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Mendeliome v0.5748 DHDDS Zornitza Stark Phenotypes for gene: DHDDS were changed from to Developmental delay and seizures with or without movement abnormalities, MIM#617836; Congenital disorder of glycosylation, type 1bb, MIM# 613861
Mendeliome v0.5747 DHDDS Zornitza Stark Publications for gene: DHDDS were set to
Mendeliome v0.5746 DHDDS Zornitza Stark Mode of inheritance for gene: DHDDS was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5745 DHDDS Zornitza Stark Tag founder tag was added to gene: DHDDS.
Mendeliome v0.5745 DHDDS Zornitza Stark edited their review of gene: DHDDS: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5745 DHDDS Zornitza Stark reviewed gene: DHDDS: Rating: GREEN; Mode of pathogenicity: None; Publications: 27343064, 29100083, 21295283; Phenotypes: Developmental delay and seizures with or without movement abnormalities, MIM#617836, Congenital disorder of glycosylation, type 1bb, MIM# 613861; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5745 FBLN1 Zornitza Stark Publications for gene: FBLN1 were set to 11836357
Mendeliome v0.5744 FBLN1 Zornitza Stark Mode of inheritance for gene: FBLN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5743 FBLN1 Zornitza Stark reviewed gene: FBLN1: Rating: RED; Mode of pathogenicity: None; Publications: 24084572; Phenotypes: Synpolydactyly, 3/3'4, associated with metacarpal and metatarsal synostoses MIM#608180; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5743 FBLN1 Zornitza Stark Gene: fbln1 has been classified as Red List (Low Evidence).
Mendeliome v0.5743 FBLN1 Zornitza Stark Phenotypes for gene: FBLN1 were changed from to Synpolydactyly, 3/3'4, associated with metacarpal and metatarsal synostoses MIM#608180
Mendeliome v0.5742 FBLN1 Zornitza Stark Publications for gene: FBLN1 were set to
Mendeliome v0.5741 FBLN1 Zornitza Stark Mode of inheritance for gene: FBLN1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5740 FBLN1 Zornitza Stark Classified gene: FBLN1 as Red List (low evidence)
Mendeliome v0.5740 FBLN1 Zornitza Stark Gene: fbln1 has been classified as Red List (Low Evidence).
Mendeliome v0.5739 TBL1X Elena Savva gene: TBL1X was added
gene: TBL1X was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TBL1X was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: TBL1X were set to PMID: 27603907
Phenotypes for gene: TBL1X were set to Hypothyroidism, congenital, nongoitrous, 8 MIM#301033
Review for gene: TBL1X was set to GREEN
Added comment: PMID: 27603907 - mostly males but also a female diagnosed with central hypothyroidism. 6 families reported (5/6 missense, 1/6 splice). Supported by functional studies ->LOF

All mutations were located in the highly conserved WD40-repeat domains.
Sources: Literature
Mendeliome v0.5739 ST3GAL5 Zornitza Stark Tag founder tag was added to gene: ST3GAL5.
Mendeliome v0.5739 ST3GAL5 Zornitza Stark Marked gene: ST3GAL5 as ready
Mendeliome v0.5739 ST3GAL5 Zornitza Stark Gene: st3gal5 has been classified as Green List (High Evidence).
Mendeliome v0.5739 ST3GAL5 Zornitza Stark Phenotypes for gene: ST3GAL5 were changed from to Salt and pepper developmental regression syndrome 609056; GM3 synthase deficiency, MONDO:0018274; Lactosylceramide alpha-2,3-sialyltransferase deficiency (Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation)
Mendeliome v0.5738 ST3GAL5 Zornitza Stark Publications for gene: ST3GAL5 were set to
Mendeliome v0.5737 ST3GAL5 Zornitza Stark Mode of inheritance for gene: ST3GAL5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5736 ST3GAL5 Zornitza Stark reviewed gene: ST3GAL5: Rating: GREEN; Mode of pathogenicity: None; Publications: 23436467, 22990144, 15502825, 27232954, 30691927, 30688114, 30576498; Phenotypes: Salt and pepper developmental regression syndrome 609056, GM3 synthase deficiency, MONDO:0018274, Lactosylceramide alpha-2,3-sialyltransferase deficiency (Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5736 FBLN1 Elena Savva reviewed gene: FBLN1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 11836357; Phenotypes: Synpolydactyly, 3/3'4, associated with metacarpal and metatarsal synostoses MIM#608180; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.5736 SUCLA2 Zornitza Stark Gene: sucla2 has been classified as Green List (High Evidence).
Mendeliome v0.5736 SUCLA2 Zornitza Stark Phenotypes for gene: SUCLA2 were changed from to Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), MIM# 612073, MONDO:0012791
Mendeliome v0.5735 SUCLA2 Zornitza Stark Publications for gene: SUCLA2 were set to
Mendeliome v0.5734 SUCLA2 Zornitza Stark Mode of inheritance for gene: SUCLA2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5733 SUCLA2 Zornitza Stark edited their review of gene: SUCLA2: Changed phenotypes: Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), MIM# 612073, MONDO:0012791
Mendeliome v0.5733 SUCLA2 Zornitza Stark reviewed gene: SUCLA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 15877282, 17287286, 17301081, 23759946, 33231368, 33230181, 28243576, 27913098, 27651038; Phenotypes: Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), MIM# 612073; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5733 RFT1 Zornitza Stark Marked gene: RFT1 as ready
Mendeliome v0.5733 RFT1 Zornitza Stark Gene: rft1 has been classified as Green List (High Evidence).
Mendeliome v0.5733 RFT1 Zornitza Stark Phenotypes for gene: RFT1 were changed from to Congenital disorder of glycosylation, type In, MIM# 612015; RFT1-CDG, MONDO:0012783
Mendeliome v0.5732 RFT1 Zornitza Stark Publications for gene: RFT1 were set to
Mendeliome v0.5731 RFT1 Zornitza Stark Mode of inheritance for gene: RFT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5730 RFT1 Zornitza Stark reviewed gene: RFT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18313027, 19701946, 19856127, 23111317, 30071302, 29923091, 27927990, 26892341; Phenotypes: Congenital disorder of glycosylation, type In, MIM# 612015, RFT1-CDG, MONDO:0012783; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5730 CHST6 Zornitza Stark Marked gene: CHST6 as ready
Mendeliome v0.5730 CHST6 Zornitza Stark Gene: chst6 has been classified as Green List (High Evidence).
Mendeliome v0.5730 CHST6 Zornitza Stark Phenotypes for gene: CHST6 were changed from to Macular corneal dystrophy, MIM# 217800, MONDO:0009020
Mendeliome v0.5729 CHST6 Zornitza Stark Publications for gene: CHST6 were set to
Mendeliome v0.5728 CHST6 Zornitza Stark Mode of inheritance for gene: CHST6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5727 CHST6 Zornitza Stark reviewed gene: CHST6: Rating: GREEN; Mode of pathogenicity: None; Publications: 11818380, 16207214, 26604660; Phenotypes: Macular corneal dystrophy, MIM# 217800, MONDO:0009020; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5727 MGAT2 Zornitza Stark Marked gene: MGAT2 as ready
Mendeliome v0.5727 MGAT2 Zornitza Stark Gene: mgat2 has been classified as Green List (High Evidence).
Mendeliome v0.5727 MGAT2 Zornitza Stark Phenotypes for gene: MGAT2 were changed from to Congenital disorder of glycosylation, type IIa, MIM# 212066; MGAT2-CDG, MONDO:0008908
Mendeliome v0.5726 MGAT2 Zornitza Stark Publications for gene: MGAT2 were set to
Mendeliome v0.5725 MGAT2 Zornitza Stark Mode of inheritance for gene: MGAT2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5724 MGAT2 Zornitza Stark reviewed gene: MGAT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 8808595, 11228641, 22105986, 33044030, 31420886; Phenotypes: Congenital disorder of glycosylation, type IIa, MIM# 212066, MGAT2-CDG, MONDO:0008908; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5724 MPI Zornitza Stark Gene: mpi has been classified as Green List (High Evidence).
Mendeliome v0.5724 MPI Zornitza Stark Phenotypes for gene: MPI were changed from to Congenital disorder of glycosylation, type Ib, MIM# 602579; MPI-CDG MONDO:0011257
Mendeliome v0.5723 MPI Zornitza Stark Publications for gene: MPI were set to
Mendeliome v0.5722 MPI Zornitza Stark Mode of inheritance for gene: MPI was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5721 MPI Zornitza Stark reviewed gene: MPI: Rating: GREEN; Mode of pathogenicity: None; Publications: 12414827, 9585601, 10980531, 33098580, 33204592, 32905087, 32266963, 30242110; Phenotypes: Congenital disorder of glycosylation, type Ib, MIM# 602579, MPI-CDG MONDO:0011257; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5721 PGM3 Zornitza Stark Gene: pgm3 has been classified as Green List (High Evidence).
Mendeliome v0.5721 PGM3 Zornitza Stark Phenotypes for gene: PGM3 were changed from to Immunodeficiency 23, MIM# 615816; PGM3-CDG, MONDO:0014353
Mendeliome v0.5720 PGM3 Zornitza Stark Publications for gene: PGM3 were set to
Mendeliome v0.5719 PGM3 Zornitza Stark Mode of inheritance for gene: PGM3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5718 PGM3 Zornitza Stark changed review comment from: Phosphoglucomutase 3 (PGM3) protein catalyzes the conversion of N-acetyl-d-glucosamine-6-phosphate (GlcNAc-6-P) to N-acetyl-d-glucosamine-1-phosphate (GlcNAc-1-P), which is required for the synthesis of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) an important precursor for protein glycosylation. Bi-allelic variants in this gene are associated with a primary immunodeficiency syndrome characterised by onset of recurrent infections, usually respiratory or cutaneous, in early childhood. Immune workup usually shows neutropenia, lymphopenia, eosinophilia, and increased serum IgE or IgA. Neutrophil chemotactic defects have also been reported. Infectious agents include bacteria, viruses, and fungi. Many patients develop atopic dermatitis, eczema, and other signs of autoinflammation. Affected individuals may also show developmental delay or cognitive impairment of varying severity. More than 10 unrelated families reported.; to: Phosphoglucomutase 3 (PGM3) protein catalyzes the conversion of N-acetyl-d-glucosamine-6-phosphate (GlcNAc-6-P) to N-acetyl-d-glucosamine-1-phosphate (GlcNAc-1-P), which is required for the synthesis of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) an important precursor for protein glycosylation.

Bi-allelic variants in this gene are associated with a primary immunodeficiency syndrome characterised by onset of recurrent infections, usually respiratory or cutaneous, in early childhood. Immune workup usually shows neutropenia, lymphopenia, eosinophilia, and increased serum IgE or IgA. Neutrophil chemotactic defects have also been reported. Infectious agents include bacteria, viruses, and fungi. Many patients develop atopic dermatitis, eczema, and other signs of autoinflammation. Affected individuals may also show developmental delay or cognitive impairment of varying severity.

More than 10 unrelated families reported.
Mendeliome v0.5718 PGM3 Zornitza Stark reviewed gene: PGM3: Rating: GREEN; Mode of pathogenicity: None; Publications: 30578875, 31231132, 33098103, 30157810, 28704707; Phenotypes: Immunodeficiency 23, MIM# 615816, PGM3-CDG, MONDO:0014353; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5718 PGAP3 Zornitza Stark Gene: pgap3 has been classified as Green List (High Evidence).
Mendeliome v0.5718 PGAP3 Zornitza Stark Phenotypes for gene: PGAP3 were changed from to Hyperphosphatasia with mental retardation syndrome 4, MIM# 615716, MONDO:0014318
Mendeliome v0.5717 PGAP3 Zornitza Stark Publications for gene: PGAP3 were set to
Mendeliome v0.5716 PGAP3 Zornitza Stark Mode of inheritance for gene: PGAP3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5715 PGAP3 Zornitza Stark reviewed gene: PGAP3: Rating: GREEN; Mode of pathogenicity: None; Publications: 24439110, 29620724, 30345601, 30217754; Phenotypes: Hyperphosphatasia with mental retardation syndrome 4, MIM# 615716, MONDO:0014318; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5715 PGAP2 Zornitza Stark Gene: pgap2 has been classified as Green List (High Evidence).
Mendeliome v0.5715 PGAP2 Zornitza Stark Phenotypes for gene: PGAP2 were changed from to Hyperphosphatasia with mental retardation syndrome 3, MIM# 614207, MONDO:0013628
Mendeliome v0.5714 PGAP2 Zornitza Stark Publications for gene: PGAP2 were set to
Mendeliome v0.5713 PGAP2 Zornitza Stark Mode of inheritance for gene: PGAP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5712 PGAP2 Zornitza Stark reviewed gene: PGAP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23561846, 23561847, 31805394, 29119105, 27871432; Phenotypes: Hyperphosphatasia with mental retardation syndrome 3, MIM# 614207, MONDO:0013628; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5712 PIGV Zornitza Stark Gene: pigv has been classified as Green List (High Evidence).
Mendeliome v0.5712 PIGV Zornitza Stark Phenotypes for gene: PIGV were changed from to Hyperphosphatasia with mental retardation syndrome 1, MIM# 239300, MONDO:0009398
Mendeliome v0.5711 PIGV Zornitza Stark Publications for gene: PIGV were set to
Mendeliome v0.5710 PIGV Zornitza Stark Mode of inheritance for gene: PIGV was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5709 PIGV Zornitza Stark reviewed gene: PIGV: Rating: GREEN; Mode of pathogenicity: None; Publications: 20802478, 22315194, 28817240, 24129430; Phenotypes: Hyperphosphatasia with mental retardation syndrome 1, MIM# 239300, MONDO:0009398; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5709 PIGT Zornitza Stark Phenotypes for gene: PIGT were changed from Multiple congenital anomalies-hypotonia-seizures syndrome 3, MIM# 615398 to Multiple congenital anomalies-hypotonia-seizures syndrome 3, MIM# 615398, MONDO:0014165
Mendeliome v0.5708 PIGT Zornitza Stark edited their review of gene: PIGT: Changed phenotypes: Multiple congenital anomalies-hypotonia-seizures syndrome 3, MIM# 615398, MONDO:0014165
Mendeliome v0.5708 PIGO Zornitza Stark Gene: pigo has been classified as Green List (High Evidence).
Mendeliome v0.5708 PIGO Zornitza Stark Phenotypes for gene: PIGO were changed from to Hyperphosphatasia with mental retardation syndrome 2, MIM# 614749, MONDO:0013882
Mendeliome v0.5707 PIGO Zornitza Stark Publications for gene: PIGO were set to
Mendeliome v0.5706 PIGO Zornitza Stark Mode of inheritance for gene: PIGO was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5705 PIGO Zornitza Stark reviewed gene: PIGO: Rating: GREEN; Mode of pathogenicity: None; Publications: 22683086, 31698102, 28900819, 28545593, 28337824; Phenotypes: Hyperphosphatasia with mental retardation syndrome 2, MIM# 614749, MONDO:0013882; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5705 PIGN Zornitza Stark Tag SV/CNV tag was added to gene: PIGN.
Tag founder tag was added to gene: PIGN.
Mendeliome v0.5705 PIGN Zornitza Stark Gene: pign has been classified as Green List (High Evidence).
Mendeliome v0.5705 PIGN Zornitza Stark Phenotypes for gene: PIGN were changed from to Multiple congenital anomalies-hypotonia-seizures syndrome 1, MIM# 614080, MONDO:0013563
Mendeliome v0.5704 PIGN Zornitza Stark Publications for gene: PIGN were set to
Mendeliome v0.5703 PIGN Zornitza Stark Mode of inheritance for gene: PIGN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5702 PIGN Zornitza Stark reviewed gene: PIGN: Rating: GREEN; Mode of pathogenicity: None; Publications: 21493957, 24253414, 26364997, 26394714, 33193741, 32585529, 29330547; Phenotypes: Multiple congenital anomalies-hypotonia-seizures syndrome 1, MIM# 614080, MONDO:0013563; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5702 PIGA Zornitza Stark Gene: piga has been classified as Green List (High Evidence).
Mendeliome v0.5702 PIGA Zornitza Stark Phenotypes for gene: PIGA were changed from to Multiple congenital anomalies-hypotonia-seizures syndrome 2, MIM# 300868, MONDO:0010466
Mendeliome v0.5701 PIGA Zornitza Stark Publications for gene: PIGA were set to
Mendeliome v0.5700 PIGA Zornitza Stark Mode of inheritance for gene: PIGA was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.5699 PIGA Zornitza Stark reviewed gene: PIGA: Rating: GREEN; Mode of pathogenicity: None; Publications: 22305531, 24357517, 24706016, 26545172, 33333793, 32694024; Phenotypes: Multiple congenital anomalies-hypotonia-seizures syndrome 2, MIM# 300868, MONDO:0010466; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.5699 PIGL Zornitza Stark Tag SV/CNV tag was added to gene: PIGL.
Tag founder tag was added to gene: PIGL.
Mendeliome v0.5699 PIGL Zornitza Stark Gene: pigl has been classified as Green List (High Evidence).
Mendeliome v0.5699 PIGL Zornitza Stark Phenotypes for gene: PIGL were changed from to CHIME syndrome, MIM# 280000, MONDO:0010221
Mendeliome v0.5698 PIGL Zornitza Stark Publications for gene: PIGL were set to
Mendeliome v0.5697 PIGL Zornitza Stark Mode of inheritance for gene: PIGL was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5696 PIGL Zornitza Stark reviewed gene: PIGL: Rating: GREEN; Mode of pathogenicity: None; Publications: 22444671, 31535386, 30023290, 29473937, 28371479, 25706356; Phenotypes: CHIME syndrome, MIM# 280000, MONDO:0010221; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5696 B3GALT6 Zornitza Stark Marked gene: B3GALT6 as ready
Mendeliome v0.5696 B3GALT6 Zornitza Stark Gene: b3galt6 has been classified as Green List (High Evidence).
Mendeliome v0.5696 B3GALT6 Zornitza Stark Phenotypes for gene: B3GALT6 were changed from to Al-Gazali syndrome, MIM# 609465; Ehlers-Danlos syndrome, spondylodysplastic type, 2, MIM# 615349, MONDO:0014139; Spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fractures, MIM# 271640, MONDO:0010075
Mendeliome v0.5695 B3GALT6 Zornitza Stark Publications for gene: B3GALT6 were set to
Mendeliome v0.5694 B3GALT6 Zornitza Stark Mode of inheritance for gene: B3GALT6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5693 B3GALT6 Zornitza Stark reviewed gene: B3GALT6: Rating: GREEN; Mode of pathogenicity: None; Publications: 25149931, 29443383, 23664117, 29931299, 23664117, 23664118, 31614862; Phenotypes: Al-Gazali syndrome, MIM# 609465, Ehlers-Danlos syndrome, spondylodysplastic type, 2, MIM# 615349, MONDO:0014139, Spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fractures, MIM# 271640, MONDO:0010075; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5693 B3GALNT2 Zornitza Stark Marked gene: B3GALNT2 as ready
Mendeliome v0.5693 B3GALNT2 Zornitza Stark Gene: b3galnt2 has been classified as Green List (High Evidence).
Mendeliome v0.5693 B3GALNT2 Zornitza Stark Phenotypes for gene: B3GALNT2 were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 11, MIM# 615181; MONDO:0014071
Mendeliome v0.5692 B3GALNT2 Zornitza Stark Publications for gene: B3GALNT2 were set to
Mendeliome v0.5691 B3GALNT2 Zornitza Stark Mode of inheritance for gene: B3GALNT2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5690 B3GALNT2 Zornitza Stark reviewed gene: B3GALNT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23453667, 33290285, 29791932, 29273094, 28688748, 28303321; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 11, MIM# 615181, MONDO:0014071; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5690 MPDU1 Zornitza Stark Gene: mpdu1 has been classified as Green List (High Evidence).
Mendeliome v0.5690 MPDU1 Zornitza Stark Phenotypes for gene: MPDU1 were changed from to Congenital disorder of glycosylation, type If, MIM# 609180; MPDU1-CDG, MONDO:0012211
Mendeliome v0.5689 MPDU1 Zornitza Stark Publications for gene: MPDU1 were set to
Mendeliome v0.5688 MPDU1 Zornitza Stark Mode of inheritance for gene: MPDU1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5687 MPDU1 Zornitza Stark reviewed gene: MPDU1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11733564, 11733556, 31741824, 29721919; Phenotypes: Congenital disorder of glycosylation, type If, MIM# 609180, MPDU1-CDG, MONDO:0012211; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5687 DPAGT1 Zornitza Stark Marked gene: DPAGT1 as ready
Mendeliome v0.5687 DPAGT1 Zornitza Stark Gene: dpagt1 has been classified as Green List (High Evidence).
Mendeliome v0.5687 DPAGT1 Zornitza Stark Phenotypes for gene: DPAGT1 were changed from to Congenital disorder of glycosylation, type Ij, MIM# 608093; DPAGT1-CDG MONDO:0011964; Myasthenic syndrome, congenital, 13, with tubular aggregates, MIM# 614750
Mendeliome v0.5686 DPAGT1 Zornitza Stark Publications for gene: DPAGT1 were set to
Mendeliome v0.5685 DPAGT1 Zornitza Stark Mode of inheritance for gene: DPAGT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5684 DPAGT1 Zornitza Stark changed review comment from: Type I CDG. More than 20 unrelated families reported. Most affected individuals have a very severe disease course, where common findings are pronounced muscular hypotonia, intractable epilepsy, global developmental delay/intellectual disability, and early death. Additional features that may be observed include apnoea and respiratory deficiency, cataracts, joint contractures, vermian hypoplasia, dysmorphic features (esotropia, arched palate, micrognathia, finger clinodactyly, single flexion creases) and feeding difficulties.

Myasthenic syndrome, congenital, 13, with tubular aggregates, MIM 614750 is a milder allelic disorder.; to: Type I CDG. More than 20 unrelated families reported. Most affected individuals have a very severe disease course, where common findings are pronounced muscular hypotonia, intractable epilepsy, global developmental delay/intellectual disability, and early death. Additional features that may be observed include apnoea and respiratory deficiency, cataracts, joint contractures, vermian hypoplasia, dysmorphic features (esotropia, arched palate, micrognathia, finger clinodactyly, single flexion creases) and feeding difficulties.

