585; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Aminoacidopathy v1.18 CA5A Sangavi Sivagnanasundram edited their review of gene: CA5A: Changed publications: 24530203, 26913920, 23589845, 25834911
Intellectual disability syndromic and non-syndromic v0.5890 LRPPRC Zornitza Stark Marked gene: LRPPRC as ready
Intellectual disability syndromic and non-syndromic v0.5890 LRPPRC Zornitza Stark Gene: lrpprc has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5890 LRPPRC Zornitza Stark Phenotypes for gene: LRPPRC were changed from to Mitochondrial complex IV deficiency, nuclear type 5, (French-Canadian), MIM#220111
Aminoacidopathy v1.18 CA5A Sangavi Sivagnanasundram gene: CA5A was added
gene: CA5A was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: CA5A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CA5A were set to 24530203, 26913920, 23589845
Phenotypes for gene: CA5A were set to hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency MONDO:0014332
Review for gene: CA5A was set to GREEN
Added comment: Classified Definitive by ClinGen Aminoacidopathy GCEP on 10/09/2018 - https://search.clinicalgenome.org/CCID:004309

Reported in >10 probands with biochemical abnormalities (inborn error of metabolism)
Sources: ClinGen
Intellectual disability syndromic and non-syndromic v0.5889 LRPPRC Zornitza Stark Publications for gene: LRPPRC were set to
Intellectual disability syndromic and non-syndromic v0.5888 LRPPRC Zornitza Stark Mode of inheritance for gene: LRPPRC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5887 LRPPRC Zornitza Stark reviewed gene: LRPPRC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 5, (French-Canadian), MIM#220111; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Aminoacidopathy v1.18 ASS1 Sangavi Sivagnanasundram gene: ASS1 was added
gene: ASS1 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: ASS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ASS1 were set to 19006241
Phenotypes for gene: ASS1 were set to citrullinemia type I MONDO:0008988
Review for gene: ASS1 was set to GREEN
Added comment: Classified Definitive by ClinGen Aminoacidopathy GCEP on 27/12/2018 - https://search.clinicalgenome.org/CCID:004190

Well-established gene-disease association. Reported individuals present with inborn error of argininosuccinate synthetase metabolism.
Sources: ClinGen
Monogenic Diabetes v0.134 NEUROG3 Zornitza Stark Marked gene: NEUROG3 as ready
Monogenic Diabetes v0.134 NEUROG3 Zornitza Stark Gene: neurog3 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.134 NEUROG3 Zornitza Stark Phenotypes for gene: NEUROG3 were changed from to congenital malabsorptive diarrhea 4 MONDO:0012479
Aminoacidopathy v1.18 ARG1 Zornitza Stark Marked gene: ARG1 as ready
Aminoacidopathy v1.18 ARG1 Zornitza Stark Gene: arg1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.18 ARG1 Zornitza Stark Publications for gene: ARG1 were set to 16747805, 23859858, 1463019, 1598908, 12052859, 23920045
Aminoacidopathy v1.17 ARG1 Zornitza Stark Classified gene: ARG1 as Green List (high evidence)
Aminoacidopathy v1.17 ARG1 Zornitza Stark Gene: arg1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.16 AMT Zornitza Stark Marked gene: AMT as ready
Aminoacidopathy v1.16 AMT Zornitza Stark Gene: amt has been classified as Green List (High Evidence).
Aminoacidopathy v1.16 AMT Zornitza Stark Publications for gene: AMT were set to 27362913, 8005589, 25231368, 26179960, 26371980, 27164344, 6863283, 18941301
Aminoacidopathy v1.15 AMT Zornitza Stark Classified gene: AMT as Green List (high evidence)
Aminoacidopathy v1.15 AMT Zornitza Stark Gene: amt has been classified as Green List (High Evidence).
Aminoacidopathy v1.14 ASL Zornitza Stark Marked gene: ASL as ready
Aminoacidopathy v1.14 ASL Zornitza Stark Gene: asl has been classified as Green List (High Evidence).
Aminoacidopathy v1.14 ASL Zornitza Stark Publications for gene: ASL were set to 2263616, 17326097, 19703900, 12559843, 22081021
Aminoacidopathy v1.13 ASL Zornitza Stark Classified gene: ASL as Green List (high evidence)
Aminoacidopathy v1.13 ASL Zornitza Stark Gene: asl has been classified as Green List (High Evidence).
Monogenic Diabetes v0.133 INS Zornitza Stark Marked gene: INS as ready
Monogenic Diabetes v0.133 INS Zornitza Stark Gene: ins has been classified as Green List (High Evidence).
Monogenic Diabetes v0.133 INS Zornitza Stark Phenotypes for gene: INS were changed from Diabetes mellitus, insulin-dependent, 2, 125852; MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 10; Diabetes mellitus, type 1, 125852; Maturity-onset diabetes of the young, type 10, 613370; Transient Neonatal Diabetes, Dominant/Recessive; Diabetes mellitus, permanent neonatal, 606176; Hyperproinsulinemia, familial, with or without diabetes; Maturity Onset Diabetes of the Young (Dominant); MODY10; Maturity Onset Diabetes of the Young; Permanent Neonatal diabetes mellitus to diabetes mellitus, permanent neonatal 4 MONDO:0030089; maturity-onset diabetes of the young type 10 MONDO:0013240
Monogenic Diabetes v0.132 INS Zornitza Stark Publications for gene: INS were set to
Aminoacidopathy v1.12 ASNS Zornitza Stark Marked gene: ASNS as ready
Aminoacidopathy v1.12 ASNS Zornitza Stark Gene: asns has been classified as Green List (High Evidence).
Aminoacidopathy v1.12 ASNS Zornitza Stark Publications for gene: ASNS were set to 29375865, 25663424, 25227173, 29405484, 28776279, 30315573
Aminoacidopathy v1.11 ASNS Zornitza Stark Classified gene: ASNS as Green List (high evidence)
Aminoacidopathy v1.11 ASNS Zornitza Stark Gene: asns has been classified as Green List (High Evidence).
Monogenic Diabetes v0.131 INSR Zornitza Stark Marked gene: INSR as ready
Monogenic Diabetes v0.131 INSR Zornitza Stark Gene: insr has been classified as Green List (High Evidence).
Monogenic Diabetes v0.131 INSR Zornitza Stark Phenotypes for gene: INSR were changed from Pineal Hyperplasia,Insulin- Resistant Diabetes Mellitus, and Somatic Abnormalities; Diabetes mellitus, insulin-resistant, with acanthosis nigricans, 610549; Hyperinsulinemic hypoglycemia, familial, 5, 609968; Diabetes Mellitus, Insulin Resistant, with Acanthosis Nigricans; Pineal Hyperplasia, Insulin-Resistant Diabetes Mellitus, And Somatic Abnormalities; DIABETES MELLITUS, INSULIN-RESISTANT, WITH ACANTHOSIS NIGRICANS; Diabetes Mellitus, Insulin-Resistant, With Acanthosis Nigricans; Leprechaunism, 246200; OMIM 610549; Diabetes mellitus, insulin-resistant, with acanthosis nigricans; Rabson-Mendenhall syndrome, 262190 to insulin-resistance syndrome type A MONDO:0012520; Rabson-Mendenhall syndrome MONDO:0009874; Donohue syndrome MONDO:0009517
Monogenic Diabetes v0.130 INSR Zornitza Stark Publications for gene: INSR were set to 8288049
Aminoacidopathy v1.10 AGA Zornitza Stark reviewed gene: AGA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Canavan disease MONDO:0010079; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Aminoacidopathy v1.10 AGA Zornitza Stark Marked gene: AGA as ready
Aminoacidopathy v1.10 AGA Zornitza Stark Gene: aga has been classified as Green List (High Evidence).
Aminoacidopathy v1.10 AGA Zornitza Stark Classified gene: AGA as Green List (high evidence)
Aminoacidopathy v1.10 AGA Zornitza Stark Gene: aga has been classified as Green List (High Evidence).
Monogenic Diabetes v0.129 GATA6 Zornitza Stark Marked gene: GATA6 as ready
Monogenic Diabetes v0.129 GATA6 Zornitza Stark Gene: gata6 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.129 GATA6 Zornitza Stark Phenotypes for gene: GATA6 were changed from Pancreatic agenesis and congenital heart defects; Metabolic syndrome (coronary artery disease, hypertension, central obesity and diabetes); PANCREATIC AGENESIS AND CONGENITAL HEART DEFECTS to pancreatic hypoplasia-diabetes-congenital heart disease syndrome MONDO:0010802
Intellectual disability syndromic and non-syndromic v0.5887 TREX1 Zornitza Stark Marked gene: TREX1 as ready
Intellectual disability syndromic and non-syndromic v0.5887 TREX1 Zornitza Stark Gene: trex1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5887 TREX1 Zornitza Stark Phenotypes for gene: TREX1 were changed from to Aicardi-Goutieres syndrome MONDO:0018866
Intellectual disability syndromic and non-syndromic v0.5886 TREX1 Zornitza Stark Publications for gene: TREX1 were set to
Intellectual disability syndromic and non-syndromic v0.5885 TREX1 Zornitza Stark Mode of inheritance for gene: TREX1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5884 SERAC1 Zornitza Stark Marked gene: SERAC1 as ready
Intellectual disability syndromic and non-syndromic v0.5884 SERAC1 Zornitza Stark Gene: serac1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5884 SERAC1 Zornitza Stark Phenotypes for gene: SERAC1 were changed from to 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome (MEGDEL), MIM#614739
Intellectual disability syndromic and non-syndromic v0.5883 SERAC1 Zornitza Stark Publications for gene: SERAC1 were set to
Intellectual disability syndromic and non-syndromic v0.5883 SERAC1 Zornitza Stark Mode of inheritance for gene: SERAC1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5882 SERAC1 Zornitza Stark Mode of inheritance for gene: SERAC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5881 SERAC1 Zornitza Stark reviewed gene: SERAC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24741715, 37711114, 37090937, 28916646, 32684373; Phenotypes: 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome (MEGDEL), MIM#614739; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v1.63 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
Combined Immunodeficiency v1.62 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 v1.1796 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
Combined Immunodeficiency v1.62 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 v1.1795 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
Intellectual disability syndromic and non-syndromic v0.5881 TREX1 Hali Van Niel changed review comment from: Established gene disease association with Aicardi-Goutières Syndrome
Heterogeneity with variable phenotype, ranges from preserved cognition to severe intellectual disability
TREX1-related Aicardi Goutières syndrome have higher impairment (31559893)
ID common presenting feature (PMID: 25604658); to: Established gene disease association with Aicardi-Goutières Syndrome
Heterogeneity with variable phenotype, ranges from preserved cognition to severe intellectual disability
TREX1-related Aicardi Goutières syndrome have higher impairment (PMID: 31559893)
ID common presenting feature (PMID: 25604658)
Intellectual disability syndromic and non-syndromic v0.5881 TREX1 Hali Van Niel edited their review of gene: TREX1: Changed publications: 25604658, 16845398, 17357087, 31559893
Intellectual disability syndromic and non-syndromic v0.5881 TREX1 Hali Van Niel reviewed gene: TREX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25604658, 16845398, 17357087; Phenotypes: Aicardi-Goutieres syndrome MONDO:0018866; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Monogenic Diabetes v0.128 EIF2AK3 Zornitza Stark Marked gene: EIF2AK3 as ready
Monogenic Diabetes v0.128 EIF2AK3 Zornitza Stark Gene: eif2ak3 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.128 EIF2AK3 Zornitza Stark Phenotypes for gene: EIF2AK3 were changed from Wolcott-Rallison syndrome; Multiple Epiphyseal Dysplasia with Early-Onset Diabetes Mellitus to Wolcott-Rallison syndrome MONDO:0009192; neonatal diabetes mellitus MONDO:0016391
Monogenic Diabetes v0.127 EIF2AK3 Zornitza Stark Publications for gene: EIF2AK3 were set to 19837917
Monogenic Diabetes v0.126 GATA4 Zornitza Stark Marked gene: GATA4 as ready
Monogenic Diabetes v0.126 GATA4 Zornitza Stark Gene: gata4 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.126 GATA4 Zornitza Stark Phenotypes for gene: GATA4 were changed from to neonatal diabetes mellitus MONDO:0016391
Monogenic Diabetes v0.125 GATA4 Zornitza Stark reviewed gene: GATA4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: neonatal diabetes mellitus MONDO:0016391; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Monogenic Diabetes v0.125 GATA4 Hali Van Niel reviewed gene: GATA4: Rating: AMBER; Mode of pathogenicity: None; Publications: 24696446, 20854389; Phenotypes: neonatal diabetes mellitus MONDO:0016391; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Monogenic Diabetes v0.125 GATA6 Hali Van Niel reviewed gene: GATA6: Rating: GREEN; Mode of pathogenicity: None; Publications: 20581743, 22962692, 32524025, 28049534; Phenotypes: pancreatic hypoplasia-diabetes-congenital heart disease syndrome MONDO:0010802; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aminoacidopathy v1.9 AGA Sangavi Sivagnanasundram gene: AGA was added
gene: AGA was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: AGA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AGA were set to 8252036, 20301412
Phenotypes for gene: AGA were set to Canavan disease MONDO:0010079
Added comment: Classified Definitive by ClinGen Aminoacidopathy GCEP on 08/10/2020 - https://search.clinicalgenome.org/CCID:004188

