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Mendeliome v0.3650 PIGP Seb Lunke Classified gene: PIGP as Green List (high evidence)
Mendeliome v0.3650 PIGP Seb Lunke Gene: pigp has been classified as Green List (High Evidence).
Mendeliome v0.3649 MYLPF Zornitza Stark Gene: mylpf has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3649 MYLPF Zornitza Stark Classified gene: MYLPF as Amber List (moderate evidence)
Mendeliome v0.3649 MYLPF Zornitza Stark Gene: mylpf has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3648 FBXL7 Hazel Phillimore changed review comment from: Homozygous deletion of exon 3 of FBXL7 (predicted to be in-frame) in a 2-year old with novel form of Hennekam syndrome. Each parent was heterozygous.
Patient had lymphedema, protein‐losing enteropathy, dental anomalies, camptodactyly, microtia, small auditory canals, ductive hearing loss, middle ear anomalies, bifid scrotum, and facial dysmorphic features including hypertelorism, telecanthus, epicanthal folds, downslanting palpebral fissures, broad and depressed nasal bridge, and thickened nasal alae.
Sources: Literature; to: Homozygous deletion of exon 3 of FBXL7 (predicted to be in-frame) in a 2-year old with novel form of Hennekam syndrome. Each parent was heterozygous.
Patient had lymphedema, protein‐losing enteropathy, dental anomalies, camptodactyly, microtia, small auditory canals, ductive hearing loss, middle ear anomalies, bifid scrotum, and facial dysmorphic features including hypertelorism, telecanthus, epicanthal folds, downslanting palpebral fissures, broad and depressed nasal bridge, and thickened nasal alae.
Sources: Literature
Mendeliome v0.3648 SCAF4 Zornitza Stark Gene: scaf4 has been classified as Green List (High Evidence).
Mendeliome v0.3648 SCAF4 Zornitza Stark Classified gene: SCAF4 as Green List (high evidence)
Mendeliome v0.3648 SCAF4 Zornitza Stark Gene: scaf4 has been classified as Green List (High Evidence).
Mendeliome v0.3647 FBXL7 Hazel Phillimore gene: FBXL7 was added
gene: FBXL7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FBXL7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FBXL7 were set to PMID: 31633297
Phenotypes for gene: FBXL7 were set to Hennekam lymphangiectasia-lymphedema syndrome; lymphedema; protein‐losing enteropathy; dental anomalies; camptodactyly; microtia; small auditory canals; ductive hearing loss; middle ear anomalies, bifid scrotum, and facial dysmorphic features including hypertelorism, telecanthus, epicanthal folds, downslanting palpebral fissures, broad and depressed nasal bridge, and thickened nasal alae.
Review for gene: FBXL7 was set to AMBER
Added comment: Homozygous deletion of exon 3 of FBXL7 (predicted to be in-frame) in a 2-year old with novel form of Hennekam syndrome. Each parent was heterozygous.
Patient had lymphedema, protein‐losing enteropathy, dental anomalies, camptodactyly, microtia, small auditory canals, ductive hearing loss, middle ear anomalies, bifid scrotum, and facial dysmorphic features including hypertelorism, telecanthus, epicanthal folds, downslanting palpebral fissures, broad and depressed nasal bridge, and thickened nasal alae.
Sources: Literature
Mendeliome v0.3647 PJA1 Zornitza Stark Gene: pja1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3647 PJA1 Zornitza Stark Classified gene: PJA1 as Amber List (moderate evidence)
Mendeliome v0.3647 PJA1 Zornitza Stark Gene: pja1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3645 MYLPF Crystle Lee gene: MYLPF was added
gene: MYLPF was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: MYLPF was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: MYLPF were set to 32707087
Phenotypes for gene: MYLPF were set to Distal arthrogryoposis
Review for gene: MYLPF was set to GREEN
Added comment: 2 different homozygous variants reported in 6 consanguineous families with DA and an additional 2 different dominantly inherited variants in 2 families, with supporting animal model.
Sources: Expert Review
Mendeliome v0.3645 NCKAP1L Michelle Torres gene: NCKAP1L was added
gene: NCKAP1L was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NCKAP1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NCKAP1L were set to 32647003
Phenotypes for gene: NCKAP1L were set to Immunodeficiency
Review for gene: NCKAP1L was set to GREEN
Added comment: 5 patients from 4 families with recurrent bacterial and viral skin infections, severe respiratory tract infections leading to pneumonia and bronchiectasis. Functional of the 4 missense reported were performed.
Sources: Literature
Mendeliome v0.3645 MCF2 Zornitza Stark Gene: mcf2 has been classified as Red List (Low Evidence).
Mendeliome v0.3645 MCF2 Zornitza Stark gene: MCF2 was added
gene: MCF2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MCF2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: MCF2 were set to 31846234
Phenotypes for gene: MCF2 were set to Perisylvian polymicrogyria
Review for gene: MCF2 was set to RED
Added comment: Single individual reported, inherited missense variant from unaffected mother, some support from mouse model.
Sources: Literature
Mendeliome v0.3644 NARS Zornitza Stark Gene: nars has been classified as Green List (High Evidence).
Mendeliome v0.3644 NARS Zornitza Stark Classified gene: NARS as Green List (high evidence)
Mendeliome v0.3644 NARS Zornitza Stark Gene: nars has been classified as Green List (High Evidence).
Mendeliome v0.3643 NARS Zornitza Stark gene: NARS was added
gene: NARS was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NARS was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: NARS were set to 32738225
Phenotypes for gene: NARS were set to Abnormal muscle tone; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Ataxia; Abnormality of the face; Demyelinating peripheral neuropathy
Review for gene: NARS was set to GREEN
Added comment: [Please note that HGNC Approved Gene Symbol for this gene is NARS1] Manole et al (2020 - PMID: 32738225) provide evidence that both biallelic and monoallelic (de novo) pathogenic NARS1 variants cause a neurodevelopmental disorder. In total 32 individuals from 21 families are reported, with biallelic variants identified in individuals from 13 families and de novo in 8 families. Similar features were reported for AR/AD occurrences of the disorder and included microcephaly (90% - most often primary), epilepsy (23/32 or 74% - variable semiology incl. partial/myoclonic/generalized tonic-clonic seizures), DD and ID (as a universal feature), abnormal tone in several (hypotonia/spasticity), ataxia, demyelinating peripheral neuropathy (in 3 or more for each inheritance mode - or a total of 25%). Some individuals had dysmorphic features. NARS1 encodes an aminoacyl-tRNA synthetase (ARS) [asparaginyl-tRNA synthetase 1]. Aminoacyl-tRNA synthetases constitute a family of enzymes catalyzing attachment of amino-acids to their cognate tRNAs. As the authors comment, mutations in genes encoding several other ARSs result in neurological disorders ranging from peripheral neuropathy to severe multi-systemic NDD. Dominant, recessive or both modes for inheritance for mutations in the same gene (e.g. AARS1, YARS1, MARS1, etc) have been reported. Some variants were recurrent, e.g. the c.1600C>T / p.Arg534* which occurred in 6 families as a de novo event or c.1633C>T p.Arg545Cys (homozygous in 6 families). 3 different variants were reported to have occured de novo (c.965G>T - p.Arg322Leu, c.1525G>A - p.Gly509Ser, p.Arg534*) with several other variants identified in hmz/compound htz individuals. A single SNV (c.1067A>C - p.Asp356Ala) was suggested to be acting as modifier and pathogenic only when in trans with a severe variant. [NM_004539.4 used as RefSeq for all]. The authors provide several lines of evidence for a partial loss-of-function effect (e.g. reduction in mRNA expression, enzyme levels and activity in fibroblasts or iNPCs) underlying pathogenicity of the variants identified in individuals with biallelic variants. A gain-of-function (dominant-negative) effect is proposed for de novo variants (such effect also demonstrated for the p.Arg534* in a zebrafish model).
Sources: Literature
Mendeliome v0.3642 ZNF407 Zornitza Stark Gene: znf407 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3639 ZNF407 Zornitza Stark Classified gene: ZNF407 as Amber List (moderate evidence)
Mendeliome v0.3639 ZNF407 Zornitza Stark Gene: znf407 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3638 DDX58 Zornitza Stark Gene: ddx58 has been classified as Green List (High Evidence).
Mendeliome v0.3638 DDX58 Zornitza Stark Phenotypes for gene: DDX58 were changed from to Singleton-Merten syndrome 2, MIM# 616298
Mendeliome v0.3635 DDX58 Zornitza Stark changed review comment from: Singleton-Merten syndrome-2 is characterized by variable expression of glaucoma, aortic calcification, and skeletal abnormalities, without dental anomalies.; to: Singleton-Merten syndrome-2 is characterized by variable expression of glaucoma, aortic calcification, and skeletal abnormalities, without dental anomalies. At least 3 families reported.
Mendeliome v0.3635 DDX58 Zornitza Stark reviewed gene: DDX58: Rating: GREEN; Mode of pathogenicity: None; Publications: 25620203; Phenotypes: Singleton-Merten syndrome 2, MIM# 616298; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3635 IVNS1ABP Zornitza Stark Gene: ivns1abp has been classified as Green List (High Evidence).
Mendeliome v0.3632 MAPK1 Zornitza Stark Gene: mapk1 has been classified as Green List (High Evidence).
Mendeliome v0.3632 MAPK1 Zornitza Stark Classified gene: MAPK1 as Green List (high evidence)
Mendeliome v0.3632 MAPK1 Zornitza Stark Gene: mapk1 has been classified as Green List (High Evidence).
Mendeliome v0.3631 MAPK1 Zornitza Stark gene: MAPK1 was added
gene: MAPK1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MAPK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAPK1 were set to 32721402
Phenotypes for gene: MAPK1 were set to Global developmental delay; Intellectual disability; Behavioral abnormality; Growth delay; Abnormality of the face; Abnormality of the neck; Abnormality of the cardiovascular system; Abnormality of the skin
Review for gene: MAPK1 was set to GREEN
Added comment: Motta et al (2020 - PMID: 32721402) report on 7 unrelated individuals harboring de novo missense MAPK1 pathogenic variants.

The phenotype corresponded to a neurodevelopmental disorder and - as the authors comment - consistently included DD, ID , behavioral problems. Postnatal growth delay was observed in approximately half. Hypertelorism, ptosis, downslant of palpebral fissures, wide nasal bridge as low-set/posteriorly rotated ears were among the facial features observed (each in 3 or more subjects within this cohort). Together with short/webbed neck and abnormalities of skin (lentigines / CAL spots) and growth delay these led to clinical suspicion of Noonan s. or disorder of the same pathway in some. Congenital heart defects (ASD, mitral valve insufficiency, though not cardiomyopathy) occurred in 4/7. Bleeding diathesis and lymphedema were reported only once.

MAPK1 encodes the mitogen-activated protein kinase 1 (also known as ERK2) a serine/threonine kinase of the RAS-RAF-MEK-(MAPK/)ERK pathway.

MAPK1 de novo variants were identified in all individuals following trio exome sequencing (and extensive previous genetic investigations which were non-diagnostic).

The distribution of variants, as well as in silico/vitro/vivo studies suggest a GoF effect (boosted signal through the MAPK cascade. MAPK signaling also upregulated in Noonan syndrome).
Sources: Literature
Mendeliome v0.3630 ASPM Zornitza Stark Gene: aspm has been classified as Green List (High Evidence).
Mendeliome v0.3630 ASPM Zornitza Stark Phenotypes for gene: ASPM were changed from to Microcephaly 5, primary, autosomal recessive, MIM#608716
Mendeliome v0.3627 ASPM Elena Savva reviewed gene: ASPM: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:29243349; Phenotypes: Microcephaly 5, primary, autosomal recessive, 608716; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3627 AMBRA1 Bryony Thompson Gene: ambra1 has been classified as Green List (High Evidence).
Mendeliome v0.3627 AMBRA1 Bryony Thompson Classified gene: AMBRA1 as Green List (high evidence)
Mendeliome v0.3627 AMBRA1 Bryony Thompson Gene: ambra1 has been classified as Green List (High Evidence).
Mendeliome v0.3625 ERLEC1 Bryony Thompson Classified gene: ERLEC1 as Green List (high evidence)
Mendeliome v0.3625 ERLEC1 Bryony Thompson Gene: erlec1 has been classified as Green List (High Evidence).
Mendeliome v0.3624 ERLEC1 Bryony Thompson gene: ERLEC1 was added
gene: ERLEC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ERLEC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ERLEC1 were set to 32442352
Phenotypes for gene: ERLEC1 were set to Class III malocclusion
Review for gene: ERLEC1 was set to GREEN
Added comment: A heterozygous missense variant was found to co-segregate with dentofacial deformity in a multi-generational Chinese pedigree (2 unaffected carriers & 11 affected carriers), and 3 additional missense variants were identified in 3 unrelated cases from a sporadic malocclusion cohort. Additional functional assays were conducted to demonstrate that the proper level of ERLEC1 expression is crucial for proper osteogenic differentiation. All identified missense variants were assessed using luciferase reporter assays, and altered activity.
Sources: Literature
Mendeliome v0.3623 RIMS2 Zornitza Stark Phenotypes for gene: RIMS2 were changed from nystagmus; retinal dysfunction; autism; night blindness to nystagmus; retinal dysfunction; autism; night blindness; Cone-rod synaptic disorder syndrome, congenital nonprogressive , MIM#618970
Mendeliome v0.3622 RIMS2 Zornitza Stark edited their review of gene: RIMS2: Changed phenotypes: nystagmus, retinal dysfunction, autism, night blindness, Cone-rod synaptic disorder syndrome, congenital nonprogressive , MIM#618970
Mendeliome v0.3622 WDR1 Zornitza Stark Gene: wdr1 has been classified as Green List (High Evidence).
Mendeliome v0.3619 KREMEN1 Bryony Thompson Gene: kremen1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3619 KREMEN1 Bryony Thompson Classified gene: KREMEN1 as Amber List (moderate evidence)
Mendeliome v0.3619 KREMEN1 Bryony Thompson Gene: kremen1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3618 KREMEN1 Bryony Thompson gene: KREMEN1 was added
gene: KREMEN1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: KREMEN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KREMEN1 were set to 27049303; 27550540
Phenotypes for gene: KREMEN1 were set to Ectodermal dysplasia 13, hair/tooth type MIM#617392
Review for gene: KREMEN1 was set to AMBER
Added comment: 4 consanguineous Palestinian families segregating the same homozygous missense (Phe209Ser) with disease phenotype which includes hair abnormalities. Possible founder variant. There are also animal model functional assays that suggest the gene is involved in hair development.
Sources: Expert list
Mendeliome v0.3617 ANO1 Zornitza Stark Phenotypes for gene: ANO1 were changed from Impaired intestinal peristalsis; dysmorphic features to Impaired intestinal peristalsis; haemorrhagic diarrhoea; dysmorphic features
Mendeliome v0.3616 ANO1 Zornitza Stark Gene: ano1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3616 ANO1 Zornitza Stark Phenotypes for gene: ANO1 were changed from to Impaired intestinal peristalsis; dysmorphic features
Mendeliome v0.3615 ANO1 Zornitza Stark Classified gene: ANO1 as Amber List (moderate evidence)
Mendeliome v0.3615 ANO1 Zornitza Stark Gene: ano1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3614 TUBB2A Zornitza Stark Gene: tubb2a has been classified as Green List (High Evidence).
Mendeliome v0.3614 TUBB2A Zornitza Stark Phenotypes for gene: TUBB2A were changed from to Cortical dysplasia, complex, with other brain malformations 5 MIM#615763
Mendeliome v0.3611 TUBB2A Zornitza Stark reviewed gene: TUBB2A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cortical dysplasia, complex, with other brain malformations 5, MIM# 615763; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3611 PMP22 Zornitza Stark Gene: pmp22 has been classified as Green List (High Evidence).
Mendeliome v0.3611 PMP22 Zornitza Stark Phenotypes for gene: PMP22 were changed from to Charcot-Marie-Tooth disease, type 1A, MIM# 118220; Charcot-Marie-Tooth disease, type 1E, MIM# 118300; Dejerine-Sottas disease, MIM# 145900; Neuropathy, recurrent, with pressure palsies 162500; Roussy-Levy syndrome 180800
Mendeliome v0.3608 PMP22 Zornitza Stark reviewed gene: PMP22: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Charcot-Marie-Tooth disease, type 1A, MIM# 118220, Charcot-Marie-Tooth disease, type 1E, MIM# 118300, Dejerine-Sottas disease, MIM# 145900, Neuropathy, recurrent, with pressure palsies 162500, Roussy-Levy syndrome 180800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3608 OTX2 Zornitza Stark Gene: otx2 has been classified as Green List (High Evidence).
Mendeliome v0.3606 CDAN1 Zornitza Stark Gene: cdan1 has been classified as Green List (High Evidence).
Mendeliome v0.3603 NGLY1 Zornitza Stark Gene: ngly1 has been classified as Green List (High Evidence).
Mendeliome v0.3598 IMPG2 Zornitza Stark Gene: impg2 has been classified as Green List (High Evidence).
Mendeliome v0.3595 GNPNAT1 Zornitza Stark Gene: gnpnat1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3595 GNPNAT1 Zornitza Stark Classified gene: GNPNAT1 as Amber List (moderate evidence)
Mendeliome v0.3595 GNPNAT1 Zornitza Stark Gene: gnpnat1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3593 EEF1A2 Zornitza Stark Gene: eef1a2 has been classified as Green List (High Evidence).
Mendeliome v0.3590 ANO1 Arina Puzriakova changed review comment from: PMID: 32487539 (2020) - Two affected sibs presenting in early infancy with impaired intestinal peristalsis, intestinal pneumatosis and dysmorphic features. Delayed motor and language development was reported in one sibling, however, the other sibling died at 5 months from cardiac arrest and therefore a psychomotor assessment was performed. Exome sequencing identified a homozygous truncating variant (c.897+3_897+6delAAGT, p.L300Vfs*58) in ANO1 which segregated with disease in the family. Functional data revealed that the variant led to lack of expression of functional TMEM16A in patient cells, which in turn abolished calcium-activated Cl- currents. Also supportive mouse model.
Sources: Literature; to: PMID: 32487539 (2020) - Two affected sibs presenting in early infancy with impaired intestinal peristalsis, intestinal pneumatosis and dysmorphic features. Delayed motor and language development was reported in one sibling, however, the other sibling died at 5 months from cardiac arrest and therefore a psychomotor assessment was not performed. Exome sequencing identified a homozygous truncating variant (c.897+3_897+6delAAGT, p.L300Vfs*58) in ANO1 which segregated with disease in the family. Functional data revealed that the variant led to lack of expression of functional TMEM16A in patient cells, which in turn abolished calcium-activated Cl- currents. Also supportive mouse model.
Sources: Literature
Mendeliome v0.3590 ANO1 Arina Puzriakova gene: ANO1 was added
gene: ANO1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ANO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ANO1 were set to 32487539
Added comment: PMID: 32487539 (2020) - Two affected sibs presenting in early infancy with impaired intestinal peristalsis, intestinal pneumatosis and dysmorphic features. Delayed motor and language development was reported in one sibling, however, the other sibling died at 5 months from cardiac arrest and therefore a psychomotor assessment was performed. Exome sequencing identified a homozygous truncating variant (c.897+3_897+6delAAGT, p.L300Vfs*58) in ANO1 which segregated with disease in the family. Functional data revealed that the variant led to lack of expression of functional TMEM16A in patient cells, which in turn abolished calcium-activated Cl- currents. Also supportive mouse model.
Sources: Literature
Mendeliome v0.3590 GNPNAT1 Arina Puzriakova changed review comment from: Four affected sibs from a consanguineous Pakistani family with skeletal dysplasia, characterised by severe short stature, rhizomelic shortening of the limbs, and metacarpal and metatarsal length irregularities in the hands and feet. WGS revealed a homozygous missense variant (c.226G>A; p.Glu76Lys) in GNPNAT1, which segregating with the phenotype.
Gnpnat1 gene knockdown in primary rat chondrocytes decreased cellular proliferation and expression of chondrocyte differentiation markers, indicating the importance of Gnpnat1 for growth plate chondrocyte proliferation and differentiation.
Sources: Literature; to: PMID: 32591345 (2020) - Four affected sibs from a consanguineous Pakistani family with skeletal dysplasia, characterised by severe short stature, rhizomelic shortening of the limbs, and metacarpal and metatarsal length irregularities in the hands and feet. WGS revealed a homozygous missense variant (c.226G>A; p.Glu76Lys) in GNPNAT1, which segregating with the phenotype.
Gnpnat1 gene knockdown in primary rat chondrocytes decreased cellular proliferation and expression of chondrocyte differentiation markers, indicating the importance of Gnpnat1 for growth plate chondrocyte proliferation and differentiation. Additional cases required to validate pathogenicity of GNPNAT1.
Sources: Literature
Mendeliome v0.3590 GNPNAT1 Arina Puzriakova gene: GNPNAT1 was added
gene: GNPNAT1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GNPNAT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GNPNAT1 were set to 32591345
Phenotypes for gene: GNPNAT1 were set to Rhizomelic skeletal dysplasia
Review for gene: GNPNAT1 was set to RED
Added comment: Four affected sibs from a consanguineous Pakistani family with skeletal dysplasia, characterised by severe short stature, rhizomelic shortening of the limbs, and metacarpal and metatarsal length irregularities in the hands and feet. WGS revealed a homozygous missense variant (c.226G>A; p.Glu76Lys) in GNPNAT1, which segregating with the phenotype.
Gnpnat1 gene knockdown in primary rat chondrocytes decreased cellular proliferation and expression of chondrocyte differentiation markers, indicating the importance of Gnpnat1 for growth plate chondrocyte proliferation and differentiation.
Sources: Literature
Mendeliome v0.3590 PKD1L1 Zornitza Stark Gene: pkd1l1 has been classified as Green List (High Evidence).
Mendeliome v0.3587 IVNS1ABP Bryony Thompson Classified gene: IVNS1ABP as Green List (high evidence)
Mendeliome v0.3587 IVNS1ABP Bryony Thompson Gene: ivns1abp has been classified as Green List (High Evidence).
Mendeliome v0.3586 IVNS1ABP Bryony Thompson gene: IVNS1ABP was added
gene: IVNS1ABP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: IVNS1ABP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IVNS1ABP were set to 32499645
Phenotypes for gene: IVNS1ABP were set to Primary immunodeficiency
Review for gene: IVNS1ABP was set to GREEN
Added comment: 3 unrelated families with putative loss of function variants. Case features and immunophenotyping of patient cells is suggestive of a combined immune deficiency, based on the ESID definitions of PID subtypes.
Sources: Literature
Mendeliome v0.3585 PTPN2 Bryony Thompson Gene: ptpn2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3585 PTPN2 Bryony Thompson Classified gene: PTPN2 as Amber List (moderate evidence)
Mendeliome v0.3585 PTPN2 Bryony Thompson Gene: ptpn2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3584 PTPN2 Bryony Thompson gene: PTPN2 was added
gene: PTPN2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PTPN2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTPN2 were set to 32499645; 27658548
Phenotypes for gene: PTPN2 were set to Lupus; arthritis; common variable immunodeficiency
Review for gene: PTPN2 was set to AMBER
Added comment: A single family with a proband diagnosed with CVID and arthiritis (among other features) with an intronic expression quantitative trait loci (eQTL) rs2847297-G in trans with a stopgain variant. The stopgain variant was also identified in the proband's mother, who was diagnosed with lupus. A Ptpn2 deficient mouse model also demonstrates an autoimmune phenotype.
Sources: Literature
Mendeliome v0.3583 SOCS1 Bryony Thompson Gene: socs1 has been classified as Green List (High Evidence).
Mendeliome v0.3583 SOCS1 Bryony Thompson Classified gene: SOCS1 as Green List (high evidence)
Mendeliome v0.3583 SOCS1 Bryony Thompson Gene: socs1 has been classified as Green List (High Evidence).
Mendeliome v0.3581 MRPS23 Zornitza Stark Phenotypes for gene: MRPS23 were changed from Hepatic disease; Combined respiratory chain complex deficienciesHepatic disease; Combined respiratory chain complex deficiencies; Cardiomyopathy; Tubulopathy; Lactic acidosis; Structural brain abnormalities to Hepatic disease; Combined respiratory chain complex deficiencies; Hepatic disease; Combined respiratory chain complex deficiencies; Cardiomyopathy; Tubulopathy; Lactic acidosis; Structural brain abnormalities; Combined oxidative phosphorylation deficiency 45, MIM#618951
Mendeliome v0.3580 MRPS23 Zornitza Stark edited their review of gene: MRPS23: Changed phenotypes: Hepatic disease, Combined respiratory chain complex deficiencies, Cardiomyopathy, Tubulopathy, Lactic acidosis, Structural brain abnormalities, Combined oxidative phosphorylation deficiency 45, MIM#618951
Mendeliome v0.3578 OXCT1 Zornitza Stark Gene: oxct1 has been classified as Green List (High Evidence).
Mendeliome v0.3575 KCNJ1 Zornitza Stark Gene: kcnj1 has been classified as Green List (High Evidence).
Mendeliome v0.3572 ZFYVE27 Zornitza Stark Gene: zfyve27 has been classified as Red List (Low Evidence).
Mendeliome v0.3569 KLF10 Zornitza Stark Gene: klf10 has been classified as Red List (Low Evidence).
Mendeliome v0.3569 KLF10 Zornitza Stark Classified gene: KLF10 as Red List (low evidence)
Mendeliome v0.3569 KLF10 Zornitza Stark Gene: klf10 has been classified as Red List (Low Evidence).
Mendeliome v0.3568 MYOZ2 Zornitza Stark Gene: myoz2 has been classified as Red List (Low Evidence).
Mendeliome v0.3565 MYOZ2 Zornitza Stark Classified gene: MYOZ2 as Red List (low evidence)
Mendeliome v0.3565 MYOZ2 Zornitza Stark Gene: myoz2 has been classified as Red List (Low Evidence).
Mendeliome v0.3564 TRIM63 Zornitza Stark Gene: trim63 has been classified as Green List (High Evidence).
Mendeliome v0.3564 TRIM63 Zornitza Stark Classified gene: TRIM63 as Green List (high evidence)
Mendeliome v0.3564 TRIM63 Zornitza Stark Gene: trim63 has been classified as Green List (High Evidence).
Mendeliome v0.3563 PDLIM3 Zornitza Stark Gene: pdlim3 has been classified as Red List (Low Evidence).
Mendeliome v0.3563 PDLIM3 Zornitza Stark Classified gene: PDLIM3 as Red List (low evidence)
Mendeliome v0.3563 PDLIM3 Zornitza Stark Gene: pdlim3 has been classified as Red List (Low Evidence).
Mendeliome v0.3562 OBSCN Zornitza Stark Gene: obscn has been classified as Red List (Low Evidence).
Mendeliome v0.3562 OBSCN Zornitza Stark Classified gene: OBSCN as Red List (low evidence)
Mendeliome v0.3562 OBSCN Zornitza Stark Gene: obscn has been classified as Red List (Low Evidence).
Mendeliome v0.3561 TRIM63 Ain Roesley gene: TRIM63 was added
gene: TRIM63 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TRIM63 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRIM63 were set to 30681346; 32451364
Phenotypes for gene: TRIM63 were set to Hypertrophic cardiomyopathy
Penetrance for gene: TRIM63 were set to unknown
Review for gene: TRIM63 was set to GREEN
Added comment: PMID: 30681346;
LIMITED by Clingen working group (last evaluated 2018)

PMID: 32451364
- 16 index cases with rare homozygous or compound heterozygous variants (15 HCM and one restrictive cardiomyopathy). None of these variants have homozygote counts in gnomAD.
- segregated in 3 families
- 1 index had another pathogenic truncating variant in MYBPC3
- 5 missense and 3 PTCs
- Familial evaluation showed that only homozygous and compound heterozygous had signs of disease, whereas all heterozygous family members were healthy
Sources: Literature
Mendeliome v0.3561 KLF10 Paul De Fazio gene: KLF10 was added
gene: KLF10 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KLF10 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KLF10 were set to 22234868
Phenotypes for gene: KLF10 were set to HCM
gene: KLF10 was marked as current diagnostic
Added comment: Curated by ClinGen and rated as limited evidence.

Misssense mutations reported in six unrelated individuals patients (two males/four females), with family history of HCM only reported for one individual (PMID: 22234868). No further reports in the literature.
Sources: Literature
Mendeliome v0.3561 KRT71 Bryony Thompson Gene: krt71 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3561 KRT71 Bryony Thompson Classified gene: KRT71 as Amber List (moderate evidence)
Mendeliome v0.3561 KRT71 Bryony Thompson Gene: krt71 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3560 KRT71 Bryony Thompson gene: KRT71 was added
gene: KRT71 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KRT71 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KRT71 were set to 14632181; 22592156; 19713490
Phenotypes for gene: KRT71 were set to ?Hypotrichosis 13, 615896
Review for gene: KRT71 was set to AMBER
Added comment: A single family with 3 affected members of a 3-generation Japanese family segregating a missense variant (F141C) with autosomal dominant woolly hair/hypotrichosis, with supporting functional assays and animal models.
Sources: Literature
Mendeliome v0.3559 ACADL Zornitza Stark Gene: acadl has been classified as Red List (Low Evidence).
Mendeliome v0.3556 ACADL Zornitza Stark Classified gene: ACADL as Red List (low evidence)
Mendeliome v0.3556 ACADL Zornitza Stark Gene: acadl has been classified as Red List (Low Evidence).
Mendeliome v0.3555 TWNK Zornitza Stark Gene: twnk has been classified as Green List (High Evidence).
Mendeliome v0.3555 TWNK Zornitza Stark Phenotypes for gene: TWNK were changed from to Mitochondrial DNA depletion syndrome 7 (hepatocerebral type) 271245; Perrault syndrome 5 616138; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 609286
Mendeliome v0.3551 TWNK Elena Savva reviewed gene: TWNK: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 32234020, 18593709; Phenotypes: Mitochondrial DNA depletion syndrome 7 (hepatocerebral type) 271245, Perrault syndrome 5 616138, Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 609286; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3551 UBE2T Zornitza Stark Classified gene: UBE2T as Green List (high evidence)
Mendeliome v0.3551 UBE2T Zornitza Stark Gene: ube2t has been classified as Green List (High Evidence).
Mendeliome v0.3550 P2RX2 Zornitza Stark Gene: p2rx2 has been classified as Green List (High Evidence).
Mendeliome v0.3547 KCNQ4 Zornitza Stark Gene: kcnq4 has been classified as Green List (High Evidence).
Mendeliome v0.3544 FLCN Zornitza Stark Gene: flcn has been classified as Green List (High Evidence).
Mendeliome v0.3539 LARS Zornitza Stark Gene: lars has been classified as Green List (High Evidence).
Mendeliome v0.3539 KERA Zornitza Stark Gene: kera has been classified as Green List (High Evidence).
Mendeliome v0.3539 KERA Zornitza Stark Phenotypes for gene: KERA were changed from to Cornea plana 2, autosomal recessive, MIM# 217300
Mendeliome v0.3536 KERA Zornitza Stark reviewed gene: KERA: Rating: GREEN; Mode of pathogenicity: None; Publications: 23834557, 11726611, 10802664; Phenotypes: Cornea plana 2, autosomal recessive, MIM# 217300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3536 CTRC Zornitza Stark Gene: ctrc has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3533 CTRC Zornitza Stark Classified gene: CTRC as Amber List (moderate evidence)
Mendeliome v0.3533 CTRC Zornitza Stark Gene: ctrc has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3532 CPA1 Zornitza Stark Gene: cpa1 has been classified as Green List (High Evidence).
Mendeliome v0.3529 CLDN2 Zornitza Stark Gene: cldn2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3526 CLDN2 Zornitza Stark Classified gene: CLDN2 as Amber List (moderate evidence)
Mendeliome v0.3526 CLDN2 Zornitza Stark Gene: cldn2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3525 BMP10 Zornitza Stark Gene: bmp10 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3525 BMP10 Zornitza Stark Classified gene: BMP10 as Amber List (moderate evidence)
Mendeliome v0.3525 BMP10 Zornitza Stark Gene: bmp10 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3524 BMP10 Zornitza Stark gene: BMP10 was added
gene: BMP10 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: BMP10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BMP10 were set to 30578383
Phenotypes for gene: BMP10 were set to Pulmonary arterial hypertension
Review for gene: BMP10 was set to AMBER
Added comment: A truncating mutation and a predicted loss-of-function missense variant were identified in BMP10 in two severely affected sporadic PAH female patients.
Sources: Expert list
Mendeliome v0.3523 SMAD1 Zornitza Stark Gene: smad1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3523 SMAD1 Zornitza Stark Classified gene: SMAD1 as Amber List (moderate evidence)
Mendeliome v0.3523 SMAD1 Zornitza Stark Gene: smad1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3522 SMAD1 Zornitza Stark gene: SMAD1 was added
gene: SMAD1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SMAD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMAD1 were set to 21898662; 23478097
Phenotypes for gene: SMAD1 were set to Pulmonary arterial hypertension
Review for gene: SMAD1 was set to AMBER
Added comment: One missense variant identified in a PAH case. Mouse model is consistent with pulmonary hypertension.
Sources: Expert list
Mendeliome v0.3521 BRAP Zornitza Stark Gene: brap has been classified as Red List (Low Evidence).
Mendeliome v0.3521 BRAP Zornitza Stark gene: BRAP was added
gene: BRAP was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: BRAP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BRAP were set to 30703135
Phenotypes for gene: BRAP were set to Pulmonary arterial hypertension
Review for gene: BRAP was set to RED
Added comment: A single BRAP missense variant in a Japanese family with PAH, with in vitro functional assays suggesting a gain-of-function.
Sources: Expert list
Mendeliome v0.3520 KLF2 Zornitza Stark Gene: klf2 has been classified as Red List (Low Evidence).
Mendeliome v0.3520 KLF2 Zornitza Stark gene: KLF2 was added
gene: KLF2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: KLF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KLF2 were set to 28188237
Phenotypes for gene: KLF2 were set to Pulmonary arterial hypertension
Review for gene: KLF2 was set to RED
Added comment: Single family reported.
Sources: Expert list
Mendeliome v0.3519 ATP13A3 Zornitza Stark Gene: atp13a3 has been classified as Green List (High Evidence).
Mendeliome v0.3519 ATP13A3 Zornitza Stark Classified gene: ATP13A3 as Green List (high evidence)
Mendeliome v0.3519 ATP13A3 Zornitza Stark Gene: atp13a3 has been classified as Green List (High Evidence).
Mendeliome v0.3518 ATP13A3 Zornitza Stark gene: ATP13A3 was added
gene: ATP13A3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ATP13A3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP13A3 were set to 31798832; 30679663; 29650961
Phenotypes for gene: ATP13A3 were set to Pulmonary arterial hypertension
Review for gene: ATP13A3 was set to GREEN
Added comment: Three heterozygous frameshift variants, three stop gained, two splice region variants in ATP13A3, which are predicted to lead to loss of ATPase catalytic activity identified in idiopathic/familial PAH cases. Also one case with putative recessive inheritance reported. ATP13A3 mRNA expression is confirmed in primary PASMCs and endothelial cells where its loss hindered proliferation and enhanced apoptosis of endothelial cells, which is known as the initiation event of PAH.
Sources: Expert list
Mendeliome v0.3517 SMARCA2 Zornitza Stark Gene: smarca2 has been classified as Green List (High Evidence).
Mendeliome v0.3517 SMARCA2 Zornitza Stark Phenotypes for gene: SMARCA2 were changed from to Nicolaides-Baraitser syndrome, MIM #601358; Blepharophimosis-intellectual disability syndrome
Mendeliome v0.3513 SMARCA2 Zornitza Stark reviewed gene: SMARCA2: 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: 26468571, 32694869; Phenotypes: Nicolaides-Baraitser syndrome, MIM #601358, Blepharophimosis-intellectual disability syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3513 MORC2 Zornitza Stark Gene: morc2 has been classified as Green List (High Evidence).
Mendeliome v0.3510 DBT Zornitza Stark Gene: dbt has been classified as Green List (High Evidence).
Mendeliome v0.3507 PLCB3 Zornitza Stark Gene: plcb3 has been classified as Red List (Low Evidence).
Mendeliome v0.3507 PLCB3 Zornitza Stark gene: PLCB3 was added
gene: PLCB3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PLCB3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLCB3 were set to 29122926
Phenotypes for gene: PLCB3 were set to Spondylometaphyseal dysplasia with corneal dystrophy, MIM# 618961
Review for gene: PLCB3 was set to RED
Added comment: Single consanguineous family reported.
Sources: Expert list
Mendeliome v0.3506 ACOX1 Zornitza Stark Gene: acox1 has been classified as Green List (High Evidence).
Mendeliome v0.3502 MPL Zornitza Stark Gene: mpl has been classified as Green List (High Evidence).
Mendeliome v0.3502 MPL Zornitza Stark Phenotypes for gene: MPL were changed from to Myelofibrosis with myeloid metaplasia, somatic, MIM#2544503; Thrombocythemia 2, MIM#601977, AD, SMu; Thrombocytopenia, congenital amegakaryocytic, MIM#604498, AR
Mendeliome v0.3499 SH2B3 Zornitza Stark Gene: sh2b3 has been classified as Green List (High Evidence).
Mendeliome v0.3499 SH2B3 Zornitza Stark Phenotypes for gene: SH2B3 were changed from to Predisposition to haematological malignancies
Mendeliome v0.3496 SH2B3 Zornitza Stark reviewed gene: SH2B3: Rating: GREEN; Mode of pathogenicity: None; Publications: 26457647, 23908464, 31102422, 31173385; Phenotypes: Predisposition to haematological malignancies; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3496 MPL Chern Lim reviewed gene: MPL: Rating: GREEN; Mode of pathogenicity: None; Publications: 28955303, 26423830; Phenotypes: Myelofibrosis with myeloid metaplasia, somatic, MIM#2544503, Thrombocythemia 2, MIM#601977, AD, SMu, Thrombocytopenia, congenital amegakaryocytic, MIM#604498, AR; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.3496 HPD Zornitza Stark Gene: hpd has been classified as Green List (High Evidence).
Mendeliome v0.3496 HPD Zornitza Stark Phenotypes for gene: HPD were changed from to Hawkinsinuria (MIM#140350), AD; Tyrosinemia type III (MIM#276710), AR
Mendeliome v0.3493 HPD Zornitza Stark reviewed gene: HPD: Rating: GREEN; Mode of pathogenicity: None; Publications: 10942115, 17560158; Phenotypes: Hawkinsinuria (MIM#140350), AD, Tyrosinemia type III (MIM#276710), AR; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.3493 FANCM Zornitza Stark Gene: fancm has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3490 FANCM Zornitza Stark Classified gene: FANCM as Amber List (moderate evidence)
Mendeliome v0.3490 FANCM Zornitza Stark Gene: fancm has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3489 HDAC8 Zornitza Stark Gene: hdac8 has been classified as Green List (High Evidence).
Mendeliome v0.3486 RBM8A Zornitza Stark Gene: rbm8a has been classified as Green List (High Evidence).
Mendeliome v0.3484 RPL15 Zornitza Stark Gene: rpl15 has been classified as Green List (High Evidence).
Mendeliome v0.3481 RPS28 Zornitza Stark Gene: rps28 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3481 RPS28 Zornitza Stark Phenotypes for gene: RPS28 were changed from to Diamond Blackfan anemia 15 with mandibulofacial dysostosis, MIM# 606164
Mendeliome v0.3478 RPS28 Zornitza Stark Classified gene: RPS28 as Amber List (moderate evidence)
Mendeliome v0.3478 RPS28 Zornitza Stark Gene: rps28 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3477 RPS28 Zornitza Stark reviewed gene: RPS28: Rating: AMBER; Mode of pathogenicity: None; Publications: 24942156; Phenotypes: Diamond Blackfan anemia 15 with mandibulofacial dysostosis, MIM# 606164; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3477 RPS29 Zornitza Stark Gene: rps29 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3474 RPS29 Zornitza Stark Classified gene: RPS29 as Amber List (moderate evidence)
Mendeliome v0.3474 RPS29 Zornitza Stark Gene: rps29 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3472 REN Zornitza Stark Gene: ren has been classified as Green List (High Evidence).
Mendeliome v0.3472 REN Zornitza Stark Phenotypes for gene: REN were changed from to Renal tubular dysgenesis, MIM# 267430; Autosomal dominant tubulointerstitial disease
Mendeliome v0.3469 REN Zornitza Stark reviewed gene: REN: Rating: GREEN; Mode of pathogenicity: None; Publications: 16116425, 31586593, 31406136, 28701203, 21473025; Phenotypes: Renal tubular dysgenesis, MIM# 267430, Autosomal dominant tubulointerstitial disease; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3467 UVSSA Zornitza Stark Gene: uvssa has been classified as Green List (High Evidence).
Mendeliome v0.3467 UVSSA Zornitza Stark Phenotypes for gene: UVSSA were changed from to UV-sensitive syndrome 3 (MIM#614640)
Mendeliome v0.3464 SEC23A Zornitza Stark Gene: sec23a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3464 SEC23A Zornitza Stark Phenotypes for gene: SEC23A were changed from to Craniolenticulosutural dysplasia (MIM# 607812)
Mendeliome v0.3461 SEC23A Zornitza Stark Classified gene: SEC23A as Amber List (moderate evidence)
Mendeliome v0.3461 SEC23A Zornitza Stark Gene: sec23a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3460 DACT1 Zornitza Stark Gene: dact1 has been classified as Red List (Low Evidence).
Mendeliome v0.3459 DACT1 Zornitza Stark Classified gene: DACT1 as Red List (low evidence)
Mendeliome v0.3459 DACT1 Zornitza Stark Gene: dact1 has been classified as Red List (Low Evidence).
Mendeliome v0.3458 VPS33A Zornitza Stark Gene: vps33a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3458 VPS33A Zornitza Stark Phenotypes for gene: VPS33A were changed from to Mucopolysaccharidosis-plus syndrome (MIM#617303)
Mendeliome v0.3455 VPS33A Zornitza Stark Classified gene: VPS33A as Amber List (moderate evidence)
Mendeliome v0.3455 VPS33A Zornitza Stark Gene: vps33a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3454 VPS33A Zornitza Stark reviewed gene: VPS33A: Rating: AMBER; Mode of pathogenicity: None; Publications: 28013294, 27547915; Phenotypes: Mucopolysaccharidosis-plus syndrome (MIM#617303); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3454 COG2 Zornitza Stark Gene: cog2 has been classified as Red List (Low Evidence).
Mendeliome v0.3451 COG2 Zornitza Stark Classified gene: COG2 as Red List (low evidence)
Mendeliome v0.3451 COG2 Zornitza Stark Gene: cog2 has been classified as Red List (Low Evidence).
Mendeliome v0.3450 DACT1 Natalie Tan gene: DACT1 was added
gene: DACT1 was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: DACT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DACT1 were set to PMID: 28054444; 22610794; 19701191
Phenotypes for gene: DACT1 were set to ?Townes-Brocks syndrome 2 (OMIM #617466)
Review for gene: DACT1 was set to RED
Added comment: Webb et al. (2017) reported 6 affected members of a 3-generation family with ?Townes-Brocks syndrome-2, identified heterozygosity for a nonsense mutation in the DACT1 gene that segregated with disease. Clinical features include imperforate anus, rectovaginal fistula, crossed fused renal ectopia, vesicoureteral reflux, unilateral microtia, overfolded helices and cupped ears. One family member (proband's mother) with scoliosis and spina bifida occulta. Neural tube defects reported in a study of human fetuses (PMID: 22610794) and a mouse model (PMID: 19701191). Listed in Decipher v10.0 for an individual with abnormalities of (i) head or neck (ii) nervous system (iii) skeletal system. Unlike the gene SALL1 that causes Townes-Brocks syndrome 1, there is no information specifically relating to DACT1 with radial dysplasia, as these were not observed in the family with ?Townes-Brocks syndrome 2 (PMID: 28054444).
Sources: NHS GMS
Mendeliome v0.3450 G6PC3 Zornitza Stark Gene: g6pc3 has been classified as Green List (High Evidence).
Mendeliome v0.3450 G6PC3 Zornitza Stark Phenotypes for gene: G6PC3 were changed from to Dursun syndrome 612541; Neutropenia, severe congenital 4, autosomal recessive 612541
Mendeliome v0.3447 POGLUT1 Zornitza Stark Gene: poglut1 has been classified as Green List (High Evidence).
Mendeliome v0.3447 POGLUT1 Zornitza Stark Phenotypes for gene: POGLUT1 were changed from to Muscular dystrophy, limb-girdle, autosomal recessive 21 (MIM# 617232), Dowling-Degos disease 4 (MIM# 615696)
Mendeliome v0.3444 G6PC3 Belinda Chong reviewed gene: G6PC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 21385794; Phenotypes: Dursun syndrome 612541, Neutropenia, severe congenital 4, autosomal recessive 612541; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.3444 POGLUT1 Ain Roesley reviewed gene: POGLUT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27807076, 24387993; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 21 (MIM# 617232), Dowling-Degos disease 4 (MIM# 615696); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3444 SEC23A Paul De Fazio reviewed gene: SEC23A: Rating: AMBER; Mode of pathogenicity: None; Publications: 16980979, 21039434, 16980978, 27148587; Phenotypes: Craniolenticulosutural dysplasia (MIM# 607812); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.3444 ARSG Zornitza Stark Gene: arsg has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3443 ARSG Zornitza Stark Classified gene: ARSG as Amber List (moderate evidence)
Mendeliome v0.3443 ARSG Zornitza Stark Gene: arsg has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3442 UVSSA Crystle Lee reviewed gene: UVSSA: Rating: GREEN; Mode of pathogenicity: None; Publications: 31421932; Phenotypes: UV-sensitive syndrome 3 (MIM#614640); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3441 FAM92A Zornitza Stark Gene: fam92a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3441 FAM92A Zornitza Stark Classified gene: FAM92A as Amber List (moderate evidence)
Mendeliome v0.3441 FAM92A Zornitza Stark Gene: fam92a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3440 FAM92A Zornitza Stark gene: FAM92A was added
gene: FAM92A was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: FAM92A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAM92A were set to 30395363
Phenotypes for gene: FAM92A were set to Polydactyly, postaxial, type A9, MIM# 618219
Review for gene: FAM92A was set to AMBER
Added comment: Single family and a mouse model reported.
Sources: Expert list
Mendeliome v0.3439 KIAA0825 Zornitza Stark Gene: kiaa0825 has been classified as Green List (High Evidence).
Mendeliome v0.3439 KIAA0825 Zornitza Stark Classified gene: KIAA0825 as Green List (high evidence)
Mendeliome v0.3439 KIAA0825 Zornitza Stark Gene: kiaa0825 has been classified as Green List (High Evidence).
Mendeliome v0.3437 ZNF141 Zornitza Stark Gene: znf141 has been classified as Red List (Low Evidence).
Mendeliome v0.3434 ZNF141 Zornitza Stark Classified gene: ZNF141 as Red List (low evidence)
Mendeliome v0.3434 ZNF141 Zornitza Stark Gene: znf141 has been classified as Red List (Low Evidence).
Mendeliome v0.3433 NR0B1 Zornitza Stark Gene: nr0b1 has been classified as Green List (High Evidence).
Mendeliome v0.3433 NR0B1 Zornitza Stark Phenotypes for gene: NR0B1 were changed from Adrenal hypoplasia, congenital (MIM# 300200) to Adrenal hypoplasia, congenital (MIM# 300200); 46XY sex reversal 2, dosage-sensitive, MIM# 300018
Mendeliome v0.3432 NR0B1 Zornitza Stark Classified gene: NR0B1 as Green List (high evidence)
Mendeliome v0.3432 NR0B1 Zornitza Stark Gene: nr0b1 has been classified as Green List (High Evidence).
Mendeliome v0.3431 NR0B1 Zornitza Stark Classified gene: NR0B1 as Amber List (moderate evidence)
Mendeliome v0.3431 NR0B1 Zornitza Stark Gene: nr0b1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3430 NR0B1 Zornitza Stark Gene: nr0b1 has been classified as Green List (High Evidence).
Mendeliome v0.3430 NR0B1 Zornitza Stark Phenotypes for gene: NR0B1 were changed from to Adrenal hypoplasia, congenital (MIM# 300200)
Mendeliome v0.3427 NSDHL Zornitza Stark Gene: nsdhl has been classified as Green List (High Evidence).
Mendeliome v0.3423 TFR2 Zornitza Stark Gene: tfr2 has been classified as Green List (High Evidence).
Mendeliome v0.3423 TFR2 Zornitza Stark Phenotypes for gene: TFR2 were changed from Hemochromatosis, type 3 (MIM#604250) to Haemochromatosis, type 3 (MIM#604250)
Mendeliome v0.3422 TFR2 Zornitza Stark Phenotypes for gene: TFR2 were changed from to Hemochromatosis, type 3 (MIM#604250)
Mendeliome v0.3419 ABCD3 Zornitza Stark Gene: abcd3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3419 ABCD3 Zornitza Stark Phenotypes for gene: ABCD3 were changed from to Bile acid synthesis defect, congenital, 5 (MIM#616278)
Mendeliome v0.3416 ABCD3 Zornitza Stark Classified gene: ABCD3 as Amber List (moderate evidence)
Mendeliome v0.3416 ABCD3 Zornitza Stark Gene: abcd3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3414 TBC1D32 Zornitza Stark Classified gene: TBC1D32 as Amber List (moderate evidence)
Mendeliome v0.3414 TBC1D32 Zornitza Stark Gene: tbc1d32 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3413 NR0B1 Ain Roesley reviewed gene: NR0B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19508677, 26030781; Phenotypes: Adrenal hypoplasia, congenital (MIM# 300200); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.3413 TFR2 Teresa Zhao reviewed gene: TFR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24847265, 29743178; Phenotypes: Hemochromatosis, type 3 (MIM#604250); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.3413 ORMDL3 Zornitza Stark Gene: ormdl3 has been classified as Red List (Low Evidence).
Mendeliome v0.3413 ORMDL3 Zornitza Stark Classified gene: ORMDL3 as Red List (low evidence)
Mendeliome v0.3413 ORMDL3 Zornitza Stark Gene: ormdl3 has been classified as Red List (Low Evidence).
Mendeliome v0.3412 ABCD3 Crystle Lee reviewed gene: ABCD3: Rating: AMBER; Mode of pathogenicity: None; Publications: 25168382; Phenotypes: ?Bile acid synthesis defect, congenital, 5 (MIM#616278); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3412 NSMF Zornitza Stark Gene: nsmf has been classified as Red List (Low Evidence).
Mendeliome v0.3409 NSMF Zornitza Stark Classified gene: NSMF as Red List (low evidence)
Mendeliome v0.3409 NSMF Zornitza Stark Gene: nsmf has been classified as Red List (Low Evidence).
Mendeliome v0.3408 SPRY4 Zornitza Stark Gene: spry4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3405 SPRY4 Zornitza Stark Classified gene: SPRY4 as Amber List (moderate evidence)
Mendeliome v0.3405 SPRY4 Zornitza Stark Gene: spry4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3404 KISS1 Zornitza Stark Gene: kiss1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3401 KISS1 Zornitza Stark Classified gene: KISS1 as Amber List (moderate evidence)
Mendeliome v0.3401 KISS1 Zornitza Stark Gene: kiss1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3400 INSL3 Zornitza Stark Gene: insl3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3397 INSL3 Zornitza Stark Classified gene: INSL3 as Amber List (moderate evidence)
Mendeliome v0.3397 INSL3 Zornitza Stark Gene: insl3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3396 IL17RD Zornitza Stark Gene: il17rd has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3393 IL17RD Zornitza Stark Classified gene: IL17RD as Amber List (moderate evidence)
Mendeliome v0.3393 IL17RD Zornitza Stark Gene: il17rd has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3391 HS6ST1 Zornitza Stark Gene: hs6st1 has been classified as Red List (Low Evidence).
Mendeliome v0.3388 HS6ST1 Zornitza Stark Classified gene: HS6ST1 as Red List (low evidence)
Mendeliome v0.3388 HS6ST1 Zornitza Stark Gene: hs6st1 has been classified as Red List (Low Evidence).
Mendeliome v0.3387 GNRH1 Zornitza Stark Gene: gnrh1 has been classified as Green List (High Evidence).
Mendeliome v0.3384 KIF3B Zornitza Stark Phenotypes for gene: KIF3B were changed from hepatic fibrosis; retinitis pigmentosa; postaxial polydactyly to hepatic fibrosis; retinitis pigmentosa; postaxial polydactyly; Retinitis pigmentosa 89, MIM#618955
Mendeliome v0.3383 KIF3B Zornitza Stark edited their review of gene: KIF3B: Changed phenotypes: hepatic fibrosis, retinitis pigmentosa, postaxial polydactyly, Retinitis pigmentosa 89, MIM#618955
Mendeliome v0.3383 CUX2 Zornitza Stark Gene: cux2 has been classified as Green List (High Evidence).
Mendeliome v0.3380 DPM1 Zornitza Stark Gene: dpm1 has been classified as Green List (High Evidence).
Mendeliome v0.3377 GIPC1 Zornitza Stark Gene: gipc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3377 GIPC1 Zornitza Stark Classified gene: GIPC1 as Amber List (moderate evidence)
Mendeliome v0.3377 GIPC1 Zornitza Stark Gene: gipc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3376 GIPC1 Zornitza Stark gene: GIPC1 was added
gene: GIPC1 was added to Mendeliome. Sources: Literature
5'UTR, STR tags were added to gene: GIPC1.
Mode of inheritance for gene: GIPC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GIPC1 were set to 32413282
Phenotypes for gene: GIPC1 were set to Oculopharyngodistal myopathy-2 (OPDM2), MIM#618940
Review for gene: GIPC1 was set to AMBER
Added comment: 19 families reported with heterozygous trinucleotide repeat expansion in the 5-prime untranslated region and onset of distal muscle weakness, mainly of the lower limbs, and/or ophthalmoplegia in the second or third decades of life. Note this is unlikely to be tractable currently by most NGS assays.
Sources: Literature
Mendeliome v0.3375 SMC3 Zornitza Stark Gene: smc3 has been classified as Green List (High Evidence).
Mendeliome v0.3372 DEAF1 Zornitza Stark Gene: deaf1 has been classified as Green List (High Evidence).
Mendeliome v0.3372 DEAF1 Zornitza Stark Phenotypes for gene: DEAF1 were changed from to Neurodevelopmental disorder with hypotonia, impaired expressive language, and with or without seizures 617171; Vulto-van Silfout-de Vries syndrome 615828
Mendeliome v0.3368 DEAF1 Elena Savva reviewed gene: DEAF1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID 30923367, PMID 24726472; Phenotypes: Neurodevelopmental disorder with hypotonia, impaired expressive language, and with or without seizures 617171, Vulto-van Silfout-de Vries syndrome 615828; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3366 ABCC9 Zornitza Stark Gene: abcc9 has been classified as Green List (High Evidence).
Mendeliome v0.3366 ABCC9 Zornitza Stark Phenotypes for gene: ABCC9 were changed from to Hypertrichotic osteochondrodysplasia, MIM# 239850; Cantu syndrome; mild ID, similar facies, myopathy, cerebral white matter hyperintensities; cardiac systolic dysfunction
Mendeliome v0.3363 ABCC9 Zornitza Stark reviewed gene: ABCC9: Rating: GREEN; Mode of pathogenicity: Other; Publications: 31575858, 22610116, 22608503; Phenotypes: Hypertrichotic osteochondrodysplasia, MIM# 239850, Cantu syndrome, mild ID, similar facies, myopathy, cerebral white matter hyperintensities, cardiac systolic dysfunction; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3363 TSPYL1 Zornitza Stark Gene: tspyl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3363 TSPYL1 Zornitza Stark Phenotypes for gene: TSPYL1 were changed from to Sudden infant death with dysgenesis of the testes syndrome (MIM#608800)
Mendeliome v0.3360 TSPYL1 Zornitza Stark Classified gene: TSPYL1 as Amber List (moderate evidence)
Mendeliome v0.3360 TSPYL1 Zornitza Stark Gene: tspyl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3359 TSPYL1 Zornitza Stark reviewed gene: TSPYL1: Rating: AMBER; Mode of pathogenicity: None; Publications: 15273283, 19463995, 22137496, 25449952, 16418600; Phenotypes: Sudden infant death with dysgenesis of the testes syndrome (MIM#608800); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3359 PIGM Zornitza Stark Gene: pigm has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3359 PIGM Zornitza Stark Phenotypes for gene: PIGM were changed from to Glycosylphosphatidylinositol deficiency, MIM# 610293; portal vein thrombosis; persistent absence seizures; macrocephaly; infantile-onset cerebrovascular thrombotic events
Mendeliome v0.3356 PIGM Zornitza Stark Classified gene: PIGM as Amber List (moderate evidence)
Mendeliome v0.3356 PIGM Zornitza Stark Gene: pigm has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3355 LEP Zornitza Stark Gene: lep has been classified as Green List (High Evidence).
Mendeliome v0.3355 LEP Zornitza Stark Phenotypes for gene: LEP were changed from to Obesity, morbid, due to leptin deficiency (MIM#614962)
Mendeliome v0.3352 LEPR Zornitza Stark Gene: lepr has been classified as Green List (High Evidence).
Mendeliome v0.3352 LEPR Zornitza Stark Phenotypes for gene: LEPR were changed from to Obesity, morbid, due to leptin receptor deficiency (MIM#614963)
Mendeliome v0.3349 FEZF1 Zornitza Stark Gene: fezf1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3346 FEZF1 Zornitza Stark Classified gene: FEZF1 as Amber List (moderate evidence)
Mendeliome v0.3346 FEZF1 Zornitza Stark Gene: fezf1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3345 ESR2 Zornitza Stark Gene: esr2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3345 ESR2 Zornitza Stark Phenotypes for gene: ESR2 were changed from to 46,XY disorder of sex development; Ovarian dysgenesis 8, MIM# 618187
Mendeliome v0.3342 ESR2 Zornitza Stark reviewed gene: ESR2: Rating: AMBER; Mode of pathogenicity: None; Publications: 29261182, 9861029, 30113650; Phenotypes: 46,XY disorder of sex development, Ovarian dysgenesis 8, MIM# 618187; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3342 PIGM Paul De Fazio reviewed gene: PIGM: Rating: AMBER; Mode of pathogenicity: None; Publications: 31445883, 16767100; Phenotypes: portal vein thrombosis, persistent absence seizures, macrocephaly, infantile-onset cerebrovascular thrombotic events; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.3342 LEP Crystle Lee reviewed gene: LEP: Rating: GREEN; Mode of pathogenicity: None; Publications: 26567097; Phenotypes: Obesity, morbid, due to leptin deficiency (MIM#614962); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3342 DMRT1 Zornitza Stark Gene: dmrt1 has been classified as Red List (Low Evidence).
Mendeliome v0.3339 DMRT1 Zornitza Stark Classified gene: DMRT1 as Red List (low evidence)
Mendeliome v0.3339 DMRT1 Zornitza Stark Gene: dmrt1 has been classified as Red List (Low Evidence).
Mendeliome v0.3338 CBX2 Zornitza Stark Gene: cbx2 has been classified as Red List (Low Evidence).
Mendeliome v0.3335 CBX2 Zornitza Stark Classified gene: CBX2 as Red List (low evidence)
Mendeliome v0.3335 CBX2 Zornitza Stark Gene: cbx2 has been classified as Red List (Low Evidence).
Mendeliome v0.3334 LEPR Crystle Lee reviewed gene: LEPR: Rating: GREEN; Mode of pathogenicity: None; Publications: 17229951, 29545012; Phenotypes: Obesity, morbid, due to leptin receptor deficiency (MIM#614963); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3334 MCM5 Zornitza Stark Gene: mcm5 has been classified as Red List (Low Evidence).
Mendeliome v0.3333 MCM5 Zornitza Stark Classified gene: MCM5 as Red List (low evidence)
Mendeliome v0.3333 MCM5 Zornitza Stark Gene: mcm5 has been classified as Red List (Low Evidence).
Mendeliome v0.3332 ATF3 Zornitza Stark Gene: atf3 has been classified as Red List (Low Evidence).
Mendeliome v0.3332 ATF3 Zornitza Stark Classified gene: ATF3 as Red List (low evidence)
Mendeliome v0.3332 ATF3 Zornitza Stark Gene: atf3 has been classified as Red List (Low Evidence).
Mendeliome v0.3331 CNPY3 Zornitza Stark Gene: cnpy3 has been classified as Green List (High Evidence).
Mendeliome v0.3328 KIF21B Zornitza Stark Gene: kif21b has been classified as Green List (High Evidence).
Mendeliome v0.3328 KIF21B Zornitza Stark Classified gene: KIF21B as Green List (high evidence)
Mendeliome v0.3328 KIF21B Zornitza Stark Gene: kif21b has been classified as Green List (High Evidence).
Mendeliome v0.3327 KIF21B Zornitza Stark gene: KIF21B was added
gene: KIF21B was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: KIF21B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF21B were set to 32415109
Phenotypes for gene: KIF21B were set to Global developmental delay; Intellectual disability; Abnormality of brain morphology; Microcephaly
Mode of pathogenicity for gene: KIF21B was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: KIF21B was set to GREEN
Added comment: Asselin et al (2020 - PMID: 32415109) report on 4 individuals with KIF21B pathogenic variants. DD/ID (borderline intellectual functioning to severe ID) was a feature in all. Variable other findings included brain malformations (CCA) and microcephaly. 3 missense variants and a 4-bp insertion were identified, in 3 cases as de novo events while in a single subject the variant was inherited from the father who was also affected. The authors provide evidence for a role of KIF21B in the regulation of processes involved in cortical development and deleterious effect of the missense variants impeding neuronal migration and kinesin autoinhibition. Phenotypes specific to variants (e.g. CCA or microcephaly) were recapitulated in animal models. Missense variants are thought to exert a gain-of-function effect. As commented on, the 4-bp duplication (/frameshift) variant might not be pathogenic. In blood sample from the respective individual, RT-qPCR analysis suggested that haploinsufficiency (NMD) applies. Although Kif21b haploinsufficiency in mice was shown to lead to impaired neuronal positioning, the gene might partially tolerate LoF variants as also suggested by 28 such variants in gnomAD. Homozygous Kif21b ko mice display severe morphological abnormalities, partial loss of commissural fibers, cognitive deficits and altered synaptic transmission (several refs to previous studies provided by the authors).
Sources: Expert Review
Mendeliome v0.3326 TBC1D2B Zornitza Stark Gene: tbc1d2b has been classified as Green List (High Evidence).
Mendeliome v0.3326 TBC1D2B Zornitza Stark Classified gene: TBC1D2B as Green List (high evidence)
Mendeliome v0.3326 TBC1D2B Zornitza Stark Gene: tbc1d2b has been classified as Green List (High Evidence).
Mendeliome v0.3325 TBC1D2B Zornitza Stark gene: TBC1D2B was added
gene: TBC1D2B was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: TBC1D2B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBC1D2B were set to 32623794
Phenotypes for gene: TBC1D2B were set to Global developmental delay; Intellectual disability; Seizures; Gingival overgrowth; Behavioral abnormality; Abnormality of the mandible; Abnormality of brain morphology; Abnormality of the eye; Hearing abnormality
Review for gene: TBC1D2B was set to GREEN
Added comment: Harms et al (2020 - PMID: 32623794) report on 3 unrelated individuals with biallelic pLoF TBC1D2B variants. Features included cognitive impairment (mild ID in one case, regression at the age of 12y in another, hypotonia and delayed milestones in a third aged 8m), seizures (3/3 - variable age of onset) and/or gingival overgrowth (2/3 - prior to initiation of AEDs). Other findings included behavioral abnormalities, mandibular anomalies, abnormal brain imaging and ophthalmologic or (rarely) audiometric evaluations. All were born to non-consanguineous couples and additional investigations were performed in some. Variants were identified by WES or trio WGS, with Sanger confirmation/compatible segregation analyses. In line with the pLoF variants, mRNA studies in fibroblasts from 2 unrelated affected individuals demonstrated significantly reduced (~80-90%) TBC1C2D mRNA levels compared to controls, restored following cycloheximide treatment. Protein was absent in patient fibroblasts. TBC-domain containing GTPase activating proteins are known as key regulators of RAB GTPase activity. TBC1D2B was shown to colocalize with RAB5-positive endocytic vesicles. CRISPR/Cas9-mediated ko of TBC1D2B in HeLa cells suggested a role in EGF receptor endocytosis and decreased cell viability of TBC1D2B-deficient HeLa cells upon serum deprivation. Genes encoding other TBC domain-containg GTPase-activating proteins, e.g. TBC1D7 and TBC1D20, TBC1D24 are associated with recessive neurodevelopmental disorders (with ID and/or seizures) and the pathophysiological defect in TBC1D2B-related disorder (deficit in vesicle trafficking and/or cell survival) is proposed to be similar to that of TBC1D24.
Sources: Expert Review
Mendeliome v0.3324 EXOC2 Zornitza Stark Gene: exoc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3324 EXOC2 Zornitza Stark Classified gene: EXOC2 as Amber List (moderate evidence)
Mendeliome v0.3324 EXOC2 Zornitza Stark Gene: exoc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3323 EXOC2 Zornitza Stark gene: EXOC2 was added
gene: EXOC2 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: EXOC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOC2 were set to 32639540
Phenotypes for gene: EXOC2 were set to Global developmental delay; Intellectual disability; Abnormality of the face; Abnormality of brain morphology
Review for gene: EXOC2 was set to AMBER
Added comment: Van Bergen et al (2020 - PMID: 32639540) report on 3 individuals from 2 families, harboring biallelic EXOC2 mutations. Clinical presentation included DD, ID (severe in 2 subjects from fam1, borderline intellectual functioning in fam2), dysmorphic features and brain abnormalities. Cerebellar anomalies were common to all with a molar tooth sign observed in one (1/3). Other findings limited to subjects from one family included acquired microcephaly, congenital contractures, spastic quadriplegia (each observed 2/3). Previous investigations were in all cases non-diagnostic. WES identified biallelic EXOC2 mutations in all affected individuals. EXOC2 encodes an exocyst subunit. The latter is an octameric complex, component of the membrane transport machinery, required for tethering and fusion of vesicles at the plasma membrane. As discussed ,vesicle transport is important for the development of brain and the function of neurons and glia. Exocyst function is also important for delivery of Arl13b to the primary cilium (biallelic ARL13B mutations cause Joubert syndrome 8) and ciliogenesis. Affected subjects from a broader consanguineous family (fam1) were homozygous for a truncating variant. Fibroblast studies revealed mRNA levels compatible with NMD (further restored in presence of CHX) as well as reduced protein levels. The female belonging to the second non-consanguineous family was found to harbor 2 missense variants in trans configuration. An exocytosis defect was demonstrated in fibroblasts from individuals belonging to both families. Ciliogenesis appeared to be normal, however Arl13b localization/recruitment to the cilia was reduced compared with control cells with the defect rescued upon exogenous expression of wt EXOC2. Mutations in other genes encoding components of the exocyst complex have been previously reported in individuals with relevant phenotypes (e.g. EXOC8 in a boy with features of Joubert s. or EXOC4 in nephrotic syndrome). The authors discuss on the essential role of EXOC2 based on model organism studies (e.g. impaired neuronal membrane traffic, failure of neuronal polarization and neuromuscular junction expansion seen in Drosophila Sec5 (EXOC2) null mutants).
Sources: Expert Review
Mendeliome v0.3322 CCDC174 Zornitza Stark Gene: ccdc174 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3322 CCDC174 Zornitza Stark Classified gene: CCDC174 as Amber List (moderate evidence)
Mendeliome v0.3322 CCDC174 Zornitza Stark Gene: ccdc174 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3321 CCDC174 Zornitza Stark gene: CCDC174 was added
gene: CCDC174 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: CCDC174 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC174 were set to 26358778
Phenotypes for gene: CCDC174 were set to Hypotonia, infantile, with psychomotor retardation - IHPMR, 616816
Review for gene: CCDC174 was set to AMBER
Added comment: Biallelic pathogenic CCDC174 variants cause Hypotonia, infantile, with psychomotor retardation - IHPMR (MIM 616816). Volodarsky et al [2015 - PMID: 26358778] describe 6 children from 2 unrelated families with - among others - severe hypotonia, psychomotor delay and abducens nerve palsy. All affected subjects were homozygous for a stoploss variant. Evidence from functional studies/animal model is provided supporting the role of the gene in this phenotype. Overall this gene can be considered for inclusion in the ID panel with amber rating (2 families, single founder variant, consistent phenotype, supportive studies) pending further reports.
Sources: Expert Review
Mendeliome v0.3320 ACOX2 Zornitza Stark Classified gene: ACOX2 as Green List (high evidence)
Mendeliome v0.3320 ACOX2 Zornitza Stark Gene: acox2 has been classified as Green List (High Evidence).
Mendeliome v0.3319 ABCA2 Zornitza Stark Gene: abca2 has been classified as Green List (High Evidence).
Mendeliome v0.3319 ABCA2 Zornitza Stark Classified gene: ABCA2 as Green List (high evidence)
Mendeliome v0.3319 ABCA2 Zornitza Stark Gene: abca2 has been classified as Green List (High Evidence).
Mendeliome v0.3318 ABCA2 Zornitza Stark gene: ABCA2 was added
gene: ABCA2 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: ABCA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABCA2 were set to 30237576; 29302074; 31047799
Phenotypes for gene: ABCA2 were set to Intellectual developmental disorder with poor growth and with or without seizures or ataxia, 618808
Review for gene: ABCA2 was set to GREEN
Added comment: Biallelic pathogenic ABCA2 variants cause Intellectual developmental disorder with poor growth and with or without seizures or ataxia (MIM 618808). There are 3 relevant publications (01-07-2020) : - Maddirevula et al [2019 - PMID: 30237576] described briefly 2 unrelated subjects (16-2987, 16DG0071) both DD and seizures among other manifestations. - Hu et al [2019 - PMID: 29302074] reported 3 sibs (M8600615 - III:1-3) born to consanguineous parents (M8600615 - III:1-3) with DD/ID (formal confirmation of moderate ID, in those (2) evaluated). One also presented with seizures. - Aslam and Naz [2019 - PMID: 31047799] provided clinical details on 2 siblings born to consanguineous parents. ID was reported for the older sib but was absent in the younger one. Seizures were not part of the phenotype. All subjects harbored biallelic pLoF variants. N.B. : Steinberg et al [2015 - PMID: 25773295], within a cohort of patients with ALS, identified one with biallelic ABCA2 variants. As however Aslam and Naz comment, this person harbored a single pathogenic variant, with a second one rather unlikely to be pathogenic due to high allele frequency. Overall this gene can be considered for inclusion with green rating in both ID and epilepsy panels (each in >=3 unrelated individuals).
Sources: Expert Review
Mendeliome v0.3317 HERC2 Zornitza Stark Gene: herc2 has been classified as Green List (High Evidence).
Mendeliome v0.3317 HERC2 Zornitza Stark Phenotypes for gene: HERC2 were changed from to Mental retardation, autosomal recessive 38 (MIM 615516)
Mendeliome v0.3314 HERC2 Zornitza Stark reviewed gene: HERC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23065719, 23243086, 30902390, 32571899, 27848944, 26077850, 27759030; Phenotypes: Mental retardation, autosomal recessive 38 (MIM 615516); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3314 ALOX12 Zornitza Stark Gene: alox12 has been classified as Red List (Low Evidence).
Mendeliome v0.3314 ALOX12 Zornitza Stark Classified gene: ALOX12 as Red List (low evidence)
Mendeliome v0.3314 ALOX12 Zornitza Stark Gene: alox12 has been classified as Red List (Low Evidence).
Mendeliome v0.3313 ETF1 Zornitza Stark Gene: etf1 has been classified as Red List (Low Evidence).
Mendeliome v0.3313 ETF1 Zornitza Stark Classified gene: ETF1 as Red List (low evidence)
Mendeliome v0.3313 ETF1 Zornitza Stark Gene: etf1 has been classified as Red List (Low Evidence).
Mendeliome v0.3309 SGMS2 Bryony Thompson Gene: sgms2 has been classified as Green List (High Evidence).
Mendeliome v0.3309 SGMS2 Bryony Thompson Classified gene: SGMS2 as Green List (high evidence)
Mendeliome v0.3309 SGMS2 Bryony Thompson Gene: sgms2 has been classified as Green List (High Evidence).
Mendeliome v0.3308 SGMS2 Bryony Thompson gene: SGMS2 was added
gene: SGMS2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SGMS2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SGMS2 were set to 30779713; 32028018
Phenotypes for gene: SGMS2 were set to Calvarial doughnut lesions with bone fragility with or without spondylometaphyseal dysplasia MIM#126550
Review for gene: SGMS2 was set to GREEN
Added comment: 12 patients from 6 unrelated families with the same stopgain variant (p.Arg50*), with osteoporosis that resembles osteogenesis imperfecta. In vitro over-expression assays of the variant demonstrate protein that was completely mislocalized in the cytosolic and nuclear compartments. 2 unrelated families were heterozygous for 2 missense (p.Ile62Ser, p.Met64Arg) with bone fragility and severe short stature, and spondylometaphyseal dysplasia. In vitro assays of each variant demonstrated an enhanced rate of de novo sphingomyelin production by blocking export of a functional enzyme from the endoplasmic reticulum.
Sources: Expert list
Mendeliome v0.3307 AKR1C4 Zornitza Stark Gene: akr1c4 has been classified as Red List (Low Evidence).
Mendeliome v0.3304 AKR1C4 Zornitza Stark Classified gene: AKR1C4 as Red List (low evidence)
Mendeliome v0.3304 AKR1C4 Zornitza Stark Gene: akr1c4 has been classified as Red List (Low Evidence).
Mendeliome v0.3303 PIP5K1C Zornitza Stark Gene: pip5k1c has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3300 PIP5K1C Zornitza Stark Classified gene: PIP5K1C as Amber List (moderate evidence)
Mendeliome v0.3300 PIP5K1C Zornitza Stark Gene: pip5k1c has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3299 ERBB3 Zornitza Stark Gene: erbb3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3296 ERBB3 Zornitza Stark Classified gene: ERBB3 as Amber List (moderate evidence)
Mendeliome v0.3296 ERBB3 Zornitza Stark Gene: erbb3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3295 DPM2 Zornitza Stark Gene: dpm2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3292 DPM2 Zornitza Stark Classified gene: DPM2 as Amber List (moderate evidence)
Mendeliome v0.3292 DPM2 Zornitza Stark Gene: dpm2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3291 C17orf62 Zornitza Stark Phenotypes for gene: C17orf62 were changed from Chronic granulomatous disease to Chronic granulomatous disease 5, autosomal recessive, MIM# 618935
Mendeliome v0.3290 C17orf62 Zornitza Stark edited their review of gene: C17orf62: Changed phenotypes: Chronic granulomatous disease 5, autosomal recessive, MIM# 618935
Mendeliome v0.3290 DYSF Zornitza Stark Gene: dysf has been classified as Green List (High Evidence).
Mendeliome v0.3290 DYSF Zornitza Stark Phenotypes for gene: DYSF were changed from to Miyoshi muscular dystrophy 1 254130; Muscular dystrophy, limb-girdle, autosomal recessive 2 253601; Myopathy, distal, with anterior tibial onset 606768
Mendeliome v0.3287 NEB Zornitza Stark Gene: neb has been classified as Green List (High Evidence).
Mendeliome v0.3287 NEB Zornitza Stark Phenotypes for gene: NEB were changed from to Nemaline myopathy 2, autosomal recessive 256030
Mendeliome v0.3284 MRPS34 Zornitza Stark Gene: mrps34 has been classified as Green List (High Evidence).
Mendeliome v0.3281 NEB Elena Savva reviewed gene: NEB: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25205138; Phenotypes: Nemaline myopathy 2, autosomal recessive 256030; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3281 DYSF Elena Savva reviewed gene: DYSF: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27602406; Phenotypes: Miyoshi muscular dystrophy 1 254130, Muscular dystrophy, limb-girdle, autosomal recessive 2 253601, Myopathy, distal, with anterior tibial onset 606768; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3281 GLS Zornitza Stark Phenotypes for gene: GLS were changed from Epileptic encephalopathy, early infantile, 71, MIM# 618328; Global developmental delay, progressive ataxia, and elevated glutamine, MIM# 618412 to Epileptic encephalopathy, early infantile, 71, MIM# 618328; Global developmental delay, progressive ataxia, and elevated glutamine, MIM# 618412; Cataract
Mendeliome v0.3278 GLS Zornitza Stark edited their review of gene: GLS: Added comment: In addition, single individual also reported with de novo, GoF variant with profound ID, cataract.; Changed publications: 30575854, 30970188, 30239721
Mendeliome v0.3278 GLS Zornitza Stark edited their review of gene: GLS: Changed phenotypes: Epileptic encephalopathy, early infantile, 71, MIM# 618328, Global developmental delay, progressive ataxia, and elevated glutamine, MIM# 618412, Catarct; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3278 PYCR1 Dean Phelan changed review comment from: Aortopathy/Connective tissue review