Myasthenic syndrome, congenital, 13, with tubular aggregates, MIM 614750 is a milder allelic disorder. More than 5 unrelated families reported with this presentation.
Mendeliome v0.5684 DPAGT1 Zornitza Stark edited their review of gene: DPAGT1: Changed publications: 12872255, 22492991, 22304930, 31153949, 30653653, 30117111, 22742743, 29356258, 28712839, 28662078
Mendeliome v0.5684 DPAGT1 Zornitza Stark reviewed gene: DPAGT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12872255, 22492991, 22304930, 31153949, 30653653, 30117111; Phenotypes: Congenital disorder of glycosylation, type Ij, MIM# 608093, DPAGT1-CDG MONDO:0011964, Myasthenic syndrome, congenital, 13, with tubular aggregates, MIM# 614750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5684 DOLK Zornitza Stark Gene: dolk has been classified as Green List (High Evidence).
Mendeliome v0.5684 DOLK Zornitza Stark Phenotypes for gene: DOLK were changed from to DK1-CDG, MONDO:0012556; Congenital disorder of glycosylation, type Im, MIM# 610768
Mendeliome v0.5683 DOLK Zornitza Stark Publications for gene: DOLK were set to
Mendeliome v0.5682 DOLK Zornitza Stark Mode of inheritance for gene: DOLK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5681 DOLK Zornitza Stark reviewed gene: DOLK: Rating: GREEN; Mode of pathogenicity: None; Publications: 17273964, 22242004, 23890587, 30653653, 28816422, 24144945; Phenotypes: DK1-CDG, MONDO:0012556, Congenital disorder of glycosylation, type Im, MIM# 610768; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5681 SLC2A1 Zornitza Stark Gene: slc2a1 has been classified as Green List (High Evidence).
Mendeliome v0.5681 SLC2A1 Zornitza Stark Phenotypes for gene: SLC2A1 were changed from to GLUT1 deficiency syndrome 1, infantile onset, severe, MIM#606777; Dystonia 9, MIM#601042; Stomatin-deficient cryohydrocytosis with neurologic defects, MIM#608885; GLUT1 deficiency syndrome 2, childhood onset, MIM#612126; {Epilepsy, idiopathic generalized, susceptibility to, 12}, MIM#614847
Mendeliome v0.5680 SLC2A1 Zornitza Stark Publications for gene: SLC2A1 were set to
Mendeliome v0.5679 SLC2A1 Zornitza Stark Mode of inheritance for gene: SLC2A1 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.5678 MTX2 Zornitza Stark Phenotypes for gene: MTX2 were changed from Mandibuloacral dysplasia; lipodystrophy; arterial calcification to Mandibuloacral dysplasia progeroid syndrome, MIM# 619127; Mandibuloacral dysplasia; lipodystrophy; arterial calcification
Mendeliome v0.5677 MTX2 Zornitza Stark edited their review of gene: MTX2: Changed phenotypes: Mandibuloacral dysplasia progeroid syndrome, MIM# 619127, Mandibuloacral dysplasia, lipodystrophy, arterial calcification
Mendeliome v0.5677 SLC2A1 Elena Savva reviewed gene: SLC2A1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:18451999, 20129935, 10980529, 20221955, 31196579; Phenotypes: GLUT1 deficiency syndrome 1, infantile onset, severe, MIM#606777, Dystonia 9, MIM#601042, Stomatin-deficient cryohydrocytosis with neurologic defects, MIM#608885, GLUT1 deficiency syndrome 2, childhood onset, MIM#612126, {Epilepsy, idiopathic generalized, susceptibility to, 12}, MIM#614847; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.5677 ERCC1 Zornitza Stark Gene: ercc1 has been classified as Green List (High Evidence).
Mendeliome v0.5677 ERCC1 Zornitza Stark Phenotypes for gene: ERCC1 were changed from to Cerebrooculofacioskeletal syndrome 4, MIM# 610758
Mendeliome v0.5676 ERCC1 Zornitza Stark Publications for gene: ERCC1 were set to
Mendeliome v0.5675 ERCC1 Zornitza Stark Mode of inheritance for gene: ERCC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5674 ERCC1 Zornitza Stark reviewed gene: ERCC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 17273966, 23623389, 33315086; Phenotypes: Cerebrooculofacioskeletal syndrome 4, MIM# 610758; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5674 POR Zornitza Stark Gene: por has been classified as Green List (High Evidence).
Mendeliome v0.5674 POR Zornitza Stark Phenotypes for gene: POR were changed from to Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis, MIM#201750; Disordered steroidogenesis due to cytochrome P450 oxidoreductase, MIM#613571
Mendeliome v0.5673 POR Zornitza Stark Publications for gene: POR were set to
Mendeliome v0.5672 POR Zornitza Stark Mode of inheritance for gene: POR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5671 MYH6 Zornitza Stark Gene: myh6 has been classified as Green List (High Evidence).
Mendeliome v0.5671 MYH6 Zornitza Stark Phenotypes for gene: MYH6 were changed from to Atrial septal defect 3 MIM#614089; Congenital heart disease; Cardiomyopathy, dilated, 1EE MIM#613252; Cardiomyopathy, hypertrophic, 14 MIM#613251; {Sick sinus syndrome 3} MIM#614090
Mendeliome v0.5670 MYH6 Zornitza Stark Publications for gene: MYH6 were set to
Mendeliome v0.5669 MYH6 Zornitza Stark Mode of inheritance for gene: MYH6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5668 MYH6 Zornitza Stark reviewed gene: MYH6: Rating: GREEN; Mode of pathogenicity: None; Publications: 32656206, 31638415, 29969989, 29536580, 29332214, 30681346; Phenotypes: Atrial septal defect 3 MIM#614089, Congenital heart disease, Cardiomyopathy, dilated, 1EE MIM#613252, Cardiomyopathy, hypertrophic, 14 MIM#613251, {Sick sinus syndrome 3} MIM#614090; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5668 EZH2 Zornitza Stark Gene: ezh2 has been classified as Green List (High Evidence).
Mendeliome v0.5668 EZH2 Zornitza Stark Phenotypes for gene: EZH2 were changed from to Weaver syndrome MIM#277590
Mendeliome v0.5667 EZH2 Zornitza Stark Publications for gene: EZH2 were set to
Mendeliome v0.5666 EZH2 Zornitza Stark Mode of inheritance for gene: EZH2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5665 EZH2 Zornitza Stark reviewed gene: EZH2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23865096; Phenotypes: Weaver syndrome MIM#277590; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5665 POR Elena Savva reviewed gene: POR: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27068427; Phenotypes: Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis, MIM#201750, Disordered steroidogenesis due to cytochrome P450 oxidoreductase, MIM#613571; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.5665 MYH6 Elena Savva reviewed gene: MYH6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Atrial septal defect 3 MIM#614089, Cardiomyopathy, dilated, 1EE MIM#613252, Cardiomyopathy, hypertrophic, 14 MIM#613251, {Sick sinus syndrome 3} MIM#614090; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.5665 EZH2 Elena Savva reviewed gene: EZH2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29244146; Phenotypes: Weaver syndrome MIM#277590; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.5665 COG6 Zornitza Stark Gene: cog6 has been classified as Green List (High Evidence).
Mendeliome v0.5665 COG6 Zornitza Stark Phenotypes for gene: COG6 were changed from to Congenital disorder of glycosylation, type IIl, MIM# 614576
Mendeliome v0.5664 COG6 Zornitza Stark Publications for gene: COG6 were set to
Mendeliome v0.5663 COG6 Zornitza Stark Mode of inheritance for gene: COG6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5662 COG6 Zornitza Stark reviewed gene: COG6: Rating: GREEN; Mode of pathogenicity: None; Publications: 20605848, 23430903, 26260076, 32905044, 32683677, 31420886; Phenotypes: Congenital disorder of glycosylation, type IIl, MIM# 614576; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5662 COG5 Zornitza Stark Gene: cog5 has been classified as Green List (High Evidence).
Mendeliome v0.5662 COG5 Zornitza Stark Phenotypes for gene: COG5 were changed from to Congenital disorder of glycosylation, type IIi, MIM# 613612
Mendeliome v0.5661 COG5 Zornitza Stark Publications for gene: COG5 were set to
Mendeliome v0.5660 COG5 Zornitza Stark Mode of inheritance for gene: COG5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5659 COG5 Zornitza Stark reviewed gene: COG5: Rating: GREEN; Mode of pathogenicity: None; Publications: 23228021, 31572517, 32174980; Phenotypes: Congenital disorder of glycosylation, type IIi, MIM# 613612; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5659 FIGLA Zornitza Stark Gene: figla has been classified as Green List (High Evidence).
Mendeliome v0.5659 FIGLA Zornitza Stark Phenotypes for gene: FIGLA were changed from to Premature ovarian failure 6, MIM# 612310
Mendeliome v0.5658 FIGLA Zornitza Stark Publications for gene: FIGLA were set to
Mendeliome v0.5657 FIGLA Zornitza Stark Mode of inheritance for gene: FIGLA was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5656 FIGLA Zornitza Stark reviewed gene: FIGLA: Rating: GREEN; Mode of pathogenicity: None; Publications: 18499083, 25314148, 29914564; Phenotypes: Premature ovarian failure 6, MIM# 612310; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5656 ESR1 Zornitza Stark Gene: esr1 has been classified as Green List (High Evidence).
Mendeliome v0.5656 ESR1 Zornitza Stark Phenotypes for gene: ESR1 were changed from to Estrogen resistance, MIM# 615363
Mendeliome v0.5655 ESR1 Zornitza Stark Publications for gene: ESR1 were set to
Mendeliome v0.5654 ESR1 Zornitza Stark Mode of inheritance for gene: ESR1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5653 ESR1 Zornitza Stark reviewed gene: ESR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27754803, 23841731, 24152274; Phenotypes: Estrogen resistance, MIM# 615363; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5653 SHMT2 Zornitza Stark Phenotypes for gene: SHMT2 were changed from Congenital microcephaly; Infantile axial hypotonia; Spastic paraparesis; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum; Abnormal cortical gyration; Hypertrophic cardiomyopathy; Abnormality of the face; Proximal placement of thumb; 2-3 toe syndactyly to Neurodevelopmental disorder with cardiomyopathy, spasticity, and brain abnormalities (NEDCASB), MIM#619121; Congenital microcephaly; Infantile axial hypotonia; Spastic paraparesis; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum; Abnormal cortical gyration; Hypertrophic cardiomyopathy; Abnormality of the face; Proximal placement of thumb; 2-3 toe syndactyly
Mendeliome v0.5652 SHMT2 Zornitza Stark edited their review of gene: SHMT2: Changed phenotypes: Neurodevelopmental disorder with cardiomyopathy, spasticity, and brain abnormalities (NEDCASB), MIM#619121, Congenital microcephaly, Infantile axial hypotonia, Spastic paraparesis, Global developmental delay, Intellectual disability, Abnormality of the corpus callosum, Abnormal cortical gyration, Hypertrophic cardiomyopathy, Abnormality of the face, Proximal placement of thumb, 2-3 toe syndactyly
Mendeliome v0.5652 BMP15 Zornitza Stark commented on gene: BMP15: Only affects females, variants inherited from asymptomatic fathers. Over 50 individuals reported.
Mendeliome v0.5652 BMP15 Zornitza Stark Gene: bmp15 has been classified as Green List (High Evidence).
Mendeliome v0.5652 BMP15 Zornitza Stark Phenotypes for gene: BMP15 were changed from to Ovarian dysgenesis 2, MIM# 300510; Premature ovarian failure 4, MIM# 300510
Mendeliome v0.5651 BMP15 Zornitza Stark Publications for gene: BMP15 were set to
Mendeliome v0.5650 BMP15 Zornitza Stark Mode of inheritance for gene: BMP15 was changed from Unknown to Other
Mendeliome v0.5649 BMP15 Zornitza Stark reviewed gene: BMP15: Rating: GREEN; Mode of pathogenicity: None; Publications: 15136966, 16508750, 16464940; Phenotypes: Ovarian dysgenesis 2, MIM# 300510, Premature ovarian failure 4, MIM# 300510; Mode of inheritance: Other
Mendeliome v0.5649 PANX1 Zornitza Stark Gene: panx1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5649 PANX1 Zornitza Stark Classified gene: PANX1 as Amber List (moderate evidence)
Mendeliome v0.5649 PANX1 Zornitza Stark Gene: panx1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5648 PANX1 Zornitza Stark gene: PANX1 was added
gene: PANX1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PANX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PANX1 were set to 30918116; 32838805
Phenotypes for gene: PANX1 were set to Oocyte maturation defect 7, MIM# 618550
Review for gene: PANX1 was set to AMBER
Added comment: Two unrelated families, some functional data. Clinical presentation is with infertility.
Sources: Expert list
Mendeliome v0.5647 NANOS3 Bryony Thompson Gene: nanos3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5647 NANOS3 Bryony Thompson Classified gene: NANOS3 as Amber List (moderate evidence)
Mendeliome v0.5647 NANOS3 Bryony Thompson Gene: nanos3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5646 NANOS3 Bryony Thompson gene: NANOS3 was added
gene: NANOS3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NANOS3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: NANOS3 were set to 25054146; 24091668
Phenotypes for gene: NANOS3 were set to Primary ovarian insufficiency
Review for gene: NANOS3 was set to AMBER
Added comment: A homozygous missense (p.Glu120Lys) was identified in two Brazillian sisters with primary amenorrhea, and supporting in vitro functional assays. A heterozygous missense (p.Arg153Trp) was identified in a Chinese woman with POI, with supporting in vitro functional assays. Also, supporting null mouse model.
Sources: Literature
Mendeliome v0.5645 MSH5 Bryony Thompson Gene: msh5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5645 MSH5 Bryony Thompson Classified gene: MSH5 as Amber List (moderate evidence)
Mendeliome v0.5645 MSH5 Bryony Thompson Gene: msh5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5644 MSH5 Bryony Thompson gene: MSH5 was added
gene: MSH5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MSH5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MSH5 were set to 28175301; 9916805; 24970489
Phenotypes for gene: MSH5 were set to Premature ovarian failure 13 MIM#617442
Review for gene: MSH5 was set to AMBER
Added comment: A homozygous missense mutation (p.D487Y) in two sisters with POI. Also, homologous mutation in mice results in atrophic ovaries without oocytes, and in vitro functional study revealed that mutant MSH5 impaired DNA homologous recombination repair. Null mouse model is viable, but sterile. A case with congenital adrenal hyperplasia, ovarian failure and Ehlers-Danlos syndrome had a de novo t(6;14)(p21;q32) translocation, including CYP21A2,TNXB and MSH5.
Sources: Literature
Mendeliome v0.5643 PATL2 Zornitza Stark Marked gene: PATL2 as ready
Mendeliome v0.5643 PATL2 Zornitza Stark Gene: patl2 has been classified as Green List (High Evidence).
Mendeliome v0.5643 PATL2 Zornitza Stark Classified gene: PATL2 as Green List (high evidence)
Mendeliome v0.5643 PATL2 Zornitza Stark Gene: patl2 has been classified as Green List (High Evidence).
Mendeliome v0.5642 PATL2 Zornitza Stark gene: PATL2 was added
gene: PATL2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PATL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PATL2 were set to 28965844; 28965849; 32048119; 30765866
Phenotypes for gene: PATL2 were set to Oocyte maturation defect 4, MIM# 617743
Review for gene: PATL2 was set to GREEN
Added comment: More than 5 unrelated families reported, presentation is with infertility.
Sources: Expert list
Mendeliome v0.5641 FANCM Bryony Thompson Phenotypes for gene: FANCM were changed from Spermatogenic failure 28, MIM# 618086 to Spermatogenic failure 28, MIM# 618086; Premature ovarian failure 15 MIM#618096
Mendeliome v0.5640 FANCM Bryony Thompson Publications for gene: FANCM were set to 30075111; 29895858; 28837162
Mendeliome v0.5639 FANCM Bryony Thompson Classified gene: FANCM as Green List (high evidence)
Mendeliome v0.5639 FANCM Bryony Thompson Added comment: Comment on list classification: Green for POI
Mendeliome v0.5639 FANCM Bryony Thompson Gene: fancm has been classified as Green List (High Evidence).
Mendeliome v0.5638 FANCM Bryony Thompson reviewed gene: FANCM: Rating: GREEN; Mode of pathogenicity: None; Publications: 29231814, 28837162, 33036707, 25010009; Phenotypes: Premature ovarian failure 15 MIM#618096; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5638 EIF4ENIF1 Bryony Thompson Gene: eif4enif1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5638 PGRMC1 Zornitza Stark Gene: pgrmc1 has been classified as Red List (Low Evidence).
Mendeliome v0.5638 PGRMC1 Zornitza Stark gene: PGRMC1 was added
gene: PGRMC1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PGRMC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PGRMC1 were set to 25246111; 18782852
Phenotypes for gene: PGRMC1 were set to Premature ovarian failure
Review for gene: PGRMC1 was set to RED
Added comment: One family with translocation reported and two affected individuals. Another individual identified as part of a cohort with a missense variant (H165R), but the variant is present in >200 hets in gnomad. Subsequent cohort study did not find an association.
Sources: Expert list
Mendeliome v0.5637 EIF4ENIF1 Bryony Thompson Classified gene: EIF4ENIF1 as Amber List (moderate evidence)
Mendeliome v0.5637 EIF4ENIF1 Bryony Thompson Gene: eif4enif1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5636 EIF4ENIF1 Bryony Thompson gene: EIF4ENIF1 was added
gene: EIF4ENIF1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EIF4ENIF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EIF4ENIF1 were set to 31810472; 23902945; 33095795
Phenotypes for gene: EIF4ENIF1 were set to Primary ovarian insufficiency
Review for gene: EIF4ENIF1 was set to AMBER
Added comment: 3 families: A missense (p.Q842P) segregated between a mother and daughter with diminished ovarian reserve (DOR) and premature ovarian insufficiency (POI). A nonsense variant (p.Ser429Ter) segregated in 7 affected women over 3 consecutive generations with early menopause at approximately age 30 years. A missense (p.Lys669Arg) was identified in a Brazilian case with POI.
Sources: Literature
Mendeliome v0.5635 POF1B Zornitza Stark Gene: pof1b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5635 POF1B Zornitza Stark Phenotypes for gene: POF1B were changed from to Premature ovarian failure 2B, MIM# 300604
Mendeliome v0.5634 POF1B Zornitza Stark Publications for gene: POF1B were set to
Mendeliome v0.5633 POF1B Zornitza Stark Mode of inheritance for gene: POF1B was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.5632 POF1B Zornitza Stark Classified gene: POF1B as Amber List (moderate evidence)
Mendeliome v0.5632 POF1B Zornitza Stark Gene: pof1b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5631 DIAPH2 Bryony Thompson Gene: diaph2 has been classified as Red List (Low Evidence).
Mendeliome v0.5631 POF1B Zornitza Stark reviewed gene: POF1B: Rating: AMBER; Mode of pathogenicity: None; Publications: 16773570, 25676666; Phenotypes: Premature ovarian failure 2B, MIM# 300604; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.5631 DIAPH2 Bryony Thompson Classified gene: DIAPH2 as Red List (low evidence)
Mendeliome v0.5631 DIAPH2 Bryony Thompson Gene: diaph2 has been classified as Red List (Low Evidence).
Mendeliome v0.5630 DIAPH2 Bryony Thompson reviewed gene: DIAPH2: Rating: RED; Mode of pathogenicity: None; Publications: 9497258, 30689869, 26175800, 11129329; Phenotypes: ?Premature ovarian failure 2A MIM#300511; 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 v0.5630 CCDC141 Bryony Thompson Gene: ccdc141 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5630 POU5F1 Zornitza Stark gene: POU5F1 was added
gene: POU5F1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: POU5F1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POU5F1 were set to 21273125
Phenotypes for gene: POU5F1 were set to Premature ovarian failure
Review for gene: POU5F1 was set to RED
Added comment: Single individual reported in 2011 and a missense variant.
Sources: Expert list
Mendeliome v0.5629 CCDC141 Bryony Thompson Classified gene: CCDC141 as Amber List (moderate evidence)
Mendeliome v0.5629 CCDC141 Bryony Thompson Gene: ccdc141 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5628 CCDC141 Bryony Thompson gene: CCDC141 was added
gene: CCDC141 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CCDC141 was set to Unknown
Publications for gene: CCDC141 were set to 27014940; 28324054; 25192046
Phenotypes for gene: CCDC141 were set to Anosmic hypogonadotropic hypogonadism
Review for gene: CCDC141 was set to AMBER
Added comment: A consanguineous family had a homozygous nonsense variant, but also had a homozygous missense in FEZF1. 3 other families reported with heterozygous variants, but other variants in other genes present. In an olfactory mouse model, Ccdc141 is expressed in GnRH neurons and olfactory fibers and that knockdown of Ccdc141 reduces GnRH neuronal migration.
Sources: Literature
Mendeliome v0.5627 SGO2 Zornitza Stark Gene: sgo2 has been classified as Red List (Low Evidence).
Mendeliome v0.5627 SGO2 Zornitza Stark gene: SGO2 was added
gene: SGO2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SGO2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SGO2 were set to 27629923
Phenotypes for gene: SGO2 were set to Perrault syndrome
Review for gene: SGO2 was set to RED
Added comment: Single affected individual reported, though deafness was thought to be explained by a CLDN14 variant. Protein is known to be involved in meiosis.
Sources: Expert list
Mendeliome v0.5626 SOHLH2 Zornitza Stark Gene: sohlh2 has been classified as Red List (Low Evidence).
Mendeliome v0.5626 SOHLH2 Zornitza Stark gene: SOHLH2 was added
gene: SOHLH2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SOHLH2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOHLH2 were set to 24524832; 19014927
Phenotypes for gene: SOHLH2 were set to Premature ovarian failure
Review for gene: SOHLH2 was set to RED
Added comment: Heterozygous variants in this gene found to be enriched in a cohort of women with POF, substantial data including mouse models implicating this gene in infertility but paucity of well characterised cases.
Sources: Expert list
Mendeliome v0.5625 SYCE1 Zornitza Stark Gene: syce1 has been classified as Green List (High Evidence).
Mendeliome v0.5625 SYCE1 Zornitza Stark Classified gene: SYCE1 as Green List (high evidence)
Mendeliome v0.5625 SYCE1 Zornitza Stark Gene: syce1 has been classified as Green List (High Evidence).
Mendeliome v0.5624 SYCE1 Zornitza Stark gene: SYCE1 was added
gene: SYCE1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SYCE1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SYCE1 were set to 25062452; 32917591; 32741963; 32402064; 31925770; 31916078
Phenotypes for gene: SYCE1 were set to Premature ovarian failure 12, MIM# 616947; Spermatogenic failure 15 ,MIM#616950
Review for gene: SYCE1 was set to GREEN
Added comment: More than 5 families reported with POF/SF and bi-allelic variants in this gene. Mechanism is thought to be disruption of meiosis, mouse model data also supports gene-disease association.
Sources: Expert list
Mendeliome v0.5623 DACH2 Zornitza Stark Gene: dach2 has been classified as Red List (Low Evidence).
Mendeliome v0.5623 DACH2 Zornitza Stark gene: DACH2 was added
gene: DACH2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: DACH2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DACH2 were set to 15459172
Phenotypes for gene: DACH2 were set to Primary ovarian insufficiency
Review for gene: DACH2 was set to RED
Added comment: In a small candidate gene study, missense were more common in POI cases than controls (p= 0.0125). 5 missense reported in 7 POI cases, although 2 of the missense are too common in gnomAD for a dominant disorder. No other reports with evidence for an association with POI.
Sources: Expert list
Mendeliome v0.5622 TUBB8 Zornitza Stark Marked gene: TUBB8 as ready
Mendeliome v0.5622 TUBB8 Zornitza Stark Gene: tubb8 has been classified as Green List (High Evidence).
Mendeliome v0.5622 TUBB8 Zornitza Stark Phenotypes for gene: TUBB8 were changed from to Oocyte maturation defect 2, MIM# 616780
Mendeliome v0.5621 TUBB8 Zornitza Stark Publications for gene: TUBB8 were set to
Mendeliome v0.5620 TUBB8 Zornitza Stark Mode of inheritance for gene: TUBB8 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5619 TUBB8 Zornitza Stark reviewed gene: TUBB8: Rating: GREEN; Mode of pathogenicity: None; Publications: 26789871, 27273344; Phenotypes: Oocyte maturation defect 2, MIM# 616780; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5619 WEE2 Zornitza Stark Gene: wee2 has been classified as Green List (High Evidence).
Mendeliome v0.5619 WEE2 Zornitza Stark Phenotypes for gene: WEE2 were changed from to Oocyte maturation defect 5, MIM# 617996
Mendeliome v0.5618 WEE2 Zornitza Stark Publications for gene: WEE2 were set to
Mendeliome v0.5617 WEE2 Zornitza Stark Mode of inheritance for gene: WEE2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5616 WEE2 Zornitza Stark reviewed gene: WEE2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29606300, 30628060; Phenotypes: Oocyte maturation defect 5, MIM# 617996; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5616 ZP1 Zornitza Stark Gene: zp1 has been classified as Green List (High Evidence).
Mendeliome v0.5616 ZP1 Zornitza Stark Classified gene: ZP1 as Green List (high evidence)
Mendeliome v0.5616 ZP1 Zornitza Stark Gene: zp1 has been classified as Green List (High Evidence).
Mendeliome v0.5615 ZP1 Zornitza Stark gene: ZP1 was added
gene: ZP1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ZP1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ZP1 were set to 24670168; 30810869; 32573113; 33272616
Phenotypes for gene: ZP1 were set to Oocyte maturation defect 1, MIM# 615774
Review for gene: ZP1 was set to GREEN
Added comment: Multiple unrelated individuals reported, presents as primary infertility.
Sources: Expert list
Mendeliome v0.5614 ZP2 Zornitza Stark Phenotypes for gene: ZP2 were changed from Female infertility to Oocyte maturation defect 6, MIM# 618353; Female infertility
Mendeliome v0.5613 ZP2 Zornitza Stark edited their review of gene: ZP2: Changed phenotypes: Oocyte maturation defect 6, MIM# 618353, Female infertility
Mendeliome v0.5613 ZP3 Zornitza Stark Gene: zp3 has been classified as Green List (High Evidence).
Mendeliome v0.5613 ZP3 Zornitza Stark Classified gene: ZP3 as Green List (high evidence)
Mendeliome v0.5613 ZP3 Zornitza Stark Gene: zp3 has been classified as Green List (High Evidence).
Mendeliome v0.5612 ZP3 Zornitza Stark gene: ZP3 was added
gene: ZP3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ZP3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZP3 were set to 28886344; 30810869; 33272616; 32573113
Phenotypes for gene: ZP3 were set to Oocyte maturation defect 3, MIM# 617712
Review for gene: ZP3 was set to GREEN
Added comment: Oocyte maturation defect with normal ovarian reserves and menstrual cycles, presents as infertility.
Sources: Expert list
Mendeliome v0.5611 ECEL1P2 Zornitza Stark Gene: ecel1p2 has been classified as Red List (Low Evidence).
Mendeliome v0.5611 ECEL1P2 Zornitza Stark Classified gene: ECEL1P2 as Red List (low evidence)
Mendeliome v0.5611 ECEL1P2 Zornitza Stark Gene: ecel1p2 has been classified as Red List (Low Evidence).
Mendeliome v0.5610 ECEL1P2 Zornitza Stark reviewed gene: ECEL1P2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.5610 CCDC32 Zornitza Stark Phenotypes for gene: CCDC32 were changed from craniofacial, cardiac and neurodevelopmental anomalies to Cardiofacioneurodevelopmental syndrome (CFNDS), MIM#619123; Craniofacial, cardiac, laterality and neurodevelopmental anomalies
Mendeliome v0.5609 CCDC32 Zornitza Stark edited their review of gene: CCDC32: Changed rating: GREEN; Changed phenotypes: Cardiofacioneurodevelopmental syndrome (CFNDS), MIM#619123, Craniofacial, cardiac, laterality and neurodevelopmental anomalies; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5609 CDC40 Zornitza Stark Gene: cdc40 has been classified as Red List (Low Evidence).
Mendeliome v0.5609 CDC40 Zornitza Stark gene: CDC40 was added
gene: CDC40 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CDC40 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDC40 were set to 33220177
Phenotypes for gene: CDC40 were set to Pontocerebellar hypoplasia; microcephaly; seizures
Review for gene: CDC40 was set to RED
Added comment: Single individual reported with bi-allelic variants in the gene and PCH, microcephaly, hypotonia, seizures, severe DD/ID, thrombocytopaenia, anaemia. Interaction with PPIL1 and mouse model support gene-disease association. Gene referred to as PRP17 in paper.
Sources: Literature
Mendeliome v0.5608 PPIL1 Zornitza Stark Gene: ppil1 has been classified as Green List (High Evidence).
Mendeliome v0.5608 PPIL1 Zornitza Stark Classified gene: PPIL1 as Green List (high evidence)
Mendeliome v0.5608 PPIL1 Zornitza Stark Gene: ppil1 has been classified as Green List (High Evidence).
Mendeliome v0.5607 PPIL1 Zornitza Stark gene: PPIL1 was added
gene: PPIL1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PPIL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPIL1 were set to 33220177
Phenotypes for gene: PPIL1 were set to Pontocerebellar hypoplasia; microcephaly; seizures
Review for gene: PPIL1 was set to GREEN
Added comment: 17 individuals from 9 unrelated families reported with bi-allelic variants in the gene and PCH, microcephaly, hypotonia, seizures, severe DD/ID. Mouse models support gene-disease association.
Sources: Literature
Mendeliome v0.5606 FRA12A Bryony Thompson Classified STR: FRA12A as Amber List (moderate evidence)
Mendeliome v0.5606 FRA12A Bryony Thompson Str: fra12a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5605 FRA12A Bryony Thompson STR: FRA12A was added
STR: FRA12A was added to Mendeliome. Sources: Other
5'UTR tags were added to STR: FRA12A.
Mode of inheritance for STR: FRA12A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: FRA12A were set to 17236128
Phenotypes for STR: FRA12A were set to Mental retardation, FRA12A type MIM#136630
Review for STR: FRA12A was set to AMBER
Added comment: NM_173602.2:c.-137CGG[X]
All individuals expressing FRA12A had CGG-repeat expansion. The length of the expanded allele in 3 unaffected FRA12A carriers was 650–850 bp. In the two affected patients from 2 families with FRA12A, the length of the expanded allele was ∼1,050-1,150 bp.
70 controls used to determine the "normal" repeat range.
Sources: Other
Mendeliome v0.5604 DIP2B Bryony Thompson Classified gene: DIP2B as No list
Mendeliome v0.5604 DIP2B Bryony Thompson Added comment: Comment on list classification: Only repeat expansion reported. Added as an STR
Mendeliome v0.5604 DIP2B Bryony Thompson Gene: dip2b has been removed from the panel.
Mendeliome v0.5603 DIP2B Bryony Thompson Classified gene: DIP2B as No list
Mendeliome v0.5603 DIP2B Bryony Thompson Added comment: Comment on list classification: Only repeat expansion reported. Added as an STR
Mendeliome v0.5603 DIP2B Bryony Thompson Gene: dip2b has been removed from the panel.
Mendeliome v0.5602 PTPRQ Zornitza Stark Publications for gene: PTPRQ were set to 20346435; 20472657; 25919374; 14534255; 22357859; 29849575; 29309402; 31655630
Mendeliome v0.5601 PTPRQ Zornitza Stark changed review comment from: Additional heterozygous variants reported in PMID: 33229591; to: Additional heterozygous variants reported in PMID: 33229591, Green for both MOIs.
Mendeliome v0.5601 PTPRQ Zornitza Stark edited their review of gene: PTPRQ: Added comment: Additional heterozygous variants reported in PMID: 33229591; Changed publications: 20346435, 20472657, 25919374, 14534255, 22357859, 29849575, 29309402, 31655630, 33229591
Mendeliome v0.5601 CANVAS_ACAGG Bryony Thompson changed review comment from: A novel RFC1 repeat expansion motif, (ACAGG)exp, identified in three affected individuals from 2 families in an Asian-Pacific cohort for CANVAS. Southern blot was used to identify the repeat was ~1000kb in one of the cases, equivalent to ~1000 repeats.
Sources: Literature; to: A novel RFC1 repeat expansion motif, (ACAGG)exp, identified homozygous in three affected individuals from 2 families in an Asian-Pacific cohort for CANVAS. Southern blot was used to identify the repeat was ~1000kb in one of the cases, equivalent to ~1000 repeats.
Sources: Literature
Mendeliome v0.5601 CANVAS_ACAGG Bryony Thompson Marked STR: CANVAS_ACAGG as ready
Mendeliome v0.5601 CANVAS_ACAGG Bryony Thompson Str: canvas_acagg has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5601 CANVAS_ACAGG Bryony Thompson Classified STR: CANVAS_ACAGG as Amber List (moderate evidence)
Mendeliome v0.5601 CANVAS_ACAGG Bryony Thompson Added comment: Comment on list classification: Used the pathogenic cut-off of 400 repeats from original CANVAS repeat
Mendeliome v0.5601 CANVAS_ACAGG Bryony Thompson Str: canvas_acagg has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5600 CANVAS_ACAGG Bryony Thompson STR: CANVAS_ACAGG was added
STR: CANVAS_ACAGG was added to Mendeliome. Sources: Literature
Mode of inheritance for STR: CANVAS_ACAGG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for STR: CANVAS_ACAGG were set to 33103729
Phenotypes for STR: CANVAS_ACAGG were set to Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome; fasciculations; elevated serum creatine kinase levels; denervation
Review for STR: CANVAS_ACAGG was set to AMBER
Added comment: A novel RFC1 repeat expansion motif, (ACAGG)exp, identified in three affected individuals from 2 families in an Asian-Pacific cohort for CANVAS. Southern blot was used to identify the repeat was ~1000kb in one of the cases, equivalent to ~1000 repeats.
Sources: Literature
Mendeliome v0.5599 CANVAS Bryony Thompson Marked STR: CANVAS as ready
Mendeliome v0.5599 CANVAS Bryony Thompson Str: canvas has been classified as Green List (High Evidence).
Mendeliome v0.5599 CANVAS Bryony Thompson Classified STR: CANVAS as Green List (high evidence)
Mendeliome v0.5599 CANVAS Bryony Thompson Str: canvas has been classified as Green List (High Evidence).
Mendeliome v0.5598 CANVAS Bryony Thompson STR: CANVAS was added
STR: CANVAS was added to Mendeliome. Sources: Expert list
Mode of inheritance for STR: CANVAS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for STR: CANVAS were set to 30926972; 32851396
Phenotypes for STR: CANVAS were set to Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome MIM#614575
Review for STR: CANVAS was set to GREEN
STR: CANVAS was marked as clinically relevant
Added comment: Simple tandem repeat (AAAAG)11 replaced with (AAGGG)n in intron 2 of RFC1. Loss of function is not the mechanism of disease. Maori population-specific CANVAS configuration (AAAGG)10-25(AAGGG)exp. (AAAGG)n repeat alone is not pathogenic.
Sources: Expert list
Mendeliome v0.5597 RFC1 Bryony Thompson Classified gene: RFC1 as No list
Mendeliome v0.5597 RFC1 Bryony Thompson Gene: rfc1 has been removed from the panel.
Mendeliome v0.5596 GDF11 Zornitza Stark Phenotypes for gene: GDF11 were changed from Cleft lip and palate to Vertebral hypersegmentation and orofacial anomalies (VHO), MIM#619122
Mendeliome v0.5595 GDF11 Zornitza Stark edited their review of gene: GDF11: Changed phenotypes: Vertebral hypersegmentation and orofacial anomalies (VHO), MIM#619122
Mendeliome v0.5595 RNASEH2C Zornitza Stark Gene: rnaseh2c has been classified as Green List (High Evidence).
Mendeliome v0.5595 RNASEH2C Zornitza Stark Phenotypes for gene: RNASEH2C were changed from to Aicardi-Goutieres syndrome 3 (MIM# 610329), AR
Mendeliome v0.5594 RNASEH2C Zornitza Stark Publications for gene: RNASEH2C were set to
Mendeliome v0.5593 RNASEH2C Zornitza Stark Mode of inheritance for gene: RNASEH2C was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5592 CFAP52 Zornitza Stark Gene: cfap52 has been classified as Green List (High Evidence).
Mendeliome v0.5592 CFAP52 Zornitza Stark Classified gene: CFAP52 as Green List (high evidence)
Mendeliome v0.5592 CFAP52 Zornitza Stark Gene: cfap52 has been classified as Green List (High Evidence).
Mendeliome v0.5591 CFAP45 Zornitza Stark Gene: cfap45 has been classified as Green List (High Evidence).
Mendeliome v0.5591 CFAP45 Zornitza Stark Classified gene: CFAP45 as Green List (high evidence)
Mendeliome v0.5591 CFAP45 Zornitza Stark Gene: cfap45 has been classified as Green List (High Evidence).
Mendeliome v0.5590 RNASEH2C Chern Lim reviewed gene: RNASEH2C: Rating: GREEN; Mode of pathogenicity: None; Publications: 24183309, 23322642; Phenotypes: Aicardi-Goutieres syndrome 3 (MIM# 610329), AR; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.5590 LMX1B Zornitza Stark Phenotypes for gene: LMX1B were changed from Nail-patella syndrome (MIM#161200), MONDO:0008061; LMX1B-related nephropathy to Nail-patella syndrome (MIM#161200), MONDO:0008061; LMX1B-related nephropathy; Focal segmental glomerulosclerosis-10 (FSGS10), MIM#256020
Mendeliome v0.5589 LMX1B Zornitza Stark edited their review of gene: LMX1B: Changed phenotypes: Nail-patella syndrome (MIM#161200), MONDO:0008061, LMX1B-related nephropathy, Focal segmental glomerulosclerosis-10 (FSGS10), MIM#256020
Mendeliome v0.5589 RAP1A Zornitza Stark Gene: rap1a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5589 RAP1A Zornitza Stark Phenotypes for gene: RAP1A were changed from to Kabuki syndrome
Mendeliome v0.5588 RAP1A Zornitza Stark Publications for gene: RAP1A were set to
Mendeliome v0.5587 RAP1A Zornitza Stark Mode of inheritance for gene: RAP1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5586 RAP1A Zornitza Stark Classified gene: RAP1A as Amber List (moderate evidence)
Mendeliome v0.5586 RAP1A Zornitza Stark Gene: rap1a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5585 RAP1A Zornitza Stark reviewed gene: RAP1A: Rating: AMBER; Mode of pathogenicity: None; Publications: 26280580; Phenotypes: Kabuki syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5585 RAP1B Zornitza Stark Publications for gene: RAP1B were set to 32627184
Mendeliome v0.5584 RAP1B Zornitza Stark Classified gene: RAP1B as Green List (high evidence)
Mendeliome v0.5584 RAP1B Zornitza Stark Gene: rap1b has been classified as Green List (High Evidence).
Mendeliome v0.5583 RAP1B Zornitza Stark edited their review of gene: RAP1B: Added comment: Another individual with de novo missense reported from a cohort of Kabuki-like patients but note facial gestalt was not typical.; Changed rating: GREEN; Changed publications: 32627184, 26280580
Mendeliome v0.5583 RAP1B Zornitza Stark Gene: rap1b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5583 RAP1B Zornitza Stark Phenotypes for gene: RAP1B were changed from to RAP1B‐associated syndrome; intellectual disability; microcephaly; thrombocytopaenia
Mendeliome v0.5582 RAP1B Zornitza Stark Publications for gene: RAP1B were set to
Mendeliome v0.5581 RAP1B Zornitza Stark Mode of inheritance for gene: RAP1B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5580 RAP1B Zornitza Stark Classified gene: RAP1B as Amber List (moderate evidence)
Mendeliome v0.5580 RAP1B Zornitza Stark Gene: rap1b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5579 RAP1B Zornitza Stark reviewed gene: RAP1B: Rating: AMBER; Mode of pathogenicity: None; Publications: 32627184; Phenotypes: RAP1B‐associated syndrome, intellectual disability, microcephaly, thrombocytopaenia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5579 EMC10 Zornitza Stark Gene: emc10 has been classified as Red List (Low Evidence).
Mendeliome v0.5579 EMC10 Zornitza Stark gene: EMC10 was added
gene: EMC10 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EMC10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EMC10 were set to 32869858
Phenotypes for gene: EMC10 were set to Intellectual disability
Review for gene: EMC10 was set to RED
Added comment: Homozygous variants of EMC1 are associated with GDD, scoliosis, and cerebellar atrophy, indicating the relevance of this pathway for neurogenetic disorders.