Canavan disease is most prevalent in the AJ population however has been reported in other individuals as well. The most common variants in AJ population are p.Glu285Ala and p.Tyr231Ter (PMID:8252036). The most common variant reported in the non-Jewish population is p.Ala305Glu (PMID:20301412). All variants have been reported as pathogenic on ClinVar with at least 2/4 stars.

Variants have been reported in >10 individuals with elevated N-acetylaspartic acid (NAA) levels and LoF is the mechanism of disease.
Sources: ClinGen
Monogenic Diabetes v0.125 INSR Hali Van Niel reviewed gene: INSR: Rating: GREEN; Mode of pathogenicity: None; Publications: 34965699, 8288049, 28765322; Phenotypes: insulin-resistance syndrome type A MONDO:0012520, Rabson-Mendenhall syndrome MONDO:0009874, Donohue syndrome MONDO:0009517; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Aminoacidopathy v1.9 ASNS Sangavi Sivagnanasundram gene: ASNS was added
gene: ASNS was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: ASNS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ASNS were set to 29375865, 25663424, 25227173, 29405484, 28776279, 30315573
Phenotypes for gene: ASNS were set to congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome MONDO:0014258
Review for gene: ASNS was set to GREEN
Added comment: Classified Definitive by ClinGen Aminoacidopathy GCEP on 29/06/2020 - https://search.clinicalgenome.org/CCID:004187

Well established gene-disease association. Individuals have been reported with an inborn error of asparagine synthetase metabolism.
Sources: ClinGen
Monogenic Diabetes v0.125 INS Hali Van Niel reviewed gene: INS: Rating: GREEN; Mode of pathogenicity: None; Publications: 17855560, 18451997, 18162506, 18192540, 32034745, 30182532; Phenotypes: diabetes mellitus, permanent neonatal 4 MONDO:0030089, maturity-onset diabetes of the young type 10 MONDO:0013240; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Aminoacidopathy v1.9 ASL Sangavi Sivagnanasundram gene: ASL was added
gene: ASL was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: ASL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ASL were set to 2263616, 17326097, 19703900, 12559843, 22081021
Phenotypes for gene: ASL were set to argininosuccinic aciduria MONDO:0008815
Review for gene: ASL was set to GREEN
Added comment: Classified Definitive by ClinGen Aminoacidopathy GCEP on 15/09/2018 - https://search.clinicalgenome.org/CCID:004186

Established gene-disease association with reported individuals having an inborn error of argininosuccinate lyase metabolism.
Sources: ClinGen
Monogenic Diabetes v0.125 INSR Hali Van Niel Deleted their review
Monogenic Diabetes v0.125 INSR Hali Van Niel Deleted their comment
Monogenic Diabetes v0.125 INSR Hali Van Niel reviewed gene: INSR: Rating: GREEN; Mode of pathogenicity: None; Publications: 17855560, 18451997, 18162506, 18192540, 32034745, 30182532; Phenotypes: diabetes mellitus, permanent neonatal 4 MONDO:0030089, maturity-onset diabetes of the young type 10 MONDO:0013240; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Aminoacidopathy v1.9 AMT Sangavi Sivagnanasundram edited their review of gene: AMT: Changed rating: GREEN
Aminoacidopathy v1.9 ARG1 Sangavi Sivagnanasundram gene: ARG1 was added
gene: ARG1 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: ARG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARG1 were set to 16747805, 23859858, 1463019, 1598908, 12052859, 23920045
Phenotypes for gene: ARG1 were set to hyperargininemia MONDO:0008814
Review for gene: ARG1 was set to GREEN
Added comment: Classified Definitive by ClinGen Aminoacidopathy GCEP on 29/06/2020 - https://search.clinicalgenome.org/CCID:004163

Reported in >5 unrelated probands with manifestations of hyperammonemia and hyperargininemia. It is an inborn error of L-arginine metabolism.
Two knock out mouse models have been conducted attesting to the LoF mechanism of disease.
Sources: ClinGen
Monogenic Diabetes v0.125 NEUROG3 Hali Van Niel reviewed gene: NEUROG3: Rating: GREEN; Mode of pathogenicity: None; Publications: 32574610; Phenotypes: congenital malabsorptive diarrhea 4 MONDO:0012479; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Aminoacidopathy v1.9 AMT Sangavi Sivagnanasundram gene: AMT was added
gene: AMT was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: AMT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AMT were set to 27362913, 8005589, 25231368, 26179960, 26371980, 27164344, 6863283, 18941301
Phenotypes for gene: AMT were set to glycine encephalopathy MONDO:0011612
Added comment: Classified Definitive by ClinGen Aminoacidopathy GCEP on 24/05/2019 - https://search.clinicalgenome.org/CCID:004120