Variants in this gene are associated with Cutis Laxa:
Cutis laxa type 2 (ARCL2, [MIM 219200]) is an autosomal-recessive multisystem disorder with prominent connective-tissue features characterized by the appearance of premature aging, particularly wrinkled and lax skin with reduced elasticity.

GEL PanelApp: Green in EDS panel - clinical features overlapping EDS
Cutis laxa, autosomal recessive, type IIIB (ARCL3B) PMID: 19648921,4076251, 22052856
Cutis laxa, autosomal recessive, type IIB (ARCL2B) PMID: 19576563, 19648921, 9648921, 22052856, 28294978 AR

PMID: 27756598: a homozygous mutation in PYCR1 segregating in the family with the affected individuals with complex connective tissue disorder and severe intellectual disability.; to: Aortopathy/Connective tissue review

Variants in this gene are associated with Cutis Laxa:
Cutis laxa type 2 (ARCL2, [MIM 219200]) is an autosomal-recessive multisystem disorder with prominent connective-tissue features characterized by the appearance of premature aging, particularly wrinkled and lax skin with reduced elasticity.

GEL PanelApp: Green in EDS panel - clinical features overlapping EDS
Cutis laxa, autosomal recessive, type IIIB (ARCL3B) PMID: 19648921,4076251, 22052856
Cutis laxa, autosomal recessive, type IIB (ARCL2B) PMID: 19576563, 19648921, 9648921, 22052856, 28294978 AR

PMID: 27756598: a homozygous mutation in PYCR1 segregating in the family with the affected individuals with complex connective tissue disorder and severe intellectual disability.
Mendeliome v0.3278 PYCR1 Seb Lunke Gene: pycr1 has been classified as Green List (High Evidence).
Mendeliome v0.3275 PIGY Zornitza Stark Gene: pigy has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3275 PIGY Zornitza Stark Phenotypes for gene: PIGY were changed from to Hyperphosphatasia with mental retardation syndrome 6, MIM# 616809
Mendeliome v0.3272 PIGY Zornitza Stark Classified gene: PIGY as Amber List (moderate evidence)
Mendeliome v0.3272 PIGY Zornitza Stark Gene: pigy has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3271 MTMR14 Zornitza Stark Added comment: Comment when marking as ready: Single family and animal models; postulated to be a modifier in the other family.
Mendeliome v0.3271 MTMR14 Zornitza Stark Gene: mtmr14 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3271 MTMR14 Zornitza Stark Classified gene: MTMR14 as Amber List (moderate evidence)
Mendeliome v0.3271 MTMR14 Zornitza Stark Gene: mtmr14 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3270 MTMR14 Zornitza Stark Gene: mtmr14 has been classified as Red List (Low Evidence).
Mendeliome v0.3268 P4HA1 Zornitza Stark Gene: p4ha1 has been classified as Red List (Low Evidence).
Mendeliome v0.3268 P4HA1 Zornitza Stark gene: P4HA1 was added
gene: P4HA1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: P4HA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: P4HA1 were set to 28419360
Phenotypes for gene: P4HA1 were set to Joint hypermobility; Contractures; Hypotonia; Mild skeletal dysplasia without bone fragility; High myopia
Review for gene: P4HA1 was set to RED
Added comment: Single family reported with two affected individuals.
Sources: Expert list
Mendeliome v0.3267 ROBO3 Ain Roesley reviewed gene: ROBO3: Rating: GREEN; Mode of pathogenicity: None; Publications: 15105459, 32373565; Phenotypes: Gaze palsy, familial horizontal, with progressive scoliosis, 1 (MIM# 607313); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3267 PIGY Elena Savva reviewed gene: PIGY: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 26293662; Phenotypes: Hyperphosphatasia with mental retardation syndrome 6, MIM# 616809; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3267 GGPS1 Zornitza Stark Gene: ggps1 has been classified as Green List (High Evidence).
Mendeliome v0.3267 GGPS1 Zornitza Stark Classified gene: GGPS1 as Green List (high evidence)
Mendeliome v0.3267 GGPS1 Zornitza Stark Gene: ggps1 has been classified as Green List (High Evidence).
Mendeliome v0.3265 DNMBP Seb Lunke Gene: dnmbp has been classified as Green List (High Evidence).
Mendeliome v0.3265 DNMBP Seb Lunke Classified gene: DNMBP as Green List (high evidence)
Mendeliome v0.3265 DNMBP Seb Lunke Gene: dnmbp has been classified as Green List (High Evidence).
Mendeliome v0.3263 CRYGA Zornitza Stark Gene: cryga has been classified as Red List (Low Evidence).
Mendeliome v0.3263 CRYGA Zornitza Stark gene: CRYGA was added
gene: CRYGA was added to Mendeliome. Sources: Expert list
refuted tags were added to gene: CRYGA.
Mode of inheritance for gene: CRYGA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CRYGA were set to 30450742; 28839118
Phenotypes for gene: CRYGA were set to Cataract
Review for gene: CRYGA was set to RED
Added comment: Reported as potentially disease causing in multiple individuals from two seperate families, but in both cases variant is present in the general population (20 Hets for one variant, >1000 hets and 9 homs in other variant)
Sources: Expert list
Mendeliome v0.3262 AKR1E2 Zornitza Stark Gene: akr1e2 has been classified as Red List (Low Evidence).
Mendeliome v0.3262 AKR1E2 Zornitza Stark gene: AKR1E2 was added
gene: AKR1E2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: AKR1E2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AKR1E2 were set to 26622071
Phenotypes for gene: AKR1E2 were set to congenital cataracts
Review for gene: AKR1E2 was set to RED
Added comment: Same family with homozygous canonical splice variants and 3 cases of congenital cataract described in 2012 (original) and 2015 (review). No other descriptions since.
Sources: Expert list
Mendeliome v0.3261 ADAMTSL4 Zornitza Stark Gene: adamtsl4 has been classified as Green List (High Evidence).
Mendeliome v0.3261 ADAMTSL4 Zornitza Stark Phenotypes for gene: ADAMTSL4 were changed from to Ectopia lentis, isolated, autosomal recessive, MIM# 225100
Mendeliome v0.3258 ADAMTSL4 Zornitza Stark reviewed gene: ADAMTSL4: Rating: GREEN; Mode of pathogenicity: None; Publications: 19200529, 20564469, 20141359, 21051722; Phenotypes: Ectopia lentis, isolated, autosomal recessive, MIM# 225100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3258 HIST1H4C Zornitza Stark Gene: hist1h4c has been classified as Green List (High Evidence).
Mendeliome v0.3255 SFTPA1 Zornitza Stark Gene: sftpa1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3255 SFTPA1 Zornitza Stark Phenotypes for gene: SFTPA1 were changed from to Idiopathic pulmonary fibrosis
Mendeliome v0.3252 SFTPA1 Zornitza Stark Classified gene: SFTPA1 as Amber List (moderate evidence)
Mendeliome v0.3252 SFTPA1 Zornitza Stark Gene: sftpa1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3251 SFTPA1 Zornitza Stark reviewed gene: SFTPA1: Rating: AMBER; Mode of pathogenicity: None; Publications: 31601679, 30854216, 28869238, 26792177; Phenotypes: Idiopathic pulmonary fibrosis; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.3251 CFAP74 Zornitza Stark Gene: cfap74 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3251 CFAP74 Zornitza Stark Classified gene: CFAP74 as Amber List (moderate evidence)
Mendeliome v0.3251 CFAP74 Zornitza Stark Gene: cfap74 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3250 CFAP74 Zornitza Stark gene: CFAP74 was added
gene: CFAP74 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CFAP74 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFAP74 were set to 32555313
Phenotypes for gene: CFAP74 were set to Primary ciliary dyskinesia; infertility
Review for gene: CFAP74 was set to AMBER
Added comment: Two unrelated individuals with compound het missense variants reported.
Sources: Literature
Mendeliome v0.3249 ASPRV1 Zornitza Stark Gene: asprv1 has been classified as Green List (High Evidence).
Mendeliome v0.3249 ASPRV1 Zornitza Stark Classified gene: ASPRV1 as Green List (high evidence)
Mendeliome v0.3249 ASPRV1 Zornitza Stark Gene: asprv1 has been classified as Green List (High Evidence).
Mendeliome v0.3248 ASPRV1 Ee Ming Wong gene: ASPRV1 was added
gene: ASPRV1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ASPRV1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ASPRV1 were set to PMID: 32516568
Phenotypes for gene: ASPRV1 were set to palmoplantar keratoderma; lamellar ichthyosis
Review for gene: ASPRV1 was set to GREEN
gene: ASPRV1 was marked as current diagnostic
Added comment: -3 heterozygous missense variants identified across 4 unrelated kindreds
-mutant ASPRV1 expressed in human keratinocytes suggests impaired filaggrin processing
Sources: Literature
Mendeliome v0.3248 LGR4 Zornitza Stark Gene: lgr4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3246 SREBF1 Seb Lunke Gene: srebf1 has been classified as Green List (High Evidence).
Mendeliome v0.3246 SREBF1 Seb Lunke Classified gene: SREBF1 as Green List (high evidence)
Mendeliome v0.3246 SREBF1 Seb Lunke Gene: srebf1 has been classified as Green List (High Evidence).
Mendeliome v0.3245 BTG4 Seb Lunke Gene: btg4 has been classified as Green List (High Evidence).
Mendeliome v0.3245 BTG4 Seb Lunke Classified gene: BTG4 as Green List (high evidence)
Mendeliome v0.3245 BTG4 Seb Lunke Gene: btg4 has been classified as Green List (High Evidence).
Mendeliome v0.3244 TRIP13 Seb Lunke Gene: trip13 has been classified as Green List (High Evidence).
Mendeliome v0.3243 LGR4 Zornitza Stark Classified gene: LGR4 as Amber List (moderate evidence)
Mendeliome v0.3243 LGR4 Zornitza Stark Gene: lgr4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3242 SREBF1 Paul De Fazio gene: SREBF1 was added
gene: SREBF1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SREBF1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SREBF1 were set to 32497488
Phenotypes for gene: SREBF1 were set to IFAP (ichthyosis follicularis, atrichia, and photophobia) syndrome
Review for gene: SREBF1 was set to GREEN
gene: SREBF1 was marked as current diagnostic
Added comment: 11 unrelated, ethnically diverse individuals with autosomal-dominant IFAP syndrome. 3 different msisense variants identified affecting the same region (residues 527, 528, and 530). Functional studies support impaired function (impaired nuclear translocation of the transcriptionally active form of SREBP1 resulting in lower expression of the SREBP1 variants). Increased keratinocyte apoptosis was observed in patient scalp samples.
Sources: Literature
Mendeliome v0.3242 RAP1GDS1 Zornitza Stark Gene: rap1gds1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3242 RAP1GDS1 Zornitza Stark Classified gene: RAP1GDS1 as Amber List (moderate evidence)
Mendeliome v0.3242 RAP1GDS1 Zornitza Stark Gene: rap1gds1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3241 KIAA1217 Zornitza Stark Gene: kiaa1217 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3241 KIAA1217 Zornitza Stark Classified gene: KIAA1217 as Amber List (moderate evidence)
Mendeliome v0.3241 KIAA1217 Zornitza Stark Gene: kiaa1217 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3239 LGR4 Elena Savva reviewed gene: LGR4: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 32493844; Phenotypes: {Bone mineral density, low, susceptibility to} 615311; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.3239 RAP1GDS1 Zornitza Stark gene: RAP1GDS1 was added
gene: RAP1GDS1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RAP1GDS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAP1GDS1 were set to 32431071
Phenotypes for gene: RAP1GDS1 were set to Intellectual disability; dysmorphic features
Review for gene: RAP1GDS1 was set to AMBER
Added comment: Four individuals from two consanguineous families, same homozygous splice site variant detected.
Sources: Literature
Mendeliome v0.3238 HOXD10 Zornitza Stark Gene: hoxd10 has been classified as Red List (Low Evidence).
Mendeliome v0.3235 HOXD10 Zornitza Stark Classified gene: HOXD10 as Red List (low evidence)
Mendeliome v0.3235 HOXD10 Zornitza Stark Gene: hoxd10 has been classified as Red List (Low Evidence).
Mendeliome v0.3234 ADPRHL2 Zornitza Stark Gene: adprhl2 has been classified as Green List (High Evidence).
Mendeliome v0.3231 ADPRHL2 Zornitza Stark changed review comment from: Ataxia is part of the phenotype.
Sources: Expert list; to: 14 families reported, onset is in the first years of life following normal early development. Patients have cyclic episodic deterioration in response to stress, such as infection or febrile illness. The severity is highly variable: some patients develop seizures early in life that are associated with loss of developmental milestones and early sudden death in childhood, whereas others present at a later age with muscle weakness, gait ataxia, impaired speech, more subtle clinical deterioration, and cognitive decline. Neurologic involvement includes gait ataxia, cerebellar signs associated with cerebellar atrophy, generalized brain atrophy, impaired intellectual development, hearing loss, and peripheral neuropathy.
Sources: Expert list
Mendeliome v0.3231 GPR161 Zornitza Stark Gene: gpr161 has been classified as Green List (High Evidence).
Mendeliome v0.3231 GPR161 Zornitza Stark Classified gene: GPR161 as Green List (high evidence)
Mendeliome v0.3231 GPR161 Zornitza Stark Gene: gpr161 has been classified as Green List (High Evidence).
Mendeliome v0.3230 GPR161 Zornitza Stark gene: GPR161 was added
gene: GPR161 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GPR161 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GPR161 were set to 31609649
Phenotypes for gene: GPR161 were set to Predisposition to paediatric medulloblastoma
Review for gene: GPR161 was set to GREEN
Added comment: 6 unrelated individuals reported with germline variants, 5 with truncating, one missense. Somatic second hit in tumour tissue.
Sources: Literature
Mendeliome v0.3229 SETD1B Zornitza Stark Gene: setd1b has been classified as Green List (High Evidence).
Mendeliome v0.3226 ARF1 Zornitza Stark Gene: arf1 has been classified as Green List (High Evidence).
Mendeliome v0.3226 ARF1 Zornitza Stark Classified gene: ARF1 as Green List (high evidence)
Mendeliome v0.3226 ARF1 Zornitza Stark Gene: arf1 has been classified as Green List (High Evidence).
Mendeliome v0.3223 MRAS Zornitza Stark Gene: mras has been classified as Green List (High Evidence).
Mendeliome v0.3223 MRAS Zornitza Stark Classified gene: MRAS as Green List (high evidence)
Mendeliome v0.3223 MRAS Zornitza Stark Gene: mras has been classified as Green List (High Evidence).
Mendeliome v0.3222 MRAS Zornitza Stark changed review comment from: Two unrelated individuals reported with de novo variants in this gene. Rated as LIMITED by ClinGen.
Sources: Expert list; to: Two unrelated individuals reported with de novo variants in this gene initially. Rated as LIMITED by ClinGen in 2018. Note 4 further individuals reported since.
Sources: Expert list
Mendeliome v0.3221 A2ML1 Zornitza Stark Gene: a2ml1 has been classified as Red List (Low Evidence).
Mendeliome v0.3218 A2ML1 Zornitza Stark Classified gene: A2ML1 as Red List (low evidence)
Mendeliome v0.3218 A2ML1 Zornitza Stark Gene: a2ml1 has been classified as Red List (Low Evidence).
Mendeliome v0.3217 NRG1 Bryony Thompson Gene: nrg1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3217 NRG1 Bryony Thompson Classified gene: NRG1 as Amber List (moderate evidence)
Mendeliome v0.3217 NRG1 Bryony Thompson Gene: nrg1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3215 FLRT3 Zornitza Stark Gene: flrt3 has been classified as Red List (Low Evidence).
Mendeliome v0.3212 FLRT3 Zornitza Stark Classified gene: FLRT3 as Red List (low evidence)
Mendeliome v0.3212 FLRT3 Zornitza Stark Gene: flrt3 has been classified as Red List (Low Evidence).
Mendeliome v0.3211 CCDC32 Zornitza Stark Added comment: Comment when marking as ready: Three affected individuals from two unrelated families, supportive animal model and other functional data consistent with this being a ciliopathy.
Mendeliome v0.3211 CCDC32 Zornitza Stark Gene: ccdc32 has been classified as Green List (High Evidence).
Mendeliome v0.3211 CCDC32 Zornitza Stark Classified gene: CCDC32 as Green List (high evidence)
Mendeliome v0.3211 CCDC32 Zornitza Stark Gene: ccdc32 has been classified as Green List (High Evidence).
Mendeliome v0.3210 CAPZA2 Zornitza Stark Gene: capza2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3210 CAPZA2 Zornitza Stark Classified gene: CAPZA2 as Amber List (moderate evidence)
Mendeliome v0.3210 CAPZA2 Zornitza Stark Gene: capza2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3209 PPP3R1 Zornitza Stark Gene: ppp3r1 has been classified as Red List (Low Evidence).
Mendeliome v0.3209 PPP3R1 Zornitza Stark Classified gene: PPP3R1 as Red List (low evidence)
Mendeliome v0.3209 PPP3R1 Zornitza Stark Gene: ppp3r1 has been classified as Red List (Low Evidence).
Mendeliome v0.3208 PLEK Zornitza Stark Gene: plek has been classified as Red List (Low Evidence).
Mendeliome v0.3208 PLEK Zornitza Stark Classified gene: PLEK as Red List (low evidence)
Mendeliome v0.3208 PLEK Zornitza Stark Gene: plek has been classified as Red List (Low Evidence).
Mendeliome v0.3207 CNRIP1 Zornitza Stark Gene: cnrip1 has been classified as Red List (Low Evidence).
Mendeliome v0.3207 CNRIP1 Zornitza Stark Classified gene: CNRIP1 as Red List (low evidence)
Mendeliome v0.3207 CNRIP1 Zornitza Stark Gene: cnrip1 has been classified as Red List (Low Evidence).
Mendeliome v0.3206 RAD21 Zornitza Stark Gene: rad21 has been classified as Green List (High Evidence).
Mendeliome v0.3202 PPP3R1 Eleanor Williams gene: PPP3R1 was added
gene: PPP3R1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PPP3R1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PPP3R1 were set to 32337552; 19159392
Phenotypes for gene: PPP3R1 were set to Deafness, autosomal dominant 58 MIM#615654
Review for gene: PPP3R1 was set to RED
Added comment: PMID: 32337552 - Lezirovitz et al 2020- ~200 Kb genomic duplication in 2p14 was found that segregates with postlingual progressive sensorineural autosomal dominant hearing loss in a large Brazilian family with 20 affected individuals (the reported DFNA58 family from PMID: 19159392). The duplication covers PLEK and CNRIP1, and the first exon of PPP3R1 (protein coding), as well as four uncharacterized long non-coding RNA genes and part of a novel protein-coding gene. Cnrip1, Plek and Ppp3r1 genes are all expressed in the adult mouse cochlea and CNRIP1 mRNA was overexpressed in affected family members.
Sources: Literature
Mendeliome v0.3202 PLEK Eleanor Williams gene: PLEK was added
gene: PLEK was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PLEK was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PLEK were set to 32337552; 19159392
Phenotypes for gene: PLEK were set to Deafness, autosomal dominant 58 MIM#615654
Review for gene: PLEK was set to RED
Added comment: PMID: 32337552 - Lezirovitz et al 2020- ~200 Kb genomic duplication in 2p14 was found that segregates with postlingual progressive sensorineural autosomal dominant hearing loss in a large Brazilian family with 20 affected individuals (the reported DFNA58 family from PMID: 19159392). The duplication covers PLEK and CNRIP1, and the first exon of PPP3R1 (protein coding), as well as four uncharacterized long non-coding RNA genes and part of a novel protein-coding gene. Cnrip1, Plek and Ppp3r1 genes are all expressed in the adult mouse cochlea and CNRIP1 mRNA was overexpressed in affected family members.
Sources: Literature
Mendeliome v0.3202 CNRIP1 Eleanor Williams gene: CNRIP1 was added
gene: CNRIP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CNRIP1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CNRIP1 were set to 32337552; 19159392
Phenotypes for gene: CNRIP1 were set to Deafness, autosomal dominant 58 MIM#615654
Review for gene: CNRIP1 was set to RED
Added comment: PMID: 32337552 - Lezirovitz et al 2020- ~200 Kb genomic duplication in 2p14 was found that segregates with postlingual progressive sensorineural autosomal dominant hearing loss in a large Brazilian family with 20 affected individuals (the reported DFNA58 family from PMID: 19159392). The duplication covers PLEK and CNRIP1, and the first exon of PPP3R1 (protein coding), as well as four uncharacterized long non-coding RNA genes and part of a novel protein-coding gene. Cnrip1, Plek and Ppp3r1 genes are all expressed in the adult mouse cochlea and CNRIP1 mRNA was overexpressed in affected family members.
Sources: Literature
Mendeliome v0.3202 SKIV2L Zornitza Stark Gene: skiv2l has been classified as Green List (High Evidence).
Mendeliome v0.3199 NLRP5 Zornitza Stark Gene: nlrp5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3199 NLRP5 Zornitza Stark Classified gene: NLRP5 as Amber List (moderate evidence)
Mendeliome v0.3199 NLRP5 Zornitza Stark Gene: nlrp5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3197 EMILIN1 Zornitza Stark Gene: emilin1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3197 EMILIN1 Zornitza Stark Classified gene: EMILIN1 as Amber List (moderate evidence)
Mendeliome v0.3197 EMILIN1 Zornitza Stark Gene: emilin1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3196 EXOC7 Zornitza Stark gene: EXOC7 was added
gene: EXOC7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EXOC7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOC7 were set to 32103185
Phenotypes for gene: EXOC7 were set to brain atrophy; seizures; developmental delay; microcephaly
Review for gene: EXOC7 was set to GREEN
Added comment: 4 families with 8 affected individuals with brain atrophy, seizures, and developmental delay, and in more severe cases microcephaly and infantile death. Four novel homozygous or comp.heterozygous variants found in EXOC7, which segregated with disease in the families. They showed that EXOC7, a member of the mammalian exocyst complex, is highly expressed in developing human cortex. In addition, a zebrafish model of Exoc7 deficiency recapitulates the human disorder with increased apoptosis and decreased progenitor cells during telencephalon development, suggesting that the brain atrophy in human cases reflects neuronal degeneration.
Sources: Literature
Mendeliome v0.3195 HNRNPH1 Zornitza Stark gene: HNRNPH1 was added
gene: HNRNPH1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HNRNPH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HNRNPH1 were set to 32335897; 29938792
Phenotypes for gene: HNRNPH1 were set to HNRNPH1‐related syndromic intellectual disability
Review for gene: HNRNPH1 was set to GREEN
Added comment: 1st patient reported in 2018 with intellectual disability and dysmorphic features and HNRNPH1 heterozygous missense variant. 2020 paper reports additional 7 cases with ID, short stature, microcephaly, distinctive dysmorphic facial features, and congenital anomalies (cranial, brain, genitourinary, palate, ophthalmologic). They all had HNRNPH1 heterozygous pathogenic variants (missense, frameshift, in‐frame deletion, entire gene duplication) and were identified using clinical networks and GeneMatcher. No comments in paper if all de novo.
Sources: Literature
Mendeliome v0.3194 PDCD6IP Zornitza Stark gene: PDCD6IP was added
gene: PDCD6IP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PDCD6IP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDCD6IP were set to 32286682
Phenotypes for gene: PDCD6IP were set to Microcephaly; intellectual disability
Review for gene: PDCD6IP was set to AMBER
Added comment: One consanguineous family with 2 affected sibs with primary microcephaly (-4SD), intellectual disability and short stature (-5/6SD), and homozygous frameshift variant in PDCD6IP. The homozygous variant was confirmed in both affected sibs, while the four healthy siblings and parents were heterozygous. The clinical features observed in the patients were similar to the phenotypes observed in mouse and zebrafish models of PDCD6IP mutations in previous studies.
Sources: Literature
Mendeliome v0.3193 NME5 Zornitza Stark Gene: nme5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3193 NME5 Zornitza Stark Classified gene: NME5 as Amber List (moderate evidence)
Mendeliome v0.3193 NME5 Zornitza Stark Gene: nme5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3192 NME5 Zornitza Stark gene: NME5 was added
gene: NME5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NME5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NME5 were set to 32185794
Phenotypes for gene: NME5 were set to Primary ciliary dyskinesia
Review for gene: NME5 was set to AMBER
Added comment: One patient with PCD with situs solitus, with radial spokes (RS) and central pair (CP) defects. Patient had a homozygous nonsense variant in NME5, with parents as carriers. Morpholino knockdown of nme5 in zebrafish embryos resulted in motile cilia defects with phenotypes compatible with ciliopathy.
Sources: Literature
Mendeliome v0.3190 ADAMTS19 Zornitza Stark Classified gene: ADAMTS19 as Green List (high evidence)
Mendeliome v0.3190 ADAMTS19 Zornitza Stark Gene: adamts19 has been classified as Green List (High Evidence).
Mendeliome v0.3189 EMILIN1 Naomi Baker changed review comment from: Missense mutations identified in two families. First family, proband presented with ascending and descending aortic aneurysms, bilateral lower leg and foot sensorimotor peripheral neuropathy, arthropathy, and increased skin elasticity. Variant segregated with disease in the affected proband, mother, and son. Second family, father and three affected children showed amyotrophy and weakness of the distal lower limbs, dating back to early childhood. Some functional studies performed in patient fibroblasts and zebrafish, however these were not conclusive as the two missense mutations are at different locations within the protein.
Sources: Literature; to: Missense mutations identified in two families. First family, proband presented with ascending and descending aortic aneurysms, bilateral lower leg and foot sensorimotor peripheral neuropathy, arthropathy, and increased skin elasticity. Variant segregated with disease in the affected proband, mother, and son. Second family, father and three affected children showed amyotrophy and weakness of the distal lower limbs, dating back to early childhood. Some functional studies performed in patient fibroblasts and zebrafish, however these were not conclusive as the two missense mutations are at different locations within the protein.
Sources: Literature
Mendeliome v0.3189 EMILIN1 Naomi Baker gene: EMILIN1 was added
gene: EMILIN1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EMILIN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EMILIN1 were set to PMID: 31978608; 26462740.
Phenotypes for gene: EMILIN1 were set to peripheral neuropathy
Penetrance for gene: EMILIN1 were set to unknown
Review for gene: EMILIN1 was set to AMBER
Added comment: Missense mutations identified in two families. First family, proband presented with ascending and descending aortic aneurysms, bilateral lower leg and foot sensorimotor peripheral neuropathy, arthropathy, and increased skin elasticity. Variant segregated with disease in the affected proband, mother, and son. Second family, father and three affected children showed amyotrophy and weakness of the distal lower limbs, dating back to early childhood. Some functional studies performed in patient fibroblasts and zebrafish, however these were not conclusive as the two missense mutations are at different locations within the protein.
Sources: Literature
Mendeliome v0.3189 ADAMTS3 Zornitza Stark Gene: adamts3 has been classified as Green List (High Evidence).
Mendeliome v0.3189 ADAMTS3 Zornitza Stark Classified gene: ADAMTS3 as Green List (high evidence)
Mendeliome v0.3189 ADAMTS3 Zornitza Stark Gene: adamts3 has been classified as Green List (High Evidence).
Mendeliome v0.3188 ADAMTS3 Zornitza Stark gene: ADAMTS3 was added
gene: ADAMTS3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ADAMTS3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAMTS3 were set to 28985353; 30450763
Phenotypes for gene: ADAMTS3 were set to Hennekam lymphangiectasia-lymphedema syndrome 3 (618154)
Review for gene: ADAMTS3 was set to GREEN
Added comment: Two families reported, supportive functional data.
Sources: Expert list
Mendeliome v0.3186 SP6 Zornitza Stark Gene: sp6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3186 SP6 Zornitza Stark Classified gene: SP6 as Amber List (moderate evidence)
Mendeliome v0.3186 SP6 Zornitza Stark Gene: sp6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3185 MCM3AP Eleanor Williams changed review comment from: PMID: 32202298 - Woldegebriel et al - report a further two families, one in the Netherlands and one in Estonia, with probands with compound heterozygous variants in MCM3AP and a peripheral neuropathy with or without impaired intellectual development (MIM 618124) phenotype. The child from the Netherlands presented with severe hypotonia and intellectual disability. The two siblings from the Estonian family had severe generalized epilepsy and mild spastic diplegia. Functional studies using skin fibroblasts from these and other affected patients showed that disease variants result in depletion of GANP (encoded by MCM3AP) except when they alter critical residues in the Sac3 mRNA binding domain. GANP depletion was associated with more severe phenotypes compared with the Sac3 variants.; to: PMID: 32202298 - Woldegebriel et al 2020 - report a further two families, one in the Netherlands and one in Estonia, with probands with compound heterozygous variants in MCM3AP and a peripheral neuropathy with or without impaired intellectual development (MIM 618124) phenotype. The child from the Netherlands presented with severe hypotonia and intellectual disability. The two siblings from the Estonian family had severe generalized epilepsy and mild spastic diplegia. Functional studies using skin fibroblasts from these and other affected patients showed that disease variants result in depletion of GANP (encoded by MCM3AP) except when they alter critical residues in the Sac3 mRNA binding domain. GANP depletion was associated with more severe phenotypes compared with the Sac3 variants.
Mendeliome v0.3185 SP6 Eleanor Williams gene: SP6 was added
gene: SP6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SP6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SP6 were set to 32167558; 18156176; 18297738; 22676574
Phenotypes for gene: SP6 were set to hypoplastic amelogenesis imperfecta
Review for gene: SP6 was set to AMBER
Added comment: PMID: 32167558 - Smith et al 2020 - report a 2 bp variant c.817_818GC>AA in SP6 in a Caucasian family with autosomal dominant hypoplastic AI which results in a missense change. Report that mice and rat knockouts also show a dental phenotype (PMID: 18156176, 18297738, 22676574 )
Sources: Literature
Mendeliome v0.3185 MYH8 Zornitza Stark Gene: myh8 has been classified as Green List (High Evidence).
Mendeliome v0.3182 CACNB1 Zornitza Stark Gene: cacnb1 has been classified as Red List (Low Evidence).
Mendeliome v0.3182 CACNB1 Zornitza Stark gene: CACNB1 was added
gene: CACNB1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: CACNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CACNB1 were set to 27832566; 8943043; 29212769
Phenotypes for gene: CACNB1 were set to Malignant hyperthermia susceptibility
Added comment: A single heterozygous case with a positive IVCT muscle biopsy has been reported with p.Val156Ala. The European non-Finnish allele frequency in gnomAD v2.1 is 0.001146 (148/129,118 alleles), which is higher than the expected population frequency for dominantly inherited malignant hyperthermia (0.1%). Additionally, functional assays of this variant, suggest it would only significantly affect function in the homozygous state (suggesting a recessive condition).
Sources: Expert list
Mendeliome v0.3181 GATA6 Zornitza Stark Gene: gata6 has been classified as Green List (High Evidence).
Mendeliome v0.3181 GATA6 Zornitza Stark Phenotypes for gene: GATA6 were changed from to Pancreatic agenesis and congenital heart defects, 600001; Atrial septal defect 9, 614475; Atrioventricular septal defect 5, 614474; Tetralogy of Fallot, 187500; Persistent truncus arteriosus, 217095
Mendeliome v0.3177 GATA6 Elena Savva reviewed gene: GATA6: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID:20581743, 19666519; Phenotypes: Pancreatic agenesis and congenital heart defects, 600001, Atrial septal defect 9, 614475, Atrioventricular septal defect 5, 614474, Tetralogy of Fallot, 187500, Persistent truncus arteriosus, 217095; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.3177 CDH2 Zornitza Stark Phenotypes for gene: CDH2 were changed from Intellectual disability; corpus callosum abnormalities; congenital abnormalities to Intellectual disability; corpus callosum abnormalities; congenital abnormalities; Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, MIM# 618929
Mendeliome v0.3176 CDH2 Zornitza Stark edited their review of gene: CDH2: Changed phenotypes: Intellectual disability, corpus callosum abnormalities, congenital abnormalities, Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, MIM# 618929
Mendeliome v0.3174 TSHZ1 Zornitza Stark changed review comment from: Two individuals reported with LoF variants, both with a phenotype of congenital aural atresia and hyposmia (PMID: 22152683). Temporal and spatial expression of Tshz1 mRNA during development of the middle ear is consistent with the phenotype (PMID: 17586487). Tsh2 null mouse model showed a middle ear malformation, and neonatal lethality. A conditional nervous system-specific Tshz1 knock out mouse model demonstrated hyposmia (PMIDs: 24487590; 17586487).; to: Two individuals reported with LoF variants, both with a phenotype of congenital aural atresia and hyposmia (PMID: 22152683). Temporal and spatial expression of Tshz1 mRNA during development of the middle ear is consistent with the phenotype (PMID: 17586487). Tsh2 null mouse model showed a middle ear malformation, and neonatal lethality. A conditional nervous system-specific Tshz1 knock out mouse model demonstrated hyposmia (PMIDs: 24487590; 17586487). Also note original report contains four individuals with deletions of this gene, further supporting gene-disease association.
Mendeliome v0.3173 TSHZ1 Zornitza Stark Gene: tshz1 has been classified as Green List (High Evidence).
Mendeliome v0.3173 TSHZ1 Zornitza Stark Phenotypes for gene: TSHZ1 were changed from to Aural atresia, congenital, MIM# 607842; Hyposmia
Mendeliome v0.3170 TSHZ1 Zornitza Stark reviewed gene: TSHZ1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15834955, 22152683, 17586487, 24487590; Phenotypes: Aural atresia, congenital, MIM# 607842, Hyposmia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3170 ZBTB18 Zornitza Stark Gene: zbtb18 has been classified as Green List (High Evidence).
Mendeliome v0.3166 ESR2 Bryony Thompson Classified gene: ESR2 as Amber List (moderate evidence)
Mendeliome v0.3166 ESR2 Bryony Thompson Gene: esr2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3164 MT-TP Bryony Thompson Gene: mt-tp has been classified as Red List (Low Evidence).
Mendeliome v0.3164 MT-TP Bryony Thompson Classified gene: MT-TP as Red List (low evidence)
Mendeliome v0.3164 MT-TP Bryony Thompson Added comment: Comment on list classification: This is a mitochondrial gene, which is on the Mitochondrial disease gene panel.
Mendeliome v0.3164 MT-TP Bryony Thompson Gene: mt-tp has been classified as Red List (Low Evidence).
Mendeliome v0.3163 SETD2 Zornitza Stark Gene: setd2 has been classified as Green List (High Evidence).
Mendeliome v0.3160 UBE2A Zornitza Stark Gene: ube2a has been classified as Green List (High Evidence).
Mendeliome v0.3157 AXL Bryony Thompson Gene: axl has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3157 AXL Bryony Thompson Classified gene: AXL as Amber List (moderate evidence)
Mendeliome v0.3157 AXL Bryony Thompson Gene: axl has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3156 AXL Bryony Thompson gene: AXL was added
gene: AXL was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AXL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AXL were set to 18787040; 24476074
Phenotypes for gene: AXL were set to Kallman syndrome; normosmic idiopathic hypogonadotropic hypogonadism
Review for gene: AXL was set to AMBER
Added comment: Axl null mice had delayed first oestrus and persistently abnormal oestrous cyclicality compared with wild-type controls. Only a single study reported screening human cases. In a screen of 104 probands with KS or nIHH, four heterozygous AXL mutations were identified in two KS and two nIHH unrelated subjects (two males and two females). Three of the variants appear to be too common in gnomAD v2.1 given the reported prevalence of KS reported in GeneReviews (1:30,000 in males and 1:125,000 in females): c.587-6C>T (normal splicing in RNA studies, NFE AF 0.0001472), p.Q361P (NFE 0.002560), p.L50F (AJ 0.004405). The other variant p.S202C (4 hets, 1 female in gnomAD v2.1) is rare enough in gnomAD for a dominant disorder. In vitro functional assays were conducted and p.S202C had an significant effect on function, but so did the more common variant p.Q361P.
Sources: Literature
Mendeliome v0.3155 GANAB Zornitza Stark Gene: ganab has been classified as Green List (High Evidence).
Mendeliome v0.3151 GOLGA2 Zornitza Stark Gene: golga2 has been classified as Green List (High Evidence).
Mendeliome v0.3151 GOLGA2 Zornitza Stark Classified gene: GOLGA2 as Green List (high evidence)
Mendeliome v0.3151 GOLGA2 Zornitza Stark Gene: golga2 has been classified as Green List (High Evidence).
Mendeliome v0.3150 GOLGA2 Elena Savva gene: GOLGA2 was added
gene: GOLGA2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: GOLGA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GOLGA2 were set to PMID: 30237576; 26742501
Phenotypes for gene: GOLGA2 were set to Nueromuscular disorder
Review for gene: GOLGA2 was set to GREEN
Added comment: PMID: 30237576 - One 11 year old patient with a homozygous PTC.
Patient had global dev delay, microcephaly, distal muscle weakness with joint contractures and elevated CK levels. Muscle biopsy showed dystrophin changes. MRI at 2 years old showed brain atrophy with thin corpus callosum and hypomyelination. No seizures or regression.

PMID: 26742501 - One infant with a homozygous PTC.
Patient had dev delay, seizures, microcephaly and muscular dystrophy. Zebrafish null model recapitulates the human phenotype with microcephaly and skeletal muscle disorganization.