One Saudi family with 2 affected individuals with mild ID, speech delay, and GDD.
WES and Sanger sequencing revealed a homozygous splice acceptor site variant (c.679‐1G>A) in EMC10 . Variant segregated within the family. RT‐qPCR showed a substantial decrease in the relative EMC10 gene expression in the patients.
Sources: Literature
Mendeliome v0.5578 FBXO28 Zornitza Stark Gene: fbxo28 has been classified as Green List (High Evidence).
Mendeliome v0.5578 FBXO28 Zornitza Stark Classified gene: FBXO28 as Green List (high evidence)
Mendeliome v0.5578 FBXO28 Zornitza Stark Gene: fbxo28 has been classified as Green List (High Evidence).
Mendeliome v0.5577 FBXO28 Zornitza Stark gene: FBXO28 was added
gene: FBXO28 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FBXO28 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FBXO28 were set to 33280099
Phenotypes for gene: FBXO28 were set to Developmental and epileptic encephalopathy
Review for gene: FBXO28 was set to GREEN
Added comment: Nine new individuals with FBXO28 pathogenic variants (four missense, including one recurrent, three nonsense, and one frameshift) and all 10 known cases reviewed to delineate the phenotypic spectrum. All had epilepsy and 9 of 10 had DEE, including infantile spasms (3) and a progressive myoclonic epilepsy (1). Median age at seizure onset was 22.5 months (range 8 months to 5 years). Nine of 10 patients had intellectual disability, which was profound in six of nine and severe in three of nine. Movement disorders occurred in eight of 10 patients, six of 10 had hypotonia, four of 10 had acquired microcephaly, and five of 10 had dysmorphic features.
Sources: Literature
Mendeliome v0.5576 CFAP52 Zornitza Stark gene: CFAP52 was added
gene: CFAP52 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CFAP52 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFAP52 were set to 25469542; 33139725
Phenotypes for gene: CFAP52 were set to Heterotaxy
Review for gene: CFAP52 was set to GREEN
Added comment: Five unrelated families and functional data.
Sources: Literature
Mendeliome v0.5575 CFAP45 Zornitza Stark gene: CFAP45 was added
gene: CFAP45 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CFAP45 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFAP45 were set to 33139725
Phenotypes for gene: CFAP45 were set to Situs inversus; asthenospermia
Review for gene: CFAP45 was set to GREEN
Added comment: Three unrelated individuals reported with bi-alleic LOF variants, mouse model recapitulated phenotype.
Sources: Literature
Mendeliome v0.5574 CLCN6 Zornitza Stark Mode of inheritance for gene: CLCN6 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5573 CLCN6 Zornitza Stark Classified gene: CLCN6 as Green List (high evidence)
Mendeliome v0.5573 CLCN6 Zornitza Stark Gene: clcn6 has been classified as Green List (High Evidence).
Mendeliome v0.5572 CLCN6 Zornitza Stark edited their review of gene: CLCN6: Added comment: Three unrelated families reported with recurrent GOF de novo c.1658A>G (p.Tyr553Cys) and severe developmental delay with pronounced generalized hypotonia, respiratory insufficiency, and variable neurodegeneration and diffusion restriction in cerebral peduncles, midbrain, and/or brainstem in MRI scans.; Changed rating: GREEN; Changed publications: 25794116, 21107136, 33217309; Changed phenotypes: Neurodegeneration, Benign partial epilepsy, febrile seizures, NCL; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5572 GDF6 Zornitza Stark Phenotypes for gene: GDF6 were changed from Klippel-Feil syndrome 1, autosomal dominant 118100; Leber congenital amaurosis 17 615360; Microphthalmia with coloboma 6, digenic 613703; Microphthalmia, isolated 4 613094; Multiple synostoses syndrome 4 617898 to Klippel-Feil syndrome 1, autosomal dominant 118100; Leber congenital amaurosis 17 615360; Microphthalmia with coloboma 6, digenic 613703; Microphthalmia, isolated 4 613094; Multiple synostoses syndrome 4 617898; CAKUT
Mendeliome v0.5571 GDF6 Zornitza Stark Gene: gdf6 has been classified as Green List (High Evidence).
Mendeliome v0.5571 GDF6 Zornitza Stark Phenotypes for gene: GDF6 were changed from to Klippel-Feil syndrome 1, autosomal dominant 118100; Leber congenital amaurosis 17 615360; Microphthalmia with coloboma 6, digenic 613703; Microphthalmia, isolated 4 613094; Multiple synostoses syndrome 4 617898
Mendeliome v0.5570 GDF6 Zornitza Stark Publications for gene: GDF6 were set to 18425797; 19129173; 32737436
Mendeliome v0.5569 GDF6 Zornitza Stark Publications for gene: GDF6 were set to
Mendeliome v0.5568 GDF6 Zornitza Stark Mode of inheritance for gene: GDF6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5567 GDF6 Zornitza Stark reviewed gene: GDF6: Rating: RED; Mode of pathogenicity: None; Publications: 18425797, 19129173; Phenotypes: Klippel-Feil syndrome 1, autosomal dominant 118100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5567 GDF6 Belinda Chong reviewed gene: GDF6: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32737436; Phenotypes: Klippel-Feil syndrome 1, autosomal dominant 118100, Leber congenital amaurosis 17 615360, Microphthalmia with coloboma 6, digenic 613703, Microphthalmia, isolated 4 613094, Multiple synostoses syndrome 4 617898; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.5567 PEX6 Dean Phelan reviewed gene: PEX6: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 32399598; Phenotypes: Perrault syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5567 VPS4A Kristin Rigbye changed review comment from: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain.
1x homozygous missense in the MIT domain (milder phenotype and unaffected parents).
Demonstrated defective CD71 trafficking in all 3 patients.

PMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly).
Demonstrated that the variants had a dominant-negative effect on VPS4A function.
"The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life."
Sources: Literature; to: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain.
1x homozygous missense in the MIT domain (milder phenotype and unaffected parents - possibly just a simple LoF mechanism for AR inheritance).
Demonstrated defective CD71 trafficking in all 3 patients.

PMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly).
Demonstrated that the variants had a dominant-negative effect on VPS4A function.

"The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life."
Mendeliome v0.5567 VPS4A Elena Savva Deleted their review
Mendeliome v0.5567 VPS4A Elena Savva changed review comment from: Comment when marking as ready: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents). Demonstrated defective CD71 trafficking in all 3 patients. PMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly). Demonstrated that the variants had a dominant-negative effect on VPS4A function. "The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life."; to: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain.
1x homozygous missense in the MIT domain (milder phenotype and unaffected parents).
Demonstrated defective CD71 trafficking in all 3 patients.

Comment when marking as ready: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents). Demonstrated defective CD71 trafficking in all 3 patients. PMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly). Demonstrated that the variants had a dominant-negative effect on VPS4A function. "The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life."
Mendeliome v0.5567 VPS4A Elena Savva Added comment: Comment when marking as ready: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents). Demonstrated defective CD71 trafficking in all 3 patients. PMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly). Demonstrated that the variants had a dominant-negative effect on VPS4A function. "The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life."
Mendeliome v0.5567 VPS4A Elena Savva Gene: vps4a has been classified as Green List (High Evidence).
Mendeliome v0.5567 VPS4A Elena Savva Added comment: Comment on mode of pathogenicity: Dominant negative
Mendeliome v0.5567 VPS4A Elena Savva Mode of pathogenicity for gene: VPS4A was changed from Other to Other
Mendeliome v0.5567 VPS4A Elena Savva Added comment: Comment on mode of pathogenicity: Dominant negative
Mendeliome v0.5567 VPS4A Elena Savva Mode of pathogenicity for gene: VPS4A was changed from None to Other
Mendeliome v0.5566 VPS4A Elena Savva Classified gene: VPS4A as Green List (high evidence)
Mendeliome v0.5566 VPS4A Elena Savva Gene: vps4a has been classified as Green List (High Evidence).
Mendeliome v0.5565 DAAM2 Zornitza Stark reviewed gene: DAAM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33232676; Phenotypes: Steroid-resistant nephrotic syndrome (SRNS); Mode of inheritance: None
Mendeliome v0.5565 DAAM2 Zornitza Stark Gene: daam2 has been classified as Green List (High Evidence).
Mendeliome v0.5565 DAAM2 Zornitza Stark Publications for gene: DAAM2 were set to
Mendeliome v0.5564 DAAM2 Zornitza Stark Classified gene: DAAM2 as Green List (high evidence)
Mendeliome v0.5564 DAAM2 Zornitza Stark Gene: daam2 has been classified as Green List (High Evidence).
Mendeliome v0.5563 HS2ST1 Zornitza Stark Marked gene: HS2ST1 as ready
Mendeliome v0.5563 HS2ST1 Zornitza Stark Gene: hs2st1 has been classified as Green List (High Evidence).
Mendeliome v0.5563 HS2ST1 Zornitza Stark Phenotypes for gene: HS2ST1 were changed from to Intellectual disability; dysmorphic features; congenital anomalies
Mendeliome v0.5563 BICRA Elena Savva Added comment: Comment when marking as ready: 12 individuals reported, 11 de novo (1 not resolved), "with neurodevelopmental phenotypes—developmental delay (HP:0001263), intellectual disability (HP:0001249), autism spectrum disorder (HP:0000729), and/or behavioral phenotypes (HP:0000708)—and variable structural birth defects and dysmorphic features". Mostly LoF or gene deletions, but 2 missense reported. Zebrafish model supports the gene-disease association.
Mendeliome v0.5563 BICRA Elena Savva Gene: bicra has been classified as Green List (High Evidence).
Mendeliome v0.5563 BICRA Elena Savva Classified gene: BICRA as Green List (high evidence)
Mendeliome v0.5563 BICRA Elena Savva Gene: bicra has been classified as Green List (High Evidence).
Mendeliome v0.5562 HS2ST1 Zornitza Stark Classified gene: HS2ST1 as Green List (high evidence)
Mendeliome v0.5562 HS2ST1 Zornitza Stark Gene: hs2st1 has been classified as Green List (High Evidence).
Mendeliome v0.5561 KDM4B Zornitza Stark Gene: kdm4b has been classified as Green List (High Evidence).
Mendeliome v0.5561 KDM4B Zornitza Stark Classified gene: KDM4B as Green List (high evidence)
Mendeliome v0.5561 KDM4B Zornitza Stark Gene: kdm4b has been classified as Green List (High Evidence).
Mendeliome v0.5560 SMG8 Zornitza Stark Classified gene: SMG8 as Green List (high evidence)
Mendeliome v0.5560 SMG8 Zornitza Stark Gene: smg8 has been classified as Green List (High Evidence).
Mendeliome v0.5559 UNC45B Zornitza Stark Gene: unc45b has been classified as Green List (High Evidence).
Mendeliome v0.5559 UNC45B Zornitza Stark Classified gene: UNC45B as Green List (high evidence)
Mendeliome v0.5559 UNC45B Zornitza Stark Gene: unc45b has been classified as Green List (High Evidence).
Mendeliome v0.5558 VPS4A Kristin Rigbye gene: VPS4A was added
gene: VPS4A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: VPS4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VPS4A were set to PMID: 33186543; 33186545
Phenotypes for gene: VPS4A were set to Neurodevelopmental disorder
Review for gene: VPS4A was set to GREEN
Added comment: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain.
1x homozygous missense in the MIT domain (milder phenotype and unaffected parents).
Demonstrated defective CD71 trafficking in all 3 patients.

PMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly).
Demonstrated that the variants had a dominant-negative effect on VPS4A function.
"The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life."
Sources: Literature
Mendeliome v0.5558 AGO2 Zornitza Stark Gene: ago2 has been classified as Green List (High Evidence).
Mendeliome v0.5558 AGO2 Zornitza Stark Classified gene: AGO2 as Green List (high evidence)
Mendeliome v0.5558 AGO2 Zornitza Stark Gene: ago2 has been classified as Green List (High Evidence).
Mendeliome v0.5557 AGO2 Zornitza Stark gene: AGO2 was added
gene: AGO2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AGO2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AGO2 were set to 33199684
Phenotypes for gene: AGO2 were set to Intellectual disability
Review for gene: AGO2 was set to GREEN
Added comment: 21 individuals reported, five variants (p.L192P, p.G201V, p.T357M, p.M364T, p.C751Y) were recurrent. Variable ID.
Sources: Literature
Mendeliome v0.5556 DAAM2 Ain Roesley gene: DAAM2 was added
gene: DAAM2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DAAM2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DAAM2 were set to steroid-resistant nephrotic syndrome (SRNS)
Penetrance for gene: DAAM2 were set to unknown
Review for gene: DAAM2 was set to GREEN
Added comment: - steroid-resistant nephrotic syndrome (SRNS) with focal segmental glomerulosclerosis on histologic analysis of kidney biopsies and foot process effacement shown by electron microscopy (authors have suggested the term nephrotic syndrome type 22 (NPHS22))
- 4 unrelated families, 3 of which were consanguineous
- 4 unique missense and 1 stop
- in vitro studies done for the missense variants
Sources: Literature
Mendeliome v0.5556 RRP7A Zornitza Stark Gene: rrp7a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5556 RRP7A Zornitza Stark Classified gene: RRP7A as Amber List (moderate evidence)
Mendeliome v0.5556 RRP7A Zornitza Stark Gene: rrp7a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5555 RRP7A Zornitza Stark gene: RRP7A was added
gene: RRP7A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RRP7A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RRP7A were set to 33199730
Phenotypes for gene: RRP7A were set to Microcephaly
Review for gene: RRP7A was set to AMBER
Added comment: 10 affected individuals from a single large consanguineous family where bi-allelic variant segregated with severe microcephaly (-6-8SD), variable ID. Supportive functional data from mouse and zebrafish.
Sources: Literature
Mendeliome v0.5554 BICRA Paul De Fazio gene: BICRA was added
gene: BICRA was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BICRA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BICRA were set to 33232675
Phenotypes for gene: BICRA were set to Developmental delay, intellectual disability, autism spectrum disorder,behavioral abnormalities, dysmorphic features
Review for gene: BICRA was set to GREEN
gene: BICRA was marked as current diagnostic
Added comment: 12 individuals reported, 11 de novo (1 not resolved), "with neurodevelopmental phenotypes—developmental delay (HP:0001263), intellectual disability (HP:0001249), autism spectrum disorder (HP:0000729), and/or behavioral phenotypes (HP:0000708)—and variable structural birth defects and dysmorphic features". Mostly LoF or gene deletions, but 2 missense reported. Zebrafish model supports the gene-disease association.
Sources: Literature
Mendeliome v0.5554 HS2ST1 Ain Roesley gene: HS2ST1 was added
gene: HS2ST1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HS2ST1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HS2ST1 were set to 33159882
Penetrance for gene: HS2ST1 were set to unknown
Review for gene: HS2ST1 was set to GREEN
Added comment: - 4 affected from 3 unrelated families
- 3 unique missense and 2 PTCs
- Developmental Delay, Corpus Callosum Hypoplasia or Aplasia, and Skeletal and Renal Abnormalities
Sources: Literature
Mendeliome v0.5554 MINPP1 Zornitza Stark Gene: minpp1 has been classified as Green List (High Evidence).
Mendeliome v0.5554 MINPP1 Zornitza Stark Classified gene: MINPP1 as Green List (high evidence)
Mendeliome v0.5554 MINPP1 Zornitza Stark Gene: minpp1 has been classified as Green List (High Evidence).
Mendeliome v0.5553 KDM4B Kristin Rigbye gene: KDM4B was added
gene: KDM4B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KDM4B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KDM4B were set to PMID: 33232677
Phenotypes for gene: KDM4B were set to Global developmental delay, intellectual disability and neuroanatomical defects
Review for gene: KDM4B was set to GREEN
Added comment: Nine individuals with mono-allelic de novo or inherited variants in KDM4B.

All individuals presented with dysmorphic features and global developmental delay (GDD) with language and motor skills most affected. Three individuals had a history of seizures, and four had anomalies on brain imaging ranging from agenesis of the corpus callosum with hydrocephalus to cystic formations, abnormal hippocampi, and polymicrogyria.

In a knockout mouse the total brain volume was significantly reduced with decreased
size of the hippocampal dentate gyrus, partial agenesis of the corpus callosum, and ventriculomegaly.
Sources: Literature
Mendeliome v0.5553 MINPP1 Zornitza Stark gene: MINPP1 was added
gene: MINPP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MINPP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MINPP1 were set to 33257696
Phenotypes for gene: MINPP1 were set to Pontocerebellar hypoplasia
Review for gene: MINPP1 was set to GREEN
Added comment: 8 individuals from 6 unrelated families reported with bi-allelic LOF variants. All presented with almost complete absence of motor and cognitive development, progressive or congenital microcephaly, spastic tetraplegia or dystonia, and vision impairments. For most, the first symptoms included neonatal severe axial hypotonia and epilepsy that started during the first months or years of life. Prenatal symptoms of microcephaly associated with increased thalami echogenicity were detected in one, while the seven other individuals presented with progressive microcephaly. Some exhibited rapidly progressive phenotype and the affected children died in their infancy or middle-childhood. Strikingly, all the affected children had a unique brain MRI showing a mild to severe PCH, fluid-filled posterior fossa, with dilated lateral ventricles. In addition, severe atrophy at the level of the basal ganglia or thalami often associated with typical T2 hypersignal were identified in all the patients MRI.

Supportive functional data showing accumulation of highly phosphorylated inositols, mostly inositol hexakisphosphate (IP6), detected in HEK293 cells, fibroblasts, iPSCs and differentiating neurons lacking MINPP1. In mutant cells, higher IP6 level is expected to be associated with an increased chelation of intracellular cations, such as iron or calcium, resulting in decreased levels of available ions.
Sources: Literature
Mendeliome v0.5552 UNC45B Paul De Fazio gene: UNC45B was added
gene: UNC45B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: UNC45B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UNC45B were set to 33217308
Phenotypes for gene: UNC45B were set to Progressive Myopathy with Eccentric Cores
Review for gene: UNC45B was set to GREEN
gene: UNC45B was marked as current diagnostic
Added comment: 10 individuals from 8 families reported with biallelic variants clinically manifesting with childhood-onset, progressive proximal and axial muscle weakness and various degrees of respiratory insufficiency. 4 missense variants and a +5 splice variant reported, p.Arg754Gln is recurrent. Functional studies support pathogenicity.
Sources: Literature
Mendeliome v0.5552 SMG8 Kristin Rigbye reviewed gene: SMG8: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33242396; Phenotypes: Neuorodevelopmental disorder; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5552 RFC1 Teresa Zhao reviewed gene: RFC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33103729; Phenotypes: Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5552 DNAJB11 Zornitza Stark Phenotypes for gene: DNAJB11 were changed from Polycystic kidney disease 6 with or without polycystic liver disease, MIM#618061 to Polycystic kidney disease 6 with or without polycystic liver disease, MIM#618061; Ivermark II syndrome.
Mendeliome v0.5551 DNAJB11 Zornitza Stark Publications for gene: DNAJB11 were set to 29706351; 29777155
Mendeliome v0.5550 DNAJB11 Zornitza Stark Mode of inheritance for gene: DNAJB11 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.5549 DNAJB11 Zornitza Stark changed review comment from: Seven unrelated. families described with phenotypes overlapping ADTKD and ADPKD, five different variants, one of these, p.Arg206* recurrent in three families.; to: Seven unrelated. families described with phenotypes overlapping ADTKD and ADPKD, five different mono-allelic variants, one of these, p.Arg206* recurrent in three families.
Mendeliome v0.5549 DNAJB11 Zornitza Stark edited their review of gene: DNAJB11: Added comment: Single family reported with bi-allelic variant and severe, fetal onset renal cystic disease, dilation and proliferation of pancreatic duct cells, and liver ductal plate malformation, an association known as Ivemark II syndrome.; Changed publications: 29706351, 29777155, 33129895; Changed phenotypes: Polycystic kidney disease 6 with or without polycystic liver disease, MIM#618061, Ivermark II syndrome.; Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.5549 MYLPF Zornitza Stark Phenotypes for gene: MYLPF were changed from Distal arthrogryoposis to Distal arthrogryposis type 1C (DA1C), MIM#619110
Mendeliome v0.5548 MYLPF Zornitza Stark edited their review of gene: MYLPF: Changed rating: AMBER; Changed phenotypes: Distal arthrogryposis type 1C (DA1C), MIM#619110; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5548 HHAT Zornitza Stark Marked gene: HHAT as ready
Mendeliome v0.5548 HHAT Zornitza Stark Gene: hhat has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5548 HHAT Zornitza Stark Classified gene: HHAT as Amber List (moderate evidence)
Mendeliome v0.5548 HHAT Zornitza Stark Gene: hhat has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5547 HHAT Zornitza Stark gene: HHAT was added
gene: HHAT was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: HHAT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HHAT were set to 24784881; 30912300
Phenotypes for gene: HHAT were set to Nivelon-Nivelon-Mabille syndrome 600092
Review for gene: HHAT was set to AMBER
Added comment: Two unrelated families reported. Clinical features include progressive microcephaly, cerebellar vermis hypoplasia, and skeletal dysplasia. Variable features include infantile-onset seizures, dwarfism, generalized chondrodysplasia, and micromelia.
Sources: Expert list
Mendeliome v0.5546 KAT5 Zornitza Stark Phenotypes for gene: KAT5 were changed from Severe global developmental delay; Intellectual disability; Seizures; Microcephaly; Behavioral abnormality; Sleep disturbance; Morphological abnormality of the central nervous system; Short stature; Oral cleft; Abnormality of the face to Neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalities (NEDFASB), MIM#619103; Severe global developmental delay; Intellectual disability; Seizures; Microcephaly; Behavioral abnormality; Sleep disturbance; Morphological abnormality of the central nervous system; Short stature; Oral cleft; Abnormality of the face
Mendeliome v0.5545 KAT5 Zornitza Stark Deleted their comment
Mendeliome v0.5545 KAT5 Zornitza Stark edited their review of gene: KAT5: Changed rating: GREEN; Changed phenotypes: Neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalities (NEDFASB), MIM#619103; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5545 H3F3B Zornitza Stark Phenotypes for gene: H3F3B were changed from to Intellectual disability; regression; seizures
Mendeliome v0.5544 H3F3B Zornitza Stark Publications for gene: H3F3B were set to
Mendeliome v0.5543 H3F3B Zornitza Stark Mode of inheritance for gene: H3F3B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5542 H3F3B Zornitza Stark Classified gene: H3F3B as Green List (high evidence)
Mendeliome v0.5542 H3F3B Zornitza Stark Gene: h3f3b has been classified as Green List (High Evidence).
Mendeliome v0.5541 H3F3B Zornitza Stark edited their review of gene: H3F3B: Added comment: 13 unrelated individuals reported with missense variants in H3F3B. Phenotype primarily comprised intellectual disability and minor congenital anomalies, regression in significant proportion. Seizures in 50%.; Changed rating: GREEN; Changed publications: 33268356; Changed phenotypes: Intellectual disability, regression, seizures; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5541 H3F3A Zornitza Stark Phenotypes for gene: H3F3A were changed from to Intellectual disability; regression; seizures
Mendeliome v0.5540 H3F3A Zornitza Stark Publications for gene: H3F3A were set to
Mendeliome v0.5539 H3F3A Zornitza Stark Mode of inheritance for gene: H3F3A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5538 H3F3A Zornitza Stark Classified gene: H3F3A as Green List (high evidence)
Mendeliome v0.5538 H3F3A Zornitza Stark Gene: h3f3a has been classified as Green List (High Evidence).
Mendeliome v0.5537 H3F3A Zornitza Stark edited their review of gene: H3F3A: Changed phenotypes: Intellectual disability, regression, seizures
Mendeliome v0.5537 H3F3A Zornitza Stark edited their review of gene: H3F3A: Added comment: 33 unrelated individuals reported with missense variants in H3F3A. Phenotype primarily comprised intellectual disability and minor congenital anomalies, regression in significant proportion. Seizures in 50%.; Changed rating: GREEN; Changed publications: 33268356; Changed phenotypes: Intellectual disability, regression; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5537 ALDH7A1 Zornitza Stark Gene: aldh7a1 has been classified as Green List (High Evidence).
Mendeliome v0.5537 ALDH7A1 Zornitza Stark Phenotypes for gene: ALDH7A1 were changed from to Epilepsy, pyridoxine-dependent, MIM# 266100
Mendeliome v0.5536 ALDH7A1 Zornitza Stark Publications for gene: ALDH7A1 were set to
Mendeliome v0.5535 ALDH7A1 Zornitza Stark Mode of inheritance for gene: ALDH7A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5534 ALDH7A1 Zornitza Stark reviewed gene: ALDH7A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Epilepsy, pyridoxine-dependent, MIM# 266100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5534 PRPS1 Zornitza Stark Gene: prps1 has been classified as Green List (High Evidence).
Mendeliome v0.5534 PRPS1 Zornitza Stark Phenotypes for gene: PRPS1 were changed from to Arts syndrome MIM#301835; Charcot-Marie-Tooth disease, X-linked recessive, 5 MIM#311070; Deafness, X-linked 1 MIM#304500; Gout, PRPS-related MIM#300661; Phosphoribosylpyrophosphate synthetase superactivity MIM#300661
Mendeliome v0.5533 PRPS1 Zornitza Stark Publications for gene: PRPS1 were set to
Mendeliome v0.5532 PRPS1 Zornitza Stark Mode of pathogenicity for gene: PRPS1 was changed from to Other
Mendeliome v0.5531 PRPS1 Zornitza Stark Mode of inheritance for gene: PRPS1 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.5530 HIVEP2 Zornitza Stark Gene: hivep2 has been classified as Green List (High Evidence).
Mendeliome v0.5530 HIVEP2 Zornitza Stark Phenotypes for gene: HIVEP2 were changed from to Mental retardation, autosomal dominant 43 MIM#616977
Mendeliome v0.5529 HIVEP2 Zornitza Stark Publications for gene: HIVEP2 were set to
Mendeliome v0.5528 HIVEP2 Zornitza Stark Mode of inheritance for gene: HIVEP2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5527 HIVEP2 Zornitza Stark reviewed gene: HIVEP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26153216, 27003583, 16836985, 31602191; Phenotypes: Mental retardation, autosomal dominant 43, MIM# 616977; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5527 HIVEP2 Elena Savva reviewed gene: HIVEP2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31207095; Phenotypes: Mental retardation, autosomal dominant 43 MIM#616977; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5527 PRPS1 Elena Savva reviewed gene: PRPS1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 32781272, 17701896, 7593598; Phenotypes: Arts syndrome MIM#301835, Charcot-Marie-Tooth disease, X-linked recessive, 5 MIM#311070, Deafness, X-linked 1 MIM#304500, Gout, PRPS-related MIM#300661, Phosphoribosylpyrophosphate synthetase superactivity MIM#300661; 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 v0.5527 YIPF5 Zornitza Stark Gene: yipf5 has been classified as Green List (High Evidence).
Mendeliome v0.5527 YIPF5 Zornitza Stark Classified gene: YIPF5 as Green List (high evidence)
Mendeliome v0.5527 YIPF5 Zornitza Stark Gene: yipf5 has been classified as Green List (High Evidence).
Mendeliome v0.5526 YIPF5 Zornitza Stark gene: YIPF5 was added
gene: YIPF5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: YIPF5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YIPF5 were set to 33164986
Phenotypes for gene: YIPF5 were set to Neonatal diabetes; microcephaly; seizures
Review for gene: YIPF5 was set to GREEN
Added comment: Six individuals from 5 unrelated consanguineous families reported with bi-allelic variants in this gene and neonatal/early-onset diabetes, severe microcephaly, and epilepsy. Functional data supports gene-disease association.
Sources: Literature
Mendeliome v0.5525 ALDH7A1 Eleanor Williams reviewed gene: ALDH7A1: Rating: ; Mode of pathogenicity: None; Publications: 32969477; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.5525 TFE3 Zornitza Stark Publications for gene: TFE3 were set to 30595499; 31833172; 33057194
Mendeliome v0.5524 TFE3 Zornitza Stark Mode of inheritance for gene: TFE3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.5523 TFE3 Zornitza Stark edited their review of gene: TFE3: Added comment: PMID: 32409512 (2020) - 14 variants reported as de novo events in 17 unrelated cases (including 5 previously published) of severe intellectual disability with pigmentary mosaicism and storage disorder-like features; Changed publications: 30595499, 31833172, 32409512; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.5523 SLC38A8 Zornitza Stark Gene: slc38a8 has been classified as Green List (High Evidence).
Mendeliome v0.5523 SLC38A8 Zornitza Stark Phenotypes for gene: SLC38A8 were changed from to Foveal hypoplasia 2, with or without optic nerve misrouting and/or anterior segment dysgenesis OMIM:609218; foveal hypoplasia - optic nerve decussation defect - anterior segment dysgenesis syndrome MONDO:0012216
Mendeliome v0.5522 SLC38A8 Zornitza Stark Publications for gene: SLC38A8 were set to
Mendeliome v0.5521 SLC38A8 Zornitza Stark Mode of inheritance for gene: SLC38A8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5520 CAPN15 Zornitza Stark Gene: capn15 has been classified as Green List (High Evidence).
Mendeliome v0.5520 CAPN15 Zornitza Stark Classified gene: CAPN15 as Green List (high evidence)
Mendeliome v0.5520 CAPN15 Zornitza Stark Gene: capn15 has been classified as Green List (High Evidence).
Mendeliome v0.5519 TONSL Zornitza Stark Marked gene: TONSL as ready
Mendeliome v0.5519 TONSL Zornitza Stark Gene: tonsl has been classified as Green List (High Evidence).
Mendeliome v0.5519 TONSL Zornitza Stark Phenotypes for gene: TONSL were changed from to Spondyloepimetaphyseal dysplasia, sponastrime type OMIM:271510; spondyloepimetaphyseal dysplasia, sponastrime type MONDO:0010068
Mendeliome v0.5518 TONSL Zornitza Stark Publications for gene: TONSL were set to
Mendeliome v0.5517 TONSL Zornitza Stark Mode of inheritance for gene: TONSL was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5516 FKBP8 Zornitza Stark Gene: fkbp8 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5516 FKBP8 Zornitza Stark Classified gene: FKBP8 as Amber List (moderate evidence)
Mendeliome v0.5516 FKBP8 Zornitza Stark Gene: fkbp8 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5515 NPPA Zornitza Stark Classified gene: NPPA as Amber List (moderate evidence)
Mendeliome v0.5515 NPPA Zornitza Stark Gene: nppa has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5514 NPPA Zornitza Stark Gene: nppa has been classified as Green List (High Evidence).
Mendeliome v0.5514 NPPA Zornitza Stark Phenotypes for gene: NPPA were changed from to Atrial fibrillation, familial, 6, (MIM#612201)
Mendeliome v0.5513 NPPA Zornitza Stark Publications for gene: NPPA were set to
Mendeliome v0.5512 NPPA Zornitza Stark Mode of inheritance for gene: NPPA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5511 NPPA Zornitza Stark reviewed gene: NPPA: Rating: AMBER; Mode of pathogenicity: None; Publications: 18614783, 20064500, 31034774, 31077706; Phenotypes: Atrial fibrillation, familial, 6, (MIM#612201); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5511 FOXA2 Zornitza Stark Gene: foxa2 has been classified as Green List (High Evidence).
Mendeliome v0.5511 FOXA2 Zornitza Stark Classified gene: FOXA2 as Green List (high evidence)
Mendeliome v0.5511 FOXA2 Zornitza Stark Gene: foxa2 has been classified as Green List (High Evidence).
Mendeliome v0.5510 FOXA2 Zornitza Stark gene: FOXA2 was added
gene: FOXA2 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: FOXA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOXA2 were set to 29329447; 28973288; 11445544
Phenotypes for gene: FOXA2 were set to Hyperinsulinaemia
Review for gene: FOXA2 was set to GREEN
Added comment: At least two families reported and functional data.
Sources: Expert Review
Mendeliome v0.5509 USP7 Zornitza Stark Phenotypes for gene: USP7 were changed from Intellectual disability; Autism to Hao-Fountain syndrome, MIM# 616863; Intellectual disability; Autism
Mendeliome v0.5508 USP7 Zornitza Stark Publications for gene: USP7 were set to 30679821
Mendeliome v0.5507 USP7 Zornitza Stark edited their review of gene: USP7: Added comment: Hao-Fountain syndrome (HAFOUS) is a neurodevelopmental disorder characterized by global developmental delay, variably impaired intellectual development with significant speech delay, behavioral abnormalities, such as autism, and mild dysmorphic facies. Additional features are variable, but may include hypotonia, feeding problems, delayed walking with unsteady gait, hypogonadism in males, and ocular anomalies, such as strabismus. Some patients develop seizures and some have mild white matter abnormalities on brain imaging.; Changed publications: 26365382, 30679821; Changed phenotypes: Hao-Fountain syndrome, MIM# 616863, Intellectual disability, Autism
Mendeliome v0.5507 FKBP8 Eleanor Williams gene: FKBP8 was added
gene: FKBP8 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FKBP8 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FKBP8 were set to 32969478
Phenotypes for gene: FKBP8 were set to spina bifida HP:0002414
Review for gene: FKBP8 was set to AMBER
Added comment: Not associated with a phenotype in OMIM.