Established gene-disease association with around 15-20% of the reported individuals having glycine encephalopathy (inborn error of glycine metabolism). LoF is the mechanism of disease that has been supported by biochemical functional assays (PMID: 6863283, 18941301)
Sources: ClinGen
Intellectual disability syndromic and non-syndromic v0.5881 LRPPRC Kirsty Choi reviewed gene: LRPPRC: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 21266382, 8392290, 8392291, 26510951; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 5, (French-Canadian), 220111, developmental delay, hypotonia, mild facial dysmorphism, chronic well-compensated metabolic acidosis, high mortality due to episodes of severe acidosis and coma, hypertension, cerebrospinal fluid lactate levels, decreased blood bicarbonate levels, microvesicular steatosis, psychomotor delay, ataxia, hypotonia, transient tachypnea of the newborn, poor sucking, tremor, hypoglycemia, seizures; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5881 SLC35A1 Anissa Johnson changed review comment from: PMID: 23873973: 1 patient identified, homozygous with a variant in SLC35A1. Parents were heterozygous for the variant. Presented with "intellectual disability, seizures, ataxia, macrothrombocytopaenia, renal and cardiac involvement, and abnormal protein glycosylation". Biochemical assay showed "combined N- and O-glycosylation abnormalities and specific reduction in sialylation".
AR inheritance.; to: PMID: 23873973: 1 patient identified, homozygous with a variant in SLC35A1. Parents, consanguineous, were heterozygous for the variant. Presented with "intellectual disability, seizures, ataxia, macrothrombocytopaenia, renal and cardiac involvement, and abnormal protein glycosylation". Biochemical assay showed "combined N- and O-glycosylation abnormalities and specific reduction in sialylation".
AR inheritance.
Intellectual disability syndromic and non-syndromic v0.5881 SLC35A1 Anissa Johnson changed review comment from: PMID: 23873973: 1 patient identified, homozygous with a variant in SLC35A1. Parents were heterozygous for the variant. Presented with "intellectual disability, seizures, ataxia, macrothrombocytopaenia, renal and cardiac involvement, and abnormal protein glycosylation". Biochemical assay showed "combined N- and O-glycosylation abnormalities and specific reduction in sialylation".; to: PMID: 23873973: 1 patient identified, homozygous with a variant in SLC35A1. Parents were heterozygous for the variant. Presented with "intellectual disability, seizures, ataxia, macrothrombocytopaenia, renal and cardiac involvement, and abnormal protein glycosylation". Biochemical assay showed "combined N- and O-glycosylation abnormalities and specific reduction in sialylation".
AR inheritance.
Intellectual disability syndromic and non-syndromic v0.5881 SLC35A1 Anissa Johnson commented on gene: SLC35A1: PMID: 23873973: 1 patient identified, homozygous with a variant in SLC35A1. Parents were heterozygous for the variant. Presented with "intellectual disability, seizures, ataxia, macrothrombocytopaenia, renal and cardiac involvement, and abnormal protein glycosylation". Biochemical assay showed "combined N- and O-glycosylation abnormalities and specific reduction in sialylation".
Intellectual disability syndromic and non-syndromic v0.5881 SLC35A1 Anissa Johnson reviewed gene: SLC35A1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 23873973; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 500+ v1.0 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: 16088910, 9823897, 15333585, 9809069, 12023982, 11040211, 15175260, 19451691, 17554302; Phenotypes: LIG4 SYNDROME, MULTIPLE MYELOMA, RESISTANCE TO; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.111 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: 16088910, 9823897, 10911993, 15333585, 9809069, 12023982, 11040211, 15175260, 19451691, 17554302, 11779494; Phenotypes: LIG4 SYNDROME, MULTIPLE MYELOMA, RESISTANCE TO; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.6 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: 16088910, 9823897, 10911993, 15333585, 9809069, 12023982, 11040211, 15175260, 19451691, 17554302; Phenotypes: LIG4 SYNDROME, MULTIPLE MYELOMA, RESISTANCE TO; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
IBMDx study v0.23 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: 16088910, 9823897, 10911993, 15333585, 9809069, 12023982, 11040211, 15175260, 19451691, 17554302, 11779494; Phenotypes: LIG4 SYNDROME, MULTIPLE MYELOMA, RESISTANCE TO; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.245 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: 15333585, 20133615, 32534991, 11779494, 16088910; Phenotypes: LIG4 SYNDROME, MULTIPLE MYELOMA, RESISTANCE TO; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Growth failure v1.76 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: 16088910, 9823897, 10911993, 15333585, 9809069, 12023982, 11040211, , images, related citations] [Full Text] 15175260, 19451691, 17554302; Phenotypes: LIG4 syndrome, MULTIPLE MYELOMA, RESISTANCE TO; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Additional findings_Paediatric v0.278 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: 16088910, 9823897, 10911993, 15333585, 9809069, 12023982, 11040211, 15175260, 19451691, 17554302; Phenotypes: LIG4 syndrome, MULTIPLE MYELOMA, RESISTANCE TO; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mackenzie's Mission_Reproductive Carrier Screening v0.109 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: 16088910, 9823897, 10911993, 15333585, 9809069, 12023982; Phenotypes: lIG4 SYNDROME, MULTIPLE MYELOMA, RESISTANCE TO; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5881 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: 16088910, 9823897, 10911993, 15333585, 9809069, 12023982, 11040211, 15175260, 19451691, 17554302; Phenotypes: lIG4 syndrome, MULTIPLE MYELOMA, RESISTANCE TO; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe Combined Immunodeficiency (absent T absent B cells) v1.7 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: 16088910, 9823897, 10911993, 15333585, 9809069, 12023982, 11040211, 15175260, 19451691, 17554302; Phenotypes: LIG4 syndrome, MULTIPLE MYELOMA, RESISTANCE TO; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Disorders of immune dysregulation v0.186 LIG4 Santosh Varughese reviewed gene: LIG4: Rating: GREEN; Mode of pathogenicity: None; Publications: 16088910, 9823897, 10911993, 15333585, 9809069, 12023982, 11040211, 15175260; Phenotypes: LIG4 SYNDROME, MULTIPLE MYELOMA, RESISTANCE TO; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Combined Immunodeficiency v1.61 LIG4 Santosh Varughese reviewed gene: LIG4: Rating: GREEN; Mode of pathogenicity: None; Publications: 16088910, 9823897, 10911993, 15333585, 9809069, 12023982, 11040211, 15175260, 19451691, 17554302, 11779494, 10395545; Phenotypes: LIG4, MULTIPLE MYELOMA, RESISTANCE TO; Mode of inheritance: None
Microcephaly v1.260 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: 16357942, 32534991, 32471509, 11779494, 16088910, 15333585; Phenotypes: LIG4 syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
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
Inflammatory bowel disease v0.118 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: 16088910, 10911993, 15333585, 9809069, 12023982, 11040211; Phenotypes: LIG4 Syndrome, Multiple Myeloma, Resistance to; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5881 SAMD9 Raluca Rusu reviewed gene: SAMD9: Rating: RED; Mode of pathogenicity: Other; Publications: PMID: 27182967, 34659124, 32194975, 29175836, 37195360, 30900330, 37745698; Phenotypes: MIRAGE Syndrome, MIM#617053; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Chromosome Breakage Disorders v1.19 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
Cataract v0.366 LIG4 Santosh Varughese reviewed gene: LIG4: Rating: RED; 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: 16088910, 9823897, 10911993, 15333585, 9809069; Phenotypes: LIG4 syndrome, MULTIPLE MYELOMA, RESISTANCE TO; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bone Marrow Failure v1.91 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, DNA ligase IV deficiency; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.5881 SCN2A sabitha sateesh reviewed gene: SCN2A: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 31230762, 31904126, 28256214, 31904120, 31924505, 31205438, 1325650, 17021166; Phenotypes: Intellectual disability, autism, motor delay, epileptic seizures, uncoordinated oral movements, gastrointestinal disturbances, sleep problems.; Mode of inheritance: Unknown; Current diagnostic: yes
Bone Marrow Failure v1.91 GATA1 Santosh Varughese reviewed gene: GATA1: 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: 14656875; Phenotypes: Thrombocytopaenia, X-linked, with or without dyserythropoietic anaemia; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Bone Marrow Failure v1.91 GALE Santosh Varughese reviewed gene: GALE: 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: 30247636' 34159722, 36395340; Phenotypes: Thrombocytopenia 12; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Bone Marrow Failure v1.91 G6PC3 Santosh Varughese reviewed gene: G6PC3: 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: 19118303, 20799326, 25492228, 17318259, 20616219; Phenotypes: Neutropaenia, severe congenital 4, autosomal recessive, Dursun syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Bone Marrow Failure v1.91 FANCL Santosh Varughese reviewed gene: FANCL: 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: 19405097, 25754594, 33394227, 33224012; Phenotypes: Fanconi anemia, complementation group L; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Bone Marrow Failure v1.91 FANCI Santosh Varughese reviewed gene: FANCI: 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: 17452773; Phenotypes: Fanconi anemia, complementation group I; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Bone Marrow Failure v1.91 FANCG Santosh Varughese reviewed gene: FANCG: 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: 9806548, 12552564; Phenotypes: Fanconi anaemia, complementation group G; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Bone Marrow Failure v1.91 FANCF Santosh Varughese reviewed gene: FANCF: 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: 10615118, 31288759; Phenotypes: Fanconi anaemia, complementation group F; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Bone Marrow Failure v1.91 FANCE Santosh Varughese reviewed gene: FANCE: 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: 11001585, 31586946, 7662964, 9382107, 9147877, 10205272; Phenotypes: Fanconi anaemia, complementation group E; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Bone Marrow Failure v1.91 FANCD2 Santosh Varughese reviewed gene: FANCD2: 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: 17436244; Phenotypes: Fanconi anaemia, complementation group D2; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Bone Marrow Failure v1.91 FANCC Santosh Varughese reviewed gene: FANCC: 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: 31044565, 30792206, 28717661; Phenotypes: Fanconi anemia, complementation group C; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Bone Marrow Failure v1.91 FANCB Santosh Varughese reviewed gene: FANCB: 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: 15502827; Phenotypes: Fanconi anaemia, complementation group B; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Bone Marrow Failure v1.91 FANCA Santosh Varughese reviewed gene: FANCA: 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: 10094191; Phenotypes: Fanconi anaemia, complementation group A; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Bone Marrow Failure v1.91 ETV6 Santosh Varughese reviewed gene: ETV6: 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: 25581430, 25807284; Phenotypes: Thrombocytopenia 5; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Bone Marrow Failure v1.91 ERCC6L2 Santosh Varughese reviewed gene: ERCC6L2: 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: 24507776, 27185855; Phenotypes: Bone marrow failure syndrome 2; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Bone Marrow Failure v1.91 ERCC4 Santosh Varughese reviewed gene: ERCC4: 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: 23623386; Phenotypes: Fanconi anemia, complementation group Q; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Bone Marrow Failure v1.91 ELANE Santosh Varughese 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: 19036076, 3124897, 33968054; Phenotypes: Neutropaenia, severe congenital 1, autosomal dominant; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Bone Marrow Failure v1.91 EFL1 Santosh Varughese reviewed gene: EFL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28331068, 31151987; Phenotypes: Shwachman-Diamond syndrome 2; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Bone Marrow Failure v1.91 DUT Santosh Varughese reviewed gene: DUT: Rating: GREEN; Mode of pathogenicity: None; Publications: 28073829, 35611808; Phenotypes: Bone marrow failure and diabetes mellitus syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Bone Marrow Failure v1.91 DNASE2 Santosh Varughese reviewed gene: DNASE2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29259162, 31775019; Phenotypes: Autoinflammatory-pancytopenia syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Bone Marrow Failure v1.91 DNAJC21 Santosh Varughese reviewed gene: DNAJC21: Rating: GREEN; Mode of pathogenicity: None; Publications: 29700810, 28062395, 27346687; Phenotypes: Bone marrow failure syndrome 3; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Bone Marrow Failure v1.91 DKC1 Santosh Varughese reviewed gene: DKC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31269755, 26951492, 29081935, 25940403; Phenotypes: Dyskeratosis congenita, X-linked 305000, Hoyeraal-Hreidarsson Syndrome; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.5881 SAMHD1 Reetoo Ramessur reviewed gene: SAMHD1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301648, 29239743, 25246298, 19525956, 21102625, 33307271, 35418820; Phenotypes: Aicardi-Goutieres syndrome 5, MIM# 612952; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bone Marrow Failure v1.91 DDX41 Santosh Varughese reviewed gene: DDX41: 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: 10607561, 26712909, 25920683; Phenotypes: MYELOPROLIFERATIVE/LYMPHOPROLIFERATIVE NEOPLASMS, FAMILIAL (MULTIPLE TYPES), SUSCEPTIBILITY TO; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Bone Marrow Failure v1.91 DCLRE1B Santosh Varughese reviewed gene: DCLRE1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 10699141, 20479256, 35007328; Phenotypes: Dyskeratosis congenita, autosomal recessive 8; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Bone Marrow Failure v1.91 CTC1 Santosh Varughese reviewed gene: CTC1: Rating: ; Mode of pathogenicity: None; Publications: 22267198, 22387016; Phenotypes: Cerebroretinal microangiopathy with calcifications and cysts; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Bone Marrow Failure v1.91 CSF3R Santosh Varughese reviewed gene: CSF3R: Rating: GREEN; Mode of pathogenicity: None; Publications: 24753537, 26324699, 33511998, 32966608; Phenotypes: Neutropaenia, severe congenital, 7, autosomal recessive; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Bone Marrow Failure v1.91 CLPB Santosh Varughese reviewed gene: CLPB: Rating: GREEN; Mode of pathogenicity: None; Publications: 34115842, 25597510, 25597511; Phenotypes: 3-@METHYLGLUTACONIC ACIDURIA, TYPE VIIB, 3-@METHYLGLUTACONIC ACIDURIA, TYPE VIIA, NEUTROPENIA, SEVERE CONGENITAL, 9, AUTOSOMAL DOMINANT; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Bone Marrow Failure v1.91 CDAN1 Santosh Varughese reviewed gene: CDAN1: 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: 32518175; Phenotypes: Dyserythropoietic anemia, congenital, type Ia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Bone Marrow Failure v1.91 C15orf41 Santosh Varughese reviewed gene: C15orf41: 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: 23716552, 32293259, 31191338, 29885034; Phenotypes: Dyserythropoietic anemia, congenital, type Ib; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Aminoacidopathy v1.9 ALDH7A1 Sangavi Sivagnanasundram gene: ALDH7A1 was added
gene: ALDH7A1 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: ALDH7A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALDH7A1 were set to 19142996, 16491085, 22784480, 29053735
Phenotypes for gene: ALDH7A1 were set to pyridoxine-dependent epilepsy MONDO:0009945
Review for gene: ALDH7A1 was set to GREEN
Added comment: Classified Definitive on 26/07/2019 by ClinGen Aminoacidopathy GCEP - https://search.clinicalgenome.org/CCID:004097