Summary: 2 patients + animal model
Sources: Expert list
Mendeliome v0.3150 MUC7 Bryony Thompson Classified gene: MUC7 as Red List (low evidence)
Mendeliome v0.3150 MUC7 Bryony Thompson Gene: muc7 has been classified as Red List (Low Evidence).
Mendeliome v0.3149 HTR3D Bryony Thompson Gene: htr3d has been classified as Red List (Low Evidence).
Mendeliome v0.3149 HTR3D Bryony Thompson Classified gene: HTR3D as Red List (low evidence)
Mendeliome v0.3149 HTR3D Bryony Thompson Gene: htr3d has been classified as Red List (Low Evidence).
Mendeliome v0.3148 ALOX5AP Bryony Thompson Gene: alox5ap has been classified as Red List (Low Evidence).
Mendeliome v0.3148 ALOX5AP Bryony Thompson Classified gene: ALOX5AP as Red List (low evidence)
Mendeliome v0.3148 ALOX5AP Bryony Thompson Gene: alox5ap has been classified as Red List (Low Evidence).
Mendeliome v0.3147 PHOX2A Zornitza Stark Gene: phox2a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3147 PHOX2A Zornitza Stark Phenotypes for gene: PHOX2A were changed from to Fibrosis of extraocular muscles, congenital, 2 602078
Mendeliome v0.3144 PHOX2A Zornitza Stark Classified gene: PHOX2A as Amber List (moderate evidence)
Mendeliome v0.3144 PHOX2A Zornitza Stark Gene: phox2a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3143 PHOX2A Elena Savva reviewed gene: PHOX2A: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 11600883, 18323871; Phenotypes: Fibrosis of extraocular muscles, congenital, 2 602078; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3140 ANKRD1 Zornitza Stark Gene: ankrd1 has been classified as Red List (Low Evidence).
Mendeliome v0.3137 ANKRD1 Zornitza Stark Classified gene: ANKRD1 as Red List (low evidence)
Mendeliome v0.3137 ANKRD1 Zornitza Stark Gene: ankrd1 has been classified as Red List (Low Evidence).
Mendeliome v0.3136 CALR3 Zornitza Stark Gene: calr3 has been classified as Red List (Low Evidence).
Mendeliome v0.3133 CALR3 Zornitza Stark Classified gene: CALR3 as Red List (low evidence)
Mendeliome v0.3133 CALR3 Zornitza Stark Gene: calr3 has been classified as Red List (Low Evidence).
Mendeliome v0.3132 ALPK3 Zornitza Stark Gene: alpk3 has been classified as Green List (High Evidence).
Mendeliome v0.3129 HSF4 Zornitza Stark Gene: hsf4 has been classified as Green List (High Evidence).
Mendeliome v0.3126 FITM2 Bryony Thompson Gene: fitm2 has been classified as Green List (High Evidence).
Mendeliome v0.3126 FITM2 Bryony Thompson Classified gene: FITM2 as Green List (high evidence)
Mendeliome v0.3126 FITM2 Bryony Thompson Gene: fitm2 has been classified as Green List (High Evidence).
Mendeliome v0.3125 FITM2 Bryony Thompson gene: FITM2 was added
gene: FITM2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: FITM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FITM2 were set to 28067622; 30214770; 30288795
Phenotypes for gene: FITM2 were set to Siddiqi syndrome MIM#618635; dystonia; deafness
Review for gene: FITM2 was set to GREEN
Added comment: 7 cases from 3 unrelated families (2 consanguineous) with a dystonia-deafness syndrome and a supporting Drosophila model.
Sources: Expert list
Mendeliome v0.3123 CHD1L Zornitza Stark Gene: chd1l has been classified as Red List (Low Evidence).
Mendeliome v0.3120 CHD1L Zornitza Stark Classified gene: CHD1L as Red List (low evidence)
Mendeliome v0.3120 CHD1L Zornitza Stark Gene: chd1l has been classified as Red List (Low Evidence).
Mendeliome v0.3119 NEXMIF Zornitza Stark Gene: nexmif has been classified as Green List (High Evidence).
Mendeliome v0.3116 MEF2C Zornitza Stark Gene: mef2c has been classified as Green List (High Evidence).
Mendeliome v0.3114 KDM6A Zornitza Stark Gene: kdm6a has been classified as Green List (High Evidence).
Mendeliome v0.3111 STAG3 Bryony Thompson Gene: stag3 has been classified as Green List (High Evidence).
Mendeliome v0.3111 STAG3 Bryony Thompson Classified gene: STAG3 as Green List (high evidence)
Mendeliome v0.3111 STAG3 Bryony Thompson Gene: stag3 has been classified as Green List (High Evidence).
Mendeliome v0.3109 SOHLH1 Bryony Thompson Gene: sohlh1 has been classified as Green List (High Evidence).
Mendeliome v0.3109 SOHLH1 Bryony Thompson Classified gene: SOHLH1 as Green List (high evidence)
Mendeliome v0.3109 SOHLH1 Bryony Thompson Gene: sohlh1 has been classified as Green List (High Evidence).
Mendeliome v0.3108 SOHLH1 Bryony Thompson gene: SOHLH1 was added
gene: SOHLH1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SOHLH1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SOHLH1 were set to 25774885; 16690745; 31042289; 20506135; 28718531
Phenotypes for gene: SOHLH1 were set to Ovarian dysgenesis 5 MIM#617690; Spermatogenic failure 32 MIM#618115
Review for gene: SOHLH1 was set to GREEN
Added comment: Women in 3 unrelated families with ovarian dysgenesis and homozygous variants, and a supporting null mouse model.
At least 4 males with heterozygous variants and spermatogenic failure.
Sources: Expert list
Mendeliome v0.3107 HFM1 Bryony Thompson Gene: hfm1 has been classified as Green List (High Evidence).
Mendeliome v0.3107 HFM1 Bryony Thompson Classified gene: HFM1 as Green List (high evidence)
Mendeliome v0.3107 HFM1 Bryony Thompson Gene: hfm1 has been classified as Green List (High Evidence).
Mendeliome v0.3106 HFM1 Bryony Thompson gene: HFM1 was added
gene: HFM1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: HFM1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: HFM1 were set to 23555294; 24597873; 31279343
Phenotypes for gene: HFM1 were set to Premature ovarian failure 9 MIM#615724
Review for gene: HFM1 was set to GREEN
Added comment: Three cases from 2 unrelated families with compound heterozygous variants, and a single family with a heterozygous variant have been reported with ovarian failure. There is also a supporting null mouse model.
Sources: Expert list
Mendeliome v0.3105 NEK9 Zornitza Stark Gene: nek9 has been classified as Red List (Low Evidence).
Mendeliome v0.3105 NEK9 Zornitza Stark Phenotypes for gene: NEK9 were changed from to Lethal congenital contracture syndrome 10, MIM# 617022; Skeletal dysplasia
Mendeliome v0.3102 NEK9 Zornitza Stark Classified gene: NEK9 as Red List (low evidence)
Mendeliome v0.3102 NEK9 Zornitza Stark Gene: nek9 has been classified as Red List (Low Evidence).
Mendeliome v0.3101 NEK9 Zornitza Stark reviewed gene: NEK9: Rating: RED; Mode of pathogenicity: None; Publications: 26908619; Phenotypes: Lethal congenital contracture syndrome 10, MIM# 617022, Skeletal dysplasia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3101 MSTN Zornitza Stark Gene: mstn has been classified as Red List (Low Evidence).
Mendeliome v0.3098 MSTN Zornitza Stark Classified gene: MSTN as Red List (low evidence)
Mendeliome v0.3098 MSTN Zornitza Stark Gene: mstn has been classified as Red List (Low Evidence).
Mendeliome v0.3097 HSPB8 Zornitza Stark Gene: hspb8 has been classified as Green List (High Evidence).
Mendeliome v0.3094 AMPD1 Zornitza Stark Gene: ampd1 has been classified as Red List (Low Evidence).
Mendeliome v0.3091 AMPD1 Zornitza Stark Classified gene: AMPD1 as Red List (low evidence)
Mendeliome v0.3091 AMPD1 Zornitza Stark Gene: ampd1 has been classified as Red List (Low Evidence).
Mendeliome v0.3089 DCAF8 Bryony Thompson Classified gene: DCAF8 as Amber List (moderate evidence)
Mendeliome v0.3089 DCAF8 Bryony Thompson Gene: dcaf8 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3088 DCAF8 Bryony Thompson gene: DCAF8 was added
gene: DCAF8 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: DCAF8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DCAF8 were set to 24500646
Phenotypes for gene: DCAF8 were set to Giant axonal neuropathy 2, autosomal dominant MIM#610100
Review for gene: DCAF8 was set to AMBER
Added comment: A single large family segregating a missense variant and in vitro functional assays demonstrating the variant reduces the association of DCAF8 and DDB1, which is important in Cul4-ubiquitin E3 function
Sources: Expert list
Mendeliome v0.3087 ARL6IP1 Bryony Thompson Gene: arl6ip1 has been classified as Green List (High Evidence).
Mendeliome v0.3087 ARL6IP1 Bryony Thompson Classified gene: ARL6IP1 as Green List (high evidence)
Mendeliome v0.3087 ARL6IP1 Bryony Thompson Gene: arl6ip1 has been classified as Green List (High Evidence).
Mendeliome v0.3086 ARL6IP1 Bryony Thompson gene: ARL6IP1 was added
gene: ARL6IP1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ARL6IP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARL6IP1 were set to 24482476; 31272422; 30980493; 28471035
Phenotypes for gene: ARL6IP1 were set to Spastic paraplegia 61, autosomal recessive MIM#615685
Review for gene: ARL6IP1 was set to GREEN
gene: ARL6IP1 was marked as current diagnostic
Added comment: At least 4 families reported with paediatric onset complicated spastic paraplegia and neuropathy. Supporting zebrafish model.
Sources: Expert list
Mendeliome v0.3085 PMP2 Bryony Thompson Gene: pmp2 has been classified as Green List (High Evidence).
Mendeliome v0.3085 PMP2 Bryony Thompson Classified gene: PMP2 as Green List (high evidence)
Mendeliome v0.3085 PMP2 Bryony Thompson Gene: pmp2 has been classified as Green List (High Evidence).
Mendeliome v0.3078 SI Zornitza Stark Marked gene: SI as ready
Mendeliome v0.3078 SI Zornitza Stark Gene: si has been classified as Green List (High Evidence).
Mendeliome v0.3078 SI Zornitza Stark Phenotypes for gene: SI were changed from to Sucrase-isomaltase deficiency, congenital #222900
Mendeliome v0.3077 SI Zornitza Stark Publications for gene: SI were set to
Mendeliome v0.3076 SI Zornitza Stark Mode of inheritance for gene: SI was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.3075 SV2B Seb Lunke Gene: sv2b has been classified as Red List (Low Evidence).
Mendeliome v0.3074 SI Elena Savva reviewed gene: SI: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 3149304, 31557950; Phenotypes: Sucrase-isomaltase deficiency, congenital #222900; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.3074 RYR3 Zornitza Stark Gene: ryr3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3074 RYR3 Zornitza Stark Classified gene: RYR3 as Amber List (moderate evidence)
Mendeliome v0.3074 RYR3 Zornitza Stark Gene: ryr3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3073 RYR3 Zornitza Stark gene: RYR3 was added
gene: RYR3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: RYR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RYR3 were set to 29498452; 32451403; 31230720
Phenotypes for gene: RYR3 were set to Nemaline myopathy; fetal akinesia; arthrogryposis
Review for gene: RYR3 was set to AMBER
Added comment: One family reported with nemaline myopathy and other cases reported as part of large fetal akinesia/arthrogryposis discovery cohorts reporting multiple novel gene candidates.
Sources: Expert list
Mendeliome v0.3072 SCN3A Zornitza Stark Gene: scn3a has been classified as Green List (High Evidence).
Mendeliome v0.3068 HMGA2 Zornitza Stark Phenotypes for gene: HMGA2 were changed from Silver-Russel syndrome to Silver-Russel syndrome, MIM#618908
Mendeliome v0.3066 HMGA2 Zornitza Stark Classified gene: HMGA2 as Green List (high evidence)
Mendeliome v0.3066 HMGA2 Zornitza Stark Gene: hmga2 has been classified as Green List (High Evidence).
Mendeliome v0.3065 HMGA2 Zornitza Stark edited their review of gene: HMGA2: Added comment: At least four families reported with SNVs.; Changed rating: GREEN; Changed publications: 29655892, 25809938, 29453418, 29655892, 28796236; Changed phenotypes: Silver-Russel syndrome, MIM#618908
Mendeliome v0.3065 PLAG1 Zornitza Stark Gene: plag1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3065 PLAG1 Zornitza Stark Phenotypes for gene: PLAG1 were changed from to Silver-Russell syndrome, MIM#618907
Mendeliome v0.3062 PLAG1 Zornitza Stark Classified gene: PLAG1 as Amber List (moderate evidence)
Mendeliome v0.3062 PLAG1 Zornitza Stark Gene: plag1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3061 PLAG1 Zornitza Stark reviewed gene: PLAG1: Rating: AMBER; Mode of pathogenicity: None; Publications: 28796236, 29913240; Phenotypes: Silver-Russell syndrome, MIM#618907; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3061 NEFH Zornitza Stark Gene: nefh has been classified as Green List (High Evidence).
Mendeliome v0.3057 SLC6A1 Zornitza Stark Gene: slc6a1 has been classified as Green List (High Evidence).
Mendeliome v0.3054 GATM Zornitza Stark Gene: gatm has been classified as Green List (High Evidence).
Mendeliome v0.3051 TRIM69 Zornitza Stark Gene: trim69 has been classified as Red List (Low Evidence).
Mendeliome v0.3051 TRIM69 Zornitza Stark gene: TRIM69 was added
gene: TRIM69 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: TRIM69 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TRIM69 were set to 22105173
Phenotypes for gene: TRIM69 were set to Susceptibility to herpes simplex encephalitis
Review for gene: TRIM69 was set to RED
Added comment: One individual with bi-allelic and one individual with mono-allelic variants in this gene described.
Sources: Expert list
Mendeliome v0.3050 LIMS2 Zornitza Stark Gene: lims2 has been classified as Red List (Low Evidence).
Mendeliome v0.3050 LIMS2 Zornitza Stark gene: LIMS2 was added
gene: LIMS2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: LIMS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LIMS2 were set to 25589244; 16317048
Phenotypes for gene: LIMS2 were set to Muscular dystrophy, autosomal recessive, with cardiomyopathy and triangular tongue MIM#616827
Review for gene: LIMS2 was set to RED
Added comment: Only one family reported and Pinch2 -/- mice were viable and fertile with no apparent phenotype.
Sources: Expert list
Mendeliome v0.3049 PSMB1 Zornitza Stark Gene: psmb1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3049 PSMB1 Zornitza Stark Classified gene: PSMB1 as Amber List (moderate evidence)
Mendeliome v0.3049 PSMB1 Zornitza Stark Gene: psmb1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3048 PSMB1 Zornitza Stark gene: PSMB1 was added
gene: PSMB1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PSMB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMB1 were set to 32129449
Phenotypes for gene: PSMB1 were set to Intellectual disability; microcephaly
Review for gene: PSMB1 was set to AMBER
Added comment: Two siblings reported with a homozygous missense variant in this gene; supportive experimental evidence including zebrafish model.
Sources: Literature
Mendeliome v0.3047 SLC12A6 Zornitza Stark Gene: slc12a6 has been classified as Green List (High Evidence).
Mendeliome v0.3047 SLC12A6 Zornitza Stark Phenotypes for gene: SLC12A6 were changed from to Andermann syndrome; Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus Callosum; Intermediate CMT
Mendeliome v0.3044 SLC12A6 Zornitza Stark reviewed gene: SLC12A6: Rating: GREEN; Mode of pathogenicity: None; Publications: 31439721; Phenotypes: Andermann syndrome, Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus Callosum, Intermediate CMT; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3044 C16orf62 Zornitza Stark changed review comment from: HGNC approved name: VPS35L. Two variants have been reported as compound heterozygotes in two sibs with features of 3C/Ritscher-Schinzel syndrome. Functional studies show that loss of VPS35L function results in impared autophagy and VPS35L knockout mouse resulted in early embrionic lethality (PMID 25434475).
Sources: Expert list; to: HGNC approved name: VPS35L. Two variants have been reported as compound heterozygotes in two sibs with features of 3C/Ritscher-Schinzel syndrome. Functional studies show that loss of VPS35L function results in impared autophagy and VPS35L knockout mouse resulted in early embrionic lethality (PMID 25434475;31712251).
Sources: Expert list
Mendeliome v0.3044 EWSR1 Seb Lunke Gene: ewsr1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3044 EWSR1 Seb Lunke Phenotypes for gene: EWSR1 were changed from to Amyotrophic lateral sclerosis
Mendeliome v0.3041 EWSR1 Seb Lunke Classified gene: EWSR1 as Amber List (moderate evidence)
Mendeliome v0.3041 EWSR1 Seb Lunke Gene: ewsr1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3040 EWSR1 Seb Lunke reviewed gene: EWSR1: Rating: AMBER; Mode of pathogenicity: None; Publications: 29731676, 22454397; Phenotypes: Amyotrophic lateral sclerosis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3040 TRPM7 Zornitza Stark Gene: trpm7 has been classified as Red List (Low Evidence).
Mendeliome v0.3040 TRPM7 Zornitza Stark Phenotypes for gene: TRPM7 were changed from to {Amyotrophic lateral sclerosis-parkinsonism/dementia complex, susceptibility to}, MIM# 105500
Mendeliome v0.3039 TRPM7 Zornitza Stark Classified gene: TRPM7 as Red List (low evidence)
Mendeliome v0.3039 TRPM7 Zornitza Stark Gene: trpm7 has been classified as Red List (Low Evidence).
Mendeliome v0.3038 TRPM7 Zornitza Stark reviewed gene: TRPM7: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Amyotrophic lateral sclerosis-parkinsonism/dementia complex, susceptibility to}, MIM# 105500; Mode of inheritance: None
Mendeliome v0.3038 C16orf62 Zornitza Stark Gene: c16orf62 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3038 C16orf62 Zornitza Stark Classified gene: C16orf62 as Amber List (moderate evidence)
Mendeliome v0.3038 C16orf62 Zornitza Stark Gene: c16orf62 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3037 C16orf62 Zornitza Stark gene: C16orf62 was added
gene: C16orf62 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: C16orf62 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C16orf62 were set to 25434475
Phenotypes for gene: C16orf62 were set to 3C/Ritscher-Schinzel-like syndrome
Review for gene: C16orf62 was set to AMBER
Added comment: HGNC approved name: VPS35L. Two variants have been reported as compound heterozygotes in two sibs with features of 3C/Ritscher-Schinzel syndrome. Functional studies show that loss of VPS35L function results in impared autophagy and VPS35L knockout mouse resulted in early embrionic lethality (PMID 25434475).
Sources: Expert list
Mendeliome v0.3036 RHOBTB2 Zornitza Stark Gene: rhobtb2 has been classified as Green List (High Evidence).
Mendeliome v0.3032 PPP1CB Zornitza Stark Gene: ppp1cb has been classified as Green List (High Evidence).
Mendeliome v0.3029 NUP88 Zornitza Stark Gene: nup88 has been classified as Green List (High Evidence).
Mendeliome v0.3029 NUP88 Zornitza Stark Classified gene: NUP88 as Green List (high evidence)
Mendeliome v0.3029 NUP88 Zornitza Stark Gene: nup88 has been classified as Green List (High Evidence).
Mendeliome v0.3028 NUP88 Zornitza Stark gene: NUP88 was added
gene: NUP88 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NUP88 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP88 were set to 30543681
Phenotypes for gene: NUP88 were set to Fetal akinesia deformation sequence 4, MIM# 618393
Review for gene: NUP88 was set to GREEN
Added comment: Two unrelated families, functional data on the variants support pathogenicity as does a zebrafish model.
Sources: Literature
Mendeliome v0.3027 SMO Zornitza Stark Gene: smo has been classified as Green List (High Evidence).
Mendeliome v0.3027 SMO Zornitza Stark Phenotypes for gene: SMO were changed from to Microcephaly, congenital heart disease, polydactyly, aganglionosis; Curry-Jones syndrome, somatic mosaic 601707
Mendeliome v0.3024 SMO Zornitza Stark reviewed gene: SMO: Rating: GREEN; Mode of pathogenicity: None; Publications: 32413283, 27236920; Phenotypes: Microcephaly, congenital heart disease, polydactyly, aganglionosis, Curry-Jones syndrome, somatic mosaic 601707; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3024 RBL2 Zornitza Stark Gene: rbl2 has been classified as Red List (Low Evidence).
Mendeliome v0.3024 RBL2 Zornitza Stark gene: RBL2 was added
gene: RBL2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RBL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RBL2 were set to 32105419; 9806916
Phenotypes for gene: RBL2 were set to Intellectual disability
Review for gene: RBL2 was set to RED
Added comment: Single family reported with pair of affected siblings. Supportive mouse model.
Sources: Literature
Mendeliome v0.3023 GRM7 Zornitza Stark Gene: grm7 has been classified as Green List (High Evidence).
Mendeliome v0.3023 GRM7 Zornitza Stark Classified gene: GRM7 as Green List (high evidence)
Mendeliome v0.3023 GRM7 Zornitza Stark Gene: grm7 has been classified as Green List (High Evidence).
Mendeliome v0.3022 GRM7 Zornitza Stark gene: GRM7 was added
gene: GRM7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GRM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GRM7 were set to 32286009; 32248644
Phenotypes for gene: GRM7 were set to Epilepsy, microcephaly, developmental delay
Review for gene: GRM7 was set to GREEN
Added comment: Eleven individuals from six families reported, three different homozygous variants (two missense, one LoF). Developmental delay, neonatal‐ or infantile‐onset epilepsy, and microcephaly were universal. Supportive mouse model.
Sources: Literature
Mendeliome v0.3021 PYGM Zornitza Stark Gene: pygm has been classified as Green List (High Evidence).
Mendeliome v0.3018 PERP Zornitza Stark Gene: perp has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3018 PERP Zornitza Stark Classified gene: PERP as Amber List (moderate evidence)
Mendeliome v0.3018 PERP Zornitza Stark Gene: perp has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3017 PERP Zornitza Stark gene: PERP was added
gene: PERP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PERP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PERP were set to 31898316
Phenotypes for gene: PERP were set to Erythrokeratoderma, no OMIM # yet
Review for gene: PERP was set to AMBER
Added comment: One extended multiplex consanguineous family with Erythrokeratoderma (striking similarity to that observed in Perp −/− mice), and a novel homozygous variant (c.466G>A; p.Gly156Arg) in PERP that fully segregated with the phenotype. Functional analysis of patient‐ and control‐derived keratinocytes revealed a deleterious effect of the identified variant on the intracellular localization of PERP. A previous report showed that PERP mutation causes a dominant form of keratoderma but a single patient in that report with a homozygous variant in PERP suggests that recessive inheritance is also possible.
Sources: Literature
Mendeliome v0.3016 ADCY6 Zornitza Stark Gene: adcy6 has been classified as Green List (High Evidence).
Mendeliome v0.3016 ADCY6 Zornitza Stark Classified gene: ADCY6 as Green List (high evidence)
Mendeliome v0.3016 ADCY6 Zornitza Stark Gene: adcy6 has been classified as Green List (High Evidence).
Mendeliome v0.3015 ADCY6 Zornitza Stark gene: ADCY6 was added
gene: ADCY6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ADCY6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADCY6 were set to 24319099; 26257172; 31846058
Phenotypes for gene: ADCY6 were set to Lethal congenital contracture syndrome 8, OMIM # 616287
Review for gene: ADCY6 was set to GREEN
Added comment: Laquerriere et al. (2014): 2 sibs from a consanguineous family with an axoglial form of lethal congenital contracture syndrome, and homozygous missense ADCY6 mutation (R1116C). The parents were heterozygous for the mutation. Knocked down ADCY6 orthologs in zebrafish showed a loss of myelin basic protein expression in the peripheral nervous system but no defects in Schwann cell migration and axonal growth. Gonzaga‐Jauregui et al. (2015): 1 patient with congenital hypotonia, distal joint contractures, hypomyelinating neuropathy, and vocal cord paralysis, and a homozygous missense ADCY6 variant. No functional studies. Deceased sister with a similar phenotype with hypotonia, areflexia, and hypomyelinating neuropathy who died at 18 months of respiratory insufficiency. Agolini et al. (2020): 1 patient with severe form of AMC, with two novel compound heterozygous variants in ADCY6 (parents confirmed carriers), but no functional studies.
Sources: Literature
Mendeliome v0.3014 DSCR3 Zornitza Stark Gene: dscr3 has been classified as Red List (Low Evidence).
Mendeliome v0.3014 DSCR3 Zornitza Stark gene: DSCR3 was added
gene: DSCR3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DSCR3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DSCR3 were set to 31845315
Phenotypes for gene: DSCR3 were set to Intellectual disability, no OMIM # yet
Review for gene: DSCR3 was set to RED
Added comment: 1 family/2 cousins with cognitive impairment, growth failure, skeletal abnormalities, and distinctive facial features. Both shared the homozygous nonsense variant c.178G>T (p.Glu60*) in the VPS26C gene. This gene encodes VPS26C, a member of the retriever integral membrane protein recycling pathway. The nature of the variant which is predicted to result in loss‐of‐function, expression studies revealing significant reduction in the mutant transcript, and the co‐segregation of the homozygous variant with the phenotype in two affected individuals.
Sources: Literature
Mendeliome v0.3013 LEF1 Zornitza Stark Gene: lef1 has been classified as Red List (Low Evidence).
Mendeliome v0.3013 LEF1 Zornitza Stark gene: LEF1 was added
gene: LEF1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LEF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LEF1 were set to 32022899
Phenotypes for gene: LEF1 were set to Ectodermal dysplasia, no OMIM# yet
Review for gene: LEF1 was set to RED
Added comment: In mice, targeted inactivation of the LEF1 gene results in a complete block of development of multiple ectodermal appendages. One report of two unrelated patients with 4q25 de novo deletion encompassing LEF1 , associated with severe oligodontia of primary and permanent dentition, hypotrichosis and hypohidrosis compatible with hypohidrotic ectodermal dysplasia. So far, no pathogenic variants or variations involving the LEF1 gene have been reported in human.
Sources: Literature
Mendeliome v0.3012 OTUD7A Zornitza Stark Gene: otud7a has been classified as Red List (Low Evidence).
Mendeliome v0.3010 OTUD7A Zornitza Stark gene: OTUD7A was added
gene: OTUD7A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: OTUD7A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OTUD7A were set to 31997314
Phenotypes for gene: OTUD7A were set to Epileptic encephalopathy, no OMIM# yet
Review for gene: OTUD7A was set to RED
Added comment: One patient with severe global developmental delay, language impairment and epileptic encephalopathy. Homozygous OTUD7A missense variant (c.697C>T, p.Leu233Phe), predicted to alter an ultraconserved amino acid, lying within the OTU catalytic domain. Its subsequent segregation analysis revealed that the parents, presenting with learning disability, and brother were heterozygous carriers. Biochemical assays demonstrated that proteasome complex formation and function were significantly reduced in patient‐derived fibroblasts and in OTUD7A knockout HAP1 cell line. Gene lies in the chromosome 15q13.3 region. Heterozygous microdeletions of chromosome 15q13.3 show incomplete penetrance and are associated with a highly variable phenotype that may include intellectual disability, epilepsy, facial dysmorphism and digit anomalies.
Sources: Literature
Mendeliome v0.3009 GATAD2B Zornitza Stark Gene: gatad2b has been classified as Green List (High Evidence).
Mendeliome v0.3005 KMT2D Zornitza Stark Gene: kmt2d has been classified as Green List (High Evidence).
Mendeliome v0.3002 COG4 Zornitza Stark Gene: cog4 has been classified as Green List (High Evidence).
Mendeliome v0.2999 ARL13B Zornitza Stark Gene: arl13b has been classified as Green List (High Evidence).
Mendeliome v0.2996 ARL13B Zornitza Stark edited their review of gene: ARL13B: Added comment: Eight families reported in the literature. Many are homozygous missense variants in consanguineous families with no further supporting evidence, but sufficient number have functional evidence at protein level. Gene has appropriate tissue expression. Zebrafish model: curved tails and cystic kidneys. Hennin mouse model discovered in ENU mutagenesis screen: has polydactyly, ciliary defect, and much more severe neurological phenotype (neural tube defect).; Changed publications: 18674751, 25138100, 26092869, 27894351, 29255182, 17488627
Mendeliome v0.2996 DNAL1 Zornitza Stark Gene: dnal1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2996 DNAL1 Zornitza Stark Phenotypes for gene: DNAL1 were changed from to Ciliary dyskinesia, primary, 16, MIM# 614017
Mendeliome v0.2993 DNAL1 Zornitza Stark Classified gene: DNAL1 as Amber List (moderate evidence)
Mendeliome v0.2993 DNAL1 Zornitza Stark Gene: dnal1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2992 DNAL1 Zornitza Stark reviewed gene: DNAL1: Rating: AMBER; Mode of pathogenicity: None; Publications: 21496787; Phenotypes: Ciliary dyskinesia, primary, 16, MIM# 614017; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2992 DNAH8 Zornitza Stark Gene: dnah8 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2992 DNAH8 Zornitza Stark Phenotypes for gene: DNAH8 were changed from to Asthenozoospermia; primary ciliary dyskinesia
Mendeliome v0.2989 DNAH8 Zornitza Stark Classified gene: DNAH8 as Amber List (moderate evidence)
Mendeliome v0.2989 DNAH8 Zornitza Stark Gene: dnah8 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2988 DNAH8 Zornitza Stark reviewed gene: DNAH8: Rating: AMBER; Mode of pathogenicity: None; Publications: 31178125, 24307375; Phenotypes: Asthenozoospermia, primary ciliary dyskinesia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2988 TTC5 Zornitza Stark Gene: ttc5 has been classified as Green List (High Evidence).
Mendeliome v0.2988 TTC5 Zornitza Stark Classified gene: TTC5 as Green List (high evidence)
Mendeliome v0.2988 TTC5 Zornitza Stark Gene: ttc5 has been classified as Green List (High Evidence).
Mendeliome v0.2986 ACAD11 Zornitza Stark Gene: acad11 has been classified as Red List (Low Evidence).
Mendeliome v0.2986 ACAD11 Zornitza Stark Classified gene: ACAD11 as Red List (low evidence)
Mendeliome v0.2986 ACAD11 Zornitza Stark Gene: acad11 has been classified as Red List (Low Evidence).
Mendeliome v0.2985 DNAH6 Zornitza Stark Gene: dnah6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2985 DNAH6 Zornitza Stark Classified gene: DNAH6 as Amber List (moderate evidence)
Mendeliome v0.2985 DNAH6 Zornitza Stark Gene: dnah6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2984 DRC1 Zornitza Stark Gene: drc1 has been classified as Green List (High Evidence).
Mendeliome v0.2984 DRC1 Zornitza Stark Phenotypes for gene: DRC1 were changed from to Ciliary dyskinesia, primary, 21, MIM# 615294
Mendeliome v0.2981 DRC1 Zornitza Stark reviewed gene: DRC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31960620; Phenotypes: Ciliary dyskinesia, primary, 21, MIM# 615294; Mode of inheritance: None
Mendeliome v0.2978 HIST1H4J Zornitza Stark Gene: hist1h4j has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2978 HIST1H4J Zornitza Stark Classified gene: HIST1H4J as Amber List (moderate evidence)
Mendeliome v0.2978 HIST1H4J Zornitza Stark Gene: hist1h4j has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2977 HIST1H4J Zornitza Stark gene: HIST1H4J was added
gene: HIST1H4J was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HIST1H4J was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HIST1H4J were set to 31804630
Phenotypes for gene: HIST1H4J were set to microcephaly; intellectual disability; dysmorphic features
Review for gene: HIST1H4J was set to AMBER
Added comment: Single case report but with functional evidence in zebrafish and phenotypic similarity to other HIST1H4C phenotype
Sources: Literature
Mendeliome v0.2976 MCIDAS Zornitza Stark Gene: mcidas has been classified as Green List (High Evidence).
Mendeliome v0.2976 MCIDAS Zornitza Stark Phenotypes for gene: MCIDAS were changed from to Ciliary dyskinesia, primary, 42 (MIM#618695)
Mendeliome v0.2973 MCIDAS Zornitza Stark reviewed gene: MCIDAS: Rating: GREEN; Mode of pathogenicity: None; Publications: 25048963; Phenotypes: Ciliary dyskinesia, primary, 42 (MIM#618695); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2973 VWA3B Zornitza Stark Gene: vwa3b has been classified as Red List (Low Evidence).
Mendeliome v0.2973 TOR1AIP1 Zornitza Stark Phenotypes for gene: TOR1AIP1 were changed from Muscular dystrophy, autosomal recessive, with rigid spine and distal joint contractures MIM#617072; Progeroid appearance; Cataracts; Microcephaly; Deafness to Muscular dystrophy, autosomal recessive, with rigid spine and distal joint contractures MIM#617072; Progeroid appearance; Cataracts; Microcephaly; Deafness; Contractures
Mendeliome v0.2972 TOR1AIP1 Zornitza Stark Phenotypes for gene: TOR1AIP1 were changed from Muscular dystrophy, autosomal recessive, with rigid spine and distal joint contractures MIM#617072 to Muscular dystrophy, autosomal recessive, with rigid spine and distal joint contractures MIM#617072; Progeroid appearance; Cataracts; Microcephaly; Deafness
Mendeliome v0.2971 TOR1AIP1 Zornitza Stark Added comment: Comment when marking as ready: Highly variable phenotype. Few of the features are consistently reported across affected individuals.
Mendeliome v0.2971 TOR1AIP1 Zornitza Stark Gene: tor1aip1 has been classified as Green List (High Evidence).
Mendeliome v0.2970 EFEMP1 Zornitza Stark Gene: efemp1 has been classified as Green List (High Evidence).
Mendeliome v0.2967 ZFYVE27 Bryony Thompson Classified gene: ZFYVE27 as Red List (low evidence)
Mendeliome v0.2967 ZFYVE27 Bryony Thompson Gene: zfyve27 has been classified as Red List (Low Evidence).
Mendeliome v0.2966 USP8 Bryony Thompson Classified gene: USP8 as Green List (high evidence)
Mendeliome v0.2966 USP8 Bryony Thompson Gene: usp8 has been classified as Green List (High Evidence).
Mendeliome v0.2965 USP8 Bryony Thompson gene: USP8 was added
gene: USP8 was added to Mendeliome. Sources: Expert list
somatic tags were added to gene: USP8.
Mode of inheritance for gene: USP8 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: USP8 were set to 25675982; 24482476; 25485838; 25942478
Phenotypes for gene: USP8 were set to Pituitary adenoma 4, ACTH-secreting, somatic MIM#219090; hereditary spastic paraplegia
Review for gene: USP8 was set to GREEN
Added comment: Recurrent somatic gain of function missense variants in pituitary adenomas cause Cushing's disease.
A single family reported with spastic paraplegia with a homozygous variant, and a zebrafish model with a movement disorder.
Sources: Expert list
Mendeliome v0.2964 RIMS2 Zornitza Stark Gene: rims2 has been classified as Green List (High Evidence).
Mendeliome v0.2963 RIMS2 Zornitza Stark Classified gene: RIMS2 as Green List (high evidence)
Mendeliome v0.2963 RIMS2 Zornitza Stark Gene: rims2 has been classified as Green List (High Evidence).
Mendeliome v0.2961 TRIM71 Seb Lunke Gene: trim71 has been classified as Green List (High Evidence).
Mendeliome v0.2961 TRIM71 Seb Lunke Classified gene: TRIM71 as Green List (high evidence)
Mendeliome v0.2961 TRIM71 Seb Lunke Gene: trim71 has been classified as Green List (High Evidence).
Mendeliome v0.2960 SCYL2 Zornitza Stark Gene: scyl2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2960 SCYL2 Zornitza Stark Classified gene: SCYL2 as Amber List (moderate evidence)
Mendeliome v0.2960 SCYL2 Zornitza Stark Gene: scyl2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2959 SCYL2 Zornitza Stark gene: SCYL2 was added
gene: SCYL2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SCYL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCYL2 were set to 31960134; 26203146
Phenotypes for gene: SCYL2 were set to Arthrogryposis multiplex congenita (AMC); Zain syndrome
Review for gene: SCYL2 was set to AMBER
Added comment: Two unrelated families reported with AMC, variable other features including microcephaly.
Sources: Literature
Mendeliome v0.2958 CNP Seb Lunke Gene: cnp has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2958 CNP Seb Lunke Classified gene: CNP as Amber List (moderate evidence)
Mendeliome v0.2958 CNP Seb Lunke Gene: cnp has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2957 VWA3B Bryony Thompson Classified gene: VWA3B as Red List (low evidence)
Mendeliome v0.2957 VWA3B Bryony Thompson Added comment: Comment on list classification: Single family and in vitro assay only
Mendeliome v0.2957 VWA3B Bryony Thompson Gene: vwa3b has been classified as Red List (Low Evidence).
Mendeliome v0.2956 RIMS2 Paul De Fazio changed review comment from: Biallelic LoF variants segregate with Syndromic Congenital Cone-Rod Synaptic Disease in 7 individuals across 4 families. Some functional studies related to insulin secretion but they are non-significant.
Sources: Literature; to: Biallelic LoF variants segregate with Syndromic Congenital Cone-Rod Synaptic Disease in 7 individuals across 4 families. Some functional studies related to insulin secretion but they are non-significant. Several individuals had autism. One had night blindness.
Sources: Literature
Mendeliome v0.2956 VWA3B Bryony Thompson Classified gene: VWA3B as Amber List (moderate evidence)
Mendeliome v0.2956 VWA3B Bryony Thompson Gene: vwa3b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2955 VWA3B Bryony Thompson gene: VWA3B was added
gene: VWA3B was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: VWA3B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VWA3B were set to 26157035
Phenotypes for gene: VWA3B were set to Spinocerebellar ataxia, autosomal recessive 22 MIM#616948
Review for gene: VWA3B was set to AMBER
Added comment: A homozygous missense variant was identified in 3 brothers from a single consanguineous Japanese family with autosomal recessive cerebellar ataxia. Transfection of the mutant VWA3B protein into several different cultured cell lines resulted in decreased cell viability.
Sources: Expert list
Mendeliome v0.2952 PLD3 Bryony Thompson Classified gene: PLD3 as Amber List (moderate evidence)
Mendeliome v0.2952 PLD3 Bryony Thompson Gene: pld3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2951 SLC12A2 Zornitza Stark Classified gene: SLC12A2 as Green List (high evidence)
Mendeliome v0.2951 SLC12A2 Zornitza Stark Gene: slc12a2 has been classified as Green List (High Evidence).
Mendeliome v0.2950 PLD3 Bryony Thompson gene: PLD3 was added
gene: PLD3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PLD3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLD3 were set to 29053796; 30312375; 30312384
Phenotypes for gene: PLD3 were set to Spinocerebellar ataxia 46 MIM#617770
Review for gene: PLD3 was set to AMBER
Added comment: A heterozygous missense was identified in 8 affected members of a single family with spinocerebellar ataxia, and supporting in vitro functional assays.
Sources: Expert list
Mendeliome v0.2949 SPATA13 Zornitza Stark Gene: spata13 has been classified as Green List (High Evidence).
Mendeliome v0.2949 SPATA13 Zornitza Stark Classified gene: SPATA13 as Green List (high evidence)
Mendeliome v0.2949 SPATA13 Zornitza Stark Gene: spata13 has been classified as Green List (High Evidence).
Mendeliome v0.2948 SOX6 Seb Lunke Gene: sox6 has been classified as Green List (High Evidence).
Mendeliome v0.2948 SOX6 Seb Lunke Classified gene: SOX6 as Green List (high evidence)
Mendeliome v0.2948 SOX6 Seb Lunke Gene: sox6 has been classified as Green List (High Evidence).
Mendeliome v0.2947 KIF3B Zornitza Stark Gene: kif3b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2946 KIF3B Zornitza Stark Classified gene: KIF3B as Amber List (moderate evidence)
Mendeliome v0.2946 KIF3B Zornitza Stark Gene: kif3b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2945 KIF3B Zornitza Stark reviewed gene: KIF3B: Rating: RED; Mode of pathogenicity: None; Publications: 32386558; Phenotypes: hepatic fibrosis, retinitis pigmentosa, postaxial polydactyly; Mode of inheritance: None
Mendeliome v0.2945 POC5 Bryony Thompson Gene: poc5 has been classified as Green List (High Evidence).
Mendeliome v0.2945 POC5 Bryony Thompson Classified gene: POC5 as Green List (high evidence)
Mendeliome v0.2945 POC5 Bryony Thompson Gene: poc5 has been classified as Green List (High Evidence).
Mendeliome v0.2944 POC5 Bryony Thompson gene: POC5 was added
gene: POC5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: POC5 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: POC5 were set to 25642776; 29272404
Phenotypes for gene: POC5 were set to Idiopathic scoliosis; retinitis pigmentosa; short stature; microcephaly; recurrent glomerulonephritis
Review for gene: POC5 was set to GREEN
Added comment: Three heterozygous missense variants identified in three families segregating with idiopathic scoliosis, and supporting zebrafish models for each of the missense variants.
Also, one case reported with retinitis pigmentosa, short stature, microcephaly, and recurrent glomerulonephritis with a homozygous truncating variant and a supporting zebrafish model.
Sources: Literature
Mendeliome v0.2943 KIF3B Paul De Fazio gene: KIF3B was added
gene: KIF3B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KIF3B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: KIF3B were set to hepatic fibrosis; retinitis pigmentosa; postaxial polydactyly
Review for gene: KIF3B was set to AMBER
Added comment: 2 families reported with missense variants, one de novo and one segregating in a six-generation pedigree. Functional studies in zebrafish showed the variants result in impaired rhodopsin trafficking.
Sources: Literature
Mendeliome v0.2943 SOX6 Paul De Fazio gene: SOX6 was added
gene: SOX6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SOX6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOX6 were set to 32442410
Phenotypes for gene: SOX6 were set to ADHD; Craniosynostosis; Osteochondromas
Added comment: 6 LoF and 4 missense variants identified in individuals with a neurodevelopmental syndrome, however the number of families is unclear to me.
Sources: Literature
Mendeliome v0.2943 CNP Kristin Rigbye gene: CNP was added
gene: CNP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CNP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CNP were set to 32128616; 12590258
Phenotypes for gene: CNP were set to Hypomyelinating leukodystrophy
Review for gene: CNP was set to AMBER
Added comment: Single consanguineous family described with homozygous missense in affected child (additional two affected deceased offspring unavailable for testing; healthy carrier parents and sibling).
Loss of protein by Western blot and defect in F-actin structure and organization observed in patient fibroblasts.
Deficiency of CNP in mouse has previously been shown to cause a lethal white matter neurodegenerative phenotype (PMID: 12590258), similar to the phenotype observed in this family.
Sources: Literature
Mendeliome v0.2943 RIMS2 Paul De Fazio changed review comment from: Segregates with Syndromic Congenital Cone-Rod Synaptic Disease in 7 individuals across 4 families. Some functional studies related to insulin secretion but they are non-significant.
Sources: Literature; to: Biallelic LoF variants segregate with Syndromic Congenital Cone-Rod Synaptic Disease in 7 individuals across 4 families. Some functional studies related to insulin secretion but they are non-significant.
Sources: Literature
Mendeliome v0.2943 RIMS2 Paul De Fazio gene: RIMS2 was added
gene: RIMS2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RIMS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RIMS2 were set to 32470375
Review for gene: RIMS2 was set to GREEN
Added comment: Segregates with Syndromic Congenital Cone-Rod Synaptic Disease in 7 individuals across 4 families. Some functional studies related to insulin secretion but they are non-significant.
Sources: Literature
Mendeliome v0.2943 RBM7 Bryony Thompson Classified gene: RBM7 as Amber List (moderate evidence)
Mendeliome v0.2943 RBM7 Bryony Thompson Gene: rbm7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2942 RBM7 Bryony Thompson gene: RBM7 was added
gene: RBM7 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: RBM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RBM7 were set to 27193168
Phenotypes for gene: RBM7 were set to SMA-like spinal motor neuropathy; dHMN/dSMA
Review for gene: RBM7 was set to AMBER
Added comment: Single case with a homozygote variant, with functional assays in patient fibroblasts. Also, supporting zebrafish model.
Sources: Expert list
Mendeliome v0.2941 SORD Seb Lunke Gene: sord has been classified as Green List (High Evidence).
Mendeliome v0.2941 SORD Seb Lunke Classified gene: SORD as Green List (high evidence)
Mendeliome v0.2941 SORD Seb Lunke Gene: sord has been classified as Green List (High Evidence).
Mendeliome v0.2940 KCNJ8 Zornitza Stark Gene: kcnj8 has been classified as Red List (Low Evidence).
Mendeliome v0.2937 KCNJ8 Zornitza Stark Classified gene: KCNJ8 as Red List (low evidence)
Mendeliome v0.2937 KCNJ8 Zornitza Stark Gene: kcnj8 has been classified as Red List (Low Evidence).
Mendeliome v0.2936 KCNE3 Zornitza Stark Gene: kcne3 has been classified as Red List (Low Evidence).
Mendeliome v0.2933 KCNE3 Zornitza Stark Classified gene: KCNE3 as Red List (low evidence)
Mendeliome v0.2933 KCNE3 Zornitza Stark Gene: kcne3 has been classified as Red List (Low Evidence).
Mendeliome v0.2932 XIST Zornitza Stark Gene: xist has been classified as Green List (High Evidence).
Mendeliome v0.2930 SYNE2 Zornitza Stark Gene: syne2 has been classified as Red List (Low Evidence).
Mendeliome v0.2928 SYNE2 Bryony Thompson Classified gene: SYNE2 as Red List (low evidence)
Mendeliome v0.2928 SYNE2 Bryony Thompson Gene: syne2 has been classified as Red List (Low Evidence).
Mendeliome v0.2927 PRKAG3 Bryony Thompson Classified gene: PRKAG3 as Amber List (moderate evidence)
Mendeliome v0.2927 PRKAG3 Bryony Thompson Gene: prkag3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2926 ANO5 Zornitza Stark Gene: ano5 has been classified as Green List (High Evidence).
Mendeliome v0.2925 ANO5 Zornitza Stark Phenotypes for gene: ANO5 were changed from to Gnathodiaphyseal dysplasia MIM#166260; Miyoshi muscular dystrophy 3 MIM#613319; Muscular dystrophy, limb-girdle, autosomal recessive 12 MIM#611307
Mendeliome v0.2923 CPT1B Zornitza Stark Gene: cpt1b has been classified as Red List (Low Evidence).
Mendeliome v0.2921 MYF6 Bryony Thompson Classified gene: MYF6 as Red List (low evidence)
Mendeliome v0.2921 MYF6 Bryony Thompson Gene: myf6 has been classified as Red List (Low Evidence).
Mendeliome v0.2920 MTMR14 Bryony Thompson Classified gene: MTMR14 as Red List (low evidence)
Mendeliome v0.2920 MTMR14 Bryony Thompson Added comment: Comment on list classification: No evidence of Mendelian disease
Mendeliome v0.2920 MTMR14 Bryony Thompson Gene: mtmr14 has been classified as Red List (Low Evidence).
Mendeliome v0.2919 CPT1B Bryony Thompson Classified gene: CPT1B as Red List (low evidence)
Mendeliome v0.2919 CPT1B Bryony Thompson Gene: cpt1b has been classified as Red List (Low Evidence).
Mendeliome v0.2918 ANO5 Bryony Thompson reviewed gene: ANO5: Rating: GREEN; Mode of pathogenicity: None; Publications: 32112655; Phenotypes: Gnathodiaphyseal dysplasia MIM#166260, Miyoshi muscular dystrophy 3 MIM#613319, Muscular dystrophy, limb-girdle, autosomal recessive 12 MIM#611307; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2918 DNAJB11 Zornitza Stark Gene: dnajb11 has been classified as Green List (High Evidence).
Mendeliome v0.2915 GPR143 Zornitza Stark Gene: gpr143 has been classified as Green List (High Evidence).
Mendeliome v0.2912 ELP1 Zornitza Stark Gene: elp1 has been classified as Green List (High Evidence).
Mendeliome v0.2909 SNRNP200 Zornitza Stark Gene: snrnp200 has been classified as Green List (High Evidence).
Mendeliome v0.2906 SNRNP200 Ain Roesley changed review comment from: PMID: 31260034; more than 20 families reported with either de novo or AD with RP or retinal dystrophy (RD)

PMID: 29320387; p.(Arg1090Gln) in a proband with RP from a consag family with unaffected het parents and sibling

PMID: 23847139; p.(Pro1045Thr) homozygous in a patient with Leber congenital amaurosis (LCA)

PMID: 31260034: p.(Arg545His) homozygous in a patient with RP with asymptomatic het parents and sister

PMID: 27735924: in a patient with RP who is cHet for p.(Pro105Thr) in SNRNP200 and a 1.4Mb deletion spanning SNRNP200. Father is a carrier of the missense and is unaffected and the deletion was de novo; to: PMID: 31260034; more than 20 families reported with either de novo or AD with RP or retinal dystrophy (RD)

PMID: 29320387; p.(Arg1090Gln) in a proband with RP from a consag family with unaffected het parents and sibling

PMID: 23847139; p.(Pro1045Thr) homozygous in a patient with Leber congenital amaurosis (LCA)

PMID: 31260034: p.(Arg545His) homozygous in a patient with RP with asymptomatic het parents and sister

PMID: 27735924: in a patient with RP who is cHet for p.(Pro105Thr) in SNRNP200 and a 1.1Mb deletion spanning SNRNP200. Father is a carrier of the missense and is unaffected and the deletion was de novo
Mendeliome v0.2906 SNRNP200 Ain Roesley changed review comment from: PMID: 31260034; more than 20 families reported with either de novo or AD with RP or retinal dystrophy (RD)

PMID: 29320387; p.(Arg1090Gln) in a proband with RP from a consag family with unaffected het parents and sibling

PMID: 23847139; p.(Pro1045Thr) homozygous in a patient with Leber congenital amaurosis (LCA)

PMID: 31260034: p.(Arg545His) homozygous in a patient with RP with asymptomatic het parents and sister

PMID: 27735924: in a patient with RP who is cHet for p.(Pro105Thr) in SNRNP200 and a 1.1Mb deletion spanning SNRNP200. Father is a carrier of the missense and is unaffected and the deletion was de novo; to: PMID: 31260034; more than 20 families reported with either de novo or AD with RP or retinal dystrophy (RD)

PMID: 29320387; p.(Arg1090Gln) in a proband with RP from a consag family with unaffected het parents and sibling

PMID: 23847139; p.(Pro1045Thr) homozygous in a patient with Leber congenital amaurosis (LCA)

PMID: 31260034: p.(Arg545His) homozygous in a patient with RP with asymptomatic het parents and sister

PMID: 27735924: in a patient with RP who is cHet for p.(Pro105Thr) in SNRNP200 and a 1.4Mb deletion spanning SNRNP200. Father is a carrier of the missense and is unaffected and the deletion was de novo
Mendeliome v0.2906 ALOXE3 Zornitza Stark Gene: aloxe3 has been classified as Green List (High Evidence).
Mendeliome v0.2906 ALOXE3 Zornitza Stark Phenotypes for gene: ALOXE3 were changed from to Ichthyosis, congenital, autosomal recessive 3, MIM#606545
Mendeliome v0.2903 ARMC1 Zornitza Stark Gene: armc1 has been classified as Red List (Low Evidence).
Mendeliome v0.2903 ARMC1 Zornitza Stark Classified gene: ARMC1 as Red List (low evidence)
Mendeliome v0.2903 ARMC1 Zornitza Stark Gene: armc1 has been classified as Red List (Low Evidence).
Mendeliome v0.2902 ALOXE3 Chern Lim reviewed gene: ALOXE3: Rating: GREEN; Mode of pathogenicity: None; Publications: 16116617, 31046801, 26370990; Phenotypes: Ichthyosis, congenital, autosomal recessive 3, MIM#606545; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.2902 STK36 Zornitza Stark Gene: stk36 has been classified as Red List (Low Evidence).
Mendeliome v0.2902 STK36 Zornitza Stark Phenotypes for gene: STK36 were changed from to Primary ciliary dyskinesia
Mendeliome v0.2899 STK36 Zornitza Stark Classified gene: STK36 as Red List (low evidence)
Mendeliome v0.2899 STK36 Zornitza Stark Gene: stk36 has been classified as Red List (Low Evidence).
Mendeliome v0.2898 STK36 Zornitza Stark reviewed gene: STK36: Rating: RED; Mode of pathogenicity: None; Publications: 28543983; Phenotypes: Primary ciliary dyskinesia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2898 NME8 Zornitza Stark Gene: nme8 has been classified as Red List (Low Evidence).
Mendeliome v0.2898 NME8 Zornitza Stark Phenotypes for gene: NME8 were changed from to Ciliary dyskinesia, primary, 6, MIM# 610852
Mendeliome v0.2895 NME8 Zornitza Stark Classified gene: NME8 as Red List (low evidence)
Mendeliome v0.2895 NME8 Zornitza Stark Gene: nme8 has been classified as Red List (Low Evidence).
Mendeliome v0.2894 TFAP2A Zornitza Stark Gene: tfap2a has been classified as Green List (High Evidence).
Mendeliome v0.2890 NME8 Elena Savva reviewed gene: NME8: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 17360648; Phenotypes: Ciliary dyskinesia, primary, 6 610852; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2890 ARL3 Bryony Thompson Gene: arl3 has been classified as Green List (High Evidence).
Mendeliome v0.2890 ARL3 Bryony Thompson Classified gene: ARL3 as Green List (high evidence)
Mendeliome v0.2890 ARL3 Bryony Thompson Gene: arl3 has been classified as Green List (High Evidence).
Mendeliome v0.2889 ARL3 Bryony Thompson gene: ARL3 was added
gene: ARL3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ARL3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ARL3 were set to 30269812; 16565502; 26964041; 30932721
Phenotypes for gene: ARL3 were set to Joubert syndrome 35 MIM#618161; Retinitis pigmentosa 83 MIM#618173
Review for gene: ARL3 was set to GREEN
Added comment: 4 patients from 2 unrelated consanguineous families with a phenotype resembling Joubert syndrome with homozygous missense mutations affecting the same residue (R149C, R149H), and supporting in vitro functional assays. All reported cases had rod-cone dystrophy. An Arl3 null mouse model has a ciliary disease phenotype affecting the kidney, biliary tract, pancreas, and retina.
Two unrelated families with retinitis pigmentosa segregating the same heterozygous missense variant (Y90C).
Sources: Expert list
Mendeliome v0.2888 RARA Zornitza Stark Gene: rara has been classified as Red List (Low Evidence).
Mendeliome v0.2888 RARA Zornitza Stark Classified gene: RARA as Red List (low evidence)
Mendeliome v0.2888 RARA Zornitza Stark Gene: rara has been classified as Red List (Low Evidence).
Mendeliome v0.2887 ERBB2 Zornitza Stark Gene: erbb2 has been classified as Red List (Low Evidence).
Mendeliome v0.2887 ERBB2 Zornitza Stark Classified gene: ERBB2 as Red List (low evidence)
Mendeliome v0.2887 ERBB2 Zornitza Stark Gene: erbb2 has been classified as Red List (Low Evidence).
Mendeliome v0.2886 ERBB2 Zornitza Stark Classified gene: ERBB2 as Red List (low evidence)
Mendeliome v0.2886 ERBB2 Zornitza Stark Gene: erbb2 has been classified as Red List (Low Evidence).
Mendeliome v0.2885 BCR Zornitza Stark Gene: bcr has been classified as Red List (Low Evidence).
Mendeliome v0.2885 BCR Zornitza Stark Phenotypes for gene: BCR were changed from to Leukemia, acute lymphocytic, Philadelphia chromosome positive, somatic 613065; Leukemia, chronic myeloid, Philadelphia chromosome positive, somatic 608232
Mendeliome v0.2884 BCR Zornitza Stark Classified gene: BCR as Red List (low evidence)
Mendeliome v0.2884 BCR Zornitza Stark Gene: bcr has been classified as Red List (Low Evidence).
Mendeliome v0.2883 BCR Zornitza Stark reviewed gene: BCR: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Leukemia, acute lymphocytic, Philadelphia chromosome positive, somatic 613065, Leukemia, chronic myeloid, Philadelphia chromosome positive, somatic 608232; Mode of inheritance: None
Mendeliome v0.2883 CEP19 Bryony Thompson Classified gene: CEP19 as Amber List (moderate evidence)
Mendeliome v0.2883 CEP19 Bryony Thompson Gene: cep19 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2882 CEP19 Bryony Thompson gene: CEP19 was added
gene: CEP19 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CEP19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP19 were set to 29127258; 24268657
Phenotypes for gene: CEP19 were set to Morbid obesity and spermatogenic failure MIM#615703
Review for gene: CEP19 was set to AMBER
Added comment: A consanguineous Arab family with morbid obesity and infertility with a homozygous predicted null variant, and a mouse model that recapitulates the phenotype. Another homozygous variant has been identified in a consanguineous Bardet Beidl syndrome.
Sources: Literature
Mendeliome v0.2881 DALRD3 Zornitza Stark Gene: dalrd3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2881 DALRD3 Zornitza Stark Classified gene: DALRD3 as Amber List (moderate evidence)
Mendeliome v0.2881 DALRD3 Zornitza Stark Gene: dalrd3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2879 GDF3 Zornitza Stark Gene: gdf3 has been classified as Red List (Low Evidence).
Mendeliome v0.2877 GDF3 Zornitza Stark Classified gene: GDF3 as Red List (low evidence)
Mendeliome v0.2877 GDF3 Zornitza Stark Gene: gdf3 has been classified as Red List (Low Evidence).
Mendeliome v0.2876 KRAS Zornitza Stark Gene: kras has been classified as Green List (High Evidence).
Mendeliome v0.2872 GAA Zornitza Stark Gene: gaa has been classified as Green List (High Evidence).
Mendeliome v0.2870 HEXA Zornitza Stark Gene: hexa has been classified as Green List (High Evidence).
Mendeliome v0.2870 HEXA Zornitza Stark Phenotypes for gene: HEXA were changed from to GM2-gangliosidosis, several forms 272800; Tay-Sachs disease 272800
Mendeliome v0.2867 DHX30 Zornitza Stark Gene: dhx30 has been classified as Green List (High Evidence).
Mendeliome v0.2864 FAT1 Zornitza Stark Gene: fat1 has been classified as Green List (High Evidence).
Mendeliome v0.2864 FAT1 Zornitza Stark Phenotypes for gene: FAT1 were changed from to facial dysmorphism; colobomatous microphthalmia; ptosis; syndactyly with or without nephropathy
Mendeliome v0.2861 HEXA Elena Savva reviewed gene: HEXA: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31388111; Phenotypes: [Hex A pseudodeficiency] 272800, GM2-gangliosidosis, several forms 272800, Tay-Sachs disease 272800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2861 PITPNM3 Bryony Thompson Gene: pitpnm3 has been classified as Red List (Low Evidence).
Mendeliome v0.2861 PITPNM3 Bryony Thompson Classified gene: PITPNM3 as Red List (low evidence)
Mendeliome v0.2861 PITPNM3 Bryony Thompson Gene: pitpnm3 has been classified as Red List (Low Evidence).
Mendeliome v0.2860 FAT1 Ee Ming Wong reviewed gene: FAT1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30862798; Phenotypes: facial dysmorphism, colobomatous microphthalmia, ptosis, syndactyly with or without nephropathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2860 JARID2 Zornitza Stark Gene: jarid2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2860 JARID2 Zornitza Stark Classified gene: JARID2 as Amber List (moderate evidence)
Mendeliome v0.2860 JARID2 Zornitza Stark Gene: jarid2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2857 ADIPOR1 Zornitza Stark Gene: adipor1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2854 ADIPOR1 Zornitza Stark Classified gene: ADIPOR1 as Amber List (moderate evidence)
Mendeliome v0.2854 ADIPOR1 Zornitza Stark Gene: adipor1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2853 TRIP12 Zornitza Stark Gene: trip12 has been classified as Green List (High Evidence).
Mendeliome v0.2850 CX3CR1 Zornitza Stark Gene: cx3cr1 has been classified as Red List (Low Evidence).
Mendeliome v0.2850 CX3CR1 Zornitza Stark Phenotypes for gene: CX3CR1 were changed from to Coronary artery disease, resistance to}, MIM# 607339; {Macular degeneration, age-related, 12} 613784; {Rapid progression to AIDS from HIV1 infection} 609423
Mendeliome v0.2849 CX3CR1 Zornitza Stark Classified gene: CX3CR1 as Red List (low evidence)
Mendeliome v0.2849 CX3CR1 Zornitza Stark Gene: cx3cr1 has been classified as Red List (Low Evidence).
Mendeliome v0.2849 CX3CR1 Bryony Thompson Classified gene: CX3CR1 as Red List (low evidence)
Mendeliome v0.2849 CX3CR1 Bryony Thompson Gene: cx3cr1 has been classified as Red List (Low Evidence).
Mendeliome v0.2848 CX3CR1 Zornitza Stark reviewed gene: CX3CR1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Coronary artery disease, resistance to}, MIM# 607339, {Macular degeneration, age-related, 12} 613784, {Rapid progression to AIDS from HIV1 infection} 609423; Mode of inheritance: None
Mendeliome v0.2848 CLCC1 Zornitza Stark Gene: clcc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2848 CLCC1 Bryony Thompson Classified gene: CLCC1 as Amber List (moderate evidence)
Mendeliome v0.2848 CLCC1 Bryony Thompson Gene: clcc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2846 B9D1 Zornitza Stark Gene: b9d1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2843 B9D1 Zornitza Stark Classified gene: B9D1 as Amber List (moderate evidence)
Mendeliome v0.2843 B9D1 Zornitza Stark Gene: b9d1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2842 B9D1 Zornitza Stark changed review comment from: Two unrelated individuals with JS and bi-allelic variants in this gene, plus one individual with a more severe Meckel phenotype described. Intellectual disability is part of the phenotype.
Sources: Expert list; to: Two unrelated individuals with JS and bi-allelic variants in this gene, plus one individual with a more severe Meckel phenotype described. This latter individual had a splice site variant and a deletion. Splice variant proven to result in exon skipping -> PTC, but the deletion spans a large region including 18 other genes. Patient also had an additional variant in CEP290 called LP. Authors perform functional studies on patient cells but given the large deletion/CEP290 variant i dont see the results are usable PMID: 25920555 - another report of digenic inheritance - not usable, patient was only heterozygous for a single B9D1 variant.
Mendeliome v0.2839 ZNF423 Zornitza Stark Classified gene: ZNF423 as Amber List (moderate evidence)
Mendeliome v0.2839 ZNF423 Zornitza Stark Gene: znf423 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2838 PACS1 Zornitza Stark Gene: pacs1 has been classified as Green List (High Evidence).
Mendeliome v0.2835 SLC15A4 Zornitza Stark Gene: slc15a4 has been classified as Red List (Low Evidence).
Mendeliome v0.2834 SLC15A4 Zornitza Stark Classified gene: SLC15A4 as Red List (low evidence)
Mendeliome v0.2834 SLC15A4 Zornitza Stark Gene: slc15a4 has been classified as Red List (Low Evidence).
Mendeliome v0.2833 STARD7 Zornitza Stark Gene: stard7 has been classified as Green List (High Evidence).
Mendeliome v0.2833 STARD7 Zornitza Stark Classified gene: STARD7 as Green List (high evidence)
Mendeliome v0.2833 STARD7 Zornitza Stark Gene: stard7 has been classified as Green List (High Evidence).
Mendeliome v0.2832 STARD7 Zornitza Stark gene: STARD7 was added
gene: STARD7 was added to Mendeliome. Sources: Expert list
STR tags were added to gene: STARD7.
Mode of inheritance for gene: STARD7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: STARD7 were set to 11701600; 24114805; 31664034
Phenotypes for gene: STARD7 were set to Epilepsy, familial adult myoclonic, 2, 607876
Mode of pathogenicity for gene: STARD7 was set to Other
Review for gene: STARD7 was set to GREEN
Added comment: 158 individuals from 22 families reported with heterozygous 5-bp repeat expansion (ATTTC)n in intron 1 of the STARD7 gene.
Sources: Expert list
Mendeliome v0.2831 ERC1 Zornitza Stark Gene: erc1 has been classified as Red List (Low Evidence).
Mendeliome v0.2831 ERC1 Zornitza Stark Classified gene: ERC1 as Red List (low evidence)
Mendeliome v0.2831 ERC1 Zornitza Stark Gene: erc1 has been classified as Red List (Low Evidence).
Mendeliome v0.2830 DHCR7 Zornitza Stark Gene: dhcr7 has been classified as Green List (High Evidence).
Mendeliome v0.2827 PDXK Zornitza Stark Gene: pdxk has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2826 PDXK Zornitza Stark Classified gene: PDXK as Amber List (moderate evidence)
Mendeliome v0.2826 PDXK Zornitza Stark Gene: pdxk has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2825 NDP Zornitza Stark Gene: ndp has been classified as Green List (High Evidence).
Mendeliome v0.2822 TMEM107 Zornitza Stark Gene: tmem107 has been classified as Green List (High Evidence).
Mendeliome v0.2819 ALPL Zornitza Stark Gene: alpl has been classified as Green List (High Evidence).
Mendeliome v0.2819 ALPL Zornitza Stark Phenotypes for gene: ALPL were changed from to Hypophosphatasia, adult 146300 (AD, AR); Hypophosphatasia, childhood 241510 AR; Hypophosphatasia, infantile 241500 AR; Odontohypophosphatasia 146300 AD, AR
Mendeliome v0.2815 LRRC56 Zornitza Stark Gene: lrrc56 has been classified as Green List (High Evidence).
Mendeliome v0.2815 LRRC56 Zornitza Stark Classified gene: LRRC56 as Green List (high evidence)
Mendeliome v0.2815 LRRC56 Zornitza Stark Gene: lrrc56 has been classified as Green List (High Evidence).
Mendeliome v0.2814 LRRC56 Zornitza Stark reviewed gene: LRRC56: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 39, MIM# 618254; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2814 ALPL Melanie Marty reviewed gene: ALPL: Rating: GREEN; Mode of pathogenicity: Other; Publications: 19500388, 23688511; Phenotypes: Hypophosphatasia, adult 146300 (AD, AR), Hypophosphatasia, childhood 241510 AR, Hypophosphatasia, infantile 241500 AR, Odontohypophosphatasia 146300 AD, AR; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.2814 LRRC56 Elena Savva gene: LRRC56 was added
gene: LRRC56 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: LRRC56 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRRC56 were set to PMID: 30388400
Phenotypes for gene: LRRC56 were set to Ciliary dyskinesia, primary, 39 618254
Added comment: PMID: 30388400 - used protist null model to show abnormal ciliary beatings, replicated the phenotype when the protist was transfected with mutant allele observed in a patient.
3 unrelated families reported with either homozygous splice, missense or chet (nonsense/splice). Patients exhibited phenotypes including chronic respiratory/ear infections, situs inversus
Sources: Expert list
Mendeliome v0.2814 MOGS Zornitza Stark Gene: mogs has been classified as Green List (High Evidence).
Mendeliome v0.2811 TCF7L1 Zornitza Stark Gene: tcf7l1 has been classified as Red List (Low Evidence).
Mendeliome v0.2808 TCF7L1 Zornitza Stark Classified gene: TCF7L1 as Red List (low evidence)
Mendeliome v0.2808 TCF7L1 Zornitza Stark Gene: tcf7l1 has been classified as Red List (Low Evidence).
Mendeliome v0.2807 GFI1B Bryony Thompson Gene: gfi1b has been classified as Green List (High Evidence).
Mendeliome v0.2807 GFI1B Bryony Thompson Classified gene: GFI1B as Green List (high evidence)
Mendeliome v0.2807 GFI1B Bryony Thompson Gene: gfi1b has been classified as Green List (High Evidence).
Mendeliome v0.2805 PRKD1 Zornitza Stark Gene: prkd1 has been classified as Green List (High Evidence).
Mendeliome v0.2805 PRKD1 Zornitza Stark Phenotypes for gene: PRKD1 were changed from to Congenital heart defects and ectodermal dysplasia, 617364
Mendeliome v0.2802 NODAL Zornitza Stark Gene: nodal has been classified as Red List (Low Evidence).
Mendeliome v0.2799 NODAL Zornitza Stark Classified gene: NODAL as Red List (low evidence)
Mendeliome v0.2799 NODAL Zornitza Stark Gene: nodal has been classified as Red List (Low Evidence).
Mendeliome v0.2798 PIH1D3 Zornitza Stark Gene: pih1d3 has been classified as Green List (High Evidence).
Mendeliome v0.2798 PIH1D3 Zornitza Stark Phenotypes for gene: PIH1D3 were changed from to Ciliary dyskinesia, primary, 36, X-linked (MIM#300991)
Mendeliome v0.2795 PIH1D3 Zornitza Stark reviewed gene: PIH1D3: Rating: GREEN; Mode of pathogenicity: None; Publications: 28041644, 24421334, 28176794; Phenotypes: Ciliary dyskinesia, primary, 36, X-linked (MIM#300991); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.2795 COL10A1 Zornitza Stark Gene: col10a1 has been classified as Green List (High Evidence).
Mendeliome v0.2795 COL10A1 Zornitza Stark Phenotypes for gene: COL10A1 were changed from to Metaphyseal chondrodysplasia, Schmid type, MIM#156500
Mendeliome v0.2792 COL10A1 Zornitza Stark reviewed gene: COL10A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15880705, 31633898; Phenotypes: Metaphyseal chondrodysplasia, Schmid type, MIM#156500; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2792 CEP112 Bryony Thompson Classified gene: CEP112 as Amber List (moderate evidence)
Mendeliome v0.2792 CEP112 Bryony Thompson Gene: cep112 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2791 CEP112 Bryony Thompson gene: CEP112 was added
gene: CEP112 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CEP112 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP112 were set to 31654588
Phenotypes for gene: CEP112 were set to Acephalic spermatozoa; infertility
Review for gene: CEP112 was set to AMBER
Added comment: Two unrelated cases reported with acephalic spermatozoa, one case with a homozygous nonsense variant and the other case with biallelic missense variants. CEP112 expression was significantly reduced in one of the cases, suggesting loss of function as a mechanism of disease.
Sources: Literature
Mendeliome v0.2790 PRKD1 Kristin Rigbye reviewed gene: PRKD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27479907; Phenotypes: Congenital heart defects and ectodermal dysplasia, 617364; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2790 KPNA7 Alison Yeung Gene: kpna7 has been classified as Red List (Low Evidence).
Mendeliome v0.2790 KPNA7 Alison Yeung gene: KPNA7 was added
gene: KPNA7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KPNA7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KPNA7 were set to 24045845; 32179771
Phenotypes for gene: KPNA7 were set to Epilepsy; intellectual disability
Review for gene: KPNA7 was set to RED
Added comment: Single family with two siblings
Sources: Literature
Mendeliome v0.2789 NR4A2 Zornitza Stark Gene: nr4a2 has been classified as Green List (High Evidence).
Mendeliome v0.2789 NR4A2 Zornitza Stark Classified gene: NR4A2 as Green List (high evidence)
Mendeliome v0.2789 NR4A2 Zornitza Stark Gene: nr4a2 has been classified as Green List (High Evidence).
Mendeliome v0.2787 TOMM70 Zornitza Stark Gene: tomm70 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2787 TOMM70 Zornitza Stark Classified gene: TOMM70 as Amber List (moderate evidence)
Mendeliome v0.2787 TOMM70 Zornitza Stark Gene: tomm70 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2786 TOMM70 Zornitza Stark gene: TOMM70 was added
gene: TOMM70 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: TOMM70 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TOMM70 were set to 31907385; 32356556
Phenotypes for gene: TOMM70 were set to Severe anaemia, lactic acidosis, developmental delay; White matter abnormalities, developmental delay, regression, movement disorder
Review for gene: TOMM70 was set to AMBER
Added comment: TOM70 is a member of the TOM complex that transports cytosolic proteins into mitochondria.
Bi-allelic disease: one individual reported with compound heterozygous variants in TOMM70 [c.794C>T (p.T265M) and c.1745C>T (p.A582V)]. Clinical features included severe anaemia, lactic acidosis, and developmental delay. Some functional data: in vitro cell model compensatory experiments.
Monoallelic disease: de novo mono allelic variants in the C-terminal region of TOMM70 reported in two individuals. While both individuals exhibited shared symptoms including hypotonia, hyperreflexia, ataxia, dystonia, and significant white matter abnormalities, there were differences between the two individuals, most prominently the age of symptom onset, with one experiencing episodes of regression. Some functional data.
Sources: Expert list
Mendeliome v0.2784 CUL3 Zornitza Stark Gene: cul3 has been classified as Green List (High Evidence).
Mendeliome v0.2781 EGR2 Zornitza Stark Gene: egr2 has been classified as Green List (High Evidence).
Mendeliome v0.2777 GAS2L2 Zornitza Stark Gene: gas2l2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2777 GAS2L2 Zornitza Stark Phenotypes for gene: GAS2L2 were changed from to Ciliary dyskinesia, primary, 41 (MIM # 618449)
Mendeliome v0.2774 GAS2L2 Zornitza Stark Classified gene: GAS2L2 as Amber List (moderate evidence)
Mendeliome v0.2774 GAS2L2 Zornitza Stark Gene: gas2l2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2773 GAS2L2 Zornitza Stark reviewed gene: GAS2L2: Rating: AMBER; Mode of pathogenicity: None; Publications: 30665704; Phenotypes: Ciliary dyskinesia, primary, 41 (MIM # 618449); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2773 KLB Zornitza Stark Gene: klb has been classified as Green List (High Evidence).
Mendeliome v0.2772 KLB Zornitza Stark Classified gene: KLB as Green List (high evidence)
Mendeliome v0.2772 KLB Zornitza Stark Gene: klb has been classified as Green List (High Evidence).
Mendeliome v0.2771 KLB Zornitza Stark gene: KLB was added
gene: KLB was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KLB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KLB were set to 28754744
Review for gene: KLB was set to GREEN
Added comment: Seven heterozygous loss‐of‐function KLB mutations in 13 individuals reported. In mice, lack of Klb led to delayed puberty, altered estrous cyclicity, and subfertility due to a hypothalamic defect associated with inability of GnRH neurons to release GnRH in response to FGF21.
Functional analysis showed decreased activity in response to FGF21 and FGF8.
KLB is an obligate coreceptor for FGF21 alongside FGFR1.
Sources: Literature
Mendeliome v0.2770 NDNF Zornitza Stark Gene: ndnf has been classified as Green List (High Evidence).
Mendeliome v0.2770 NDNF Zornitza Stark Classified gene: NDNF as Green List (high evidence)
Mendeliome v0.2770 NDNF Zornitza Stark Gene: ndnf has been classified as Green List (High Evidence).
Mendeliome v0.2768 UGDH Zornitza Stark Gene: ugdh has been classified as Green List (High Evidence).
Mendeliome v0.2768 UGDH Zornitza Stark Classified gene: UGDH as Green List (high evidence)
Mendeliome v0.2768 UGDH Zornitza Stark Gene: ugdh has been classified as Green List (High Evidence).
Mendeliome v0.2767 UGDH Zornitza Stark gene: UGDH was added
gene: UGDH was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: UGDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UGDH were set to 32001716
Phenotypes for gene: UGDH were set to Epileptic encephalopathy, early infantile, 84 - MIM #618792
Review for gene: UGDH was set to GREEN
Added comment: 36 individuals with biallelic UGDH pathogenic variants reported. The phenotype corresponded overall to a developmental epileptic encephalopathy with hypotonia, feeding difficulties, severe global DD, moderate or commonly severe ID in all. Hypotonia and motor disorder (incl. spasticity, dystonia, ataxia, chorea, etc) often occurred prior to the onset of seizures. A single individual did not present seizures and 2 sibs had only seizures in the setting of fever. There were no individuals with biallelic pLoF variants identified. Parental/sib studies were all compatible with AR inheritance mode.

UGDH encodes the enzyme UDP-glucose dehydrogenase which converts UDP-glucose to UDP-glucuronate, the latter being a critical component of the glycosaminoglycans, hyaluronan, chondroitin sulfate, and heparan sulfate. Patient fibroblast and biochemical assays suggested a LoF effect of variants leading to impairment of UGDH stability, oligomerization or enzymatic activity (decreased UGDH-catalyzed reduction of NAD+ to NADH / hyaluronic acid production which requires UDP-glucuronate).

Attempts to model the disorder using an already developped zebrafish model (for a hypomorphic LoF allele) were unsuccessful as fish did not exhibit seizures spontaneously or upon induction with PTZ. Modelling of the disorder in vitro using patient-derived cerebral organoids demonstrated smaller organoids due to reduced number of proliferating neural progenitors
Sources: Literature
Mendeliome v0.2766 TRIM33 Zornitza Stark Gene: trim33 has been classified as Red List (Low Evidence).
Mendeliome v0.2766 TRIM33 Zornitza Stark Classified gene: TRIM33 as Red List (low evidence)
Mendeliome v0.2766 TRIM33 Zornitza Stark Gene: trim33 has been classified as Red List (Low Evidence).
Mendeliome v0.2765 YIF1B Zornitza Stark Gene: yif1b has been classified as Green List (High Evidence).
Mendeliome v0.2765 YIF1B Zornitza Stark Classified gene: YIF1B as Green List (high evidence)
Mendeliome v0.2765 YIF1B Zornitza Stark Gene: yif1b has been classified as Green List (High Evidence).
Mendeliome v0.2764 YIF1B Zornitza Stark gene: YIF1B was added
gene: YIF1B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: YIF1B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YIF1B were set to 32006098; 26077767
Phenotypes for gene: YIF1B were set to Central hypotonia; Failure to thrive; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Spasticity; Abnormality of movement
Review for gene: YIF1B was set to GREEN
Added comment: 6 individuals (from 5 families) with biallelic YIF1B truncating variants reported. Presenting features: hypotonia, failure to thrive, microcephaly (5/6), severe global DD and ID as well as features suggestive of a motor disorder (dystonia/spasticity/dyskinesia). Seizures were reported in 2 unrelated individuals (2/6). MRI abnormalities were observed in some with thin CC being a feature in 3. Affected individuals were found to be homozygous for truncating variants (4/5 families being consanguineous). The following 3 variants were identified (NM_001039672.2) : c.186dupT or p.Ala64fs / c.360_361insACAT or p.Gly121fs / c.598G>T or p.Glu200*. Yif1B KO mice demonstrate a disorganized Golgi architecture in pyramidal hippocampal neurons (Alterio et al 2015 - PMID: 26077767). Functional/network analysis of genes co-regulated with YIF1B based on available RNAseq data, suggest enrichement in in genes important for nervous system development and function.
Sources: Literature
Mendeliome v0.2760 TNRC6B Zornitza Stark Classified gene: TNRC6B as Green List (high evidence)
Mendeliome v0.2760 TNRC6B Zornitza Stark Gene: tnrc6b has been classified as Green List (High Evidence).
Mendeliome v0.2759 TNRC6B Zornitza Stark edited their review of gene: TNRC6B: Added comment: 17 unrelated individuals with heterozygous TNRC6B variants reported. Features included hypotonia (10/17), DD/ID (17/17 - ID was not universal: average IQ of 12 individuals was 73 (range : 50-113) with 4 having below 70), ADHD (11/17), ASD or autistic traits (8/17 and 5/17). Some/few presented with abnormal OFC (micro- / macrocephaly in 3/17 and 2/17), abnormal vision or hearing, variable other congenital anomalies, echocardiographic, GI or renal abnormalities, etc. Epilepsy was reported in 1/17. There was no recognisable gestalt.Detected variants included 14 pLoF, 1 missense SNV and 2 intragenic deletions. Variants had occurred as de novo events in 10/13 subjects for whom testing of both parents was possible. 3/13 subjects had inherited the variant from a parent with milder phenotype. Based on the type of variants identified, the pLI score of 1 in gnomAD and the HI index of 5.61%, the authors suggest haploinsufficiency as the most likely mechanism. Individuals with de novo TNRC6B variants have also been reported in larger cohorts (e.g. DDD study - PMID: 28135719, Iossifov et al - PMID: 25363768, Lelieveld et al - PMID: 27479843, Jónsson et al - PMID: 28959963). A previous study provided details on 2 sibs harboring a translocation which disrupted both TNRC6B and TCF20 (also associated with ID)(Babbs et al - PMID: 25228304).; Changed rating: GREEN; Changed publications: 32152250, 28135719, 25363768, 27479843, 28959963, 25228304; Changed phenotypes: Global developmental delay, Intellectual disability, Autistic behavior; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2759 CDC42BPB Zornitza Stark Gene: cdc42bpb has been classified as Green List (High Evidence).
Mendeliome v0.2759 CDC42BPB Zornitza Stark Classified gene: CDC42BPB as Green List (high evidence)
Mendeliome v0.2759 CDC42BPB Zornitza Stark Gene: cdc42bpb has been classified as Green List (High Evidence).
Mendeliome v0.2757 DNAJB13 Zornitza Stark Gene: dnajb13 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2757 DNAJB13 Zornitza Stark Phenotypes for gene: DNAJB13 were changed from to Ciliary dyskinesia, primary, 34, MIM# 617091
Mendeliome v0.2754 DNAJB13 Zornitza Stark Classified gene: DNAJB13 as Amber List (moderate evidence)
Mendeliome v0.2754 DNAJB13 Zornitza Stark Gene: dnajb13 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2753 DNAJB13 Zornitza Stark reviewed gene: DNAJB13: Rating: AMBER; Mode of pathogenicity: None; Publications: 27486783; Phenotypes: Ciliary dyskinesia, primary, 34, MIM# 617091; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2753 CFC1 Zornitza Stark Gene: cfc1 has been classified as Green List (High Evidence).
Mendeliome v0.2750 CFAP53 Zornitza Stark Gene: cfap53 has been classified as Green List (High Evidence).
Mendeliome v0.2750 CFAP53 Zornitza Stark Phenotypes for gene: CFAP53 were changed from to Heterotaxy, visceral, 6, autosomal recessive 614779
Mendeliome v0.2747 CFAP53 Zornitza Stark reviewed gene: CFAP53: Rating: GREEN; Mode of pathogenicity: None; Publications: 28621423, 22577226, 26531781; Phenotypes: Heterotaxy, visceral, 6, autosomal recessive 614779; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2747 TTC25 Zornitza Stark Gene: ttc25 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2747 TTC25 Zornitza Stark Phenotypes for gene: TTC25 were changed from to Ciliary dyskinesia, primary, 35 (MIM#617092)
Mendeliome v0.2744 TTC25 Zornitza Stark Classified gene: TTC25 as Amber List (moderate evidence)
Mendeliome v0.2744 TTC25 Zornitza Stark Gene: ttc25 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2743 TTC25 Zornitza Stark reviewed gene: TTC25: Rating: AMBER; Mode of pathogenicity: None; Publications: 27486780; Phenotypes: Ciliary dyskinesia, primary, 35 (MIM#617092); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2743 CFAP43 Zornitza Stark Gene: cfap43 has been classified as Green List (High Evidence).
Mendeliome v0.2743 CFAP43 Zornitza Stark Classified gene: CFAP43 as Green List (high evidence)
Mendeliome v0.2743 CFAP43 Zornitza Stark Gene: cfap43 has been classified as Green List (High Evidence).
Mendeliome v0.2742 CFAP43 Elena Savva gene: CFAP43 was added
gene: CFAP43 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CFAP43 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: CFAP43 were set to PMID: 31884020; 28552195; 31004071; 29449551
Phenotypes for gene: CFAP43 were set to Hydrocephalus, normal pressure, 1 236690; Spermatogenic failure 19 617592
Added comment: aka WDR96

PMID: 31884020 - animal models (mouse, frog) demonstrate the protein localizes in ciliary axoneme and is involved in MOTILE cilia movement. LOF CFAP43 caused mucus acucmulation in airways, impaired spermatogenesis and hydrocephalus.

PMID: 28552195 - 3x chet (bilallelic PTCs or chet PTC/missense) with abnormal sperm motility. Null mouse models were also infertile.

PMID: 31004071 - one family with a heterozygous nonsense and AD inheritance of late onset hydrocephaly (checked in Mutalyzer, variant is NMD predicted). Abnormal cilia observed from mucosa sample. Null mice also show abnormal sperm and dilation of brain ventricles.