PMID: 32969478 - Tian et al 2020 - performed Sanger sequencing of FKBP8 on DNA samples from 472 spina bifida (SB) affected fetuses and 565 unaffected controls. 5 different rare heterozygous variants (MAF ≤ 0.001) were identified among the SB patients, while no deleterious rare variants were identified in the controls. 4 of the variants are missense, the other is a stop-gain. 2 cases were in white-Hispanic patients while the other 3 were non-white Hispanic. Functional studies showed that p.Glu140* affected FKBP8 localization to the mitochondria and impaired its interaction with BCL2 ultimately leading to an increase in cellular apoptosis. p.Ser3Leu, p.Lys315Asn and p.Ala292Ser variants decreased FKBP8 protein level. Gene expression was studied in mouse Fkbp8-/- embryos and found to be abnormal. Previous mouse models have shown neural tube defects.

Sufficient cases to rate green, but only the FKBP8 gene looked at so perhaps some caution required while further evidence is gathered.
Sources: Literature
Mendeliome v0.5507 TONSL Eleanor Williams reviewed gene: TONSL: Rating: GREEN; Mode of pathogenicity: None; Publications: 30773277, 30773278, 32959051; Phenotypes: Spondyloepimetaphyseal dysplasia, sponastrime type OMIM:271510, spondyloepimetaphyseal dysplasia, sponastrime type MONDO:0010068; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5507 CAPN15 Eleanor Williams changed review comment from: PMID: 32885237 - Zha et al 2020 - report 5 individuals with microphthalmia and/or coloboma from 4 independent families who, through WES, were identified as carrying homozygous or compound heterozygous missense variants in CAPN15 that are predicted to be damanging. the variants segregated with the disease in all 4 families, with parents being unaffected heterozygous carriers. Several individuals had additional phenotypes including growth deficits (2 families), developmental delay (2 families) and hearing loss (2 families).
Sources: Literature; to: PMID: 32885237 - Zha et al 2020 - report 5 individuals with microphthalmia and/or coloboma from 4 independent families who, through WES, were identified as carrying homozygous or compound heterozygous missense variants in CAPN15 that are predicted to be damanging. the variants segregated with the disease in all 4 families, with parents being unaffected heterozygous carriers. Several individuals had additional phenotypes including growth deficits (2 families), developmental delay (2 families) and hearing loss (2 families). Capn15 knockout mice showed similar severe developmental eye defects, including anophthalmia, microphthalmia and cataract, and diminished growth.

Sources: Literature
Mendeliome v0.5507 CAPN15 Eleanor Williams gene: CAPN15 was added
gene: CAPN15 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CAPN15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAPN15 were set to 32885237
Phenotypes for gene: CAPN15 were set to microphthalmia HP:0000568; coloboma HP:0000589
Review for gene: CAPN15 was set to GREEN
Added comment: PMID: 32885237 - Zha et al 2020 - report 5 individuals with microphthalmia and/or coloboma from 4 independent families who, through WES, were identified as carrying homozygous or compound heterozygous missense variants in CAPN15 that are predicted to be damanging. the variants segregated with the disease in all 4 families, with parents being unaffected heterozygous carriers. Several individuals had additional phenotypes including growth deficits (2 families), developmental delay (2 families) and hearing loss (2 families).
Sources: Literature
Mendeliome v0.5507 SLC38A8 Eleanor Williams reviewed gene: SLC38A8: Rating: GREEN; Mode of pathogenicity: None; Publications: 32744312; Phenotypes: Foveal hypoplasia 2, with or without optic nerve misrouting and/or anterior segment dysgenesis OMIM:609218, foveal hypoplasia - optic nerve decussation defect - anterior segment dysgenesis syndrome MONDO:0012216; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5507 MYF5 Zornitza Stark Gene: myf5 has been classified as Green List (High Evidence).
Mendeliome v0.5507 MYF5 Zornitza Stark Phenotypes for gene: MYF5 were changed from to Ophthalmoplegia, external, with rib and vertebral anomalies, OMIM 61855
Mendeliome v0.5506 MYF5 Zornitza Stark Publications for gene: MYF5 were set to
Mendeliome v0.5505 MYF5 Zornitza Stark Mode of inheritance for gene: MYF5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5504 MYF5 Zornitza Stark reviewed gene: MYF5: Rating: GREEN; Mode of pathogenicity: None; Publications: 29887215, 15386014, 1423602, 9268580, 8918877; Phenotypes: Ophthalmoplegia, external, with rib and vertebral anomalies, OMIM 61855; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5504 TARS2 Zornitza Stark Publications for gene: TARS2 were set to 24827421; 26811336
Mendeliome v0.5503 TARS2 Zornitza Stark edited their review of gene: TARS2: Added comment: Second family reported, single affected individual, compound heterozygous missense variants, computational data only in support of pathogenicity.; Changed publications: 24827421, 26811336, 33153448
Mendeliome v0.5503 COX16 Bryony Thompson Gene: cox16 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5503 COX16 Bryony Thompson Classified gene: COX16 as Amber List (moderate evidence)
Mendeliome v0.5503 COX16 Bryony Thompson Gene: cox16 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5502 COX16 Bryony Thompson gene: COX16 was added
gene: COX16 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: COX16 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COX16 were set to 33169484
Phenotypes for gene: COX16 were set to Hypertrophic cardiomyopathy; encephalopathy; severe fatal lactic acidosis
Review for gene: COX16 was set to AMBER
Added comment: 2 unrelated patients with the same homozygous (non-consanguineous) nonsense variant c.244C>T (p.Arg82*), and isolated complex IV deficiency present in both patient fibroblasts/skeletal muscle biopsy. COX16 is involved in the biogenesis of complex IV, the terminal complex of the mitochondrial respiratory chain (RC)
Sources: Literature
Mendeliome v0.5501 THBD Bryony Thompson Classified gene: THBD as Green List (high evidence)
Mendeliome v0.5501 THBD Bryony Thompson Gene: thbd has been classified as Green List (High Evidence).
Mendeliome v0.5500 THBD Bryony Thompson reviewed gene: THBD: Rating: GREEN; Mode of pathogenicity: None; Publications: 32634856, 25564403, 32935436, 25049278, 27436851, 28267383, 10627464; Phenotypes: Thrombomodulin‐associated coagulopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5500 KCNJ18 Zornitza Stark Gene: kcnj18 has been classified as Red List (Low Evidence).
Mendeliome v0.5500 KCNJ18 Zornitza Stark gene: KCNJ18 was added
gene: KCNJ18 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: KCNJ18 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNJ18 were set to 20074522; 27008341
Phenotypes for gene: KCNJ18 were set to {Thyrotoxic periodic paralysis, susceptibility to, 2}, MIM# 613239
Review for gene: KCNJ18 was set to RED
Added comment: Six variants reported in original publication, however note lack of segregation data and limited functional data. Subsequently, concerns raised about high nucleotide sequence homology between multiple potassium channel genes, with variant misattribution.
Sources: Expert Review
Mendeliome v0.5499 DPM3 Zornitza Stark Gene: dpm3 has been classified as Green List (High Evidence).
Mendeliome v0.5499 DPM3 Zornitza Stark Phenotypes for gene: DPM3 were changed from to Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 15 , MIM#612937; Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 15 618992
Mendeliome v0.5498 DPM3 Zornitza Stark Publications for gene: DPM3 were set to
Mendeliome v0.5497 DPM3 Zornitza Stark Mode of inheritance for gene: DPM3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5496 DPM3 Zornitza Stark reviewed gene: DPM3: Rating: GREEN; Mode of pathogenicity: None; Publications: 31266720, 28803818, 19576565, 31266720, 31469168; Phenotypes: Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 15 , MIM#612937, Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 15 618992; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5496 B3GAT3 Zornitza Stark Marked gene: B3GAT3 as ready
Mendeliome v0.5496 B3GAT3 Zornitza Stark Gene: b3gat3 has been classified as Green List (High Evidence).
Mendeliome v0.5496 B3GAT3 Zornitza Stark Phenotypes for gene: B3GAT3 were changed from to Multiple joint dislocations, short stature, craniofacial dysmorphism, with or without congenital heart defects, MIM# 245600
Mendeliome v0.5495 B3GAT3 Zornitza Stark Publications for gene: B3GAT3 were set to
Mendeliome v0.5494 B3GAT3 Zornitza Stark Mode of inheritance for gene: B3GAT3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5493 B3GAT3 Zornitza Stark reviewed gene: B3GAT3: Rating: GREEN; Mode of pathogenicity: None; Publications: 26754439, 31988067, 26086840, 25893793, 21763480, 24668659; Phenotypes: Multiple joint dislocations, short stature, craniofacial dysmorphism, with or without congenital heart defects, MIM# 245600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5493 SLC10A7 Zornitza Stark Gene: slc10a7 has been classified as Green List (High Evidence).
Mendeliome v0.5493 SLC10A7 Zornitza Stark Phenotypes for gene: SLC10A7 were changed from to Short stature, amelogenesis imperfecta, and skeletal dysplasia with scoliosis, MIM# 618363
Mendeliome v0.5492 SLC10A7 Zornitza Stark Publications for gene: SLC10A7 were set to
Mendeliome v0.5491 SLC10A7 Zornitza Stark Mode of inheritance for gene: SLC10A7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5490 SLC10A7 Zornitza Stark reviewed gene: SLC10A7: Rating: GREEN; Mode of pathogenicity: None; Publications: 30082715, 29878199, 31191616; Phenotypes: Short stature, amelogenesis imperfecta, and skeletal dysplasia with scoliosis, MIM# 618363; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5490 PIGP Zornitza Stark Phenotypes for gene: PIGP were changed from Epileptic encephalopathy, early infantile, 55, MIM# 617599 to Developmental and epileptic encephalopathy 55, MIM# 617599
Mendeliome v0.5489 PIGK Zornitza Stark Phenotypes for gene: PIGK were changed from Intellectual disability; seizures; cerebellar atrophy to Neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures, MIM# 618879
Mendeliome v0.5488 PIGK Zornitza Stark edited their review of gene: PIGK: Changed phenotypes: Neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures, MIM# 618879
Mendeliome v0.5488 PIGH Zornitza Stark Publications for gene: PIGH were set to 29573052; 29603516
Mendeliome v0.5487 PIGH Zornitza Stark edited their review of gene: PIGH: Added comment: Further three families reported.

Common clinical features include developmental delay/intellectual disability and hypotonia. Variable clinical features include seizures, autism spectrum disorder, apraxia, severe language delay, dysarthria, feeding difficulties, facial dysmorphisms, microcephaly, strabismus, and musculoskeletal anomalies.; Changed publications: 29573052, 29603516, 33156547
Mendeliome v0.5487 PIGB Zornitza Stark Phenotypes for gene: PIGB were changed from Epileptic encephalopathy, early infantile, 80; OMIM #618580 to Developmental and epileptic encephalopathy 80, MIM# 618580
Mendeliome v0.5486 PIGB Zornitza Stark edited their review of gene: PIGB: Changed phenotypes: Developmental and epileptic encephalopathy 80, MIM# 618580
Mendeliome v0.5486 GPAA1 Zornitza Stark Gene: gpaa1 has been classified as Green List (High Evidence).
Mendeliome v0.5486 GPAA1 Zornitza Stark Phenotypes for gene: GPAA1 were changed from to Glycosylphosphatidylinositol biosynthesis defect 15, MIM#617810
Mendeliome v0.5485 GPAA1 Zornitza Stark Publications for gene: GPAA1 were set to
Mendeliome v0.5484 GPAA1 Zornitza Stark Mode of inheritance for gene: GPAA1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5483 GPAA1 Zornitza Stark Deleted their comment
Mendeliome v0.5483 GPAA1 Zornitza Stark edited their review of gene: GPAA1: Added comment: At least 5 unrelated families reported with bi-allelic variants in this gene and delayed psychomotor development, variable intellectual disability, hypotonia, early-onset seizures in most, and cerebellar atrophy, resulting in cerebellar signs including gait ataxia and dysarthria. The disorder is caused by a defect in glycosylphosphatidylinositol (GPI) biosynthesis.; Changed publications: 29100095
Mendeliome v0.5483 ATP7A Zornitza Stark Marked gene: ATP7A as ready
Mendeliome v0.5483 ATP7A Zornitza Stark Gene: atp7a has been classified as Green List (High Evidence).
Mendeliome v0.5483 ATP7A Zornitza Stark Phenotypes for gene: ATP7A were changed from to Occipital horn syndrome, 304150; X-linked recessive Menkes disease, 309400 Spinal muscular atrophy, distal, X-linked 3, 300489
Mendeliome v0.5482 ATP7A Zornitza Stark Publications for gene: ATP7A were set to
Mendeliome v0.5481 ATP7A Zornitza Stark Mode of inheritance for gene: ATP7A was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.5480 PEX1 Zornitza Stark Gene: pex1 has been classified as Green List (High Evidence).
Mendeliome v0.5480 PEX1 Zornitza Stark Phenotypes for gene: PEX1 were changed from to Heimler syndrome 1 234580; Peroxisome biogenesis disorder 1A (Zellweger) 214100; . Peroxisome biogenesis disorder 1B (NALD/IRD) 601539
Mendeliome v0.5479 PEX1 Zornitza Stark Publications for gene: PEX1 were set to
Mendeliome v0.5478 PEX1 Zornitza Stark Mode of inheritance for gene: PEX1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5477 HDAC4 Bryony Thompson Publications for gene: HDAC4 were set to 24715439; 20691407; 31209962
Mendeliome v0.5476 HDAC4 Bryony Thompson Classified gene: HDAC4 as Green List (high evidence)
Mendeliome v0.5476 HDAC4 Bryony Thompson Gene: hdac4 has been classified as Green List (High Evidence).
Mendeliome v0.5475 HDAC4 Bryony Thompson Phenotypes for gene: HDAC4 were changed from Brachydactyly mental retardation syndrome; Brachydactyly without intellectual disability to Brachydactyly mental retardation syndrome; Brachydactyly without intellectual disability; Intellectual disability syndrome
Mendeliome v0.5474 HDAC4 Bryony Thompson reviewed gene: HDAC4: Rating: GREEN; Mode of pathogenicity: None; Publications: https://doi.org/10.1016/j.xhgg.2020.100015; Phenotypes: Intellectual disability, hypotonia, dysmorphism; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5474 SEC61A1 Elena Savva reviewed gene: SEC61A1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28782633, 27392076; Phenotypes: Hyperuricemic nephropathy, familial juvenile, 4, MIM# 617056, Hypogammaglobulinaemia, Neutropaenia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.5474 ATP7A Elena Savva reviewed gene: ATP7A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 21221114; Phenotypes: Occipital horn syndrome, 304150, X-linked recessive Menkes disease, 309400 Spinal muscular atrophy, distal, X-linked 3, 300489; 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 v0.5474 PEX1 Elena Savva reviewed gene: PEX1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 26387595; Phenotypes: Heimler syndrome 1 234580, Peroxisome biogenesis disorder 1A (Zellweger) 214100, . Peroxisome biogenesis disorder 1B (NALD/IRD) 601539; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5474 TMEM218 Bryony Thompson Marked gene: TMEM218 as ready
Mendeliome v0.5474 TMEM218 Bryony Thompson Gene: tmem218 has been classified as Green List (High Evidence).
Mendeliome v0.5474 TMEM218 Bryony Thompson Classified gene: TMEM218 as Green List (high evidence)
Mendeliome v0.5474 TMEM218 Bryony Thompson Gene: tmem218 has been classified as Green List (High Evidence).
Mendeliome v0.5473 TMEM218 Bryony Thompson gene: TMEM218 was added
gene: TMEM218 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TMEM218 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM218 were set to https://doi.org/10.1016/j.xhgg.2020.100016; 25161209
Phenotypes for gene: TMEM218 were set to Joubert syndrome; retinal dystrophy; polycystic kidneys; occipital encephalocele
Review for gene: TMEM218 was set to GREEN
Added comment: 11 cases in 6 families with homozygous or compound heterozygous missense and nonsense (1) variants, with a Joubert/Meckel syndrome phenotype. Clinical features included the molar tooth sign (N=2), occipital encephalocele (N=5, all fetuses), retinal dystrophy (N=4, all living individuals), polycystic kidneys (N=2), and polydactyly (N=2), without liver involvement. A null mouse model had nephronophthisis and retinal degeneration. No OMIM entry.
Sources: Literature
Mendeliome v0.5472 AGBL1 Zornitza Stark Gene: agbl1 has been classified as Red List (Low Evidence).
Mendeliome v0.5472 AGBL1 Zornitza Stark gene: AGBL1 was added
gene: AGBL1 was added to Mendeliome. Sources: Expert Review
disputed tags were added to gene: AGBL1.
Mode of inheritance for gene: AGBL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AGBL1 were set to 24094747; 31555324
Phenotypes for gene: AGBL1 were set to Corneal dystrophy, Fuchs endothelial, 8, MIM# 615523
Review for gene: AGBL1 was set to RED
Added comment: Gene disease association first reported in 2013 in PMID 24094747, in a large multigenerational family. However, note the variant reported, p.Arg1028Ter is present in over 400 hets in gnomad. Another variant reported in same paper, p.Cys990Ser in three unrelated individuals, is present in over 300 hets in gnomad and 1 hom.

Two further variants reported in PMID 31555324, one is missense, p.Arg748His, present in 60 hets, and the other, p.Arg1028Ter, is present is the variant identified in the previous publication, present in over 400 hets.

These variant frequencies are out of keeping for a rare disorder.
Sources: Expert Review
Mendeliome v0.5471 TLE6 Zornitza Stark Marked gene: TLE6 as ready
Mendeliome v0.5471 TLE6 Zornitza Stark Gene: tle6 has been classified as Green List (High Evidence).
Mendeliome v0.5471 TLE6 Zornitza Stark Classified gene: TLE6 as Green List (high evidence)
Mendeliome v0.5471 TLE6 Zornitza Stark Gene: tle6 has been classified as Green List (High Evidence).
Mendeliome v0.5470 TLE6 Zornitza Stark gene: TLE6 was added
gene: TLE6 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: TLE6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TLE6 were set to 26537248; 31897846
Phenotypes for gene: TLE6 were set to Preimplantation embryonic lethality, MIM# 616814
Review for gene: TLE6 was set to GREEN
Added comment: At least 5 individuals reported with bi-allelic variants and early embryonic lethality.
Sources: Expert Review
Mendeliome v0.5469 OGT Zornitza Stark Marked gene: OGT as ready
Mendeliome v0.5469 OGT Zornitza Stark Gene: ogt has been classified as Green List (High Evidence).
Mendeliome v0.5469 OGT Zornitza Stark Phenotypes for gene: OGT were changed from to Mental retardation, X-linked 106, MIM# 300997
Mendeliome v0.5468 OGT Zornitza Stark Publications for gene: OGT were set to
Mendeliome v0.5467 OGT Zornitza Stark Mode of inheritance for gene: OGT was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.5466 OGT Zornitza Stark reviewed gene: OGT: Rating: GREEN; Mode of pathogenicity: None; Publications: 28302723, 28584052, 31296563, 31627256, 29769320, 29606577; Phenotypes: Mental retardation, X-linked 106, MIM# 300997; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.5466 EXTL3 Zornitza Stark Marked gene: EXTL3 as ready
Mendeliome v0.5466 EXTL3 Zornitza Stark Gene: extl3 has been classified as Green List (High Evidence).
Mendeliome v0.5466 EXTL3 Zornitza Stark Phenotypes for gene: EXTL3 were changed from to Immunoskeletal dysplasia with neurodevelopmental abnormalities, MIM# 617425
Mendeliome v0.5465 EXTL3 Zornitza Stark Publications for gene: EXTL3 were set to
Mendeliome v0.5464 EXTL3 Zornitza Stark Mode of inheritance for gene: EXTL3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5463 EXTL3 Zornitza Stark reviewed gene: EXTL3: Rating: GREEN; Mode of pathogenicity: None; Publications: 28132690, 28148688, 28331220; Phenotypes: Immunoskeletal dysplasia with neurodevelopmental abnormalities, MIM# 617425; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5463 SSR3 Zornitza Stark Gene: ssr3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5463 SSR3 Zornitza Stark Classified gene: SSR3 as Amber List (moderate evidence)
Mendeliome v0.5463 SSR3 Zornitza Stark Gene: ssr3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5462 SSR3 Zornitza Stark gene: SSR3 was added
gene: SSR3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SSR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SSR3 were set to 30945312
Phenotypes for gene: SSR3 were set to Congenital disorder of glycosylation
Review for gene: SSR3 was set to AMBER
Added comment: Single individual reported with an unsolved type I CDG, intellectual disability, homozygous LOF variant in SSR3, supportive functional evidence.
Sources: Literature
Mendeliome v0.5461 LCP2 Zornitza Stark Gene: lcp2 has been classified as Red List (Low Evidence).
Mendeliome v0.5461 LCP2 Zornitza Stark gene: LCP2 was added
gene: LCP2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LCP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LCP2 were set to 33231617
Phenotypes for gene: LCP2 were set to Severe combined immunodeficiency
Review for gene: LCP2 was set to RED
Added comment: Infant with bi-allelic variants in this gene and early-onset life-threatening infections, combined T and B cell immunodeficiency, severe neutrophil defects, and impaired platelet aggregation.
Sources: Literature
Mendeliome v0.5460 DPM2 Zornitza Stark Publications for gene: DPM2 were set to 23109149
Mendeliome v0.5459 DPM2 Zornitza Stark Classified gene: DPM2 as Green List (high evidence)
Mendeliome v0.5459 DPM2 Zornitza Stark Gene: dpm2 has been classified as Green List (High Evidence).
Mendeliome v0.5458 DPM2 Zornitza Stark edited their review of gene: DPM2: Added comment: Further unrelated individual reported, main clinical features were truncal hypotonia, hypertonicity, congenital heart defects, intellectual disability, and generalized muscle wasting.; Changed rating: GREEN; Changed publications: 23109149, 33129689
Mendeliome v0.5458 ATP6V0A2 Zornitza Stark Marked gene: ATP6V0A2 as ready
Mendeliome v0.5458 ATP6V0A2 Zornitza Stark Gene: atp6v0a2 has been classified as Green List (High Evidence).
Mendeliome v0.5458 ATP6V0A2 Zornitza Stark Phenotypes for gene: ATP6V0A2 were changed from to Cutis laxa, autosomal recessive, type IIA, MIM# 219200; Wrinkly skin syndrome, MIM#278250
Mendeliome v0.5457 ATP6V0A2 Zornitza Stark Publications for gene: ATP6V0A2 were set to
Mendeliome v0.5456 ATP6V0A2 Zornitza Stark Mode of inheritance for gene: ATP6V0A2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5455 ATP6V0A2 Zornitza Stark reviewed gene: ATP6V0A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29952037, 22773132; Phenotypes: Cutis laxa, autosomal recessive, type IIA, MIM# 219200, Wrinkly skin syndrome, MIM#278250; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5455 ALG9 Zornitza Stark Gene: alg9 has been classified as Green List (High Evidence).
Mendeliome v0.5455 ALG9 Zornitza Stark Phenotypes for gene: ALG9 were changed from to Congenital disorder of glycosylation, type Il, MIM#608776; Gillessen-Kaesbach-Nishimura syndrome, MIM# 263210; Polycystic kidney disease
Mendeliome v0.5454 ALG9 Zornitza Stark Publications for gene: ALG9 were set to
Mendeliome v0.5453 ALG9 Zornitza Stark Mode of inheritance for gene: ALG9 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5452 ALG9 Zornitza Stark reviewed gene: ALG9: Rating: GREEN; Mode of pathogenicity: None; Publications: 28932688, 25966638, 26453364, 30676690; Phenotypes: Congenital disorder of glycosylation, type Il, MIM#608776, Gillessen-Kaesbach-Nishimura syndrome, MIM# 263210, Polycystic kidney disease; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5452 ALG8 Zornitza Stark Phenotypes for gene: ALG8 were changed from Congenital disorder of glycosylation, type Ih, MIM# 608104 to Congenital disorder of glycosylation, type Ih, MIM# 608104; Polycystic liver disease 3 with or without kidney cysts, MIM# 617874
Mendeliome v0.5451 ALG8 Zornitza Stark Publications for gene: ALG8 were set to 26066342
Mendeliome v0.5450 ALG8 Zornitza Stark Mode of inheritance for gene: ALG8 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5449 ALG8 Zornitza Stark changed review comment from: Review of 15 reported individuals in PMID: 26066342: multiple prenatal abnormalities were present in 6/12 patients. In 13/15, there were symptoms at birth, 9/15 died within 12 months. Birth weight was appropriate in 11/12, only one was small for gestational age. Prematurity was reported in 7/12. Hydrops fetalis was noticed in 3, edemas in 11/13; gastrointestinal symptoms in 9/14; structural brain pathology, psychomental retardation, seizures, ataxia in 12/13, muscle hypotonia in 13/14. Common dysmorphic signs were: low set ears, macroglossia, hypertelorism, pes equinovarus, campto- and brachydactyly (13/15). In 10/11, there was coagulopathy, in 8/11 elevated transaminases; thrombocytopenia was present in 9/9. Eye involvement was reported in 9/14. CDG typical skin involvement was reported in 8/13.; to: Bi-allelic variants and CDG: Review of 15 reported individuals in PMID: 26066342. Multiple prenatal abnormalities were present in 6/12 patients. In 13/15, there were symptoms at birth, 9/15 died within 12 months. Birth weight was appropriate in 11/12, only one was small for gestational age. Prematurity was reported in 7/12. Hydrops fetalis was noticed in 3, edemas in 11/13; gastrointestinal symptoms in 9/14; structural brain pathology, psychomental retardation, seizures, ataxia in 12/13, muscle hypotonia in 13/14. Common dysmorphic signs were: low set ears, macroglossia, hypertelorism, pes equinovarus, campto- and brachydactyly (13/15). In 10/11, there was coagulopathy, in 8/11 elevated transaminases; thrombocytopenia was present in 9/9. Eye involvement was reported in 9/14. CDG typical skin involvement was reported in 8/13.
Mendeliome v0.5449 ALG8 Zornitza Stark edited their review of gene: ALG8: Added comment: Monoallelic variants are associated with polycystic liver disease.; Changed publications: 26066342, 28375157, 15235028; Changed phenotypes: Congenital disorder of glycosylation, type Ih, MIM# 608104, Polycystic liver disease 3 with or without kidney cysts, MIM# 617874; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5449 ALG8 Zornitza Stark Gene: alg8 has been classified as Green List (High Evidence).
Mendeliome v0.5449 ALG8 Zornitza Stark Phenotypes for gene: ALG8 were changed from to Congenital disorder of glycosylation, type Ih, MIM# 608104
Mendeliome v0.5448 ALG8 Zornitza Stark Publications for gene: ALG8 were set to
Mendeliome v0.5447 ALG8 Zornitza Stark Mode of inheritance for gene: ALG8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5446 ALG8 Zornitza Stark reviewed gene: ALG8: Rating: GREEN; Mode of pathogenicity: None; Publications: 26066342; Phenotypes: Congenital disorder of glycosylation, type Ih, MIM# 608104; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5446 ALG3 Zornitza Stark Gene: alg3 has been classified as Green List (High Evidence).
Mendeliome v0.5446 ALG3 Zornitza Stark Phenotypes for gene: ALG3 were changed from to Congenital disorder of glycosylation, type Id, MIM# 601110
Mendeliome v0.5445 ALG3 Zornitza Stark Publications for gene: ALG3 were set to
Mendeliome v0.5444 ALG3 Zornitza Stark Mode of inheritance for gene: ALG3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5443 ALG3 Zornitza Stark reviewed gene: ALG3: Rating: GREEN; Mode of pathogenicity: None; Publications: 31067009; Phenotypes: Congenital disorder of glycosylation, type Id, MIM# 601110; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5443 SLC3A2 Zornitza Stark Phenotypes for gene: SLC3A2 were changed from to Autism
Mendeliome v0.5442 SLC3A2 Zornitza Stark Publications for gene: SLC3A2 were set to
Mendeliome v0.5441 SLC3A2 Zornitza Stark reviewed gene: SLC3A2: Rating: RED; Mode of pathogenicity: None; Publications: 31701662; Phenotypes: Autism; Mode of inheritance: None
Mendeliome v0.5441 SLC3A2 Naomi Baker changed review comment from: No evidence of mendelian gene-disease association reported in the literature.; to: Weak evidence of mendelian gene-disease association reported in the literature.