Reported in 10 individuals and functional evidence supporting the gene-disease association.
Sources: ClinGen
Bone Marrow Failure v1.91 BRIP1 Santosh Varughese reviewed gene: BRIP1: 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: 27107905; Phenotypes: Fanconi anaemia, complementation group J; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Bone Marrow Failure v1.91 BRCA2 Santosh Varughese reviewed gene: BRCA2: Rating: ; 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: 16825431; Phenotypes: Fanconi anaemia, complementation group D1; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Bone Marrow Failure v1.91 BRCA1 Santosh Varughese reviewed gene: BRCA1: 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: 23269703, 29133208, 25472942, 29712865; Phenotypes: Fanconi anemia, complementation group S; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Bone Marrow Failure v1.91 ANKRD26 Santosh Varughese reviewed gene: ANKRD26: 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: Thrombocytopaenia 2; Phenotypes: 21211618; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Bone Marrow Failure v1.91 ALAS2 Santosh Varughese reviewed gene: ALAS2: 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: 10029606; Phenotypes: Anemia, sideroblastic, 1; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Bone Marrow Failure v1.91 AK2 Santosh Varughese reviewed gene: AK2: 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: 19043417, 19043416; Phenotypes: Reticular dysgenesis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Aminoacidopathy v1.9 ALDH4A1 Sangavi Sivagnanasundram gene: ALDH4A1 was added
gene: ALDH4A1 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: ALDH4A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALDH4A1 were set to 2624476, 13835167, 4369405, 8621661
Phenotypes for gene: ALDH4A1 were set to hyperprolinemia type 2 MONDO:0009401
Review for gene: ALDH4A1 was set to GREEN
Added comment: Classified Definitive on 23/10/2020 by ClinGen Aminoacidopathy GCEP - https://search.clinicalgenome.org/CCID:004094

Well reported gene-disease association in individuals with abnormal biochemistry. Most individuals present with elevated P5C levels
Sources: ClinGen
Bone Marrow Failure v1.91 ADA2 Santosh Varughese edited their review of gene: ADA2: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bone Marrow Failure v1.91 ACD Santosh Varughese edited their review of gene: ACD: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Bone Marrow Failure v1.91 ADH5 Santosh Varughese reviewed gene: ADH5: 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: 33147438; Phenotypes: AMED syndrome, digenic, Aplastic anaemia, myelodysplasia, short stature; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Bone Marrow Failure v1.91 ADA2 Santosh Varughese reviewed gene: ADA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25075847, 30406060, 12804991, 24552285, 10756095, 31652311, 26867732, 15926889, 20147294, 24552284; Phenotypes: VASCULITIS, AUTOINFLAMMATION, IMMUNODEFICIENCY, AND HEMATOLOGIC DEFECTS SYNDROME, SNEDDON SYNDROME; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Heterotaxy v1.32 ARL2BP Andrew Fennell reviewed gene: ARL2BP: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38649918, 36507858; Phenotypes: Retinitis pigmentosa with or without situs inversus MIM#615434; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bone Marrow Failure v1.91 ACTB Santosh Varughese reviewed gene: ACTB: Rating: GREEN; Mode of pathogenicity: None; Publications: 32170967, 24458642, 28347698, 28487785, 29220674, 11311002, 23756437, 2837653, 31970217, 10928857, 12325076; Phenotypes: Dystonia-Deafness Syndrome 1, Baraitser-Winter Syndrome 1, Becker Nevus Syndrome and Becker Nevi, Congenital Smooth Muscle Hamartoma with or without Hemihypertrophy, Thrombocytopenia 8 with Dysmorphic Features and Developmental Delay; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Bone Marrow Failure v1.91 ACD Santosh Varughese reviewed gene: ACD: 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: 25205116, 15537664, 25233904, 15181449, 18535244, 23103865, 17237768, 17237767, 15231715; Phenotypes: Dyskeratosis Congenita; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.5881 SIX3 Laura Mazurkijevic reviewed gene: SIX3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20531442, 19346217, 20157829, 15635066; Phenotypes: Holoprosencephaly 2, autosomal dominant, MIM#157170; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5881 THRA Hnin Aung changed review comment from: Over 10 sequence variants (including truncating nonsense and frameshift as well as missense) have been reported in the literature in association with consistent phenotype of mild hypothyroidism (growth retardation, relatively high birth length and weight, mild-to-moderate mental retardation, mild skeletal dysplasia, delayed dentition and constipation) and specific facial features. Milder outcomes for missense variants and more severe phenotype manifestation for truncating variants have been observed.

Most of the variants are located in the last exon of the THRA isoform 1 (NM_199334.5; a shorter isoform) affecting the C-terminal ligand binding domain with nonsense and frameshift variants predicted to escape nonsense mediated decay. These variants are either de novo or inherited from an affected parent. A few pedigrees are also available with segregation data. Truncating variants appear to have near complete penetrance whereas missense variants may be associated with variable expressivity (Family C - PMID: 27144938).

Functional evidence suggests altered gene product with possible dominant negative effect (PMID: 22168587, 28471274). Knock in mouse model available for E403X presenting with similar phenotype as seen in the human patients, including growth retardation and variable presentation of psychomotor deficit (PMID: 32924834). A small number THRA sequence variant (missense) reported among autism cohort [PMID: 28856816, 25621899].; to: Over 10 sequence variants (including truncating nonsense and frameshift as well as missense) have been reported in the literature in association with consistent phenotype of mild hypothyroidism (growth retardation, relatively high birth length and weight, mild-to-moderate mental retardation, mild skeletal dysplasia, delayed dentition and constipation) and specific facial features. Milder outcomes for missense variants and more severe phenotype manifestations for truncating variants have been observed.

Most of the variants are located in the last exon of the THRA isoform 1 (NM_199334.5; a shorter isoform) affecting the C-terminal ligand binding domain with nonsense and frameshift variants predicted to escape nonsense mediated decay. These variants are either de novo or inherited from an affected parent. A few pedigrees are also available with segregation data. Truncating variants appear to have near complete penetrance whereas missense variants may be associated with variable expressivity (Family C - PMID: 27144938).

Functional evidence suggests altered gene product with possible dominant negative effect (PMID: 22168587, 28471274). Knock in mouse model available for E403X presenting with similar phenotype as seen in the human patients, including growth retardation and variable presentation of psychomotor deficit (PMID: 32924834). A small number THRA sequence variant (missense) reported among autism cohort [PMID: 28856816, 25621899].
Intellectual disability syndromic and non-syndromic v0.5881 THRA Hnin Aung changed review comment from: Over 10 sequence variants (including truncating nonsense and frameshift as well as missense) have been reported in the literature in association with consistent phenotype of mild hypothyroidism (growth retardation, relatively high birth length and weight, mild-to-moderate mental retardation, mild skeletal dysplasia, delayed dentition and constipation) and specific facial features. Milder outcomes for missense variants and more severe phenotype manifestation for truncating variants have been observed.

Most of the variants are located in the last exon of the THRA isoform 1 (NM_199334.5; a shorter isoform) affecting the C-terminal ligand binding domain with nonsense and frameshift variants predicted to escape nonsense mediated decay. These variants are either de novo or inherited from an affected parent. A few pedigrees are also available with segregation data. Truncating variants appear to have near complete penetrance whereas missense variants may be associated with variable expressivity (Family C - PMID: 27144938).

Functional evidence suggests altered gene product with possible dominant negative effect (PMID: 22168587, 28471274). Knock in mouse model available for E403X presenting with similar phenotype as seen in the human patients, including growth retardation and variable presentation of psychomotor deficit (PMID: 32924834). A small number THRA sequence variant (missense) reported among autism cohort [PMID: 28856816, 25621899].; to: Over 10 sequence variants (including truncating nonsense and frameshift as well as missense) have been reported in the literature in association with consistent phenotype of mild hypothyroidism (growth retardation, relatively high birth length and weight, mild-to-moderate mental retardation, mild skeletal dysplasia, delayed dentition and constipation) and specific facial features. Milder outcomes for missense variants and more severe phenotype manifestation for truncating variants have been observed.

Most of the variants are located in the last exon of the THRA isoform 1 (NM_199334.5; a shorter isoform) affecting the C-terminal ligand binding domain with nonsense and frameshift variants predicted to escape nonsense mediated decay. These variants are either de novo or inherited from an affected parent. A few pedigrees are also available with segregation data. Truncating variants appear to have near complete penetrance whereas missense variants may be associated with variable expressivity (Family C - PMID: 27144938).

Functional evidence suggests altered gene product with possible dominant negative effect (PMID: 22168587, 28471274). Knock in mouse model available for E403X presenting with similar phenotype as seen in the human patients, including growth retardation and variable presentation of psychomotor deficit (PMID: 32924834). A small number THRA sequence variant (missense) reported among autism cohort [PMID: 28856816, 25621899].
Intellectual disability syndromic and non-syndromic v0.5881 THRA Hnin Aung reviewed gene: THRA: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 22494134, 23940126, 24847461, 25670821, 26037512, 25621899, 27144938, 28856816, 30842990, 37469961; Phenotypes: Hypothyroidism congenital nongoitrous 6 (MIM 614450), Intellectual disability syndromic, Growth retardation, Facial dysmorphism, Constipation; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aminoacidopathy v1.9 ALDH18A1 Sangavi Sivagnanasundram edited their review of gene: ALDH18A1: Changed rating: GREEN
Aminoacidopathy v1.9 ALDH18A1 Sangavi Sivagnanasundram gene: ALDH18A1 was added
gene: ALDH18A1 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: ALDH18A1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ALDH18A1 were set to 32017139, 26026163, 26320891
Phenotypes for gene: ALDH18A1 were set to P5CS deficiency MONDO:0100126
Added comment: Classified Definitive on 18/05/2021 by ClinGen Aminoacidopathy GCEP - https://search.clinicalgenome.org/CCID:004093

P5CS is an important enzyme in several amino acid pathways. >10 Individuals with abnormal biochemistry and function studies have been conducted.

Mechanism of disease is variable LOF depending on the mutation present which results in the spectrum of severity in the phenotype.
Dominant negative mutations have a less severe phenotype (AD cutis laxa/hsp) to the severely affected proteins having no activity (AR cutis laxa/hsp) (PMID: 32017139).
Sources: ClinGen
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
Aminoacidopathy v1.9 AHCY Sangavi Sivagnanasundram gene: AHCY was added
gene: AHCY was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: AHCY was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AHCY were set to 13641268, 15024124, 16736098, 20852937, 22959829, 30121674, 26527160, 26095522, 27848944, 31957987, 35463910
Phenotypes for gene: AHCY were set to hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase MONDO:0013404
Review for gene: AHCY was set to GREEN
Added comment: Individuals present with psychomotor delay along with biochemical abnormalities (elevated plasma SAH, SAM, methionione and creatine kinase with decreased SAM/SAH ratio).
At least 10 probands (majority having missense variants but nonsense variants have been reported as well) have been reported with a biochemical abnormality. LoF is the mechanism of disease.