PMID: 29449551 - reports an additional 10 patients with either homozygous PTCs or chet PTC/missense who were infertile with flagella defects

Summary: single report of AD hydrocephaly
Sources: Literature
Mendeliome v0.2742 MYLK2 Zornitza Stark Gene: mylk2 has been classified as Red List (Low Evidence).
Mendeliome v0.2739 MYLK2 Zornitza Stark Classified gene: MYLK2 as Red List (low evidence)
Mendeliome v0.2739 MYLK2 Zornitza Stark Gene: mylk2 has been classified as Red List (Low Evidence).
Mendeliome v0.2738 CDX2 Zornitza Stark Gene: cdx2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2738 CDX2 Zornitza Stark Phenotypes for gene: CDX2 were changed from to Persistent cloaca
Mendeliome v0.2735 CDX2 Zornitza Stark Classified gene: CDX2 as Amber List (moderate evidence)
Mendeliome v0.2735 CDX2 Zornitza Stark Gene: cdx2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2734 CDX2 Zornitza Stark reviewed gene: CDX2: Rating: AMBER; Mode of pathogenicity: None; Publications: 29177441; Phenotypes: Persistent cloaca; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2734 TAPT1 Zornitza Stark Gene: tapt1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2734 TAPT1 Zornitza Stark Phenotypes for gene: TAPT1 were changed from to Osteochondrodysplasia, complex lethal, Symoens-Barnes-Gistelinck type (MIM#616897)
Mendeliome v0.2731 TAPT1 Zornitza Stark Classified gene: TAPT1 as Amber List (moderate evidence)
Mendeliome v0.2731 TAPT1 Zornitza Stark Gene: tapt1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2730 TAPT1 Zornitza Stark reviewed gene: TAPT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 26365339; Phenotypes: Osteochondrodysplasia, complex lethal, Symoens-Barnes-Gistelinck type (MIM#616897); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2730 CCDC28B Zornitza Stark Classified gene: CCDC28B as Amber List (moderate evidence)
Mendeliome v0.2730 CCDC28B Zornitza Stark Gene: ccdc28b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2729 CCDC28B Zornitza Stark edited their review of gene: CCDC28B: Added comment: PMID: 32139166 - Single family with Joubert syndrome. Patient was homozygous for a missense, with polydactyly, severe ID, and the molar tooth sign observed in MRI. Sibling fetus MRI showed vermis hypoplasia, and was also homozygous for the variant. Parents confirmed unaffected carriers. Knockdown of CCDC28B in human TERT retinal pigment epithelial cells reduced both the number and length of cilia 430C-T variant is postulated to be a modifier of BBS.; Changed rating: AMBER; Changed publications: 32139166; Changed phenotypes: {Bardet-Biedl syndrome 1, modifier of}, MIM#209900, Joubert syndrome
Mendeliome v0.2729 C21orf59 Zornitza Stark Gene: c21orf59 has been classified as Green List (High Evidence).
Mendeliome v0.2729 C11orf70 Zornitza Stark Gene: c11orf70 has been classified as Green List (High Evidence).
Mendeliome v0.2729 C11orf70 Zornitza Stark Phenotypes for gene: C11orf70 were changed from to Ciliary dyskinesia, primary, 38, MIM# 618063
Mendeliome v0.2726 C11orf70 Zornitza Stark reviewed gene: C11orf70: Rating: GREEN; Mode of pathogenicity: None; Publications: 29727693, 29727692; Phenotypes: Ciliary dyskinesia, primary, 38, MIM# 618063; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2726 ARMC9 Zornitza Stark Gene: armc9 has been classified as Green List (High Evidence).
Mendeliome v0.2723 ARMC9 Zornitza Stark edited their review of gene: ARMC9: Added comment: ARMC9 localizes to the ciliary basal body and daughter centriole and is predicted to function in ciliogenesis PMID: 28625504 - 8 families with Joubert syndrome, all variant types detected. Functional studies show protein localizes at the basal body and upregulates during ciliogenesis. Zebrafish with frameshift mutation recapitulated the human phenotype including a curved body, coloboma, retinal dystrophy and less cilia.; Changed rating: GREEN; Changed publications: 28625504
Mendeliome v0.2723 ARMC8 Zornitza Stark Gene: armc8 has been classified as Red List (Low Evidence).
Mendeliome v0.2723 ARMC8 Zornitza Stark Classified gene: ARMC8 as Red List (low evidence)
Mendeliome v0.2723 ARMC8 Zornitza Stark Gene: armc8 has been classified as Red List (Low Evidence).
Mendeliome v0.2722 ARMC4 Zornitza Stark Gene: armc4 has been classified as Green List (High Evidence).
Mendeliome v0.2722 ARMC4 Zornitza Stark Phenotypes for gene: ARMC4 were changed from to Ciliary dyskinesia, primary, 23, MIM# 615451
Mendeliome v0.2719 ARMC4 Zornitza Stark reviewed gene: ARMC4: Rating: GREEN; Mode of pathogenicity: None; Publications: 31765523, 23849778; Phenotypes: Ciliary dyskinesia, primary, 23, MIM# 615451; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2719 ACVR2B Zornitza Stark Gene: acvr2b has been classified as Red List (Low Evidence).
Mendeliome v0.2716 ACVR2B Zornitza Stark Classified gene: ACVR2B as Red List (low evidence)
Mendeliome v0.2716 ACVR2B Zornitza Stark Gene: acvr2b has been classified as Red List (Low Evidence).
Mendeliome v0.2715 NID1 Zornitza Stark Gene: nid1 has been classified as Green List (High Evidence).
Mendeliome v0.2712 DARS Zornitza Stark Gene: dars has been classified as Green List (High Evidence).
Mendeliome v0.2709 CCDC65 Zornitza Stark Gene: ccdc65 has been classified as Green List (High Evidence).
Mendeliome v0.2709 CCDC65 Zornitza Stark Phenotypes for gene: CCDC65 were changed from to Ciliary dyskinesia, primary, 27, MIM# 615504
Mendeliome v0.2706 CCDC65 Zornitza Stark reviewed gene: CCDC65: Rating: GREEN; Mode of pathogenicity: None; Publications: 23991085, 24094744; Phenotypes: Ciliary dyskinesia, primary, 27, MIM# 615504; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2706 C21orf59 Zornitza Stark Gene: c21orf59 has been classified as Green List (High Evidence).
Mendeliome v0.2706 C21orf59 Zornitza Stark Phenotypes for gene: C21orf59 were changed from to Ciliary dyskinesia, primary, 26, MIM# 615500
Mendeliome v0.2703 C21orf59 Zornitza Stark reviewed gene: C21orf59: Rating: GREEN; Mode of pathogenicity: None; Publications: 24094744; Phenotypes: Ciliary dyskinesia, primary, 26, MIM# 615500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2703 WISP3 Zornitza Stark Gene: wisp3 has been classified as Green List (High Evidence).
Mendeliome v0.2703 WISP3 Zornitza Stark Phenotypes for gene: WISP3 were changed from to Arthropathy, progressive pseudorheumatoid, of childhood, MIM# 208230; Spondyloepiphyseal dysplasia tarda with progressive arthropathy, MIM# 208230
Mendeliome v0.2700 WISP3 Zornitza Stark reviewed gene: WISP3: Rating: GREEN; Mode of pathogenicity: None; Publications: 10471507; Phenotypes: Arthropathy, progressive pseudorheumatoid, of childhood, MIM# 208230, Spondyloepiphyseal dysplasia tarda with progressive arthropathy, MIM# 208230; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2700 ATP5E Zornitza Stark Gene: atp5e has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2697 ATP5E Zornitza Stark Classified gene: ATP5E as Amber List (moderate evidence)
Mendeliome v0.2697 ATP5E Zornitza Stark Gene: atp5e has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2696 ATP5D Zornitza Stark Gene: atp5d has been classified as Green List (High Evidence).
Mendeliome v0.2693 ATP5A1 Zornitza Stark Gene: atp5a1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2690 ATP5A1 Zornitza Stark Classified gene: ATP5A1 as Amber List (moderate evidence)
Mendeliome v0.2690 ATP5A1 Zornitza Stark Gene: atp5a1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2689 GLDC Zornitza Stark Gene: gldc has been classified as Green List (High Evidence).
Mendeliome v0.2686 CD4 Zornitza Stark reviewed gene: CD4: Rating: AMBER; Mode of pathogenicity: None; Publications: 31781092; Phenotypes: Absence of CD4+ T cells, exuberant, relapsing, treatment-refractory warts; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2685 TNK2 Zornitza Stark Gene: tnk2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2682 TNK2 Zornitza Stark Classified gene: TNK2 as Amber List (moderate evidence)
Mendeliome v0.2682 TNK2 Zornitza Stark Gene: tnk2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2681 MAN2B2 Zornitza Stark Gene: man2b2 has been classified as Red List (Low Evidence).
Mendeliome v0.2681 MAN2B2 Zornitza Stark gene: MAN2B2 was added
gene: MAN2B2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MAN2B2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAN2B2 were set to 31775018
Phenotypes for gene: MAN2B2 were set to Congenital disorder of glycosylation; immunodeficiency
Review for gene: MAN2B2 was set to RED
Added comment: Single individual reported.
Sources: Literature
Mendeliome v0.2680 RIPK1 Zornitza Stark Gene: ripk1 has been classified as Green List (High Evidence).
Mendeliome v0.2677 PIK3CG Zornitza Stark Gene: pik3cg has been classified as Green List (High Evidence).
Mendeliome v0.2677 PIK3CG Zornitza Stark Classified gene: PIK3CG as Green List (high evidence)
Mendeliome v0.2677 PIK3CG Zornitza Stark Gene: pik3cg has been classified as Green List (High Evidence).
Mendeliome v0.2675 RC3H1 Zornitza Stark Gene: rc3h1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2675 RC3H1 Zornitza Stark Classified gene: RC3H1 as Amber List (moderate evidence)
Mendeliome v0.2675 RC3H1 Zornitza Stark Gene: rc3h1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2675 RC3H1 Zornitza Stark Classified gene: RC3H1 as Amber List (moderate evidence)
Mendeliome v0.2675 RC3H1 Zornitza Stark Gene: rc3h1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2674 RC3H1 Zornitza Stark changed review comment from: Single individual with bi-allelic LoF variant and relapsing HLH reported, some functional data.
Sources: Literature; to: Single individual with bi-allelic LoF variant and relapsing HLH reported, some functional data including mouse model.
Sources: Literature
Mendeliome v0.2674 RC3H1 Zornitza Stark gene: RC3H1 was added
gene: RC3H1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RC3H1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RC3H1 were set to 31636267
Phenotypes for gene: RC3H1 were set to Relapsing HLH
Review for gene: RC3H1 was set to RED
Added comment: Single individual with bi-allelic LoF variant and relapsing HLH reported, some functional data.
Sources: Literature
Mendeliome v0.2673 IFNG Zornitza Stark Gene: ifng has been classified as Red List (Low Evidence).
Mendeliome v0.2670 IFNG Zornitza Stark Classified gene: IFNG as Red List (low evidence)
Mendeliome v0.2670 IFNG Zornitza Stark Gene: ifng has been classified as Red List (Low Evidence).
Mendeliome v0.2669 ITPKB Zornitza Stark gene: ITPKB was added
gene: ITPKB was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ITPKB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ITPKB were set to 31987846
Phenotypes for gene: ITPKB were set to Severe combined immunodeficiency, absent T cells, present B cells and NK cells
Review for gene: ITPKB was set to RED
Added comment: Single individual with homozygous bi-allelic LoF variant reported.
Sources: Literature
Mendeliome v0.2668 PSMB10 Zornitza Stark Gene: psmb10 has been classified as Red List (Low Evidence).
Mendeliome v0.2668 PSMB10 Zornitza Stark gene: PSMB10 was added
gene: PSMB10 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PSMB10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMB10 were set to 31783057
Phenotypes for gene: PSMB10 were set to Autoinflammatory syndrome
Review for gene: PSMB10 was set to RED
Added comment: PSMB10 is part of the immunoproteasome, and other components cause auto inflammatory disorders. Single individual with homozygous missense variant reported.
Sources: Literature
Mendeliome v0.2667 ABHD12 Zornitza Stark Gene: abhd12 has been classified as Green List (High Evidence).
Mendeliome v0.2665 ABCC6 Zornitza Stark Gene: abcc6 has been classified as Green List (High Evidence).
Mendeliome v0.2665 AAAS Zornitza Stark Gene: aaas has been classified as Green List (High Evidence).
Mendeliome v0.2665 AAAS Zornitza Stark Phenotypes for gene: AAAS were changed from to Achalasia-addisonianism-alacrimia syndrome, MIM#231550
Mendeliome v0.2663 NOS2 Zornitza Stark Gene: nos2 has been classified as Red List (Low Evidence).
Mendeliome v0.2663 NOS2 Zornitza Stark Phenotypes for gene: NOS2 were changed from to {Malaria, resistance to} 611162; Disseminated CMV disease
Mendeliome v0.2661 NOS2 Zornitza Stark Classified gene: NOS2 as Red List (low evidence)
Mendeliome v0.2661 NOS2 Zornitza Stark Gene: nos2 has been classified as Red List (Low Evidence).
Mendeliome v0.2660 NOS2 Zornitza Stark reviewed gene: NOS2: Rating: AMBER; Mode of pathogenicity: None; Publications: 12433515, 31995689; Phenotypes: {Malaria, resistance to} 611162, Disseminated CMV disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2660 SNORA31 Zornitza Stark Gene: snora31 has been classified as Green List (High Evidence).
Mendeliome v0.2660 SNORA31 Zornitza Stark Classified gene: SNORA31 as Green List (high evidence)
Mendeliome v0.2660 SNORA31 Zornitza Stark Gene: snora31 has been classified as Green List (High Evidence).
Mendeliome v0.2659 SNORA31 Zornitza Stark gene: SNORA31 was added
gene: SNORA31 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SNORA31 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SNORA31 were set to 31806906
Phenotypes for gene: SNORA31 were set to Susceptibility to HSV1 encephalitis
Review for gene: SNORA31 was set to GREEN
Added comment: Five unrelated individuals reported with rare missense variants in this gene, functional data to support susceptibility to herpes simplex encephalitis.
Sources: Expert list
Mendeliome v0.2658 TCOF1 Zornitza Stark Gene: tcof1 has been classified as Green List (High Evidence).
Mendeliome v0.2655 EMX2 Zornitza Stark Gene: emx2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2652 EMX2 Zornitza Stark Classified gene: EMX2 as Amber List (moderate evidence)
Mendeliome v0.2652 EMX2 Zornitza Stark Gene: emx2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2651 ATAD3A Zornitza Stark Phenotypes for gene: ATAD3A were changed from Harel-Yoon syndrome, MIM# 617183 to Harel-Yoon syndrome, MIM# 617183; Pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal (PHRINL SYNDROME) 618810
Mendeliome v0.2649 ATAD3A Zornitza Stark edited their review of gene: ATAD3A: Added comment: Mode of pathogenicity includes:
i) bi-allelic missense and nonsense variants and bi-allelic deletions that create an ATAD3B/ATAD3A fusion gene under the lowly expressed ATAD3B promoter
ii) monoallelic dominant-negative missense variants (either de novo or inherited) and de novo monoallelic duplications creating a dominant negative ATAD3A/ATAD3C fusion gene; Changed publications: 27640307, 32004445, 28549128; Changed phenotypes: Harel-Yoon syndrome, MIM# 617183, Pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal (PHRINL SYNDROME) 618810
Mendeliome v0.2649 CTSA Zornitza Stark Gene: ctsa has been classified as Green List (High Evidence).
Mendeliome v0.2649 CTSA Zornitza Stark Phenotypes for gene: CTSA were changed from to Galactosialidosis, MIM# 256540; Cathepsin A-related arteriopathy with strokes and leukoencephalopathy
Mendeliome v0.2646 MN1 Zornitza Stark Phenotypes for gene: MN1 were changed from Intellectual disability; dysmophic features; rhombencephalosynapsis to CEBALID syndrome, MIM#618774; Intellectual disability; dysmophic features; rhombencephalosynapsis
Mendeliome v0.2645 MN1 Zornitza Stark edited their review of gene: MN1: Changed phenotypes: CEBALID syndrome, MIM#618774, Intellectual disability, dysmophic features, rhombencephalosynapsis
Mendeliome v0.2645 PI4KA Zornitza Stark Gene: pi4ka has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2645 PI4KA Zornitza Stark Phenotypes for gene: PI4KA were changed from to Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis, MIM# 616531
Mendeliome v0.2642 PI4KA Zornitza Stark Classified gene: PI4KA as Amber List (moderate evidence)
Mendeliome v0.2642 PI4KA Zornitza Stark Gene: pi4ka has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2641 PI4KA Zornitza Stark reviewed gene: PI4KA: Rating: AMBER; Mode of pathogenicity: None; Publications: 25855803; Phenotypes: Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis, MIM# 616531; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2641 CDK5 Zornitza Stark changed review comment from: Single consanguineous family with multiple affected individuals reported.; to: Single consanguineous family with multiple affected individuals reported.
Mendeliome v0.2641 CDK5 Zornitza Stark Gene: cdk5 has been classified as Red List (Low Evidence).
Mendeliome v0.2641 CDK5 Zornitza Stark Phenotypes for gene: CDK5 were changed from to Lissencephaly 7 with cerebellar hypoplasia, MIM# 616342
Mendeliome v0.2638 CDK5 Zornitza Stark Classified gene: CDK5 as Red List (low evidence)
Mendeliome v0.2638 CDK5 Zornitza Stark Gene: cdk5 has been classified as Red List (Low Evidence).
Mendeliome v0.2637 CDK5 Zornitza Stark reviewed gene: CDK5: Rating: RED; Mode of pathogenicity: None; Publications: 25560765; Phenotypes: Lissencephaly 7 with cerebellar hypoplasia, MIM# 616342; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2637 VPS51 Zornitza Stark Gene: vps51 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2637 VPS51 Zornitza Stark Classified gene: VPS51 as Amber List (moderate evidence)
Mendeliome v0.2637 VPS51 Zornitza Stark Gene: vps51 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2636 VPS51 Zornitza Stark gene: VPS51 was added
gene: VPS51 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: VPS51 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS51 were set to 30624672; 31207318
Phenotypes for gene: VPS51 were set to Pontocerebellar hypoplasia, type 13, MIM# 618606
Review for gene: VPS51 was set to AMBER
Added comment: Two families reported with bi-allelic variants in this gene and global developmental delay, impaired intellectual development with absent speech, microcephaly, and progressive atrophy of the cerebellar vermis and brainstem. Additional features, including seizures and visual impairment, are variable.
Sources: Expert list
Mendeliome v0.2635 CTSA Zornitza Stark changed review comment from: Bi-allelic variants cause galactosialidosis, and mono-allelic variants cause CARASAL.; to: Bi-allelic variants associated with galactosialidosis, and mono-allelic variants associated with CARASAL.
Mendeliome v0.2635 CTSA Zornitza Stark reviewed gene: CTSA: Rating: GREEN; Mode of pathogenicity: None; Publications: 31177426; Phenotypes: Galactosialidosis, MIM# 256540, Cathepsin A-related arteriopathy with strokes and leukoencephalopathy; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2635 CDK19 Zornitza Stark Gene: cdk19 has been classified as Green List (High Evidence).
Mendeliome v0.2635 CDK19 Zornitza Stark Classified gene: CDK19 as Green List (high evidence)
Mendeliome v0.2635 CDK19 Zornitza Stark Gene: cdk19 has been classified as Green List (High Evidence).
Mendeliome v0.2633 MNS1 Zornitza Stark Gene: mns1 has been classified as Green List (High Evidence).
Mendeliome v0.2633 MNS1 Zornitza Stark Classified gene: MNS1 as Green List (high evidence)
Mendeliome v0.2633 MNS1 Zornitza Stark Gene: mns1 has been classified as Green List (High Evidence).
Mendeliome v0.2631 DHX37 Zornitza Stark Gene: dhx37 has been classified as Green List (High Evidence).
Mendeliome v0.2631 DHX37 Zornitza Stark Classified gene: DHX37 as Green List (high evidence)
Mendeliome v0.2631 DHX37 Zornitza Stark Gene: dhx37 has been classified as Green List (High Evidence).
Mendeliome v0.2630 DHX37 Zornitza Stark gene: DHX37 was added
gene: DHX37 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DHX37 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DHX37 were set to 31337883; 31745530
Phenotypes for gene: DHX37 were set to 46,XY gonadal dysgenesis; testicular regression syndrome (TRS)
Review for gene: DHX37 was set to GREEN
Added comment: Seventeen individuals with 46,XY gonadal dysgenesis reported in two studies.
Sources: Literature
Mendeliome v0.2629 ALPK1 Zornitza Stark Phenotypes for gene: ALPK1 were changed from Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome to Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome; ROSAH syndrome; retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache
Mendeliome v0.2628 ALPK1 Zornitza Stark Classified gene: ALPK1 as Green List (high evidence)
Mendeliome v0.2628 ALPK1 Zornitza Stark Gene: alpk1 has been classified as Green List (High Evidence).
Mendeliome v0.2627 RAMP2 Zornitza Stark Gene: ramp2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2627 RAMP2 Zornitza Stark Classified gene: RAMP2 as Amber List (moderate evidence)
Mendeliome v0.2627 RAMP2 Zornitza Stark Gene: ramp2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2626 RAMP2 Zornitza Stark gene: RAMP2 was added
gene: RAMP2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RAMP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAMP2 were set to 31000793
Phenotypes for gene: RAMP2 were set to Primary open angle glaucoma
Review for gene: RAMP2 was set to AMBER
Added comment: Six variants identified in 16 of 4763 POAG patients from large cohorts; none identified in 10,953 control individuals. Some functional data.
Sources: Literature
Mendeliome v0.2625 ALPK1 Zornitza Stark edited their review of gene: ALPK1: Added comment: Six unrelated families reported with same recurrent missense variant c.710C>T, (p.Thr237Met) and ROSAH syndrome phenotype. Pancytopaenia and recurrent infections present in some.; Changed rating: GREEN; Changed publications: 31053777, 30967659, 31939038; Changed phenotypes: Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome, ROSAH syndrome, retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache
Mendeliome v0.2625 MEPE Zornitza Stark Classified gene: MEPE as Amber List (moderate evidence)
Mendeliome v0.2625 MEPE Zornitza Stark Gene: mepe has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2624 MEPE Zornitza Stark gene: MEPE was added
gene: MEPE was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MEPE was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MEPE were set to 30287925
Phenotypes for gene: MEPE were set to hereditary congenital facial paresis; otosclerosis
Review for gene: MEPE was set to AMBER
Added comment: Single four-generation family reported with variant in this gene segregating nonprogressive HCFP and mixed hearing loss (HL). Damaging variants (truncating/frameshift) found to be enriched in otosclerosis cohort (p = 0.0006–0.0060).
Sources: Literature
Mendeliome v0.2623 PAICS Zornitza Stark Gene: paics has been classified as Red List (Low Evidence).
Mendeliome v0.2623 PAICS Zornitza Stark gene: PAICS was added
gene: PAICS was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PAICS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PAICS were set to 31600779
Phenotypes for gene: PAICS were set to Polyhydramnios; multiple congenital abnormalities
Review for gene: PAICS was set to RED
Added comment: Two sibs from single family reported with homozygous missense variant. Functional data to demonstrate effect on protein function.
Sources: Literature
Mendeliome v0.2622 GALM Zornitza Stark Gene: galm has been classified as Green List (High Evidence).
Mendeliome v0.2622 GALM Zornitza Stark Classified gene: GALM as Green List (high evidence)
Mendeliome v0.2622 GALM Zornitza Stark Gene: galm has been classified as Green List (High Evidence).
Mendeliome v0.2621 POLR3GL Zornitza Stark Gene: polr3gl has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2621 POLR3GL Zornitza Stark Classified gene: POLR3GL as Amber List (moderate evidence)
Mendeliome v0.2621 POLR3GL Zornitza Stark Gene: polr3gl has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2620 GALM Hazel Phillimore gene: GALM was added
gene: GALM was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GALM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GALM were set to PMID: 30451973; 30910422
Phenotypes for gene: GALM were set to galactosaemia; type IV galactosaemia
Review for gene: GALM was set to GREEN
Added comment: Homozygous and compound heterozygous variants (missense, nonsense and frameshift) found in 8 Japanese patients from unrelated families with unexplained galactosaemia. (No variants in GALT, GALK1, and GALE). This is therefore type IV galactosaemia.
In vitro expression analysis and enzyme activity assay of the patients’ peripheral blood mononuclear cells showed total lack of or compromised expression of GALM protein. Loss-of-function mechanism. One homozygote for one of these variants p.(Gly142Arg) in gnomAD (African population). (Wada, Y. et al 2019; PMID: 30451973)
In vitro expression assay and an enzyme activity assay of 67 GALM variants, taken from ExAc database (missense, nonsense, frameshift and splice). 30 variants concluded to be pathogenic due to no protein expression or faint expression. 5 variants with mildly lower levels were determined as likely pathogenic. All concluded to be loss-of-function mechanism. Incidence of galactosaemia by GALM deficiency is comparable to that of other galactosaemias. Carrier frequency and incidence was estimated for different populations. (Iwasawa, S. et al. (2019); PMID: 30910422)
Sources: Literature
Mendeliome v0.2620 POLR3GL Paul De Fazio gene: POLR3GL was added
gene: POLR3GL was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: POLR3GL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR3GL were set to 31089205; 31695177
Phenotypes for gene: POLR3GL were set to endosteal hyperostosis; oligodontia; growth retardation; facial dysmorphisms; lipodystrophy
Review for gene: POLR3GL was set to AMBER
gene: POLR3GL was marked as current diagnostic
Added comment: Biallelic canonical splice variants were identified in monozygotic twins and another individual with similar phenotypes from 2 unrelated families. Variants were inherited from carrier parents. RNA studies confirmed exon skipping occurs in all affected individuals.

A separate study identified a homozygous nonsense variant in an individual with features of Neonatal progeroid syndrome/Wiedemann–Rautenstrauch syndrome. Quantitative PCR showed reduction in mRNA suggestive of NMD.
Sources: Literature
Mendeliome v0.2620 TSPEAR Zornitza Stark Gene: tspear has been classified as Green List (High Evidence).
Mendeliome v0.2620 TSPEAR Zornitza Stark Phenotypes for gene: TSPEAR were changed from to Ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis, MIM#618180
Mendeliome v0.2617 PDGFRB Zornitza Stark Gene: pdgfrb has been classified as Green List (High Evidence).
Mendeliome v0.2613 TBL1Y Zornitza Stark Added comment: Comment when marking as ready: Single family, some functional data.
Mendeliome v0.2613 TBL1Y Zornitza Stark Gene: tbl1y has been classified as Red List (Low Evidence).
Mendeliome v0.2613 TBL1Y Zornitza Stark Classified gene: TBL1Y as Red List (low evidence)
Mendeliome v0.2613 TBL1Y Zornitza Stark Gene: tbl1y has been classified as Red List (Low Evidence).
Mendeliome v0.2612 DGCR8 Zornitza Stark Gene: dgcr8 has been classified as Red List (Low Evidence).
Mendeliome v0.2612 DGCR8 Zornitza Stark Classified gene: DGCR8 as Red List (low evidence)
Mendeliome v0.2612 DGCR8 Zornitza Stark Gene: dgcr8 has been classified as Red List (Low Evidence).
Mendeliome v0.2611 TSPEAR Chern Lim changed review comment from: Still a rare disease gene for ectodermal dysplasia but has been reported in at least 3 unrelated families. Functional study supported LoF. (PMIDs: 27736875, 30046887); to: Still a rare disease gene for ectodermal dysplasia but has been reported in at least 3 unrelated families in 2 papers. Functional study supported LoF. (PMIDs: 27736875, 30046887)
Mendeliome v0.2611 TSPEAR Chern Lim reviewed gene: TSPEAR: Rating: GREEN; Mode of pathogenicity: None; Publications: 27736875, 30046887; Phenotypes: Ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis, MIM#618180; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.2611 PDGFRB Ee Ming Wong changed review comment from: - > 3 unrelated families
- Functional studies on patient fibroblasts, HeLa and HEK293 cells harbouring mutant constructs demonstrate constitutive tyrosine kinase activation (gain of function) compared with WT constructs; to: - > 3 unrelated individuals diagnosed with Penttinen syndrome
- Functional studies on patient fibroblasts, HeLa and HEK293 cells harbouring mutant constructs demonstrate constitutive tyrosine kinase activation (gain of function) compared with WT constructs
Mendeliome v0.2611 TBL1Y Paul De Fazio changed review comment from: 9 affected males in a single 5-generation pedigree described with Y-linked inheritance pattern. Functional studies show the missense variant causes reduced protein stability. The gene has restricted expression in the cochlea and prostate.
Sources: Literature; to: Y-linked inheritance pattern. Complete segregation of a missense variant demonstrated in 9 affected males in a 5-generation pedigree. Functional studies show the missense variant causes reduced protein stability. The gene has restricted expression in the cochlea and prostate.
Sources: Literature
Mendeliome v0.2611 TBL1Y Paul De Fazio changed review comment from: 9 affected males in a single pedigree described with Y-linked inheritance pattern. Functional studies show the missense variant causes reduced protein stability. The gene has restricted expression in the cochlea and prostate.
Sources: Literature; to: 9 affected males in a single 5-generation pedigree described with Y-linked inheritance pattern. Functional studies show the missense variant causes reduced protein stability. The gene has restricted expression in the cochlea and prostate.
Sources: Literature
Mendeliome v0.2611 TBL1Y Paul De Fazio gene: TBL1Y was added
gene: TBL1Y was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TBL1Y was set to Other
Publications for gene: TBL1Y were set to 30341416
Phenotypes for gene: TBL1Y were set to Hearing loss
Review for gene: TBL1Y was set to RED
gene: TBL1Y was marked as current diagnostic
Added comment: 9 affected males in a single pedigree described with Y-linked inheritance pattern. Functional studies show the missense variant causes reduced protein stability. The gene has restricted expression in the cochlea and prostate.
Sources: Literature
Mendeliome v0.2611 FOXF2 Zornitza Stark Added comment: Comment when marking as ready: Single family: variant has functional data to demonstrate effect on protein, plus mouse model supports gene-disease association.
Mendeliome v0.2611 FOXF2 Zornitza Stark Gene: foxf2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2611 FOXF2 Zornitza Stark Classified gene: FOXF2 as Amber List (moderate evidence)
Mendeliome v0.2611 FOXF2 Zornitza Stark Gene: foxf2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2610 DGCR8 Chern Lim gene: DGCR8 was added
gene: DGCR8 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DGCR8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DGCR8 were set to 31805011
Phenotypes for gene: DGCR8 were set to Early-onset multinodular goiter and schwannomatosis
Review for gene: DGCR8 was set to RED
Added comment: A germline missense variant segregates in one family with autosomal dominant mendelian tumor susceptibility syndrome: familial multinodular goiter (MNG) with schwannomatosis. The missense is also a recurrent somatic missense variant in Wilms tumour. (PMID:31805011)
Sources: Literature
Mendeliome v0.2610 TDRD7 Zornitza Stark Phenotypes for gene: TDRD7 were changed from to Cataract 36 613887; glaucoma; nonobstructive azoospermia; arrested spermatogenesis
Mendeliome v0.2607 TDRD7 Ee Ming Wong reviewed gene: TDRD7: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28837160, 21436445; Phenotypes: cataract, glaucoma, nonobstructive azoospermia, arrested spermatogenesis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2607 FOXF2 Hazel Phillimore changed review comment from: Homozygous missense, NM_001452.1: c.325A>T (p.I109F), in a 10 year old girl (consanguineous, parents were first cousins) with profound sensorineural hearing loss (SNHL) associated with incomplete partition type I anomaly of the cochlea. This variant is absent in the gnomAD v2.1.1. In vitro studies indicated instability, shorter half-life of the protein compared to wildtype. Embryonic knockout mouse showed shortened and malformed cochleae, in addition to altered shape of hair cells with innervation and planar cell polarity defects. Homozygous knockout mice do not survive. (Bademci, G. et al. (2019); PMID: 30561639).
This gene has also been reported in association with other anomalies including cleft lip, cleft palate, brain anomalies, intestine anomalies, and eye anomalies. Eye anomalies include anterior segment dysgenesis, as shown in mice with variant, W174R, affecting the Fox domain. Homozygote mice do not survive. (McKeone, R. et al. (2011); PMID: 22022403).
Sources: Literature; to: Homozygous missense, NM_001452.1: c.325A>T (p.I109F), in a 10 year old girl (consanguineous, parents were first cousins) with profound sensorineural hearing loss (SNHL) associated with incomplete partition type I anomaly of the cochlea. This variant is absent in the gnomAD v2.1.1. In vitro studies indicated instability, shorter half-life of the protein compared to wildtype. Embryonic knockout mouse showed shortened and malformed cochleae, in addition to altered shape of hair cells with innervation and planar cell polarity defects. Homozygous knockout mice do not survive. (Bademci, G. et al. (2019); PMID: 30561639).
This gene has also been reported in association with other anomalies including cleft lip, cleft palate, brain anomalies, intestine anomalies, and eye anomalies. Eye anomalies include anterior segment dysgenesis, as shown in mice with variant, W174R, affecting the Fox domain. Homozygote mice do not survive. (McKeone, R. et al. (2011); PMID: 22022403).
Previous names for FOXF2 include FKHL6 and FREAC2.
Sources: Literature
Mendeliome v0.2607 FOXF2 Hazel Phillimore gene: FOXF2 was added
gene: FOXF2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FOXF2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FOXF2 were set to PMID: 30561639; 22022403
Phenotypes for gene: FOXF2 were set to profound sensorineural hearing loss (SNHL); cochlea malformations; incomplete partition type I anomaly of the cochlea
Review for gene: FOXF2 was set to AMBER
Added comment: Homozygous missense, NM_001452.1: c.325A>T (p.I109F), in a 10 year old girl (consanguineous, parents were first cousins) with profound sensorineural hearing loss (SNHL) associated with incomplete partition type I anomaly of the cochlea. This variant is absent in the gnomAD v2.1.1. In vitro studies indicated instability, shorter half-life of the protein compared to wildtype. Embryonic knockout mouse showed shortened and malformed cochleae, in addition to altered shape of hair cells with innervation and planar cell polarity defects. Homozygous knockout mice do not survive. (Bademci, G. et al. (2019); PMID: 30561639).
This gene has also been reported in association with other anomalies including cleft lip, cleft palate, brain anomalies, intestine anomalies, and eye anomalies. Eye anomalies include anterior segment dysgenesis, as shown in mice with variant, W174R, affecting the Fox domain. Homozygote mice do not survive. (McKeone, R. et al. (2011); PMID: 22022403).
Sources: Literature
Mendeliome v0.2607 COL13A1 Zornitza Stark Gene: col13a1 has been classified as Green List (High Evidence).
Mendeliome v0.2604 KIAA1161 Zornitza Stark Phenotypes for gene: KIAA1161 were changed from Basal ganglia calcification, idiopathic, 7, autosomal recessive; OMIM #618317 to Basal ganglia calcification, idiopathic, 7, autosomal recessive; OMIM #618317; primary familial brain calcifications (PFBC); ataxia; dysarthria; cerebellar atrophy; akinetic-hypertonic syndrome
Mendeliome v0.2602 KIAA1161 Hazel Phillimore reviewed gene: KIAA1161: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29910000, 31009047; Phenotypes: Basal ganglia calcification, idiopathic, 7, autosomal recessive (OMIM #618317), primary familial brain calcifications (PFBC), ataxia, dysarthria, cerebellar atrophy, akinetic-hypertonic syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2602 CACNB4 Zornitza Stark edited their review of gene: CACNB4: Added comment: PMID 32176688: A homozygous missense variant (Leu126Pro) reported in two siblings with intellectual disability, psychomotor retardation, blindness, epilepsy, movement disorder and cerebellar atrophy. Some functional data.; Changed publications: 10762541, 9628818, 27003325, 32176688; Changed phenotypes: Episodic ataxia, type 5, MIM#613855, Intellectual disability, Epilepsy, Movement disorder
Mendeliome v0.2602 WDR83OS Zornitza Stark Gene: wdr83os has been classified as Red List (Low Evidence).
Mendeliome v0.2601 WDR83OS Zornitza Stark Classified gene: WDR83OS as Red List (low evidence)
Mendeliome v0.2601 WDR83OS Zornitza Stark Gene: wdr83os has been classified as Red List (Low Evidence).
Mendeliome v0.2600 LSR Zornitza Stark Gene: lsr has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2599 LSR Zornitza Stark Classified gene: LSR as Amber List (moderate evidence)
Mendeliome v0.2599 LSR Zornitza Stark Gene: lsr has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2598 WDR83OS Ee Ming Wong gene: WDR83OS was added
gene: WDR83OS was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: WDR83OS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR83OS were set to PMID: 30250217
Phenotypes for gene: WDR83OS were set to Cholestasis
Review for gene: WDR83OS was set to RED
Added comment: - 1 consanguineous family with 3 affected individuals found to carry a homozygous splice site variant in WDR83OS
- The variant results in an aberrant truncated RNA transcript as demonstrated by RT-PCR
Sources: Literature
Mendeliome v0.2598 LSR Zornitza Stark reviewed gene: LSR: Rating: AMBER; Mode of pathogenicity: None; Publications: 32303357, 30250217; Phenotypes: Cholestasis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2598 LSR Zornitza Stark Classified gene: LSR as Green List (high evidence)
Mendeliome v0.2598 LSR Zornitza Stark Gene: lsr has been classified as Green List (High Evidence).
Mendeliome v0.2597 LSR Zornitza Stark reviewed gene: LSR: Rating: GREEN; Mode of pathogenicity: None; Publications: 32303357; Phenotypes: Cholestasis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2597 LSR Zornitza Stark Classified gene: LSR as Amber List (moderate evidence)
Mendeliome v0.2597 LSR Zornitza Stark Gene: lsr has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2595 LSR Ee Ming Wong reviewed gene: LSR: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 32303357, 30250217; Phenotypes: Intrahepatic cholestasis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2595 USP53 Zornitza Stark Gene: usp53 has been classified as Green List (High Evidence).
Mendeliome v0.2595 USP53 Zornitza Stark Phenotypes for gene: USP53 were changed from Deafness to Cholestasis; deafness
Mendeliome v0.2594 USP53 Zornitza Stark Classified gene: USP53 as Green List (high evidence)
Mendeliome v0.2594 USP53 Zornitza Stark Gene: usp53 has been classified as Green List (High Evidence).
Mendeliome v0.2593 USP53 Zornitza Stark reviewed gene: USP53: Rating: GREEN; Mode of pathogenicity: None; Publications: 32124521; Phenotypes: Cholestasis, deafness; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2593 USP53 Zornitza Stark Classified gene: USP53 as Red List (low evidence)
Mendeliome v0.2593 USP53 Zornitza Stark Gene: usp53 has been classified as Red List (Low Evidence).
Mendeliome v0.2592 LSR Ee Ming Wong gene: LSR was added
gene: LSR was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LSR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LSR were set to PMID: 30250217
Phenotypes for gene: LSR were set to transient neonatal cholestasis; intellectual disability; short stature
Review for gene: LSR was set to RED
Added comment: 1 individual from 1 consanguineous family carrying a homozygous missense variant in LSR
Sources: Literature
Mendeliome v0.2592 PPM1F Zornitza Stark Gene: ppm1f has been classified as Red List (Low Evidence).
Mendeliome v0.2592 PPM1F Zornitza Stark Classified gene: PPM1F as Red List (low evidence)
Mendeliome v0.2592 PPM1F Zornitza Stark Gene: ppm1f has been classified as Red List (Low Evidence).
Mendeliome v0.2591 PPM1F Ee Ming Wong gene: PPM1F was added
gene: PPM1F was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PPM1F was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPM1F were set to PMID: 30250217
Phenotypes for gene: PPM1F were set to sclerosing cholangitis; short stature; hypothyroidism; abnormal tongue pigmentation
Review for gene: PPM1F was set to RED
Added comment: 1 consanguineous family found to carry a homozygous missense variant in PPM1F
Sources: Literature
Mendeliome v0.2591 SPEF2 Zornitza Stark Phenotypes for gene: SPEF2 were changed from Spermatogenic failure 43, MIM#618751 to Spermatogenic failure 43, MIM#618751; Spermatogenic failure 43, MIM#618751; Primary ciliary dyskinesia-like phenotype
Mendeliome v0.2589 SPEF2 Zornitza Stark reviewed gene: SPEF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31942643; Phenotypes: Spermatogenic failure 43, MIM#618751, Primary ciliary dyskinesia-like phenotype; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2589 KLC2 Zornitza Stark Gene: klc2 has been classified as Green List (High Evidence).
Mendeliome v0.2589 KLC2 Zornitza Stark Classified gene: KLC2 as Green List (high evidence)
Mendeliome v0.2589 KLC2 Zornitza Stark Gene: klc2 has been classified as Green List (High Evidence).
Mendeliome v0.2588 KLC2 Zornitza Stark gene: KLC2 was added
gene: KLC2 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: KLC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KLC2 were set to 26385635
Phenotypes for gene: KLC2 were set to Spastic paraplegia, optic atrophy, and neuropathy MIM#609541
Review for gene: KLC2 was set to GREEN
Added comment: In 73 Brazilian patients and 2 sibs of Egyptian descent with SPOAN, a homozygous 216-bp deletion in the noncoding upstream region of the KLC2 gene was identified. Only reported cause of condition is the upstream large deletion, which is not detected by whole-exome sequencing.
Sources: Expert Review
Mendeliome v0.2587 KIF12 Zornitza Stark Phenotypes for gene: KIF12 were changed from Prenatal cholestasis; High Gamma-Glutamyltransferase (GGT) to Cholestasis; High Gamma-Glutamyltransferase (GGT)
Mendeliome v0.2586 KIF12 Zornitza Stark Gene: kif12 has been classified as Green List (High Evidence).
Mendeliome v0.2585 KIF12 Zornitza Stark Classified gene: KIF12 as Green List (high evidence)
Mendeliome v0.2585 KIF12 Zornitza Stark Gene: kif12 has been classified as Green List (High Evidence).
Mendeliome v0.2584 KIF12 Zornitza Stark reviewed gene: KIF12: Rating: GREEN; Mode of pathogenicity: None; Publications: 30250217, 30976738; Phenotypes: Cholestasis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2584 ALPK1 Zornitza Stark Gene: alpk1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2584 ALPK1 Zornitza Stark Classified gene: ALPK1 as Amber List (moderate evidence)
Mendeliome v0.2584 ALPK1 Zornitza Stark Gene: alpk1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2582 LRRC32 Zornitza Stark Gene: lrrc32 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2582 LRRC32 Zornitza Stark Classified gene: LRRC32 as Amber List (moderate evidence)
Mendeliome v0.2582 LRRC32 Zornitza Stark Gene: lrrc32 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2580 KIF12 Ee Ming Wong gene: KIF12 was added
gene: KIF12 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KIF12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF12 were set to PMID: 30250217; 30976738
Phenotypes for gene: KIF12 were set to Prenatal cholestasis; High Gamma-Glutamyltransferase (GGT)
Review for gene: KIF12 was set to AMBER
gene: KIF12 was marked as current diagnostic
Added comment: > 3 unrelated families,but they are all consanguineous families
Sources: Literature
Mendeliome v0.2579 CSGALNACT1 Zornitza Stark reviewed gene: CSGALNACT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31705726, 31325655; Phenotypes: Congenital disorder of glycosylation, skeletal dysplasia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2577 RHOA Zornitza Stark Phenotypes for gene: RHOA were changed from normal cognition; leukoencephalopathy; micro-ophthalmia; strabismus; linear hypopigmentation; malar hypoplasia; downslanting palpebral fissures; microstomia to normal cognition; leukoencephalopathy; micro-ophthalmia; strabismus; linear hypopigmentation; malar hypoplasia; downslanting palpebral fissures; microstomia; dental anomalies; body asymmetry; limb length discrepancy
Mendeliome v0.2575 IQCE Zornitza Stark Gene: iqce has been classified as Green List (High Evidence).
Mendeliome v0.2575 IQCE Zornitza Stark Classified gene: IQCE as Green List (high evidence)
Mendeliome v0.2575 IQCE Zornitza Stark Gene: iqce has been classified as Green List (High Evidence).
Mendeliome v0.2574 IQCE Zornitza Stark gene: IQCE was added
gene: IQCE was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: IQCE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IQCE were set to 31549751; 28488682
Phenotypes for gene: IQCE were set to Postaxial polydactyly
Review for gene: IQCE was set to GREEN
Added comment: Four families reported with bi-allelic variants in this gene. The c.895_904del (p.Val301Serfs*8) was found in three of the families without sharing a common haplotype, suggesting a recurrent mechanism. RNA expression analysis on patients’ fibroblasts showed that the dysfunction of IQCE leads to the dysregulation of genes associated with the hedgehog‐signaling pathway, and zebrafish experiments demonstrated a full spectrum of phenotypes linked to defective cilia: Body curvature, kidney cysts, left–right asymmetry, misdirected cilia in the pronephric duct, and retinal defects.
Sources: Literature
Mendeliome v0.2573 NKX2-3 Zornitza Stark Gene: nkx2-3 has been classified as Red List (Low Evidence).
Mendeliome v0.2573 NKX2-3 Zornitza Stark gene: NKX2-3 was added
gene: NKX2-3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NKX2-3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NKX2-3 were set to 31498527
Phenotypes for gene: NKX2-3 were set to Intestinal varicosities
Review for gene: NKX2-3 was set to RED
Added comment: Single multiplex family where truncating variant in this gene segregated with intestinal varicosities with a LOD score of 3.3. NKX2‐3 is a component of a molecular pathway underlying spleen and gut vasculature development in mice.
Sources: Literature
Mendeliome v0.2572 RPSA Zornitza Stark Gene: rpsa has been classified as Green List (High Evidence).
Mendeliome v0.2569 TBX6 Zornitza Stark Phenotypes for gene: TBX6 were changed from to Skeletal dysplasia; spondylocostal dysostosis; congenital scoliosis
Mendeliome v0.2567 CRAT Zornitza Stark Gene: crat has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2567 CRAT Zornitza Stark Classified gene: CRAT as Amber List (moderate evidence)
Mendeliome v0.2567 CRAT Zornitza Stark Gene: crat has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2565 CWF19L1 Zornitza Stark Gene: cwf19l1 has been classified as Green List (High Evidence).
Mendeliome v0.2565 CWF19L1 Zornitza Stark Phenotypes for gene: CWF19L1 were changed from to Spinocerebellar ataxia, autosomal recessive 17, MIM#616127; intellectual disability, developmental delay
Mendeliome v0.2562 CWF19L1 Zornitza Stark reviewed gene: CWF19L1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25361784, 15981765, 26197978, 27016154, 30167849; Phenotypes: Spinocerebellar ataxia, autosomal recessive 17, MIM#616127, intellectual disability, developmental delay; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2562 B4GAT1 Zornitza Stark Classified gene: B4GAT1 as Green List (high evidence)
Mendeliome v0.2562 B4GAT1 Zornitza Stark Gene: b4gat1 has been classified as Green List (High Evidence).
Mendeliome v0.2561 B4GAT1 Zornitza Stark Gene: b4gat1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2558 B4GAT1 Zornitza Stark Classified gene: B4GAT1 as Amber List (moderate evidence)
Mendeliome v0.2558 B4GAT1 Zornitza Stark Gene: b4gat1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2557 RSRC1 Zornitza Stark Classified gene: RSRC1 as Green List (high evidence)
Mendeliome v0.2557 RSRC1 Zornitza Stark Gene: rsrc1 has been classified as Green List (High Evidence).
Mendeliome v0.2556 THG1L Zornitza Stark edited their review of gene: THG1L: Changed rating: GREEN; Changed phenotypes: Spinocerebellar ataxia, autosomal recessive 28, MIM# 618800
Mendeliome v0.2556 THG1L Zornitza Stark Gene: thg1l has been classified as Green List (High Evidence).
Mendeliome v0.2556 THG1L Zornitza Stark Classified gene: THG1L as Green List (high evidence)
Mendeliome v0.2556 THG1L Zornitza Stark Gene: thg1l has been classified as Green List (High Evidence).
Mendeliome v0.2555 THG1L Zornitza Stark Classified gene: THG1L as Amber List (moderate evidence)
Mendeliome v0.2555 THG1L Zornitza Stark Gene: thg1l has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2554 THG1L Zornitza Stark gene: THG1L was added
gene: THG1L was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: THG1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: THG1L were set to 27307223; 31168944; 30214071
Phenotypes for gene: THG1L were set to Spinocerebellar ataxia, autosomal recessive 28, MIM# 618800
Review for gene: THG1L was set to AMBER
Added comment: Five individuals from two Ashkenazi Jewish families with same homozygous missense variant, and another family ascertained through a large microcephaly cohort, also with SCA.
Sources: Literature
Mendeliome v0.2553 TRPV1 Zornitza Stark Gene: trpv1 has been classified as Red List (Low Evidence).
Mendeliome v0.2552 ZP2 Zornitza Stark Gene: zp2 has been classified as Green List (High Evidence).
Mendeliome v0.2552 ZP2 Zornitza Stark Classified gene: ZP2 as Green List (high evidence)
Mendeliome v0.2552 ZP2 Zornitza Stark Gene: zp2 has been classified as Green List (High Evidence).
Mendeliome v0.2550 RSRC1 Zornitza Stark edited their review of gene: RSRC1: Added comment: 17 additional individuals reported.; Changed rating: GREEN; Changed publications: 28640246, 29522154, 32227164; Changed phenotypes: Intellectual developmental disorder, autosomal recessive 70, MIM# 618402
Mendeliome v0.2550 GAD1 Zornitza Stark Classified gene: GAD1 as Green List (high evidence)
Mendeliome v0.2550 GAD1 Zornitza Stark Gene: gad1 has been classified as Green List (High Evidence).
Mendeliome v0.2549 GAD1 Zornitza Stark changed review comment from: Single family reported with bi-allelic variants. Association studies linking with neuropsychiatric issues.; to: Single family reported with bi-allelic variants and CP phenotype. Association studies linking with neuropsychiatric issues.
Mendeliome v0.2549 GAD1 Zornitza Stark edited their review of gene: GAD1: Added comment: 2020: 11 individuals from 6 consanguineous families reported with bi-allelic LOF variant and a developmental/epileptic encephalopathy. Seizure onset occurred in the first 2 months of life in all. All 10 individuals, from whom early disease history was available, presented with seizure onset in the first month of life, mainly consisting of epileptic spasms or myoclonic seizures. Early EEG showed suppression-burst or pattern of burst attenuation or hypsarrhythmia if only recorded in the post-neonatal period. Eight individuals had joint contractures and/or pes equinovarus. Seven presented a cleft palate and two also had an omphalocele, reproducing the phenotype of the knockout Gad1−/− mouse model. Four individuals died before 4 years of age.; Changed rating: GREEN; Changed publications: 15571623, 32282878; Changed phenotypes: Cerebral palsy, spastic quadriplegic, 1, MIM#603513, Developmental and epileptic encephalopathy
Mendeliome v0.2549 GALNT2 Zornitza Stark Classified gene: GALNT2 as Green List (high evidence)
Mendeliome v0.2549 GALNT2 Zornitza Stark Gene: galnt2 has been classified as Green List (High Evidence).
Mendeliome v0.2548 GALNT2 Zornitza Stark gene: GALNT2 was added
gene: GALNT2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GALNT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GALNT2 were set to 32293671
Phenotypes for gene: GALNT2 were set to Congenital disorder of glycosylation
Review for gene: GALNT2 was set to GREEN
Added comment: Seven individuals from four families reported with bi-allelic LOF variants and global developmental delay, intellectual disability with language deficit, autistic features, behavioural abnormalities, epilepsy, chronic insomnia, white matter changes on brain MRI, dysmorphic features, decreased stature, and decreased high density lipoprotein cholesterol levels. Rodent (mouse and rat) models of GALNT2-CDG recapitulated much of the human phenotype, including poor growth and neurodevelopmental abnormalities.
Sources: Literature
Mendeliome v0.2547 C7orf43 Zornitza Stark Gene: c7orf43 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2547 C7orf43 Zornitza Stark Classified gene: C7orf43 as Amber List (moderate evidence)
Mendeliome v0.2547 C7orf43 Zornitza Stark Gene: c7orf43 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2546 C7orf43 Zornitza Stark gene: C7orf43 was added
gene: C7orf43 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: C7orf43 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C7orf43 were set to 30715179
Phenotypes for gene: C7orf43 were set to Microcephaly 25, primary, autosomal recessive, MIM# 618351
Review for gene: C7orf43 was set to AMBER
Added comment: Single family reported: three affected siblings with homozygous truncating variant. Supportive zebrafish model.
Sources: Literature
Mendeliome v0.2543 GRIN2A Zornitza Stark Gene: grin2a has been classified as Green List (High Evidence).
Mendeliome v0.2539 TSEN34 Zornitza Stark Gene: tsen34 has been classified as Red List (Low Evidence).
Mendeliome v0.2539 TSEN34 Zornitza Stark Phenotypes for gene: TSEN34 were changed from to Pontocerebellar hypoplasia type 2C, MIM# 612390
Mendeliome v0.2536 TSEN34 Zornitza Stark Classified gene: TSEN34 as Red List (low evidence)
Mendeliome v0.2536 TSEN34 Zornitza Stark Gene: tsen34 has been classified as Red List (Low Evidence).
Mendeliome v0.2535 TSEN34 Zornitza Stark reviewed gene: TSEN34: Rating: RED; Mode of pathogenicity: None; Publications: 18711368; Phenotypes: Pontocerebellar hypoplasia type 2C, MIM# 612390; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2535 TSEN54 Zornitza Stark Gene: tsen54 has been classified as Green List (High Evidence).
Mendeliome v0.2535 TSEN54 Zornitza Stark Phenotypes for gene: TSEN54 were changed from to Pontocerebellar hypoplasia type 2A 277470; Pontocerebellar hypoplasia type 4 225753; Ataxia
Mendeliome v0.2532 TSEN54 Zornitza Stark reviewed gene: TSEN54: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pontocerebellar hypoplasia type 2A 277470, Pontocerebellar hypoplasia type 4 225753, Ataxia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2530 TMPRSS9 Zornitza Stark Gene: tmprss9 has been classified as Red List (Low Evidence).
Mendeliome v0.2530 SLC6A6 Zornitza Stark Gene: slc6a6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2526 NDE1 Zornitza Stark Gene: nde1 has been classified as Green List (High Evidence).
Mendeliome v0.2523 CDC45 Zornitza Stark Gene: cdc45 has been classified as Green List (High Evidence).
Mendeliome v0.2519 CPSF1 Zornitza Stark Gene: cpsf1 has been classified as Green List (High Evidence).
Mendeliome v0.2519 CPSF1 Zornitza Stark Classified gene: CPSF1 as Green List (high evidence)
Mendeliome v0.2519 CPSF1 Zornitza Stark Gene: cpsf1 has been classified as Green List (High Evidence).
Mendeliome v0.2518 CHD4 Zornitza Stark Gene: chd4 has been classified as Green List (High Evidence).
Mendeliome v0.2518 CHD4 Zornitza Stark Phenotypes for gene: CHD4 were changed from to Sifrim-Hitz-Weiss syndrome, MIM 617159
Mendeliome v0.2512 CFAP69 Zornitza Stark Gene: cfap69 has been classified as Green List (High Evidence).
Mendeliome v0.2509 ABCA4 Zornitza Stark Gene: abca4 has been classified as Green List (High Evidence).
Mendeliome v0.2506 TLK2 Zornitza Stark Gene: tlk2 has been classified as Green List (High Evidence).
Mendeliome v0.2503 DYRK1A Zornitza Stark Gene: dyrk1a has been classified as Green List (High Evidence).
Mendeliome v0.2500 WARS Zornitza Stark Gene: wars has been classified as Green List (High Evidence).
Mendeliome v0.2500 WARS Zornitza Stark Classified gene: WARS as Green List (high evidence)
Mendeliome v0.2500 WARS Zornitza Stark Gene: wars has been classified as Green List (High Evidence).
Mendeliome v0.2498 POLR1B Zornitza Stark Gene: polr1b has been classified as Green List (High Evidence).
Mendeliome v0.2498 POLR1B Zornitza Stark Phenotypes for gene: POLR1B were changed from bilateral malar and mandibular hypoplasia; microtia; coloboma; downslanting palpebral fissures; conductive deafness; cleft palate; heart malformations to Treacher-Collins syndrome
Mendeliome v0.2497 POLR1B Zornitza Stark Classified gene: POLR1B as Green List (high evidence)
Mendeliome v0.2497 POLR1B Zornitza Stark Gene: polr1b has been classified as Green List (High Evidence).
Mendeliome v0.2496 POLR1B Zornitza Stark changed review comment from: Five unrelated families and a zebrafish model.; to: Five unrelated families and a zebrafish model. Note four of the families had missense variants affecting same residue, p.Arg1003
Mendeliome v0.2496 POLR1B Zornitza Stark changed review comment from: Six unrelated families and a zebrafish model.; to: Five unrelated families and a zebrafish model.
Mendeliome v0.2496 SLC35D1 Zornitza Stark Gene: slc35d1 has been classified as Green List (High Evidence).
Mendeliome v0.2496 SLC35D1 Zornitza Stark Phenotypes for gene: SLC35D1 were changed from to Schneckenbecken dysplasia, MIM 269250
Mendeliome v0.2493 C1orf194 Zornitza Stark Gene: c1orf194 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2492 C1orf194 Zornitza Stark Classified gene: C1orf194 as Amber List (moderate evidence)
Mendeliome v0.2492 C1orf194 Zornitza Stark Gene: c1orf194 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2491 REC114 Zornitza Stark Gene: rec114 has been classified as Green List (High Evidence).
Mendeliome v0.2491 REC114 Zornitza Stark Classified gene: REC114 as Green List (high evidence)
Mendeliome v0.2491 REC114 Zornitza Stark Gene: rec114 has been classified as Green List (High Evidence).
Mendeliome v0.2490 UBA2 Zornitza Stark Gene: uba2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2490 UBA2 Zornitza Stark Classified gene: UBA2 as Amber List (moderate evidence)
Mendeliome v0.2490 UBA2 Zornitza Stark Gene: uba2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2489 STIM1 Zornitza Stark Gene: stim1 has been classified as Green List (High Evidence).
Mendeliome v0.2485 ORAI1 Zornitza Stark Gene: orai1 has been classified as Green List (High Evidence).
Mendeliome v0.2481 RTTN Zornitza Stark Gene: rttn has been classified as Green List (High Evidence).
Mendeliome v0.2478 UBAP1 Zornitza Stark Gene: ubap1 has been classified as Green List (High Evidence).
Mendeliome v0.2475 SLC6A6 Zornitza Stark Classified gene: SLC6A6 as Amber List (moderate evidence)
Mendeliome v0.2475 SLC6A6 Zornitza Stark Gene: slc6a6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2473 TMPRSS9 Zornitza Stark Classified gene: TMPRSS9 as Red List (low evidence)
Mendeliome v0.2473 TMPRSS9 Zornitza Stark Gene: tmprss9 has been classified as Red List (Low Evidence).
Mendeliome v0.2472 MCAT Zornitza Stark Gene: mcat has been classified as Red List (Low Evidence).
Mendeliome v0.2472 MCAT Zornitza Stark Classified gene: MCAT as Red List (low evidence)
Mendeliome v0.2472 MCAT Zornitza Stark Gene: mcat has been classified as Red List (Low Evidence).
Mendeliome v0.2471 ABCC1 Zornitza Stark Gene: abcc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2471 ABCC1 Zornitza Stark Classified gene: ABCC1 as Amber List (moderate evidence)
Mendeliome v0.2471 ABCC1 Zornitza Stark Gene: abcc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2469 GABRA1 Zornitza Stark Gene: gabra1 has been classified as Green List (High Evidence).
Mendeliome v0.2466 SIGMAR1 Zornitza Stark Marked gene: SIGMAR1 as ready
Mendeliome v0.2466 SIGMAR1 Zornitza Stark Gene: sigmar1 has been classified as Green List (High Evidence).
Mendeliome v0.2466 SIGMAR1 Zornitza Stark Phenotypes for gene: SIGMAR1 were changed from to Amyotrophic lateral sclerosis 16, juvenile 614373; ?Spinal muscular atrophy, distal, autosomal recessive, 2 605726; distal hereditary motor neuropathy of Jerash type (HMNJ)
Mendeliome v0.2465 SIGMAR1 Zornitza Stark Publications for gene: SIGMAR1 were set to
Mendeliome v0.2464 SIGMAR1 Zornitza Stark Mode of inheritance for gene: SIGMAR1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2463 ATOH7 Zornitza Stark Gene: atoh7 has been classified as Green List (High Evidence).
Mendeliome v0.2463 ATOH7 Zornitza Stark Phenotypes for gene: ATOH7 were changed from to Persistent hyperplastic primary vitreous, autosomal recessive, MIM# 221900; microphthalmia; cataract; glaucoma; congenital retinal nonattachment
Mendeliome v0.2460 GNAI2 Zornitza Stark Classified gene: GNAI2 as Amber List (moderate evidence)
Mendeliome v0.2460 GNAI2 Zornitza Stark Gene: gnai2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2459 GNAI2 Zornitza Stark Gene: gnai2 has been classified as Red List (Low Evidence).
Mendeliome v0.2459 GNAI2 Zornitza Stark Classified gene: GNAI2 as Red List (low evidence)
Mendeliome v0.2459 GNAI2 Zornitza Stark Gene: gnai2 has been classified as Red List (Low Evidence).
Mendeliome v0.2458 KLHL24 Zornitza Stark Phenotypes for gene: KLHL24 were changed from Epidermolysis bullosa simplex, generalized, with scarring and hair loss OMIM#617294; dilated cardiomyopathy to Epidermolysis bullosa simplex, generalized, with scarring and hair loss OMIM#617294; dilated cardiomyopathy; Hypertrophic cardiomyopathy
Mendeliome v0.2455 FEM1B Zornitza Stark Gene: fem1b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2454 FEM1B Zornitza Stark Classified gene: FEM1B as Amber List (moderate evidence)
Mendeliome v0.2454 FEM1B Zornitza Stark Gene: fem1b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2453 WIPI2 Zornitza Stark Classified gene: WIPI2 as Red List (low evidence)
Mendeliome v0.2453 WIPI2 Zornitza Stark Gene: wipi2 has been classified as Red List (Low Evidence).
Mendeliome v0.2452 SEC31A Zornitza Stark Gene: sec31a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2451 SEC31A Zornitza Stark Classified gene: SEC31A as Amber List (moderate evidence)
Mendeliome v0.2451 SEC31A Zornitza Stark Gene: sec31a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2450 SLC44A1 Zornitza Stark Gene: slc44a1 has been classified as Green List (High Evidence).
Mendeliome v0.2450 SLC44A1 Zornitza Stark Classified gene: SLC44A1 as Green List (high evidence)
Mendeliome v0.2450 SLC44A1 Zornitza Stark Gene: slc44a1 has been classified as Green List (High Evidence).
Mendeliome v0.2449 SMCHD1 Zornitza Stark Added comment: Comment when marking as ready: Note association with FSHD2 is postulated to have digenic inheritance, caused by the combination of a heterozygous mutation in the SMCHD1 gene (614982) on chromosome 18p and presence of a haplotype on chromosome 4 that is permissive for DUX4 (606009) expression.
Mendeliome v0.2449 SMCHD1 Zornitza Stark Gene: smchd1 has been classified as Green List (High Evidence).
Mendeliome v0.2446 CDKL5 Zornitza Stark Gene: cdkl5 has been classified as Green List (High Evidence).
Mendeliome v0.2443 AEBP1 Zornitza Stark Gene: aebp1 has been classified as Green List (High Evidence).
Mendeliome v0.2443 AEBP1 Zornitza Stark Phenotypes for gene: AEBP1 were changed from to Ehlers-Danlos syndrome, classic-like, 2, MIM# 618000
Mendeliome v0.2440 AEBP1 Zornitza Stark reviewed gene: AEBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29606302, 30668708, 30548383, 30759870; Phenotypes: Ehlers-Danlos syndrome, classic-like, 2, MIM# 618000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2440 SLC6A6 Chern Lim gene: SLC6A6 was added
gene: SLC6A6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC6A6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC6A6 were set to 31345061; 31903486; 29886034
Phenotypes for gene: SLC6A6 were set to Early retinal degeneration; cardiomyopathy
Review for gene: SLC6A6 was set to AMBER
Added comment: Different homozygous missense variants in 2 unrelated consanguineous families with early retinal degeneration, some functional studies. Patients in one of the families also had cardiomyopathy. (PMIDs: 31345061, 31903486)

One dilated cardiomyopathy patient with a homozygous deletion at a splice site (PMID: 29886034).
Sources: Literature
Mendeliome v0.2440 TMPRSS9 Chern Lim gene: TMPRSS9 was added
gene: TMPRSS9 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TMPRSS9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMPRSS9 were set to 31943016
Phenotypes for gene: TMPRSS9 were set to autism spectrum disorder
Review for gene: TMPRSS9 was set to RED
Added comment: Association with Mendelian disease not established.