Three monoallelic missense variants reported in patients with Autism spectrum disorder (ASD) from one publication (PMID: 31701662).
Mendeliome v0.5441 SLC3A2 Zornitza Stark Gene: slc3a2 has been classified as Red List (Low Evidence).
Mendeliome v0.5441 SLC3A2 Zornitza Stark Classified gene: SLC3A2 as Red List (low evidence)
Mendeliome v0.5441 SLC3A2 Zornitza Stark Gene: slc3a2 has been classified as Red List (Low Evidence).
Mendeliome v0.5440 HOXA4 Zornitza Stark Gene: hoxa4 has been classified as Red List (Low Evidence).
Mendeliome v0.5440 HOXA4 Zornitza Stark Publications for gene: HOXA4 were set to 33193662
Mendeliome v0.5439 HOXA4 Zornitza Stark Phenotypes for gene: HOXA4 were changed from to Microtia-Atresia; CAKUT
Mendeliome v0.5438 HOXA4 Zornitza Stark Publications for gene: HOXA4 were set to
Mendeliome v0.5437 HOXA4 Zornitza Stark Mode of inheritance for gene: HOXA4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5436 HOXA4 Zornitza Stark Classified gene: HOXA4 as Red List (low evidence)
Mendeliome v0.5436 HOXA4 Zornitza Stark Gene: hoxa4 has been classified as Red List (Low Evidence).
Mendeliome v0.5435 ASTE1 Zornitza Stark Marked gene: ASTE1 as ready
Mendeliome v0.5435 ASTE1 Zornitza Stark Gene: aste1 has been classified as Red List (Low Evidence).
Mendeliome v0.5435 ASTE1 Zornitza Stark Phenotypes for gene: ASTE1 were changed from to palmar and plantar fibromatosis
Mendeliome v0.5434 ASTE1 Zornitza Stark Publications for gene: ASTE1 were set to
Mendeliome v0.5433 ASTE1 Zornitza Stark Mode of inheritance for gene: ASTE1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5432 ASTE1 Zornitza Stark Classified gene: ASTE1 as Red List (low evidence)
Mendeliome v0.5432 ASTE1 Zornitza Stark Gene: aste1 has been classified as Red List (Low Evidence).
Mendeliome v0.5431 SLC3A2 Naomi Baker reviewed gene: SLC3A2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.5431 HOXA4 Naomi Baker reviewed gene: HOXA4: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 33193662; Phenotypes: Microtia-Atresia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5431 ASTE1 Naomi Baker reviewed gene: ASTE1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 29104234; Phenotypes: palmar and plantar fibromatosis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5431 SMARCA1 Zornitza Stark Gene: smarca1 has been classified as Red List (Low Evidence).
Mendeliome v0.5431 SMARCA1 Zornitza Stark Phenotypes for gene: SMARCA1 were changed from to Intellectual disability
Mendeliome v0.5430 SMARCA1 Zornitza Stark Publications for gene: SMARCA1 were set to
Mendeliome v0.5429 SMARCA1 Zornitza Stark Mode of inheritance for gene: SMARCA1 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.5428 SMARCA1 Zornitza Stark Classified gene: SMARCA1 as Red List (low evidence)
Mendeliome v0.5428 SMARCA1 Zornitza Stark Gene: smarca1 has been classified as Red List (Low Evidence).
Mendeliome v0.5427 CDKAL1 Zornitza Stark Gene: cdkal1 has been classified as Red List (Low Evidence).
Mendeliome v0.5427 CDKAL1 Zornitza Stark Classified gene: CDKAL1 as Red List (low evidence)
Mendeliome v0.5427 CDKAL1 Zornitza Stark Gene: cdkal1 has been classified as Red List (Low Evidence).
Mendeliome v0.5426 TCHH Zornitza Stark Marked gene: TCHH as ready
Mendeliome v0.5426 TCHH Zornitza Stark Gene: tchh has been classified as Red List (Low Evidence).
Mendeliome v0.5426 TCHH Zornitza Stark Phenotypes for gene: TCHH were changed from to Uncombable hair syndrome 3 MIM#617252
Mendeliome v0.5425 TCHH Zornitza Stark Publications for gene: TCHH were set to
Mendeliome v0.5424 TCHH Zornitza Stark Mode of inheritance for gene: TCHH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5423 TCHH Zornitza Stark Classified gene: TCHH as Red List (low evidence)
Mendeliome v0.5423 TCHH Zornitza Stark Gene: tchh has been classified as Red List (Low Evidence).
Mendeliome v0.5422 TCHH Naomi Baker reviewed gene: TCHH: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 27866708; Phenotypes: Uncombable hair syndrome 3 MIM#617252; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5422 CDKAL1 Naomi Baker reviewed gene: CDKAL1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.5422 SMARCA1 Naomi Baker reviewed gene: SMARCA1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 26740508, 26539891, 29249292.; Phenotypes: ; 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 v0.5422 CRTAP Zornitza Stark Marked gene: CRTAP as ready
Mendeliome v0.5422 CRTAP Zornitza Stark Gene: crtap has been classified as Green List (High Evidence).
Mendeliome v0.5422 CRTAP Zornitza Stark Phenotypes for gene: CRTAP were changed from to Osteogenesis imperfecta, type VII MIM#610682
Mendeliome v0.5421 CRTAP Zornitza Stark Publications for gene: CRTAP were set to
Mendeliome v0.5420 CRTAP Zornitza Stark Mode of inheritance for gene: CRTAP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5419 USP9X Zornitza Stark Gene: usp9x has been classified as Green List (High Evidence).
Mendeliome v0.5419 USP9X Zornitza Stark Phenotypes for gene: USP9X were changed from to Mental retardation, X-linked 99, XLR (MIM#300919) and XLD (MIM#300968)
Mendeliome v0.5418 USP9X Zornitza Stark Publications for gene: USP9X were set to
Mendeliome v0.5417 USP9X Zornitza Stark Mode of inheritance for gene: USP9X was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.5416 ALG6 Zornitza Stark Gene: alg6 has been classified as Green List (High Evidence).
Mendeliome v0.5416 ALG6 Zornitza Stark Phenotypes for gene: ALG6 were changed from to Congenital disorder of glycosylation, type Ic (MIM#603147)
Mendeliome v0.5415 ALG6 Zornitza Stark Publications for gene: ALG6 were set to
Mendeliome v0.5414 ALG6 Zornitza Stark Mode of inheritance for gene: ALG6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5413 ALG6 Zornitza Stark reviewed gene: ALG6: Rating: GREEN; Mode of pathogenicity: None; Publications: 10914684, 27498540; Phenotypes: Congenital disorder of glycosylation, type Ic (MIM#603147); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5413 MOGS Zornitza Stark Publications for gene: MOGS were set to 31925597
Mendeliome v0.5412 MOGS Zornitza Stark reviewed gene: MOGS: Rating: GREEN; Mode of pathogenicity: None; Publications: 31925597, 30587846, 33058492; Phenotypes: Congenital disorder of glycosylation, type IIb, MIM# 606056; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5412 RORB Zornitza Stark Gene: rorb has been classified as Green List (High Evidence).
Mendeliome v0.5412 RORB Zornitza Stark Phenotypes for gene: RORB were changed from to {Epilepsy, idiopathic generalized, susceptibility to, 15} (MIM#618357), AD; Genetic generalized epilepsy (GGE); Photosensitive generalized and occipital epilepsy
Mendeliome v0.5411 RORB Zornitza Stark Publications for gene: RORB were set to
Mendeliome v0.5410 RORB Zornitza Stark Mode of inheritance for gene: RORB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5409 RORB Zornitza Stark reviewed gene: RORB: Rating: GREEN; Mode of pathogenicity: None; Publications: 27352968, 32162308; Phenotypes: {Epilepsy, idiopathic generalized, susceptibility to, 15} (MIM#618357), AD, Genetic generalized epilepsy (GGE), Photosensitive generalized and occipital epilepsy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5409 MYL9 Zornitza Stark Gene: myl9 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5409 MYL9 Zornitza Stark Classified gene: MYL9 as Amber List (moderate evidence)
Mendeliome v0.5409 MYL9 Zornitza Stark Gene: myl9 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5408 MYL9 Zornitza Stark gene: MYL9 was added
gene: MYL9 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MYL9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYL9 were set to 29453416; 33031641
Phenotypes for gene: MYL9 were set to Megacystis-microcolon-intestinal hypoperistalsis syndrome
Review for gene: MYL9 was set to AMBER
Added comment: Two unrelated families reported.
Sources: Literature
Mendeliome v0.5407 CRTAP Paul De Fazio reviewed gene: CRTAP: Rating: GREEN; Mode of pathogenicity: None; Publications: 21955071, 19846465, 17192541; Phenotypes: Osteogenesis imperfecta, type VII MIM#610682; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.5407 USP9X Paul De Fazio reviewed gene: USP9X: Rating: GREEN; Mode of pathogenicity: None; Publications: 31443933, 26833328; Phenotypes: Mental retardation, X-linked 99, XLR (MIM#300919) and XLD (MIM#300968); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males); Current diagnostic: yes
Mendeliome v0.5407 M1AP Zornitza Stark Phenotypes for gene: M1AP were changed from non-obstructive azoospermia (NOA); severe spermatogenic failure; male infertility to Spermatogenic failure 48, MIM# 619108; non-obstructive azoospermia (NOA); severe spermatogenic failure; male infertility
Mendeliome v0.5406 M1AP Zornitza Stark reviewed gene: M1AP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spermatogenic failure 48, MIM# 619108; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5406 NEMF Zornitza Stark Phenotypes for gene: NEMF were changed from Intellectual disability; neuropathy to Intellectual developmental disorder with speech delay and axonal peripheral neuropathy, MIM# 619099; Intellectual disability; neuropathy
Mendeliome v0.5405 NEMF Zornitza Stark edited their review of gene: NEMF: Changed phenotypes: Intellectual developmental disorder with speech delay and axonal peripheral neuropathy, MIM# 619099, Intellectual disability, neuropathy
Mendeliome v0.5405 PHYKPL Zornitza Stark Gene: phykpl has been classified as Red List (Low Evidence).
Mendeliome v0.5405 PHYKPL Zornitza Stark Phenotypes for gene: PHYKPL were changed from to [?Phosphohydroxylysinuria] 615011
Mendeliome v0.5404 PHYKPL Zornitza Stark Publications for gene: PHYKPL were set to
Mendeliome v0.5403 PHYKPL Zornitza Stark Mode of inheritance for gene: PHYKPL was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5402 PHYKPL Zornitza Stark Classified gene: PHYKPL as Red List (low evidence)
Mendeliome v0.5402 PHYKPL Zornitza Stark Gene: phykpl has been classified as Red List (Low Evidence).
Mendeliome v0.5401 MTCL1 Bryony Thompson Classified gene: MTCL1 as Green List (high evidence)
Mendeliome v0.5401 MTCL1 Bryony Thompson Gene: mtcl1 has been classified as Green List (High Evidence).
Mendeliome v0.5400 MTCL1 Bryony Thompson edited their review of gene: MTCL1: Added comment: A new report of another case with a homozygous loss of function variant and a similar phenotype to the previously reported early onset homozygous Polish case (2 independent cases), and the supporting null mouse model.; Changed rating: GREEN; Changed publications: 30548255, 28283581, 32961396; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5400 PHYKPL Elena Savva reviewed gene: PHYKPL: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 23242558; Phenotypes: [?Phosphohydroxylysinuria] 615011; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5400 POLE Zornitza Stark Gene: pole has been classified as Green List (High Evidence).
Mendeliome v0.5400 POLE Zornitza Stark Phenotypes for gene: POLE were changed from to FILS syndrome, 615139; IMAGE-I syndrome, 618336; {Colorectal cancer, susceptibility to, 12}, 615083
Mendeliome v0.5399 POLE Zornitza Stark Publications for gene: POLE were set to
Mendeliome v0.5398 POLE Zornitza Stark Mode of pathogenicity for gene: POLE was changed from to Other
Mendeliome v0.5397 POLE Zornitza Stark Mode of inheritance for gene: POLE was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5396 POLE Zornitza Stark Tag deep intronic tag was added to gene: POLE.
Mendeliome v0.5396 OFD1 Zornitza Stark Gene: ofd1 has been classified as Green List (High Evidence).
Mendeliome v0.5396 OFD1 Zornitza Stark Phenotypes for gene: OFD1 were changed from to Joubert syndrome 10, 300804; Simpson-Golabi-Behmel syndrome, type 2, 300209; Orofaciodigital syndrome I, 311200; Retinitis pigmentosa 23, 300424
Mendeliome v0.5395 OFD1 Zornitza Stark Publications for gene: OFD1 were set to
Mendeliome v0.5394 OFD1 Zornitza Stark Mode of inheritance for gene: OFD1 was changed from Unknown to Other
Mendeliome v0.5393 POLE Elena Savva reviewed gene: POLE: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 30503519, 23230001; Phenotypes: FILS syndrome, 615139, IMAGE-I syndrome, 618336, {Colorectal cancer, susceptibility to, 12}, 615083; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5393 OFD1 Elena Savva reviewed gene: OFD1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31373179, 23033313, 16783569; Phenotypes: ?Retinitis pigmentosa 23, 300424, Joubert syndrome 10, 300804, Simpson-Golabi-Behmel syndrome, type 2, 300209, Orofaciodigital syndrome I, 311200; Mode of inheritance: Other
Mendeliome v0.5393 NARS Zornitza Stark Phenotypes for gene: NARS were changed from Abnormal muscle tone; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Ataxia; Abnormality of the face; Demyelinating peripheral neuropathy to Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities (NEDMILG), MIM#619091; Neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities (NEDMILEG), MIM#619092; Abnormal muscle tone; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Ataxia; Abnormality of the face; Demyelinating peripheral neuropathy
Mendeliome v0.5392 NARS Zornitza Stark Tag new gene name tag was added to gene: NARS.
Mendeliome v0.5392 NARS Zornitza Stark edited their review of gene: NARS: Changed phenotypes: Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities (NEDMILG), MIM#619091, Neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities (NEDMILEG), MIM#619092, Abnormal muscle tone, Microcephaly, Global developmental delay, Intellectual disability, Seizures, Ataxia, Abnormality of the face, Demyelinating peripheral neuropathy
Mendeliome v0.5392 ANAPC1 Zornitza Stark Tag deep intronic tag was added to gene: ANAPC1.
Mendeliome v0.5392 ANAPC1 Zornitza Stark reviewed gene: ANAPC1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Rothmund-Thomson syndrome, type 1 618625; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5392 DZIP1 Zornitza Stark Phenotypes for gene: DZIP1 were changed from Mitral valve prolapse, MIM#610840 to Mitral valve prolapse, MIM#610840; Spermatogenic failure 47, MIM# 619102
Mendeliome v0.5391 DZIP1 Zornitza Stark Publications for gene: DZIP1 were set to 31118289
Mendeliome v0.5390 DZIP1 Zornitza Stark Mode of inheritance for gene: DZIP1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5389 DZIP1 Zornitza Stark changed review comment from: One large 4-generation family reported, where missense variant segregated with disease. Two additional individuals identified from a cohort. All variants present at low frequency in population databases. Mouse model recapitulated phenotype.
Sources: Literature; to: Association with MVP: One large 4-generation family reported, where missense variant segregated with disease. Two additional individuals identified from a cohort. All variants present at low frequency in population databases. Mouse model recapitulated phenotype.
Sources: Literature
Mendeliome v0.5389 DZIP1 Zornitza Stark edited their review of gene: DZIP1: Added comment: Two individuals reported in PMID 32051257 with bi-allelic variants and spermatogenic failure.; Changed publications: 31118289, 32051257; Changed phenotypes: Mitral valve prolapse, MIM#610840, Spermatogenic failure 47, MIM# 619102; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5389 DZIP1 Zornitza Stark Gene: dzip1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5389 DZIP1 Zornitza Stark Phenotypes for gene: DZIP1 were changed from Mitral valve prolapse to Mitral valve prolapse, MIM#610840
Mendeliome v0.5388 DZIP1 Zornitza Stark Classified gene: DZIP1 as Amber List (moderate evidence)
Mendeliome v0.5388 DZIP1 Zornitza Stark Gene: dzip1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5387 DZIP1 Zornitza Stark edited their review of gene: DZIP1: Changed phenotypes: Mitral valve prolapse, MIM#610840
Mendeliome v0.5387 DZIP1 Zornitza Stark gene: DZIP1 was added
gene: DZIP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DZIP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DZIP1 were set to 31118289
Phenotypes for gene: DZIP1 were set to Mitral valve prolapse
Review for gene: DZIP1 was set to AMBER
Added comment: One large 4-generation family reported, where missense variant segregated with disease. Two additional individuals identified from a cohort. All variants present at low frequency in population databases. Mouse model recapitulated phenotype.
Sources: Literature
Mendeliome v0.5386 ADH5 Zornitza Stark Gene: adh5 has been classified as Green List (High Evidence).
Mendeliome v0.5386 ADH5 Zornitza Stark Classified gene: ADH5 as Green List (high evidence)
Mendeliome v0.5386 ADH5 Zornitza Stark Gene: adh5 has been classified as Green List (High Evidence).
Mendeliome v0.5385 ADH5 Zornitza Stark gene: ADH5 was added
gene: ADH5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ADH5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADH5 were set to 33147438
Phenotypes for gene: ADH5 were set to Aplastic anaemia; myelodysplasia; short stature
Review for gene: ADH5 was set to GREEN
Added comment: 7 individuals reported with bi-allelic variants in this gene and a Fanconi syndrome-like phenotype. All had aplastic anaemia, 4 developed a myelodysplastic syndrome, and one developed AML. Short stature and abnormal skin pigmentation were additional features.

Note, all also had the ALDH2*2 allele, which is common in East Asian populations, and may be contributory.

Extensive experimental data.
Sources: Literature
Mendeliome v0.5384 NPHS2 Zornitza Stark Gene: nphs2 has been classified as Green List (High Evidence).
Mendeliome v0.5384 NPHS2 Zornitza Stark Phenotypes for gene: NPHS2 were changed from to Nephrotic syndrome, type 2 (MIM#600995), AR
Mendeliome v0.5383 NPHS2 Zornitza Stark Publications for gene: NPHS2 were set to
Mendeliome v0.5382 NPHS2 Zornitza Stark Mode of inheritance for gene: NPHS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5381 NPHS2 Chern Lim reviewed gene: NPHS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32467597, 30260545, 24509478; Phenotypes: Nephrotic syndrome, type 2 (MIM#600995), AR; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.5381 LRIF1 Bryony Thompson changed review comment from: A single consanguineous case with a homozygous truncating variant. DZ4Z hypomethylation and increased DUX expression was present in patient cells. siRNA-mediated depletion of LRIF1L in immortalized myoblasts derepressed the DUX4 locus.
Sources: Literature; to: A single consanguineous case with a homozygous truncating variant, and D4Z4 repeat of 13 units on a 4qA haplotype (permissive haplotype). DZ4Z hypomethylation and increased DUX expression was present in patient cells. siRNA-mediated depletion of LRIF1L in immortalized myoblasts derepressed the DUX4 locus.
Sources: Literature
Mendeliome v0.5381 LRIF1 Bryony Thompson Classified gene: LRIF1 as Amber List (moderate evidence)
Mendeliome v0.5381 LRIF1 Bryony Thompson Gene: lrif1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5380 LRIF1 Bryony Thompson gene: LRIF1 was added
gene: LRIF1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LRIF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRIF1 were set to 32467133
Phenotypes for gene: LRIF1 were set to Facioscapulohumeral muscular dystrophy
Review for gene: LRIF1 was set to AMBER
Added comment: A single consanguineous case with a homozygous truncating variant. DZ4Z hypomethylation and increased DUX expression was present in patient cells. siRNA-mediated depletion of LRIF1L in immortalized myoblasts derepressed the DUX4 locus.
Sources: Literature
Mendeliome v0.5379 DNAH8 Zornitza Stark Phenotypes for gene: DNAH8 were changed from Asthenozoospermia; primary ciliary dyskinesia to Spermatogenic failure 46, MIM#619095; Asthenozoospermia; primary ciliary dyskinesia
Mendeliome v0.5378 DNAH8 Zornitza Stark edited their review of gene: DNAH8: Changed phenotypes: Spermatogenic failure 46, MIM#619095, Asthenozoospermia, primary ciliary dyskinesia
Mendeliome v0.5378 MYRF Zornitza Stark Phenotypes for gene: MYRF were changed from Nanophthalmos; High hyperopia to Nanophthalmos and high hyperopia; Cardiac-urogenital syndrome, MIM# 618280; Encephalitis/encephalopathy, mild, with reversible myelin vacuolization, MIM# 618113
Mendeliome v0.5377 MYRF Zornitza Stark Publications for gene: MYRF were set to 31048900; 31172260; 31266062; 31700225
Mendeliome v0.5376 MYRF Zornitza Stark edited their review of gene: MYRF: Added comment: Association with Encephalitis/encephalopathy, mild, with reversible myelin vacuolization 618113: limited evidence, two multiplex families with same missense variant (likely founder effect) reported (p.Gln403Arg); Changed publications: 31048900, 31172260, 31266062, 31700225, 29446546, 29446546, 30532227, 31069960, 29265453; Changed phenotypes: Nanophthalmos and high hyperopia, Cardiac-urogenital syndrome, MIM# 618280, Encephalitis/encephalopathy, mild, with reversible myelin vacuolization, MIM# 618113
Mendeliome v0.5376 MYRF Zornitza Stark changed review comment from: Cardiac-urogenital syndrome is characterized by partial anomalous pulmonary venous return in association with tracheal anomalies, pulmonary hypoplasia, congenital diaphragmatic hernia, thyroid fibrosis, thymic involution, cleft spleen, penoscrotal hypospadias, and cryptorchidism. More than 10 unrelated individuals reported.; to: Cardiac-urogenital syndrome MIM# 618280 is characterized by partial anomalous pulmonary venous return in association with tracheal anomalies, pulmonary hypoplasia, congenital diaphragmatic hernia, thyroid fibrosis, thymic involution, cleft spleen, penoscrotal hypospadias, and cryptorchidism. More than 10 unrelated individuals reported.
Mendeliome v0.5376 MYRF Zornitza Stark edited their review of gene: MYRF: Added comment: Cardiac-urogenital syndrome is characterized by partial anomalous pulmonary venous return in association with tracheal anomalies, pulmonary hypoplasia, congenital diaphragmatic hernia, thyroid fibrosis, thymic involution, cleft spleen, penoscrotal hypospadias, and cryptorchidism. More than 10 unrelated individuals reported.; Changed publications: 31048900, 31172260, 31266062, 31700225, 29446546, 29446546, 30532227, 31069960; Changed phenotypes: Nanophthalmos and high hyperopia, Cardiac-urogenital syndrome, MIM# 618280
Mendeliome v0.5376 MYRF Zornitza Stark changed review comment from: Multiple affected individuals reported.
Sources: Expert list; to: Multiple affected individuals reported with nanophthalmos and high hyperopia and C-terminal frameshift variants, with or without dextrocardia or congenital diaphragmatic hernia.
Sources: Expert list
Mendeliome v0.5376 RLIM Zornitza Stark Gene: rlim has been classified as Green List (High Evidence).
Mendeliome v0.5376 RLIM Zornitza Stark Phenotypes for gene: RLIM were changed from to Tonne-Kalscheuer syndrome, MIM# 300978
Mendeliome v0.5375 RLIM Zornitza Stark Publications for gene: RLIM were set to
Mendeliome v0.5374 RLIM Zornitza Stark Mode of inheritance for gene: RLIM was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.5373 RLIM Zornitza Stark reviewed gene: RLIM: Rating: GREEN; Mode of pathogenicity: None; Publications: 29728705, 25735484, 25644381; Phenotypes: Tonne-Kalscheuer syndrome, MIM# 300978; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.5373 GABBR2 Zornitza Stark commented on gene: GABBR2: At least 3 unrelated individuals reported with DEE 59, MIM# 617904. Neurodevelopmental disorder with poor language and loss of hand skills, MIM# 617903 is an allelic disorder, which is less severe. The two may represent a spectrum.
Mendeliome v0.5373 GABBR2 Zornitza Stark edited their review of gene: GABBR2: Changed publications: 29100083, 28061363, 28135719, 28856709, 29369404, 29377213, 25262651, 28856709; Changed phenotypes: Neurodevelopmental disorder with poor language and loss of hand skills, 617903, Developmental and epileptic encephalopathy 59, MIM# 617904
Mendeliome v0.5373 DNAH2 Zornitza Stark Gene: dnah2 has been classified as Green List (High Evidence).
Mendeliome v0.5373 DNAH2 Zornitza Stark Classified gene: DNAH2 as Green List (high evidence)
Mendeliome v0.5373 DNAH2 Zornitza Stark Gene: dnah2 has been classified as Green List (High Evidence).
Mendeliome v0.5372 DNAH2 Zornitza Stark gene: DNAH2 was added
gene: DNAH2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: DNAH2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAH2 were set to 30811583
Phenotypes for gene: DNAH2 were set to Spermatogenic failure 45, MIM# 619094
Review for gene: DNAH2 was set to GREEN
Added comment: Three unrelated families reported.
Sources: Expert list
Mendeliome v0.5371 CLDN9 Zornitza Stark Phenotypes for gene: CLDN9 were changed from Deafness, autosomal recessive to Deafness, autosomal recessive 116, MIM#619093
Mendeliome v0.5370 CLDN9 Zornitza Stark edited their review of gene: CLDN9: Changed phenotypes: Deafness, autosomal recessive 116, MIM#619093
Mendeliome v0.5370 UBA1 Zornitza Stark Phenotypes for gene: UBA1 were changed from Spinal muscular atrophy, X-linked 2, infantile, MIM# 301830; Autoinflammatory disease, adult onset: VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) to Spinal muscular atrophy, X-linked 2, infantile, MIM# 301830; Autoinflammatory disease, adult onset: VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) #301054
Mendeliome v0.5369 UBA1 Zornitza Stark edited their review of gene: UBA1: Changed phenotypes: Spinal muscular atrophy, X-linked 2, infantile, MIM# 301830, Autoinflammatory disease, adult onset: VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) #301054
Mendeliome v0.5369 FGFR1 Zornitza Stark Gene: fgfr1 has been classified as Green List (High Evidence).
Mendeliome v0.5369 FGFR1 Zornitza Stark Tag somatic tag was added to gene: FGFR1.
Mendeliome v0.5369 FGFR1 Zornitza Stark Phenotypes for gene: FGFR1 were changed from to Encephalocraniocutaneous lipomatosis, somatic mosaic 613001; Hartsfield syndrome 615465; Hypogonadotropic hypogonadism 2 with or without anosmia 147950; Jackson-Weiss syndrome 123150; Osteoglophonic dysplasia 166250; Pfeiffer syndrome 101600; Trigonocephaly 1 190440
Mendeliome v0.5368 FGFR1 Zornitza Stark Publications for gene: FGFR1 were set to
Mendeliome v0.5367 FGFR1 Zornitza Stark Mode of pathogenicity for gene: FGFR1 was changed from to Other
Mendeliome v0.5366 FGFR1 Zornitza Stark Mode of inheritance for gene: FGFR1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5365 B4GALT7 Zornitza Stark Marked gene: B4GALT7 as ready
Mendeliome v0.5365 B4GALT7 Zornitza Stark Gene: b4galt7 has been classified as Green List (High Evidence).
Mendeliome v0.5365 B4GALT7 Zornitza Stark Phenotypes for gene: B4GALT7 were changed from to Ehlers-Danlos syndrome, spondylodysplastic type, 1, MIM# 130070
Mendeliome v0.5364 B4GALT7 Zornitza Stark Publications for gene: B4GALT7 were set to
Mendeliome v0.5363 B4GALT7 Zornitza Stark Mode of inheritance for gene: B4GALT7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5362 B4GALT7 Zornitza Stark Tag founder tag was added to gene: B4GALT7.
Mendeliome v0.5362 B4GALT7 Zornitza Stark reviewed gene: B4GALT7: Rating: GREEN; Mode of pathogenicity: None; Publications: 23956117, 24755949; Phenotypes: Ehlers-Danlos syndrome, spondylodysplastic type, 1, MIM# 130070; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5362 TBX6 Zornitza Stark Phenotypes for gene: TBX6 were changed from Skeletal dysplasia; spondylocostal dysostosis; congenital scoliosis to Spondylocostal dysostosis 5, 122600
Mendeliome v0.5361 KCNQ2 Zornitza Stark edited their review of gene: KCNQ2: Changed rating: GREEN
Mendeliome v0.5361 KCNQ2 Zornitza Stark Gene: kcnq2 has been classified as Green List (High Evidence).
Mendeliome v0.5361 KCNQ2 Zornitza Stark Phenotypes for gene: KCNQ2 were changed from to Epileptic encephalopathy, early infantile, 7, 613720; Seizures, benign neonatal, 1, 121200; Myokymia, 121200
Mendeliome v0.5360 KCNQ2 Zornitza Stark Publications for gene: KCNQ2 were set to
Mendeliome v0.5359 KCNQ2 Zornitza Stark Mode of pathogenicity for gene: KCNQ2 was changed from to Other
Mendeliome v0.5358 KCNQ2 Zornitza Stark Mode of inheritance for gene: KCNQ2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5357 KCNQ2 Elena Savva reviewed gene: KCNQ2: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID 25959266, 32917465, 24318194; Phenotypes: Epileptic encephalopathy, early infantile, 7, 613720, Seizures, benign neonatal, 1, 121200, Myokymia, 121200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.5357 B4GALT7 Elena Savva reviewed gene: B4GALT7: Rating: GREEN; Mode of pathogenicity: None; Publications: Ehlers-Danlos syndrome, spondylodysplastic type, 1, 130070; Phenotypes: PMID: 31278392, 31614862, 31862401; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5357 FGFR1 Elena Savva reviewed gene: FGFR1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 18034870, 23812909, 26942290; Phenotypes: Encephalocraniocutaneous lipomatosis, somatic mosaic 613001, Hartsfield syndrome 615465, Hypogonadotropic hypogonadism 2 with or without anosmia 147950, Jackson-Weiss syndrome 123150, Osteoglophonic dysplasia 166250, Pfeiffer syndrome 101600, Trigonocephaly 1 190440; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.5357 ADAR Zornitza Stark Gene: adar has been classified as Green List (High Evidence).
Mendeliome v0.5357 ADAR Zornitza Stark Phenotypes for gene: ADAR were changed from to Aicardi-Goutieres syndrome 6, MIM# 615010; Dyschromatosis symmetrica hereditaria, MIM# 127400
Mendeliome v0.5356 ADAR Zornitza Stark Mode of inheritance for gene: ADAR was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5355 ADAR Zornitza Stark reviewed gene: ADAR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Aicardi-Goutieres syndrome 6, MIM# 615010, Dyschromatosis symmetrica hereditaria, MIM# 127400; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5355 NDUFB10 Zornitza Stark Classified gene: NDUFB10 as Green List (high evidence)
Mendeliome v0.5355 NDUFB10 Zornitza Stark Gene: ndufb10 has been classified as Green List (High Evidence).
Mendeliome v0.5354 NDUFB10 Zornitza Stark Publications for gene: NDUFB10 were set to 28040730; 32025618
Mendeliome v0.5353 NDUFB10 Zornitza Stark edited their review of gene: NDUFB10: Added comment: Second family reported, functional data, upgrade to Green.; Changed rating: GREEN; Changed publications: 28040730, 32025618, 33169436
Mendeliome v0.5353 FOXJ1 Zornitza Stark Phenotypes for gene: FOXJ1 were changed from hydrocephalus; chronic destructive airway disease; randomization of left/right body asymmetry to Ciliary dyskinesia, primary, 43, MIM#618699; hydrocephalus; chronic destructive airway disease; randomization of left/right body asymmetry
Mendeliome v0.5352 FOXJ1 Zornitza Stark edited their review of gene: FOXJ1: Changed phenotypes: Ciliary dyskinesia, primary, 43, MIM#618699, hydrocephalus, chronic destructive airway disease, randomization of left/right body asymmetry
Mendeliome v0.5352 MAPK1 Zornitza Stark Phenotypes for gene: MAPK1 were changed from 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 to Noonan syndrome 13, MIM#619087; 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
Mendeliome v0.5351 MAPK1 Zornitza Stark edited their review of gene: MAPK1: Changed phenotypes: Noonan syndrome 13, MIM# 619087, 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
Mendeliome v0.5351 SCD5 Zornitza Stark Gene: scd5 has been classified as Red List (Low Evidence).
Mendeliome v0.5351 SCD5 Zornitza Stark gene: SCD5 was added
gene: SCD5 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SCD5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SCD5 were set to 31972369
Phenotypes for gene: SCD5 were set to Deafness, autosomal dominant 79, MIM#619086
Review for gene: SCD5 was set to RED
Added comment: Single 5-generation family reported with a missense variant segregating in 19 affected individuals. Variant is found at a low frequency in ExAC.
Sources: Expert list
Mendeliome v0.5350 SLC12A2 Zornitza Stark Phenotypes for gene: SLC12A2 were changed from Kilquist syndrome, MIM#619080; deafness, intellectual disability, dysmorphic features, absent salivation; Deafness, autosomal dominant 78, MIM#619081; Congenital, severe to profound hearing loss to Delpire-McNeill syndrome, MIM# 619083; Kilquist syndrome, MIM#619080; deafness, intellectual disability, dysmorphic features, absent salivation; Deafness, autosomal dominant 78, MIM#619081; Congenital, severe to profound hearing loss
Mendeliome v0.5349 SLC12A2 Zornitza Stark edited their review of gene: SLC12A2: Changed phenotypes: Delpire-McNeill syndrome, MIM#619083, Kilquist syndrome, MIM#619080, deafness, intellectual disability, dysmorphic features, absent salivation, ectodermal dysplasia, constipation, intestinal malrotation, multiple congenital anomalies, Deafness, autosomal dominant 78, MIM# 619081
Mendeliome v0.5349 SLC12A2 Zornitza Stark Phenotypes for gene: SLC12A2 were changed from Kilquist syndrome, MIM#619080; deafness, intellectual disability, dysmorphic features, absent salivation; Congenital, severe to profound hearing loss to Kilquist syndrome, MIM#619080; deafness, intellectual disability, dysmorphic features, absent salivation; Deafness, autosomal dominant 78, MIM#619081; Congenital, severe to profound hearing loss
Mendeliome v0.5348 SLC12A2 Zornitza Stark edited their review of gene: SLC12A2: Changed phenotypes: Kilquist syndrome, MIM#619080, deafness, intellectual disability, dysmorphic features, absent salivation, ectodermal dysplasia, constipation, intestinal malrotation, multiple congenital anomalies, Deafness, autosomal dominant 78, MIM# 619081
Mendeliome v0.5348 SLC12A2 Zornitza Stark Phenotypes for gene: SLC12A2 were changed from Kilquist syndrome: deafness, intellectual disability, dysmorphic features, absent salivation; Congenital, severe to profound hearing loss to Kilquist syndrome, MIM#619080; deafness, intellectual disability, dysmorphic features, absent salivation; Congenital, severe to profound hearing loss
Mendeliome v0.5347 SLC12A2 Zornitza Stark edited their review of gene: SLC12A2: Changed phenotypes: Kilquist syndrome, MIM#619080, deafness, intellectual disability, dysmorphic features, absent salivation, ectodermal dysplasia, constipation, intestinal malrotation, multiple congenital anomalies
Mendeliome v0.5347 OCLN Zornitza Stark Gene: ocln has been classified as Green List (High Evidence).
Mendeliome v0.5347 OCLN Zornitza Stark Phenotypes for gene: OCLN were changed from to Pseudo-TORCH syndrome 1, MIM#251290
Mendeliome v0.5346 OCLN Zornitza Stark Publications for gene: OCLN were set to
Mendeliome v0.5345 OCLN Zornitza Stark Mode of inheritance for gene: OCLN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5344 OCLN Zornitza Stark reviewed gene: OCLN: Rating: GREEN; Mode of pathogenicity: None; Publications: 20727516, 32240828, 29192239, 28386946; Phenotypes: Pseudo-TORCH syndrome 1, MIM#251290; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5344 JAM3 Zornitza Stark Gene: jam3 has been classified as Green List (High Evidence).
Mendeliome v0.5344 JAM3 Zornitza Stark Phenotypes for gene: JAM3 were changed from to Hemorrhagic destruction of the brain, subependymal calcification, and cataracts, MIM# 613730
Mendeliome v0.5343 JAM3 Zornitza Stark Publications for gene: JAM3 were set to
Mendeliome v0.5342 JAM3 Zornitza Stark Mode of inheritance for gene: JAM3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5341 JAM3 Zornitza Stark reviewed gene: JAM3: Rating: GREEN; Mode of pathogenicity: None; Publications: 23255084, 21109224; Phenotypes: Hemorrhagic destruction of the brain, subependymal calcification, and cataracts, MIM# 613730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5341 NCKAP1 Zornitza Stark Gene: nckap1 has been classified as Green List (High Evidence).
Mendeliome v0.5341 NCKAP1 Zornitza Stark Phenotypes for gene: NCKAP1 were changed from to Intellectual disability; autism
Mendeliome v0.5340 NCKAP1 Zornitza Stark Publications for gene: NCKAP1 were set to
Mendeliome v0.5339 NCKAP1 Zornitza Stark Mode of inheritance for gene: NCKAP1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5338 NCKAP1 Zornitza Stark reviewed gene: NCKAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33157009; Phenotypes: Intellectual disability, autism; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5338 ACAD9 Zornitza Stark Gene: acad9 has been classified as Green List (High Evidence).
Mendeliome v0.5338 ACAD9 Zornitza Stark Phenotypes for gene: ACAD9 were changed from to Mitochondrial complex I deficiency, nuclear type 20 MIM#611126
Mendeliome v0.5337 ACAD9 Zornitza Stark Publications for gene: ACAD9 were set to
Mendeliome v0.5336 ACAD9 Zornitza Stark Mode of inheritance for gene: ACAD9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5335 ACAD9 Zornitza Stark reviewed gene: ACAD9: Rating: GREEN; Mode of pathogenicity: None; Publications: 30025539; Phenotypes: Mitochondrial complex I deficiency, nuclear type 20 MIM#611126; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5335 CNP Zornitza Stark Phenotypes for gene: CNP were changed from Hypomyelinating leukodystrophy to Leukodystrophy, hypomyelinating, 20, MIM# 619071
Mendeliome v0.5334 CNP Zornitza Stark reviewed gene: CNP: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Leukodystrophy, hypomyelinating, 20, MIM# 619071; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5334 ALDOB Zornitza Stark Gene: aldob has been classified as Green List (High Evidence).
Mendeliome v0.5334 ALDOB Zornitza Stark Phenotypes for gene: ALDOB were changed from to Fructose intolerance, hereditary, 229600
Mendeliome v0.5333 ALDOB Zornitza Stark Publications for gene: ALDOB were set to
Mendeliome v0.5332 ALDOB Zornitza Stark Mode of inheritance for gene: ALDOB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5331 ALDOB Elena Savva reviewed gene: ALDOB: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 3083321; Phenotypes: Fructose intolerance, hereditary, 229600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.5331 ITFG2 Zornitza Stark Publications for gene: ITFG2 were set to 28397838; https://doi.org/10.1038/s41525-020-00150-z
Mendeliome v0.5330 ITFG2 Zornitza Stark edited their review of gene: ITFG2: Changed publications: 28397838, 33083013
Mendeliome v0.5330 MYO1A Zornitza Stark Gene: myo1a has been classified as Red List (Low Evidence).
Mendeliome v0.5330 MYO1A Zornitza Stark Classified gene: MYO1A as Red List (low evidence)
Mendeliome v0.5330 MYO1A Zornitza Stark Gene: myo1a has been classified as Red List (Low Evidence).
Mendeliome v0.5329 MYO1A Zornitza Stark reviewed gene: MYO1A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5329 ARL2 Zornitza Stark Gene: arl2 has been classified as Red List (Low Evidence).
Mendeliome v0.5329 ARL2 Zornitza Stark gene: ARL2 was added
gene: ARL2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ARL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARL2 were set to 30945270
Phenotypes for gene: ARL2 were set to Microcornea, rod-cone dystrophy, cataract, and posterior staphyloma-1 (MRCS1), MIM#619082
Review for gene: ARL2 was set to RED
Added comment: Single family reported, missense variant segregating with structural eye abnormalities in 4 individuals (father and three daughters).
Sources: Expert list
Mendeliome v0.5328 LMX1B Zornitza Stark Publications for gene: LMX1B were set to 27450397
Mendeliome v0.5327 LMX1B Zornitza Stark commented on gene: LMX1B: Nail-patella syndrome (NPS) is an autosomal-dominant disease characterized by dysplastic nails, absent or hypoplastic patellae, elbow dysplasia, and iliac horns. Varying degrees of proteinuria or hematuria are present, and can occasionally progress to chronic renal failure. Some variants in the homeodomain of LMX1B cause isolated nephropathy without nail, patellar or skeletal abnormality (LMX1B-associated nephropathy).