Classified Moderate on 12/12/2022 by ClinGen Aminoacidopathy GCEP - https://search.clinicalgenome.org/CCID:004077
Sources: ClinGen
Genetic Epilepsy v1.0 Zornitza Stark promoted panel to version 1.0
Genetic Epilepsy v0.2805 LMNB2 Zornitza Stark Marked gene: LMNB2 as ready
Genetic Epilepsy v0.2805 LMNB2 Zornitza Stark Gene: lmnb2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2805 LMNB2 Zornitza Stark Classified gene: LMNB2 as Amber List (moderate evidence)
Genetic Epilepsy v0.2805 LMNB2 Zornitza Stark Gene: lmnb2 has been classified as Amber List (Moderate Evidence).
Aminoacidopathy v1.9 ADK Sangavi Sivagnanasundram changed review comment from: Classified Definitive on 08/04/2021 by ClinGen Aminoacidopathy GCEP - https://search.clinicalgenome.org/CCID:004066

Multiple reported in individuals with ADK deficiency.
LoF is the mechanism of disease and functional studies have been conducted to confirm loss ADK activity.
Sources: ClinGen; to: Classified Definitive on 08/04/2021 by ClinGen Aminoacidopathy GCEP - https://search.clinicalgenome.org/CCID:004066

ADK is a multisystem disorder. individuals can present with other phenotypes (such as DD, seizures, hypotonia) in the neonatal period.
Multiple reported in individuals with ADK deficiency.
LoF is the mechanism of disease and functional studies have been conducted to confirm loss ADK activity.
Sources: ClinGen
Genetic Epilepsy v0.2804 GABRA6 Zornitza Stark Marked gene: GABRA6 as ready
Genetic Epilepsy v0.2804 GABRA6 Zornitza Stark Gene: gabra6 has been classified as Red List (Low Evidence).
Aminoacidopathy v1.9 ADK Sangavi Sivagnanasundram edited their review of gene: ADK: Changed phenotypes: adenosine kinase deficiency MONDO:0100255
Aminoacidopathy v1.9 ADK Sangavi Sivagnanasundram changed review comment from: Classified Definitive on 08/04/2021 by ClinGen Aminoacidopathy GCEP - https://search.clinicalgenome.org/CCID:004066

ADK is a multisystem disorder. individuals can present with other phenotypes (such as DD, seizures, hypotonia) in the neonatal period.
Multiple reported in individuals with ADK deficiency.
LoF is the mechanism of disease and functional studies have been conducted to confirm loss ADK activity.
Sources: ClinGen; to: Classified Definitive on 08/04/2021 by ClinGen Aminoacidopathy GCEP - https://search.clinicalgenome.org/CCID:004066

Multiple reported in individuals with ADK deficiency.
LoF is the mechanism of disease and functional studies have been conducted to confirm loss ADK activity.
Sources: ClinGen
Genetic Epilepsy v0.2804 FAME1 Zornitza Stark Marked STR: FAME1 as ready
Genetic Epilepsy v0.2804 FAME1 Zornitza Stark Str: fame1 has been removed from the panel.
Genetic Epilepsy v0.2804 FAME1 Zornitza Stark Classified STR: FAME1 as No list
Genetic Epilepsy v0.2804 FAME1 Zornitza Stark Str: fame1 has been removed from the panel.
Aminoacidopathy v1.9 ADK Sangavi Sivagnanasundram edited their review of gene: ADK: Changed phenotypes: hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase MONDO:0013404
Aminoacidopathy v1.9 ADK Sangavi Sivagnanasundram gene: ADK was added
gene: ADK was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: ADK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADK were set to 21963049, 26642971, 33309011, 27671891
Phenotypes for gene: ADK were set to adenosine kinase deficiency MONDO:0100255
Review for gene: ADK was set to GREEN
Added comment: Classified Definitive on 08/04/2021 by ClinGen Aminoacidopathy GCEP - https://search.clinicalgenome.org/CCID:004066

ADK is a multisystem disorder. individuals can present with other phenotypes (such as DD, seizures, hypotonia) in the neonatal period.
Multiple reported in individuals with ADK deficiency.
LoF is the mechanism of disease and functional studies have been conducted to confirm loss ADK activity.
Sources: ClinGen
Aminoacidopathy v1.9 ACY1 Sangavi Sivagnanasundram gene: ACY1 was added
gene: ACY1 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: ACY1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACY1 were set to 4997716, 24117009, 16465618, 17562838, 21414403, 16274666, 20480396
Phenotypes for gene: ACY1 were set to aminoacylase 1 deficiency MONDO:0012368
Review for gene: ACY1 was set to GREEN
Added comment: Classified Definitive on 25/09/2020 by ClinGen Aminoacidopathy GCEP - https://search.clinicalgenome.org/CCID:004051

Reported in >5 unrelated individuals with biochemically abnormal organic aciduria.
LoF appears to be the mechanism of disease but no functional studies conducted at this stage.
Sources: ClinGen
Genetic Epilepsy v0.2803 RAPGEF2 Zornitza Stark Marked gene: RAPGEF2 as ready
Genetic Epilepsy v0.2803 RAPGEF2 Zornitza Stark Gene: rapgef2 has been removed from the panel.
Genetic Epilepsy v0.2803 PEX10 Zornitza Stark Classified gene: PEX10 as Green List (high evidence)
Genetic Epilepsy v0.2803 PEX10 Zornitza Stark Gene: pex10 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2802 PEX10 Zornitza Stark reviewed gene: PEX10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 6A (Zellweger), MIM#614870; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2802 KATNB1 Zornitza Stark Marked gene: KATNB1 as ready
Genetic Epilepsy v0.2802 KATNB1 Zornitza Stark Gene: katnb1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2802 KATNB1 Zornitza Stark Classified gene: KATNB1 as Green List (high evidence)
Genetic Epilepsy v0.2802 KATNB1 Zornitza Stark Gene: katnb1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2801 KATNB1 Zornitza Stark reviewed gene: KATNB1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Lissencephaly 6, with microcephaly MIM#616212; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2801 JARID2 Zornitza Stark Marked gene: JARID2 as ready
Genetic Epilepsy v0.2801 JARID2 Zornitza Stark Gene: jarid2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2801 JARID2 Zornitza Stark Marked gene: JARID2 as ready
Genetic Epilepsy v0.2801 JARID2 Zornitza Stark Gene: jarid2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2801 KIF4A Zornitza Stark Marked gene: KIF4A as ready
Genetic Epilepsy v0.2801 KIF4A Zornitza Stark Gene: kif4a has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2801 UBE3A Zornitza Stark Marked gene: UBE3A as ready
Genetic Epilepsy v0.2801 UBE3A Zornitza Stark Gene: ube3a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2801 UBE3A Zornitza Stark Phenotypes for gene: UBE3A were changed from to Angelman syndrome, MIM#105830
Genetic Epilepsy v0.2800 UBE3A Zornitza Stark Publications for gene: UBE3A were set to
Genetic Epilepsy v0.2799 UBE3A Zornitza Stark Mode of inheritance for gene: UBE3A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Genetic Epilepsy v0.2798 UBE2A Zornitza Stark Marked gene: UBE2A as ready
Genetic Epilepsy v0.2798 UBE2A Zornitza Stark Gene: ube2a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2798 UBE2A Zornitza Stark Phenotypes for gene: UBE2A were changed from to Intellectual developmental disorder, X-linked syndromic, Nascimento type 300860
Genetic Epilepsy v0.2797 UBE2A Zornitza Stark Publications for gene: UBE2A were set to
Genetic Epilepsy v0.2796 UBE2A Zornitza Stark Mode of inheritance for gene: UBE2A was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Genetic Epilepsy v0.2795 UBE2A Zornitza Stark changed review comment from: >3 families reported. Obligate carrier females unaffected.
ClinGen: Definitively associated with syndromic X-linked ID; to: >3 families reported. Obligate carrier females unaffected.
ClinGen: Definitively associated with syndromic X-linked ID. Seizures are part of the phenotype.
Genetic Epilepsy v0.2795 UBE2A Zornitza Stark edited their review of gene: UBE2A: Changed phenotypes: Intellectual developmental disorder, X-linked syndromic, Nascimento type 300860
Genetic Epilepsy v0.2795 TUBG1 Zornitza Stark Marked gene: TUBG1 as ready
Genetic Epilepsy v0.2795 TUBG1 Zornitza Stark Gene: tubg1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2795 TUBG1 Zornitza Stark Phenotypes for gene: TUBG1 were changed from to Cortical dysplasia, complex, with other brain malformations 4, MIM# 615412
Genetic Epilepsy v0.2794 TUBG1 Zornitza Stark Publications for gene: TUBG1 were set to
Genetic Epilepsy v0.2793 TUBG1 Zornitza Stark Mode of inheritance for gene: TUBG1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2792 TUBB4A Zornitza Stark Marked gene: TUBB4A as ready
Genetic Epilepsy v0.2792 TUBB4A Zornitza Stark Gene: tubb4a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2792 TUBB4A Zornitza Stark Phenotypes for gene: TUBB4A were changed from to Leukodystrophy, hypomyelinating, 6, OMIM # 612438
Genetic Epilepsy v0.2791 TUBB4A Zornitza Stark Publications for gene: TUBB4A were set to
Genetic Epilepsy v0.2790 TUBB4A Zornitza Stark Mode of inheritance for gene: TUBB4A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2789 TUBB4A Zornitza Stark edited their review of gene: TUBB4A: Changed phenotypes: Leukodystrophy, hypomyelinating, 6, OMIM # 612438
Genetic Epilepsy v0.2789 TUBB4A Zornitza Stark changed review comment from: Dystonia-4, also known as whispering dysphonia, is an autosomal dominant neurologic disorder characterized by onset in the second to third decade of progressive laryngeal dysphonia followed by the involvement of other muscles, such as the neck or limbs. Some patients develop an ataxic gait. At least 8 unrelated families reported.