Is a candidate gene for autism spectrum disorder: single patient, compound heterozygous nonsense variants. Functional studies showed Tmprss9 gene is expressed in mouse brain, knockout mice had decreased social interest and social recognition. (PMID: 31943016)
Sources: Literature
Mendeliome v0.2440 MCAT Chern Lim gene: MCAT was added
gene: MCAT was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MCAT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCAT were set to 31915829
Phenotypes for gene: MCAT were set to progressive autosomal recessive optic neuropathy
Review for gene: MCAT was set to RED
Added comment: One family reported - a consanguineous family, two homozygous missense variants in both affected siblings. Functional studies showed both missense together have synergic impact on MCAT protein misfolding; p.(L81R) had more impact on MCAT protein expression reduction than did the p.(R212W); some study in conditional knockout mice. (PMID:31915829)
Sources: Literature
Mendeliome v0.2440 ATOH7 Paul De Fazio changed review comment from: Segregates with disease in 3 consanguineous families from Pakistan/Turkey and one non-consanguineous family of Swiss origin. Functional effect was demonstrated in the latter family. The mouse homolog is required for retinal ganglion cell and optic nerve formation.; to: Segregates with disease in 3 consanguineous families from Pakistan/Turkey with global eye abnormalities, and one non-consanguineous family of Swiss origin with optic nerve hypoplasia. Functional effect was demonstrated in the latter family. The mouse homolog is required for retinal ganglion cell and optic nerve formation (in mice).
Mendeliome v0.2440 GFAP Paul De Fazio changed review comment from: Many (>20) de novo individuals described with Alexander disease. Three forms of disease are described with decreasing severity: infant-onset, juveline-onset, and adult-onset. Later-onset cases are more phenotypically heterogeneous.; to: Many (>10) de novo individuals described with Alexander disease. Three forms of disease are described with decreasing severity: infant-onset, juveline-onset, and adult-onset. Later-onset cases are more phenotypically heterogeneous.
Mendeliome v0.2440 GFAP Paul De Fazio changed review comment from: Many (>10) de novo individuals described with Alexander disease. Three forms of disease are described with decreasing severity: infant-onset, juveline-onset, and adult-onset. Later-onset cases are more phenotypically heterogeneous.; to: Many (>20) de novo individuals described with Alexander disease. Three forms of disease are described with decreasing severity: infant-onset, juveline-onset, and adult-onset. Later-onset cases are more phenotypically heterogeneous.
Mendeliome v0.2440 PKDCC Paul De Fazio changed review comment from: 2 ("apparently") unrelated individuals with homozygous LoF (1x nonsense, 1x canonical splice) variants reported. Their phenotype is similar to knockout mice.
Sources: Literature; to: 2 apparently unrelated individuals with homozygous LoF (1x nonsense, 1x canonical splice) variants reported. Their phenotype is similar to knockout mice.
Sources: Literature
Mendeliome v0.2440 ORAI1 Natalie Tan changed review comment from: PMID 31448844 (comprehensive review, summarises all published cases, references functional evidence):
- Dominant ORAI1 missense variants via a GOF mechanism cause a spectrum of myopathy covering tubular aggregate myopathy/TAM and Stormorken syndrome/STRMK (slowly progressive muscle weakness with variable multisystemic disease including non-specific dysmorphism, a/hyposplenia, ichthyosis, cytopenias)
- Recessive ORAI1 variants via a LOF mechanism cause a combined immunodeficiency (recurrent and chronic infections, autoimmunity, ectodermal dysplasia, non-progressive myopathy); to: PMID 31448844 (comprehensive review, summarises all published cases, references functional evidence):
- Dominant ORAI1 missense variants via a GOF mechanism cause a slowly progressive myopathy (tubular aggregate myopathy/TAM)
- Recessive ORAI1 variants via a LOF mechanism cause a combined immunodeficiency (recurrent and chronic infections, autoimmunity, ectodermal dysplasia, non-progressive myopathy)
Mendeliome v0.2440 UBA2 Elena Savva gene: UBA2 was added
gene: UBA2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: UBA2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: UBA2 were set to PMID: 31332306; 31587267
Phenotypes for gene: UBA2 were set to Split-Hand/Foot Malformation; Aplasia Cutis Congenita; Ectrodactyly
Penetrance for gene: UBA2 were set to unknown
Review for gene: UBA2 was set to AMBER
Added comment: No OMIM phenotype

PMID: 31332306 - a single patient with a de novo PTC and split hand/foot malformation (SHFM). Additional two multigenic CNVs including this gene in patients with SHFM and ectrodactyly. Authors mention an additional de novo missense but the patient didnt have SHFM, argue low penetrance

PMID: 31587267 - a mother and son with aplasia cutis congenita (ACC), with a heterozygous PTC. Son also has ectrodactyly. Authors note an additional de novo missense in a patient with ACC.
Sources: Literature
Mendeliome v0.2440 ORAI1 Natalie Tan changed review comment from: PMID 31448844 (comprehensive review, summarises all published cases, references functional evidence):
- Dominant ORAI1 missense variants via a GOF mechanism cause a spectrum of myopathy covering tubular aggregate myopathy/TAM and Stormorken syndrome/STRMK (slowly progressive muscle weakness with variable multisystemic disease including non-specific dysmorphism, a/hyposplenia, ichthyosis, cytopenias)
- Recessive ORAI1 variants via a LOF mechanism cause a combined immunodeficiency (recurrent and chronic infections, autoimmunity, ectodermal dysplasia, non-progressive myopathy); to: PMID 31448844 (comprehensive review, summarises all published cases, references functional evidence):
- Dominant ORAI1 missense variants via a GOF mechanism cause a spectrum of myopathy covering tubular aggregate myopathy/TAM and Stormorken syndrome/STRMK (slowly progressive muscle weakness with variable multisystemic disease including non-specific dysmorphism, a/hyposplenia, ichthyosis, cytopenias)
- Recessive ORAI1 variants via a LOF mechanism cause a combined immunodeficiency (recurrent and chronic infections, autoimmunity, ectodermal dysplasia, non-progressive myopathy)
Mendeliome v0.2440 ORAI1 Natalie Tan reviewed gene: ORAI1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 31448844; Phenotypes: Progressive myopathy, contractures; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.2440 GSX2 Zornitza Stark Added comment: Comment when marking as ready: Intellectual disability, spastic tetraparesis, dystonia
Mendeliome v0.2440 GSX2 Zornitza Stark Gene: gsx2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2440 GSX2 Zornitza Stark Gene: gsx2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2440 GSX2 Zornitza Stark Classified gene: GSX2 as Amber List (moderate evidence)
Mendeliome v0.2440 GSX2 Zornitza Stark Gene: gsx2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2439 SLC35D1 Teresa Zhao reviewed gene: SLC35D1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31423530, 19508970; Phenotypes: Schneckenbecken dysplasia, MIM 269250; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.2439 POLR1B Paul De Fazio gene: POLR1B was added
gene: POLR1B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: POLR1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POLR1B were set to 31649276
Phenotypes for gene: POLR1B were set to bilateral malar and mandibular hypoplasia; microtia; coloboma; downslanting palpebral fissures; conductive deafness; cleft palate; heart malformations
Review for gene: POLR1B was set to AMBER
gene: POLR1B was marked as current diagnostic
Added comment: 6 individuals with Treacher-Collins syndrome described: 3 with de novo variants, one inherited from a mosaic father, and two inherited from affected mothers. Knockdown in zebrafish mimics the phenotype.
Sources: Literature
Mendeliome v0.2439 CREB3L1 Zornitza Stark Gene: creb3l1 has been classified as Green List (High Evidence).
Mendeliome v0.2439 CREB3L1 Zornitza Stark Phenotypes for gene: CREB3L1 were changed from to Osteogenesis imperfecta, type XVI, MIM#616229
Mendeliome v0.2436 WARS Naomi Baker gene: WARS was added
gene: WARS was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: WARS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WARS were set to PMID: 28369220; 31321409; 31069783.
Phenotypes for gene: WARS were set to Neuronopathy, distal hereditary motor, type IX (OMIM:617721); juvenile to adult onset (15-23 years); distal wasting; distal weakness; length-dependent motor axonal degeneration
Review for gene: WARS was set to GREEN
Added comment: 14 patients from five families were reported to have WARS-related neuropathy across three publications. Expression studies of mutant demonstrated decreased protein when compared to wild-type.
Sources: Literature
Mendeliome v0.2436 ACKR3 Zornitza Stark Gene: ackr3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2436 ACKR3 Zornitza Stark Phenotypes for gene: ACKR3 were changed from Oculomotor synkinesis to Oculomotor synkinesis; Ptosis
Mendeliome v0.2435 ACKR3 Zornitza Stark Classified gene: ACKR3 as Amber List (moderate evidence)
Mendeliome v0.2435 ACKR3 Zornitza Stark Gene: ackr3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2434 CYLD Zornitza Stark Gene: cyld has been classified as Green List (High Evidence).
Mendeliome v0.2434 CYLD Zornitza Stark Phenotypes for gene: CYLD were changed from to Brooke-Spiegler syndrome, 605041; Cylindromatosis, familial, 132700; Trichoepithelioma, multiple familial, 1, 601606; Frontotemporal dementia and amyotrophic lateral sclerosis
Mendeliome v0.2431 PCDH19 Zornitza Stark Gene: pcdh19 has been classified as Green List (High Evidence).
Mendeliome v0.2428 GFAP Zornitza Stark Gene: gfap has been classified as Green List (High Evidence).
Mendeliome v0.2425 COPA Zornitza Stark Gene: copa has been classified as Green List (High Evidence).
Mendeliome v0.2421 PLOD3 Alison Yeung Gene: plod3 has been classified as Green List (High Evidence).
Mendeliome v0.2421 FOXG1 Zornitza Stark Gene: foxg1 has been classified as Green List (High Evidence).
Mendeliome v0.2418 TBX6 Alison Yeung Added comment: Comment when marking as ready: Biallelic variants associated with spondylocostal dysostosis in >3 unrelated individuals
Mouse model recapitulates phenotype
Mendeliome v0.2418 TBX6 Alison Yeung Gene: tbx6 has been classified as Green List (High Evidence).
Mendeliome v0.2418 SAMD12 Zornitza Stark Gene: samd12 has been classified as Green List (High Evidence).
Mendeliome v0.2417 SAMD12 Zornitza Stark Classified gene: SAMD12 as Green List (high evidence)
Mendeliome v0.2417 SAMD12 Zornitza Stark Gene: samd12 has been classified as Green List (High Evidence).
Mendeliome v0.2416 UBE3A Alison Yeung Gene: ube3a has been classified as Green List (High Evidence).
Mendeliome v0.2416 ADAMTS19 Alison Yeung Gene: adamts19 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2416 ADAMTS19 Alison Yeung Classified gene: ADAMTS19 as Amber List (moderate evidence)
Mendeliome v0.2416 ADAMTS19 Alison Yeung Added comment: Comment on list classification: Two different homozygous variants in two consanguineous families. Animal model demonstrates cardiac phenotype
Await further reported families
Mendeliome v0.2416 ADAMTS19 Alison Yeung Gene: adamts19 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2415 YARS Zornitza Stark Gene: yars has been classified as Green List (High Evidence).
Mendeliome v0.2412 CFAP65 Zornitza Stark Gene: cfap65 has been classified as Green List (High Evidence).
Mendeliome v0.2412 CFAP65 Zornitza Stark Classified gene: CFAP65 as Green List (high evidence)
Mendeliome v0.2412 CFAP65 Zornitza Stark Gene: cfap65 has been classified as Green List (High Evidence).
Mendeliome v0.2411 CAP2 Alison Yeung Gene: cap2 has been classified as Red List (Low Evidence).
Mendeliome v0.2411 CAP2 Alison Yeung Classified gene: CAP2 as Red List (low evidence)
Mendeliome v0.2411 CAP2 Alison Yeung Added comment: Comment on list classification: Currently only one consanguineous family reported.
Knockout mouse model shows cardiomyopathy but not other clinical features reported in this family
Mendeliome v0.2411 CAP2 Alison Yeung Gene: cap2 has been classified as Red List (Low Evidence).
Mendeliome v0.2410 IGF1R Zornitza Stark Gene: igf1r has been classified as Green List (High Evidence).
Mendeliome v0.2410 IGF1R Zornitza Stark Phenotypes for gene: IGF1R were changed from to Insulin-like growth factor I, resistance to, MIM# 270450
Mendeliome v0.2407 SHANK3 Zornitza Stark Gene: shank3 has been classified as Green List (High Evidence).
Mendeliome v0.2406 CHD4 Teresa Zhao reviewed gene: CHD4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:31388190; Phenotypes: Sifrim-Hitz-Weiss syndrome, MIM 617159; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.2404 SCN1A Zornitza Stark Gene: scn1a has been classified as Green List (High Evidence).
Mendeliome v0.2401 CPSF1 Kristin Rigbye changed review comment from: 6 unrelated probands reported (3 nonsense, 1 frameshift, 1 splice, 1 missense) with variants all assumed to result in a loss of function. Variants were shown to be inherited from affected parents in 2 families. Gene-disease association was supported by knockdown of cpsf1 in zebrafish which caused abnormal ocular morphogenesis (30689892).
Sources: Literature; to: 6 unrelated probands reported (3 nonsense, 1 frameshift, 1 splice, 1 missense) with variants all assumed to result in a loss of function. Variants were shown to be inherited from affected parents in 2 families. Gene-disease association was supported by knockdown of cpsf1 in zebrafish which caused abnormal ocular morphogenesis (PMID: 30689892).
Sources: Literature
Mendeliome v0.2401 CPSF1 Kristin Rigbye gene: CPSF1 was added
gene: CPSF1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CPSF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CPSF1 were set to 30689892
Phenotypes for gene: CPSF1 were set to Myopia 27, 618827; high myopia; early-onset high myopiaHigh myopia
Review for gene: CPSF1 was set to GREEN
Added comment: 6 unrelated probands reported (3 nonsense, 1 frameshift, 1 splice, 1 missense) with variants all assumed to result in a loss of function. Variants were shown to be inherited from affected parents in 2 families. Gene-disease association was supported by knockdown of cpsf1 in zebrafish which caused abnormal ocular morphogenesis (30689892).
Sources: Literature
Mendeliome v0.2401 STXBP1 Zornitza Stark Gene: stxbp1 has been classified as Green List (High Evidence).
Mendeliome v0.2398 NAA10 Zornitza Stark Gene: naa10 has been classified as Green List (High Evidence).
Mendeliome v0.2395 WDR45 Zornitza Stark Gene: wdr45 has been classified as Green List (High Evidence).
Mendeliome v0.2395 SIGMAR1 Michelle Torres changed review comment from: PMID: 31511340:
- N167I (1 het in gnomAD): in 7 consanguinous families from region of Jordan with a specific type of distal hereditary motor neuropathy of Jerash type (HMNJ). Experiments show loss of function effect.
- Lists recent publications with other variants (missense and truncating) in patients with distal hereditary motor neuropathy (dHMN) with mild pyramidal signs and jALS (juvenile ALS); to: PMID: 31511340:
- N167I (1 het in gnomAD): in 7 consanguinous families from region of Jordan with a specific type of distal hereditary motor neuropathy of Jerash type (HMNJ). Experiments show loss of function effect.
- Lists recent publications with other variants (missense and truncating) in patients with distal hereditary motor neuropathy (dHMN) with mild pyramidal signs and jALS (juvenile ALS)
Mendeliome v0.2392 SIGMAR1 Michelle Torres reviewed gene: SIGMAR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31511340; Phenotypes: ?Amyotrophic lateral sclerosis 16, juvenile 614373, ?Spinal muscular atrophy, distal, autosomal recessive, 2 605726, distal hereditary motor neuropathy of Jerash type (HMNJ); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2392 GNAI2 Elena Savva gene: GNAI2 was added
gene: GNAI2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GNAI2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: GNAI2 were set to PMID: 31036916
Phenotypes for gene: GNAI2 were set to Pituitary adenoma, ACTH-secreting, somatic; Ventricular tachycardia, idiopathic 192605; Syndromic developmental disorder
Review for gene: GNAI2 was set to AMBER
Added comment: Papers associating this gene to tachycardia are very old (pre 2000, OMIM).

PMID: 31036916 - a single de novo patient with syndromic developmental disorder

Summary: AMBER - one report, may be a coincidental de novo finding
Sources: Literature
Mendeliome v0.2389 ASCC1 Zornitza Stark Gene: ascc1 has been classified as Green List (High Evidence).
Mendeliome v0.2386 FEM1B Elena Savva gene: FEM1B was added
gene: FEM1B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FEM1B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FEM1B were set to PMID: 31036916
Phenotypes for gene: FEM1B were set to Syndromic global developmental delay
Review for gene: FEM1B was set to AMBER
Added comment: No OMIM phenotype

PMID: 31036916 - a single de novo patient reported in a neurodevelopmental disorder cohort. Authors note another de novo case with the exact same variant (p.Arg126Gln) from the DDD study, and a 3rd patient from GeneMatcher with the same de novo missense again. Decipher shows this variant to be in a highly constrained region of the protein.

Have selected AMBER for now - not sure if GeneMatcher findings can be used as a 3rd case
Sources: Literature
Mendeliome v0.2386 SMAD2 Zornitza Stark Gene: smad2 has been classified as Green List (High Evidence).
Mendeliome v0.2384 RXFP2 Alison Yeung Classified gene: RXFP2 as Red List (low evidence)
Mendeliome v0.2384 RXFP2 Alison Yeung Added comment: Comment on list classification: Only single reported family with animal model reported. Both reviews to date are based on same publication. No new publications/reported cases since this one.
Mendeliome v0.2384 RXFP2 Alison Yeung Gene: rxfp2 has been classified as Red List (Low Evidence).
Mendeliome v0.2383 GFAP Paul De Fazio changed review comment from: Many (>10) de novo individuals described with Alexander disease. Three forms of disease are described with decreasing severity: infant-onset, juveline-onset, and adult-onset. Later-onset cases are more phenotypically heterogeneous.; to: Many (>10) de novo individuals described with Alexander disease. Three forms of disease are described with decreasing severity: infant-onset, juveline-onset, and adult-onset. Later-onset cases are more phenotypically heterogeneous.
Mendeliome v0.2383 GFAP Paul De Fazio changed review comment from: Many (>10) de novo individuals described with Alexander disease. Three forms of disease are described with decreasing severity: infant-onset, juveline-onset, and adult-onset. Later-onset cases are more phenotypically heterogeneous.; to: Many (>10) de novo individuals described with Alexander disease. Three forms of disease are described with decreasing severity: infant-onset, juveline-onset, and adult-onset. Later-onset cases are more phenotypically heterogeneous.
Mendeliome v0.2382 RXFP2 Zornitza Stark Gene: rxfp2 has been classified as Red List (Low Evidence).
Mendeliome v0.2379 RXFP2 Zornitza Stark Classified gene: RXFP2 as Red List (low evidence)
Mendeliome v0.2379 RXFP2 Zornitza Stark Gene: rxfp2 has been classified as Red List (Low Evidence).
Mendeliome v0.2378 SEC31A Hazel Phillimore gene: SEC31A was added
gene: SEC31A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SEC31A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SEC31A were set to PMID: 30464055
Phenotypes for gene: SEC31A were set to congenital neurodevelopmental syndrome; spastic paraplegia; multiple contractures; profound developmental delay; epilepsy; failure to thrive
Review for gene: SEC31A was set to AMBER
Added comment: Frameshift. c.2776_2777, TA duplication, causing predicted p.A927fs*61 truncation and predicted NMD in 2 affected siblings in consanguineous Bedouin family with severe congenital neurological syndrome with spastic paraplegia, multiple contractures, profound developmental delay and convulsions. Failure to thrive. Lethal by age 4 years. Also had hearing defect, bilateral congenital cataract, horizontal nystagmus, with flat retina and optic atrophy. Supporting functional assays from knockout drosophila.
Sources: Literature
Mendeliome v0.2378 SLC44A1 Sebastian Lunke gene: SLC44A1 was added
gene: SLC44A1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC44A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC44A1 were set to 31855247
Phenotypes for gene: SLC44A1 were set to progressive ataxia; tremor; cognitive decline; dysphagia; optic atrophy; dysarthria
Review for gene: SLC44A1 was set to GREEN
Added comment: Four affected individuals from three families with homozygous frameshift variants. Functional evidence points to impaired choline transporter function yet unchanged membrane phosphatidylcholine content. Choline treatments may be beneficial.
Sources: Literature
Mendeliome v0.2377 TBX6 Dean Phelan reviewed gene: TBX6: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30307510, 31015262; Phenotypes: congenital vertebral malformations, congenital scoliosis, spondylocostal dysostosis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.2377 GSX2 Elena Savva gene: GSX2 was added
gene: GSX2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GSX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GSX2 were set to PMID: 31412107
Phenotypes for gene: GSX2 were set to Diencephalic-mesencephalic junction dysplasia syndrome 2 618646
Review for gene: GSX2 was set to GREEN
Added comment: PMID: 31412107 - 2 unrelated patients with homozygous mutations (nonsense, missense). Functional analysis of the missense in transfected HeLa cells demonstrated protein mislocalization and protein expression. Downstream gene expression was also reduced by both mutations.

Summary: GREEN - 2 patients and functional evidence
Sources: Literature
Mendeliome v0.2377 SPEF2 Zornitza Stark Gene: spef2 has been classified as Green List (High Evidence).
Mendeliome v0.2377 SPEF2 Zornitza Stark Classified gene: SPEF2 as Green List (high evidence)
Mendeliome v0.2377 SPEF2 Zornitza Stark Gene: spef2 has been classified as Green List (High Evidence).
Mendeliome v0.2376 CREB3L1 Kristin Rigbye reviewed gene: CREB3L1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24079343, 28817112, 29936144, 30657919; Phenotypes: Osteogenesis imperfecta, type XVI, 616229; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2376 PKDCC Alison Yeung Gene: pkdcc has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2376 PKDCC Alison Yeung Classified gene: PKDCC as Amber List (moderate evidence)
Mendeliome v0.2376 PKDCC Alison Yeung Added comment: Comment on list classification: Two unrelated consanguineous families reported with different homozygous variants
Pre-existing mouse model has similar phenotype
Needs more functional evidence or further reported families
Mendeliome v0.2376 PKDCC Alison Yeung Gene: pkdcc has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2375 DHH Zornitza Stark Phenotypes for gene: DHH were changed from to 46XY partial gonadal dysgenesis, with minifascicular neuropathy, MIM# 607080
Mendeliome v0.2372 ACKR3 Elena Savva gene: ACKR3 was added
gene: ACKR3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ACKR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACKR3 were set to PMID: 3121183
Phenotypes for gene: ACKR3 were set to Oculomotor synkinesis
Review for gene: ACKR3 was set to AMBER
Added comment: No phenotype currently listed in OMIM

PMID: 3121183 - 1 family (3 siblings and a cousin) with congenital ptosis and oculomotor synkinesis. Mouse model reciprocated the phenotype. Functional assay using transfected HEK293 cells show protein mislocalization and lower binding affinity

Emerging gene-disease association
Sources: Literature
Mendeliome v0.2372 MYCN Zornitza Stark Gene: mycn has been classified as Green List (High Evidence).
Mendeliome v0.2372 CYLD Kristin Rigbye reviewed gene: CYLD: Rating: GREEN; Mode of pathogenicity: None; Publications: 10835629, 16307661, 12950348, 19807742; Phenotypes: Brooke-Spiegler syndrome, 605041, Cylindromatosis, familial, 132700, Trichoepithelioma, multiple familial, 1, 601606, Frontotemporal dementia and amyotrophic lateral sclerosis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2371 CNNM4 Zornitza Stark Gene: cnnm4 has been classified as Green List (High Evidence).
Mendeliome v0.2371 CNNM4 Zornitza Stark Phenotypes for gene: CNNM4 were changed from to Jalili syndrome 217080; amelogenesis imperfecta, cone-rod dystrophy
Mendeliome v0.2368 ATM Zornitza Stark Gene: atm has been classified as Green List (High Evidence).
Mendeliome v0.2365 SAMD12 Melanie Marty gene: SAMD12 was added
gene: SAMD12 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SAMD12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SAMD12 were set to 30194086; 29507423
Phenotypes for gene: SAMD12 were set to Epilepsy, familial adult myoclonic, 1 601068
Review for gene: SAMD12 was set to GREEN
Added comment: Repeat expansions of intronic TTTCA and TTTTA motifs within SAMD12 have been identified in over 50 Japanese and Chinese families. Most families with affected individuals were heterozygous however 4 patients from 3 families had homozygous repeat expansions, which was associated with a more severe phenotype. Western blot analysis showed decreased levels of the protein in patient brains.
Sources: Literature
Mendeliome v0.2365 FUS Elena Savva gene: FUS was added
gene: FUS was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FUS was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FUS were set to PMID: 32281455; 20668259; 20385912
Phenotypes for gene: FUS were set to Amyotrophic lateral sclerosis 6, with or without frontotemporal dementia 608030; Essential tremor, hereditary, 4 614782
Mode of pathogenicity for gene: FUS was set to Other
Review for gene: FUS was set to GREEN
Added comment: PMID: 32281455 - Reports a case of Pediatric Amyotrophic Lateral Sclerosis. Reviews and shows multiple other reports of ALS casued by FUS

PMID: 20668259 - additional reports of ALS

PMID: 20385912 - postulated that disruption of this region may disrupt subcellular distribution of FUS, in turn affecting transcription and RNA processing and conferring a toxic gain of function.
Sources: Literature
Mendeliome v0.2365 TBX6 Sarah Pantaleo reviewed gene: TBX6: Rating: GREEN; Mode of pathogenicity: None; Publications: 8954725, 20503311, 23335591, 25564734, 31015262; Phenotypes: Skeletal dysplasia, spondylocostal dysostosis, congenital scoliosis; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.2365 C9orf72 Elena Savva gene: C9orf72 was added
gene: C9orf72 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: C9orf72 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: C9orf72 were set to PMID: 30120348; 23284068
Phenotypes for gene: C9orf72 were set to Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 105550
Review for gene: C9orf72 was set to AMBER
Added comment: Possibly RED

Caused by expansion of GGGGCC repeats, dont know if these qualify for mendeliome
Sources: Literature
Mendeliome v0.2365 ELOVL1 Hazel Phillimore reviewed gene: ELOVL1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 30487246, 29496980; Phenotypes: ichthyosis, acanthosis nigricans, hypomyelination, spastic paraplegia, high frequency deafness, optic atrophy, nystagmus; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2365 TNFRSF21 Alison Yeung Gene: tnfrsf21 has been classified as Red List (Low Evidence).
Mendeliome v0.2365 TNFRSF21 Alison Yeung Classified gene: TNFRSF21 as Red List (low evidence)
Mendeliome v0.2365 TNFRSF21 Alison Yeung Added comment: Comment on list classification: Report of single family
Limited functional evidence: tissue expression studies
Mendeliome v0.2365 TNFRSF21 Alison Yeung Gene: tnfrsf21 has been classified as Red List (Low Evidence).
Mendeliome v0.2364 USP45 Alison Yeung Gene: usp45 has been classified as Green List (High Evidence).
Mendeliome v0.2364 USP45 Alison Yeung Classified gene: USP45 as Green List (high evidence)
Mendeliome v0.2364 USP45 Alison Yeung Added comment: Comment on list classification: Two unrelated families
Functional studies in animal model recapitulate retinal phenotype
Mendeliome v0.2364 USP45 Alison Yeung Gene: usp45 has been classified as Green List (High Evidence).
Mendeliome v0.2363 SYCP2 Zornitza Stark Gene: sycp2 has been classified as Green List (High Evidence).
Mendeliome v0.2363 SYCP2 Zornitza Stark Classified gene: SYCP2 as Green List (high evidence)
Mendeliome v0.2363 SYCP2 Zornitza Stark Gene: sycp2 has been classified as Green List (High Evidence).
Mendeliome v0.2362 IGF1R Michelle Torres reviewed gene: IGF1R: Rating: GREEN; Mode of pathogenicity: None; Publications: 31586944; Phenotypes: Insulin-like growth factor I, resistance to 270450; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2361 ASCC1 Sarah Pantaleo reviewed gene: ASCC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30327447, 12077347, 26924529, 31880396, 26503956; Phenotypes: Arthrogryposis, congenital bone fractures, spinal muscular atrophy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.2361 PKDCC Paul De Fazio gene: PKDCC was added
gene: PKDCC was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PKDCC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PKDCC were set to PMID:30478137; 19097194
Phenotypes for gene: PKDCC were set to Dysmorphism; shortening of extremities
Review for gene: PKDCC was set to AMBER
gene: PKDCC was marked as current diagnostic
Added comment: 2 ("apparently") unrelated individuals with homozygous LoF (1x nonsense, 1x canonical splice) variants reported. Their phenotype is similar to knockout mice.
Sources: Literature
Mendeliome v0.2361 DHH Naomi Baker reviewed gene: DHH: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31018998, 29471294, 11017805; Phenotypes: gonadal dysgenesis, minifascicular neuropathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2361 USP45 Kristin Rigbye gene: USP45 was added
gene: USP45 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: USP45 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: USP45 were set to 30573563
Phenotypes for gene: USP45 were set to Leber congenital amaurosis; retinal dystrophy
Review for gene: USP45 was set to GREEN
Added comment: 2 unrelated Chinese families reported with rare homozygous variants (one missense, one nonsense) and Leber congenital amaurosis. Animal knockout functional studies supported gene-disease association.

PMID: 30573563 "By analysing WES data based on allele frequencies of in-house controls, population allele frequencies and in silico prediction tools, two rare homozygous mutations in USP45 were identified in two unrelated families. Immunohistochemistry of USP45 in the human and zebrafish retinal sections revealed enriched expression in the inner segments of photoreceptors. The knockdown of usp45 transcript in zebrafish led to abnormal retinal development with effects on photoreceptors, which could be successfully rescued by wild-type usp45 mRNA. Moreover, targeted knockout of Usp45 in mice caused abnormal electroretinography responses, similar to that seen in patients with LCA."
Sources: Literature
Mendeliome v0.2361 CNNM4 Ain Roesley reviewed gene: CNNM4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30705057; Phenotypes: Jalili syndrome (amelogenesis imperfecta, cone-rod dystrophy); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2361 ATM Kristin Rigbye reviewed gene: ATM: Rating: GREEN; Mode of pathogenicity: None; Publications: 30819809; Phenotypes: Ataxia-telangiectasia MIM#208900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2361 BAZ2B Zornitza Stark Gene: baz2b has been classified as Green List (High Evidence).
Mendeliome v0.2361 BAZ2B Zornitza Stark Classified gene: BAZ2B as Green List (high evidence)
Mendeliome v0.2361 BAZ2B Zornitza Stark Gene: baz2b has been classified as Green List (High Evidence).
Mendeliome v0.2360 BAZ2B Zornitza Stark gene: BAZ2B was added
gene: BAZ2B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BAZ2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BAZ2B were set to 31999386; 28135719; 25363768
Phenotypes for gene: BAZ2B were set to Intellectual disability; autism
Review for gene: BAZ2B was set to GREEN
Added comment: Postulated as a candidate gene for ID/ASD by large-scale studies. Case series reports two individuals with small CNVs and and six with SNVs, mostly LoF type variants. Although the gene is generally intolerant of LoF, some LoF variants present in gnomad ?incomplete penetrance. Additional reported features were inconsistent
Sources: Literature
Mendeliome v0.2359 TPI1 Zornitza Stark Gene: tpi1 has been classified as Green List (High Evidence).
Mendeliome v0.2359 TPI1 Zornitza Stark Classified gene: TPI1 as Green List (high evidence)
Mendeliome v0.2359 TPI1 Zornitza Stark Gene: tpi1 has been classified as Green List (High Evidence).
Mendeliome v0.2357 EMG1 Zornitza Stark Gene: emg1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2357 EMG1 Zornitza Stark Classified gene: EMG1 as Amber List (moderate evidence)
Mendeliome v0.2357 EMG1 Zornitza Stark Gene: emg1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2355 EIF2AK4 Zornitza Stark Gene: eif2ak4 has been classified as Green List (High Evidence).
Mendeliome v0.2355 EIF2AK4 Zornitza Stark Classified gene: EIF2AK4 as Green List (high evidence)
Mendeliome v0.2355 EIF2AK4 Zornitza Stark Gene: eif2ak4 has been classified as Green List (High Evidence).
Mendeliome v0.2354 EIF2AK4 Zornitza Stark gene: EIF2AK4 was added
gene: EIF2AK4 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: EIF2AK4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: EIF2AK4 were set to Pulmonary venoocclusive disease 2, MIM#234810
Review for gene: EIF2AK4 was set to GREEN
Added comment: Sources: Expert list
Mendeliome v0.2353 AGBL5 Zornitza Stark Gene: agbl5 has been classified as Green List (High Evidence).
Mendeliome v0.2353 AGBL5 Zornitza Stark Classified gene: AGBL5 as Green List (high evidence)
Mendeliome v0.2353 AGBL5 Zornitza Stark Gene: agbl5 has been classified as Green List (High Evidence).
Mendeliome v0.2351 CPT1C Bryony Thompson Gene: cpt1c has been classified as Green List (High Evidence).
Mendeliome v0.2351 CPT1C Bryony Thompson Classified gene: CPT1C as Green List (high evidence)
Mendeliome v0.2351 CPT1C Bryony Thompson Gene: cpt1c has been classified as Green List (High Evidence).
Mendeliome v0.2349 ATP2B4 Bryony Thompson Gene: atp2b4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2349 ATP2B4 Bryony Thompson Classified gene: ATP2B4 as Amber List (moderate evidence)
Mendeliome v0.2349 ATP2B4 Bryony Thompson Gene: atp2b4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2345 SEC63 Zornitza Stark Gene: sec63 has been classified as Green List (High Evidence).
Mendeliome v0.2342 CYP1B1 Zornitza Stark Gene: cyp1b1 has been classified as Green List (High Evidence).
Mendeliome v0.2342 CYP1B1 Zornitza Stark Phenotypes for gene: CYP1B1 were changed from to Anterior segment dysgenesis 6, multiple subtypes, 617315; Glaucoma 3A, primary open angle, congenital, juvenile, or adult onset, 231300
Mendeliome v0.2339 DAG1 Zornitza Stark Gene: dag1 has been classified as Green List (High Evidence).
Mendeliome v0.2336 DPYD Zornitza Stark Gene: dpyd has been classified as Green List (High Evidence).
Mendeliome v0.2333 MFSD8 Zornitza Stark Gene: mfsd8 has been classified as Green List (High Evidence).
Mendeliome v0.2333 MFSD8 Zornitza Stark Phenotypes for gene: MFSD8 were changed from to Ceroid lipofuscinosis, neuronal, 7 610951; Macular dystrophy with central cone involvement 616170
Mendeliome v0.2330 NF1 Zornitza Stark Gene: nf1 has been classified as Green List (High Evidence).
Mendeliome v0.2330 NF1 Zornitza Stark Phenotypes for gene: NF1 were changed from to Leukemia, juvenile myelomonocytic 607785; Neurofibromatosis, familial spinal 162210; Neurofibromatosis, type 1 162200; Neurofibromatosis-Noonan syndrome 601321; Watson syndrome 193520
Mendeliome v0.2328 TECTA Zornitza Stark Added comment: Comment when marking as ready: Both recessive and dominant deafness associations assessed as DEFINITIVE by ClinGen.
Mendeliome v0.2328 TECTA Zornitza Stark Gene: tecta has been classified as Green List (High Evidence).
Mendeliome v0.2328 TECTA Zornitza Stark Phenotypes for gene: TECTA were changed from to Deafness, autosomal recessive 21 603629; Deafness, autosomal dominant 8/12 601543
Mendeliome v0.2323 TRAPPC9 Zornitza Stark Gene: trappc9 has been classified as Green List (High Evidence).
Mendeliome v0.2323 TRAPPC9 Zornitza Stark Phenotypes for gene: TRAPPC9 were changed from to Mental retardation, autosomal recessive 13, MIM# 613192
Mendeliome v0.2320 TRAPPC9 Zornitza Stark reviewed gene: TRAPPC9: Rating: GREEN; Mode of pathogenicity: None; Publications: 22549410, 20004765, 20004763; Phenotypes: Mental retardation, autosomal recessive 13, MIM# 613192; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2320 SOS1 Zornitza Stark Added comment: Comment when marking as ready: The association with Noonan syndrome is well established; the association with gingival fibromatosis is questionable.
Mendeliome v0.2320 SOS1 Zornitza Stark Gene: sos1 has been classified as Green List (High Evidence).
Mendeliome v0.2320 SOS1 Zornitza Stark Phenotypes for gene: SOS1 were changed from to ?Fibromatosis, gingival, 1, 135300; Noonan syndrome 4, 610733
Mendeliome v0.2316 F11 Zornitza Stark Gene: f11 has been classified as Green List (High Evidence).
Mendeliome v0.2316 F11 Zornitza Stark Phenotypes for gene: F11 were changed from to Factor XI deficiency, autosomal dominant 612416; Factor XI deficiency, autosomal recessive, MIM#612416
Mendeliome v0.2313 MED13L Zornitza Stark Gene: med13l has been classified as Green List (High Evidence).
Mendeliome v0.2313 MED13L Zornitza Stark Phenotypes for gene: MED13L were changed from to Mental retardation and distinctive facial features with or without cardiac defects 616789; Transposition of the great arteries, dextro-looped 1 608808
Mendeliome v0.2310 PROKR2 Zornitza Stark Gene: prokr2 has been classified as Green List (High Evidence).
Mendeliome v0.2310 CCT5 Bryony Thompson Classified gene: CCT5 as Amber List (moderate evidence)
Mendeliome v0.2310 CCT5 Bryony Thompson Gene: cct5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2305 MED13L Elena Savva reviewed gene: MED13L: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID 29511999; Phenotypes: Mental retardation and distinctive facial features with or without cardiac defects 616789, Transposition of the great arteries, dextro-looped 1 608808; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.2305 F11 Elena Savva reviewed gene: F11: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:18446632, 15026311; Phenotypes: Factor XI deficiency, autosomal dominant 612416, Factor XI deficiency, autosomal recessive; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2305 SOS1 Elena Savva reviewed gene: SOS1: 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: 25062969, 17143285, 17143282; Phenotypes: ?Fibromatosis, gingival, 1, 135300, Noonan syndrome 4, 610733; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.2305 XRCC1 Bryony Thompson Gene: xrcc1 has been classified as Green List (High Evidence).
Mendeliome v0.2305 XRCC1 Bryony Thompson Classified gene: XRCC1 as Green List (high evidence)
Mendeliome v0.2305 XRCC1 Bryony Thompson Gene: xrcc1 has been classified as Green List (High Evidence).
Mendeliome v0.2304 XRCC1 Bryony Thompson gene: XRCC1 was added
gene: XRCC1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: XRCC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: XRCC1 were set to 28002403; 29472272
Phenotypes for gene: XRCC1 were set to Spinocerebellar ataxia, autosomal recessive 26 MIM#617633
Review for gene: XRCC1 was set to GREEN
Added comment: Three South Asian cases (one with early adult onset and the other two with onset in childhood) reported with slowly progressive cerebellar ataxia accompanied by sensorimotor neuropathy. All with the recurrent splice variant (c.1293G>C, 2 homozygotes and a compound heterozygote). Mice with conditional deletion of the Xrcc1 gene in the brain showed cerebellar ataxia.
Sources: Expert list
Mendeliome v0.2303 TRAPPC9 Elena Savva reviewed gene: TRAPPC9: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mental retardation, autosomal recessive 13, 613192; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2303 TECTA Elena Savva reviewed gene: TECTA: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID:22718023, 17136632, 31554319, 21520338; Phenotypes: Deafness, autosomal recessive 21 603629, Deafness, autosomal dominant 8/12 601543; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.2303 NF1 Elena Savva reviewed gene: NF1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Leukemia, juvenile myelomonocytic 607785, Neurofibromatosis, familial spinal 162210, Neurofibromatosis, type 1 162200, Neurofibromatosis-Noonan syndrome 601321, Watson syndrome 193520; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.2303 TRPC3 Bryony Thompson Gene: trpc3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2303 TRPC3 Bryony Thompson Classified gene: TRPC3 as Amber List (moderate evidence)
Mendeliome v0.2303 TRPC3 Bryony Thompson Gene: trpc3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2301 MFSD8 Elena Savva reviewed gene: MFSD8: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:31006324; Phenotypes: Ceroid lipofuscinosis, neuronal, 7 610951, Macular dystrophy with central cone involvement 616170; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2301 CYP1B1 Elena Savva reviewed gene: CYP1B1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:21730847, 27243976; Phenotypes: Anterior segment dysgenesis 6, multiple subtypes, 617315, Glaucoma 3A, primary open angle, congenital, juvenile, or adult onset, 231300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2301 SLC9A1 Zornitza Stark Gene: slc9a1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2301 SLC9A1 Zornitza Stark Classified gene: SLC9A1 as Amber List (moderate evidence)
Mendeliome v0.2301 SLC9A1 Zornitza Stark Gene: slc9a1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2299 MTCL1 Bryony Thompson Gene: mtcl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2299 MTCL1 Bryony Thompson Classified gene: MTCL1 as Amber List (moderate evidence)
Mendeliome v0.2299 MTCL1 Bryony Thompson Gene: mtcl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2298 MTCL1 Bryony Thompson gene: MTCL1 was added
gene: MTCL1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: MTCL1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: MTCL1 were set to 30548255; 28283581
Phenotypes for gene: MTCL1 were set to slowly progressive cerebellar ataxia; mild intellectual disability; seizures; episodic pain; spinocerebellar ataxia
Review for gene: MTCL1 was set to AMBER
Added comment: Single case with a homozygous loss of function variant in a Polish study of early-onset cerebellar ataxia, and a single family with a single heterozygous missense (p.Val1435Met) identified in two family members with adult-onset spinocerebellar ataxia. Mtcl1 gene disruption in mice results in abnormal motor coordination with Purkinje cell degeneration
Sources: Expert list
Mendeliome v0.2297 ATG5 Bryony Thompson Classified gene: ATG5 as Amber List (moderate evidence)
Mendeliome v0.2297 ATG5 Bryony Thompson Gene: atg5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2296 ATG5 Bryony Thompson gene: ATG5 was added
gene: ATG5 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ATG5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATG5 were set to 16625204; 26812546
Phenotypes for gene: ATG5 were set to Spinocerebellar ataxia, autosomal recessive 25 MIM#617584
Review for gene: ATG5 was set to AMBER
Added comment: A homozgyous variant was identified in a single family with two affected siblings. Mice deficient for Atg5 specifically in neural cells and Atg5 null Drosophila develop progressive deficits in motor function.
Sources: Expert list
Mendeliome v0.2295 IL18BP Zornitza Stark gene: IL18BP was added
gene: IL18BP was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: IL18BP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL18BP were set to 31213488
Phenotypes for gene: IL18BP were set to {?Hepatitis, fulminant viral, susceptibility to} 618549
Review for gene: IL18BP was set to RED
Added comment: Single individual reported with homozygous 40bp deletion in this gene and fulminant Hep A hepatitis.
Sources: Expert list
Mendeliome v0.2291 IRF4 Zornitza Stark Classified gene: IRF4 as Red List (low evidence)
Mendeliome v0.2291 IRF4 Zornitza Stark Gene: irf4 has been classified as Red List (Low Evidence).
Mendeliome v0.2290 ACOX2 Zornitza Stark Added comment: Comment when marking as ready: The ACOX2 gene encodes a peroxisomal branched-chain acyl-CoA oxidase involved in bile acid synthesis.
Mendeliome v0.2290 ACOX2 Zornitza Stark Gene: acox2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2290 ACOX2 Zornitza Stark Classified gene: ACOX2 as Amber List (moderate evidence)
Mendeliome v0.2290 ACOX2 Zornitza Stark Gene: acox2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2289 ACOX2 Zornitza Stark gene: ACOX2 was added
gene: ACOX2 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: ACOX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACOX2 were set to 27647924; 27884763
Phenotypes for gene: ACOX2 were set to Bile acid synthesis defect, congenital, 6, 617308
Review for gene: ACOX2 was set to AMBER
Added comment: Two unrelated families reported.
Sources: Expert Review
Mendeliome v0.2288 LARS Zornitza Stark Gene: lars has been classified as Green List (High Evidence).
Mendeliome v0.2288 LARS Zornitza Stark Classified gene: LARS as Green List (high evidence)
Mendeliome v0.2288 LARS Zornitza Stark Gene: lars has been classified as Green List (High Evidence).
Mendeliome v0.2287 LARS Zornitza Stark gene: LARS was added
gene: LARS was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: LARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LARS were set to 28774368; 30349989; 22607940
Phenotypes for gene: LARS were set to Infantile liver failure syndrome 1, MIM# 615438
Review for gene: LARS was set to GREEN
gene: LARS was marked as current diagnostic
Added comment: Six unrelated families reported in the literature, reviewed in PMID: 30349989.
Sources: NHS GMS
Mendeliome v0.2286 KCNJ11 Zornitza Stark Gene: kcnj11 has been classified as Green List (High Evidence).
Mendeliome v0.2286 KCNJ11 Zornitza Stark Phenotypes for gene: KCNJ11 were changed from to {Diabetes mellitus, type 2, susceptibility to} 125853; Diabetes mellitus, transient neonatal, 3 610582; Diabetes, permanent neonatal, with or without neurologic features 606176; Hyperinsulinemic hypoglycemia, familial, 2 601820; Maturity-onset diabetes of the young, type 13 616329 AD
Mendeliome v0.2282 SIPA1L3 Bryony Thompson Marked gene: SIPA1L3 as ready
Mendeliome v0.2282 SIPA1L3 Bryony Thompson Gene: sipa1l3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2282 SIPA1L3 Bryony Thompson Classified gene: SIPA1L3 as Amber List (moderate evidence)
Mendeliome v0.2282 SIPA1L3 Bryony Thompson Gene: sipa1l3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2281 SIPA1L3 Bryony Thompson gene: SIPA1L3 was added
gene: SIPA1L3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SIPA1L3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SIPA1L3 were set to 28951961; 27993984; 25804400
Phenotypes for gene: SIPA1L3 were set to Cataract 45 MIM#616851
Review for gene: SIPA1L3 was set to AMBER
Added comment: A consanguineous German family segregating a homozygous nonsense mutation in two sisters with congenital cataracts (PMID: 25804400). Null Zebrafish, Xenopus and mouse models recapitulate the human cataract phenotype. A case with congenital cataracts as a feature of their condition harboured a de novo balanced chromosomal translocation, 46,XY,t(2;19)(q37.3;q13.1), where breakpoint mapping and sequencing showed a physical disruption of the 5′UTR of SIPA1L3 (PMID: 26231217). In a case with bilateral congenital cataracts a heterozygous missense (D148Y) was identified and in vitro functional assays of the variant resulted in abnormal actin morphology (PMID: 26231217).
Sources: Expert list
Mendeliome v0.2280 KCNJ11 Elena Savva edited their review of gene: KCNJ11: Added comment: Congenital hyperinsulinism (HI) variants are generally reported in heterozygous patients where they also carry a somatic 2nd hit, or have isodisomy of the paternal allele (focal HI), or in bilallelic patients (diffuse HI). This condition can be dominant (but rarely), where patients with these missense are diazoxide-responsive. Patients with recessively inherited variants are diazoxide-unresponsive (OMIM, PMID:11395395, PMID: 23275527, PMID: 23345197).

Genotype-phenotype correlation:
Permanent neonatal diabetes – GOF (OMIM)
Permanent neonatal diabetes + other features – GOF (OMIM)
Congenital hyperinsulinism – LOF (PMID:18250167).

PTCs - LOF
Missense - Loss and gain of function
LOF – cause reduce channel expression, channel activity and increase current decay (PMID:18250167)
GOF - impair ATP-based sensitivity, more open state channel (OMIM)