>300 families reported.
Mendeliome v0.5327 LMX1B Zornitza Stark edited their review of gene: LMX1B: Changed publications: 27450397, 32457516
Mendeliome v0.5327 LMX1B Zornitza Stark Phenotypes for gene: LMX1B were changed from Nail-patella syndrome (MIM#161200); LMX1B-related nephropathy to Nail-patella syndrome (MIM#161200), MONDO:0008061; LMX1B-related nephropathy
Mendeliome v0.5326 LMX1B Zornitza Stark reviewed gene: LMX1B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Nail-patella syndrome (MIM#161200), MONDO:0008061, LMX1B-related nephropathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5326 UNC80 Zornitza Stark Gene: unc80 has been classified as Green List (High Evidence).
Mendeliome v0.5326 UNC80 Zornitza Stark Phenotypes for gene: UNC80 were changed from to Hypotonia, infantile, with psychomotor retardation and characteristic facies 2, MIM# 616801; MONDO:0014777
Mendeliome v0.5325 UNC80 Zornitza Stark Publications for gene: UNC80 were set to
Mendeliome v0.5324 UNC80 Zornitza Stark Mode of inheritance for gene: UNC80 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5323 UNC80 Zornitza Stark reviewed gene: UNC80: Rating: GREEN; Mode of pathogenicity: None; Publications: 26708751, 26708753, 26545877, 32620897, 30167850, 30167850; Phenotypes: Hypotonia, infantile, with psychomotor retardation and characteristic facies 2, MIM# 616801, MONDO:0014777; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5323 ZFHX4 Zornitza Stark Tag SV/CNV tag was added to gene: ZFHX4.
Mendeliome v0.5323 ZFHX4 Zornitza Stark Classified gene: ZFHX4 as Green List (high evidence)
Mendeliome v0.5323 ZFHX4 Zornitza Stark Gene: zfhx4 has been classified as Green List (High Evidence).
Mendeliome v0.5322 ZFHX4 Zornitza Stark reviewed gene: ZFHX4: Rating: GREEN; Mode of pathogenicity: None; Publications: 21802062; Phenotypes: Intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5322 AP2S1 Zornitza Stark Publications for gene: AP2S1 were set to
Mendeliome v0.5321 AP2S1 Zornitza Stark Gene: ap2s1 has been classified as Green List (High Evidence).
Mendeliome v0.5321 AP2S1 Zornitza Stark Phenotypes for gene: AP2S1 were changed from Hypocalciuric hypercalcemia, type III MIM#600740 to Hypocalciuric hypercalcemia, type III MIM#600740; Developmental disorder
Mendeliome v0.5320 CARD8 Zornitza Stark Gene: card8 has been classified as Red List (Low Evidence).
Mendeliome v0.5320 CARD8 Zornitza Stark gene: CARD8 was added
gene: CARD8 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: CARD8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CARD8 were set to 29408806
Phenotypes for gene: CARD8 were set to Inflammatory bowel disease-30, MIM#619079
Review for gene: CARD8 was set to RED
Added comment: Two individuals from one family reported segregating a missense variant, dominant negative effect postulated.
Sources: Expert list
Mendeliome v0.5319 UBA1 Zornitza Stark Phenotypes for gene: UBA1 were changed from Spinal muscular atrophy, X-linked 2, infantile, MIM# 301830 to Spinal muscular atrophy, X-linked 2, infantile, MIM# 301830; Autoinflammatory disease, adult onset: VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic)
Mendeliome v0.5318 UBA1 Zornitza Stark Publications for gene: UBA1 were set to 18179898; 32181232; 31932168; 29034082; 27699224; 26028276; 23518311
Mendeliome v0.5317 UBA1 Zornitza Stark edited their review of gene: UBA1: Added comment: Association with VEXAS: 25 men reported with somatic mutations affecting methionine-41 (p.Met41) in UBA1, the major E1 enzyme that initiates ubiquitylation, and an often fatal, treatment-refractory inflammatory syndrome develops in late adulthood, with fevers, cytopaenias, characteristic vacuoles in myeloid and erythroid precursor cells, dysplastic bone marrow, neutrophilic cutaneous and pulmonary inflammation, chondritis, and vasculitis.; Changed publications: 18179898, 32181232, 31932168, 29034082, 27699224, 26028276, 23518311, 33108101; Changed phenotypes: Spinal muscular atrophy, X-linked 2, infantile, MIM# 301830, Autoinflammatory disease, adult onset: VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic)
Mendeliome v0.5317 ZFHX4 Bryony Thompson Gene: zfhx4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5317 ZFHX4 Bryony Thompson Publications for gene: ZFHX4 were set to 33057194
Mendeliome v0.5316 ZFHX4 Bryony Thompson Classified gene: ZFHX4 as Amber List (moderate evidence)
Mendeliome v0.5316 ZFHX4 Bryony Thompson Gene: zfhx4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5315 ZFHX4 Bryony Thompson edited their review of gene: ZFHX4: Changed publications: 33057194, 24038936
Mendeliome v0.5315 ZFHX4 Bryony Thompson changed review comment from: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 16 de novo variants (5 frameshift, 5 missense, 4 stopgain, 2 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Literature; to: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 16 de novo variants (5 frameshift, 5 missense, 4 stopgain, 2 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
PMID: 24038936 - a single case with developmental delay, macrocephaly, ventriculomegaly, hypermetropia, recurrent
infections, dysmorphism and a de novo deletion of the last 7 exons of the gene.
Sources: Literature
Mendeliome v0.5315 ZFHX4 Bryony Thompson edited their review of gene: ZFHX4: Changed phenotypes: Developmental disorders, intellectual disability, dysmorphic features
Mendeliome v0.5315 ZFHX4 Bryony Thompson edited their review of gene: ZFHX4: Changed rating: AMBER
Mendeliome v0.5315 ZFHX4 Bryony Thompson gene: ZFHX4 was added
gene: ZFHX4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZFHX4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZFHX4 were set to 33057194
Phenotypes for gene: ZFHX4 were set to Developmental disorders
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 16 de novo variants (5 frameshift, 5 missense, 4 stopgain, 2 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Literature
Mendeliome v0.5314 UPF1 Bryony Thompson Gene: upf1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5314 UPF1 Bryony Thompson Classified gene: UPF1 as Amber List (moderate evidence)
Mendeliome v0.5314 UPF1 Bryony Thompson Gene: upf1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5313 UPF1 Bryony Thompson gene: UPF1 was added
gene: UPF1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: UPF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: UPF1 were set to 33057194
Phenotypes for gene: UPF1 were set to Developmental disorders
Review for gene: UPF1 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 16 de novo variants (1 frameshift, 11 missense, 4 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Literature
Mendeliome v0.5312 U2AF2 Bryony Thompson Classified gene: U2AF2 as Amber List (moderate evidence)
Mendeliome v0.5312 U2AF2 Bryony Thompson Gene: u2af2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5311 U2AF2 Bryony Thompson gene: U2AF2 was added
gene: U2AF2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: U2AF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: U2AF2 were set to 33057194
Phenotypes for gene: U2AF2 were set to Developmental disorders
Review for gene: U2AF2 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 10 de novo variants (1 in-frame, 8 missense, 1 synoymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Literature
Mendeliome v0.5310 TFE3 Bryony Thompson Publications for gene: TFE3 were set to 30595499; 31833172
Mendeliome v0.5309 TCF7L2 Bryony Thompson Marked gene: TCF7L2 as ready
Mendeliome v0.5309 TCF7L2 Bryony Thompson Gene: tcf7l2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5309 TCF7L2 Bryony Thompson Phenotypes for gene: TCF7L2 were changed from to Developmental disorders
Mendeliome v0.5308 TCF7L2 Bryony Thompson Publications for gene: TCF7L2 were set to
Mendeliome v0.5307 TCF7L2 Bryony Thompson Mode of inheritance for gene: TCF7L2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5306 TCF7L2 Bryony Thompson Classified gene: TCF7L2 as Amber List (moderate evidence)
Mendeliome v0.5306 TCF7L2 Bryony Thompson Gene: tcf7l2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5305 TCF7L2 Bryony Thompson reviewed gene: TCF7L2: Rating: AMBER; Mode of pathogenicity: None; Publications: 33057194; Phenotypes: Developmental disorders; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5305 SRRM2 Bryony Thompson Gene: srrm2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5305 SRRM2 Bryony Thompson Classified gene: SRRM2 as Amber List (moderate evidence)
Mendeliome v0.5305 SRRM2 Bryony Thompson Gene: srrm2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5304 SRRM2 Bryony Thompson gene: SRRM2 was added
gene: SRRM2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SRRM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SRRM2 were set to 33057194
Phenotypes for gene: SRRM2 were set to Developmental disorders
Review for gene: SRRM2 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 28 de novo variants (11 frameshift, 7 missense, 1 splice acceptor, 5 stopgain, 4 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Literature
Mendeliome v0.5303 SPEN Bryony Thompson Gene: spen has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5303 SPEN Bryony Thompson Classified gene: SPEN as Amber List (moderate evidence)
Mendeliome v0.5303 SPEN Bryony Thompson Gene: spen has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5302 SPEN Bryony Thompson gene: SPEN was added
gene: SPEN was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SPEN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPEN were set to 33057194
Phenotypes for gene: SPEN were set to Developmental disorders
Review for gene: SPEN was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 25 de novo variants (6 frameshift, 1 in-frame, 7 missense, 8 stopgain, 3 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Literature
Mendeliome v0.5301 SATB1 Bryony Thompson Marked gene: SATB1 as ready
Mendeliome v0.5301 SATB1 Bryony Thompson Gene: satb1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5301 SATB1 Bryony Thompson Classified gene: SATB1 as Amber List (moderate evidence)
Mendeliome v0.5301 SATB1 Bryony Thompson Gene: satb1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5300 SATB1 Bryony Thompson gene: SATB1 was added
gene: SATB1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SATB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SATB1 were set to 33057194
Phenotypes for gene: SATB1 were set to Developmental disorders
Review for gene: SATB1 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 12 de novo (2 frameshift, 7 missense, 1 stopgain, 2 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Literature
Mendeliome v0.5299 RAB14 Bryony Thompson Gene: rab14 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5299 RAB14 Bryony Thompson Classified gene: RAB14 as Amber List (moderate evidence)
Mendeliome v0.5299 RAB14 Bryony Thompson Gene: rab14 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5298 RAB14 Bryony Thompson gene: RAB14 was added
gene: RAB14 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RAB14 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAB14 were set to 33057194
Phenotypes for gene: RAB14 were set to Developmental disorders
Review for gene: RAB14 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 8 de novo variants (1 in-frame, 7 missense) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Literature
Mendeliome v0.5297 PSMC5 Bryony Thompson Gene: psmc5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5297 PSMC5 Bryony Thompson Classified gene: PSMC5 as Amber List (moderate evidence)
Mendeliome v0.5297 PSMC5 Bryony Thompson Gene: psmc5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5296 PSMC5 Bryony Thompson gene: PSMC5 was added
gene: PSMC5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PSMC5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PSMC5 were set to 33057194
Phenotypes for gene: PSMC5 were set to Developmental disorders
Review for gene: PSMC5 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 10 de novo variants (1 in-frame, 9 missense) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Literature
Mendeliome v0.5295 PRPF8 Bryony Thompson Gene: prpf8 has been classified as Green List (High Evidence).
Mendeliome v0.5295 PRPF8 Bryony Thompson Added comment: Comment on phenotypes: Established Retinitis pigmentosa gene.
PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 29 de novo variants (2 frameshift, 19 missense, 1 stopgain, 7 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Mendeliome v0.5295 PRPF8 Bryony Thompson Phenotypes for gene: PRPF8 were changed from to Retinitis pigmentosa 13, MIM#600059
Mendeliome v0.5294 PRPF8 Bryony Thompson Publications for gene: PRPF8 were set to
Mendeliome v0.5293 PRPF8 Bryony Thompson Mode of inheritance for gene: PRPF8 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5292 MSL2 Bryony Thompson Gene: msl2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5292 MSL2 Bryony Thompson Classified gene: MSL2 as Amber List (moderate evidence)
Mendeliome v0.5292 MSL2 Bryony Thompson Gene: msl2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5291 PRKAR1B Bryony Thompson Publications for gene: PRKAR1B were set to https://doi.org/10.1101/2020.09.10.20190314; 25414040
Mendeliome v0.5290 MSL2 Bryony Thompson gene: MSL2 was added
gene: MSL2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MSL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MSL2 were set to 31332282; 33057194
Phenotypes for gene: MSL2 were set to Developmental disorders; autism
Review for gene: MSL2 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 13 de novo variants (9 frameshift, 4 missense) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
PMID: 31332282 - candidate gene in a single autism study, with recurrent de novo variants in a potential oligogenic model
Sources: Literature
Mendeliome v0.5289 MMGT1 Bryony Thompson Classified gene: MMGT1 as Amber List (moderate evidence)
Mendeliome v0.5289 MMGT1 Bryony Thompson Gene: mmgt1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5288 MMGT1 Bryony Thompson gene: MMGT1 was added
gene: MMGT1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MMGT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MMGT1 were set to 33057194
Phenotypes for gene: MMGT1 were set to Developmental disorders
Review for gene: MMGT1 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 3 de novo missense identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Literature
Mendeliome v0.5287 MIB1 Bryony Thompson Publications for gene: MIB1 were set to
Mendeliome v0.5286 MIB1 Bryony Thompson Added comment: Comment on phenotypes: Established congenital cardiac disease gene.
PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 11 de novo variants (1 frameshift, 2 missense, 2 splice acceptor, 1 splice donor, 5 stopgain) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Mendeliome v0.5286 MIB1 Bryony Thompson Phenotypes for gene: MIB1 were changed from to Left ventricular noncompaction 7 MIM#615092
Mendeliome v0.5285 MIB1 Bryony Thompson Mode of inheritance for gene: MIB1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5284 MFN2 Bryony Thompson Added comment: Comment on phenotypes: Established cause of hereditary neuropathy.
PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 9 de novo variants (8 missense, 1 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Mendeliome v0.5284 MFN2 Bryony Thompson Phenotypes for gene: MFN2 were changed from to Charcot-Marie-Tooth disease, axonal, type 2A2A, OMIM #609260; Charcot-Marie-Tooth disease, axonal, type 2A2B, OMIM #617087; Hereditary motor and sensory neuropathy VIA, OMIM #601152
Mendeliome v0.5283 MFN2 Bryony Thompson Mode of inheritance for gene: MFN2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5282 KCNK3 Bryony Thompson Added comment: Comment on phenotypes: Established pulmonary hypertension gene.
PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 8 de novo variants (7 missense, 1 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Mendeliome v0.5282 KCNK3 Bryony Thompson Phenotypes for gene: KCNK3 were changed from to Pulmonary hypertension, primary, 4 MIM#615344
Mendeliome v0.5281 KCNK3 Bryony Thompson Mode of inheritance for gene: KCNK3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5280 HNRNPD Bryony Thompson Gene: hnrnpd has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5280 HNRNPD Bryony Thompson Classified gene: HNRNPD as Amber List (moderate evidence)
Mendeliome v0.5280 HNRNPD Bryony Thompson Gene: hnrnpd has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5279 HNRNPD Bryony Thompson gene: HNRNPD was added
gene: HNRNPD was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HNRNPD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HNRNPD were set to 33057194
Phenotypes for gene: HNRNPD were set to Developmental disorders
Review for gene: HNRNPD was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 8 de novo variants (5 frameshift, 1 missense, 1 splice acceptor, 1 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Literature
Mendeliome v0.5278 H3F3A Bryony Thompson reviewed gene: H3F3A: Rating: AMBER; Mode of pathogenicity: None; Publications: 33057194, 31942419; Phenotypes: Developmental disorders, intellectual disability, microcephaly, severe developmental delay; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5278 PRKG2 Zornitza Stark Gene: prkg2 has been classified as Green List (High Evidence).
Mendeliome v0.5278 PRKG2 Zornitza Stark Classified gene: PRKG2 as Green List (high evidence)
Mendeliome v0.5278 PRKG2 Zornitza Stark Gene: prkg2 has been classified as Green List (High Evidence).
Mendeliome v0.5277 PLXND1 Zornitza Stark Gene: plxnd1 has been classified as Green List (High Evidence).
Mendeliome v0.5277 PLXND1 Zornitza Stark Classified gene: PLXND1 as Green List (high evidence)
Mendeliome v0.5277 PLXND1 Zornitza Stark Gene: plxnd1 has been classified as Green List (High Evidence).
Mendeliome v0.5276 PLXND1 Zornitza Stark gene: PLXND1 was added
gene: PLXND1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PLXND1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLXND1 were set to 26068067
Phenotypes for gene: PLXND1 were set to Möbius syndrome
Review for gene: PLXND1 was set to GREEN
Added comment: De novo variants in 3 unrelated individuals with Moebius syndrome with some functional evidence.
Sources: Literature
Mendeliome v0.5275 ECEL1 Zornitza Stark Gene: ecel1 has been classified as Green List (High Evidence).
Mendeliome v0.5275 ECEL1 Zornitza Stark Phenotypes for gene: ECEL1 were changed from to Arthrogryposis, distal, type 5D, MIM# 615065
Mendeliome v0.5274 MYMK Zornitza Stark Tag founder tag was added to gene: MYMK.
Mendeliome v0.5274 MYMK Zornitza Stark changed review comment from: Sources: Expert list; to: Carey-Fineman-Ziter syndrome (CFZS) is a multisystem congenital disorder characterized by hypotonia, Moebius sequence (bilateral congenital facial palsy with impairment of ocular abduction), Pierre Robin complex (micrognathia, glossoptosis, and high-arched or cleft palate), delayed motor milestones, and failure to thrive. Intellect has been normal in molecularly confirmed cases. Defect in myoblast fusion. 6 unrelated families reported with CFZ phenotype and bi-allelic MYMK variants. p.Pro91Thr is a common founder variant, which is hypomorphic.
Mendeliome v0.5274 MYMK Zornitza Stark edited their review of gene: MYMK: Changed phenotypes: Carey-Fineman-Ziter syndrome, OMIM #254940
Mendeliome v0.5274 ECEL1 Zornitza Stark Publications for gene: ECEL1 were set to
Mendeliome v0.5273 ECEL1 Zornitza Stark Mode of inheritance for gene: ECEL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5272 ECEL1 Zornitza Stark reviewed gene: ECEL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23261301, 23236030, 25099528, 24782201; Phenotypes: Arthrogryposis, distal, type 5D, MIM# 615065; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5272 PRKG2 Arina Puzriakova gene: PRKG2 was added
gene: PRKG2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PRKG2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRKG2 were set to 33106379
Phenotypes for gene: PRKG2 were set to Acromesomelic dysplasia
Review for gene: PRKG2 was set to GREEN
Added comment: - PMID: 33106379 (2020) - Distinct homozygous variants in PRKG2 identified in two unrelated individuals, both with a skeletal dysplasia associated with severe short stature due to acromesomelic limb shortening, brachydactyly, mild to moderate platyspondyly and progressively increasing metaphyseal alterations of the long bones.