Leukodystrophy: multiple individuals reported, onset of symptoms is typically in infancy and early childhood.; to: Leukodystrophy: multiple individuals reported, onset of symptoms is typically in infancy and early childhood. Seizures are part of the phenotype.
Genetic Epilepsy v0.2789 TUBB2B Zornitza Stark Marked gene: TUBB2B as ready
Genetic Epilepsy v0.2789 TUBB2B Zornitza Stark Gene: tubb2b has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2789 TUBB2B Zornitza Stark Phenotypes for gene: TUBB2B were changed from to Cortical dysplasia, complex, with other brain malformations 7, MIM# 610031
Genetic Epilepsy v0.2788 TUBB2B Zornitza Stark Publications for gene: TUBB2B were set to
Genetic Epilepsy v0.2787 TUBB2B Zornitza Stark Mode of inheritance for gene: TUBB2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2786 TUBB Zornitza Stark Marked gene: TUBB as ready
Genetic Epilepsy v0.2786 TUBB Zornitza Stark Gene: tubb has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2786 TUBB Zornitza Stark Phenotypes for gene: TUBB were changed from to Cortical dysplasia, complex, with other brain malformations 6, MIM# 615771
Genetic Epilepsy v0.2785 TUBB Zornitza Stark Publications for gene: TUBB were set to
Genetic Epilepsy v0.2784 TUBB Zornitza Stark Mode of inheritance for gene: TUBB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2783 TUBB Zornitza Stark changed review comment from: Established gene-disease association.; to: Established gene-disease association. Seizures are part of the phenotype.
Genetic Epilepsy v0.2783 TUBA1A Zornitza Stark Marked gene: TUBA1A as ready
Genetic Epilepsy v0.2783 TUBA1A Zornitza Stark Gene: tuba1a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2783 TUBA1A Zornitza Stark Phenotypes for gene: TUBA1A were changed from to Lissencephaly 3, MIM# 611603
Genetic Epilepsy v0.2782 TUBA1A Zornitza Stark Mode of inheritance for gene: TUBA1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2781 TSEN54 Zornitza Stark Marked gene: TSEN54 as ready
Genetic Epilepsy v0.2781 TSEN54 Zornitza Stark Gene: tsen54 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2781 TSEN54 Zornitza Stark Phenotypes for gene: TSEN54 were changed from to Pontocerebellar hypoplasia type 2A, MIM# 277470
Genetic Epilepsy v0.2780 TSEN54 Zornitza Stark Mode of inheritance for gene: TSEN54 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2779 TSEN54 Zornitza Stark changed review comment from: Gene-disease association between bi-allelic variants and PCH is well established, limited evidence for mono-allelic variants causing ataxia as per Bryony's review.; to: Gene-disease association between bi-allelic variants and PCH is well established, limited evidence for mono-allelic variants causing ataxia as per Bryony's review. Seizures are part of the PCH phenotype.
Genetic Epilepsy v0.2779 TSC2 Zornitza Stark Marked gene: TSC2 as ready
Genetic Epilepsy v0.2779 TSC2 Zornitza Stark Gene: tsc2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2779 TSC2 Zornitza Stark Phenotypes for gene: TSC2 were changed from to Tuberous sclerosis 2, MIM# 613254
Genetic Epilepsy v0.2778 TSC2 Zornitza Stark Mode of inheritance for gene: TSC2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2777 TSC2 Zornitza Stark reviewed gene: TSC2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Tuberous sclerosis 2, MIM# 613254; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2777 TSC1 Zornitza Stark Marked gene: TSC1 as ready
Genetic Epilepsy v0.2777 TSC1 Zornitza Stark Gene: tsc1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2777 TSC1 Zornitza Stark Phenotypes for gene: TSC1 were changed from to Tuberous sclerosis 1, MIM# 191100
Genetic Epilepsy v0.2776 TSC1 Zornitza Stark Mode of inheritance for gene: TSC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2775 TSC1 Zornitza Stark reviewed gene: TSC1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Tuberous sclerosis 1, MIM# 191100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2775 TPP1 Zornitza Stark Marked gene: TPP1 as ready
Genetic Epilepsy v0.2775 TPP1 Zornitza Stark Gene: tpp1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2775 TPP1 Zornitza Stark Phenotypes for gene: TPP1 were changed from to Ceroid lipofuscinosis, neuronal, 2, MIM# 204500; MONDO:0008769
Genetic Epilepsy v0.2774 TPP1 Zornitza Stark Publications for gene: TPP1 were set to
Genetic Epilepsy v0.2773 TPP1 Zornitza Stark Mode of inheritance for gene: TPP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2772 TPP1 Zornitza Stark edited their review of gene: TPP1: Changed phenotypes: Ceroid lipofuscinosis, neuronal, 2, MIM# 204500, MONDO:0008769
Genetic Epilepsy v0.2772 TCF4 Zornitza Stark Marked gene: TCF4 as ready
Genetic Epilepsy v0.2772 TCF4 Zornitza Stark Gene: tcf4 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2772 TCF4 Zornitza Stark Phenotypes for gene: TCF4 were changed from to Pitt-Hopkins syndrome, MIM# 610954
Genetic Epilepsy v0.2771 TCF4 Zornitza Stark Publications for gene: TCF4 were set to
Genetic Epilepsy v0.2770 TCF4 Zornitza Stark Mode of inheritance for gene: TCF4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2769 TCF4 Zornitza Stark changed review comment from: The association with Pitt-Hopkins syndrome is well established.

Corneal dystrophy is associated with STR.; to: The association with Pitt-Hopkins syndrome is well established. Seizures are part of the phenotype.

Corneal dystrophy is associated with STR.
Genetic Epilepsy v0.2769 TBL1XR1 Zornitza Stark Marked gene: TBL1XR1 as ready
Genetic Epilepsy v0.2769 TBL1XR1 Zornitza Stark Gene: tbl1xr1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2769 TBL1XR1 Zornitza Stark Phenotypes for gene: TBL1XR1 were changed from to Intellectual disability, autosomal dominant 41, MIM# 616944; Pierpont syndrome, MIM# 602342
Genetic Epilepsy v0.2768 TBL1XR1 Zornitza Stark Publications for gene: TBL1XR1 were set to
Genetic Epilepsy v0.2767 TBL1XR1 Zornitza Stark Mode of inheritance for gene: TBL1XR1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2766 TBL1XR1 Zornitza Stark edited their review of gene: TBL1XR1: Changed phenotypes: Intellectual disability, autosomal dominant 41, MIM# 616944, Pierpont syndrome, MIM# 602342
Genetic Epilepsy v0.2766 TBC1D24 Zornitza Stark Marked gene: TBC1D24 as ready
Genetic Epilepsy v0.2766 TBC1D24 Zornitza Stark Gene: tbc1d24 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2766 TBC1D24 Zornitza Stark Phenotypes for gene: TBC1D24 were changed from to Developmental and epileptic encephalopathy 16 MIM#615338; DOORS syndrome MIM#220500; Epilepsy, rolandic, with proxysmal exercise-induce dystonia and writer's cramp MIM#608105; Myoclonic epilepsy, infantile, familial MIM#605021
Genetic Epilepsy v0.2765 TBC1D24 Zornitza Stark Mode of inheritance for gene: TBC1D24 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Bone Marrow Failure v1.91 ABCB7 Santosh Varughese reviewed gene: ABCB7: 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: 8040304, 23835273, 25835712, 7825602, 7581394, 8566952, 11748843, 7825602; Phenotypes: ANEMIA, SIDEROBLASTIC, AND SPINOCEREBELLAR ATAXIA; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.5881 SCN8A Tinashe Nhindiri reviewed gene: SCN8A: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 34353676, 38233770, 30171078; Phenotypes: Epileptic encephalopathy, Developmental delay, Intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5881 SLX4 Lovepreet Gill reviewed gene: SLX4: Rating: RED; 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: 21240277, 21240275, 23093618, 26453996); Phenotypes: Franconia anemia, complementation group P; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.5881 SLC4A4 Adam Ivey reviewed gene: SLC4A4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29914390, 11274232, 15930088; Phenotypes: OMIM:604278-RENAL TUBULAR ACIDOSIS, PROXIMAL, WITH OCULAR ABNORMALITIES AND IMPAIRED INTELLECTUAL DEVELOPMENT; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5881 SOX10 David Fairbairn changed review comment from: Main mutation mechanism: truncated proteins, potent dominant-negative activity and more severe phenotype only when escapes NMD. Decipher: SOX 10 copy number losses and gains associated with intellectual disability. PCWH Gene2Phenotype: monoallelic-altered gene product structure, DD definitive. Waardenburg syndrome, type 2E Gene2Phenotype: monoallelic-absent gene product, DD definitive. GenCC definitive. OMIM #609136: dominant-negative heterozygous SOX 10 variants in multiple (>3) unrelated cases resulting in neurologic features.; to: Main mutation mechanism: truncated proteins, potent dominant-negative activity and more severe phenotype only when escapes NMD. Decipher: SOX 10 copy number losses and gains associated with intellectual disability. PCWH Gene2Phenotype: monoallelic-altered gene product structure, DD definitive. Waardenburg syndrome, type 2E Gene2Phenotype: monoallelic-absent gene product, DD definitive. GenCC definitive. OMIM #609136: dominant-negative heterozygous SOX 10 variants in multiple (>3) unrelated cases resulting in neurologic features.
Intellectual disability syndromic and non-syndromic v0.5881 SOX10 David Fairbairn reviewed gene: SOX10: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 10762540, 34667088, 38132479; Phenotypes: PCWH (Peripheral demyelinating neuropathy Central demyelination, Waardenburg and Hirschsprung disease) syndrome (OMIM #609136), Waardenburg syndrome, type 2E, with or without neurologic involvement (OMIM #611584); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability syndromic and non-syndromic v0.5881 ROR2 Shani Stuart reviewed gene: ROR2: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 33937263, 32954672, 32172608; Phenotypes: Intellectual disability; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5881 SLC25A1 Alyson Lewis reviewed gene: SLC25A1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31527857, PMID: 26870663; Phenotypes: Impaired intellectual development, mild, Learning disabilities, Delayed motor development; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic Diabetes v0.125 EIF2S3 Hali Van Niel reviewed gene: EIF2S3: Rating: GREEN; Mode of pathogenicity: None; Publications: 28055140, 9781023, 32799315, 35765291; Phenotypes: MEHMO syndrome MONDO:0010258; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Monogenic Diabetes v0.125 EIF2AK3 Hali Van Niel reviewed gene: EIF2AK3: Rating: GREEN; Mode of pathogenicity: None; Publications: 20202148, 11997520, 16813601, 10932183, 37873802, 36106422; Phenotypes: Wolcott-Rallison syndrome MONDO:0009192, neonatal diabetes mellitus MONDO:0016391; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic Diabetes v0.125 WFS1 Hali Van Niel reviewed gene: WFS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 7490992, 33693650, 34792487; Phenotypes: Wolfram syndrome 1 MONDO:0009101, type 1 diabetes mellitus MONDO:0005147; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic Diabetes v0.125 PPP1R15B Hali Van Niel edited their review of gene: PPP1R15B: Changed rating: AMBER
Monogenic Diabetes v0.125 IL2RA Hali Van Niel reviewed gene: IL2RA: Rating: AMBER; Mode of pathogenicity: None; Publications: 15776395, 17196245; Phenotypes: immunodeficiency due to CD25 deficiency MONDO:0011664, neonatal diabetes mellitus MONDO:0016391; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5881 TBCE Leanne Baxter reviewed gene: TBCE: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID:27666369: PMID:17699660: PMID:34356170: PMID: 34134906; Phenotypes: Encephalopathy, progressive, with amyotrophy and optic atrophy MIM:617207, Hypoparathyroidism-retardation-dysmorphism syndrome MIM:241410, Kenny-Caffey syndrome, type 1 MIM:244460; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic Diabetes v0.125 LMNA Hali Van Niel reviewed gene: LMNA: Rating: GREEN; Mode of pathogenicity: None; Publications: 15028826, 10587585, 17250669, 37843397; Phenotypes: familial partial lipodystrophy, Dunnigan type MONDO:0007906, type 2 diabetes mellitus MONDO:0005148; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2764 WASF1 Ain Roesley Phenotypes for gene: WASF1 were changed from Neurodevelopmental disorder with absent language and variable seizures , MIM#618707 to Neurodevelopmental disorder with absent language and variable seizures , MIM#618707
Genetic Epilepsy v0.2763 WASF1 Ain Roesley Publications for gene: WASF1 were set to 29961568; 34845217; 34478686; 34356165
Genetic Epilepsy v0.2763 WASF1 Ain Roesley Marked gene: WASF1 as ready
Genetic Epilepsy v0.2763 WASF1 Ain Roesley Gene: wasf1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2763 WASF1 Ain Roesley Phenotypes for gene: WASF1 were changed from Neurodevelopmental disorder with absent language and variable seizures , MIM#618707 to Neurodevelopmental disorder with absent language and variable seizures , MIM#618707
Genetic Epilepsy v0.2763 WASF1 Ain Roesley Phenotypes for gene: WASF1 were changed from to Neurodevelopmental disorder with absent language and variable seizures , MIM#618707
Genetic Epilepsy v0.2763 WASF1 Ain Roesley Publications for gene: WASF1 were set to
Genetic Epilepsy v0.2762 WASF1 Ain Roesley Mode of inheritance for gene: WASF1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2762 WASF1 Ain Roesley Mode of inheritance for gene: WASF1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2762 WASF1 Ain Roesley Mode of inheritance for gene: WASF1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2761 WDR45 Ain Roesley Phenotypes for gene: WDR45 were changed from Neurodegeneration with brain iron accumulation 5, MIM# 300894; Rett syndrome; Rett-like phenotypes to Neurodegeneration with brain iron accumulation 5, MIM# 300894; Rett syndrome; Rett-like phenotypes
Genetic Epilepsy v0.2761 WDR45 Ain Roesley Mode of inheritance for gene: WDR45 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Genetic Epilepsy v0.2761 WDR45 Ain Roesley Publications for gene: WDR45 were set to 23176820; 30842224
Genetic Epilepsy v0.2760 WDR45 Ain Roesley Marked gene: WDR45 as ready
Genetic Epilepsy v0.2760 WDR45 Ain Roesley Gene: wdr45 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2760 WDR45 Ain Roesley Phenotypes for gene: WDR45 were changed from to Neurodegeneration with brain iron accumulation 5, MIM# 300894; Rett syndrome; Rett-like phenotypes
Genetic Epilepsy v0.2760 WDR45 Ain Roesley Publications for gene: WDR45 were set to
Genetic Epilepsy v0.2760 WDR45 Ain Roesley Mode of inheritance for gene: WDR45 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Genetic Epilepsy v0.2759 WDR73 Ain Roesley Phenotypes for gene: WDR73 were changed from Galloway-Mowat syndrome 1 MIM#251300 to Galloway-Mowat syndrome 1 MIM#251300
Genetic Epilepsy v0.2759 SYNJ1 Zornitza Stark Phenotypes for gene: SYNJ1 were changed from Developmental and epileptic encephalopathy 53, MIM# 617389 to Developmental and epileptic encephalopathy 53, MIM# 617389
Genetic Epilepsy v0.2759 SYNJ1 Zornitza Stark Phenotypes for gene: SYNJ1 were changed from Developmental and epileptic encephalopathy 53, MIM# 617389 to Developmental and epileptic encephalopathy 53, MIM# 617389
Genetic Epilepsy v0.2759 SYNJ1 Zornitza Stark Marked gene: SYNJ1 as ready
Genetic Epilepsy v0.2759 SYNJ1 Zornitza Stark Gene: synj1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2759 SYNJ1 Zornitza Stark Phenotypes for gene: SYNJ1 were changed from Developmental and epileptic encephalopathy 53, MIM# 617389; Parkinson disease 20, early-onset, MIM# 615530 to Developmental and epileptic encephalopathy 53, MIM# 617389
Genetic Epilepsy v0.2759 WDR73 Ain Roesley Phenotypes for gene: WDR73 were changed from Galloway-Mowat syndrome 1 MIM#251300 to Galloway-Mowat syndrome 1 MIM#251300
Genetic Epilepsy v0.2759 WDR73 Ain Roesley Publications for gene: WDR73 were set to 25466283; 26123727; 25873735; 26070982; 30315938
Genetic Epilepsy v0.2758 WDR73 Ain Roesley Marked gene: WDR73 as ready
Genetic Epilepsy v0.2758 WDR73 Ain Roesley Gene: wdr73 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2758 WDR73 Ain Roesley Phenotypes for gene: WDR73 were changed from to Galloway-Mowat syndrome 1 MIM#251300
Genetic Epilepsy v0.2758 WDR73 Ain Roesley Publications for gene: WDR73 were set to
Monogenic Diabetes v0.125 LRBA Hali Van Niel changed review comment from: Established gene disease association with Immunodeficiency, common variable, 8, with autoimmunity, feature may present with type 1 diabetes, possibly neonatal