Mutations generally occur on the paternal allele (PMID: 23345197).; Changed publications: PMID:18250167, 11395395, 23275527, 23345197
Mendeliome v0.2280 KCNJ11 Elena Savva reviewed gene: KCNJ11: Rating: GREEN; Mode of pathogenicity: Other; Publications: ; Phenotypes: {Diabetes mellitus, type 2, susceptibility to} 125853, Diabetes mellitus, transient neonatal, 3 610582, Diabetes, permanent neonatal, with or without neurologic features 606176, Hyperinsulinemic hypoglycemia, familial, 2 601820, Maturity-onset diabetes of the young, type 13 616329 AD; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2280 SLC18A2 Zornitza Stark Gene: slc18a2 has been classified as Green List (High Evidence).
Mendeliome v0.2280 SLC18A2 Zornitza Stark Classified gene: SLC18A2 as Green List (high evidence)
Mendeliome v0.2280 SLC18A2 Zornitza Stark Gene: slc18a2 has been classified as Green List (High Evidence).
Mendeliome v0.2278 RNU4ATAC Zornitza Stark Gene: rnu4atac has been classified as Green List (High Evidence).
Mendeliome v0.2275 IFT172 Zornitza Stark Gene: ift172 has been classified as Green List (High Evidence).
Mendeliome v0.2275 IFT172 Zornitza Stark Phenotypes for gene: IFT172 were changed from to Retinitis pigmentosa 71 616394; Short-rib thoracic dysplasia 10 with or without polydactyly - 615630; Bardet-Biedl syndrome
Mendeliome v0.2272 KMT2E Zornitza Stark Gene: kmt2e has been classified as Green List (High Evidence).
Mendeliome v0.2269 MACF1 Zornitza Stark Gene: macf1 has been classified as Green List (High Evidence).
Mendeliome v0.2269 MAP1B Zornitza Stark Gene: map1b has been classified as Green List (High Evidence).
Mendeliome v0.2266 MAP3K20 Zornitza Stark Gene: map3k20 has been classified as Green List (High Evidence).
Mendeliome v0.2266 MAP3K7 Zornitza Stark Gene: map3k7 has been classified as Green List (High Evidence).
Mendeliome v0.2266 MAP3K7 Zornitza Stark Phenotypes for gene: MAP3K7 were changed from to Cardiospondylocarpofacial syndrome 157800 AD; Frontometaphyseal dysplasia 2 617137 AD
Mendeliome v0.2262 MARS2 Zornitza Stark Gene: mars2 has been classified as Green List (High Evidence).
Mendeliome v0.2262 MARS2 Zornitza Stark Phenotypes for gene: MARS2 were changed from to Combined oxidative phosphorylation deficiency 25, OMIM #616430; Spastic ataxia 3, autosomal recessive, OMIM #611390
Mendeliome v0.2259 MARS2 Zornitza Stark changed review comment from: 1 family with 2 sibs with combined oxidative phosphorylation deficiency-25 (with ID) with compound heterozygous mutations in the MARS2 gene. Patient fibroblasts showed decreased activities of mitochondrial complexes I and IV, consistent with a mitochondrial translation defect. Immunoblot analysis showed reduced MARS2 protein levels as well as reduced levels of selected subunits of complexes I and IV.; to: 1 family with 2 sibs with combined oxidative phosphorylation deficiency-25 (with ID) with compound heterozygous mutations in the MARS2 gene. Patient fibroblasts showed decreased activities of mitochondrial complexes I and IV, consistent with a mitochondrial translation defect. Immunoblot analysis showed reduced MARS2 protein levels as well as reduced levels of selected subunits of complexes I and IV. Spastic ataxia association: note complex chromosomal rearrangements rather than SNVs reported in group of 54 French Canadians.
Mendeliome v0.2259 MECOM Zornitza Stark Gene: mecom has been classified as Green List (High Evidence).
Mendeliome v0.2259 MECOM Zornitza Stark Phenotypes for gene: MECOM were changed from to Radioulnar synostosis with amegakaryocytic thrombocytopenia 2, MIM#616738
Mendeliome v0.2256 MED17 Zornitza Stark Gene: med17 has been classified as Green List (High Evidence).
Mendeliome v0.2256 MED17 Zornitza Stark Phenotypes for gene: MED17 were changed from to Microcephaly, postnatal progressive, with seizures and brain atrophy, MIM#613668
Mendeliome v0.2253 MTHFS Zornitza Stark Gene: mthfs has been classified as Green List (High Evidence).
Mendeliome v0.2253 NEBL Zornitza Stark Gene: nebl has been classified as Green List (High Evidence).
Mendeliome v0.2250 NPHP3 Zornitza Stark Gene: nphp3 has been classified as Green List (High Evidence).
Mendeliome v0.2250 NPHP3 Zornitza Stark Phenotypes for gene: NPHP3 were changed from to Meckel syndrome 7, MIM# 267010; Nephronophthisis 3, MIM# 604387; Renal-hepatic-pancreatic dysplasia 1, MIM# 208540
Mendeliome v0.2248 NPHP3 Zornitza Stark reviewed gene: NPHP3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Meckel syndrome 7, MIM# 267010, Nephronophthisis 3, MIM# 604387, Renal-hepatic-pancreatic dysplasia 1, MIM# 208540; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2248 NR2E1 Zornitza Stark Gene: nr2e1 has been classified as Red List (Low Evidence).
Mendeliome v0.2248 NR2E1 Zornitza Stark Classified gene: NR2E1 as Red List (low evidence)
Mendeliome v0.2248 NR2E1 Zornitza Stark Gene: nr2e1 has been classified as Red List (Low Evidence).
Mendeliome v0.2247 NRROS Zornitza Stark Gene: nrros has been classified as Green List (High Evidence).
Mendeliome v0.2247 NUP214 Zornitza Stark Gene: nup214 has been classified as Green List (High Evidence).
Mendeliome v0.2247 NUP214 Zornitza Stark Phenotypes for gene: NUP214 were changed from epileptic encephalopathy; developmental regression; microcephaly to Encephalopathy, acute, infection-induced, susceptibility to, 9, MIM# 618426; epileptic encephalopathy; developmental regression; microcephaly
Mendeliome v0.2246 NXN Zornitza Stark Gene: nxn has been classified as Green List (High Evidence).
Mendeliome v0.2246 PAX1 Zornitza Stark Gene: pax1 has been classified as Green List (High Evidence).
Mendeliome v0.2242 PDE8B Zornitza Stark Gene: pde8b has been classified as Green List (High Evidence).
Mendeliome v0.2239 ANLN Zornitza Stark Gene: anln has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2239 ANLN Zornitza Stark Phenotypes for gene: ANLN were changed from to Focal segmental glomerulosclerosis 8, OMIM #616032
Mendeliome v0.2237 PIGG Zornitza Stark Gene: pigg has been classified as Green List (High Evidence).
Mendeliome v0.2237 PIGG Zornitza Stark Phenotypes for gene: PIGG were changed from to Mental retardation, autosomal recessive 53, MIM#616917
Mendeliome v0.2234 PIGU Zornitza Stark Gene: pigu has been classified as Green List (High Evidence).
Mendeliome v0.2234 PIGU Zornitza Stark Phenotypes for gene: PIGU were changed from to Glycosylphosphatidylinositol biosynthesis defect 21; OMIM #618590
Mendeliome v0.2231 PUS3 Zornitza Stark Gene: pus3 has been classified as Green List (High Evidence).
Mendeliome v0.2231 PUS3 Zornitza Stark Phenotypes for gene: PUS3 were changed from to Mental retardation, autosomal recessive 55, MIM# 617051
Mendeliome v0.2228 RUBCN Zornitza Stark Gene: rubcn has been classified as Green List (High Evidence).
Mendeliome v0.2228 RUBCN Zornitza Stark Phenotypes for gene: RUBCN were changed from to Spinocerebellar ataxia, autosomal recessive 15, MIM#615705
Mendeliome v0.2225 SHANK2 Zornitza Stark Gene: shank2 has been classified as Green List (High Evidence).
Mendeliome v0.2222 SLC26A4 Zornitza Stark Gene: slc26a4 has been classified as Green List (High Evidence).
Mendeliome v0.2222 SLC26A4 Zornitza Stark Phenotypes for gene: SLC26A4 were changed from to Deafness, autosomal recessive 4, with enlarged vestibular aqueduct 600791; Pendred syndrome 274600
Mendeliome v0.2219 SMPD4 Zornitza Stark Gene: smpd4 has been classified as Green List (High Evidence).
Mendeliome v0.2219 SMPD4 Zornitza Stark Phenotypes for gene: SMPD4 were changed from to Severe neurodevelopmental delay, microcephaly, arthrogryposis
Mendeliome v0.2216 SOX11 Zornitza Stark Gene: sox11 has been classified as Green List (High Evidence).
Mendeliome v0.2216 SOX11 Zornitza Stark Phenotypes for gene: SOX11 were changed from to Coffin-Siris syndrome 9, MIM# 615866; Congenital abnormalities of the kidneys and urinary tract
Mendeliome v0.2213 SOX11 Zornitza Stark changed review comment from: Heterozygous variant in a patient with Coffin-Siris like syndrome and small kidney; but also rare variants identified in a non-syndromic CAKUT cohort with some functional data.
Sources: Expert list; to: Coffin-Siris syndrome: two individuals with de novo mono-allelic missense variants in this gene, mouse model.
CAKUT: Heterozygous variant in a patient with Coffin-Siris like syndrome and small kidney; but also rare variants identified in a non-syndromic CAKUT cohort with some functional data.
Sources: Expert list
Mendeliome v0.2213 SOX11 Zornitza Stark edited their review of gene: SOX11: Changed rating: GREEN; Changed phenotypes: Coffin-Siris syndrome 9, MIM# 615866, Congenital abnormalities of the kidneys and urinary tract
Mendeliome v0.2213 ADAM22 Zornitza Stark Gene: adam22 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2213 ADAM22 Zornitza Stark Classified gene: ADAM22 as Amber List (moderate evidence)
Mendeliome v0.2213 ADAM22 Zornitza Stark Gene: adam22 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2212 NDUFA12 Zornitza Stark Gene: ndufa12 has been classified as Red List (Low Evidence).
Mendeliome v0.2212 HOXB6 Zornitza Stark Classified gene: HOXB6 as Amber List (moderate evidence)
Mendeliome v0.2212 HOXB6 Zornitza Stark Gene: hoxb6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2211 QRSL1 Zornitza Stark Gene: qrsl1 has been classified as Green List (High Evidence).
Mendeliome v0.2208 PPCS Zornitza Stark Gene: ppcs has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2205 PPCS Zornitza Stark Classified gene: PPCS as Amber List (moderate evidence)
Mendeliome v0.2205 PPCS Zornitza Stark Gene: ppcs has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2204 PET117 Zornitza Stark Gene: pet117 has been classified as Red List (Low Evidence).
Mendeliome v0.2204 PET117 Zornitza Stark gene: PET117 was added
gene: PET117 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PET117 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PET117 were set to 28386624
Phenotypes for gene: PET117 were set to Developmental delay; Regression; Complex IV deficiency
Review for gene: PET117 was set to RED
Added comment: Two siblings reported, some functional data. PET117 postulated to be a Complex IV assembly factor.
Sources: Expert list
Mendeliome v0.2201 NUP188 Zornitza Stark Classified gene: NUP188 as Green List (high evidence)
Mendeliome v0.2201 NUP188 Zornitza Stark Gene: nup188 has been classified as Green List (High Evidence).
Mendeliome v0.2200 TMTC2 Zornitza Stark Gene: tmtc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2198 TBCD Zornitza Stark Gene: tbcd has been classified as Green List (High Evidence).
Mendeliome v0.2198 TBCD Zornitza Stark Phenotypes for gene: TBCD were changed from to Encephalopathy, progressive, early-onset, with brain atrophy and thin corpus callosum, MIM#617193
Mendeliome v0.2194 TMTC2 Zornitza Stark Classified gene: TMTC2 as Amber List (moderate evidence)
Mendeliome v0.2194 TMTC2 Zornitza Stark Gene: tmtc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2193 UMOD Zornitza Stark Gene: umod has been classified as Green List (High Evidence).
Mendeliome v0.2193 TOR1AIP1 Zornitza Stark Gene: tor1aip1 has been classified as Green List (High Evidence).
Mendeliome v0.2193 UPK3A Zornitza Stark Gene: upk3a has been classified as Red List (Low Evidence).
Mendeliome v0.2190 UPK3A Zornitza Stark Classified gene: UPK3A as Red List (low evidence)
Mendeliome v0.2190 UPK3A Zornitza Stark Gene: upk3a has been classified as Red List (Low Evidence).
Mendeliome v0.2189 VARS Zornitza Stark Gene: vars has been classified as Green List (High Evidence).
Mendeliome v0.2188 WNT10A Zornitza Stark Gene: wnt10a has been classified as Green List (High Evidence).
Mendeliome v0.2188 WNT10A Zornitza Stark Phenotypes for gene: WNT10A were changed from to Odontoonychodermal dysplasia; Schopf-Schulz-Passarge syndrome; Tooth agenesis, selective, 4
Mendeliome v0.2185 ZNF592 Zornitza Stark Gene: znf592 has been classified as Red List (Low Evidence).
Mendeliome v0.2185 ZNF592 Zornitza Stark Phenotypes for gene: ZNF592 were changed from to SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 5
Mendeliome v0.2182 ZNF592 Zornitza Stark Classified gene: ZNF592 as Red List (low evidence)
Mendeliome v0.2182 ZNF592 Zornitza Stark Gene: znf592 has been classified as Red List (Low Evidence).
Mendeliome v0.2181 CLIC5 Zornitza Stark Gene: clic5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2181 GNB2 Zornitza Stark Gene: gnb2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2181 MIR96 Zornitza Stark Gene: mir96 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2181 MYL1 Zornitza Stark Gene: myl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2181 APOL1 Zornitza Stark Gene: apol1 has been classified as Red List (Low Evidence).
Mendeliome v0.2181 ARHGEF6 Zornitza Stark Gene: arhgef6 has been classified as Red List (Low Evidence).
Mendeliome v0.2181 CEP85L Zornitza Stark Gene: cep85l has been classified as Green List (High Evidence).
Mendeliome v0.2181 CEP85L Zornitza Stark Classified gene: CEP85L as Green List (high evidence)
Mendeliome v0.2181 CEP85L Zornitza Stark Gene: cep85l has been classified as Green List (High Evidence).
Mendeliome v0.2180 MIEF2 Zornitza Stark Gene: mief2 has been classified as Red List (Low Evidence).
Mendeliome v0.2180 POLE2 Zornitza Stark Gene: pole2 has been classified as Red List (Low Evidence).
Mendeliome v0.2180 PTCD1 Zornitza Stark Gene: ptcd1 has been classified as Red List (Low Evidence).
Mendeliome v0.2180 TFAM Zornitza Stark Gene: tfam has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2180 TFAM Zornitza Stark Classified gene: TFAM as Amber List (moderate evidence)
Mendeliome v0.2180 TFAM Zornitza Stark Gene: tfam has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2179 NME3 Zornitza Stark Gene: nme3 has been classified as Red List (Low Evidence).
Mendeliome v0.2179 NME3 Zornitza Stark gene: NME3 was added
gene: NME3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: NME3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NME3 were set to 30587587
Phenotypes for gene: NME3 were set to Hypotonia; Neurodegeneration; Abnormal mitochondrial dynamics
Review for gene: NME3 was set to RED
Added comment: Single individual reported. NME3 is a mitochondrial outer-membrane protein capable of interacting with MFN1/2, and its depletion causes dysfunction in mitochondrial dynamics
Sources: Expert list
Mendeliome v0.2178 MRPS28 Zornitza Stark Gene: mrps28 has been classified as Red List (Low Evidence).
Mendeliome v0.2178 MRPS28 Zornitza Stark gene: MRPS28 was added
gene: MRPS28 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: MRPS28 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MRPS28 were set to 30566640
Phenotypes for gene: MRPS28 were set to Intrauterine growth retardation; developmental delay; dysmorphism
Review for gene: MRPS28 was set to RED
Added comment: Single individual reported.
Sources: Expert list
Mendeliome v0.2177 MRPS25 Zornitza Stark Gene: mrps25 has been classified as Red List (Low Evidence).
Mendeliome v0.2177 MRPS25 Zornitza Stark gene: MRPS25 was added
gene: MRPS25 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: MRPS25 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MRPS25 were set to 31039582
Phenotypes for gene: MRPS25 were set to Dyskinetic cerebral palsy; Mitochondrial myopathy; Partial agenesis of the corpus callosum
Review for gene: MRPS25 was set to RED
Added comment: Single individual reported.
Sources: Expert list
Mendeliome v0.2176 MRPS23 Zornitza Stark Phenotypes for gene: MRPS23 were changed from Hepatic disease; Combined respiratory chain complex deficiencies to Hepatic disease; Combined respiratory chain complex deficienciesHepatic disease; Combined respiratory chain complex deficiencies; Cardiomyopathy; Tubulopathy; Lactic acidosis; Structural brain abnormalities
Mendeliome v0.2174 MRPS23 Zornitza Stark Classified gene: MRPS23 as Green List (high evidence)
Mendeliome v0.2174 MRPS23 Zornitza Stark Gene: mrps23 has been classified as Green List (High Evidence).
Mendeliome v0.2173 MRPS23 Zornitza Stark edited their review of gene: MRPS23: Added comment: Four families reported.; Changed rating: GREEN; Changed publications: 26741492, 17873122, 25663021, 28752220; Changed phenotypes: Hepatic disease, Combined respiratory chain complex deficiencies, Cardiomyopathy, Tubulopathy, Lactic acidosis, Structural brain abnormalities
Mendeliome v0.2173 MIEF2 Zornitza Stark gene: MIEF2 was added
gene: MIEF2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: MIEF2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MIEF2 were set to 29361167
Phenotypes for gene: MIEF2 were set to Progressive muscle weakness; Exercise intolerance; Ragged red and COX negative fibres; Complex I and IV deficiency
Review for gene: MIEF2 was set to RED
Added comment: Single individual reported.
Sources: Expert list
Mendeliome v0.2172 ERAL1 Zornitza Stark Gene: eral1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2172 ERAL1 Zornitza Stark Classified gene: ERAL1 as Amber List (moderate evidence)
Mendeliome v0.2172 ERAL1 Zornitza Stark Gene: eral1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2170 COX5A Zornitza Stark Gene: cox5a has been classified as Red List (Low Evidence).
Mendeliome v0.2170 COX5A Zornitza Stark gene: COX5A was added
gene: COX5A was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: COX5A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COX5A were set to 2824752
Phenotypes for gene: COX5A were set to pulmonary arterial hypertension; lactic acidemia; failure to thrive; isolated complex IV deficiency
Review for gene: COX5A was set to RED
Added comment: Single family reported.
Sources: Expert list
Mendeliome v0.2169 TRAF3IP2 Zornitza Stark Gene: traf3ip2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2169 TRAF3IP2 Zornitza Stark Phenotypes for gene: TRAF3IP2 were changed from to Candidiasis, familial, 8, MIM# 615527
Mendeliome v0.2166 TRAF3IP2 Zornitza Stark Classified gene: TRAF3IP2 as Amber List (moderate evidence)
Mendeliome v0.2166 TRAF3IP2 Zornitza Stark Gene: traf3ip2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2165 TRAF3IP2 Zornitza Stark reviewed gene: TRAF3IP2: Rating: AMBER; Mode of pathogenicity: None; Publications: 24120361, 31292894, 20660351; Phenotypes: Candidiasis, familial, 8, MIM# 615527; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2165 TRAF3 Zornitza Stark Gene: traf3 has been classified as Red List (Low Evidence).
Mendeliome v0.2162 TRAF3 Zornitza Stark Classified gene: TRAF3 as Red List (low evidence)
Mendeliome v0.2162 TRAF3 Zornitza Stark Gene: traf3 has been classified as Red List (Low Evidence).
Mendeliome v0.2161 TNFSF12 Zornitza Stark Gene: tnfsf12 has been classified as Red List (Low Evidence).
Mendeliome v0.2158 TNFSF12 Zornitza Stark Classified gene: TNFSF12 as Red List (low evidence)
Mendeliome v0.2158 TNFSF12 Zornitza Stark Gene: tnfsf12 has been classified as Red List (Low Evidence).
Mendeliome v0.2157 TNFRSF4 Zornitza Stark Gene: tnfrsf4 has been classified as Red List (Low Evidence).
Mendeliome v0.2154 TNFRSF4 Zornitza Stark Classified gene: TNFRSF4 as Red List (low evidence)
Mendeliome v0.2154 TNFRSF4 Zornitza Stark Gene: tnfrsf4 has been classified as Red List (Low Evidence).
Mendeliome v0.2153 TNFRSF13C Zornitza Stark Gene: tnfrsf13c has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2150 TNFRSF13C Zornitza Stark Classified gene: TNFRSF13C as Amber List (moderate evidence)
Mendeliome v0.2150 TNFRSF13C Zornitza Stark Gene: tnfrsf13c has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2149 TNFRSF13B Zornitza Stark Gene: tnfrsf13b has been classified as Green List (High Evidence).
Mendeliome v0.2146 THBD Zornitza Stark Gene: thbd has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2143 THBD Zornitza Stark Classified gene: THBD as Amber List (moderate evidence)
Mendeliome v0.2143 THBD Zornitza Stark Gene: thbd has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2142 TAPBP Zornitza Stark Gene: tapbp has been classified as Red List (Low Evidence).
Mendeliome v0.2140 NXN Zornitza Stark Phenotypes for gene: NXN were changed from to Robinow syndrome, autosomal recessive 2 618529
Mendeliome v0.2137 NXN Zornitza Stark reviewed gene: NXN: Rating: GREEN; Mode of pathogenicity: None; Publications: 29276006; Phenotypes: Robinow syndrome, autosomal recessive 2 618529; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2136 TAPBP Zornitza Stark Classified gene: TAPBP as Red List (low evidence)
Mendeliome v0.2136 TAPBP Zornitza Stark Gene: tapbp has been classified as Red List (Low Evidence).
Mendeliome v0.2136 TAPBP Zornitza Stark Classified gene: TAPBP as Red List (low evidence)
Mendeliome v0.2136 TAPBP Zornitza Stark Gene: tapbp has been classified as Red List (Low Evidence).
Mendeliome v0.2135 SEMA3E Zornitza Stark Gene: sema3e has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2133 SEMA3E Zornitza Stark Classified gene: SEMA3E as Amber List (moderate evidence)
Mendeliome v0.2133 SEMA3E Zornitza Stark Gene: sema3e has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2132 RNF31 Zornitza Stark Gene: rnf31 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2129 RNF31 Zornitza Stark Classified gene: RNF31 as Amber List (moderate evidence)
Mendeliome v0.2129 RNF31 Zornitza Stark Gene: rnf31 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2128 RHOH Zornitza Stark Gene: rhoh has been classified as Red List (Low Evidence).
Mendeliome v0.2128 RHOH Zornitza Stark Phenotypes for gene: RHOH were changed from to {?Epidermodysplasia verruciformis, susceptibility to, 4}, MIM# 618307
Mendeliome v0.2125 RHOH Zornitza Stark Classified gene: RHOH as Red List (low evidence)
Mendeliome v0.2125 RHOH Zornitza Stark Gene: rhoh has been classified as Red List (Low Evidence).
Mendeliome v0.2124 RHOH Zornitza Stark reviewed gene: RHOH: Rating: RED; Mode of pathogenicity: None; Publications: 22850876, 27574848; Phenotypes: {?Epidermodysplasia verruciformis, susceptibility to, 4}, MIM# 618307; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2124 PSMB9 Zornitza Stark Gene: psmb9 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2121 PSMB9 Zornitza Stark Classified gene: PSMB9 as Amber List (moderate evidence)
Mendeliome v0.2121 PSMB9 Zornitza Stark Gene: psmb9 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2120 PSMB4 Zornitza Stark Gene: psmb4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2117 PSMB4 Zornitza Stark Classified gene: PSMB4 as Amber List (moderate evidence)
Mendeliome v0.2117 PSMB4 Zornitza Stark Gene: psmb4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2116 PSMA3 Zornitza Stark Gene: psma3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2113 PSMA3 Zornitza Stark Classified gene: PSMA3 as Amber List (moderate evidence)
Mendeliome v0.2113 PSMA3 Zornitza Stark Gene: psma3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2112 NFKBID Zornitza Stark Gene: nfkbid has been classified as Red List (Low Evidence).
Mendeliome v0.2111 NFKBID Zornitza Stark Classified gene: NFKBID as Red List (low evidence)
Mendeliome v0.2111 NFKBID Zornitza Stark Gene: nfkbid has been classified as Red List (Low Evidence).
Mendeliome v0.2110 NFAT5 Zornitza Stark Gene: nfat5 has been classified as Red List (Low Evidence).
Mendeliome v0.2107 NFAT5 Zornitza Stark Classified gene: NFAT5 as Red List (low evidence)
Mendeliome v0.2107 NFAT5 Zornitza Stark Gene: nfat5 has been classified as Red List (Low Evidence).
Mendeliome v0.2106 MS4A1 Zornitza Stark Gene: ms4a1 has been classified as Red List (Low Evidence).
Mendeliome v0.2103 MS4A1 Zornitza Stark Classified gene: MS4A1 as Red List (low evidence)
Mendeliome v0.2103 MS4A1 Zornitza Stark Gene: ms4a1 has been classified as Red List (Low Evidence).
Mendeliome v0.2103 MS4A1 Zornitza Stark Classified gene: MS4A1 as Red List (low evidence)
Mendeliome v0.2103 MS4A1 Zornitza Stark Gene: ms4a1 has been classified as Red List (Low Evidence).
Mendeliome v0.2102 MASP2 Zornitza Stark Gene: masp2 has been classified as Red List (Low Evidence).
Mendeliome v0.2100 MASP2 Zornitza Stark Classified gene: MASP2 as Red List (low evidence)
Mendeliome v0.2100 MASP2 Zornitza Stark Gene: masp2 has been classified as Red List (Low Evidence).
Mendeliome v0.2099 ITGAM Zornitza Stark Gene: itgam has been classified as Red List (Low Evidence).
Mendeliome v0.2099 ITGAM Zornitza Stark Classified gene: ITGAM as Red List (low evidence)
Mendeliome v0.2099 ITGAM Zornitza Stark Gene: itgam has been classified as Red List (Low Evidence).
Mendeliome v0.2098 IRF7 Zornitza Stark Gene: irf7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2095 IRF7 Zornitza Stark Classified gene: IRF7 as Amber List (moderate evidence)
Mendeliome v0.2095 IRF7 Zornitza Stark Gene: irf7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2094 IL21 Zornitza Stark Gene: il21 has been classified as Red List (Low Evidence).
Mendeliome v0.2091 IL21 Zornitza Stark Classified gene: IL21 as Red List (low evidence)
Mendeliome v0.2091 IL21 Zornitza Stark Gene: il21 has been classified as Red List (Low Evidence).
Mendeliome v0.2090 IL17F Zornitza Stark Gene: il17f has been classified as Red List (Low Evidence).
Mendeliome v0.2090 IL17F Zornitza Stark Phenotypes for gene: IL17F were changed from to Candidiasis, familial, 6, autosomal dominant, MIM# 613956
Mendeliome v0.2087 IL17F Zornitza Stark Classified gene: IL17F as Red List (low evidence)
Mendeliome v0.2087 IL17F Zornitza Stark Gene: il17f has been classified as Red List (Low Evidence).
Mendeliome v0.2086 IL17F Zornitza Stark reviewed gene: IL17F: Rating: RED; Mode of pathogenicity: None; Publications: 21350122; Phenotypes: Candidiasis, familial, 6, autosomal dominant, MIM# 613956; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2086 FPR1 Zornitza Stark Gene: fpr1 has been classified as Red List (Low Evidence).
Mendeliome v0.2084 FPR1 Zornitza Stark Classified gene: FPR1 as Red List (low evidence)
Mendeliome v0.2084 FPR1 Zornitza Stark Gene: fpr1 has been classified as Red List (Low Evidence).
Mendeliome v0.2083 FCN3 Zornitza Stark Gene: fcn3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2080 FCN3 Zornitza Stark Classified gene: FCN3 as Amber List (moderate evidence)
Mendeliome v0.2080 FCN3 Zornitza Stark Gene: fcn3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2079 FCGR3A Zornitza Stark Gene: fcgr3a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2076 FCGR3A Zornitza Stark Classified gene: FCGR3A as Amber List (moderate evidence)
Mendeliome v0.2076 FCGR3A Zornitza Stark Gene: fcgr3a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2075 CR2 Zornitza Stark Gene: cr2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2072 CR2 Zornitza Stark Classified gene: CR2 as Amber List (moderate evidence)
Mendeliome v0.2072 CR2 Zornitza Stark Gene: cr2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2071 CFHR4 Zornitza Stark Gene: cfhr4 has been classified as Red List (Low Evidence).
Mendeliome v0.2071 CFHR4 Zornitza Stark Classified gene: CFHR4 as Red List (low evidence)
Mendeliome v0.2071 CFHR4 Zornitza Stark Gene: cfhr4 has been classified as Red List (Low Evidence).
Mendeliome v0.2070 CFHR2 Zornitza Stark Gene: cfhr2 has been classified as Green List (High Evidence).
Mendeliome v0.2064 CFB Zornitza Stark Classified gene: CFB as Green List (high evidence)
Mendeliome v0.2064 CFB Zornitza Stark Gene: cfb has been classified as Green List (High Evidence).
Mendeliome v0.2063 CFB Zornitza Stark changed review comment from: Single individual reported, supportive immunophenotyping data.; to: Single individual reported with bi-allelic variants and complement deficiency, supportive immunophenotyping data. Mono-allelic variants linked to susceptibility to aHUS.
Mendeliome v0.2063 CFB Zornitza Stark Gene: cfb has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2060 CFB Zornitza Stark Classified gene: CFB as Amber List (moderate evidence)
Mendeliome v0.2060 CFB Zornitza Stark Gene: cfb has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2059 CD8A Zornitza Stark Gene: cd8a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2056 CD8A Zornitza Stark Classified gene: CD8A as Amber List (moderate evidence)
Mendeliome v0.2056 CD8A Zornitza Stark Gene: cd8a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2055 CD81 Zornitza Stark Gene: cd81 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2052 CD81 Zornitza Stark Classified gene: CD81 as Amber List (moderate evidence)
Mendeliome v0.2052 CD81 Zornitza Stark Gene: cd81 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2051 CD247 Zornitza Stark Classified gene: CD247 as Green List (high evidence)
Mendeliome v0.2051 CD247 Zornitza Stark Gene: cd247 has been classified as Green List (High Evidence).
Mendeliome v0.2050 CD247 Zornitza Stark changed review comment from: Also known as CD3Z. Single individual reported with homozygous germline nonsense variant, which was present in some T cells, but others had the nonsense variant in combination with one of three different missense somatic variants.; to: Also known as CD3Z. Note one individual reported with homozygous germline nonsense variant, which was present in some T cells, but others had the nonsense variant in combination with one of three different missense somatic variants.
Mendeliome v0.2050 C8G Zornitza Stark Gene: c8g has been classified as Red List (Low Evidence).
Mendeliome v0.2050 C8G Zornitza Stark Classified gene: C8G as Red List (low evidence)
Mendeliome v0.2050 C8G Zornitza Stark Gene: c8g has been classified as Red List (Low Evidence).
Mendeliome v0.2049 BLOC1S6 Zornitza Stark Gene: bloc1s6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2046 BLOC1S6 Zornitza Stark Classified gene: BLOC1S6 as Amber List (moderate evidence)
Mendeliome v0.2046 BLOC1S6 Zornitza Stark Gene: bloc1s6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2045 MIR140 Zornitza Stark Gene: mir140 has been classified as Green List (High Evidence).
Mendeliome v0.2045 MIR140 Zornitza Stark Classified gene: MIR140 as Green List (high evidence)
Mendeliome v0.2045 MIR140 Zornitza Stark Gene: mir140 has been classified as Green List (High Evidence).
Mendeliome v0.2044 MIR140 Zornitza Stark gene: MIR140 was added
gene: MIR140 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: MIR140 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MIR140 were set to 30804514; 31633310
Phenotypes for gene: MIR140 were set to Spondyloepiphyseal dysplasia, Nishimura type, MIM# 618618
Review for gene: MIR140 was set to GREEN
Added comment: Single clinical paper (30804514) reports variant in affected mother and child (de novo in mother) and in a separate unrelated female (de novo) with spondylo-epiphyseal dysplasia. Mouse model (21576357) deletion of gene causes impaired longitudinal bone growth. Separate mouse model studies by same authors as clinical paper above (30804514) showed phenotype of mice with same mutation in this gene consistent with the skeletal dysplasia features of patients with the n.24A-G mutation, suggestive of neomorphic effects (mutation produces both loss-of-function and gain-of-function effects.)
Sources: Expert Review
Mendeliome v0.2042 APOL1 Zornitza Stark Phenotypes for gene: APOL1 were changed from to {Glomerulosclerosis, focal segmental, 4, susceptibility to} 612551
Mendeliome v0.2040 APOL1 Zornitza Stark Classified gene: APOL1 as Red List (low evidence)
Mendeliome v0.2040 APOL1 Zornitza Stark Gene: apol1 has been classified as Red List (Low Evidence).
Mendeliome v0.2039 APOL1 Zornitza Stark reviewed gene: APOL1: Rating: RED; Mode of pathogenicity: None; Publications: 29470556, 20647424, 24206458, 20635188; Phenotypes: {Glomerulosclerosis, focal segmental, 4, susceptibility to} 612551; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2039 AP1S3 Zornitza Stark Gene: ap1s3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2039 AP1S3 Zornitza Stark Phenotypes for gene: AP1S3 were changed from to {Psoriasis 15, pustular, susceptibility to} 616106
Mendeliome v0.2036 AP1S3 Zornitza Stark Classified gene: AP1S3 as Amber List (moderate evidence)
Mendeliome v0.2036 AP1S3 Zornitza Stark Gene: ap1s3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2035 AP1S3 Zornitza Stark reviewed gene: AP1S3: Rating: AMBER; Mode of pathogenicity: None; Publications: 24791904, 27388993; Phenotypes: {Psoriasis 15, pustular, susceptibility to} 616106; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2033 PIEZO1 Zornitza Stark Gene: piezo1 has been classified as Green List (High Evidence).
Mendeliome v0.2032 PIEZO1 Zornitza Stark Phenotypes for gene: PIEZO1 were changed from to Lymphatic malformation 6, 616843; Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema, 194380
Mendeliome v0.2029 TBX19 Zornitza Stark Gene: tbx19 has been classified as Green List (High Evidence).
Mendeliome v0.2026 TCF20 Zornitza Stark Gene: tcf20 has been classified as Green List (High Evidence).
Mendeliome v0.2023 TFE3 Zornitza Stark Gene: tfe3 has been classified as Green List (High Evidence).
Mendeliome v0.2020 ICOSLG Zornitza Stark Gene: icoslg has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2017 ICOSLG Zornitza Stark Classified gene: ICOSLG as Amber List (moderate evidence)
Mendeliome v0.2017 ICOSLG Zornitza Stark Gene: icoslg has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2016 IL6ST Zornitza Stark Phenotypes for gene: IL6ST were changed from Hyper-IgE recurrent infection syndrome 4, autosomal recessive, MIM# 618523; Stuve-Wiedemann-like syndrome: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response. to Hyper-IgE recurrent infection syndrome 4, autosomal recessive, MIM# 618523; Stuve-Wiedemann-like syndrome: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response; Hyper-IgE syndrome, autosomal dominant
Mendeliome v0.2013 IL6ST Zornitza Stark changed review comment from: Also known as gp130. Two families with bi-allelic missense variants and immunological phenotype described initially. More recently, five individuals from three families reported with a more complex Stuve-Wiedemann-like phenotype reported, including skeletal dysplasia and neonatal lung dysfunction with additional features such as congenital thrombocytopenia, eczematoid dermatitis, renal abnormalities, and defective acute-phase response. These three families had bi-allelic LoF variants (nonsense and canonical splice site). Several mouse models support gene-disease association.
Sources: Expert list; to: Also known as gp130. Two families with bi-allelic missense variants and immunological phenotype described initially. More recently, five individuals from three families reported with a more complex Stuve-Wiedemann-like phenotype reported, including skeletal dysplasia and neonatal lung dysfunction with additional features such as congenital thrombocytopenia, eczematoid dermatitis, renal abnormalities, and defective acute-phase response. These three families had bi-allelic LoF variants (nonsense and canonical splice site). Several mouse models support gene-disease association.
2020: 12 individuals from 8 unrelated families with seven different mono-allelic truncating variants, dominant negative effect proposed.
Sources: Expert list
Mendeliome v0.2013 IL6ST Zornitza Stark edited their review of gene: IL6ST: Changed publications: 28747427, 30309848, 12370259, 16041381, 31914175, 32207811; Changed phenotypes: Hyper-IgE recurrent infection syndrome 4, autosomal recessive, MIM# 618523, Stuve-Wiedemann-like syndrome: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response, Hyper-IgE syndrome, autosomal dominant; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2013 PIEZO1 Kristin Rigbye reviewed gene: PIEZO1: Rating: GREEN; Mode of pathogenicity: Other; Publications: 23695678, 26333996; Phenotypes: Lymphatic malformation 6, 616843, Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema, 194380; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2013 SAMD9L Zornitza Stark Gene: samd9l has been classified as Green List (High Evidence).
Mendeliome v0.2009 RFWD3 Zornitza Stark Gene: rfwd3 has been classified as Red List (Low Evidence).
Mendeliome v0.2006 RFWD3 Zornitza Stark Classified gene: RFWD3 as Red List (low evidence)
Mendeliome v0.2006 RFWD3 Zornitza Stark Gene: rfwd3 has been classified as Red List (Low Evidence).
Mendeliome v0.2005 MAD2L2 Zornitza Stark Gene: mad2l2 has been classified as Red List (Low Evidence).
Mendeliome v0.2005 MAD2L2 Zornitza Stark gene: MAD2L2 was added
gene: MAD2L2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: MAD2L2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAD2L2 were set to 27500492
Phenotypes for gene: MAD2L2 were set to Fanconi anemia, complementation group V, MIM# 617243
Review for gene: MAD2L2 was set to RED
Added comment: Single family reported.
Sources: Expert list
Mendeliome v0.2004 UBE2T Zornitza Stark Gene: ube2t has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2001 UBE2T Zornitza Stark Classified gene: UBE2T as Amber List (moderate evidence)
Mendeliome v0.2001 UBE2T Zornitza Stark Gene: ube2t has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2000 HAVCR2 Zornitza Stark Gene: havcr2 has been classified as Green List (High Evidence).
Mendeliome v0.2000 HAVCR2 Zornitza Stark Classified gene: HAVCR2 as Green List (high evidence)
Mendeliome v0.2000 HAVCR2 Zornitza Stark Gene: havcr2 has been classified as Green List (High Evidence).
Mendeliome v0.1998 TRIM22 Zornitza Stark Gene: trim22 has been classified as Green List (High Evidence).
Mendeliome v0.1998 TRIM22 Zornitza Stark Classified gene: TRIM22 as Green List (high evidence)
Mendeliome v0.1998 TRIM22 Zornitza Stark Gene: trim22 has been classified as Green List (High Evidence).
Mendeliome v0.1996 ALPI Zornitza Stark Gene: alpi has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1996 ALPI Zornitza Stark Classified gene: ALPI as Amber List (moderate evidence)
Mendeliome v0.1996 ALPI Zornitza Stark Gene: alpi has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1994 PSMG2 Zornitza Stark Gene: psmg2 has been classified as Red List (Low Evidence).
Mendeliome v0.1994 PSMG2 Zornitza Stark gene: PSMG2 was added
gene: PSMG2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PSMG2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMG2 were set to 30664889
Phenotypes for gene: PSMG2 were set to CANDLE syndrome; Chronic atypical neutrophilic dermatitis with lipodystrophy
Review for gene: PSMG2 was set to RED
Added comment: Single individual reported.
Sources: Expert list
Mendeliome v0.1993 NLRP1 Zornitza Stark Gene: nlrp1 has been classified as Green List (High Evidence).
Mendeliome v0.1993 NLRP1 Zornitza Stark Phenotypes for gene: NLRP1 were changed from to Autoinflammation with arthritis and dyskeratosis, MIM# 617388; Palmoplantar carcinoma, multiple self-healing, MIM# 615225; Recurrent respiratory papillomatosis
Mendeliome v0.1990 NLRP1 Zornitza Stark reviewed gene: NLRP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27965258, 31484767, 27662089; Phenotypes: Autoinflammation with arthritis and dyskeratosis, MIM# 617388, Palmoplantar carcinoma, multiple self-healing 615225, Recurrent respiratory papillomatosis; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.1990 POLA1 Zornitza Stark Gene: pola1 has been classified as Green List (High Evidence).
Mendeliome v0.1987 IRAK1 Zornitza Stark Gene: irak1 has been classified as Red List (Low Evidence).
Mendeliome v0.1987 IRAK1 Zornitza Stark gene: IRAK1 was added
gene: IRAK1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: IRAK1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: IRAK1 were set to 28069966
Phenotypes for gene: IRAK1 were set to Susceptibility to bacterial infections
Review for gene: IRAK1 was set to RED
Added comment: Single individual with MECP2 and IRAK1 deletion, died in infancy, immunological phenotype not fully elucidated. In vitro studies.
Sources: Expert list
Mendeliome v0.1986 DBR1 Zornitza Stark Gene: dbr1 has been classified as Green List (High Evidence).
Mendeliome v0.1986 DBR1 Zornitza Stark Classified gene: DBR1 as Green List (high evidence)
Mendeliome v0.1986 DBR1 Zornitza Stark Gene: dbr1 has been classified as Green List (High Evidence).
Mendeliome v0.1984 POLR3F Zornitza Stark Gene: polr3f has been classified as Red List (Low Evidence).
Mendeliome v0.1983 POLR3C Zornitza Stark Gene: polr3c has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1983 POLR3C Zornitza Stark Classified gene: POLR3C as Amber List (moderate evidence)
Mendeliome v0.1983 POLR3C Zornitza Stark Gene: polr3c has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1981 POLR3A Zornitza Stark Gene: polr3a has been classified as Green List (High Evidence).
Mendeliome v0.1979 IFNAR2 Zornitza Stark Gene: ifnar2 has been classified as Red List (Low Evidence).
Mendeliome v0.1976 IFNAR2 Zornitza Stark Classified gene: IFNAR2 as Red List (low evidence)
Mendeliome v0.1976 IFNAR2 Zornitza Stark Gene: ifnar2 has been classified as Red List (Low Evidence).
Mendeliome v0.1975 IFNAR1 Zornitza Stark Gene: ifnar1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1975 IFNAR1 Zornitza Stark Classified gene: IFNAR1 as Amber List (moderate evidence)
Mendeliome v0.1975 IFNAR1 Zornitza Stark Gene: ifnar1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1973 IRF9 Zornitza Stark Gene: irf9 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1973 IRF9 Zornitza Stark Classified gene: IRF9 as Amber List (moderate evidence)
Mendeliome v0.1973 IRF9 Zornitza Stark Gene: irf9 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1971 CIB1 Zornitza Stark Gene: cib1 has been classified as Green List (High Evidence).
Mendeliome v0.1971 CIB1 Zornitza Stark Classified gene: CIB1 as Green List (high evidence)
Mendeliome v0.1971 CIB1 Zornitza Stark Gene: cib1 has been classified as Green List (High Evidence).
Mendeliome v0.1970 CIB1 Zornitza Stark gene: CIB1 was added
gene: CIB1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: CIB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CIB1 were set to 30068544
Phenotypes for gene: CIB1 were set to Epidermodysplasia verruciformis 3 618267; HPV infections and cancer of the skin
Review for gene: CIB1 was set to GREEN
Added comment: 24 individuals from 6 families reported.
Sources: Expert list
Mendeliome v0.1969 JAK1 Zornitza Stark Phenotypes for gene: JAK1 were changed from Eosinophilia; Eosinophilic enteritis; Thyroid disease; Poor growth; Viral infections to Eosinophilia; Eosinophilic enteritis; Thyroid disease; Poor growth; Viral infections; Susceptibility to mycobacteria and viruses
Mendeliome v0.1966 JAK1 Zornitza Stark Classified gene: JAK1 as Amber List (moderate evidence)
Mendeliome v0.1966 JAK1 Zornitza Stark Gene: jak1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1965 JAK1 Zornitza Stark changed review comment from: Single family reported (mother and two children) with GoF variant.
Sources: Expert list; to: Single family reported (mother and two children) with GoF variant and immune dysregulation phenotype. Another individual reported with bi-allelic LoF and susceptibility to mycobacterial infections. Mouse model with NK defect.
Sources: Expert list
Mendeliome v0.1965 JAK1 Zornitza Stark edited their review of gene: JAK1: Changed rating: AMBER; Changed publications: 28111307, 28008925, 30671064; Changed phenotypes: Eosinophilia, Eosinophilic enteritis, Thyroid disease, Poor growth, Viral infections, Susceptibility to mycobacteria and viruses; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.1965 SPPL2A Zornitza Stark Gene: sppl2a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1965 SPPL2A Zornitza Stark Classified gene: SPPL2A as Amber List (moderate evidence)
Mendeliome v0.1965 SPPL2A Zornitza Stark Gene: sppl2a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1964 SPPL2A Zornitza Stark gene: SPPL2A was added
gene: SPPL2A was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SPPL2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPPL2A were set to 30127434
Phenotypes for gene: SPPL2A were set to Susceptibility to mycobacteria and Salmonella
Review for gene: SPPL2A was set to AMBER
Added comment: Three individuals from two unrelated consanguineous family with two different homozygous splice site variants, functional data.
Sources: Expert list
Mendeliome v0.1963 IL23R Zornitza Stark Gene: il23r has been classified as Red List (Low Evidence).
Mendeliome v0.1960 IL23R Zornitza Stark Classified gene: IL23R as Red List (low evidence)
Mendeliome v0.1960 IL23R Zornitza Stark Gene: il23r has been classified as Red List (Low Evidence).
Mendeliome v0.1959 IL12RB2 Zornitza Stark Gene: il12rb2 has been classified as Red List (Low Evidence).
Mendeliome v0.1959 IL12RB2 Zornitza Stark gene: IL12RB2 was added
gene: IL12RB2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: IL12RB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL12RB2 were set to 30578351
Phenotypes for gene: IL12RB2 were set to Susceptibility to mycobacteria and Salmonella
Review for gene: IL12RB2 was set to RED
Added comment: Single individual reported, some functional data.
Sources: Expert list
Mendeliome v0.1958 C17orf62 Zornitza Stark Gene: c17orf62 has been classified as Green List (High Evidence).
Mendeliome v0.1958 C17orf62 Zornitza Stark Classified gene: C17orf62 as Green List (high evidence)
Mendeliome v0.1958 C17orf62 Zornitza Stark Gene: c17orf62 has been classified as Green List (High Evidence).
Mendeliome v0.1957 C17orf62 Zornitza Stark gene: C17orf62 was added
gene: C17orf62 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: C17orf62 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C17orf62 were set to 30361506; 30312704; 28351984
Phenotypes for gene: C17orf62 were set to Chronic granulomatous disease
Review for gene: C17orf62 was set to GREEN
Added comment: Seven Icelandic families reported with same homozygous variant, p.Tyr2Ter and an additional family from different ethnic background with different homozygous splice site variant. Functional data, including mouse model. Gene also known as EROS and CYBC1 (HGNC approved name)
Sources: Expert list
Mendeliome v0.1956 MKL1 Zornitza Stark Gene: mkl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1956 MKL1 Zornitza Stark Classified gene: MKL1 as Amber List (moderate evidence)
Mendeliome v0.1956 MKL1 Zornitza Stark Gene: mkl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1954 HYOU1 Zornitza Stark Gene: hyou1 has been classified as Red List (Low Evidence).
Mendeliome v0.1954 HYOU1 Zornitza Stark gene: HYOU1 was added
gene: HYOU1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: HYOU1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HYOU1 were set to 27913302
Phenotypes for gene: HYOU1 were set to Immunodeficiency 59 and hypoglycemia, MIM# 233600
Review for gene: HYOU1 was set to RED
Added comment: Single individual reported.
Sources: Expert list
Mendeliome v0.1953 SMARCD2 Zornitza Stark Gene: smarcd2 has been classified as Green List (High Evidence).
Mendeliome v0.1953 SMARCD2 Zornitza Stark Classified gene: SMARCD2 as Green List (high evidence)
Mendeliome v0.1953 SMARCD2 Zornitza Stark Gene: smarcd2 has been classified as Green List (High Evidence).
Mendeliome v0.1952 SMARCD2 Zornitza Stark gene: SMARCD2 was added
gene: SMARCD2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SMARCD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SMARCD2 were set to 28369036; 28369034
Phenotypes for gene: SMARCD2 were set to Specific granule deficiency 2, MIM# 617475; Neutropaenia; Neurodevelopmental abnormalities in some; Myelodysplasia
Review for gene: SMARCD2 was set to GREEN
Added comment: Three unrelated families and functional data.
Sources: Expert list
Mendeliome v0.1951 TNFRSF9 Zornitza Stark Gene: tnfrsf9 has been classified as Green List (High Evidence).
Mendeliome v0.1951 TNFRSF9 Zornitza Stark Classified gene: TNFRSF9 as Green List (high evidence)
Mendeliome v0.1951 TNFRSF9 Zornitza Stark Gene: tnfrsf9 has been classified as Green List (High Evidence).
Mendeliome v0.1950 TNFRSF9 Zornitza Stark gene: TNFRSF9 was added
gene: TNFRSF9 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: TNFRSF9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TNFRSF9 were set to 30872117; 31501153
Phenotypes for gene: TNFRSF9 were set to EBV lymphoproliferation; B-cell lymphoma; Chronic active EBV infection
Review for gene: TNFRSF9 was set to GREEN
Added comment: Six unrelated individuals, two with same homozygous G109S missense variant, functional data.
Sources: Expert list
Mendeliome v0.1949 CTPS1 Zornitza Stark Gene: ctps1 has been classified as Green List (High Evidence).
Mendeliome v0.1946 JAK1 Zornitza Stark Gene: jak1 has been classified as Red List (Low Evidence).
Mendeliome v0.1946 JAK1 Zornitza Stark gene: JAK1 was added
gene: JAK1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: JAK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: JAK1 were set to 28111307
Phenotypes for gene: JAK1 were set to Eosinophilia; Eosinophilic enteritis; Thyroid disease; Poor growth; Viral infections
Review for gene: JAK1 was set to RED
Added comment: Single family reported (mother and two children) with GoF variant.
Sources: Expert list
Mendeliome v0.1945 IL2RB Zornitza Stark Gene: il2rb has been classified as Green List (High Evidence).
Mendeliome v0.1945 IL2RB Zornitza Stark Classified gene: IL2RB as Green List (high evidence)
Mendeliome v0.1945 IL2RB Zornitza Stark Gene: il2rb has been classified as Green List (High Evidence).
Mendeliome v0.1943 AP3D1 Zornitza Stark Gene: ap3d1 has been classified as Red List (Low Evidence).
Mendeliome v0.1943 AP3D1 Zornitza Stark gene: AP3D1 was added
gene: AP3D1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: AP3D1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP3D1 were set to 26744459; 9697856
Phenotypes for gene: AP3D1 were set to Hermansky-Pudlak syndrome 10, MIM# 617050; Oculocutaneous albinism; Severe neutropaenia; Recurrent infections; Seizures; Hearing loss; Neurodevelopmental delay
Review for gene: AP3D1 was set to RED
Added comment: Single family and a mouse model.
Sources: Expert list
Mendeliome v0.1942 FAAP24 Zornitza Stark Gene: faap24 has been classified as Red List (Low Evidence).
Mendeliome v0.1942 FAAP24 Zornitza Stark gene: FAAP24 was added
gene: FAAP24 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: FAAP24 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAAP24 were set to 27473539
Phenotypes for gene: FAAP24 were set to EBV infection-driven lymphoproliferative disease
Review for gene: FAAP24 was set to RED
Added comment: Single sib pair with homozygous missense variant, some functional data.
Sources: Expert list
Mendeliome v0.1941 SH3KBP1 Zornitza Stark Gene: sh3kbp1 has been classified as Red List (Low Evidence).
Mendeliome v0.1941 SH3KBP1 Zornitza Stark gene: SH3KBP1 was added
gene: SH3KBP1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SH3KBP1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SH3KBP1 were set to 29636373; 21708930
Phenotypes for gene: SH3KBP1 were set to Immunodeficiency 61, MIM# 300310
Review for gene: SH3KBP1 was set to RED
Added comment: Single family reported, 247.5-kb intragenic deletion detected by array.
Sources: Expert list
Mendeliome v0.1940 ARHGEF1 Zornitza Stark Gene: arhgef1 has been classified as Red List (Low Evidence).
Mendeliome v0.1940 ARHGEF1 Zornitza Stark gene: ARHGEF1 was added
gene: ARHGEF1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ARHGEF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARHGEF1 were set to 30521495
Phenotypes for gene: ARHGEF1 were set to Immunodeficiency 62, MIM#618459
Review for gene: ARHGEF1 was set to RED
Added comment: Single family, functional data.
Sources: Expert list
Mendeliome v0.1939 ATP6AP1 Zornitza Stark Gene: atp6ap1 has been classified as Green List (High Evidence).
Mendeliome v0.1936 IRF2BP2 Zornitza Stark Gene: irf2bp2 has been classified as Red List (Low Evidence).
Mendeliome v0.1936 IRF2BP2 Zornitza Stark gene: IRF2BP2 was added
gene: IRF2BP2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: IRF2BP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IRF2BP2 were set to 27016798
Phenotypes for gene: IRF2BP2 were set to Immunodeficiency, common variable, 14, MIM# 617765
Review for gene: IRF2BP2 was set to RED
Added comment: Single family reported only.
Sources: Expert list
Mendeliome v0.1933 TOP2B Zornitza Stark Classified gene: TOP2B as Green List (high evidence)
Mendeliome v0.1933 TOP2B Zornitza Stark Gene: top2b has been classified as Green List (High Evidence).
Mendeliome v0.1932 SLC39A7 Zornitza Stark Gene: slc39a7 has been classified as Green List (High Evidence).
Mendeliome v0.1932 SLC39A7 Zornitza Stark Classified gene: SLC39A7 as Green List (high evidence)
Mendeliome v0.1932 SLC39A7 Zornitza Stark Gene: slc39a7 has been classified as Green List (High Evidence).
Mendeliome v0.1931 SLC39A7 Zornitza Stark gene: SLC39A7 was added
gene: SLC39A7 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SLC39A7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC39A7 were set to 30718914
Phenotypes for gene: SLC39A7 were set to Antibody deficiency; early onset infections; blistering dermatosis; failure to thrive; thrombocytopaenia
Review for gene: SLC39A7 was set to GREEN
Added comment: Five unrelated families with hypomorphic variants and a mouse model recapitulating phenotype.
Sources: Expert list
Mendeliome v0.1930 NFE2L2 Zornitza Stark Gene: nfe2l2 has been classified as Green List (High Evidence).
Mendeliome v0.1930 NFE2L2 Zornitza Stark Classified gene: NFE2L2 as Green List (high evidence)
Mendeliome v0.1930 NFE2L2 Zornitza Stark Gene: nfe2l2 has been classified as Green List (High Evidence).
Mendeliome v0.1929 NFE2L2 Zornitza Stark gene: NFE2L2 was added
gene: NFE2L2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: NFE2L2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NFE2L2 were set to 29018201
Phenotypes for gene: NFE2L2 were set to Immunodeficiency, developmental delay, and hypohomocysteinemia, MIM# 617744; Recurrent respiratory and skin infection; Growth retardation; Developmental delay, borderline ID; White matter cerebral lesions
Review for gene: NFE2L2 was set to GREEN
Added comment: Four unrelated individuals reported.
Sources: Expert list
Mendeliome v0.1928 ERBIN Zornitza Stark Gene: erbin has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1928 ERBIN Zornitza Stark Classified gene: ERBIN as Amber List (moderate evidence)
Mendeliome v0.1928 ERBIN Zornitza Stark Gene: erbin has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1927 ERBIN Zornitza Stark gene: ERBIN was added
gene: ERBIN was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ERBIN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ERBIN were set to 28126831
Phenotypes for gene: ERBIN were set to Recurrent respiratory infections; Susceptibility to S.aureus; Eczema; Hyperextensible joints; Scoliosis; Arterial dilatation in some
Review for gene: ERBIN was set to AMBER
Added comment: Single family and functional data.
Sources: Expert list
Mendeliome v0.1926 ZNF341 Zornitza Stark Gene: znf341 has been classified as Green List (High Evidence).
Mendeliome v0.1926 ZNF341 Zornitza Stark Classified gene: ZNF341 as Green List (high evidence)
Mendeliome v0.1926 ZNF341 Zornitza Stark Gene: znf341 has been classified as Green List (High Evidence).
Mendeliome v0.1925 ZNF341 Zornitza Stark gene: ZNF341 was added
gene: ZNF341 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ZNF341 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNF341 were set to 29907691; 29907690
Phenotypes for gene: ZNF341 were set to Hyper-IgE recurrent infection syndrome 3, autosomal recessive, MIM# 618282; Mild facial dysmorphism; Early onset eczema; Recurrent bacterial skin infections, abscesses; Recurrent respiratory infections, lung abscesses and pneumothoraces; Hyperextensible joints, bone fractures, retention of primary teeth
Review for gene: ZNF341 was set to GREEN
Added comment: 19 individuals from 10 families reported, some sharing the same homozygous variants (at least 4 different LoF variants reported).
Sources: Expert list
Mendeliome v0.1924 IL6ST Zornitza Stark Gene: il6st has been classified as Green List (High Evidence).
Mendeliome v0.1924 IL6ST Zornitza Stark Classified gene: IL6ST as Green List (high evidence)
Mendeliome v0.1924 IL6ST Zornitza Stark Gene: il6st has been classified as Green List (High Evidence).
Mendeliome v0.1923 IL6ST Zornitza Stark gene: IL6ST was added
gene: IL6ST was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: IL6ST was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL6ST were set to 28747427; 30309848; 12370259; 16041381; 31914175
Phenotypes for gene: IL6ST were set to Hyper-IgE recurrent infection syndrome 4, autosomal recessive, MIM# 618523; Stuve-Wiedemann-like syndrome: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response.
Review for gene: IL6ST was set to GREEN
Added comment: Also known as gp130. Two families with bi-allelic missense variants and immunological phenotype described initially. More recently, five individuals from three families reported with a more complex Stuve-Wiedemann-like phenotype reported, including skeletal dysplasia and neonatal lung dysfunction with additional features such as congenital thrombocytopenia, eczematoid dermatitis, renal abnormalities, and defective acute-phase response. These three families had bi-allelic LoF variants (nonsense and canonical splice site). Several mouse models support gene-disease association.
Sources: Expert list
Mendeliome v0.1922 IL6R Zornitza Stark Gene: il6r has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1919 IL6R Zornitza Stark Classified gene: IL6R as Amber List (moderate evidence)
Mendeliome v0.1919 IL6R Zornitza Stark Gene: il6r has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1918 NSMCE2 Zornitza Stark Gene: nsmce2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1918 LIG1 Zornitza Stark Gene: lig1 has been classified as Green List (High Evidence).
Mendeliome v0.1918 LIG1 Zornitza Stark Classified gene: LIG1 as Green List (high evidence)
Mendeliome v0.1918 LIG1 Zornitza Stark Gene: lig1 has been classified as Green List (High Evidence).
Mendeliome v0.1917 LIG1 Zornitza Stark gene: LIG1 was added
gene: LIG1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: LIG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LIG1 were set to 30395541
Phenotypes for gene: LIG1 were set to Combined immunodeficiency; Lymphopaenia; Hypogammaglobulinaemia; Recurrent bacterial and viral infections; Growth retardation; Sun sensitivity, radiation sensitivity; Macrocytosis
Review for gene: LIG1 was set to GREEN
Added comment: Five individuals from three families.
Sources: Expert list
Mendeliome v0.1916 POLE2 Zornitza Stark gene: POLE2 was added
gene: POLE2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: POLE2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLE2 were set to 26365386
Phenotypes for gene: POLE2 were set to Combined immunodeficiency; Lymphopaenia; Lack of TRECS, absent proliferation in response to antigens; Hypoglobulinaemia; Recurrent infections, disseminated BCG infections; Autoimmunity; Facial dysmorphism
Review for gene: POLE2 was set to RED
Added comment: Single family reported with homozygous splice site variant.
Sources: Expert list
Mendeliome v0.1915 FCHO1 Zornitza Stark Gene: fcho1 has been classified as Green List (High Evidence).
Mendeliome v0.1915 FCHO1 Zornitza Stark Classified gene: FCHO1 as Green List (high evidence)
Mendeliome v0.1915 FCHO1 Zornitza Stark Gene: fcho1 has been classified as Green List (High Evidence).
Mendeliome v0.1914 FCHO1 Zornitza Stark gene: FCHO1 was added
gene: FCHO1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: FCHO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FCHO1 were set to 32098969; 30822429
Phenotypes for gene: FCHO1 were set to Combined immunodeficiency; T cells: low, poor proliferation; B cells: normal number; Recurrent infections (viral, mycobacteria, bacterial, fungal); lymphoproliferation; Failure to thrive; Increased activation-induced T-cell death; Defective clathrin-mediated endocytosis
Review for gene: FCHO1 was set to GREEN
Added comment: More than 10 affected individuals with bi-allelic variants in this gene reported. Functional data.
Sources: Expert list
Mendeliome v0.1913 REL Zornitza Stark Gene: rel has been classified as Red List (Low Evidence).
Mendeliome v0.1913 REL Zornitza Stark gene: REL was added
gene: REL was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: REL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: REL were set to 31103457
Phenotypes for gene: REL were set to Combined immunodeficiency; T cells: normal, decreased memory CD4, poor proliferation; B cells: low, mostly naive, few switched memory B cells, impaired proliferation; Recurrent infections with bacteria, mycobacteria, salmonella and opportunistic organisms; Defective innate immunity
Review for gene: REL was set to RED
Added comment: Single individual from consanguineous family reported with homozygous canonical splice site variant, no functional data.
Sources: Expert list
Mendeliome v0.1912 TFRC Zornitza Stark Gene: tfrc has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1909 TFRC Zornitza Stark Classified gene: TFRC as Amber List (moderate evidence)
Mendeliome v0.1909 TFRC Zornitza Stark Gene: tfrc has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1908 TET2 Zornitza Stark changed review comment from: No evidence for Mendelian gene-disease association. Somatic TET2 variants are commonly found in cancers. One Finnish family reported where germline variant present 7 individuals, of whom 3 had lymphoma.; to: No evidence for Mendelian gene-disease association. Somatic TET2 variants are commonly found in cancers. One Finnish family reported where germline variant present 7 individuals, of whom 3 had lymphoma. Another French family reported with three sibs: frameshift variant and myeloid malignancies. Contribution of germline variants to malignancy risk to be established.
Mendeliome v0.1908 RELA Zornitza Stark Gene: rela has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1908 RELA Zornitza Stark Classified gene: RELA as Amber List (moderate evidence)
Mendeliome v0.1908 RELA Zornitza Stark Gene: rela has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1906 RELB Zornitza Stark Gene: relb has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1906 RELB Zornitza Stark Classified gene: RELB as Amber List (moderate evidence)
Mendeliome v0.1906 RELB Zornitza Stark Gene: relb has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1905 RELB Zornitza Stark gene: RELB was added
gene: RELB was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: RELB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RELB were set to 7834753; 26385063
Phenotypes for gene: RELB were set to Immunodeficiency 53, MIM# 617585; T cells: normal number, poor diversity, poor function; recurrent infections
Review for gene: RELB was set to AMBER
Added comment: Single family reported, functional data.
Sources: Expert list
Mendeliome v0.1904 CD247 Zornitza Stark Gene: cd247 has been classified as Red List (Low Evidence).
Mendeliome v0.1902 CD247 Zornitza Stark Classified gene: CD247 as Red List (low evidence)
Mendeliome v0.1902 CD247 Zornitza Stark Gene: cd247 has been classified as Red List (Low Evidence).
Mendeliome v0.1901 NSMCE2 Tiong Tan Classified gene: NSMCE2 as Amber List (moderate evidence)
Mendeliome v0.1901 NSMCE2 Tiong Tan Added comment: Comment on list classification: Two unrelated women with good functional evidence; but no additional cases since 2014
Mendeliome v0.1901 NSMCE2 Tiong Tan Gene: nsmce2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1900 NSMCE2 Tiong Tan gene: NSMCE2 was added
gene: NSMCE2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NSMCE2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NSMCE2 were set to 25105364
Phenotypes for gene: NSMCE2 were set to SECKEL SYNDROME 10
Penetrance for gene: NSMCE2 were set to Complete
Review for gene: NSMCE2 was set to AMBER
Added comment: Biallelic hypomorphic variants in two unrelated women with microcephalic primordial dwarfism, insulin-resistant diabetes, fatty liver, and hypertriglyceridemia developing in childhood; and primary gonadal failure. Good quality functional evidence. No additional confirmatory cases since 2014 publication
Sources: Literature
Mendeliome v0.1899 PLEKHA5 Zornitza Stark Classified gene: PLEKHA5 as Amber List (moderate evidence)
Mendeliome v0.1899 PLEKHA5 Zornitza Stark Gene: plekha5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1898 TRPA1 Zornitza Stark Gene: trpa1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1898 TRPA1 Zornitza Stark Classified gene: TRPA1 as Amber List (moderate evidence)
Mendeliome v0.1898 TRPA1 Zornitza Stark Gene: trpa1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1897 TRPA1 Zornitza Stark gene: TRPA1 was added
gene: TRPA1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: TRPA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRPA1 were set to 20547126; 16564016; 21468319; 28314413; 24778270; 24564660; 20718100
Phenotypes for gene: TRPA1 were set to Episodic pain syndrome, familial, 1, MIM# 615040
Review for gene: TRPA1 was set to AMBER
Added comment: Single family and a lot of functional data.
Sources: Expert list
Mendeliome v0.1896 PLEKHA5 Tiong Tan Gene: plekha5 has been classified as Red List (Low Evidence).
Mendeliome v0.1895 CNKSR1 Zornitza Stark Gene: cnksr1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1895 CNKSR1 Zornitza Stark Classified gene: CNKSR1 as Amber List (moderate evidence)
Mendeliome v0.1895 CNKSR1 Zornitza Stark Gene: cnksr1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1893 FRMD4A Zornitza Stark Gene: frmd4a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1893 FRMD4A Zornitza Stark Classified gene: FRMD4A as Amber List (moderate evidence)
Mendeliome v0.1893 FRMD4A Zornitza Stark Gene: frmd4a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1892 FRMD4A Zornitza Stark gene: FRMD4A was added
gene: FRMD4A was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: FRMD4A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FRMD4A were set to 25388005; 30214071
Phenotypes for gene: FRMD4A were set to Intellectual disability; microcephaly; Corpus callosum, agenesis of, with facial anomalies and cerebellar ataxia, MIM# 616819
Review for gene: FRMD4A was set to AMBER
Added comment: Single Bedouin Israeli family reported with homozygous variant initially. Good segregation data. No functional data. Another family reported as part of a large consanguineous microcephaly cohort, different variant.
Sources: Expert Review
Mendeliome v0.1891 NEK10 Zornitza Stark Gene: nek10 has been classified as Green List (High Evidence).
Mendeliome v0.1891 NEK10 Zornitza Stark Classified gene: NEK10 as Green List (high evidence)
Mendeliome v0.1891 NEK10 Zornitza Stark Gene: nek10 has been classified as Green List (High Evidence).
Mendeliome v0.1890 NEK10 Zornitza Stark gene: NEK10 was added
gene: NEK10 was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: NEK10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NEK10 were set to 31959991
Phenotypes for gene: NEK10 were set to Primary ciliary dyskinesia; bronchiectasis
Review for gene: NEK10 was set to GREEN
Added comment: Nine individuals from 5 unrelated families, some functional data.
Sources: NHS GMS
Mendeliome v0.1889 PIGK Zornitza Stark Gene: pigk has been classified as Green List (High Evidence).
Mendeliome v0.1889 PIGK Zornitza Stark Classified gene: PIGK as Green List (high evidence)
Mendeliome v0.1889 PIGK Zornitza Stark Gene: pigk has been classified as Green List (High Evidence).
Mendeliome v0.1887 ADARB1 Zornitza Stark Gene: adarb1 has been classified as Green List (High Evidence).
Mendeliome v0.1887 ADARB1 Zornitza Stark Classified gene: ADARB1 as Green List (high evidence)
Mendeliome v0.1887 ADARB1 Zornitza Stark Gene: adarb1 has been classified as Green List (High Evidence).
Mendeliome v0.1885 HSPB3 Zornitza Stark Gene: hspb3 has been classified as Red List (Low Evidence).
Mendeliome v0.1882 HSPB3 Zornitza Stark Classified gene: HSPB3 as Red List (low evidence)
Mendeliome v0.1882 HSPB3 Zornitza Stark Gene: hspb3 has been classified as Red List (Low Evidence).
Mendeliome v0.1881 FBXO38 Zornitza Stark Gene: fbxo38 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1878 FBXO38 Zornitza Stark Classified gene: FBXO38 as Amber List (moderate evidence)
Mendeliome v0.1878 FBXO38 Zornitza Stark Gene: fbxo38 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1877 DRP2 Zornitza Stark Gene: drp2 has been classified as Green List (High Evidence).
Mendeliome v0.1877 DRP2 Zornitza Stark Classified gene: DRP2 as Green List (high evidence)
Mendeliome v0.1877 DRP2 Zornitza Stark Gene: drp2 has been classified as Green List (High Evidence).
Mendeliome v0.1875 DGAT2 Zornitza Stark Gene: dgat2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1875 DGAT2 Zornitza Stark Classified gene: DGAT2 as Amber List (moderate evidence)
Mendeliome v0.1875 DGAT2 Zornitza Stark Gene: dgat2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1874 DGAT2 Zornitza Stark gene: DGAT2 was added
gene: DGAT2 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: DGAT2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DGAT2 were set to 26786738
Phenotypes for gene: DGAT2 were set to axonal Charcot-Marie-Tooth disease
Review for gene: DGAT2 was set to AMBER
Added comment: Single family (father and son) reported, with supporting in vitro functional assays and a zebrafish model.
Sources: Expert Review
Mendeliome v0.1873 ERLIN1 Bryony Thompson Classified gene: ERLIN1 as Green List (high evidence)
Mendeliome v0.1873 ERLIN1 Bryony Thompson Gene: erlin1 has been classified as Green List (High Evidence).
Mendeliome v0.1871 BTBD7 Zornitza Stark Gene: btbd7 has been classified as Red List (Low Evidence).
Mendeliome v0.1871 BTBD7 Zornitza Stark Classified gene: BTBD7 as Red List (low evidence)
Mendeliome v0.1871 BTBD7 Zornitza Stark Gene: btbd7 has been classified as Red List (Low Evidence).
Mendeliome v0.1870 NOS1AP Zornitza Stark Gene: nos1ap has been classified as Red List (Low Evidence).
Mendeliome v0.1870 NOS1AP Zornitza Stark Classified gene: NOS1AP as Red List (low evidence)
Mendeliome v0.1870 NOS1AP Zornitza Stark Gene: nos1ap has been classified as Red List (Low Evidence).
Mendeliome v0.1869 ARID2 Zornitza Stark Gene: arid2 has been classified as Green List (High Evidence).
Mendeliome v0.1869 ARID2 Zornitza Stark Phenotypes for gene: ARID2 were changed from to Coffin-Siris syndrome 6, MIM#617808
Mendeliome v0.1865 DYNC1H1 Zornitza Stark Gene: dync1h1 has been classified as Green List (High Evidence).
Mendeliome v0.1861 PQBP1 Zornitza Stark Gene: pqbp1 has been classified as Green List (High Evidence).
Mendeliome v0.1857 CHD3 Zornitza Stark Gene: chd3 has been classified as Green List (High Evidence).
Mendeliome v0.1853 DLG3 Zornitza Stark Gene: dlg3 has been classified as Green List (High Evidence).
Mendeliome v0.1850 FBN2 Zornitza Stark Added comment: Comment when marking as ready: The gene-disease association with Contractual arachnodactyly is extremely well established. The gene-disease association with macular degeneration much less so. There are ~4 families reported in the literature, and some discussion about whether the contribution of rare FBN2 variants in this context are under a 'monogenic' or 'polygenic' model.
Mendeliome v0.1850 FBN2 Zornitza Stark Gene: fbn2 has been classified as Green List (High Evidence).
Mendeliome v0.1846 AGTPBP1 Zornitza Stark Gene: agtpbp1 has been classified as Green List (High Evidence).
Mendeliome v0.1846 AGTPBP1 Zornitza Stark Classified gene: AGTPBP1 as Green List (high evidence)
Mendeliome v0.1846 AGTPBP1 Zornitza Stark Gene: agtpbp1 has been classified as Green List (High Evidence).
Mendeliome v0.1845 AGTPBP1 Zornitza Stark gene: AGTPBP1 was added
gene: AGTPBP1 was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: AGTPBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AGTPBP1 were set to 30420557
Phenotypes for gene: AGTPBP1 were set to Early onset cerebellar atrophy, developmental delay, and feeding and respiratory difficulties, severe motor neuronopathy; Neurodegeneration, childhood-onset, with cerebellar atrophy, 618276
Review for gene: AGTPBP1 was set to GREEN
Added comment: Thirteen individuals with bi-allelic variants in this gene, complex neurological phenotype of dev delay/ID, cerebellar atrophy and neuropathy, severe progressive course in six.
Sources: NHS GMS
Mendeliome v0.1843 ADGRG6 Zornitza Stark Classified gene: ADGRG6 as Green List (high evidence)
Mendeliome v0.1843 ADGRG6 Zornitza Stark Gene: adgrg6 has been classified as Green List (High Evidence).
Mendeliome v0.1842 ADGRG6 Zornitza Stark edited their review of gene: ADGRG6: Added comment: Three families reported originally with severe prenatal-onset arthrogryposis (PMID: 26004201), one family with more complex neurological phenotype (PMID:30549416).; Changed rating: GREEN; Changed publications: 30549416, 26004201; Changed phenotypes: Lethal congenital contracture syndrome 9, OMIM #616503; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1842 ARID2 Elena Savva reviewed gene: ARID2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:30838730; Phenotypes: Coffin-Siris syndrome 6; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.1842 EIF2AK2 Zornitza Stark Gene: eif2ak2 has been classified as Green List (High Evidence).
Mendeliome v0.1842 EIF2AK2 Zornitza Stark Classified gene: EIF2AK2 as Green List (high evidence)
Mendeliome v0.1842 EIF2AK2 Zornitza Stark Gene: eif2ak2 has been classified as Green List (High Evidence).
Mendeliome v0.1841 EIF2AK2 Zornitza Stark gene: EIF2AK2 was added
gene: EIF2AK2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EIF2AK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EIF2AK2 were set to 32197074
Phenotypes for gene: EIF2AK2 were set to Intellectual disability; white matter abnormalities; ataxia; regression with febrile illness
Review for gene: EIF2AK2 was set to GREEN
Added comment: Eight individuals with de novo variants and complex neurodevelopmental phenotype.
Sources: Literature
Mendeliome v0.1840 EIF2AK1 Zornitza Stark Gene: eif2ak1 has been classified as Red List (Low Evidence).
Mendeliome v0.1840 EIF2AK1 Zornitza Stark gene: EIF2AK1 was added
gene: EIF2AK1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EIF2AK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EIF2AK1 were set to 32197074
Phenotypes for gene: EIF2AK1 were set to Intellectual disability; white matter abnormalities
Review for gene: EIF2AK1 was set to RED
Added comment: Single individual reported with de novo variant in this gene.
Sources: Literature
Mendeliome v0.1839 NOVA2 Zornitza Stark Gene: nova2 has been classified as Green List (High Evidence).
Mendeliome v0.1839 NOVA2 Zornitza Stark Classified gene: NOVA2 as Green List (high evidence)
Mendeliome v0.1839 NOVA2 Zornitza Stark Gene: nova2 has been classified as Green List (High Evidence).
Mendeliome v0.1838 NOVA2 Zornitza Stark gene: NOVA2 was added
gene: NOVA2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NOVA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NOVA2 were set to 32197073
Phenotypes for gene: NOVA2 were set to Intellectual disability; autism; hypotonia; spasticity; ataxia
Mode of pathogenicity for gene: NOVA2 was set to Other
Review for gene: NOVA2 was set to GREEN
Added comment: Six individuals with de novo frameshift variants resulting in C-terminal extension suggesting partial LoF as mechanism.
Sources: Literature
Mendeliome v0.1837 GNB2 Sue White Classified gene: GNB2 as Amber List (moderate evidence)
Mendeliome v0.1837 GNB2 Sue White Gene: gnb2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1836 GNB2 Sue White gene: GNB2 was added
gene: GNB2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GNB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GNB2 were set to 31698099
Phenotypes for gene: GNB2 were set to intellectual disability; dysmorphic features
Penetrance for gene: GNB2 were set to Complete
Review for gene: GNB2 was set to AMBER
Added comment: single report of patient with de novo missense variant in GNB2 and intellectual disability. Emerging evidence of other de no missense variants in GNB2 and ID
Sources: Literature
Mendeliome v0.1835 NRROS Sue White Classified gene: NRROS as Green List (high evidence)
Mendeliome v0.1835 NRROS Sue White Gene: nrros has been classified as Green List (High Evidence).
Mendeliome v0.1834 NRROS Sue White gene: NRROS was added
gene: NRROS was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NRROS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NRROS were set to 32100099; 32197075
Phenotypes for gene: NRROS were set to neurodegeneration; intracranial calcification; epilepsy
Penetrance for gene: NRROS were set to Complete
Review for gene: NRROS was set to GREEN
Added comment: normal development or mild developmental delay until onset of regression around age of 1 concurrent with epilepsy
biallelic LOF mutations with functional evidence of pathogenicity
Sources: Literature
Mendeliome v0.1833 CNOT3 Zornitza Stark Gene: cnot3 has been classified as Green List (High Evidence).
Mendeliome v0.1830 CBS Zornitza Stark Gene: cbs has been classified as Green List (High Evidence).
Mendeliome v0.1830 CBS Zornitza Stark Phenotypes for gene: CBS were changed from to Homocystinuria, B6-responsive and nonresponsive types, 236200; Thrombosis, hyperhomocysteinemic, 236200
Mendeliome v0.1827 CBS Kristin Rigbye reviewed gene: CBS: Rating: GREEN; Mode of pathogenicity: None; Publications: 7506602, 10338090; Phenotypes: Homocystinuria, B6-responsive and nonresponsive types, 236200, Thrombosis, hyperhomocysteinemic, 236200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1827 HTR3C Zornitza Stark Gene: htr3c has been classified as Red List (Low Evidence).
Mendeliome v0.1826 HTR3C Zornitza Stark Classified gene: HTR3C as Red List (low evidence)
Mendeliome v0.1826 HTR3C Zornitza Stark Gene: htr3c has been classified as Red List (Low Evidence).
Mendeliome v0.1825 ZFP42 Zornitza Stark Gene: zfp42 has been classified as Red List (Low Evidence).
Mendeliome v0.1825 ZFP42 Zornitza Stark Classified gene: ZFP42 as Red List (low evidence)
Mendeliome v0.1825 ZFP42 Zornitza Stark Gene: zfp42 has been classified as Red List (Low Evidence).
Mendeliome v0.1824 SLC25A21 Zornitza Stark Gene: slc25a21 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1824 SLC25A21 Zornitza Stark Classified gene: SLC25A21 as Amber List (moderate evidence)
Mendeliome v0.1824 SLC25A21 Zornitza Stark Gene: slc25a21 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1822 SLC25A10 Zornitza Stark Gene: slc25a10 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1822 SLC25A10 Zornitza Stark Classified gene: SLC25A10 as Amber List (moderate evidence)
Mendeliome v0.1822 SLC25A10 Zornitza Stark Gene: slc25a10 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1820 QARS Zornitza Stark Gene: qars has been classified as Green List (High Evidence).
Mendeliome v0.1820 QARS Zornitza Stark Phenotypes for gene: QARS were changed from to Microcephaly, progressive, seizures, and cerebral and cerebellar atrophy, MIM# 615760
Mendeliome v0.1816 QARS Zornitza Stark reviewed gene: QARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 28620870, 25471517, 25432320, 25041233, 24656866, 32042906; Phenotypes: Microcephaly, progressive, seizures, and cerebral and cerebellar atrophy, MIM# 615760; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1816 PTCD3 Zornitza Stark Gene: ptcd3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1816 PTCD3 Zornitza Stark Classified gene: PTCD3 as Amber List (moderate evidence)
Mendeliome v0.1816 PTCD3 Zornitza Stark Gene: ptcd3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1814 PTCD1 Zornitza Stark gene: PTCD1 was added
gene: PTCD1 was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: PTCD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTCD1 were set to 25058219
Phenotypes for gene: PTCD1 were set to Cardiomyopathy
Review for gene: PTCD1 was set to RED
Added comment: Single case reported with no functional characterisation. Biochemical analyses of heart tissue identified global COX defect. No OMIM phenotype.
Sources: NHS GMS
Mendeliome v0.1813 PNPLA4 Zornitza Stark Gene: pnpla4 has been classified as Red List (Low Evidence).
Mendeliome v0.1811 PNPLA4 Zornitza Stark Classified gene: PNPLA4 as Red List (low evidence)
Mendeliome v0.1811 PNPLA4 Zornitza Stark Gene: pnpla4 has been classified as Red List (Low Evidence).
Mendeliome v0.1810 OXA1L Zornitza Stark Gene: oxa1l has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1810 OXA1L Zornitza Stark Classified gene: OXA1L as Amber List (moderate evidence)
Mendeliome v0.1810 OXA1L Zornitza Stark Gene: oxa1l has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1809 OXA1L Zornitza Stark gene: OXA1L was added
gene: OXA1L was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: OXA1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OXA1L were set to 30201738; 16435202
Phenotypes for gene: OXA1L were set to Encephalopathy; hypotonia; developmental delay
Review for gene: OXA1L was set to AMBER
Added comment: Single family reported with biochemical and molecular analyses of patient skeletal muscle and fibroblasts. In vitro functional assays in human cell lines, Drosophila model, and yeast-based assays. Loss of function affects oxidative phosphorylation complexes IV and V.
Sources: NHS GMS
Mendeliome v0.1808 NSUN3 Zornitza Stark Gene: nsun3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1808 NSUN3 Zornitza Stark Classified gene: NSUN3 as Amber List (moderate evidence)
Mendeliome v0.1808 NSUN3 Zornitza Stark Gene: nsun3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1807 NSUN3 Zornitza Stark gene: NSUN3 was added
gene: NSUN3 was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: NSUN3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NSUN3 were set to 27356879
Phenotypes for gene: NSUN3 were set to combined mitochondrial respiratory chain complex deficiency
Review for gene: NSUN3 was set to AMBER
Added comment: A single compound heterozygous case. Patient-derived fibroblasts exhibited severe defects in mitochondrial translation that can be rescued by exogenous expression of NSun3. In vitro functional assays also conducted.
Sources: NHS GMS
Mendeliome v0.1806 NDUFB10 Zornitza Stark Gene: ndufb10 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1806 NDUFB10 Zornitza Stark Classified gene: NDUFB10 as Amber List (moderate evidence)
Mendeliome v0.1806 NDUFB10 Zornitza Stark Gene: ndufb10 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1805 NDUFB10 Zornitza Stark gene: NDUFB10 was added
gene: NDUFB10 was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: NDUFB10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDUFB10 were set to 28040730; 32025618
Phenotypes for gene: NDUFB10 were set to fatal infantile lactic acidosis; cardiomyopathy
Review for gene: NDUFB10 was set to AMBER
Added comment: Single compound heterozygote case and mitochondrial phenotype. Assays of respiratory chain enzyme activities and functions in patient tissues/fibroblasts and in vitro functional assays. Plant model system supporting mitochondrial complex I dysfunction.
Sources: NHS GMS
Mendeliome v0.1804 NDUFA4 Zornitza Stark Classified gene: NDUFA4 as Green List (high evidence)
Mendeliome v0.1804 NDUFA4 Zornitza Stark Gene: ndufa4 has been classified as Green List (High Evidence).
Mendeliome v0.1803 NDUFA4 Zornitza Stark changed review comment from: Single family and a lot of functional data. Encodes a complex IV subunit.; to: Single family and a lot of functional data. Unpublished data on another family. Encodes a complex IV subunit.
Mendeliome v0.1803 MRPS14 Zornitza Stark Gene: mrps14 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1803 MRPS14 Zornitza Stark Classified gene: MRPS14 as Amber List (moderate evidence)
Mendeliome v0.1803 MRPS14 Zornitza Stark Gene: mrps14 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1802 MRM2 Zornitza Stark Gene: mrm2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1802 MRM2 Zornitza Stark Classified gene: MRM2 as Amber List (moderate evidence)
Mendeliome v0.1802 MRM2 Zornitza Stark Gene: mrm2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1801 MRM2 Zornitza Stark gene: MRM2 was added
gene: MRM2 was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: MRM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MRM2 were set to 28973171
Phenotypes for gene: MRM2 were set to MELAS-like
Review for gene: MRM2 was set to AMBER
Added comment: Single individual reported plus functional data. MRM2 encodes an enzyme responsible for 2'-O-methyl modification at position U1369 in the human mitochondrial 16S rRNA.
Sources: NHS GMS
Mendeliome v0.1800 MRPL3 Zornitza Stark Classified gene: MRPL3 as Green List (high evidence)
Mendeliome v0.1800 MRPL3 Zornitza Stark Gene: mrpl3 has been classified as Green List (High Evidence).
Mendeliome v0.1799 MRPL3 Zornitza Stark changed review comment from: 1 French family with 4 sibs with severe mitochondrial disorder - compound heterozygous mutations in the MRPL3 gene, no functional studies. 1 male infant with a severe mitochondrial disorder - compound heterozygous mutations in the MRPL3 gene, no functional studies.; to: 1 French family with 4 sibs with severe mitochondrial disorder - compound heterozygous mutations in the MRPL3 gene, some functional studies. 1 male infant with a severe mitochondrial disorder - compound heterozygous mutations in the MRPL3 gene, no functional studies.
Mendeliome v0.1799 IDH3A Zornitza Stark Gene: idh3a has been classified as Green List (High Evidence).
Mendeliome v0.1799 IDH3A Zornitza Stark Classified gene: IDH3A as Green List (high evidence)
Mendeliome v0.1799 IDH3A Zornitza Stark Gene: idh3a has been classified as Green List (High Evidence).
Mendeliome v0.1798 IDH3A Zornitza Stark gene: IDH3A was added
gene: IDH3A was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: IDH3A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IDH3A were set to 31012789; 30478029; 30058936; 28412069
Phenotypes for gene: IDH3A were set to Retinitis pigmentosa
Review for gene: IDH3A was set to GREEN
Added comment: Six unrelated families reported with retinitis pigmentosa. Mouse model.
Sources: NHS GMS
Mendeliome v0.1797 GATC Zornitza Stark Gene: gatc has been classified as Red List (Low Evidence).
Mendeliome v0.1796 GATB Zornitza Stark Gene: gatb has been classified as Red List (Low Evidence).
Mendeliome v0.1796 GATB Zornitza Stark gene: GATB was added
gene: GATB was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: GATB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GATB were set to 30283131
Phenotypes for gene: GATB were set to Mitochondrial cardiomyopathy
Review for gene: GATB was set to RED
Added comment: Single family reported with two affected siblings
Sources: NHS GMS
Mendeliome v0.1795 EFTUD2 Elena Savva reviewed gene: EFTUD2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mandibulofacial dysostosis, Guion-Almeida type 610536; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.1795 IFT172 Elena Savva reviewed gene: IFT172: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 26763875; Phenotypes: Retinitis pigmentosa 71 616394, Short-rib thoracic dysplasia 10 with or without polydactyly - 615630, Bardet-Biedl syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1795 FECH Zornitza Stark Gene: fech has been classified as Green List (High Evidence).
Mendeliome v0.1792 ADAM17 Zornitza Stark Gene: adam17 has been classified as Green List (High Evidence).
Mendeliome v0.1789 ADAM17 Zornitza Stark Classified gene: ADAM17 as Green List (high evidence)
Mendeliome v0.1789 ADAM17 Zornitza Stark Gene: adam17 has been classified as Green List (High Evidence).
Mendeliome v0.1788 ZNF462 Zornitza Stark Added comment: Comment when marking as ready: Multiple congenital anomaly syndrome characterised by variable but usually mild global developmental delay and common craniofacial abnormalities, including ptosis, abnormal head shape, downslanting palpebral fissures, epicanthal folds, arched eyebrows, and short upturned nose. Many patients have hypotonia and feeding difficulties. A few patients show agenesis of the corpus callosum on brain imaging. Most cases occur sporadically, but there are rare familial cases that show highly variable expressivity in the phenotypic manifestations.
Mendeliome v0.1788 ZNF462 Zornitza Stark Gene: znf462 has been classified as Green List (High Evidence).
Mendeliome v0.1784 HCFC1 Zornitza Stark Gene: hcfc1 has been classified as Green List (High Evidence).
Mendeliome v0.1780 TIMM22 Zornitza Stark Gene: timm22 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1780 TIMM22 Zornitza Stark Classified gene: TIMM22 as Amber List (moderate evidence)
Mendeliome v0.1780 TIMM22 Zornitza Stark Gene: timm22 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1778 TIMMDC1 Zornitza Stark Gene: timmdc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1778 TIMMDC1 Zornitza Stark Classified gene: TIMMDC1 as Amber List (moderate evidence)
Mendeliome v0.1778 TIMMDC1 Zornitza Stark Gene: timmdc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1776 TMEM65 Zornitza Stark Gene: tmem65 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1776 TMEM65 Zornitza Stark Classified gene: TMEM65 as Amber List (moderate evidence)
Mendeliome v0.1776 TMEM65 Zornitza Stark Gene: tmem65 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1774 SSBP1 Bryony Thompson Gene: ssbp1 has been classified as Green List (High Evidence).
Mendeliome v0.1774 SSBP1 Bryony Thompson Classified gene: SSBP1 as Green List (high evidence)
Mendeliome v0.1774 SSBP1 Bryony Thompson Gene: ssbp1 has been classified as Green List (High Evidence).
Mendeliome v0.1773 SSBP1 Bryony Thompson gene: SSBP1 was added
gene: SSBP1 was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: SSBP1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SSBP1 were set to 31298765; 31479473; 31550237; 31550240
Phenotypes for gene: SSBP1 were set to Optic atrophy with or without extraocular phenotypes
Review for gene: SSBP1 was set to GREEN
Added comment: At least 9 dominant families/cases and 1 recessive with optic atrophy with/without additional clinical features, including retinal macular dystrophy, sensorineural deafness, mitochondrial myopathy, and kidney failure. Supporting evidence in functional assays and zebrafish model.
Sources: NHS GMS
Mendeliome v0.1772 COX6A2 Zornitza Stark Gene: cox6a2 has been classified as Green List (High Evidence).
Mendeliome v0.1772 COX6A2 Zornitza Stark Classified gene: COX6A2 as Green List (high evidence)
Mendeliome v0.1772 COX6A2 Zornitza Stark Gene: cox6a2 has been classified as Green List (High Evidence).
Mendeliome v0.1770 YME1L1 Zornitza Stark Gene: yme1l1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1770 YME1L1 Zornitza Stark Classified gene: YME1L1 as Amber List (moderate evidence)
Mendeliome v0.1770 YME1L1 Zornitza Stark Gene: yme1l1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1766 ANXA11 Bryony Thompson gene: ANXA11 was added
gene: ANXA11 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ANXA11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ANXA11 were set to 28469040; 29845112; 30109997
Phenotypes for gene: ANXA11 were set to Amytrophic lateral sclerosis 23 MIM#617839
Review for gene: ANXA11 was set to GREEN
Added comment: 4 different missense variants in 10 patients from 7 unrelated families with amyotrophic lateral sclerosis and functional assays supporting association.
Sources: Expert list
Mendeliome v0.1765 UQCRQ Zornitza Stark Gene: uqcrq has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1762 UQCRQ Zornitza Stark Classified gene: UQCRQ as Amber List (moderate evidence)
Mendeliome v0.1762 UQCRQ Zornitza Stark Gene: uqcrq has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1761 UQCRC2 Zornitza Stark Gene: uqcrc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1758 UQCRC2 Zornitza Stark Classified gene: UQCRC2 as Amber List (moderate evidence)
Mendeliome v0.1758 UQCRC2 Zornitza Stark Gene: uqcrc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1757 UQCC3 Zornitza Stark Gene: uqcc3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1754 UQCC3 Zornitza Stark Classified gene: UQCC3 as Amber List (moderate evidence)
Mendeliome v0.1754 UQCC3 Zornitza Stark Gene: uqcc3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1753 TXN2 Zornitza Stark Gene: txn2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1750 TXN2 Zornitza Stark Classified gene: TXN2 as Amber List (moderate evidence)
Mendeliome v0.1750 TXN2 Zornitza Stark Gene: txn2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1749 TARS2 Zornitza Stark Gene: tars2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1746 TARS2 Zornitza Stark Classified gene: TARS2 as Amber List (moderate evidence)
Mendeliome v0.1746 TARS2 Zornitza Stark Gene: tars2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1745 SLC25A32 Zornitza Stark Gene: slc25a32 has been classified as Green List (High Evidence).
Mendeliome v0.1745 SLC25A32 Zornitza Stark Classified gene: SLC25A32 as Green List (high evidence)
Mendeliome v0.1745 SLC25A32 Zornitza Stark Gene: slc25a32 has been classified as Green List (High Evidence).
Mendeliome v0.1744 SLC25A32 Zornitza Stark gene: SLC25A32 was added
gene: SLC25A32 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SLC25A32 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A32 were set to 26933868; 28443623
Phenotypes for gene: SLC25A32 were set to Exercise intolerance, riboflavin-responsive, MIM# 616839
Review for gene: SLC25A32 was set to GREEN
Added comment: Two unrelated families reported with functional data. Muscle biopsy showed ragged-red fibers and lipid storage mainly in type I oxidative fibers, small type II fibers, and poor immunostaining for succinate dehydrogenase (FAD-dependent mitochondrial respiratory chain complex II). Oral supplementation with riboflavin led to dramatic improvement in the clinical and biologic abnormalities.
Sources: Expert list
Mendeliome v0.1743 NFS1 Zornitza Stark Gene: nfs1 has been classified as Red List (Low Evidence).
Mendeliome v0.1740 NFS1 Zornitza Stark Classified gene: NFS1 as Red List (low evidence)
Mendeliome v0.1740 NFS1 Zornitza Stark Gene: nfs1 has been classified as Red List (Low Evidence).
Mendeliome v0.1739 NDUFA6 Zornitza Stark Gene: ndufa6 has been classified as Green List (High Evidence).
Mendeliome v0.1736 NDUFA4 Zornitza Stark Gene: ndufa4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1733 NDUFA4 Zornitza Stark Classified gene: NDUFA4 as Amber List (moderate evidence)
Mendeliome v0.1733 NDUFA4 Zornitza Stark Gene: ndufa4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1732 NDUFA13 Zornitza Stark Gene: ndufa13 has been classified as Red List (Low Evidence).
Mendeliome v0.1729 NDUFA13 Zornitza Stark Classified gene: NDUFA13 as Red List (low evidence)
Mendeliome v0.1729 NDUFA13 Zornitza Stark Gene: ndufa13 has been classified as Red List (Low Evidence).
Mendeliome v0.1728 NADK2 Zornitza Stark Gene: nadk2 has been classified as Green List (High Evidence).
Mendeliome v0.1728 NADK2 Zornitza Stark Classified gene: NADK2 as Green List (high evidence)
Mendeliome v0.1728 NADK2 Zornitza Stark Gene: nadk2 has been classified as Green List (High Evidence).
Mendeliome v0.1726 ISCA1 Zornitza Stark Gene: isca1 has been classified as Green List (High Evidence).
Mendeliome v0.1726 ISCA1 Zornitza Stark Classified gene: ISCA1 as Green List (high evidence)
Mendeliome v0.1726 ISCA1 Zornitza Stark Gene: isca1 has been classified as Green List (High Evidence).
Mendeliome v0.1725 ISCA1 Zornitza Stark gene: ISCA1 was added
gene: ISCA1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ISCA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ISCA1 were set to 28356563; 32092383; 31016283; 30113620; 30105122
Phenotypes for gene: ISCA1 were set to Multiple mitochondrial dysfunctions syndrome 5, MIM# 617613
Review for gene: ISCA1 was set to GREEN
gene: ISCA1 was marked as current diagnostic
Added comment: Multiple unrelated families reported. Severe disorder characterised by progressive neurologic deterioration beginning in early infancy. Affected individuals have essentially no psychomotor development and have early-onset seizures with neurologic decline and spasticity. Brain imaging shows severe leukodystrophy with evidence of dys- or delayed myelination. Rat model results in early lethality. Founder variant c.259G > A, p.(Glu87Lys) reported in Indian families.
Sources: Expert list
Mendeliome v0.1724 ERCC5 Zornitza Stark Gene: ercc5 has been classified as Green List (High Evidence).
Mendeliome v0.1721 BTD Zornitza Stark Gene: btd has been classified as Green List (High Evidence).
Mendeliome v0.1718 CTNNB1 Zornitza Stark Gene: ctnnb1 has been classified as Green List (High Evidence).
Mendeliome v0.1714 TET2 Zornitza Stark Gene: tet2 has been classified as Red List (Low Evidence).
Mendeliome v0.1714 TET2 Zornitza Stark Classified gene: TET2 as Red List (low evidence)
Mendeliome v0.1714 TET2 Zornitza Stark Gene: tet2 has been classified as Red List (Low Evidence).
Mendeliome v0.1713 ARL11 Zornitza Stark Gene: arl11 has been classified as Red List (Low Evidence).
Mendeliome v0.1712 ARL11 Zornitza Stark Classified gene: ARL11 as Red List (low evidence)
Mendeliome v0.1712 ARL11 Zornitza Stark Gene: arl11 has been classified as Red List (Low Evidence).
Mendeliome v0.1711 CLCN6 Zornitza Stark Gene: clcn6 has been classified as Red List (Low Evidence).
Mendeliome v0.1708 CLCN6 Zornitza Stark Classified gene: CLCN6 as Red List (low evidence)
Mendeliome v0.1708 CLCN6 Zornitza Stark Gene: clcn6 has been classified as Red List (Low Evidence).
Mendeliome v0.1707 SEMA6B Zornitza Stark Gene: sema6b has been classified as Green List (High Evidence).
Mendeliome v0.1707 SEMA6B Zornitza Stark Classified gene: SEMA6B as Green List (high evidence)
Mendeliome v0.1707 SEMA6B Zornitza Stark Gene: sema6b has been classified as Green List (High Evidence).
Mendeliome v0.1706 SEMA6B Zornitza Stark gene: SEMA6B was added
gene: SEMA6B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SEMA6B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SEMA6B were set to 32169168
Phenotypes for gene: SEMA6B were set to Progressive myoclonic epilepsy
Mode of pathogenicity for gene: SEMA6B was set to Other
Review for gene: SEMA6B was set to GREEN
Added comment: Five individuals from unrelated families reported with de novo variants in the last exon, escaping NMD.
Sources: Literature
Mendeliome v0.1704 IFT74 Zornitza Stark Classified gene: IFT74 as Green List (high evidence)
Mendeliome v0.1704 IFT74 Zornitza Stark Gene: ift74 has been classified as Green List (High Evidence).
Mendeliome v0.1703 CAMTA1 Zornitza Stark Gene: camta1 has been classified as Green List (High Evidence).
Mendeliome v0.1703 CAMTA1 Zornitza Stark Phenotypes for gene: CAMTA1 were changed from to Cerebellar ataxia, nonprogressive, with mental retardation (614756 AD)
Mendeliome v0.1700 CAMTA1 Zornitza Stark reviewed gene: CAMTA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32157189, 22693284; Phenotypes: Cerebellar ataxia, nonprogressive, with mental retardation (614756 AD); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1700 TNNI3K Zornitza Stark Gene: tnni3k has been classified as Green List (High Evidence).
Mendeliome v0.1700 TNNI3K Zornitza Stark Classified gene: TNNI3K as Green List (high evidence)
Mendeliome v0.1700 TNNI3K Zornitza Stark Gene: tnni3k has been classified as Green List (High Evidence).
Mendeliome v0.1698 GPT2 Zornitza Stark Gene: gpt2 has been classified as Green List (High Evidence).
Mendeliome v0.1698 GPT2 Zornitza Stark Phenotypes for gene: GPT2 were changed from to Mental retardation, autosomal recessive 49, MIM#616281
Mendeliome v0.1695 GPT2 Zornitza Stark reviewed gene: GPT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 27601654, 25758935; Phenotypes: Mental retardation, autosomal recessive 49, MIM#616281; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1695 ERCC6L2 Zornitza Stark Gene: ercc6l2 has been classified as Green List (High Evidence).
Mendeliome v0.1692 PPM1E Zornitza Stark Gene: ppm1e has been classified as Red List (Low Evidence).
Mendeliome v0.1692 PPM1E Zornitza Stark Classified gene: PPM1E as Red List (low evidence)
Mendeliome v0.1692 PPM1E Zornitza Stark Gene: ppm1e has been classified as Red List (Low Evidence).
Mendeliome v0.1691 SUPT16H Zornitza Stark Gene: supt16h has been classified as Green List (High Evidence).
Mendeliome v0.1691 SUPT16H Zornitza Stark Classified gene: SUPT16H as Green List (high evidence)
Mendeliome v0.1691 SUPT16H Zornitza Stark Gene: supt16h has been classified as Green List (High Evidence).
Mendeliome v0.1689 RARS Zornitza Stark Gene: rars has been classified as Green List (High Evidence).
Mendeliome v0.1686 CXorf56 Zornitza Stark Classified gene: CXorf56 as Green List (high evidence)
Mendeliome v0.1686 CXorf56 Zornitza Stark Gene: cxorf56 has been classified as Green List (High Evidence).
Mendeliome v0.1685 TNR Zornitza Stark Gene: tnr has been classified as Green List (High Evidence).
Mendeliome v0.1685 TNR Zornitza Stark Classified gene: TNR as Green List (high evidence)
Mendeliome v0.1685 TNR Zornitza Stark Gene: tnr has been classified as Green List (High Evidence).
Mendeliome v0.1684 TNR Zornitza Stark gene: TNR was added
gene: TNR was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TNR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TNR were set to 32099069
Phenotypes for gene: TNR were set to Spastic para- or tetraparesis; Axial muscular hypotonia; Intellectual disability; Transient opisthotonus
Review for gene: TNR was set to GREEN
Added comment: 13 individuals from 8 unrelated families reported.
Sources: Literature
Mendeliome v0.1683 RSPRY1 Zornitza Stark Gene: rspry1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1683 RSPRY1 Zornitza Stark Phenotypes for gene: RSPRY1 were changed from to Spondyloepimetaphyseal dysplasia, Faden-Alkuraya type, 616585
Mendeliome v0.1680 RSPRY1 Zornitza Stark Classified gene: RSPRY1 as Amber List (moderate evidence)
Mendeliome v0.1680 RSPRY1 Zornitza Stark Gene: rspry1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1679 RSPRY1 Zornitza Stark reviewed gene: RSPRY1: Rating: AMBER; Mode of pathogenicity: None; Publications: 26365341; Phenotypes: Spondyloepimetaphyseal dysplasia, Faden-Alkuraya type, 616585; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1679 RPS23 Zornitza Stark Gene: rps23 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1675 RPS23 Zornitza Stark Classified gene: RPS23 as Amber List (moderate evidence)
Mendeliome v0.1675 RPS23 Zornitza Stark Gene: rps23 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1674 KANK1 Zornitza Stark Classified gene: KANK1 as Red List (low evidence)
Mendeliome v0.1674 KANK1 Zornitza Stark Gene: kank1 has been classified as Red List (Low Evidence).
Mendeliome v0.1673 KANK1 Zornitza Stark changed review comment from: Comment on list classification: Amber for nephrotic after discussion with Chirag Patel.; to: Comment on list classification: Red for nephrotic after discussion with Chirag Patel.
Mendeliome v0.1673 FUT6 Zornitza Stark Gene: fut6 has been classified as Red List (Low Evidence).
Mendeliome v0.1672 FUT6 Zornitza Stark Classified gene: FUT6 as Red List (low evidence)
Mendeliome v0.1672 FUT6 Zornitza Stark Gene: fut6 has been classified as Red List (Low Evidence).
Mendeliome v0.1671 FUT2 Zornitza Stark Gene: fut2 has been classified as Red List (Low Evidence).
Mendeliome v0.1671 FUT2 Zornitza Stark Phenotypes for gene: FUT2 were changed from to [Bombay phenotype, digenic] 616754; {Norwalk virus infection, resistance to}; {Vitamin B12 plasma level QTL1} 612542
Mendeliome v0.1670 FUT2 Zornitza Stark Classified gene: FUT2 as Red List (low evidence)
Mendeliome v0.1670 FUT2 Zornitza Stark Gene: fut2 has been classified as Red List (Low Evidence).
Mendeliome v0.1669 FUT2 Zornitza Stark reviewed gene: FUT2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: [Bombay phenotype, digenic] 616754, {Norwalk virus infection, resistance to}, {Vitamin B12 plasma level QTL1} 612542; Mode of inheritance: None
Mendeliome v0.1669 HMGA2 Zornitza Stark Gene: hmga2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1669 HMGA2 Zornitza Stark Phenotypes for gene: HMGA2 were changed from to Silver-Russel syndrome
Mendeliome v0.1666 HMGA2 Zornitza Stark Classified gene: HMGA2 as Amber List (moderate evidence)
Mendeliome v0.1666 HMGA2 Zornitza Stark Gene: hmga2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1665 HMGA2 Zornitza Stark reviewed gene: HMGA2: Rating: AMBER; Mode of pathogenicity: None; Publications: 29655892, 25809938; Phenotypes: Silver-Russel syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1665 DTD1 Zornitza Stark Gene: dtd1 has been classified as Red List (Low Evidence).
Mendeliome v0.1665 DTD1 Zornitza Stark Classified gene: DTD1 as Red List (low evidence)
Mendeliome v0.1665 DTD1 Zornitza Stark Gene: dtd1 has been classified as Red List (Low Evidence).
Mendeliome v0.1664 UTS2B Zornitza Stark Gene: uts2b has been classified as Red List (Low Evidence).
Mendeliome v0.1664 UTS2B Zornitza Stark Classified gene: UTS2B as Red List (low evidence)
Mendeliome v0.1664 UTS2B Zornitza Stark Gene: uts2b has been classified as Red List (Low Evidence).
Mendeliome v0.1663 MFSD2A Zornitza Stark Gene: mfsd2a has been classified as Green List (High Evidence).
Mendeliome v0.1663 MFSD2A Zornitza Stark Phenotypes for gene: MFSD2A were changed from to Microcephaly 15, primary, autosomal recessive, MIM# 616486
Mendeliome v0.1660 MFSD2A Zornitza Stark reviewed gene: MFSD2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 26005865, 26005868, 24828044; Phenotypes: Microcephaly 15, primary, autosomal recessive, MIM# 616486; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1660 MED12L Zornitza Stark Gene: med12l has been classified as Green List (High Evidence).
Mendeliome v0.1660 MED12L Zornitza Stark Classified gene: MED12L as Green List (high evidence)
Mendeliome v0.1660 MED12L Zornitza Stark Gene: med12l has been classified as Green List (High Evidence).
Mendeliome v0.1659 MED12L Zornitza Stark gene: MED12L was added
gene: MED12L was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: MED12L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MED12L were set to 31155615
Phenotypes for gene: MED12L were set to Intellectual disability; Seizures; Autism
Review for gene: MED12L was set to GREEN
Added comment: 7 individuals reported, 3 with CNVs (encompassing other genes) and 4 with SNVs (frameshift, nonsense and splice site).
Sources: Expert list
Mendeliome v0.1658 MCM3AP Zornitza Stark Gene: mcm3ap has been classified as Green List (High Evidence).
Mendeliome v0.1658 MCM3AP Zornitza Stark Classified gene: MCM3AP as Green List (high evidence)
Mendeliome v0.1658 MCM3AP Zornitza Stark Gene: mcm3ap has been classified as Green List (High Evidence).
Mendeliome v0.1657 MCM3AP Zornitza Stark gene: MCM3AP was added
gene: MCM3AP was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: MCM3AP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCM3AP were set to 24123876; 28633435; 28969388; 29982295
Phenotypes for gene: MCM3AP were set to Peripheral neuropathy, autosomal recessive, with or without impaired intellectual development, MIM#618124
Review for gene: MCM3AP was set to GREEN
gene: MCM3AP was marked as current diagnostic
Added comment: At least 10 families reported.
Sources: Expert list
Mendeliome v0.1656 MAPRE2 Zornitza Stark Gene: mapre2 has been classified as Green List (High Evidence).
Mendeliome v0.1653 PURA Zornitza Stark Gene: pura has been classified as Green List (High Evidence).
Mendeliome v0.1650 BPTF Zornitza Stark Gene: bptf has been classified as Green List (High Evidence).
Mendeliome v0.1647 TRIO Zornitza Stark Gene: trio has been classified as Green List (High Evidence).
Mendeliome v0.1644 MAN1B1 Zornitza Stark Gene: man1b1 has been classified as Green List (High Evidence).
Mendeliome v0.1644 MAN1B1 Zornitza Stark Phenotypes for gene: MAN1B1 were changed from to Mental retardation, autosomal recessive 15, MIM#614202
Mendeliome v0.1641 KMT2C Zornitza Stark Gene: kmt2c has been classified as Green List (High Evidence).
Mendeliome v0.1639 GLRX5 Zornitza Stark Gene: glrx5 has been classified as Green List (High Evidence).
Mendeliome v0.1639 GLRX5 Zornitza Stark Phenotypes for gene: GLRX5 were changed from to Anemia, sideroblastic, 3, pyridoxine-refractory; Spasticity, childhood-onset, with hyperglycinemia
Mendeliome v0.1637 NUDT2 Zornitza Stark Gene: nudt2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1637 NUDT2 Zornitza Stark Classified gene: NUDT2 as Amber List (moderate evidence)
Mendeliome v0.1637 NUDT2 Zornitza Stark Gene: nudt2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1635 SLC26A4 Elena Savva reviewed gene: SLC26A4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 24599119; Phenotypes: Deafness, autosomal recessive 4, with enlarged vestibular aqueduct 600791, Pendred syndrome 274600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1635 MAP3K7 Michelle Torres reviewed gene: MAP3K7: Rating: GREEN; Mode of pathogenicity: Other; Publications: 27426734, 27426733; Phenotypes: Cardiospondylocarpofacial syndrome 157800 AD, Frontometaphyseal dysplasia 2 617137 AD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1635 MAN1B1 Elena Savva reviewed gene: MAN1B1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 24348268; Phenotypes: Mental retardation, autosomal recessive 15; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.1635 GLRX5 Elena Savva reviewed gene: GLRX5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Anemia, sideroblastic, 3, pyridoxine-refractory, Spasticity, childhood-onset, with hyperglycinemia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1635 NKAP Zornitza Stark Gene: nkap has been classified as Green List (High Evidence).
Mendeliome v0.1635 NKAP Zornitza Stark Classified gene: NKAP as Green List (high evidence)
Mendeliome v0.1635 NKAP Zornitza Stark Gene: nkap has been classified as Green List (High Evidence).
Mendeliome v0.1633 TBR1 Zornitza Stark Gene: tbr1 has been classified as Green List (High Evidence).
Mendeliome v0.1630 GNRHR Zornitza Stark Gene: gnrhr has been classified as Green List (High Evidence).
Mendeliome v0.1627 MYO9A Zornitza Stark Gene: myo9a has been classified as Green List (High Evidence).
Mendeliome v0.1624 ZDHHC15 Zornitza Stark Gene: zdhhc15 has been classified as Red List (Low Evidence).
Mendeliome v0.1622 ZDHHC15 Zornitza Stark Classified gene: ZDHHC15 as Red List (low evidence)
Mendeliome v0.1622 ZDHHC15 Zornitza Stark Gene: zdhhc15 has been classified as Red List (Low Evidence).
Mendeliome v0.1621 ZBTB16 Zornitza Stark Gene: zbtb16 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1621 ZBTB16 Zornitza Stark Phenotypes for gene: ZBTB16 were changed from to Skeletal defects, genital hypoplasia, and mental retardation, OMIM #612447
Mendeliome v0.1618 ZBTB16 Zornitza Stark Classified gene: ZBTB16 as Amber List (moderate evidence)
Mendeliome v0.1618 ZBTB16 Zornitza Stark Gene: zbtb16 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1617 ZBTB16 Zornitza Stark reviewed gene: ZBTB16: Rating: AMBER; Mode of pathogenicity: None; Publications: 18611983; Phenotypes: Skeletal defects, genital hypoplasia, and mental retardation, OMIM #612447; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1617 ZBTB11 Zornitza Stark Gene: zbtb11 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1617 ZBTB11 Zornitza Stark Phenotypes for gene: ZBTB11 were changed from to Intellectual developmental disorder, autosomal recessive 69, OMIM #618383
Mendeliome v0.1614 ZBTB11 Zornitza Stark Classified gene: ZBTB11 as Amber List (moderate evidence)
Mendeliome v0.1614 ZBTB11 Zornitza Stark Gene: zbtb11 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1613 ZBTB11 Zornitza Stark reviewed gene: ZBTB11: Rating: AMBER; Mode of pathogenicity: None; Publications: 29893856; Phenotypes: Intellectual developmental disorder, autosomal recessive 69, OMIM #618383; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1613 WNT3 Zornitza Stark Gene: wnt3 has been classified as Red List (Low Evidence).
Mendeliome v0.1610 WNT3 Zornitza Stark Classified gene: WNT3 as Red List (low evidence)
Mendeliome v0.1610 WNT3 Zornitza Stark Gene: wnt3 has been classified as Red List (Low Evidence).
Mendeliome v0.1609 RS1 Zornitza Stark Gene: rs1 has been classified as Green List (High Evidence).
Mendeliome v0.1609 RS1 Zornitza Stark Phenotypes for gene: RS1 were changed from to Retinoschisis, MIM#312700
Mendeliome v0.1606 SMC1A Zornitza Stark Gene: smc1a has been classified as Green List (High Evidence).
Mendeliome v0.1603 LOXHD1 Zornitza Stark Gene: loxhd1 has been classified as Green List (High Evidence).
Mendeliome v0.1603 AIRE Zornitza Stark Gene: aire has been classified as Green List (High Evidence).
Mendeliome v0.1603 AIRE Zornitza Stark Phenotypes for gene: AIRE were changed from to Autoimmune polyendocrinopathy syndrome , type I, with or without reversible metaphyseal dysplasia, MIM#240300
Mendeliome v0.1599 LOXHD1 Zornitza Stark Phenotypes for gene: LOXHD1 were changed from to Deafness, autosomal recessive 77, MIM# 613079
Mendeliome v0.1596 LOXHD1 Zornitza Stark reviewed gene: LOXHD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19732867, 25792669; Phenotypes: Deafness, autosomal recessive 77, MIM# 613079; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1596 WFS1 Zornitza Stark Gene: wfs1 has been classified as Green List (High Evidence).
Mendeliome v0.1596 WFS1 Zornitza Stark Phenotypes for gene: WFS1 were changed from to ?Cataract 41; Deafness, autosomal dominant 6/14/38; Wolfram syndrome, autosomal recessive 1; Wolfram-like syndrome, autosomal dominant; {Diabetes mellitus, noninsulin-dependent, association with}
Mendeliome v0.1593 ING3 Zornitza Stark Gene: ing3 has been classified as Red List (Low Evidence).
Mendeliome v0.1593 ING3 Zornitza Stark Classified gene: ING3 as Red List (low evidence)
Mendeliome v0.1593 ING3 Zornitza Stark Gene: ing3 has been classified as Red List (Low Evidence).
Mendeliome v0.1592 SYN3 Zornitza Stark Gene: syn3 has been classified as Red List (Low Evidence).
Mendeliome v0.1592 SYN3 Zornitza Stark Classified gene: SYN3 as Red List (low evidence)
Mendeliome v0.1592 SYN3 Zornitza Stark Gene: syn3 has been classified as Red List (Low Evidence).
Mendeliome v0.1591 SIM1 Zornitza Stark Marked gene: SIM1 as ready
Mendeliome v0.1591 SIM1 Zornitza Stark Gene: sim1 has been classified as Red List (Low Evidence).
Mendeliome v0.1591 SIM1 Zornitza Stark Classified gene: SIM1 as Red List (low evidence)
Mendeliome v0.1591 SIM1 Zornitza Stark Gene: sim1 has been classified as Red List (Low Evidence).
Mendeliome v0.1590 SIM1 Zornitza Stark reviewed gene: SIM1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.1590 RS1 Kristin Rigbye reviewed gene: RS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15932525, 23453514, 23847049; Phenotypes: Retinoschisis, 312700; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.1590 AIRE Teresa Zhao reviewed gene: AIRE: Rating: GREEN; Mode of pathogenicity: Other; Publications: ; Phenotypes: Autoimmune polyendocrinopathy syndrome , type I, with or without reversible metaphyseal dysplasia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1588 KRT6A Zornitza Stark Gene: krt6a has been classified as Green List (High Evidence).
Mendeliome v0.1583 TUBA8 Zornitza Stark Gene: tuba8 has been classified as Red List (Low Evidence).
Mendeliome v0.1583 TUBA8 Zornitza Stark Phenotypes for gene: TUBA8 were changed from to Cortical dysplasia, complex, with other brain malformations 8, MIM# 613180
Mendeliome v0.1580 TUBA8 Zornitza Stark Classified gene: TUBA8 as Red List (low evidence)
Mendeliome v0.1580 TUBA8 Zornitza Stark Gene: tuba8 has been classified as Red List (Low Evidence).
Mendeliome v0.1579 TUBA8 Zornitza Stark reviewed gene: TUBA8: Rating: RED; Mode of pathogenicity: None; Publications: 19896110, 31481326, 28388629; Phenotypes: Cortical dysplasia, complex, with other brain malformations 8, MIM# 613180; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1579 RPL26 Zornitza Stark Gene: rpl26 has been classified as Red List (Low Evidence).
Mendeliome v0.1576 RPL26 Zornitza Stark Classified gene: RPL26 as Red List (low evidence)
Mendeliome v0.1576 RPL26 Zornitza Stark Gene: rpl26 has been classified as Red List (Low Evidence).
Mendeliome v0.1575 ABCC6 Zornitza Stark Gene: abcc6 has been classified as Green List (High Evidence).
Mendeliome v0.1570 TRIM8 Zornitza Stark Gene: trim8 has been classified as Green List (High Evidence).
Mendeliome v0.1567 TPH2 Zornitza Stark Gene: tph2 has been classified as Red List (Low Evidence).
Mendeliome v0.1564 TPH2 Zornitza Stark Classified gene: TPH2 as Red List (low evidence)
Mendeliome v0.1564 TPH2 Zornitza Stark Gene: tph2 has been classified as Red List (Low Evidence).
Mendeliome v0.1563 SPOP Zornitza Stark Gene: spop has been classified as Green List (High Evidence).
Mendeliome v0.1563 SPOP Zornitza Stark Classified gene: SPOP as Green List (high evidence)
Mendeliome v0.1563 SPOP Zornitza Stark Gene: spop has been classified as Green List (High Evidence).
Mendeliome v0.1561 TNIK Zornitza Stark Gene: tnik has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1561 TNIK Zornitza Stark Phenotypes for gene: TNIK were changed from to Mental retardation, autosomal recessive 54, MIM# 617028
Mendeliome v0.1558 TNIK Zornitza Stark Classified gene: TNIK as Amber List (moderate evidence)
Mendeliome v0.1558 TNIK Zornitza Stark Gene: tnik has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1557 TNIK Zornitza Stark reviewed gene: TNIK: Rating: AMBER; Mode of pathogenicity: None; Publications: 27106596, 23035106; Phenotypes: Mental retardation, autosomal recessive 54, MIM# 617028; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1557 TMLHE Zornitza Stark Gene: tmlhe has been classified as Green List (High Evidence).
Mendeliome v0.1554 TMEM94 Zornitza Stark Gene: tmem94 has been classified as Green List (High Evidence).
Mendeliome v0.1554 TMEM94 Zornitza Stark Classified gene: TMEM94 as Green List (high evidence)
Mendeliome v0.1554 TMEM94 Zornitza Stark Gene: tmem94 has been classified as Green List (High Evidence).
Mendeliome v0.1552 TMEM260 Zornitza Stark Gene: tmem260 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1549 TMEM260 Zornitza Stark Classified gene: TMEM260 as Amber List (moderate evidence)
Mendeliome v0.1549 TMEM260 Zornitza Stark Gene: tmem260 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1548 TKT Zornitza Stark Gene: tkt has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1545 TKT Zornitza Stark Classified gene: TKT as Amber List (moderate evidence)
Mendeliome v0.1545 TKT Zornitza Stark Gene: tkt has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1544 TELO2 Zornitza Stark Gene: telo2 has been classified as Green List (High Evidence).
Mendeliome v0.1541 TECR Zornitza Stark Gene: tecr has been classified as Red List (Low Evidence).
Mendeliome v0.1541 TECR Zornitza Stark Phenotypes for gene: TECR were changed from to Mental retardation, autosomal recessive, MIM#614020
Mendeliome v0.1538 TECR Zornitza Stark Classified gene: TECR as Red List (low evidence)
Mendeliome v0.1538 TECR Zornitza Stark Gene: tecr has been classified as Red List (Low Evidence).
Mendeliome v0.1537 TECR Zornitza Stark reviewed gene: TECR: Rating: RED; Mode of pathogenicity: None; Publications: 21212097; Phenotypes: Mental retardation, autosomal recessive, MIM#614020; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1537 TBC1D7 Zornitza Stark Gene: tbc1d7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1537 TBC1D7 Zornitza Stark Phenotypes for gene: TBC1D7 were changed from to Macrocephaly/megalencephaly syndrome, autosomal recessive, MIM# 248000
Mendeliome v0.1534 TBC1D7 Zornitza Stark Classified gene: TBC1D7 as Amber List (moderate evidence)
Mendeliome v0.1534 TBC1D7 Zornitza Stark Gene: tbc1d7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1533 TBC1D7 Zornitza Stark reviewed gene: TBC1D7: Rating: AMBER; Mode of pathogenicity: None; Publications: 24515783, 23687350; Phenotypes: Macrocephaly/megalencephaly syndrome, autosomal recessive, MIM# 248000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1533 TAF2 Zornitza Stark Gene: taf2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1533 TAF2 Zornitza Stark Phenotypes for gene: TAF2 were changed from to Mental retardation, autosomal recessive 40, MIM# 615599
Mendeliome v0.1530 TAF2 Zornitza Stark Classified gene: TAF2 as Amber List (moderate evidence)
Mendeliome v0.1530 TAF2 Zornitza Stark Gene: taf2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1529 TAF2 Zornitza Stark reviewed gene: TAF2: Rating: AMBER; Mode of pathogenicity: None; Publications: 21937992, 22633631, 26350204; Phenotypes: Mental retardation, autosomal recessive 40, MIM# 615599; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1529 TAF13 Zornitza Stark Gene: taf13 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1529 TAF13 Zornitza Stark Phenotypes for gene: TAF13 were changed from to Mental retardation, autosomal recessive 60, MIM# 617432
Mendeliome v0.1526 TAF13 Zornitza Stark Classified gene: TAF13 as Amber List (moderate evidence)
Mendeliome v0.1526 TAF13 Zornitza Stark Gene: taf13 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1525 TAF13 Zornitza Stark reviewed gene: TAF13: Rating: AMBER; Mode of pathogenicity: None; Publications: 28257693; Phenotypes: Mental retardation, autosomal recessive 60, MIM# 617432; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1525 SYT14 Zornitza Stark Gene: syt14 has been classified as Red List (Low Evidence).
Mendeliome v0.1525 SYT14 Zornitza Stark Phenotypes for gene: SYT14 were changed from to Spinocerebellar ataxia, autosomal recessive 11, MIM# 614229
Mendeliome v0.1522 SYT14 Zornitza Stark Classified gene: SYT14 as Red List (low evidence)
Mendeliome v0.1522 SYT14 Zornitza Stark Gene: syt14 has been classified as Red List (Low Evidence).
Mendeliome v0.1521 SYT14 Zornitza Stark reviewed gene: SYT14: Rating: RED; Mode of pathogenicity: None; Publications: 21835308; Phenotypes: Spinocerebellar ataxia, autosomal recessive 11, MIM# 614229; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1521 SRPX2 Zornitza Stark Gene: srpx2 has been classified as Red List (Low Evidence).
Mendeliome v0.1518 SRPX2 Zornitza Stark Classified gene: SRPX2 as Red List (low evidence)
Mendeliome v0.1518 SRPX2 Zornitza Stark Gene: srpx2 has been classified as Red List (Low Evidence).
Mendeliome v0.1517 SPRTN Zornitza Stark Gene: sprtn has been classified as Green List (High Evidence).
Mendeliome v0.1514 MC4R Zornitza Stark Gene: mc4r has been classified as Green List (High Evidence).
Mendeliome v0.1514 MC4R Zornitza Stark Phenotypes for gene: MC4R were changed from to {Obesity, resistence to (BMIQ20)} 618306; Obesity (BMIQ20) 618406 AD, AR
Mendeliome v0.1511 KMT2A Zornitza Stark Gene: kmt2a has been classified as Green List (High Evidence).
Mendeliome v0.1508 RBM20 Zornitza Stark Gene: rbm20 has been classified as Green List (High Evidence).
Mendeliome v0.1505 SLC52A1 Zornitza Stark Gene: slc52a1 has been classified as Red List (Low Evidence).
Mendeliome v0.1505 SLC52A1 Zornitza Stark Gene: slc52a1 has been classified as Red List (Low Evidence).
Mendeliome v0.1502 SLC52A1 Zornitza Stark Classified gene: SLC52A1 as Red List (low evidence)
Mendeliome v0.1502 SLC52A1 Zornitza Stark Gene: slc52a1 has been classified as Red List (Low Evidence).
Mendeliome v0.1500 PTCH2 Zornitza Stark Gene: ptch2 has been classified as Red List (Low Evidence).
Mendeliome v0.1497 PTCH2 Zornitza Stark Classified gene: PTCH2 as Red List (low evidence)
Mendeliome v0.1497 PTCH2 Zornitza Stark Gene: ptch2 has been classified as Red List (Low Evidence).
Mendeliome v0.1496 ZNF592 Chern Lim changed review comment from: No patients reported with ZNF592 variant that is clearly disease causing.