Functional studies showed both variants result in NMD and disrupt the downstream MAPK signalling pathway in response to FGF2. The role of cGKII, encoded by PRKG2, in skeletal growth has been established in several animal models (references provided in paper).
Sources: Literature
Mendeliome v0.5272 PRKACA Zornitza Stark Phenotypes for gene: PRKACA were changed from Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability to Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth
Mendeliome v0.5271 FOXP4 Zornitza Stark Gene: foxp4 has been classified as Green List (High Evidence).
Mendeliome v0.5271 FOXP4 Zornitza Stark Classified gene: FOXP4 as Green List (high evidence)
Mendeliome v0.5271 FOXP4 Zornitza Stark Gene: foxp4 has been classified as Green List (High Evidence).
Mendeliome v0.5270 FOXP4 Zornitza Stark gene: FOXP4 was added
gene: FOXP4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FOXP4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOXP4 were set to 33110267
Phenotypes for gene: FOXP4 were set to Neurodevelopmental disorder; multiple congenital abnormalities
Review for gene: FOXP4 was set to GREEN
Added comment: Eight unrelated individuals reported, seven de novo missense, and one individual with a truncating variant. Detailed phenotypic information available on 6. Overlapping features included speech and language delays, growth abnormalities, congenital diaphragmatic hernia (2/6), cervical spine abnormalities, and ptosis. Intellectual disability described as mild in 2, some had normal intellect despite the early speech and language delays.
Sources: Literature
Mendeliome v0.5269 ASAH1 Zornitza Stark Gene: asah1 has been classified as Green List (High Evidence).
Mendeliome v0.5269 ASAH1 Zornitza Stark Phenotypes for gene: ASAH1 were changed from to Spinal muscular atrophy with progressive myoclonic epilepsy, MIM# 159950; Farber lipogranulomatosis, MIM# 228000
Mendeliome v0.5268 ASAH1 Zornitza Stark Mode of inheritance for gene: ASAH1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5267 ASAH1 Zornitza Stark reviewed gene: ASAH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinal muscular atrophy with progressive myoclonic epilepsy, MIM# 159950, Farber lipogranulomatosis, MIM# 228000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5267 DHX32 Zornitza Stark Gene: dhx32 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5267 DHX32 Zornitza Stark Classified gene: DHX32 as Amber List (moderate evidence)
Mendeliome v0.5267 DHX32 Zornitza Stark Gene: dhx32 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5266 TNF Zornitza Stark Marked gene: TNF as ready
Mendeliome v0.5266 TNF Zornitza Stark Gene: tnf has been classified as Red List (Low Evidence).
Mendeliome v0.5266 TNF Zornitza Stark Publications for gene: TNF were set to
Mendeliome v0.5265 TNF Zornitza Stark Classified gene: TNF as Red List (low evidence)
Mendeliome v0.5265 TNF Zornitza Stark Gene: tnf has been classified as Red List (Low Evidence).
Mendeliome v0.5264 ALK Zornitza Stark Gene: alk has been classified as Green List (High Evidence).
Mendeliome v0.5264 ALK Zornitza Stark Phenotypes for gene: ALK were changed from to {Neuroblastoma, susceptibility to, 3} 613014; Spastic-dystonic diplegia
Mendeliome v0.5263 ALK Zornitza Stark Publications for gene: ALK were set to
Mendeliome v0.5262 ALK Zornitza Stark Mode of inheritance for gene: ALK was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5261 ALK Zornitza Stark reviewed gene: ALK: Rating: GREEN; Mode of pathogenicity: None; Publications: 32989326, 18724359; Phenotypes: {Neuroblastoma, susceptibility to, 3} 613014, Spastic-dystonic diplegia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5261 RHOB Zornitza Stark Gene: rhob has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5261 RHOB Zornitza Stark Phenotypes for gene: RHOB were changed from Cerebral Palsy (PMID:32989326) to Cerebral Palsy
Mendeliome v0.5260 RHOB Zornitza Stark Classified gene: RHOB as Amber List (moderate evidence)
Mendeliome v0.5260 RHOB Zornitza Stark Gene: rhob has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5259 ASAH1 Sue White edited their review of gene: ASAH1: Changed publications: 32875576, 32449975
Mendeliome v0.5259 FBXO31 Zornitza Stark Phenotypes for gene: FBXO31 were changed from Mental retardation, autosomal recessive 45, MIM#615979 to Mental retardation, autosomal recessive 45, MIM#615979; Cerebral palsy, intellectual disability, autosomal dominant
Mendeliome v0.5258 DHX32 Dean Phelan gene: DHX32 was added
gene: DHX32 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DHX32 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DHX32 were set to PMID: 32989326
Phenotypes for gene: DHX32 were set to Intellectual disability, spastic diplegia, dystonia, brain abnormalities
Review for gene: DHX32 was set to AMBER
Added comment: PMID: 32989326 - Large cohort study of cerebral palsy cases identified two de novo variants in two unrelated patients with intellectual disability, one with spastic diplegia, and the other characterised as generalised dystonia. Brain abnormalities were identified also.
Sources: Literature
Mendeliome v0.5258 FBXO31 Zornitza Stark Publications for gene: FBXO31 were set to 24623383
Mendeliome v0.5257 ASAH1 Sue White reviewed gene: ASAH1: Rating: ; Mode of pathogenicity: None; Publications: 32875576; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5257 FBXO31 Zornitza Stark Mode of pathogenicity for gene: FBXO31 was changed from None to Other
Mendeliome v0.5256 FBXO31 Zornitza Stark Mode of inheritance for gene: FBXO31 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5255 FBXO31 Zornitza Stark Classified gene: FBXO31 as Amber List (moderate evidence)
Mendeliome v0.5255 FBXO31 Zornitza Stark Gene: fbxo31 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5254 TNF Seb Lunke reviewed gene: TNF: Rating: RED; Mode of pathogenicity: None; Publications: 26117714; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.5254 FBXO31 Kristin Rigbye changed review comment from: 2 unrelated probands with CP harbouring the same de novo missense variant (p.Asp334Asn). The variant affects the cyclin D interaction site, leading to an apparent gain of function of cyclin D degradation, supported by Western blots from patient fibroblasts which showed decreased cyclin D expression.; to: 2 unrelated probands with CP harbouring the same de novo missense variant (p.Asp334Asn). The variant affects the cyclin D interaction site, leading to an apparent gain of function of cyclin D degradation, supported by Western blots from patient fibroblasts which showed decreased cyclin D expression.

Extended patient phenotypes: Spastic diplegia, with esotropia, ID, dysarthria, mixed receptive/expressive language disorder, ADHD, cleft palate, intestinal malrotation and midgut volvulus (patient 1); Spastic paraplegia with ventricular dilation and thin corpus callosum, ID, attention deficit, anxiety, language impairments, strabismus, severe constipation (patient 2).
Mendeliome v0.5254 NHLRC2 Zornitza Stark Gene: nhlrc2 has been classified as Green List (High Evidence).
Mendeliome v0.5254 NHLRC2 Zornitza Stark Phenotypes for gene: NHLRC2 were changed from to Fibrosis, neurodegeneration, and cerebral angiomatosis (FINCA) syndrome MIM#618278
Mendeliome v0.5253 FBXO31 Kristin Rigbye reviewed gene: FBXO31: Rating: AMBER; Mode of pathogenicity: Other; Publications: PMID: 32989326; Phenotypes: Cerebral palsy; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5253 NHLRC2 Zornitza Stark Publications for gene: NHLRC2 were set to
Mendeliome v0.5252 NHLRC2 Zornitza Stark Mode of inheritance for gene: NHLRC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5251 RHOB Crystle Lee gene: RHOB was added
gene: RHOB was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: RHOB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RHOB were set to 32989326
Phenotypes for gene: RHOB were set to Cerebral Palsy (PMID:32989326)
Mode of pathogenicity for gene: RHOB was set to Other
Review for gene: RHOB was set to AMBER
Added comment: Candidate disease-causing gene for CP. Recurrent de novo missense variant reported in 2 unrelated families with supporting functional studies.
Sources: Expert list
Mendeliome v0.5251 CTLA4 Zornitza Stark Marked gene: CTLA4 as ready
Mendeliome v0.5251 CTLA4 Zornitza Stark Gene: ctla4 has been classified as Green List (High Evidence).
Mendeliome v0.5251 CTLA4 Zornitza Stark Phenotypes for gene: CTLA4 were changed from to Autoimmune lymphoproliferative syndrome, type V (MIM#616100), AD
Mendeliome v0.5250 CTLA4 Zornitza Stark Mode of inheritance for gene: CTLA4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5249 VIM Zornitza Stark Gene: vim has been classified as Green List (High Evidence).
Mendeliome v0.5249 VIM Zornitza Stark Phenotypes for gene: VIM were changed from to Cataract 30, pulverulent 116300; frontonasal dysostosis and premature aging
Mendeliome v0.5248 NHLRC2 Paul De Fazio changed review comment from: 3 families with compound het variants in total, all share one missense variant (p.Asp148Ty)

PMID 29423877: 3 patients from 2 Finnish families compound het for the same missense variant (122 hets 0 homs) and the same frameshift variant (12 hets 0 homs), main clinical features included progressive cerebropulmonary symptoms, malabsorption, progressive growth failure, recurrent infections, chronic haemolytic anaemia and transient liver dysfunction. Expression studies in patient-derived fibroblasts supported the frameshift variant leading to NMD. Zebrafish knockdown affected the integrity of cells in the midbrain region.

PMID 32435055: patient with the same phenotype from a Ukrainian family chet for two missense variants, one shared with the Finnish families and one novel.; to: 3 families with compound het variants in total, all share one missense variant (p.Asp148Ty)

PMID 29423877: 3 patients from 2 Finnish families compound het for the same missense variant (122 hets 0 homs) and the same frameshift variant (12 hets 0 homs), main clinical features included progressive cerebropulmonary symptoms, malabsorption, progressive growth failure, recurrent infections, chronic haemolytic anaemia and transient liver dysfunction. Expression studies in patient-derived fibroblasts supported the frameshift variant leading to NMD. Zebrafish knockdown affected the integrity of cells in the midbrain region.

PMID 32435055: patient with the same phenotype from a Ukrainian family chet for two missense variants, one shared with the Finnish families and one novel.
Mendeliome v0.5248 NHLRC2 Paul De Fazio changed review comment from: 3 families with compound het variants in total, all share one missense variant (p.Asp148Ty)

PMID 29423877: 3 patients from 2 Finnish families compound het for the same missense variant (122 hets 0 homs) and the same frameshift variant (12 hets 0 homs), main clinical features included progressive cerebropulmonary symptoms, malabsorption, progressive growth failure, recurrent infections, chronic haemolytic anaemia and transient liver dysfunction. Zebrafish knockdown affected the integrity of cells in the midbrain region.

PMID 32435055: patient with the same phenotype from a Ukrainian family chet for two missense variants, one shared with the Finnish families and one novel.; to: 3 families with compound het variants in total, all share one missense variant (p.Asp148Ty)

PMID 29423877: 3 patients from 2 Finnish families compound het for the same missense variant (122 hets 0 homs) and the same frameshift variant (12 hets 0 homs), main clinical features included progressive cerebropulmonary symptoms, malabsorption, progressive growth failure, recurrent infections, chronic haemolytic anaemia and transient liver dysfunction. Expression studies in patient-derived fibroblasts supported the frameshift variant leading to NMD. Zebrafish knockdown affected the integrity of cells in the midbrain region.

PMID 32435055: patient with the same phenotype from a Ukrainian family chet for two missense variants, one shared with the Finnish families and one novel.
Mendeliome v0.5248 VIM Zornitza Stark Publications for gene: VIM were set to
Mendeliome v0.5247 VIM Zornitza Stark Mode of inheritance for gene: VIM was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5246 VIM Zornitza Stark reviewed gene: VIM: Rating: GREEN; Mode of pathogenicity: None; Publications: 19126778, 26694549, 28450710; Phenotypes: Cataract 30, pulverulent 116300; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5246 NHLRC2 Paul De Fazio reviewed gene: NHLRC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29423877, 32435055; Phenotypes: Fibrosis, neurodegeneration, and cerebral angiomatosis (FINCA) syndrome MIM#618278; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.5246 STN1 Zornitza Stark Publications for gene: STN1 were set to 27432940
Mendeliome v0.5245 STN1 Zornitza Stark Classified gene: STN1 as Green List (high evidence)
Mendeliome v0.5245 STN1 Zornitza Stark Gene: stn1 has been classified as Green List (High Evidence).
Mendeliome v0.5244 STN1 Zornitza Stark edited their review of gene: STN1: Added comment: Third unrelated family reported, promote to Green.; Changed rating: GREEN; Changed publications: 27432940, 32627942
Mendeliome v0.5244 CTLA4 Teresa Zhao reviewed gene: CTLA4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Autoimmune lymphoproliferative syndrome, type V (MIM#616100), AD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.5244 ITPR3 Zornitza Stark Marked gene: ITPR3 as ready
Mendeliome v0.5244 ITPR3 Zornitza Stark Gene: itpr3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5244 VIM Ee Ming Wong reviewed gene: VIM: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 32066935; Phenotypes: frontonasal dysostosis, premature aging; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5244 ITPR3 Zornitza Stark Classified gene: ITPR3 as Amber List (moderate evidence)
Mendeliome v0.5244 ITPR3 Zornitza Stark Gene: itpr3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5243 ITPR3 Zornitza Stark gene: ITPR3 was added
gene: ITPR3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ITPR3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ITPR3 were set to 32949214
Phenotypes for gene: ITPR3 were set to Charcot-Marie-Tooth disease
Review for gene: ITPR3 was set to AMBER
Added comment: Two unrelated families reported: variant segregated in four affected individuals in one family and was de novo in the second family where there was a single affected person. Some evidence for dominant-negative effect.
Sources: Literature
Mendeliome v0.5242 SOCS1 Zornitza Stark Phenotypes for gene: SOCS1 were changed from Common variable immunodeficiency to Common variable immunodeficiency; Early-onset autoimmunity
Mendeliome v0.5241 SOCS1 Zornitza Stark Publications for gene: SOCS1 were set to 32499645; 10490099; 10490100
Mendeliome v0.5240 SOCS1 Zornitza Stark reviewed gene: SOCS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33087723; Phenotypes: Early-onset autoimmunity; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5240 AMOTL1 Zornitza Stark Marked gene: AMOTL1 as ready
Mendeliome v0.5240 AMOTL1 Zornitza Stark Gene: amotl1 has been classified as Red List (Low Evidence).
Mendeliome v0.5240 AMOTL1 Zornitza Stark gene: AMOTL1 was added
gene: AMOTL1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AMOTL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AMOTL1 were set to 33026150
Phenotypes for gene: AMOTL1 were set to Cleft lip and palate; imperforate anus; dysmorphism
Review for gene: AMOTL1 was set to RED
Added comment: Two unrelated families reported. In one, the variant was identified in parent and child who had orofacial cleft and cardiac abnormalities. Second report in PMID 33026150, de novo missense variant and cleft lip/palate, imperforate anus and dysmorphism. Mouse model does not recapitulate phenotype.
Sources: Literature
Mendeliome v0.5239 KIRREL1 Zornitza Stark Gene: kirrel1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5239 KIRREL1 Zornitza Stark Classified gene: KIRREL1 as Amber List (moderate evidence)
Mendeliome v0.5239 KIRREL1 Zornitza Stark Gene: kirrel1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5238 KIRREL1 Zornitza Stark gene: KIRREL1 was added
gene: KIRREL1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KIRREL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIRREL1 were set to 31472902
Phenotypes for gene: KIRREL1 were set to Steroid-resistant nephrotic syndrome
Review for gene: KIRREL1 was set to AMBER
Added comment: Two unrelated families reported with bi-allelic variants and limited functional data.
Sources: Literature
Mendeliome v0.5237 GFRA1 Zornitza Stark Gene: gfra1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5237 GFRA1 Zornitza Stark Classified gene: GFRA1 as Amber List (moderate evidence)
Mendeliome v0.5237 GFRA1 Zornitza Stark Gene: gfra1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5236 GFRA1 Zornitza Stark gene: GFRA1 was added
gene: GFRA1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GFRA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GFRA1 were set to 33020172
Phenotypes for gene: GFRA1 were set to Renal agenesis
Review for gene: GFRA1 was set to AMBER
Added comment: Two unrelated families reported with bi-allelic LOF variants identified in individuals with bilateral renal agenesis. GFRA1 gene encodes a receptor on the Wolffian duct that regulates ureteric bud outgrowth in the development of a functional renal system.
Sources: Literature
Mendeliome v0.5235 GNB2 Bryony Thompson reviewed gene: GNB2: Rating: AMBER; Mode of pathogenicity: None; Publications: 33057194; Phenotypes: Developmental disorder, sinus node dysfunction and atrioventricular block; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5235 GIGYF1 Bryony Thompson Gene: gigyf1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5235 GIGYF1 Bryony Thompson Classified gene: GIGYF1 as Amber List (moderate evidence)
Mendeliome v0.5235 GIGYF1 Bryony Thompson Gene: gigyf1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5234 GIGYF1 Bryony Thompson gene: GIGYF1 was added
gene: GIGYF1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GIGYF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GIGYF1 were set to 33057194
Phenotypes for gene: GIGYF1 were set to Developmental disorder
Review for gene: GIGYF1 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 14 de novo variants (4 frameshift, 5 missense, 1 splice donor, 3 stopgain, 1 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Literature
Mendeliome v0.5233 FBXW7 Bryony Thompson Gene: fbxw7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5233 FBXW7 Bryony Thompson Classified gene: FBXW7 as Amber List (moderate evidence)
Mendeliome v0.5233 FBXW7 Bryony Thompson Gene: fbxw7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5232 FBXW7 Bryony Thompson gene: FBXW7 was added
gene: FBXW7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FBXW7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FBXW7 were set to 33057194
Phenotypes for gene: FBXW7 were set to Developmental disorder
Review for gene: FBXW7 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio developmental disorder study. 12 de novo missense and 1 de novo synonymous variant identified in ~10,000 cases with developmental disorders (no other phenotype info provided)
Sources: Literature
Mendeliome v0.5231 TKFC Zornitza Stark Phenotypes for gene: TKFC were changed from Developmental delay; cataracts; liver dysfunction to Triokinase and FMN cyclase deficiency syndrome, MIM#618805; Developmental delay; cataracts; liver dysfunction
Mendeliome v0.5230 TKFC Zornitza Stark edited their review of gene: TKFC: Changed phenotypes: Triokinase and FMN cyclase deficiency syndrome, MIM#618805, Developmental delay, cataracts, liver dysfunction
Mendeliome v0.5230 PRKAR1B Zornitza Stark Gene: prkar1b has been classified as Green List (High Evidence).
Mendeliome v0.5230 PRKAR1B Zornitza Stark Classified gene: PRKAR1B as Green List (high evidence)
Mendeliome v0.5230 PRKAR1B Zornitza Stark Gene: prkar1b has been classified as Green List (High Evidence).
Mendeliome v0.5229 PRKAR1B Konstantinos Varvagiannis gene: PRKAR1B was added
gene: PRKAR1B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PRKAR1B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PRKAR1B were set to https://doi.org/10.1101/2020.09.10.20190314; 25414040
Phenotypes for gene: PRKAR1B were set to Global developmental delay; Intellectual disability; Autism; Attention deficit hyperactivity disorder; Aggressive behavior; Abnormality of movement; Upslanted palpebral fissure
Penetrance for gene: PRKAR1B were set to unknown
Review for gene: PRKAR1B was set to AMBER
Added comment: Please consider inclusion of this gene with amber rating pending publication of the preprint and/or additional evidence.

Marbach et al. (2020 - medRxiv : https://doi.org/10.1101/2020.09.10.20190314 - last author : C. Schaaf) report 6 unrelated individuals with heterozygous missense PRKAR1B variants.

All presented formal ASD diagnosis (6/6), global developmental delay (6/6) and intellectual disability (all - formal evaluations were lacking though). Additional features included neurologic anomalies (movement disorders : dyspraxia, apraxia, clumsiness in all, with tremor/dystonia or involuntary movements as single occurrences). Three displayed high pain tolerance. Regression in speech was a feature in two. Additional behavior anomalies included ADHD (4-5/6) or aggression (3/6). There was no consistent pattern of malformations, physical anomalies or facial features (with the exception of uplsanted palpebral fissures reported in 4).

3 different missense variants were identified (NM_00116470:c.1003C>T - p.Arg335Trp, c.586G>A - p.Glu196Lys, c.500_501delAAinsTT - p.Gln167Leu) with Arg355Trp being a recurrent one within this cohort (4/6 subjects). A possible splicing effect may apply for the MNV. All variants are absent from gnomAD and the SNVs had CADD scores > 24.

In all cases were parental samples were available (5/6), the variant had occurred as a de novo event.

Protein kinase A (PKA) is a tetrameric holoenzyme formed by the association of 2 catalytic (C) subunits with a regulatory (R) subunit dimer. Activation of PKA is achieved through binding of 2 cAMP molecules to each R-subunit, and unleashing(/dissociation) of C-subunits to engage substrates. PRKACA/B genes encode the Cα- and Cβ-subunits while the 4 functionally non-redundant regulatory subunits are encoded by PRKAR1A/1B/2A/2B genes. As the authors comment, the RIβ subunit is primarily expressed in brain with higher expression in cortex and hypothalamus.

The functional consequences of the variants at cellular level were not studied.

Previous studies have demonstrated that downregulation of RIβ in murine hippocampal cultures, reduced phosphorylation of CREB, a transcription factor involved in long-term memory formation. The authors speculate that a similar effect on cAMP/PKA/CREB cascade may mediate the cognitive effects in humans. RIβ deficient mice also display diminished nociceptive pain, similar to the human phenotype. [Several refs provided].

The authors cite the study by Kaplanis et al (2020 - PMID: 33057194), where in a large sample of 31,058 trio exomes of children with developmental disorders, PRKAR1B was among the genes with significant enrichment for de novo missense variants. [The gene has a pLI score of 0.18 in gnomAD / o/e = 0.26 - so pLoF variants may not be deleterious].

Please note that a specific PRKAR1B variant (NM_002735.2:c.149T>G - p.Leu50Arg) has been previous reported to segregate with a late-onset neurodegenerative disorder characterized by dementia and/or parkinsonism within a large pedigree with 12 affected individuals [Wong et al 2014 - PMID: 25414040].
Sources: Literature
Mendeliome v0.5229 NR1H4 Zornitza Stark Gene: nr1h4 has been classified as Green List (High Evidence).
Mendeliome v0.5229 NR1H4 Zornitza Stark Phenotypes for gene: NR1H4 were changed from to Cholestasis, progressive familial intrahepatic, 5, MIM# 617049
Mendeliome v0.5228 NR1H4 Zornitza Stark Publications for gene: NR1H4 were set to
Mendeliome v0.5227 NR1H4 Zornitza Stark Mode of inheritance for gene: NR1H4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5226 NR1H4 Zornitza Stark reviewed gene: NR1H4: Rating: GREEN; Mode of pathogenicity: None; Publications: 26888176, 32443034; Phenotypes: Cholestasis, progressive familial intrahepatic, 5, MIM# 617049; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5226 PTF1A Zornitza Stark Marked gene: PTF1A as ready
Mendeliome v0.5226 PTF1A Zornitza Stark Gene: ptf1a has been classified as Green List (High Evidence).
Mendeliome v0.5226 PTF1A Zornitza Stark Phenotypes for gene: PTF1A were changed from to Pancreatic agenesis 2, MIM# 615935; Pancreatic and cerebellar agenesis, MIM# 609069
Mendeliome v0.5225 PTF1A Zornitza Stark Publications for gene: PTF1A were set to
Mendeliome v0.5224 PTF1A Zornitza Stark Mode of inheritance for gene: PTF1A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5223 PTF1A Zornitza Stark reviewed gene: PTF1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 24212882, 21749365, 10507728, 15543146, 19650412; Phenotypes: Pancreatic agenesis 2, MIM# 615935, Pancreatic and cerebellar agenesis, MIM# 609069; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5223 MPP5 Zornitza Stark Gene: mpp5 has been classified as Green List (High Evidence).
Mendeliome v0.5223 MPP5 Zornitza Stark Classified gene: MPP5 as Green List (high evidence)
Mendeliome v0.5223 MPP5 Zornitza Stark Gene: mpp5 has been classified as Green List (High Evidence).
Mendeliome v0.5222 MPP5 Konstantinos Varvagiannis gene: MPP5 was added
gene: MPP5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MPP5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MPP5 were set to 33073849
Phenotypes for gene: MPP5 were set to Global developmental delay; Intellectual disability; Delayed speech and language development; Developmental regression; Behavioral abnormality
Penetrance for gene: MPP5 were set to unknown
Review for gene: MPP5 was set to GREEN
Added comment: Sterling et al (2020 - PMID: 33073849) provide information on the phenotype of 3 individuals with de novo MPP5 variants.

Common features included global developmental delay, intellectual disability (3/3 - severe in 2/3), speech delay/regression (the latter in at least 2) and behavioral abnormalities. Variable other features were reported, among others microcephaly (1/3), abnormal vision (1/3 : CVI, retinal dystrophy, nystagmus), brain MRI abnormalities (2/3), late-onset seizures (1/3). These subjects displayed variable and non-specific dysmorphic features.

All were investigated by exome sequencing (previous investigations not mentioned).

One subject was found to harbor a de novo mosaic (5/25 reads) stopgain variant, further confirmed by Sanger sequencing [NM_022474.4:c.1555C>T - p.(Arg519Ter). The specific variant is reported once in gnomAD (1/251338). Two de novo missense variants were identified in the remaining individuals [c.1289A>G - p.Glu430Gly / c.974A>C - p.His325Pro). All variants had in silico predictions in favor of a deleterious effect (CADD score >24).

The authors comment that MPP5 encodes an apical complex protein with asymmetric localization to the apical side of polarized cells. It is expressed in brain, peripheral nervous system and other tissues. MPP5 is a member of the membrane-associated guanylate kinase family of proteins (MAGUK p55 subfamily), determining cell polarity at tight junctions.

Previous animal models suggest that complete Mpp5(Pals1) KO in mice leads to near absence of cerebral cortical neurons. Htz KO display reduction in size of cerebral cortex and hippocampus. The gene is expressed in proliferating cell populations of cerebellum and important for establishment cerebellar architecture. Conditional KO of Mpp5(Pals1) in retinal progenitor cells mimics the retinal pathology observed in LCA. [Several refs. provided]

The authors studied a heterozygous CNS-specific Mpp5 KO mouse model. These mice presented microcephaly, decreased cerebellar volume and cortical thickness, decreased ependymal cells and Mpp5 at the apical surface of cortical vertrical zone. The proportion of cortical cells undergoing apoptotic cell death was increased. Mice displayed behavioral abnormalities (hyperactivity) and visual deficits, with ERG traces further suggesting retinal blindness.

Overall the mouse model was thought to recapitulate the behavioral abnormalities observed in affected subjects as well as individual rare features such as microcephaly and abnormal vision.