25468195: 1 patient T1DM
26768763: 5 patients with T1DM
27057999: 1 patient T1DM at 20months
26745254: 2 patients with T1DM, 1 at 2 years, one at infancy
25479458: 1 patient T1DM at 6 years
28473463: 8 patients with T1DM, three of which diagnosed <6months (neonatal diabetes)
26206937: 2 patient T1Dm, 2 years and 18months; to: Established gene disease association with Immunodeficiency, common variable, 8, with autoimmunity, feature may present with type 1 diabetes, possibly neonatal

25468195: 1 patient T1DM
26768763: 5 patients with T1DM
27057999: 1 patient T1DM at 20months
26745254: 2 patients with T1DM, 1 at 2 years, one at infancy
25479458: 1 patient T1DM at 6 years
28473463: 8 patients with T1DM, three of which diagnosed <6months (neonatal diabetes)
26206937: 2 patient T1Dm, 2 years and 18months
all with AR null LRBA variants
Monogenic Diabetes v0.125 LRBA Hali Van Niel reviewed gene: LRBA: Rating: GREEN; Mode of pathogenicity: None; Publications: 25468195, 26768763, 27057999, 26745254, 25479458, 28473463, 26206937; Phenotypes: type 1 diabetes mellitus MONDO:0005147, neonatal diabetes mellitus MONDO:0016391, combined immunodeficiency due to LRBA deficiency MONDO:0013863; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2758 WDR73 Ain Roesley Mode of inheritance for gene: WDR73 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2757 RAB18 Zornitza Stark Marked gene: RAB18 as ready
Genetic Epilepsy v0.2757 RAB18 Zornitza Stark Gene: rab18 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2757 RAB18 Zornitza Stark Phenotypes for gene: RAB18 were changed from to Warburg micro syndrome 3, MIM# 614222
Genetic Epilepsy v0.2756 RAB18 Zornitza Stark Publications for gene: RAB18 were set to
Genetic Epilepsy v0.2755 RAB18 Zornitza Stark Mode of inheritance for gene: RAB18 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2754 RAB18 Zornitza Stark changed review comment from: Autosomal recessive syndrome characterised by microcephaly, microphthalmia, microcornea, congenital cataracts, optic atrophy, cortical dysplasia, in particular corpus callosum hypoplasia, severe mental retardation, spastic diplegia, and hypogonadism. At least 7 families reported, including 4 Pakistani families with a founder variant, p.Leu24Gln; to: Autosomal recessive syndrome characterised by microcephaly, microphthalmia, microcornea, congenital cataracts, optic atrophy, cortical dysplasia, in particular corpus callosum hypoplasia, severe mental retardation, spastic diplegia, and hypogonadism. At least 7 families reported, including 4 Pakistani families with a founder variant, p.Leu24Gln. Seizures are part of the phenotype.
Intellectual disability syndromic and non-syndromic v0.5881 SLC19A3 Zornitza Stark Marked gene: SLC19A3 as ready
Intellectual disability syndromic and non-syndromic v0.5881 SLC19A3 Zornitza Stark Gene: slc19a3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5881 SLC19A3 Zornitza Stark Publications for gene: SLC19A3 were set to
Intellectual disability syndromic and non-syndromic v0.5880 SLC19A3 Zornitza Stark Phenotypes for gene: SLC19A3 were changed from to Thiamine metabolism dysfunction syndrome 2 (biotin- or thiamine-responsive encephalopathy type 2), MIM# 607483
Intellectual disability syndromic and non-syndromic v0.5879 SLC19A3 Zornitza Stark Mode of inheritance for gene: SLC19A3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Monogenic Diabetes v0.125 ZBTB20 Zornitza Stark Marked gene: ZBTB20 as ready
Monogenic Diabetes v0.125 ZBTB20 Zornitza Stark Gene: zbtb20 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.125 ZBTB20 Zornitza Stark Phenotypes for gene: ZBTB20 were changed from Primrose syndrome (tall stature, macrocephaly, intellectual disability, disturbed behaviour, unusual facial features, diabetes, deafness, progressive muscle wasting and ectopic calcifications); Primrose syndrome, 259050 to Primrose syndrome MONDO:0009798; Primrose syndrome (tall stature, macrocephaly, intellectual disability, disturbed behaviour, unusual facial features, diabetes, deafness, progressive muscle wasting and ectopic calcifications); Primrose syndrome, 259050
Monogenic Diabetes v0.124 ZBTB20 Zornitza Stark Publications for gene: ZBTB20 were set to 20644156; 25017102
Monogenic Diabetes v0.123 PIK3R1 Zornitza Stark Marked gene: PIK3R1 as ready
Monogenic Diabetes v0.123 PIK3R1 Zornitza Stark Gene: pik3r1 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.123 PIK3R1 Zornitza Stark Phenotypes for gene: PIK3R1 were changed from Short stature, hyperextensibility of joints and/or inguinal hernia, ocular depression, Rieger anomaly, and teething delay (SHORT) syndrome, 269880; SHORT syndrome to SHORT syndrome MONDO:0010026; Short stature, hyperextensibility of joints and/or inguinal hernia, ocular depression, Rieger anomaly, and teething delay (SHORT) syndrome, MIM#269880
Monogenic Diabetes v0.122 PIK3R1 Zornitza Stark Publications for gene: PIK3R1 were set to 23810378
Intellectual disability syndromic and non-syndromic v0.5878 SPECC1L Zornitza Stark Marked gene: SPECC1L as ready
Intellectual disability syndromic and non-syndromic v0.5878 SPECC1L Zornitza Stark Gene: specc1l has been classified as Green List (High Evidence).
Monogenic Diabetes v0.121 PIK3R1 Hali Van Niel reviewed gene: PIK3R1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32879144, 32602265, 3651536, 34249805, 32439336; Phenotypes: SHORT syndrome MONDO:0010026; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Monogenic Diabetes v0.121 ZBTB20 Hali Van Niel reviewed gene: ZBTB20: Rating: GREEN; Mode of pathogenicity: None; Publications: 27061120, 25017102, 29737001, 38087819, 32473227, 30637921, 32266967; Phenotypes: Primrose syndrome MONDO:0009798; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5878 SLC19A3 Jane Lin changed review comment from: Rare disorder of thiamine metabolism and transport. Has well characterised gene-phenotype link in more than 3 families (multiple publications, in different subpopulations). Many symptoms in this disorder, for example confusion, seizures, ataxia, dystonia, supranuclear facial palsy, external ophthalmoplegia, and dysphagia. ID has been described as a sequela in many cases.; to: Rare disorder of thiamine metabolism and transport. Has well characterised gene-phenotype link for THMD2 in more than 3 families (multiple publications, in different subpopulations). Many CNS related symptoms in this disorder, for example confusion, seizures, ataxia, dystonia, supranuclear facial palsy, external ophthalmoplegia, and dysphagia. ID has been described as a sequela in many cases.
Intellectual disability syndromic and non-syndromic v0.5878 SLC19A3 Jane Lin reviewed gene: SLC19A3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 15871139, PMID: 34276785, PMID: 23482991, PMID: 20065143; Phenotypes: # 607483 BASAL GANGLIA DISEASE, BIOTIN-THIAMINE RESPONSIVE (BBTGD), THIAMINE METABOLISM DYSFUNCTION SYNDROME 2; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5878 SASS6 Zornitza Stark Marked gene: SASS6 as ready
Intellectual disability syndromic and non-syndromic v0.5878 SASS6 Zornitza Stark Gene: sass6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5878 SASS6 Zornitza Stark Classified gene: SASS6 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5878 SASS6 Zornitza Stark Gene: sass6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5877 SASS6 Zornitza Stark gene: SASS6 was added
gene: SASS6 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review
Mode of inheritance for gene: SASS6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SASS6 were set to 24951542; 30639237
Phenotypes for gene: SASS6 were set to Microcephaly 14, primary, autosomal recessive, MIM# 616402
Review for gene: SASS6 was set to GREEN
Added comment: At least 3 unrelated families reported, severe ID is part of the phenotype.
Sources: Expert Review
Monogenic Diabetes v0.121 ZMPSTE24 Hali Van Niel reviewed gene: ZMPSTE24: Rating: GREEN; Mode of pathogenicity: None; Publications: 20814950, 18435794, 36927562, 31856865; Phenotypes: Mandibuloacral dysplasia with type B lipodystrophy, MONDO:0012074; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic Diabetes v0.121 AGPS Hali Van Niel reviewed gene: AGPS: Rating: RED; Mode of pathogenicity: None; Publications: 9553082, 21990100, 35070570; Phenotypes: rhizomelic chondrodysplasia punctata type 3 MONDO:0010823; Mode of inheritance: Unknown
Intellectual disability syndromic and non-syndromic v0.5876 SPECC1L Zornitza Stark Phenotypes for gene: SPECC1L were changed from to Teebi hypertelorism syndrome 1, MIM# 145420
Intellectual disability syndromic and non-syndromic v0.5875 SPECC1L Zornitza Stark Publications for gene: SPECC1L were set to