A 2010 paper published a biallelic missense variant segregating in one family with non-progressive, autosomal recessive, congenital cerebellar ataxia; however functional data not strongly supportive of pathogenicity (PMID: 20531441). Same authors later identified a homozygous WDR73 variant in that family which explains the phenotype (PMID: 26123727).; to: No patients reported with ZNF592 variant that is clearly disease causing.

A 2010 paper published a biallelic missense variant segregating in one family with non-progressive, autosomal recessive, congenital cerebellar ataxia; however functional data not strongly conclusive for pathogenicity (PMID: 20531441). Same authors later identified a homozygous WDR73 variant in that family which explains the phenotype (PMID: 26123727).
Mendeliome v0.1496 COL2A1 Zornitza Stark Gene: col2a1 has been classified as Green List (High Evidence).
Mendeliome v0.1496 COL2A1 Zornitza Stark Phenotypes for gene: COL2A1 were changed from to Achondrogenesis, type II or hypochondrogenesis 200610; Avascular necrosis of the femoral head 608805; Czech dysplasia 609162; Epiphyseal dysplasia, multiple, with myopia and deafness 132450; Kniest dysplasia 156550; Legg-Calve-Perthes disease 150600; Osteoarthritis with mild chondrodysplasia 604864; Platyspondylic skeletal dysplasia, Torrance type 151210; SED congenita 183900; SMED Strudwick type 184250; Spondyloepiphyseal dysplasia, Stanescu type 616583; Spondyloperipheral dysplasia 271700; Stickler sydrome, type I, nonsyndromic ocular 609508; Stickler syndrome, type I 108300; Vitreoretinopathy with phalangeal epiphyseal dysplasia
Mendeliome v0.1493 DNMT1 Zornitza Stark Gene: dnmt1 has been classified as Green List (High Evidence).
Mendeliome v0.1490 CEP135 Zornitza Stark Gene: cep135 has been classified as Green List (High Evidence).
Mendeliome v0.1490 CEP135 Zornitza Stark Phenotypes for gene: CEP135 were changed from to Microcephalic primordial dwarfism; Microcephaly 8, primary, autosomal recessive, 614673
Mendeliome v0.1487 CYP21A2 Zornitza Stark Gene: cyp21a2 has been classified as Green List (High Evidence).
Mendeliome v0.1487 CYP21A2 Zornitza Stark Phenotypes for gene: CYP21A2 were changed from to Adrenal hyperplasia, congenital, due to 21-hydroxylase deficiency, 201910; Hyperandrogenism, nonclassic type, due to 21-hydroxylase deficiency, 201910
Mendeliome v0.1485 CDK13 Zornitza Stark Gene: cdk13 has been classified as Green List (High Evidence).
Mendeliome v0.1482 F13B Zornitza Stark Gene: f13b has been classified as Green List (High Evidence).
Mendeliome v0.1479 FMO3 Zornitza Stark Gene: fmo3 has been classified as Green List (High Evidence).
Mendeliome v0.1476 PNPLA6 Zornitza Stark Gene: pnpla6 has been classified as Green List (High Evidence).
Mendeliome v0.1476 PNPLA6 Zornitza Stark Phenotypes for gene: PNPLA6 were changed from to Boucher-Neuhauser syndrome, 215470; ?Laurence-Moon syndrome, 245800; Oliver-McFarlane syndrome, 275400; Spastic paraplegia 39, autosomal recessive, 612020
Mendeliome v0.1473 MC4R Michelle Torres reviewed gene: MC4R: Rating: GREEN; Mode of pathogenicity: None; Publications: 29970488; Phenotypes: {Obesity, resistence to (BMIQ20)} 618306, Obesity (BMIQ20) 618406 AD, AR; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.1473 COL2A1 Elena Savva reviewed gene: COL2A1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 15895462, 17721977, 27234559, 20179744; Phenotypes: Achondrogenesis, type II or hypochondrogenesis 200610, Avascular necrosis of the femoral head 608805, Czech dysplasia 609162, Epiphyseal dysplasia, multiple, with myopia and deafness 132450, Kniest dysplasia 156550, Legg-Calve-Perthes disease 150600, Osteoarthritis with mild chondrodysplasia 604864, Platyspondylic skeletal dysplasia, Torrance type 151210, SED congenita 183900, SMED Strudwick type 184250, Spondyloepiphyseal dysplasia, Stanescu type 616583, Spondyloperipheral dysplasia 271700, Stickler sydrome, type I, nonsyndromic ocular 609508, Stickler syndrome, type I 108300, Vitreoretinopathy with phalangeal epiphyseal dysplasia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.1473 CEP135 Elena Savva reviewed gene: CEP135: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30214071, 22521416; Phenotypes: Microcephalic primordial dwarfism, Microcephaly 8, primary, autosomal recessive, 614673; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1473 CEP135 Elena Savva changed review comment from: Microcephalic primordial dwarfism - single case

Incomplete NMD shown, LOF mechanism; to: Microcephalic primordial dwarfism - single case

Incomplete NMD shown, LOF mechanism
Mendeliome v0.1473 CEP135 Elena Savva reviewed gene: CEP135: Rating: ; Mode of pathogenicity: None; Publications: PMID: 30214071, 22521416; Phenotypes: Microcephalic primordial dwarfism, Microcephaly 8, primary, autosomal recessive, 614673; Mode of inheritance: None
Mendeliome v0.1473 CYP21A2 Elena Savva reviewed gene: CYP21A2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Adrenal hyperplasia, congenital, due to 21-hydroxylase deficiency, 201910, Hyperandrogenism, nonclassic type, due to 21-hydroxylase deficiency, 201910; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1473 PNPLA6 Elena Savva reviewed gene: PNPLA6: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25480986, 24355708; Phenotypes: Boucher-Neuhauser syndrome, 215470, ?Laurence-Moon syndrome, 245800, Oliver-McFarlane syndrome, 275400, Spastic paraplegia 39, autosomal recessive, 612020; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1472 COX4I2 Zornitza Stark Classified gene: COX4I2 as Red List (low evidence)
Mendeliome v0.1472 COX4I2 Zornitza Stark Gene: cox4i2 has been classified as Red List (Low Evidence).
Mendeliome v0.1471 COX4I2 Zornitza Stark edited their review of gene: COX4I2: Added comment: Glu138Lys present in 3 homozygotes in gnomad, wich is out of keeping for this rare metabolic disorder. Note no other variants reported in this gene since original report in 2009. All variants submitted to ClinVar are VOUS/LB/B.; Changed rating: RED
Mendeliome v0.1471 SOBP Zornitza Stark Gene: sobp has been classified as Red List (Low Evidence).
Mendeliome v0.1471 SOBP Zornitza Stark Phenotypes for gene: SOBP were changed from to Mental retardation, anterior maxillary protrusion, and strabismus, MIM# 613671
Mendeliome v0.1468 SOBP Zornitza Stark Classified gene: SOBP as Red List (low evidence)
Mendeliome v0.1468 SOBP Zornitza Stark Gene: sobp has been classified as Red List (Low Evidence).
Mendeliome v0.1467 SOBP Zornitza Stark reviewed gene: SOBP: Rating: RED; Mode of pathogenicity: None; Publications: 21035105; Phenotypes: Mental retardation, anterior maxillary protrusion, and strabismus, MIM# 613671; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1467 SNIP1 Zornitza Stark Gene: snip1 has been classified as Red List (Low Evidence).
Mendeliome v0.1464 SNIP1 Zornitza Stark Classified gene: SNIP1 as Red List (low evidence)
Mendeliome v0.1464 SNIP1 Zornitza Stark Gene: snip1 has been classified as Red List (Low Evidence).
Mendeliome v0.1463 SMG9 Zornitza Stark Gene: smg9 has been classified as Green List (High Evidence).
Mendeliome v0.1460 TMPRSS3 Zornitza Stark Gene: tmprss3 has been classified as Green List (High Evidence).
Mendeliome v0.1459 TMPRSS3 Zornitza Stark Phenotypes for gene: TMPRSS3 were changed from to Deafness, autosomal recessive 8/10, MIM#601072
Mendeliome v0.1457 TMPRSS3 Zornitza Stark reviewed gene: TMPRSS3: Rating: GREEN; Mode of pathogenicity: None; Publications: 21786053, 17551081; Phenotypes: Deafness, autosomal recessive 8/10, MIM#601072; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1457 POU3F4 Zornitza Stark Gene: pou3f4 has been classified as Green List (High Evidence).
Mendeliome v0.1454 SLIT2 Zornitza Stark Gene: slit2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1451 SLIT2 Zornitza Stark Classified gene: SLIT2 as Amber List (moderate evidence)
Mendeliome v0.1451 SLIT2 Zornitza Stark Gene: slit2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1450 CEL Zornitza Stark Gene: cel has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1447 CEL Zornitza Stark Classified gene: CEL as Amber List (moderate evidence)
Mendeliome v0.1447 CEL Zornitza Stark Gene: cel has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1446 WDR81 Zornitza Stark Gene: wdr81 has been classified as Green List (High Evidence).
Mendeliome v0.1443 ARSG Zornitza Stark Gene: arsg has been classified as Red List (Low Evidence).
Mendeliome v0.1443 ARSG Zornitza Stark gene: ARSG was added
gene: ARSG was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ARSG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARSG were set to 29300381; 20679209; 25452429; 26975023
Phenotypes for gene: ARSG were set to Usher syndrome, type IV, MIM# 618144
Review for gene: ARSG was set to RED
Added comment: Atypical late-onset RP/HL phenotype described in 5 individuals from three Yemenite Jewish families. Same homozygous missense variant identified in all, founder effect. Animal models associated with neuronal ceroid lipofuscinosis.
Sources: Expert list
Mendeliome v0.1442 OTOF Zornitza Stark Gene: otof has been classified as Green List (High Evidence).
Mendeliome v0.1442 OTOF Zornitza Stark Phenotypes for gene: OTOF were changed from to Auditory neuropathy, autosomal recessive, 1 (MIM # 601071); Deafness, autosomal recessive 9 (MIM # 601071)
Mendeliome v0.1439 OTOF Zornitza Stark reviewed gene: OTOF: Rating: GREEN; Mode of pathogenicity: None; Publications: 16371502, 22906306; Phenotypes: Auditory neuropathy, autosomal recessive, 1 (MIM # 601071), Deafness, autosomal recessive 9 (MIM # 601071); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1439 MYL1 Bryony Thompson Classified gene: MYL1 as Amber List (moderate evidence)
Mendeliome v0.1439 MYL1 Bryony Thompson Gene: myl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1437 FXR1 Bryony Thompson Classified gene: FXR1 as Green List (high evidence)
Mendeliome v0.1437 FXR1 Bryony Thompson Added comment: Comment on list classification: Only two families, but a lot of functional supporting evidence including a mouse model. Pathogenic variants likely to be found in exon 15 of the skeletal muscle isoform, specifically.
Mendeliome v0.1437 FXR1 Bryony Thompson Gene: fxr1 has been classified as Green List (High Evidence).
Mendeliome v0.1435 TBCE Zornitza Stark Gene: tbce has been classified as Green List (High Evidence).
Mendeliome v0.1435 TBCE Zornitza Stark Phenotypes for gene: TBCE were changed from to Encephalopathy, progressive, with amyotrophy and optic atrophy; Hypoparathyroidism-retardation-dysmorphism syndrome; Kenny-Caffey syndrome, type 1
Mendeliome v0.1432 HTRA1 Zornitza Stark Gene: htra1 has been classified as Green List (High Evidence).
Mendeliome v0.1432 HTRA1 Zornitza Stark Phenotypes for gene: HTRA1 were changed from to {Macular degeneration, age-related, 7}, 6101493; {Macular degeneration, age-related, neovascular type}, 610149; CARASIL syndrome, 600142; Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 2, 616779
Mendeliome v0.1428 PLPBP Zornitza Stark Gene: plpbp has been classified as Green List (High Evidence).
Mendeliome v0.1425 PTPN11 Zornitza Stark Gene: ptpn11 has been classified as Green List (High Evidence).
Mendeliome v0.1425 PTPN11 Zornitza Stark Phenotypes for gene: PTPN11 were changed from to LEOPARD syndrome 1 (MIM#151100); Noonan syndrome 1 (MIM#163950); Metachondromatosis (MIM#156250)
Mendeliome v0.1421 SYNE1 Zornitza Stark Gene: syne1 has been classified as Green List (High Evidence).
Mendeliome v0.1421 SYNE1 Zornitza Stark Phenotypes for gene: SYNE1 were changed from to Arthrogryposis multiplex congenita, myogenic type, MIM# 618484; Emery-Dreifuss muscular dystrophy 4, autosomal dominant, MIM# 612998; Spinocerebellar ataxia, autosomal recessive 8, MIM# 610743
Mendeliome v0.1418 SYNE1 Zornitza Stark edited their review of gene: SYNE1: Added comment: Well established gene-disease association with Emery-Dreifuss muscular dystrophy (AD), and with recessive ataxia.
Distal arthrogryposis: three families reported with bi-allelic distal truncating variants in the KASH domain. This appears to be a specific genotype-phenotype correlation.; Changed rating: GREEN; Changed publications: 23352163, 27782104; Changed phenotypes: Arthrogryposis multiplex congenita, myogenic type, MIM# 618484, Emery-Dreifuss muscular dystrophy 4, autosomal dominant, MIM# 612998, Spinocerebellar ataxia, autosomal recessive 8, MIM# 610743; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.1418 PNPT1 Zornitza Stark Added comment: Comment when marking as ready: Those initially presenting with deafness may be at risk of progressive complex neurological course.
Mendeliome v0.1418 PNPT1 Zornitza Stark Gene: pnpt1 has been classified as Green List (High Evidence).
Mendeliome v0.1418 PNPT1 Zornitza Stark Gene: pnpt1 has been classified as Green List (High Evidence).
Mendeliome v0.1418 PNPT1 Zornitza Stark Phenotypes for gene: PNPT1 were changed from to Combined oxidative phosphorylation deficiency 13 (MIM#614932); Deafness, autosomal recessive 70 (MIM#614934)
Mendeliome v0.1415 TBCE Elena Savva reviewed gene: TBCE: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27666369; Phenotypes: Encephalopathy, progressive, with amyotrophy and optic atrophy, Hypoparathyroidism-retardation-dysmorphism syndrome, Kenny-Caffey syndrome, type 1; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1415 HTRA1 Elena Savva reviewed gene: HTRA1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 29895533, 19387015; Phenotypes: {Macular degeneration, age-related, 7}, 6101493, {Macular degeneration, age-related, neovascular type}, 610149, CARASIL syndrome, 600142, Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 2, 616779; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.1415 PTPN11 Crystle Lee reviewed gene: PTPN11: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 24935154, 11704759, 21533187; Phenotypes: LEOPARD syndrome 1 (MIM#151100), Noonan syndrome 1 (MIM#163950), Metachondromatosis (MIM#156250); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1415 SYNE1 Crystle Lee reviewed gene: SYNE1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30573412; Phenotypes: Spinocerebellar ataxia, autosomal recessive 8 (MIM#610743); Mode of inheritance: None
Mendeliome v0.1415 PNPT1 Crystle Lee reviewed gene: PNPT1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:31752325, PMID: 30244537, PMID: 28594066, PMID: 28645153; Phenotypes: Combined oxidative phosphorylation deficiency 13 (MIM#614932), Deafness, autosomal recessive 70 (MIM#614934); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1415 MPP3 Zornitza Stark Gene: mpp3 has been classified as Red List (Low Evidence).
Mendeliome v0.1415 MPP3 Zornitza Stark Classified gene: MPP3 as Red List (low evidence)
Mendeliome v0.1415 MPP3 Zornitza Stark Gene: mpp3 has been classified as Red List (Low Evidence).
Mendeliome v0.1414 GLRX Zornitza Stark Gene: glrx has been classified as Red List (Low Evidence).
Mendeliome v0.1414 GLRX Zornitza Stark Classified gene: GLRX as Red List (low evidence)
Mendeliome v0.1414 GLRX Zornitza Stark Gene: glrx has been classified as Red List (Low Evidence).
Mendeliome v0.1413 GC Zornitza Stark Gene: gc has been classified as Red List (Low Evidence).
Mendeliome v0.1413 GC Zornitza Stark Classified gene: GC as Red List (low evidence)
Mendeliome v0.1413 GC Zornitza Stark Gene: gc has been classified as Red List (Low Evidence).
Mendeliome v0.1412 AANAT Zornitza Stark Gene: aanat has been classified as Red List (Low Evidence).
Mendeliome v0.1409 AANAT Zornitza Stark Classified gene: AANAT as Red List (low evidence)
Mendeliome v0.1409 AANAT Zornitza Stark Gene: aanat has been classified as Red List (Low Evidence).
Mendeliome v0.1408 DUX4 Zornitza Stark Gene: dux4 has been classified as Red List (Low Evidence).
Mendeliome v0.1406 DUX4 Zornitza Stark Classified gene: DUX4 as Red List (low evidence)
Mendeliome v0.1406 DUX4 Zornitza Stark Gene: dux4 has been classified as Red List (Low Evidence).
Mendeliome v0.1405 SLC6A4 Zornitza Stark Gene: slc6a4 has been classified as Red List (Low Evidence).
Mendeliome v0.1405 SLC6A4 Zornitza Stark Phenotypes for gene: SLC6A4 were changed from to {Obsessive-compulsive disorder}, MIM# 164230; depression; alcohol dependence
Mendeliome v0.1402 SLC6A4 Zornitza Stark Classified gene: SLC6A4 as Red List (low evidence)
Mendeliome v0.1402 SLC6A4 Zornitza Stark Gene: slc6a4 has been classified as Red List (Low Evidence).
Mendeliome v0.1401 SLC6A4 Zornitza Stark reviewed gene: SLC6A4: Rating: RED; Mode of pathogenicity: None; Publications: 31629822; Phenotypes: {Obsessive-compulsive disorder}, MIM# 164230, depression, alcohol dependence; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1401 TREX1 Zornitza Stark Gene: trex1 has been classified as Green List (High Evidence).
Mendeliome v0.1401 TREX1 Zornitza Stark Phenotypes for gene: TREX1 were changed from to Aicardi-Goutieres syndrome 1, dominant and recessive; Chilblain lupus; {Systemic lupus erythematosus, susceptibility to}; Vasculopathy, retinal, with cerebral leukodystrophy
Mendeliome v0.1398 HGSNAT Zornitza Stark Gene: hgsnat has been classified as Green List (High Evidence).
Mendeliome v0.1398 HGSNAT Zornitza Stark Phenotypes for gene: HGSNAT were changed from to Mucopolysaccharidosis type IIIC (Sanfilippo C) (MIM #252930); Retinitis pigmentosa 73 (MIM # 616544)
Mendeliome v0.1395 PNKP Zornitza Stark Gene: pnkp has been classified as Green List (High Evidence).
Mendeliome v0.1392 DNAH5 Zornitza Stark Gene: dnah5 has been classified as Green List (High Evidence).
Mendeliome v0.1392 DNAH5 Zornitza Stark Phenotypes for gene: DNAH5 were changed from to Ciliary dyskinesia, primary, 3, with or without situs inversus (MIM #608644)
Mendeliome v0.1389 CDH23 Zornitza Stark Gene: cdh23 has been classified as Green List (High Evidence).
Mendeliome v0.1389 CDH23 Zornitza Stark Phenotypes for gene: CDH23 were changed from to Usher syndrome, type 1D (MIM# 601067); Deafness, autosomal recessive 12 (MIM # 601386) Usher syndrome, type 1D/F digenic (MIM #601067)
Mendeliome v0.1386 TREX1 Kristin Rigbye reviewed gene: TREX1: Rating: GREEN; Mode of pathogenicity: Other; Publications: 21937424; Phenotypes: Aicardi-Goutieres syndrome 1, dominant and recessive, Chilblain lupus, {Systemic lupus erythematosus, susceptibility to}, Vasculopathy, retinal, with cerebral leukodystrophy; Mode of inheritance: None; Current diagnostic: yes
Mendeliome v0.1386 HGSNAT Ain Roesley reviewed gene: HGSNAT: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 19479962, 31228227, 20825431, 20583299; Phenotypes: Mucopolysaccharidosis type IIIC (Sanfilippo C) (MIM #252930), Retinitis pigmentosa 73 (MIM # 616544); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1386 DNAH5 Ain Roesley reviewed gene: DNAH5: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 16627867; Phenotypes: Ciliary dyskinesia, primary, 3, with or without situs inversus (MIM #608644); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1386 CDH23 Ain Roesley reviewed gene: CDH23: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 11138009, 25468891, 21940737; Phenotypes: Usher syndrome, type 1D (MIM# 601067), Deafness, autosomal recessive 12 (MIM # 601386) Usher syndrome, type 1D/F digenic (MIM #601067); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1386 SHROOM4 Zornitza Stark Gene: shroom4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1383 SHROOM4 Zornitza Stark Classified gene: SHROOM4 as Amber List (moderate evidence)
Mendeliome v0.1383 SHROOM4 Zornitza Stark Gene: shroom4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1382 F2 Zornitza Stark Gene: f2 has been classified as Green List (High Evidence).
Mendeliome v0.1379 CHD2 Zornitza Stark Gene: chd2 has been classified as Green List (High Evidence).
Mendeliome v0.1377 INTS1 Zornitza Stark Gene: ints1 has been classified as Green List (High Evidence).
Mendeliome v0.1374 UGT1A4 Zornitza Stark Gene: ugt1a4 has been classified as Red List (Low Evidence).
Mendeliome v0.1374 UGT1A4 Zornitza Stark Classified gene: UGT1A4 as Red List (low evidence)
Mendeliome v0.1374 UGT1A4 Zornitza Stark Gene: ugt1a4 has been classified as Red List (Low Evidence).
Mendeliome v0.1372 SOX3 Zornitza Stark Gene: sox3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1369 SOX3 Zornitza Stark Classified gene: SOX3 as Amber List (moderate evidence)
Mendeliome v0.1369 SOX3 Zornitza Stark Gene: sox3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1368 AKT1 Zornitza Stark Gene: akt1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1364 AKT1 Zornitza Stark Classified gene: AKT1 as Amber List (moderate evidence)
Mendeliome v0.1364 AKT1 Zornitza Stark Gene: akt1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1363 PEX6 Zornitza Stark Gene: pex6 has been classified as Green List (High Evidence).
Mendeliome v0.1363 PEX6 Zornitza Stark Phenotypes for gene: PEX6 were changed from to Heimler syndrome 2, MIM# 616617; Peroxisome biogenesis disorder 4A (Zellweger), MIM# 614862; Peroxisome biogenesis disorder 4B, MIM# 614863
Mendeliome v0.1361 PUF60 Zornitza Stark Gene: puf60 has been classified as Green List (High Evidence).
Mendeliome v0.1359 ATRX Zornitza Stark Gene: atrx has been classified as Green List (High Evidence).
Mendeliome v0.1357 PEX6 Elena Savva reviewed gene: PEX6: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29220678; Phenotypes: Peroxisome biogenesis disorder 4B, Heimler syndrome 2, Peroxisome biogenesis disorder 4A (Zellweger); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.1357 ATRX Elena Savva reviewed gene: ATRX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Alpha-thalassemia myelodysplasia syndrome, somatic, Alpha-thalassemia/mental retardation syndrome, Mental retardation-hypotonic facies syndrome, X-linked; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.1357 PTRHD1 Zornitza Stark Gene: ptrhd1 has been classified as Green List (High Evidence).
Mendeliome v0.1357 PTRHD1 Zornitza Stark Classified gene: PTRHD1 as Green List (high evidence)
Mendeliome v0.1357 PTRHD1 Zornitza Stark Gene: ptrhd1 has been classified as Green List (High Evidence).
Mendeliome v0.1355 GFER Zornitza Stark Gene: gfer has been classified as Green List (High Evidence).
Mendeliome v0.1355 GFER Zornitza Stark Phenotypes for gene: GFER were changed from to Myopathy, mitochondrial progressive, with congenital cataract, hearing loss, and developmental delay (MIM #613076)
Mendeliome v0.1352 KRT14 Zornitza Stark Gene: krt14 has been classified as Green List (High Evidence).
Mendeliome v0.1352 KRT14 Zornitza Stark Phenotypes for gene: KRT14 were changed from to Epidermolysis bullosa simplex, recessive 1, 601001; Dermatopathia pigmentosa reticularis, 125595; Epidermolysis bullosa simplex, Dowling-Meara type, 131760; Epidermolysis bullosa simplex, Koebner type, 131900; Epidermolysis bullosa simplex, Weber-Cockayne type, 131800; Naegeli-Franceschetti-Jadassohn syndrome, 161000
Mendeliome v0.1348 KRT14 Zornitza Stark reviewed gene: KRT14: Rating: GREEN; Mode of pathogenicity: None; Publications: 16960809, 18049449; Phenotypes: Epidermolysis bullosa simplex, recessive 1, 601001, Dermatopathia pigmentosa reticularis, 125595, Epidermolysis bullosa simplex, Dowling-Meara type, 131760, Epidermolysis bullosa simplex, Koebner type, 131900, Epidermolysis bullosa simplex, Weber-Cockayne type, 131800, Naegeli-Franceschetti-Jadassohn syndrome, 161000; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.1348 GFER Ain Roesley reviewed gene: GFER: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28155230; Phenotypes: Myopathy, mitochondrial progressive, with congenital cataract, hearing loss, and developmental delay (MIM #613076); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1348 PLEKHG2 Zornitza Stark Classified gene: PLEKHG2 as Amber List (moderate evidence)
Mendeliome v0.1348 PLEKHG2 Zornitza Stark Gene: plekhg2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1347 PITRM1 Zornitza Stark Gene: pitrm1 has been classified as Green List (High Evidence).
Mendeliome v0.1347 PITRM1 Zornitza Stark Classified gene: PITRM1 as Green List (high evidence)
Mendeliome v0.1347 PITRM1 Zornitza Stark Gene: pitrm1 has been classified as Green List (High Evidence).
Mendeliome v0.1345 CSGALNACT1 Tiong Tan Gene: csgalnact1 has been classified as Green List (High Evidence).
Mendeliome v0.1345 CSGALNACT1 Tiong Tan Classified gene: CSGALNACT1 as Green List (high evidence)
Mendeliome v0.1345 CSGALNACT1 Tiong Tan Gene: csgalnact1 has been classified as Green List (High Evidence).
Mendeliome v0.1344 CSGALNACT1 Tiong Tan gene: CSGALNACT1 was added
gene: CSGALNACT1 was added to Mendeliome. Sources: Expert Review,Literature
Mode of inheritance for gene: CSGALNACT1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CSGALNACT1 were set to Congenital disorders of glycosylation; skeletal dysplasia; advanced bone age
Review for gene: CSGALNACT1 was set to GREEN
Added comment: Two unrelated families and functional studies
Sources: Expert Review, Literature
Mendeliome v0.1343 UNC13A Zornitza Stark Gene: unc13a has been classified as Red List (Low Evidence).
Mendeliome v0.1343 UNC13A Zornitza Stark Phenotypes for gene: UNC13A were changed from to Congenital myasthenia; dyskinesia; autism; developmental delay
Mendeliome v0.1340 UNC13A Zornitza Stark Classified gene: UNC13A as Red List (low evidence)
Mendeliome v0.1340 UNC13A Zornitza Stark Gene: unc13a has been classified as Red List (Low Evidence).
Mendeliome v0.1339 UNC13A Zornitza Stark reviewed gene: UNC13A: Rating: RED; Mode of pathogenicity: None; Publications: 27648472, 28192369; Phenotypes: Congenital myasthenia, dyskinesia, autism, developmental delay; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.1339 TOR1AIP1 Bryony Thompson Classified gene: TOR1AIP1 as Green List (high evidence)
Mendeliome v0.1339 TOR1AIP1 Bryony Thompson Added comment: Comment on list classification: Phenotype appears to be variable depending on which isoform is affected by the variants.
Mendeliome v0.1339 TOR1AIP1 Bryony Thompson Gene: tor1aip1 has been classified as Green List (High Evidence).
Mendeliome v0.1338 TOR1AIP1 Bryony Thompson gene: TOR1AIP1 was added
gene: TOR1AIP1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: TOR1AIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TOR1AIP1 were set to 24856141; 31299614; 30723199; 27342937
Phenotypes for gene: TOR1AIP1 were set to Muscular dystrophy, autosomal recessive, with rigid spine and distal joint contractures MIM#617072
Review for gene: TOR1AIP1 was set to GREEN
Added comment: At least 5 families/cases reported with muscular dystrophy and sometimes cardiomyopathy.
Sources: Expert list
Mendeliome v0.1337 EML1 Zornitza Stark Gene: eml1 has been classified as Green List (High Evidence).
Mendeliome v0.1334 ELMO2 Zornitza Stark Gene: elmo2 has been classified as Green List (High Evidence).
Mendeliome v0.1334 ELMO2 Zornitza Stark Classified gene: ELMO2 as Green List (high evidence)
Mendeliome v0.1334 ELMO2 Zornitza Stark Gene: elmo2 has been classified as Green List (High Evidence).
Mendeliome v0.1332 HHIP Zornitza Stark Gene: hhip has been classified as Red List (Low Evidence).
Mendeliome v0.1331 HHIP Zornitza Stark Classified gene: HHIP as Red List (low evidence)
Mendeliome v0.1331 HHIP Zornitza Stark Gene: hhip has been classified as Red List (Low Evidence).
Mendeliome v0.1330 FRA10AC1 Zornitza Stark Gene: fra10ac1 has been classified as Red List (Low Evidence).
Mendeliome v0.1329 FRA10AC1 Zornitza Stark Classified gene: FRA10AC1 as Red List (low evidence)
Mendeliome v0.1329 FRA10AC1 Zornitza Stark Gene: fra10ac1 has been classified as Red List (Low Evidence).
Mendeliome v0.1328 MMP25 Zornitza Stark Gene: mmp25 has been classified as Red List (Low Evidence).
Mendeliome v0.1328 MMP25 Zornitza Stark Classified gene: MMP25 as Red List (low evidence)
Mendeliome v0.1328 MMP25 Zornitza Stark Gene: mmp25 has been classified as Red List (Low Evidence).
Mendeliome v0.1326 MAP3K20 Bryony Thompson Classified gene: MAP3K20 as Green List (high evidence)
Mendeliome v0.1326 MAP3K20 Bryony Thompson Gene: map3k20 has been classified as Green List (High Evidence).
Mendeliome v0.1324 PCDH10 Zornitza Stark Gene: pcdh10 has been classified as Red List (Low Evidence).
Mendeliome v0.1321 PCDH10 Zornitza Stark Classified gene: PCDH10 as Red List (low evidence)
Mendeliome v0.1321 PCDH10 Zornitza Stark Gene: pcdh10 has been classified as Red List (Low Evidence).
Mendeliome v0.1320 LNPK Zornitza Stark Gene: lnpk has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1320 LNPK Zornitza Stark Phenotypes for gene: LNPK were changed from to Neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum, MIM# 618090
Mendeliome v0.1317 LNPK Zornitza Stark Classified gene: LNPK as Amber List (moderate evidence)
Mendeliome v0.1317 LNPK Zornitza Stark Gene: lnpk has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1316 LNPK Zornitza Stark reviewed gene: LNPK: Rating: AMBER; Mode of pathogenicity: None; Publications: 30032983; Phenotypes: Neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum, MIM# 618090; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1316 KIF4A Zornitza Stark Gene: kif4a has been classified as Red List (Low Evidence).
Mendeliome v0.1313 KIF4A Zornitza Stark Classified gene: KIF4A as Red List (low evidence)
Mendeliome v0.1313 KIF4A Zornitza Stark Gene: kif4a has been classified as Red List (Low Evidence).
Mendeliome v0.1312 KCNK4 Zornitza Stark Gene: kcnk4 has been classified as Green List (High Evidence).
Mendeliome v0.1312 KCNK4 Zornitza Stark Phenotypes for gene: KCNK4 were changed from to Facial dysmorphism, hypertrichosis, epilepsy, intellectual/developmental delay, and gingival overgrowth syndrome 618381
Mendeliome v0.1308 KCNK4 Zornitza Stark reviewed gene: KCNK4: Rating: GREEN; Mode of pathogenicity: Other; Publications: 30290154; Phenotypes: Facial dysmorphism, hypertrichosis, epilepsy, intellectual/developmental delay, and gingival overgrowth syndrome 618381; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1308 INTS8 Zornitza Stark Gene: ints8 has been classified as Red List (Low Evidence).
Mendeliome v0.1308 INTS8 Zornitza Stark Phenotypes for gene: INTS8 were changed from to Neurodevelopmental disorder with cerebellar hypoplasia and spasticity, MIM# 618572
Mendeliome v0.1305 INTS8 Zornitza Stark Classified gene: INTS8 as Red List (low evidence)
Mendeliome v0.1305 INTS8 Zornitza Stark Gene: ints8 has been classified as Red List (Low Evidence).
Mendeliome v0.1304 INTS8 Zornitza Stark reviewed gene: INTS8: Rating: RED; Mode of pathogenicity: None; Publications: 28542170; Phenotypes: Neurodevelopmental disorder with cerebellar hypoplasia and spasticity, MIM# 618572; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1304 SCO2 Zornitza Stark Gene: sco2 has been classified as Green List (High Evidence).
Mendeliome v0.1304 SCO2 Zornitza Stark Phenotypes for gene: SCO2 were changed from to Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1; Myopia 6; Charcot-Marie-Tooth type 4; Cerebellar ataxia and progressive peripheral axonal neuropthy
Mendeliome v0.1301 IDUA Zornitza Stark Gene: idua has been classified as Green List (High Evidence).
Mendeliome v0.1301 IDUA Zornitza Stark Phenotypes for gene: IDUA were changed from to Mucopolysaccharidosis Ih (MIM#607014); Mucopolysaccharidosis Ih/s (MIM#607015); Mucopolysaccharidosis Is (MIM#6070)
Mendeliome v0.1298 AHI1 Zornitza Stark Gene: ahi1 has been classified as Green List (High Evidence).
Mendeliome v0.1295 TGM5 Zornitza Stark Gene: tgm5 has been classified as Green List (High Evidence).
Mendeliome v0.1292 PLEC Zornitza Stark Gene: plec has been classified as Green List (High Evidence).
Mendeliome v0.1292 PLEC Zornitza Stark Phenotypes for gene: PLEC were changed from to ?Epidermolysis bullosa simplex with nail dystrophy, MIM# 616487; Epidermolysis bullosa simplex with muscular dystrophy, MIM# 226670; Epidermolysis bullosa simplex with pyloric atresia, MIM# 612138; Epidermolysis bullosa simplex, Ogna type MIM#131950; Muscular dystrophy, limb-girdle, autosomal recessive 17, MIM# 613723
Mendeliome v0.1289 SCO2 Elena Savva reviewed gene: SCO2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31844624, 29351582, 26427993; Phenotypes: Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1, Myopia 6, Charcot-Marie-Tooth type 4, Cerebellar ataxia and progressive peripheral axonal neuropthy; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.1289 IDUA Crystle Lee reviewed gene: IDUA: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28752568, 12865757; Phenotypes: Mucopolysaccharidosis Ih (MIM#607014), Mucopolysaccharidosis Ih/s (MIM#607015), Mucopolysaccharidosis Is (MIM#6070); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1289 AHI1 Elena Savva commented on gene: AHI1: Functional assays using zebrafish model support that the C-terminal SH3 domain is not required (PMID: 25616960)
Mendeliome v0.1289 PLEC Elena Savva reviewed gene: PLEC: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 22144912; Phenotypes: ?Epidermolysis bullosa simplex with nail dystrophy, Epidermolysis bullosa simplex with muscular dystrophy, Epidermolysis bullosa simplex with pyloric atresia, Epidermolysis bullosa simplex, Ogna type, Muscular dystrophy, limb-girdle; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.1289 HSPG2 Zornitza Stark Gene: hspg2 has been classified as Green List (High Evidence).
Mendeliome v0.1289 HSPG2 Zornitza Stark Phenotypes for gene: HSPG2 were changed from to Dyssegmental dysplasia, Silverman-Handmaker type; Schwartz-Jampel syndrome, type 1
Mendeliome v0.1286 BEST1 Zornitza Stark Gene: best1 has been classified as Green List (High Evidence).
Mendeliome v0.1285 WNT10A Elena Savva reviewed gene: WNT10A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 19559398, 30426266; Phenotypes: Odontoonychodermal dysplasia, Schopf-Schulz-Passarge syndrome, Tooth agenesis, selective, 4; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.1284 BEST1 Zornitza Stark Phenotypes for gene: BEST1 were changed from to Bestrophinopathy, autosomal recessive, MIM# 611809; Macular dystrophy, vitelliform, 2 MIM# 153700; Microcornea, rod-cone dystrophy, cataract, and posterior staphyloma, MIM# 193220; Retinitis pigmentosa-50, MIM# 613194; Retinitis pigmentosa, concentric, MIM# 61319; Vitreoretinochoroidopathy,MIM# 193220
Mendeliome v0.1282 IGBP1 Zornitza Stark Gene: igbp1 has been classified as Red List (Low Evidence).
Mendeliome v0.1282 IGBP1 Zornitza Stark Phenotypes for gene: IGBP1 were changed from to Corpus callosum, agenesis of, with mental retardation, ocular coloboma and micrognathia, MIM# 300472
Mendeliome v0.1279 IGBP1 Zornitza Stark Classified gene: IGBP1 as Red List (low evidence)
Mendeliome v0.1279 IGBP1 Zornitza Stark Gene: igbp1 has been classified as Red List (Low Evidence).
Mendeliome v0.1278 IGBP1 Zornitza Stark reviewed gene: IGBP1: Rating: RED; Mode of pathogenicity: None; Publications: 14556245; Phenotypes: Corpus callosum, agenesis of, with mental retardation, ocular coloboma and micrognathia, MIM# 300472; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.1278 HSPG2 Elena Savva reviewed gene: HSPG2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 16927315; Phenotypes: Dyssegmental dysplasia, Silverman-Handmaker type, Schwartz-Jampel syndrome, type 1; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1278 IQSEC2 Zornitza Stark Gene: iqsec2 has been classified as Green List (High Evidence).
Mendeliome v0.1274 GRIA1 Zornitza Stark Gene: gria1 has been classified as Green List (High Evidence).
Mendeliome v0.1274 GRIA1 Zornitza Stark Classified gene: GRIA1 as Green List (high evidence)
Mendeliome v0.1274 GRIA1 Zornitza Stark Gene: gria1 has been classified as Green List (High Evidence).
Mendeliome v0.1272 RCC1L Zornitza Stark Gene: rcc1l has been classified as Red List (Low Evidence).
Mendeliome v0.1272 RCC1L Zornitza Stark Classified gene: RCC1L as Red List (low evidence)
Mendeliome v0.1272 RCC1L Zornitza Stark Gene: rcc1l has been classified as Red List (Low Evidence).
Mendeliome v0.1271 HDAC4 Zornitza Stark Gene: hdac4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1267 HDAC4 Zornitza Stark Classified gene: HDAC4 as Amber List (moderate evidence)
Mendeliome v0.1267 HDAC4 Zornitza Stark Gene: hdac4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1266 UBR4 Zornitza Stark Gene: ubr4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1266 UBR4 Zornitza Stark Phenotypes for gene: UBR4 were changed from to Episodic ataxia; progressive neurological deterioration
Mendeliome v0.1263 UBR4 Zornitza Stark Classified gene: UBR4 as Amber List (moderate evidence)
Mendeliome v0.1263 UBR4 Zornitza Stark Gene: ubr4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1262 UBR4 Zornitza Stark reviewed gene: UBR4: Rating: AMBER; Mode of pathogenicity: None; Publications: 29062094, 23982692, 28600779; Phenotypes: Episodic ataxia, progressive neurological deterioration; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1262 GMNN Zornitza Stark Gene: gmnn has been classified as Green List (High Evidence).
Mendeliome v0.1259 TRAPPC4 Zornitza Stark Gene: trappc4 has been classified as Green List (High Evidence).
Mendeliome v0.1259 TRAPPC4 Zornitza Stark Classified gene: TRAPPC4 as Green List (high evidence)
Mendeliome v0.1259 TRAPPC4 Zornitza Stark Gene: trappc4 has been classified as Green List (High Evidence).
Mendeliome v0.1258 TRAPPC4 Zornitza Stark gene: TRAPPC4 was added
gene: TRAPPC4 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: TRAPPC4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRAPPC4 were set to 31794024
Phenotypes for gene: TRAPPC4 were set to intellectual disability; epilepsy; spasticity; microcephaly
Review for gene: TRAPPC4 was set to GREEN
Added comment: Seven individuals from three unrelated families reported; recurrent splice site variant (hg19:chr11:g.118890966A>G; TRAPPC4: NM_016146.5; c.454+3A>G), not a founder variant.
Sources: Expert Review
Mendeliome v0.1257 SNX27 Zornitza Stark Gene: snx27 has been classified as Green List (High Evidence).
Mendeliome v0.1257 SNX27 Zornitza Stark Classified gene: SNX27 as Green List (high evidence)
Mendeliome v0.1257 SNX27 Zornitza Stark Gene: snx27 has been classified as Green List (High Evidence).
Mendeliome v0.1255 NSF Zornitza Stark Gene: nsf has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1255 NSF Zornitza Stark Classified gene: NSF as Amber List (moderate evidence)
Mendeliome v0.1255 NSF Zornitza Stark Gene: nsf has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1254 NSF Zornitza Stark gene: NSF was added
gene: NSF was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NSF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NSF were set to 31675180
Phenotypes for gene: NSF were set to Seizures; EEG with burst suppression; Global developmental delay; Intellectual disability
Review for gene: NSF was set to AMBER
Added comment: Two individuals reported with de novo missense variants in this gene.
Sources: Literature
Mendeliome v0.1253 KAT8 Zornitza Stark Gene: kat8 has been classified as Green List (High Evidence).
Mendeliome v0.1253 KAT8 Zornitza Stark Classified gene: KAT8 as Green List (high evidence)
Mendeliome v0.1253 KAT8 Zornitza Stark Gene: kat8 has been classified as Green List (High Evidence).
Mendeliome v0.1251 GABBR2 Zornitza Stark Gene: gabbr2 has been classified as Green List (High Evidence).
Mendeliome v0.1248 HNRNPU Zornitza Stark Gene: hnrnpu has been classified as Green List (High Evidence).
Mendeliome v0.1248 SERPINI1 Zornitza Stark Gene: serpini1 has been classified as Green List (High Evidence).
Mendeliome v0.1244 SERPINI1 Zornitza Stark Phenotypes for gene: SERPINI1 were changed from to Encephalopathy, familial, with neuroserpin inclusion bodies MIM#604218
Mendeliome v0.1242 SERPINI1 Zornitza Stark reviewed gene: SERPINI1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28631894, 25401298, 12103288; Phenotypes: Encephalopathy, familial, with neuroserpin inclusion bodies MIM#604218; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1242 TTC7A Zornitza Stark Gene: ttc7a has been classified as Green List (High Evidence).
Mendeliome v0.1239 OPA1 Zornitza Stark Gene: opa1 has been classified as Green List (High Evidence).
Mendeliome v0.1237 SASS6 Zornitza Stark Gene: sass6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1237 SASS6 Zornitza Stark Phenotypes for gene: SASS6 were changed from to Microcephaly 14, primary, autosomal recessive, MIM# 616402
Mendeliome v0.1234 SASS6 Zornitza Stark Classified gene: SASS6 as Amber List (moderate evidence)
Mendeliome v0.1234 SASS6 Zornitza Stark Gene: sass6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1233 SASS6 Zornitza Stark reviewed gene: SASS6: Rating: AMBER; Mode of pathogenicity: None; Publications: 24951542, 30639237; Phenotypes: Microcephaly 14, primary, autosomal recessive, MIM# 616402; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1233 ACTB Sebastian Lunke Gene: actb has been classified as Green List (High Evidence).
Mendeliome v0.1229 ELMOD2 Sebastian Lunke Gene: elmod2 has been classified as Red List (Low Evidence).
Mendeliome v0.1228 ELMOD2 Sebastian Lunke Classified gene: ELMOD2 as Red List (low evidence)
Mendeliome v0.1228 ELMOD2 Sebastian Lunke Gene: elmod2 has been classified as Red List (Low Evidence).
Mendeliome v0.1227 GCKR Sebastian Lunke Gene: gckr has been classified as Red List (Low Evidence).
Mendeliome v0.1225 GCKR Sebastian Lunke Classified gene: GCKR as Red List (low evidence)
Mendeliome v0.1225 GCKR Sebastian Lunke Gene: gckr has been classified as Red List (Low Evidence).
Mendeliome v0.1224 CNTN1 Zornitza Stark Gene: cntn1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1221 CNTN1 Zornitza Stark Classified gene: CNTN1 as Amber List (moderate evidence)
Mendeliome v0.1221 CNTN1 Zornitza Stark Gene: cntn1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1220 OPA1 Ee Ming Wong reviewed gene: OPA1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30165240; Phenotypes: 1. ?Mitochondrial DNA depletion syndrome 14 (encephalocardiomyopathic type) 6168963, 2. {Glaucoma, normal tension, susceptibility to} 6066573, 3. Behr syndrome 210000 AR, 4. Optic atrophy 1 165500 AD, 5. Optic atrophy plus syndrome 125250 AD; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.1217 NDUFA12 Zornitza Stark Classified gene: NDUFA12 as Red List (low evidence)
Mendeliome v0.1217 NDUFA12 Zornitza Stark Gene: ndufa12 has been classified as Red List (Low Evidence).
Mendeliome v0.1216 MRPS7 Zornitza Stark Gene: mrps7 has been classified as Red List (Low Evidence).
Mendeliome v0.1213 MRPS7 Zornitza Stark Classified gene: MRPS7 as Red List (low evidence)
Mendeliome v0.1213 MRPS7 Zornitza Stark Gene: mrps7 has been classified as Red List (Low Evidence).
Mendeliome v0.1212 MRPS23 Zornitza Stark Gene: mrps23 has been classified as Red List (Low Evidence).
Mendeliome v0.1209 MRPS23 Zornitza Stark Classified gene: MRPS23 as Red List (low evidence)
Mendeliome v0.1209 MRPS23 Zornitza Stark Gene: mrps23 has been classified as Red List (Low Evidence).
Mendeliome v0.1208 MRPL12 Zornitza Stark Gene: mrpl12 has been classified as Red List (Low Evidence).
Mendeliome v0.1205 MRPL12 Zornitza Stark Classified gene: MRPL12 as Red List (low evidence)
Mendeliome v0.1205 MRPL12 Zornitza Stark Gene: mrpl12 has been classified as Red List (Low Evidence).
Mendeliome v0.1204 LYRM4 Zornitza Stark Gene: lyrm4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1201 LYRM4 Zornitza Stark Classified gene: LYRM4 as Amber List (moderate evidence)
Mendeliome v0.1201 LYRM4 Zornitza Stark Gene: lyrm4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1200 COX8A Zornitza Stark Gene: cox8a has been classified as Red List (Low Evidence).
Mendeliome v0.1197 COX8A Zornitza Stark Classified gene: COX8A as Red List (low evidence)
Mendeliome v0.1197 COX8A Zornitza Stark Gene: cox8a has been classified as Red List (Low Evidence).
Mendeliome v0.1196 COA5 Zornitza Stark Gene: coa5 has been classified as Red List (Low Evidence).
Mendeliome v0.1193 COA5 Zornitza Stark Classified gene: COA5 as Red List (low evidence)
Mendeliome v0.1193 COA5 Zornitza Stark Gene: coa5 has been classified as Red List (Low Evidence).
Mendeliome v0.1192 CLCN5 Zornitza Stark Gene: clcn5 has been classified as Green List (High Evidence).
Mendeliome v0.1192 CLCN5 Zornitza Stark Phenotypes for gene: CLCN5 were changed from to Dent disease, MIM#300009; Hypophosphatemic rickets, MIM#300554; Nephrolithiasis, type I, MIM#310468; Proteinuria, low molecular weight, with hypercalciuric nephrocalcinosis, MIM#308990
Mendeliome v0.1190 CLCN5 Zornitza Stark reviewed gene: CLCN5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Dent disease, MIM#300009, Hypophosphatemic rickets, MIM#300554, Nephrolithiasis, type I, MIM#310468, Proteinuria, low molecular weight, with hypercalciuric nephrocalcinosis, MIM#308990; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.1190 PHEX Zornitza Stark Gene: phex has been classified as Green List (High Evidence).
Mendeliome v0.1188 EHMT1 Zornitza Stark Gene: ehmt1 has been classified as Green List (High Evidence).
Mendeliome v0.1185 FIBP Zornitza Stark Gene: fibp has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1182 FIBP Zornitza Stark Classified gene: FIBP as Amber List (moderate evidence)
Mendeliome v0.1182 FIBP Zornitza Stark Gene: fibp has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1181 CHST8 Zornitza Stark Gene: chst8 has been classified as Red List (Low Evidence).
Mendeliome v0.1178 CHST8 Zornitza Stark Classified gene: CHST8 as Red List (low evidence)
Mendeliome v0.1178 CHST8 Zornitza Stark Gene: chst8 has been classified as Red List (Low Evidence).
Mendeliome v0.1177 RASA2 Sebastian Lunke Gene: rasa2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1176 RASA2 Sebastian Lunke Classified gene: RASA2 as Amber List (moderate evidence)
Mendeliome v0.1176 RASA2 Sebastian Lunke Gene: rasa2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1175 TKFC Zornitza Stark Gene: tkfc has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1175 TKFC Zornitza Stark Classified gene: TKFC as Amber List (moderate evidence)
Mendeliome v0.1175 TKFC Zornitza Stark Gene: tkfc has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1173 RALGAPA1 Zornitza Stark Gene: ralgapa1 has been classified as Green List (High Evidence).
Mendeliome v0.1173 RALGAPA1 Zornitza Stark Classified gene: RALGAPA1 as Green List (high evidence)
Mendeliome v0.1173 RALGAPA1 Zornitza Stark Gene: ralgapa1 has been classified as Green List (High Evidence).
Mendeliome v0.1171 EPB41L1 Zornitza Stark Gene: epb41l1 has been classified as Red List (Low Evidence).
Mendeliome v0.1168 EPB41L1 Zornitza Stark Classified gene: EPB41L1 as Red List (low evidence)
Mendeliome v0.1168 EPB41L1 Zornitza Stark Gene: epb41l1 has been classified as Red List (Low Evidence).
Mendeliome v0.1167 EMC1 Zornitza Stark Gene: emc1 has been classified as Green List (High Evidence).
Mendeliome v0.1164 SOD2 Zornitza Stark Gene: sod2 has been classified as Red List (Low Evidence).
Mendeliome v0.1162 SOD2 Zornitza Stark Classified gene: SOD2 as Red List (low evidence)
Mendeliome v0.1162 SOD2 Zornitza Stark Gene: sod2 has been classified as Red List (Low Evidence).
Mendeliome v0.1161 ATAD3A Zornitza Stark Gene: atad3a has been classified as Green List (High Evidence).
Mendeliome v0.1158 MYOM1 Zornitza Stark Gene: myom1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1155 MYOM1 Zornitza Stark Classified gene: MYOM1 as Amber List (moderate evidence)
Mendeliome v0.1155 MYOM1 Zornitza Stark Gene: myom1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1151 DLG4 Zornitza Stark Classified gene: DLG4 as Green List (high evidence)
Mendeliome v0.1151 DLG4 Zornitza Stark Gene: dlg4 has been classified as Green List (High Evidence).
Mendeliome v0.1150 DIP2B Zornitza Stark Gene: dip2b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1146 DIP2B Zornitza Stark Classified gene: DIP2B as Amber List (moderate evidence)
Mendeliome v0.1146 DIP2B Zornitza Stark Gene: dip2b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1145 DCPS Zornitza Stark Gene: dcps has been classified as Green List (High Evidence).
Mendeliome v0.1145 DCPS Zornitza Stark Classified gene: DCPS as Green List (high evidence)
Mendeliome v0.1145 DCPS Zornitza Stark Gene: dcps has been classified as Green List (High Evidence).
Mendeliome v0.1143 CUX1 Zornitza Stark Gene: cux1 has been classified as Green List (High Evidence).
Mendeliome v0.1143 CUX1 Zornitza Stark Classified gene: CUX1 as Green List (high evidence)
Mendeliome v0.1143 CUX1 Zornitza Stark Gene: cux1 has been classified as Green List (High Evidence).
Mendeliome v0.1142 CUX1 Zornitza Stark gene: CUX1 was added
gene: CUX1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: CUX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CUX1 were set to 25059644; 20510857; 30014507
Phenotypes for gene: CUX1 were set to Global developmental delay with or without impaired intellectual development, 618330
Review for gene: CUX1 was set to GREEN
gene: CUX1 was marked as current diagnostic
Added comment: Nine individuals from 7 families reported. Three individuals had normal intelligence at school age despite significant early developmental delay.
Sources: Expert list
Mendeliome v0.1141 COA3 Zornitza Stark Gene: coa3 has been classified as Red List (Low Evidence).
Mendeliome v0.1138 COA3 Zornitza Stark Classified gene: COA3 as Red List (low evidence)
Mendeliome v0.1138 COA3 Zornitza Stark Gene: coa3 has been classified as Red List (Low Evidence).
Mendeliome v0.1137 CNTN3 Zornitza Stark Gene: cntn3 has been classified as Red List (Low Evidence).
Mendeliome v0.1134 CNTN3 Zornitza Stark Classified gene: CNTN3 as Red List (low evidence)
Mendeliome v0.1134 CNTN3 Zornitza Stark Gene: cntn3 has been classified as Red List (Low Evidence).
Mendeliome v0.1133 CDK5R1 Zornitza Stark Gene: cdk5r1 has been classified as Red List (Low Evidence).
Mendeliome v0.1130 CDK5R1 Zornitza Stark Classified gene: CDK5R1 as Red List (low evidence)
Mendeliome v0.1130 CDK5R1 Zornitza Stark Gene: cdk5r1 has been classified as Red List (Low Evidence).
Mendeliome v0.1129 LIPN Zornitza Stark Gene: lipn has been classified as Red List (Low Evidence).
Mendeliome v0.1129 LIPN Zornitza Stark Phenotypes for gene: LIPN were changed from to Ichthyosis, congenital, autosomal recessive 8, MIM# 613943
Mendeliome v0.1126 LIPN Zornitza Stark Classified gene: LIPN as Red List (low evidence)
Mendeliome v0.1126 LIPN Zornitza Stark Gene: lipn has been classified as Red List (Low Evidence).
Mendeliome v0.1125 LIPN Zornitza Stark reviewed gene: LIPN: Rating: RED; Mode of pathogenicity: None; Publications: 21439540; Phenotypes: Ichthyosis, congenital, autosomal recessive 8, MIM# 613943; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1125 SDR9C7 Zornitza Stark Gene: sdr9c7 has been classified as Green List (High Evidence).
Mendeliome v0.1125 SDR9C7 Zornitza Stark Classified gene: SDR9C7 as Green List (high evidence)
Mendeliome v0.1125 SDR9C7 Zornitza Stark Gene: sdr9c7 has been classified as Green List (High Evidence).
Mendeliome v0.1124 SDR9C7 Zornitza Stark gene: SDR9C7 was added
gene: SDR9C7 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SDR9C7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SDR9C7 were set to 28173123; 28369735
Phenotypes for gene: SDR9C7 were set to Ichthyosis, congenital, autosomal recessive 13 MIM#617574
Review for gene: SDR9C7 was set to GREEN
Added comment: Three homozygous variants in 4 families with congenital ichthyosis.
Sources: Expert list
Mendeliome v0.1123 ACSL4 Zornitza Stark Gene: acsl4 has been classified as Green List (High Evidence).
Mendeliome v0.1120 RBBP8 Zornitza Stark Added comment: Comment when marking as ready: Individuals from 3 families reported in the literature with bi-allelic variants in this gene: clinical diagnosis was Jawad syndrome in one, and Seckel syndrome in 2. ID is a reported feature. Additional variant in ClinVar, so overall rating Green.
Mendeliome v0.1120 RBBP8 Zornitza Stark Gene: rbbp8 has been classified as Green List (High Evidence).
Mendeliome v0.1116 NIPBL Zornitza Stark Gene: nipbl has been classified as Green List (High Evidence).
Mendeliome v0.1114 HUWE1 Zornitza Stark Gene: huwe1 has been classified as Green List (High Evidence).
Mendeliome v0.1114 HUWE1 Zornitza Stark Phenotypes for gene: HUWE1 were changed from to Mental retardation, X-linked syndromic, Turner type; Say-Meyer syndrome; Juberg-Marsidi syndrome
Mendeliome v0.1111 FLNA Zornitza Stark Gene: flna has been classified as Green List (High Evidence).
Mendeliome v0.1111 FLNA Zornitza Stark Phenotypes for gene: FLNA were changed from to ?FG syndrome 2, XL; Cardiac valvular dysplasia, X-linked; Congenital short bowel syndrome; Frontometaphyseal dysplasia 1; Heterotopia, periventricular, 1; Intestinal pseudoobstruction, neuronal Melnick-Needles syndrome; Otopalatodigital syndrome, type I; Otopalatodigital syndrome, type II; Terminal osseous dysplasia
Mendeliome v0.1108 WDR35 Zornitza Stark Gene: wdr35 has been classified as Green List (High Evidence).
Mendeliome v0.1108 WDR35 Zornitza Stark Phenotypes for gene: WDR35 were changed from to Cranioectodermal dysplasia 2, MIM#613610; Short-rib thoracic dysplasia 7 with or without polydactyly, MIM#614091
Mendeliome v0.1106 DNAH11 Zornitza Stark Gene: dnah11 has been classified as Green List (High Evidence).
Mendeliome v0.1106 DNAH11 Zornitza Stark Phenotypes for gene: DNAH11 were changed from to Ciliary dyskinesia, primary, 7, with or without situs inversus, MIM#611884
Mendeliome v0.1104 ELOVL1 Zornitza Stark Gene: elovl1 has been classified as Green List (High Evidence).
Mendeliome v0.1102 CLDN10 Zornitza Stark Gene: cldn10 has been classified as Green List (High Evidence).
Mendeliome v0.1102 CLDN10 Zornitza Stark Phenotypes for gene: CLDN10 were changed from to HELIX syndrome MIM#617671; hypohidrosis, electrolyte imbalance, lacrimal gland dysfunction, ichthyosis, and xerostomia (HELIX)
Mendeliome v0.1100 CLDN10 Zornitza Stark reviewed gene: CLDN10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: HELIX syndrome MIM#617671, hypohidrosis, electrolyte imbalance, lacrimal gland dysfunction, ichthyosis, and xerostomia (HELIX); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1100 CACNA2D3 Zornitza Stark Gene: cacna2d3 has been classified as Red List (Low Evidence).
Mendeliome v0.1099 CACNA2D3 Zornitza Stark Classified gene: CACNA2D3 as Red List (low evidence)
Mendeliome v0.1099 CACNA2D3 Zornitza Stark Gene: cacna2d3 has been classified as Red List (Low Evidence).
Mendeliome v0.1098 CSTA Zornitza Stark Gene: csta has been classified as Green List (High Evidence).
Mendeliome v0.1098 CSTA Zornitza Stark Phenotypes for gene: CSTA were changed from to Peeling skin syndrome 4 MIM#607936; exfoliative ichthyosis
Mendeliome v0.1095 CSTA Zornitza Stark reviewed gene: CSTA: Rating: GREEN; Mode of pathogenicity: None; Publications: 21944047, 23534700, 25400170; Phenotypes: Peeling skin syndrome 4 MIM#607936, exfoliative ichthyosis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1095 CDSN Zornitza Stark Gene: cdsn has been classified as Green List (High Evidence).
Mendeliome v0.1095 CDSN Zornitza Stark Phenotypes for gene: CDSN were changed from to Peeling skin syndrome 1 MIM#270300; ichthyosiform erythroderma
Mendeliome v0.1092 CDSN Zornitza Stark reviewed gene: CDSN: Rating: GREEN; Mode of pathogenicity: None; Publications: 24794518, 18436651, 20691404, 21191406; Phenotypes: Peeling skin syndrome 1 MIM#270300, ichthyosiform erythroderma; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1092 CASP14 Zornitza Stark Gene: casp14 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1092 CASP14 Zornitza Stark Classified gene: CASP14 as Amber List (moderate evidence)
Mendeliome v0.1092 CASP14 Zornitza Stark Gene: casp14 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1091 CASP14 Zornitza Stark gene: CASP14 was added
gene: CASP14 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: CASP14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CASP14 were set to 27494380; 23014340; 17515931
Phenotypes for gene: CASP14 were set to Ichthyosis, congenital, autosomal recessive 12 MIM#617320
Review for gene: CASP14 was set to AMBER
Added comment: The same 2bp deletion was identified in 3 patients with a mild form of generalised ichthyosis from 2 Algerian families. Casp14-/- mouse models had prominent dermatological features.
Sources: Expert Review
Mendeliome v0.1090 LIPE Zornitza Stark Gene: lipe has been classified as Green List (High Evidence).
Mendeliome v0.1090 LIPE Zornitza Stark Classified gene: LIPE as Green List (high evidence)
Mendeliome v0.1090 LIPE Zornitza Stark Gene: lipe has been classified as Green List (High Evidence).
Mendeliome v0.1089 ALDH3A2 Zornitza Stark Gene: aldh3a2 has been classified as Green List (High Evidence).
Mendeliome v0.1089 ALDH3A2 Zornitza Stark Phenotypes for gene: ALDH3A2 were changed from to Sjogren-Larsson syndrome MIM#270200; spasticity; ichthyosis; intellectual disability
Mendeliome v0.1086 ALDH3A2 Zornitza Stark reviewed gene: ALDH3A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31273323; Phenotypes: Sjogren-Larsson syndrome MIM#270200, spasticity, ichthyosis, intellectual disability; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1086 MYT1L Zornitza Stark Gene: myt1l has been classified as Green List (High Evidence).
Mendeliome v0.1086 ABHD5 Zornitza Stark Gene: abhd5 has been classified as Green List (High Evidence).
Mendeliome v0.1086 ABHD5 Zornitza Stark Phenotypes for gene: ABHD5 were changed from to Chanarin-Dorfman syndrome MIM#275630; neutral lipid storage disease with ichthyosis; non-bullous congenital ichthyosiform erythroderma
Mendeliome v0.1083 ABHD5 Zornitza Stark reviewed gene: ABHD5: Rating: GREEN; Mode of pathogenicity: None; Publications: 30795549; Phenotypes: Chanarin-Dorfman syndrome MIM#275630, neutral lipid storage disease with ichthyosis, non-bullous congenital ichthyosiform erithroderma; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1083 TUBGCP6 Zornitza Stark Gene: tubgcp6 has been classified as Green List (High Evidence).
Mendeliome v0.1083 TUBGCP6 Zornitza Stark Phenotypes for gene: TUBGCP6 were changed from to Microcephaly and chorioretinopathy, autosomal recessive, 1, MIM#251270
Mendeliome v0.1080 TUBGCP6 Zornitza Stark reviewed gene: TUBGCP6: Rating: GREEN; Mode of pathogenicity: None; Publications: 25344692, 22279524; Phenotypes: Microcephaly and chorioretinopathy, autosomal recessive, 1, MIM#251270; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1077 LIPT1 Zornitza Stark Gene: lipt1 has been classified as Green List (High Evidence).
Mendeliome v0.1075 ARSA Zornitza Stark Gene: arsa has been classified as Green List (High Evidence).
Mendeliome v0.1073 ACTA1 Zornitza Stark Gene: acta1 has been classified as Green List (High Evidence).
Mendeliome v0.1069 FLNA Elena Savva reviewed gene: FLNA: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30089473; Phenotypes: ?FG syndrome 2, XL, Cardiac valvular dysplasia, X-linked, Congenital short bowel syndrome, Frontometaphyseal dysplasia 1, Heterotopia, periventricular, 1, Intestinal pseudoobstruction, neuronal Melnick-Needles syndrome, Otopalatodigital syndrome, type I, Otopalatodigital syndrome, type II, Terminal osseous dysplasia; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.1069 WDR35 Elena Savva reviewed gene: WDR35: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cranioectodermal dysplasia 2, Short-rib thoracic dysplasia 7 with or without polydactyly; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1069 DNAH11 Elena Savva reviewed gene: DNAH11: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 7, with or without situs inversus; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1069 FGF3 Zornitza Stark Phenotypes for gene: FGF3 were changed from Deafness, congenital with inner ear agenesis, microtia, and microdontiaDeafness, congenital with inner ear agenesis, microtia, and microdontia, MIM#610706 to Deafness, congenital with inner ear agenesis, microtia, and microdontia, MIM#610706
Mendeliome v0.1068 FGF3 Zornitza Stark Gene: fgf3 has been classified as Green List (High Evidence).
Mendeliome v0.1068 PHF8 Zornitza Stark Gene: phf8 has been classified as Green List (High Evidence).
Mendeliome v0.1068 IRF2BPL Zornitza Stark Gene: irf2bpl has been classified as Green List (High Evidence).
Mendeliome v0.1068 FGF3 Zornitza Stark Phenotypes for gene: FGF3 were changed from to Deafness, congenital with inner ear agenesis, microtia, and microdontiaDeafness, congenital with inner ear agenesis, microtia, and microdontia, MIM#610706
Mendeliome v0.1066 IRF2BPL Zornitza Stark Phenotypes for gene: IRF2BPL were changed from to Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures, MIM#618088
Mendeliome v0.1062 PHF8 Zornitza Stark Phenotypes for gene: PHF8 were changed from to Mental retardation syndrome, X-linked, Siderius type, MIM#300263
Mendeliome v0.1061 IARS Zornitza Stark Gene: iars has been classified as Green List (High Evidence).
Mendeliome v0.1059 PHF8 Zornitza Stark reviewed gene: PHF8: Rating: GREEN; Mode of pathogenicity: None; Publications: 17661819, 17594395, 16199551; Phenotypes: Mental retardation syndrome, X-linked, Siderius type, MIM#300263; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.1058 LONP1 Zornitza Stark Gene: lonp1 has been classified as Green List (High Evidence).
Mendeliome v0.1054 FGF3 Elena Savva reviewed gene: FGF3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, congenital with inner ear agenesis, microtia, and microdontia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1054 FGF3 Elena Savva reviewed gene: FGF3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, congenital with inner ear agenesis, microtia, and microdontia; Mode of inheritance: None
Mendeliome v0.1054 IRF2BPL Elena Savva reviewed gene: IRF2BPL: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30057031; Phenotypes: Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.1054 KMT5B Zornitza Stark Gene: kmt5b has been classified as Green List (High Evidence).
Mendeliome v0.1052 GNAO1 Zornitza Stark Gene: gnao1 has been classified as Green List (High Evidence).
Mendeliome v0.1048 CACNG2 Zornitza Stark Gene: cacng2 has been classified as Red List (Low Evidence).
Mendeliome v0.1046 CACNG2 Zornitza Stark Classified gene: CACNG2 as Red List (low evidence)
Mendeliome v0.1046 CACNG2 Zornitza Stark Gene: cacng2 has been classified as Red List (Low Evidence).
Mendeliome v0.1045 PPM1D Zornitza Stark Gene: ppm1d has been classified as Green List (High Evidence).
Mendeliome v0.1042 EGFR Zornitza Stark Gene: egfr has been classified as Red List (Low Evidence).
Mendeliome v0.1039 EGFR Zornitza Stark Classified gene: EGFR as Red List (low evidence)
Mendeliome v0.1039 EGFR Zornitza Stark Gene: egfr has been classified as Red List (Low Evidence).
Mendeliome v0.1038 CLCNKA Zornitza Stark Gene: clcnka has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1036 SLC9A3R1 Zornitza Stark Gene: slc9a3r1 has been classified as Red List (Low Evidence).
Mendeliome v0.1036 SLC9A3R1 Zornitza Stark Phenotypes for gene: SLC9A3R1 were changed from to Nephrolithiasis/osteoporosis, hypophosphatemic, 2, MIM# 612287
Mendeliome v0.1034 CLCNKA Zornitza Stark Classified gene: CLCNKA as Amber List (moderate evidence)
Mendeliome v0.1034 CLCNKA Zornitza Stark Gene: clcnka has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1031 SLC9A3R1 Zornitza Stark Classified gene: SLC9A3R1 as Red List (low evidence)
Mendeliome v0.1031 SLC9A3R1 Zornitza Stark Gene: slc9a3r1 has been classified as Red List (Low Evidence).
Mendeliome v0.1030 SLC9A3R1 Zornitza Stark reviewed gene: SLC9A3R1: Rating: RED; Mode of pathogenicity: None; Publications: 18784102; Phenotypes: Nephrolithiasis/osteoporosis, hypophosphatemic, 2, MIM# 612287; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1030 EGF Zornitza Stark Gene: egf has been classified as Red List (Low Evidence).
Mendeliome v0.1027 EGF Zornitza Stark Classified gene: EGF as Red List (low evidence)
Mendeliome v0.1027 EGF Zornitza Stark Gene: egf has been classified as Red List (Low Evidence).
Mendeliome v0.1026 FST Zornitza Stark Gene: fst has been classified as Red List (Low Evidence).
Mendeliome v0.1026 MYRF Zornitza Stark Gene: myrf has been classified as Green List (High Evidence).
Mendeliome v0.1026 MYRF Zornitza Stark Classified gene: MYRF as Green List (high evidence)
Mendeliome v0.1026 MYRF Zornitza Stark Gene: myrf has been classified as Green List (High Evidence).
Mendeliome v0.1024 FBXW11 Alison Yeung Gene: fbxw11 has been classified as Green List (High Evidence).
Mendeliome v0.1024 FBXW11 Alison Yeung Classified gene: FBXW11 as Green List (high evidence)
Mendeliome v0.1024 FBXW11 Alison Yeung Gene: fbxw11 has been classified as Green List (High Evidence).
Mendeliome v0.1023 MAB21L1 Zornitza Stark Gene: mab21l1 has been classified as Green List (High Evidence).
Mendeliome v0.1021 ANAPC1 Alison Yeung Gene: anapc1 has been classified as Green List (High Evidence).
Mendeliome v0.1021 ANAPC1 Alison Yeung Classified gene: ANAPC1 as Green List (high evidence)
Mendeliome v0.1021 ANAPC1 Alison Yeung Gene: anapc1 has been classified as Green List (High Evidence).
Mendeliome v0.1019 RINT1 Alison Yeung Gene: rint1 has been classified as Green List (High Evidence).
Mendeliome v0.1019 RINT1 Alison Yeung Classified gene: RINT1 as Green List (high evidence)
Mendeliome v0.1019 RINT1 Alison Yeung Gene: rint1 has been classified as Green List (High Evidence).
Mendeliome v0.1017 MAB21L1 Sue White Classified gene: MAB21L1 as Green List (high evidence)
Mendeliome v0.1017 MAB21L1 Sue White Gene: mab21l1 has been classified as Green List (High Evidence).
Mendeliome v0.1015 ASMT Zornitza Stark Gene: asmt has been classified as Red List (Low Evidence).
Mendeliome v0.1015 ASMT Zornitza Stark Classified gene: ASMT as Red List (low evidence)
Mendeliome v0.1015 ASMT Zornitza Stark Gene: asmt has been classified as Red List (Low Evidence).
Mendeliome v0.1011 ARHGEF6 Zornitza Stark Classified gene: ARHGEF6 as Red List (low evidence)
Mendeliome v0.1011 ARHGEF6 Zornitza Stark Gene: arhgef6 has been classified as Red List (Low Evidence).
Mendeliome v0.1010 XRCC4 Zornitza Stark Gene: xrcc4 has been classified as Green List (High Evidence).
Mendeliome v0.1007 AIMP2 Zornitza Stark Gene: aimp2 has been classified as Red List (Low Evidence).
Mendeliome v0.1007 NUP37 Zornitza Stark Gene: nup37 has been classified as Red List (Low Evidence).
Mendeliome v0.1007 SCRIB Zornitza Stark Gene: scrib has been classified as Red List (Low Evidence).
Mendeliome v0.1006 ANK3 Zornitza Stark Gene: ank3 has been classified as Red List (Low Evidence).
Mendeliome v0.1006 ANK3 Zornitza Stark Phenotypes for gene: ANK3 were changed from to Mental retardation, autosomal recessive, 37, MIM# 615493
Mendeliome v0.1003 ANK3 Zornitza Stark Classified gene: ANK3 as Red List (low evidence)
Mendeliome v0.1003 ANK3 Zornitza Stark Gene: ank3 has been classified as Red List (Low Evidence).
Mendeliome v0.1002 ANK3 Zornitza Stark reviewed gene: ANK3: Rating: RED; Mode of pathogenicity: None; Publications: 23390136, 28687526; Phenotypes: Mental retardation, autosomal recessive, 37 615493; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.1002 ALKBH8 Zornitza Stark Classified gene: ALKBH8 as Green List (high evidence)
Mendeliome v0.1002 ALKBH8 Zornitza Stark Gene: alkbh8 has been classified as Green List (High Evidence).
Mendeliome v0.1001 ATP6V1C2 Zornitza Stark Gene: atp6v1c2 has been classified as Red List (Low Evidence).
Mendeliome v0.1001 ATP6V1C2 Zornitza Stark gene: ATP6V1C2 was added
gene: ATP6V1C2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATP6V1C2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP6V1C2 were set to 31959358
Phenotypes for gene: ATP6V1C2 were set to Distal renal tubular acidosis
Review for gene: ATP6V1C2 was set to RED
Added comment: Single family reported, limited functional data.
Sources: Literature
Mendeliome v0.1000 ANKRD11 Zornitza Stark Gene: ankrd11 has been classified as Green List (High Evidence).
Mendeliome v0.997 AGGF1 Zornitza Stark Gene: aggf1 has been classified as Red List (Low Evidence).
Mendeliome v0.997 AGGF1 Zornitza Stark Classified gene: AGGF1 as Red List (low evidence)
Mendeliome v0.997 AGGF1 Zornitza Stark Gene: aggf1 has been classified as Red List (Low Evidence).
Mendeliome v0.993 HCN2 Zornitza Stark Classified gene: HCN2 as Green List (high evidence)
Mendeliome v0.993 HCN2 Zornitza Stark Gene: hcn2 has been classified as Green List (High Evidence).
Mendeliome v0.992 HCN2 Zornitza Stark edited their review of gene: HCN2: Added comment: Further cases identified. Evidence for both mono-allelic and bi-allelic variants causing disease; also evidence for both GoF and LoF as mechanism.; Changed rating: GREEN; Changed publications: 22131395, 30986657, 29064616, 20437590, 12514127, 17931874; Changed phenotypes: Genetic epilepsy with febrile seizures plus, Other seizure disorders; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.992 CTBP1 Zornitza Stark Gene: ctbp1 has been classified as Green List (High Evidence).
Mendeliome v0.992 CTBP1 Zornitza Stark Classified gene: CTBP1 as Green List (high evidence)
Mendeliome v0.992 CTBP1 Zornitza Stark Gene: ctbp1 has been classified as Green List (High Evidence).
Mendeliome v0.990 AGO1 Zornitza Stark Gene: ago1 has been classified as Green List (High Evidence).
Mendeliome v0.990 AGO1 Zornitza Stark Classified gene: AGO1 as Green List (high evidence)
Mendeliome v0.990 AGO1 Zornitza Stark Gene: ago1 has been classified as Green List (High Evidence).
Mendeliome v0.988 CNOT2 Sebastian Lunke Gene: cnot2 has been classified as Green List (High Evidence).
Mendeliome v0.988 CNOT2 Sebastian Lunke Classified gene: CNOT2 as Green List (high evidence)
Mendeliome v0.988 CNOT2 Sebastian Lunke Gene: cnot2 has been classified as Green List (High Evidence).
Mendeliome v0.986 CCDC88C Sebastian Lunke Phenotypes for gene: CCDC88C were changed from Spinocerebellar ataxia 40, MIM#616053 to Spinocerebellar ataxia 40, MIM#616053; Hydrocephalus, nonsyndromic, autosomal recessive 236600 AR
Mendeliome v0.983 CCDC88C Sebastian Lunke Classified gene: CCDC88C as Green List (high evidence)
Mendeliome v0.983 CCDC88C Sebastian Lunke Gene: ccdc88c has been classified as Green List (High Evidence).
Mendeliome v0.982 CCDC88C Sebastian Lunke reviewed gene: CCDC88C: Rating: GREEN; Mode of pathogenicity: None; Publications: 23042809, 21031079, 25062847, 30398676; Phenotypes: Spinocerebellar ataxia 40, MIM#616053, Hydrocephalus, nonsyndromic, autosomal recessive 236600 AR; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.982 CCDC47 Sebastian Lunke Classified gene: CCDC47 as Green List (high evidence)
Mendeliome v0.982 CCDC47 Sebastian Lunke Gene: ccdc47 has been classified as Green List (High Evidence).
Mendeliome v0.981 CCDC47 Sebastian Lunke gene: CCDC47 was added
gene: CCDC47 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: CCDC47 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC47 were set to 30401460
Phenotypes for gene: CCDC47 were set to Trichohepatoneurodevelopmental syndrome, 618268
Review for gene: CCDC47 was set to GREEN
gene: CCDC47 was marked as current diagnostic
Added comment: From GEL: Morimoto el al. (PMID: 30401460) report on 4 individuals from 4 unrelated families with biallelic LoF variants in CCDC47. The phenotype consisted of abnormal (woolly) hair, liver dysfunction, common facial features as well as DD/ID
Sources: Expert list
Mendeliome v0.980 CLIC2 Zornitza Stark Gene: clic2 has been classified as Red List (Low Evidence).
Mendeliome v0.977 CLIC2 Zornitza Stark Classified gene: CLIC2 as Red List (low evidence)
Mendeliome v0.977 CLIC2 Zornitza Stark Gene: clic2 has been classified as Red List (Low Evidence).
Mendeliome v0.976 IKZF5 Zornitza Stark Gene: ikzf5 has been classified as Green List (High Evidence).
Mendeliome v0.976 IKZF5 Zornitza Stark Classified gene: IKZF5 as Green List (high evidence)
Mendeliome v0.976 IKZF5 Zornitza Stark Gene: ikzf5 has been classified as Green List (High Evidence).
Mendeliome v0.974 TTC12 Zornitza Stark Gene: ttc12 has been classified as Green List (High Evidence).
Mendeliome v0.974 TTC12 Zornitza Stark Classified gene: TTC12 as Green List (high evidence)
Mendeliome v0.974 TTC12 Zornitza Stark Gene: ttc12 has been classified as Green List (High Evidence).
Mendeliome v0.973 TTC12 Zornitza Stark gene: TTC12 was added
gene: TTC12 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TTC12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTC12 were set to 31978331
Phenotypes for gene: TTC12 were set to Ciliary dyskinesia
Review for gene: TTC12 was set to GREEN
Added comment: Four unrelated families reported, LoF variants, respiratory phenotype.
Sources: Literature
Mendeliome v0.972 GCSH Zornitza Stark Gene: gcsh has been classified as Red List (Low Evidence).
Mendeliome v0.971 STT3B Zornitza Stark Gene: stt3b has been classified as Red List (Low Evidence).
Mendeliome v0.969 GCSH Zornitza Stark Classified gene: GCSH as Red List (low evidence)
Mendeliome v0.969 GCSH Zornitza Stark Gene: gcsh has been classified as Red List (Low Evidence).
Mendeliome v0.964 STT3B Zornitza Stark Classified gene: STT3B as Red List (low evidence)
Mendeliome v0.964 STT3B Zornitza Stark Gene: stt3b has been classified as Red List (Low Evidence).
Mendeliome v0.963 SLC39A8 Zornitza Stark Gene: slc39a8 has been classified as Green List (High Evidence).
Mendeliome v0.960 PIGS Zornitza Stark Gene: pigs has been classified as Green List (High Evidence).
Mendeliome v0.960 PIGS Zornitza Stark Classified gene: PIGS as Green List (high evidence)
Mendeliome v0.960 PIGS Zornitza Stark Gene: pigs has been classified as Green List (High Evidence).
Mendeliome v0.959 PIGS Zornitza Stark gene: PIGS was added
gene: PIGS was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: PIGS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGS were set to 30269814
Phenotypes for gene: PIGS were set to Glycosylphosphatidylinositol biosynthesis defect 18 618143
Review for gene: PIGS was set to GREEN
Added comment: Three unrelated families reported. Severe neurological phenotype ranging from fetal akinesia to ID/EE
Sources: Expert Review
Mendeliome v0.958 FUK Zornitza Stark Gene: fuk has been classified as Amber List (Moderate Evidence).
Mendeliome v0.958 FUK Zornitza Stark Classified gene: FUK as Amber List (moderate evidence)
Mendeliome v0.958 FUK Zornitza Stark Gene: fuk has been classified as Amber List (Moderate Evidence).
Mendeliome v0.956 ZNF142 Zornitza Stark Gene: znf142 has been classified as Green List (High Evidence).
Mendeliome v0.956 ZNF142 Zornitza Stark Classified gene: ZNF142 as Green List (high evidence)
Mendeliome v0.956 ZNF142 Zornitza Stark Gene: znf142 has been classified as Green List (High Evidence).
Mendeliome v0.954 RALA Zornitza Stark Gene: rala has been classified as Green List (High Evidence).
Mendeliome v0.954 RALA Zornitza Stark Classified gene: RALA as Green List (high evidence)
Mendeliome v0.954 RALA Zornitza Stark Gene: rala has been classified as Green List (High Evidence).
Mendeliome v0.952 NBEA Zornitza Stark Gene: nbea has been classified as Green List (High Evidence).
Mendeliome v0.952 NBEA Zornitza Stark Classified gene: NBEA as Green List (high evidence)
Mendeliome v0.952 NBEA Zornitza Stark Gene: nbea has been classified as Green List (High Evidence).
Mendeliome v0.950 MACF1 Zornitza Stark Classified gene: MACF1 as Green List (high evidence)
Mendeliome v0.950 MACF1 Zornitza Stark Gene: macf1 has been classified as Green List (High Evidence).
Mendeliome v0.947 KATNB1 Zornitza Stark Gene: katnb1 has been classified as Green List (High Evidence).
Mendeliome v0.944 NLGN4X Zornitza Stark Gene: nlgn4x has been classified as Red List (Low Evidence).
Mendeliome v0.941 NLGN4X Zornitza Stark Classified gene: NLGN4X as Red List (low evidence)
Mendeliome v0.941 NLGN4X Zornitza Stark Gene: nlgn4x has been classified as Red List (Low Evidence).
Mendeliome v0.940 HNRNPR Zornitza Stark Gene: hnrnpr has been classified as Green List (High Evidence).
Mendeliome v0.940 HNRNPR Zornitza Stark Classified gene: HNRNPR as Green List (high evidence)
Mendeliome v0.940 HNRNPR Zornitza Stark Gene: hnrnpr has been classified as Green List (High Evidence).
Mendeliome v0.938 USB1 Zornitza Stark Gene: usb1 has been classified as Green List (High Evidence).
Mendeliome v0.935 GNB5 Zornitza Stark Gene: gnb5 has been classified as Green List (High Evidence).
Mendeliome v0.932 FAR1 Zornitza Stark Gene: far1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.929 FAR1 Zornitza Stark Classified gene: FAR1 as Amber List (moderate evidence)
Mendeliome v0.929 FAR1 Zornitza Stark Gene: far1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.928 EFHC1 Zornitza Stark Gene: efhc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.925 EFHC1 Zornitza Stark Classified gene: EFHC1 as Amber List (moderate evidence)
Mendeliome v0.925 EFHC1 Zornitza Stark Gene: efhc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.924 CEP89 Zornitza Stark Gene: cep89 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.921 CEP89 Zornitza Stark Classified gene: CEP89 as Amber List (moderate evidence)
Mendeliome v0.921 CEP89 Zornitza Stark Gene: cep89 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.920 MAP4K4 Zornitza Stark Gene: map4k4 has been classified as Red List (Low Evidence).
Mendeliome v0.920 MAP4K4 Zornitza Stark Classified gene: MAP4K4 as Red List (low evidence)
Mendeliome v0.920 MAP4K4 Zornitza Stark Gene: map4k4 has been classified as Red List (Low Evidence).
Mendeliome v0.919 NAGA Zornitza Stark Gene: naga has been classified as Green List (High Evidence).
Mendeliome v0.916 RAB11A Zornitza Stark Gene: rab11a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.916 RAB11A Zornitza Stark Classified gene: RAB11A as Amber List (moderate evidence)
Mendeliome v0.916 RAB11A Zornitza Stark Gene: rab11a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.915 RAB11A Zornitza Stark Classified gene: RAB11A as Amber List (moderate evidence)
Mendeliome v0.915 RAB11A Zornitza Stark Gene: rab11a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.913 DHPS Zornitza Stark Gene: dhps has been classified as Green List (High Evidence).
Mendeliome v0.913 DHPS Zornitza Stark Classified gene: DHPS as Green List (high evidence)
Mendeliome v0.913 DHPS Zornitza Stark Gene: dhps has been classified as Green List (High Evidence).
Mendeliome v0.912 DHPS Zornitza Stark gene: DHPS was added
gene: DHPS was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: DHPS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DHPS were set to 30661771
Phenotypes for gene: DHPS were set to Neurodevelopmental disorder with seizures and speech and walking impairment, MIM#618480
Review for gene: DHPS was set to GREEN
gene: DHPS was marked as current diagnostic
Added comment: 5 individuals from 4 unrelated families with biallelic pathogenic variants in DHPS, note one variant is recurrent (c.518A>G or p.Asn173Ser). The phenotype consisted of DD/ID (5/5), tone abnormalities (hypotonia/hypertonia/spasticity - 5/5), seizures (5/5 - in one case though unclear staring spells) with EEG abnormalities (5/5). Additionally most individuals displayed behavioral issues, or some common facial features
Sources: Expert list
Mendeliome v0.911 RBFOX1 Zornitza Stark Gene: rbfox1 has been classified as Red List (Low Evidence).
Mendeliome v0.908 RBFOX1 Zornitza Stark Classified gene: RBFOX1 as Red List (low evidence)
Mendeliome v0.908 RBFOX1 Zornitza Stark Gene: rbfox1 has been classified as Red List (Low Evidence).
Mendeliome v0.907 DDOST Zornitza Stark Gene: ddost has been classified as Amber List (Moderate Evidence).
Mendeliome v0.904 DDOST Zornitza Stark Classified gene: DDOST as Amber List (moderate evidence)
Mendeliome v0.904 DDOST Zornitza Stark Gene: ddost has been classified as Amber List (Moderate Evidence).
Mendeliome v0.903 PIK3C2A Zornitza Stark Gene: pik3c2a has been classified as Green List (High Evidence).
Mendeliome v0.902 PIK3C2A Zornitza Stark Classified gene: PIK3C2A as Green List (high evidence)
Mendeliome v0.902 PIK3C2A Zornitza Stark Gene: pik3c2a has been classified as Green List (High Evidence).
Mendeliome v0.900 FGF16 Zornitza Stark Gene: fgf16 has been classified as Green List (High Evidence).
Mendeliome v0.900 FGF16 Zornitza Stark Classified gene: FGF16 as Green List (high evidence)
Mendeliome v0.900 FGF16 Zornitza Stark Gene: fgf16 has been classified as Green List (High Evidence).
Mendeliome v0.899 FGF16 Zornitza Stark gene: FGF16 was added
gene: FGF16 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: FGF16 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: FGF16 were set to Metacarpal 4-5 fusion, MIM# 309630
Review for gene: FGF16 was set to GREEN
gene: FGF16 was marked as current diagnostic
Added comment: Sources: Expert list
Mendeliome v0.898 NTNG1 Zornitza Stark Gene: ntng1 has been classified as Red List (Low Evidence).
Mendeliome v0.898 NTNG1 Zornitza Stark Classified gene: NTNG1 as Red List (low evidence)
Mendeliome v0.898 NTNG1 Zornitza Stark Gene: ntng1 has been classified as Red List (Low Evidence).
Mendeliome v0.897 GAS1 Zornitza Stark Gene: gas1 has been classified as Red List (Low Evidence).
Mendeliome v0.894 GAS1 Zornitza Stark Classified gene: GAS1 as Red List (low evidence)
Mendeliome v0.894 GAS1 Zornitza Stark Gene: gas1 has been classified as Red List (Low Evidence).
Mendeliome v0.893 IMMP2L Zornitza Stark Gene: immp2l has been classified as Red List (Low Evidence).
Mendeliome v0.890 IMMP2L Zornitza Stark Classified gene: IMMP2L as Red List (low evidence)
Mendeliome v0.890 IMMP2L Zornitza Stark Gene: immp2l has been classified as Red List (Low Evidence).
Mendeliome v0.889 PTPRR Zornitza Stark Gene: ptprr has been classified as Red List (Low Evidence).
Mendeliome v0.889 STAT4 Zornitza Stark Gene: stat4 has been classified as Red List (Low Evidence).
Mendeliome v0.889 MTHFS Zornitza Stark Classified gene: MTHFS as Green List (high evidence)
Mendeliome v0.889 MTHFS Zornitza Stark Gene: mthfs has been classified as Green List (High Evidence).
Mendeliome v0.887 HOXB6 Zornitza Stark Gene: hoxb6 has been classified as Green List (High Evidence).
Mendeliome v0.884 LIFR Zornitza Stark Gene: lifr has been classified as Green List (High Evidence).
Mendeliome v0.880 CACNA1B Zornitza Stark Gene: cacna1b has been classified as Green List (High Evidence).
Mendeliome v0.877 CDH2 Zornitza Stark Gene: cdh2 has been classified as Green List (High Evidence).
Mendeliome v0.877 CDH2 Zornitza Stark Classified gene: CDH2 as Green List (high evidence)
Mendeliome v0.877 CDH2 Zornitza Stark Gene: cdh2 has been classified as Green List (High Evidence).
Mendeliome v0.874 NTNG2 Zornitza Stark Gene: ntng2 has been classified as Green List (High Evidence).
Mendeliome v0.871 RPL13 Zornitza Stark Gene: rpl13 has been classified as Green List (High Evidence).
Mendeliome v0.871 RPL13 Zornitza Stark Classified gene: RPL13 as Green List (high evidence)
Mendeliome v0.871 RPL13 Zornitza Stark Gene: rpl13 has been classified as Green List (High Evidence).
Mendeliome v0.870 RPL13 Zornitza Stark gene: RPL13 was added
gene: RPL13 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RPL13 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPL13 were set to 31630789
Phenotypes for gene: RPL13 were set to Spondyloepimetaphyseal Dysplasia with Severe Short Stature
Review for gene: RPL13 was set to GREEN
Added comment: Four unrelated individuals reported with de novo variants.
Sources: Literature
Mendeliome v0.869 FOXJ1 Zornitza Stark Gene: foxj1 has been classified as Green List (High Evidence).
Mendeliome v0.866 TUBGCP2 Zornitza Stark Gene: tubgcp2 has been classified as Green List (High Evidence).
Mendeliome v0.866 TUBGCP2 Zornitza Stark Classified gene: TUBGCP2 as Green List (high evidence)
Mendeliome v0.866 TUBGCP2 Zornitza Stark Gene: tubgcp2 has been classified as Green List (High Evidence).
Mendeliome v0.864 RRAS2 Zornitza Stark Gene: rras2 has been classified as Green List (High Evidence).
Mendeliome v0.861 TP73 Alison Yeung Gene: tp73 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.861 TP73 Alison Yeung Classified gene: TP73 as Amber List (moderate evidence)
Mendeliome v0.861 TP73 Alison Yeung Gene: tp73 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.859 SMG8 Alison Yeung Gene: smg8 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.859 SMG8 Alison Yeung Classified gene: SMG8 as Amber List (moderate evidence)
Mendeliome v0.859 SMG8 Alison Yeung Gene: smg8 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.857 IQSEC3 Alison Yeung Gene: iqsec3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.857 IQSEC3 Alison Yeung Classified gene: IQSEC3 as Amber List (moderate evidence)
Mendeliome v0.857 IQSEC3 Alison Yeung Gene: iqsec3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.855 ICE1 Alison Yeung Gene: ice1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.855 ICE1 Alison Yeung Classified gene: ICE1 as Amber List (moderate evidence)
Mendeliome v0.855 ICE1 Alison Yeung Gene: ice1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.853 EIF2A Alison Yeung Gene: eif2a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.853 EIF2A Alison Yeung Classified gene: EIF2A as Amber List (moderate evidence)
Mendeliome v0.853 EIF2A Alison Yeung Gene: eif2a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.845 KCNN3 Alison Yeung Gene: kcnn3 has been classified as Green List (High Evidence).
Mendeliome v0.845 KCNN3 Alison Yeung Classified gene: KCNN3 as Green List (high evidence)
Mendeliome v0.845 KCNN3 Alison Yeung Gene: kcnn3 has been classified as Green List (High Evidence).
Mendeliome v0.843 CTNND2 Zornitza Stark Gene: ctnnd2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.840 CTNND2 Zornitza Stark Classified gene: CTNND2 as Amber List (moderate evidence)
Mendeliome v0.840 CTNND2 Zornitza Stark Gene: ctnnd2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.839 ADCY8 Zornitza Stark Gene: adcy8 has been classified as Red List (Low Evidence).
Mendeliome v0.839 ADCY8 Zornitza Stark Classified gene: ADCY8 as Red List (low evidence)
Mendeliome v0.839 ADCY8 Zornitza Stark Gene: adcy8 has been classified as Red List (Low Evidence).
Mendeliome v0.838 CNOT1 Alison Yeung Gene: cnot1 has been classified as Green List (High Evidence).
Mendeliome v0.838 CNOT1 Alison Yeung Classified gene: CNOT1 as Green List (high evidence)
Mendeliome v0.838 CNOT1 Alison Yeung Gene: cnot1 has been classified as Green List (High Evidence).
Mendeliome v0.837 CNOT1 Alison Yeung gene: CNOT1 was added
gene: CNOT1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CNOT1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CNOT1 were set to PMID: 31006513
Phenotypes for gene: CNOT1 were set to Holoprosencephaly 12, with or without pancreatic agenesis; OMIM# 618500
Review for gene: CNOT1 was set to GREEN
gene: CNOT1 was marked as current diagnostic
Added comment: Reported in 3 unrelated individuals
Sources: Literature
Mendeliome v0.836 IQSEC1 Zornitza Stark Gene: iqsec1 has been classified as Green List (High Evidence).
Mendeliome v0.836 IQSEC1 Zornitza Stark Classified gene: IQSEC1 as Green List (high evidence)
Mendeliome v0.836 IQSEC1 Zornitza Stark Gene: iqsec1 has been classified as Green List (High Evidence).
Mendeliome v0.834 ACAN Zornitza Stark Gene: acan has been classified as Green List (High Evidence).
Mendeliome v0.834 ACAN Zornitza Stark Classified gene: ACAN as Green List (high evidence)
Mendeliome v0.834 ACAN Zornitza Stark Gene: acan has been classified as Green List (High Evidence).
Mendeliome v0.833 ACAN Zornitza Stark gene: ACAN was added
gene: ACAN was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ACAN was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: ACAN were set to Short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans, OMIM# 165800; Spondyloepimetaphyseal dysplasia, aggrecan type 612813
Review for gene: ACAN was set to GREEN
Added comment: Sources: Expert list
Mendeliome v0.832 NKX2-2 Zornitza Stark Gene: nkx2-2 has been classified as Green List (High Evidence).
Mendeliome v0.832 NKX2-2 Zornitza Stark Classified gene: NKX2-2 as Green List (high evidence)
Mendeliome v0.832 NKX2-2 Zornitza Stark Gene: nkx2-2 has been classified as Green List (High Evidence).
Mendeliome v0.830 KDM3B Alison Yeung Gene: kdm3b has been classified as Green List (High Evidence).
Mendeliome v0.830 KDM3B Alison Yeung Classified gene: KDM3B as Green List (high evidence)
Mendeliome v0.830 KDM3B Alison Yeung Gene: kdm3b has been classified as Green List (High Evidence).
Mendeliome v0.829 LEMD2 Alison Yeung Gene: lemd2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.829 LEMD2 Alison Yeung Classified gene: LEMD2 as Amber List (moderate evidence)
Mendeliome v0.829 LEMD2 Alison Yeung Gene: lemd2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.829 LEMD2 Alison Yeung Classified gene: LEMD2 as Amber List (moderate evidence)