Intellectual disability syndromic and non-syndromic v0.5874 SPECC1L Zornitza Stark Mode of inheritance for gene: SPECC1L was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5873 SPECC1L Zornitza Stark reviewed gene: SPECC1L: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Teebi hypertelorism syndrome 1, MIM# 145420; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5873 SPECC1L Ibrahim El-Deek changed review comment from: There is paucity of literature directly linking SPECC1L variants to intellectual disability and developmental delay. However, Zhang et al. (PMID: 31953237) reviewed 33 patients from 14 families with SPECC1L variants, noting that the most common features were dysmorphic facial characteristics. Developmental delays were reported in 24.2% of patients (8/33), with some achieving normal development during childhood.; to: There is paucity of literature directly linking SPECC1L variants to intellectual disability and developmental delay. However, Zhang et al. (PMID: 31953237) reviewed 33 patients from 14 families with SPECC1L variants (including 10 missense point mutation and 1 deletion), noting that the most common features were dysmorphic facial characteristics. Developmental delays were reported in 24.2% of patients (8/33), with some achieving normal development during childhood.
Intellectual disability syndromic and non-syndromic v0.5873 SPECC1L Ibrahim El-Deek reviewed gene: SPECC1L: Rating: RED; Mode of pathogenicity: Other; Publications: 31953237, 30472488; Phenotypes: Teebi hypertelorism syndrome 1, Oblique Facial Clefting 1, Opitz GBBB syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5873 GABRA4 Adam Ivey gene: GABRA4 was added
gene: GABRA4 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: GABRA4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GABRA4 were set to PMID: 38565639
Phenotypes for gene: GABRA4 were set to Developmental delay; Intellectual disability; Epileptic seizures
Penetrance for gene: GABRA4 were set to Complete
Review for gene: GABRA4 was set to GREEN
Added comment: Four unrelated individuals with unique de novo missense variants in the transmembrane domain of GABRA4 have developmental delay and varying degrees of intellectual disability (PMID: 38565639). These variants are not present in gnomAD and three of the four variants have pathogenic REVEL scores. Two of the GABRA4 variants were heterozygous, while the remaining two were mosaic.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5873 L1CAM Zornitza Stark Marked gene: L1CAM as ready
Intellectual disability syndromic and non-syndromic v0.5873 L1CAM Zornitza Stark Gene: l1cam has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5873 L1CAM Zornitza Stark Phenotypes for gene: L1CAM were changed from to L1 syndrome MONDO:0017140
Intellectual disability syndromic and non-syndromic v0.5872 L1CAM Zornitza Stark Mode of inheritance for gene: L1CAM was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5871 LAMC3 Zornitza Stark Marked gene: LAMC3 as ready
Intellectual disability syndromic and non-syndromic v0.5871 LAMC3 Zornitza Stark Gene: lamc3 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5871 LAMC3 Zornitza Stark Phenotypes for gene: LAMC3 were changed from to complex neurodevelopmental disorder MONDO:0100038; Cortical malformations, occipital, MIM# 614115
Intellectual disability syndromic and non-syndromic v0.5870 LAMC3 Zornitza Stark Publications for gene: LAMC3 were set to
Intellectual disability syndromic and non-syndromic v0.5869 LAMC3 Zornitza Stark Mode of inheritance for gene: LAMC3 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5868 LAMC3 Zornitza Stark Classified gene: LAMC3 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5868 LAMC3 Zornitza Stark Gene: lamc3 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5867 LAMC3 Zornitza Stark reviewed gene: LAMC3: Rating: AMBER; Mode of pathogenicity: None; Publications: 38758065, 21572413; Phenotypes: complex neurodevelopmental disorder MONDO:0100038, Cortical malformations, occipital, MIM# 614115; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5867 MAGT1 Zornitza Stark Phenotypes for gene: MAGT1 were changed from Congenital disorder of glycosylation, type Icc, OMIM #301031; Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia, OMIM #300853 to X-linked intellectual disability MONDO:0100284; Congenital disorder of glycosylation, type Icc, OMIM #301031
Intellectual disability syndromic and non-syndromic v0.5866 MAGT1 Zornitza Stark Classified gene: MAGT1 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.5866 MAGT1 Zornitza Stark Gene: magt1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5865 MAGT1 Zornitza Stark Tag disputed tag was added to gene: MAGT1.
Intellectual disability syndromic and non-syndromic v0.5865 MBTPS2 Zornitza Stark Marked gene: MBTPS2 as ready
Intellectual disability syndromic and non-syndromic v0.5865 MBTPS2 Zornitza Stark Gene: mbtps2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5865 MBTPS2 Zornitza Stark Phenotypes for gene: MBTPS2 were changed from to IFAP syndrome 1, with or without BRESHECK syndrome MONDO:0100213
Intellectual disability syndromic and non-syndromic v0.5864 MBTPS2 Zornitza Stark Mode of inheritance for gene: MBTPS2 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5863 MED12 Zornitza Stark Marked gene: MED12 as ready
Intellectual disability syndromic and non-syndromic v0.5863 MED12 Zornitza Stark Gene: med12 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5863 MED12 Zornitza Stark Phenotypes for gene: MED12 were changed from to MED12-related intellectual disability syndrome MONDO:0100000
Intellectual disability syndromic and non-syndromic v0.5862 MED12 Zornitza Stark Mode of inheritance for gene: MED12 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.5861 MED13L Zornitza Stark Marked gene: MED13L as ready
Intellectual disability syndromic and non-syndromic v0.5861 MED13L Zornitza Stark Gene: med13l has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5861 MED13L Zornitza Stark Phenotypes for gene: MED13L were changed from to syndromic intellectual disability MONDO:0000508
Intellectual disability syndromic and non-syndromic v0.5860 MED13L Zornitza Stark Publications for gene: MED13L were set to
Intellectual disability syndromic and non-syndromic v0.5859 MED13L Zornitza Stark Mode of inheritance for gene: MED13L was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5858 MED23 Zornitza Stark Marked gene: MED23 as ready
Intellectual disability syndromic and non-syndromic v0.5858 MED23 Zornitza Stark Gene: med23 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5858 MED23 Zornitza Stark Phenotypes for gene: MED23 were changed from to syndromic intellectual disability MONDO:0000508
Intellectual disability syndromic and non-syndromic v0.5857 MED23 Zornitza Stark Publications for gene: MED23 were set to
Intellectual disability syndromic and non-syndromic v0.5856 MED23 Zornitza Stark Mode of inheritance for gene: MED23 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5855 MID1 Zornitza Stark Marked gene: MID1 as ready
Intellectual disability syndromic and non-syndromic v0.5855 MID1 Zornitza Stark Gene: mid1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5855 MID1 Zornitza Stark Phenotypes for gene: MID1 were changed from to X-linked Opitz G/BBB syndrome MONDO:0010222
Intellectual disability syndromic and non-syndromic v0.5854 MID1 Zornitza Stark Mode of inheritance for gene: MID1 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.5853 NDP Zornitza Stark Marked gene: NDP as ready
Intellectual disability syndromic and non-syndromic v0.5853 NDP Zornitza Stark Gene: ndp has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5853 NDP Zornitza Stark Phenotypes for gene: NDP were changed from to Norrie disease MONDO:0010691
Intellectual disability syndromic and non-syndromic v0.5852 NDP Zornitza Stark Mode of inheritance for gene: NDP was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5851 NSD1 Zornitza Stark Marked gene: NSD1 as ready
Intellectual disability syndromic and non-syndromic v0.5851 NSD1 Zornitza Stark Gene: nsd1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5851 NSD1 Zornitza Stark Phenotypes for gene: NSD1 were changed from to Sotos syndrome MONDO:0019349
Intellectual disability syndromic and non-syndromic v0.5850 NSD1 Zornitza Stark Mode of inheritance for gene: NSD1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1792 RBBP8 Zornitza Stark Publications for gene: RBBP8 were set to 21998596
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
Intellectual disability syndromic and non-syndromic v0.5849 OCRL Zornitza Stark Marked gene: OCRL as ready
Intellectual disability syndromic and non-syndromic v0.5849 OCRL Zornitza Stark Gene: ocrl has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5849 OCRL Zornitza Stark Phenotypes for gene: OCRL were changed from to oculocerebrorenal syndrome MONDO:0010645
Intellectual disability syndromic and non-syndromic v0.5848 OCRL Zornitza Stark Mode of inheritance for gene: OCRL was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5847 OFD1 Zornitza Stark Marked gene: OFD1 as ready