Haploinsufficiency (rather than a dominant negative effect) is favored as the underlying disease mechanism. This is also in line with a dose dependent effect observed in mice.
Sources: Literature
Mendeliome v0.5222 AKR1D1 Zornitza Stark Gene: akr1d1 has been classified as Green List (High Evidence).
Mendeliome v0.5222 AKR1D1 Zornitza Stark Phenotypes for gene: AKR1D1 were changed from to Bile acid synthesis defect, congenital, 2, MIM# 235555
Mendeliome v0.5221 AKR1D1 Zornitza Stark Publications for gene: AKR1D1 were set to
Mendeliome v0.5220 AKR1D1 Zornitza Stark Mode of inheritance for gene: AKR1D1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5219 AKR1D1 Zornitza Stark reviewed gene: AKR1D1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12970144, 20522910; Phenotypes: Bile acid synthesis defect, congenital, 2, MIM# 235555; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5219 SCYL1 Zornitza Stark Gene: scyl1 has been classified as Green List (High Evidence).
Mendeliome v0.5219 SCYL1 Zornitza Stark Phenotypes for gene: SCYL1 were changed from to Spinocerebellar ataxia, autosomal recessive 21, MIM# 616719
Mendeliome v0.5218 SCYL1 Zornitza Stark Publications for gene: SCYL1 were set to
Mendeliome v0.5217 SCYL1 Zornitza Stark Mode of inheritance for gene: SCYL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5216 SCYL1 Zornitza Stark Deleted their comment
Mendeliome v0.5216 SCYL1 Zornitza Stark commented on gene: SCYL1: Autosomal recessive spinocerebellar ataxia-21 is a neurologic disorder characterized by onset of cerebellar ataxia associated with cerebellar atrophy in early childhood. Affected individuals also have recurrent episodes of liver failure in the first decade, resulting in chronic liver fibrosis, as well as later onset of a peripheral neuropathy. Mild learning disabilities may also occur. More than 5 unrelated families reported.
Mendeliome v0.5216 SLC30A10 Zornitza Stark Gene: slc30a10 has been classified as Green List (High Evidence).
Mendeliome v0.5216 SLC30A10 Zornitza Stark Phenotypes for gene: SLC30A10 were changed from to Hypermanganesemia with dystonia 1, MIM# 613280
Mendeliome v0.5215 SLC30A10 Zornitza Stark Publications for gene: SLC30A10 were set to
Mendeliome v0.5214 SLC30A10 Zornitza Stark Mode of inheritance for gene: SLC30A10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5213 SLC30A10 Zornitza Stark reviewed gene: SLC30A10: Rating: GREEN; Mode of pathogenicity: None; Publications: 22341972, 22341971, 29193034; Phenotypes: Hypermanganesemia with dystonia 1, MIM# 613280; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5213 DDX23 Bryony Thompson Classified gene: DDX23 as Amber List (moderate evidence)
Mendeliome v0.5213 DDX23 Bryony Thompson Gene: ddx23 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5212 DDX23 Bryony Thompson gene: DDX23 was added
gene: DDX23 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DDX23 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DDX23 were set to 33057194
Phenotypes for gene: DDX23 were set to Developmental disorder
Review for gene: DDX23 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio developmental disorder study. 6 de novo missense identified in ~10,000 cases with developmental disorders (no other phenotype info provided)
Sources: Literature
Mendeliome v0.5211 ATP6V0A1 Bryony Thompson Classified gene: ATP6V0A1 as Amber List (moderate evidence)
Mendeliome v0.5211 ATP6V0A1 Bryony Thompson Gene: atp6v0a1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5210 ATP6V0A1 Bryony Thompson gene: ATP6V0A1 was added
gene: ATP6V0A1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATP6V0A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP6V0A1 were set to 30842224; 33057194
Phenotypes for gene: ATP6V0A1 were set to Developmental disorder; Rett syndrome-like
Review for gene: ATP6V0A1 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio developmental disorder study. 11 de novo missense identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
PMID: 30842224 - identified a de novo missense variant in a single individual with atypical Rett syndrome phenotype
Sources: Literature
Mendeliome v0.5209 ARHGAP35 Bryony Thompson Gene: arhgap35 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5209 ARHGAP35 Bryony Thompson Classified gene: ARHGAP35 as Amber List (moderate evidence)
Mendeliome v0.5209 ARHGAP35 Bryony Thompson Gene: arhgap35 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5208 ARHGAP35 Bryony Thompson gene: ARHGAP35 was added
gene: ARHGAP35 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ARHGAP35 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARHGAP35 were set to 33057194
Phenotypes for gene: ARHGAP35 were set to Developmental disorder
Review for gene: ARHGAP35 was set to AMBER
Added comment: Has been identified as a gene with significant de novo enrichment in a large trio developmental disorder study. 16 de novo variants (3 frameshift, 2 in-frame, 10 missense, 1 stopgain) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Literature
Mendeliome v0.5207 AP2S1 Bryony Thompson Added comment: Comment on phenotypes: Established hypercalcaemia gene.
PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio developmental disorder study. 5 de novo missense identified in ~10,000 cases with developmental disorders (no other phenotype info provided)
Mendeliome v0.5207 AP2S1 Bryony Thompson Phenotypes for gene: AP2S1 were changed from Hypocalciuric hypercalcemia, type III MIM#600740 to Hypocalciuric hypercalcemia, type III MIM#600740
Mendeliome v0.5206 AP2S1 Bryony Thompson Mode of inheritance for gene: AP2S1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5205 AP2S1 Bryony Thompson Phenotypes for gene: AP2S1 were changed from to Hypocalciuric hypercalcemia, type III MIM#600740
Mendeliome v0.5204 ASCL1 Zornitza Stark Gene: ascl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5204 ASCL1 Zornitza Stark Phenotypes for gene: ASCL1 were changed from to Central hypoventilation syndrome, congenital, MIM# 209880
Mendeliome v0.5203 ASCL1 Zornitza Stark Publications for gene: ASCL1 were set to
Mendeliome v0.5202 ASCL1 Zornitza Stark Mode of inheritance for gene: ASCL1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5201 ASCL1 Zornitza Stark Classified gene: ASCL1 as Amber List (moderate evidence)
Mendeliome v0.5201 ASCL1 Zornitza Stark Gene: ascl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5200 ASCL1 Zornitza Stark reviewed gene: ASCL1: Rating: AMBER; Mode of pathogenicity: None; Publications: 14532329; Phenotypes: Central hypoventilation syndrome, congenital, MIM# 209880; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5200 ODC1 Zornitza Stark Phenotypes for gene: ODC1 were changed from Intellectual disability; macrocephaly; dysmorphism to Neurodevelopmental disorder with alopecia and brain imaging abnormalities (NEDABIA), MIM#619075
Mendeliome v0.5199 ODC1 Zornitza Stark Publications for gene: ODC1 were set to 30475435
Mendeliome v0.5198 ODC1 Zornitza Stark commented on gene: ODC1: Fifth individual reported in PMID 30239107: de novo nonsense variant identified, molecular modeling suggested that due to lack of a C terminus in the mutant protein, antizyme binding does not induce ODC degradation, leading to accumulation of active protein.
Mendeliome v0.5198 ODC1 Zornitza Stark changed review comment from: Four individuals with de novo GoF variants in this gene reported.
Sources: Literature; to: Four individuals with de novo GoF variants in this gene reported.
Sources: Literature
Mendeliome v0.5198 ODC1 Zornitza Stark edited their review of gene: ODC1: Changed publications: 30475435, 30239107
Mendeliome v0.5198 ODC1 Zornitza Stark edited their review of gene: ODC1: Changed phenotypes: Neurodevelopmental disorder with alopecia and brain imaging abnormalities (NEDABIA), MIM#619075
Mendeliome v0.5198 KDELR2 Zornitza Stark Gene: kdelr2 has been classified as Green List (High Evidence).
Mendeliome v0.5198 KDELR2 Zornitza Stark Classified gene: KDELR2 as Green List (high evidence)
Mendeliome v0.5198 KDELR2 Zornitza Stark Gene: kdelr2 has been classified as Green List (High Evidence).
Mendeliome v0.5197 KDELR2 Zornitza Stark gene: KDELR2 was added
gene: KDELR2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: KDELR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KDELR2 were set to 33053334
Phenotypes for gene: KDELR2 were set to Increased susceptibility to fractures; joint hypermobility; Scoliosis; Bowing of the legs; Bowing of the arms
Review for gene: KDELR2 was set to GREEN
Added comment: 4 families with osteogenesis imperfecta reported with functional studies.
Sources: Expert list
Mendeliome v0.5196 SCN8A Zornitza Stark Gene: scn8a has been classified as Green List (High Evidence).
Mendeliome v0.5196 SCN8A Zornitza Stark Phenotypes for gene: SCN8A were changed from to Developmental and epileptic encephalopathy 13, MIM#614558, dominant and recessive; Myoclonus, familial, 2, MIM# 618364; paroxysmal kinesigenic dyskinesias; Cognitive impairment with or without cerebellar ataxia, MIM# 614306
Mendeliome v0.5195 SCN8A Zornitza Stark Publications for gene: SCN8A were set to
Mendeliome v0.5194 SCN8A Zornitza Stark Mode of pathogenicity for gene: SCN8A was changed from to Other
Mendeliome v0.5193 SCN8A Zornitza Stark Mode of inheritance for gene: SCN8A was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5192 SCN8A Zornitza Stark reviewed gene: SCN8A: Rating: GREEN; Mode of pathogenicity: Other; Publications: 31625145, 29726066, 27098556, 28702509, 16236810, 31904124, 31887642, 31675620; Phenotypes: Developmental and epileptic encephalopathy 13, MIM#614558, dominant and recessive, Myoclonus, familial, 2, MIM# 618364, paroxysmal kinesigenic dyskinesias, Cognitive impairment with or without cerebellar ataxia, MIM# 614306; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5192 LRRC32 Zornitza Stark Phenotypes for gene: LRRC32 were changed from Intellectual disability; cleft palate; proliferative retinopathy to Cleft palate, proliferative retinopathy, and developmental delay (CPPRDD) syndrome, MIM# 619074
Mendeliome v0.5191 LRRC32 Zornitza Stark edited their review of gene: LRRC32: Changed phenotypes: Cleft palate, proliferative retinopathy, and developmental delay (CPPRDD) syndrome, MIM# 619074
Mendeliome v0.5191 ALPK1 Zornitza Stark edited their review of gene: ALPK1: Changed phenotypes: Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome, Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache (ROSAH) syndrome, MIM#614979
Mendeliome v0.5191 ALPK1 Zornitza Stark Publications for gene: ALPK1 were set to 31053777
Mendeliome v0.5190 ALPK1 Zornitza Stark Phenotypes for gene: ALPK1 were changed from Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome; Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome ROSAH syndrome, MIM#614979 to Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome; Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache (ROSAH) syndrome, MIM#614979
Mendeliome v0.5189 ALPK1 Zornitza Stark Phenotypes for gene: ALPK1 were changed from Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome; ROSAH syndrome; retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache to Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome; Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome ROSAH syndrome, MIM#614979
Mendeliome v0.5188 ALPK1 Zornitza Stark edited their review of gene: ALPK1: Changed phenotypes: Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome, Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndromeROSAH syndrome, MIM#614979
Mendeliome v0.5188 NUS1 Zornitza Stark Phenotypes for gene: NUS1 were changed from Epilepsy; intellectual disability to Congenital disorder of glycosylation, type 1aa 617082; Mental retardation, autosomal dominant 55, with seizures 617831
Mendeliome v0.5187 NUS1 Zornitza Stark Publications for gene: NUS1 were set to 31656175; 29100083
Mendeliome v0.5186 NUS1 Zornitza Stark Mode of inheritance for gene: NUS1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.5185 COG8 Zornitza Stark Gene: cog8 has been classified as Green List (High Evidence).
Mendeliome v0.5185 COG8 Zornitza Stark Phenotypes for gene: COG8 were changed from to Congenital disorder of glycosylation, type IIh, MIM# 611182
Mendeliome v0.5184 COG8 Zornitza Stark Publications for gene: COG8 were set to
Mendeliome v0.5183 COG8 Zornitza Stark reviewed gene: COG8: Rating: GREEN; Mode of pathogenicity: None; Publications: 17220172, 28619360; Phenotypes: Congenital disorder of glycosylation, type IIh, MIM# 611182; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5183 COG8 Zornitza Stark Mode of inheritance for gene: COG8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5182 HBB Zornitza Stark Gene: hbb has been classified as Green List (High Evidence).
Mendeliome v0.5182 HBB Zornitza Stark Phenotypes for gene: HBB were changed from to Delta-beta thalassemia 141749; Erythrocytosis 6 617980; Heinz body anemia 140700; Hereditary persistence of fetal hemoglobin 141749; Methemoglobinemia, beta type 617971; Sickle cell anemia 603903; Thalassemia-beta, dominant inclusion-body 603902; Thalassemia, beta 613985
Mendeliome v0.5181 HBB Zornitza Stark Publications for gene: HBB were set to
Mendeliome v0.5180 SCN8A Elena Savva reviewed gene: SCN8A: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID 30615093, 31904124; Phenotypes: ?Myoclonus, familial, 2 618364, Cognitive impairment with or without cerebellar ataxia 614306, Epileptic encephalopathy, early infantile, 13 614558, Seizures, benign familial infantile, 5 617080; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.5180 HBB Zornitza Stark Mode of inheritance for gene: HBB was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5179 ISPD Zornitza Stark Tag SV/CNV tag was added to gene: ISPD.
Mendeliome v0.5179 ISPD Zornitza Stark Publications for gene: ISPD were set to 22522421; 23217329; 23390185; 30060766; 28688748; 26404900
Mendeliome v0.5178 RAD51D Zornitza Stark Gene: rad51d has been classified as Red List (Low Evidence).
Mendeliome v0.5178 RAD51D Zornitza Stark Phenotypes for gene: RAD51D were changed from to {Breast-ovarian cancer, familial, susceptibility to, 4} 614291
Mendeliome v0.5177 RAD51D Zornitza Stark Publications for gene: RAD51D were set to
Mendeliome v0.5176 RAD51D Zornitza Stark Mode of inheritance for gene: RAD51D was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5175 RAD51D Zornitza Stark Classified gene: RAD51D as Red List (low evidence)
Mendeliome v0.5175 RAD51D Zornitza Stark Gene: rad51d has been classified as Red List (Low Evidence).
Mendeliome v0.5174 NUS1 Elena Savva reviewed gene: NUS1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25066056, 29100083, 31656175, 32485575; Phenotypes: ?Congenital disorder of glycosylation, type 1aa 617082, Mental retardation, autosomal dominant 55, with seizures 617831; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.5174 COG8 Elena Savva reviewed gene: COG8: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30690882, 17331980; Phenotypes: Congenital disorder of glycosylation, type IIh 611182; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5174 HBB Elena Savva reviewed gene: HBB: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31788855, 20301599, 29700171; Phenotypes: {Malaria, resistance to} 611162, Delta-beta thalassemia 141749, Erythrocytosis 6 617980, Heinz body anemia 140700, Hereditary persistence of fetal hemoglobin 141749, Methemoglobinemia, beta type 617971, Sickle cell anemia 603903, Thalassemia-beta, dominant inclusion-body 603902, Thalassemia, beta 613985; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.5174 ISPD Elena Savva reviewed gene: ISPD: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28688748, 30060766, 22522420; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7 614643, Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 7 616052; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5174 TPO Zornitza Stark Marked gene: TPO as ready
Mendeliome v0.5174 TPO Zornitza Stark Gene: tpo has been classified as Green List (High Evidence).
Mendeliome v0.5174 TPO Zornitza Stark Phenotypes for gene: TPO were changed from to Thyroid dyshormonogenesis 2A, MIM# 274500
Mendeliome v0.5173 TPO Zornitza Stark Publications for gene: TPO were set to
Mendeliome v0.5172 TPO Zornitza Stark Mode of inheritance for gene: TPO was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5171 TPO Zornitza Stark reviewed gene: TPO: Rating: GREEN; Mode of pathogenicity: None; Publications: 8027236, 10084596; Phenotypes: Thyroid dyshormonogenesis 2A, MIM# 274500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5171 RAD51D Elena Savva reviewed gene: RAD51D: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 28646019, 31937788, 26057125; Phenotypes: {Breast-ovarian cancer, familial, susceptibility to, 4} 614291; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.5171 SLC35A3 Zornitza Stark Phenotypes for gene: SLC35A3 were changed from Arthrogryposis, mental retardation, and seizures; OMIM #615553 to Arthrogryposis, mental retardation, and seizures OMIM #615553; Skeletal dysplasia; Congenital disorder of glycosylation
Mendeliome v0.5170 SLC35A3 Zornitza Stark Publications for gene: SLC35A3 were set to 28328131; 24031089
Mendeliome v0.5169 SLC35A3 Zornitza Stark Classified gene: SLC35A3 as Green List (high evidence)
Mendeliome v0.5169 SLC35A3 Zornitza Stark Gene: slc35a3 has been classified as Green List (High Evidence).
Mendeliome v0.5168 SLC35A3 Zornitza Stark edited their review of gene: SLC35A3: Added comment: Third unrelated family reported in PMID 28777481 with prenatally diagnosed anomalous vertebrae, including butterfly, and hemivertebrae throughout the spine, as well as cleft palate, micrognathia, patent foramen ovale, patent ductus arteriosus, posterior embryotoxon, short limbs, camptodactyly, talipes valgus, rocker bottom feet, and facial dysmorphism including proptosis, nevus flammeus, and a cupped left ear. Unclear if this is a distinct phenotype (note Holstein cows with variants in this gene have a skeletal phenotype) or part of a spectrum for a CDG. However, abnormal protein glycosylation, consistent with a defective Golgi UDP-GlcNAc transporter demonstrated, so overall, promoted to Green for CDG.; Changed rating: GREEN; Changed publications: 28777481, 28328131, 24031089; Changed phenotypes: Arthrogryposis, mental retardation, and seizures OMIM #615553, Skeletal dysplasia, Congenital disorder of glycosylation; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5168 VAC14 Zornitza Stark Gene: vac14 has been classified as Green List (High Evidence).
Mendeliome v0.5168 VAC14 Zornitza Stark Phenotypes for gene: VAC14 were changed from to Striatonigral degeneration, childhood-onset, MIM#617054
Mendeliome v0.5167 VAC14 Zornitza Stark Publications for gene: VAC14 were set to
Mendeliome v0.5166 VAC14 Zornitza Stark Mode of inheritance for gene: VAC14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5165 VAC14 Zornitza Stark reviewed gene: VAC14: Rating: GREEN; Mode of pathogenicity: None; Publications: 27292112, 31392254, 31591492, 31387860, 31876398; Phenotypes: Striatonigral degeneration, childhood-onset, MIM#617054; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5165 PHOX2A Zornitza Stark Publications for gene: PHOX2A were set to 11600883; 18323871
Mendeliome v0.5164 PHOX2A Zornitza Stark reviewed gene: PHOX2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 16815872; Phenotypes: Fibrosis of extraocular muscles, congenital, 2 602078; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5164 PHOX2A Zornitza Stark Classified gene: PHOX2A as Green List (high evidence)
Mendeliome v0.5164 PHOX2A Zornitza Stark Gene: phox2a has been classified as Green List (High Evidence).
Mendeliome v0.5163 COL25A1 Zornitza Stark Gene: col25a1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5163 COL25A1 Zornitza Stark Phenotypes for gene: COL25A1 were changed from to Fibrosis of extraocular muscles, congenital, 5, MIM# 616219
Mendeliome v0.5162 COL25A1 Zornitza Stark Publications for gene: COL25A1 were set to
Mendeliome v0.5161 COL25A1 Zornitza Stark Mode of inheritance for gene: COL25A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5160 COL25A1 Zornitza Stark Classified gene: COL25A1 as Amber List (moderate evidence)
Mendeliome v0.5160 COL25A1 Zornitza Stark Gene: col25a1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5159 COL25A1 Zornitza Stark reviewed gene: COL25A1: Rating: AMBER; Mode of pathogenicity: None; Publications: 25500261, 26486031; Phenotypes: Fibrosis of extraocular muscles, congenital, 5, MIM# 616219; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5159 KIF21A Zornitza Stark Gene: kif21a has been classified as Green List (High Evidence).
Mendeliome v0.5159 KIF21A Zornitza Stark Phenotypes for gene: KIF21A were changed from to Fibrosis of extraocular muscles, congenital, 1/3B, MIM# 135700
Mendeliome v0.5158 KIF21A Zornitza Stark Publications for gene: KIF21A were set to
Mendeliome v0.5157 KIF21A Zornitza Stark Mode of inheritance for gene: KIF21A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5156 KIF21A Zornitza Stark reviewed gene: KIF21A: Rating: GREEN; Mode of pathogenicity: None; Publications: 15621876, 15223798, 15621877, 18332320, 28930843, 27513105, 26190014, 24656932; Phenotypes: Fibrosis of extraocular muscles, congenital, 1/3B, MIM# 135700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5156 NDUFAF6 Zornitza Stark Gene: ndufaf6 has been classified as Green List (High Evidence).
Mendeliome v0.5156 NDUFAF6 Zornitza Stark Phenotypes for gene: NDUFAF6 were changed from to Mitochondrial complex I deficiency, nuclear type 17 (MIM#618239)
Mendeliome v0.5155 NDUFAF6 Zornitza Stark Publications for gene: NDUFAF6 were set to
Mendeliome v0.5154 NDUFAF6 Zornitza Stark Mode of inheritance for gene: NDUFAF6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5153 NDUFAF6 Ain Roesley reviewed gene: NDUFAF6: Rating: GREEN; Mode of pathogenicity: None; Publications: 30642748; Phenotypes: Mitochondrial complex I deficiency, nuclear type 17 (MIM#618239); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5153 WNT5A Zornitza Stark Marked gene: WNT5A as ready
Mendeliome v0.5153 WNT5A Zornitza Stark Gene: wnt5a has been classified as Green List (High Evidence).
Mendeliome v0.5153 WNT5A Zornitza Stark Phenotypes for gene: WNT5A were changed from to Robinow syndrome, autosomal dominant 1, MIM#180700
Mendeliome v0.5152 WNT5A Zornitza Stark Publications for gene: WNT5A were set to
Mendeliome v0.5151 WNT5A Zornitza Stark Mode of inheritance for gene: WNT5A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5150 WNT5A Zornitza Stark reviewed gene: WNT5A: Rating: GREEN; Mode of pathogenicity: None; Publications: 19918918, 24716670, 27092434, 29276006, 31032853, 16602827, 12839624, 10021340; Phenotypes: Robinow syndrome, autosomal dominant 1, MIM#180700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5150 CYP3A4 Zornitza Stark Gene: cyp3a4 has been classified as Green List (High Evidence).
Mendeliome v0.5150 CYP3A4 Zornitza Stark Phenotypes for gene: CYP3A4 were changed from to Vitamin D-dependent rickets-3, MIM#619073
Mendeliome v0.5149 CYP3A4 Zornitza Stark Publications for gene: CYP3A4 were set to
Mendeliome v0.5148 CYP3A4 Zornitza Stark Mode of pathogenicity for gene: CYP3A4 was changed from to Other
Mendeliome v0.5147 CYP3A4 Zornitza Stark Mode of inheritance for gene: CYP3A4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5146 CYP3A4 Zornitza Stark reviewed gene: CYP3A4: Rating: GREEN; Mode of pathogenicity: Other; Publications: 29461981; Phenotypes: Vitamin D-dependent rickets-3, MIM#619073; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5146 KCTD17 Zornitza Stark Marked gene: KCTD17 as ready
Mendeliome v0.5146 KCTD17 Zornitza Stark Gene: kctd17 has been classified as Green List (High Evidence).
Mendeliome v0.5146 KCTD17 Zornitza Stark Phenotypes for gene: KCTD17 were changed from to Dystonia 26, myoclonic MIM#616398
Mendeliome v0.5145 KCTD17 Zornitza Stark Publications for gene: KCTD17 were set to
Mendeliome v0.5144 KCTD17 Zornitza Stark Mode of inheritance for gene: KCTD17 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5143 KCTD17 Zornitza Stark reviewed gene: KCTD17: Rating: GREEN; Mode of pathogenicity: None; Publications: 25983243, 30642807, 30579817; Phenotypes: Dystonia 26, myoclonic MIM#616398; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5143 TAF1 Zornitza Stark Tag deep intronic tag was added to gene: TAF1.
Tag founder tag was added to gene: TAF1.
Mendeliome v0.5143 TAF1 Zornitza Stark Marked gene: TAF1 as ready
Mendeliome v0.5143 TAF1 Zornitza Stark Gene: taf1 has been classified as Green List (High Evidence).
Mendeliome v0.5143 TAF1 Zornitza Stark Phenotypes for gene: TAF1 were changed from to Dystonia-Parkinsonism, X-linked, MIM# 314250; Mental retardation, X-linked, syndromic 33, MIM# 300966
Mendeliome v0.5142 TAF1 Zornitza Stark Publications for gene: TAF1 were set to
Mendeliome v0.5141 TAF1 Zornitza Stark Mode of inheritance for gene: TAF1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.5140 TAF1 Zornitza Stark reviewed gene: TAF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 17273961, 31646703; Phenotypes: Dystonia-Parkinsonism, X-linked, MIM# 314250, Mental retardation, X-linked, syndromic 33, MIM# 300966; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.5140 CTNNA3 Bryony Thompson Marked gene: CTNNA3 as ready
Mendeliome v0.5140 CTNNA3 Bryony Thompson Gene: ctnna3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5140 CTNNA3 Bryony Thompson Classified gene: CTNNA3 as Amber List (moderate evidence)
Mendeliome v0.5140 CTNNA3 Bryony Thompson Gene: ctnna3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5139 CTNNA3 Bryony Thompson gene: CTNNA3 was added
gene: CTNNA3 was added to Mendeliome. Sources: ClinGen
Mode of inheritance for gene: CTNNA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CTNNA3 were set to 23136403; 21254927; 22421363; 30415094; 31539150
Phenotypes for gene: CTNNA3 were set to Arrhythmogenic right ventricular cardiomyopathy; Arrhythmogenic right ventricular dysplasia, familial, 13 MIM#615616
Review for gene: CTNNA3 was set to AMBER
Added comment: Gene is classified as Limited by the ClinGen ARVC GCEP (Classification - 08/06/2019). PMID: 23136403 - an assumed de novo missense (V94D) was identified in an Italian proband with arrhythmogenic right ventricular dysplasia. An inframe deletion (Leu765del) was identified in a proband with arrhythmogenic right ventricular dysplasia, and was also present in the proband's asymptomatic father and paternal aunt, who had mild right ventricular dilation on echocardiography and increased trabeculations in the right ventricular apex on MRI, respectively, as well as in the aunt's asymptomatic son. There was supporting in vitro functional assay evidence for both variants. PMID: 21254927 - a missense variant was found in one of 55 Danish ARVD patients, but was found 37 times in 276,338 (1 homozygous) reference alleles in gnomAD making it less likely as a causal variant. PMID: 22421363 - null mice exhibit progressive dilated cardiomyopathy, gap junction remodelling, and increased sensitivity to ventricular arrhythmia following acute ischaemia, but not spontaneous ARVC. Additional publications identified - PMID: 30415094 - a VUS identified in a sudden unexpected death case with slight LV hypertrophy. PMID: 31539150 - 2 VUS and a nonsense variant identified in 3 probands with atrial fibrillation, with the nonsense variant segregating in an affected first-degree relative.
Sources: ClinGen
Mendeliome v0.5138 STXBP1 Zornitza Stark Phenotypes for gene: STXBP1 were changed from Epileptic encephalopathy, early infantile, 4 612164; Rett syndrome; Rett-like phenotypes to Developmental and epileptic encephalopathy 4, MIM# 612164; Rett syndrome; Rett-like phenotypes
Mendeliome v0.5137 STXBP1 Zornitza Stark reviewed gene: STXBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 4, MIM# 612164; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5137 UBE3A Zornitza Stark Tag SV/CNV tag was added to gene: UBE3A.
Mendeliome v0.5137 UBE3A Zornitza Stark Phenotypes for gene: UBE3A were changed from to Angelman syndrome, MIM#105830
Mendeliome v0.5136 UBE3A Zornitza Stark Mode of inheritance for gene: UBE3A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Mendeliome v0.5135 UBE3A Zornitza Stark reviewed gene: UBE3A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Angelman syndrome, MIM#105830; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Mendeliome v0.5135 CHRNE Zornitza Stark Gene: chrne has been classified as Green List (High Evidence).
Mendeliome v0.5135 CHRNE Zornitza Stark Phenotypes for gene: CHRNE were changed from to Myasthenic syndrome, congenital, 4B, fast-channel, 616324; Myasthenic syndrome, congenital, 4C, associated with acetylcholine receptor deficiency, 608931; Myasthenic syndrome, slow-channel congenital, 601462; Myasthenic syndrome, congenital, 4A, slow-channel, 605809
Mendeliome v0.5134 CHRNE Zornitza Stark Publications for gene: CHRNE were set to
Mendeliome v0.5133 CHRNE Zornitza Stark Mode of inheritance for gene: CHRNE was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5132 CHRNE Zornitza Stark reviewed gene: CHRNE: Rating: GREEN; Mode of pathogenicity: None; Publications: 8755487, 8957026, 11030414, 12417530, 32727330, 32070632, 31773638; Phenotypes: Myasthenic syndrome, congenital, 4B, fast-channel, 616324, Myasthenic syndrome, congenital, 4C, associated with acetylcholine receptor deficiency, 608931, Myasthenic syndrome, slow-channel congenital, 601462, Myasthenic syndrome, congenital, 4A, slow-channel, 605809; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5132 COLQ Zornitza Stark Gene: colq has been classified as Green List (High Evidence).
Mendeliome v0.5132 COLQ Zornitza Stark Phenotypes for gene: COLQ were changed from to Myasthenic syndrome, congenital, 5, MIM# 603034
Mendeliome v0.5131 COLQ Zornitza Stark Publications for gene: COLQ were set to
Mendeliome v0.5130 COLQ Zornitza Stark Mode of inheritance for gene: COLQ was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5129 COLQ Zornitza Stark reviewed gene: COLQ: Rating: GREEN; Mode of pathogenicity: None; Publications: 9689136, 9758617, 11865139, 32978031, 31831253; Phenotypes: Myasthenic syndrome, congenital, 5, MIM# 603034; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5129 NDUFA4 Zornitza Stark Phenotypes for gene: NDUFA4 were changed from Leigh syndrome; Complex IV deficiency to Mitochondrial complex IV deficiency, nuclear type 21, MIM#619065; Leigh syndrome; Complex IV deficiency
Mendeliome v0.5128 NDUFA4 Zornitza Stark edited their review of gene: NDUFA4: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 21, MIM#619065, Leigh syndrome, Complex IV deficiency
Mendeliome v0.5128 COX5A Zornitza Stark Phenotypes for gene: COX5A were changed from pulmonary arterial hypertension; lactic acidemia; failure to thrive; isolated complex IV deficiency to Mitochondrial complex IV deficiency, nuclear type 20, MIM#619064; pulmonary arterial hypertension; lactic acidemia; failure to thrive; isolated complex IV deficiency
Mendeliome v0.5127 COX5A Zornitza Stark edited their review of gene: COX5A: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 20, MIM#619064, pulmonary arterial hypertension, lactic acidemia, failure to thrive, isolated complex IV deficiency
Mendeliome v0.5127 PET117 Zornitza Stark Phenotypes for gene: PET117 were changed from Developmental delay; Regression; Complex IV deficiency to Mitochondrial complex IV deficiency, nuclear type 19, MIM#619063; Developmental delay; Regression; Complex IV deficiency
Mendeliome v0.5126 PET117 Zornitza Stark edited their review of gene: PET117: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 19, MIM#619063, Developmental delay, Regression, Complex IV deficiency
Mendeliome v0.5126 COX6A2 Zornitza Stark Phenotypes for gene: COX6A2 were changed from Mitochondrial complex IV deficiency, MIM# 220110 to Mitochondrial complex IV deficiency, nuclear type 18, MIM#619062
Mendeliome v0.5125 COX6A2 Zornitza Stark edited their review of gene: COX6A2: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 18, MIM#619062
Mendeliome v0.5125 APOPT1 Zornitza Stark Marked gene: APOPT1 as ready
Mendeliome v0.5125 APOPT1 Zornitza Stark Gene: apopt1 has been classified as Green List (High Evidence).
Mendeliome v0.5125 APOPT1 Zornitza Stark Phenotypes for gene: APOPT1 were changed from to Mitochondrial complex IV deficiency, nuclear type 17, MIM#619061
Mendeliome v0.5124 APOPT1 Zornitza Stark Publications for gene: APOPT1 were set to
Mendeliome v0.5123 APOPT1 Zornitza Stark Mode of inheritance for gene: APOPT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5122 APOPT1 Zornitza Stark reviewed gene: APOPT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25175347]; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 17, MIM#619061; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5122 COX4I1 Zornitza Stark Gene: cox4i1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5122 COX4I1 Zornitza Stark Classified gene: COX4I1 as Amber List (moderate evidence)
Mendeliome v0.5122 COX4I1 Zornitza Stark Gene: cox4i1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5121 COX4I1 Zornitza Stark gene: COX4I1 was added
gene: COX4I1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: COX4I1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COX4I1 were set to 28766551; 22592081; 31290619
Phenotypes for gene: COX4I1 were set to Mitochondrial complex IV deficiency, nuclear type 16, MIM#619060
Review for gene: COX4I1 was set to AMBER
Added comment: Two unrelated families reported.

Two more variants reported in PMID: 22592081: one is non-coding and the other rare missense, appear to have been identified in separate individuals, i.e. heterozygous in each individual.
Sources: Expert list
Mendeliome v0.5120 COX8A Zornitza Stark Phenotypes for gene: COX8A were changed from Mitochondrial complex IV deficiency, MIM# 220110 to Mitochondrial complex IV deficiency, nuclear type 15, MIM#619059
Mendeliome v0.5119 COX8A Zornitza Stark edited their review of gene: COX8A: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 15, MIM#619059
Mendeliome v0.5119 COA3 Zornitza Stark Phenotypes for gene: COA3 were changed from Mitochondrial complex IV deficiency to Mitochondrial complex IV deficiency, nuclear type 14, MIM# 619058
Mendeliome v0.5118 COA3 Zornitza Stark edited their review of gene: COA3: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 14, MIM# 619058
Mendeliome v0.5118 PET100 Zornitza Stark Marked gene: PET100 as ready
Mendeliome v0.5118 PET100 Zornitza Stark Gene: pet100 has been classified as Green List (High Evidence).
Mendeliome v0.5118 PET100 Zornitza Stark Phenotypes for gene: PET100 were changed from to Mitochondrial complex IV deficiency, nuclear type 12, MIM# 619055
Mendeliome v0.5117 PET100 Zornitza Stark Publications for gene: PET100 were set to
Mendeliome v0.5116 PET100 Zornitza Stark Mode of inheritance for gene: PET100 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5115 PET100 Zornitza Stark Tag founder tag was added to gene: PET100.
Mendeliome v0.5115 PET100 Zornitza Stark reviewed gene: PET100: Rating: GREEN; Mode of pathogenicity: None; Publications: 24462369, 25293719, 31406627; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 12, MIM# 619055; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5115 COX20 Zornitza Stark Gene: cox20 has been classified as Green List (High Evidence).
Mendeliome v0.5115 COX20 Zornitza Stark Phenotypes for gene: COX20 were changed from to Mitochondrial complex IV deficiency, nuclear type 11, MIM#619054
Mendeliome v0.5114 COX20 Zornitza Stark Publications for gene: COX20 were set to
Mendeliome v0.5113 COX20 Zornitza Stark Mode of inheritance for gene: COX20 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5112 COX20 Zornitza Stark reviewed gene: COX20: Rating: GREEN; Mode of pathogenicity: None; Publications: 24202787, 31079202, 30656193, 23125284, 32606554; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 11, MIM#619054; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5112 COX14 Zornitza Stark Phenotypes for gene: COX14 were changed from Mitochondrial complex IV deficiency, MIM#220110 to Mitochondrial complex IV deficiency, nuclear type 10, MIM#619053
Mendeliome v0.5111 COX14 Zornitza Stark edited their review of gene: COX14: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 10, MIM#619053
Mendeliome v0.5111 TACO1 Zornitza Stark Marked gene: TACO1 as ready
Mendeliome v0.5111 TACO1 Zornitza Stark Gene: taco1 has been classified as Green List (High Evidence).
Mendeliome v0.5111 TACO1 Zornitza Stark Phenotypes for gene: TACO1 were changed from to Mitochondrial complex IV deficiency, nuclear type 8, MIM# 619052
Mendeliome v0.5110 TACO1 Zornitza Stark Publications for gene: TACO1 were set to
Mendeliome v0.5109 TACO1 Zornitza Stark Mode of inheritance for gene: TACO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5108 TACO1 Zornitza Stark reviewed gene: TACO1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19503089, 20727754, 25044680, 27319982; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 8, MIM# 619052; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5108 PRKACA Zornitza Stark Gene: prkaca has been classified as Green List (High Evidence).
Mendeliome v0.5108 PRKACA Zornitza Stark Classified gene: PRKACA as Green List (high evidence)
Mendeliome v0.5108 PRKACA Zornitza Stark Gene: prkaca has been classified as Green List (High Evidence).
Mendeliome v0.5107 PRKACB Zornitza Stark Classified gene: PRKACB as Green List (high evidence)
Mendeliome v0.5107 PRKACB Zornitza Stark Gene: prkacb has been classified as Green List (High Evidence).
Mendeliome v0.5106 CNGA2 Zornitza Stark Gene: cnga2 has been classified as Red List (Low Evidence).
Mendeliome v0.5106 CNGA2 Zornitza Stark gene: CNGA2 was added
gene: CNGA2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CNGA2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: CNGA2 were set to 28572688
Phenotypes for gene: CNGA2 were set to Congenital anosmia
Review for gene: CNGA2 was set to RED
Added comment: Single multiplex family with high-impact variant segregating with anosmia.
Sources: Literature
Mendeliome v0.5105 COX6B1 Zornitza Stark Gene: cox6b1 has been classified as Green List (High Evidence).
Mendeliome v0.5105 COX6B1 Zornitza Stark Phenotypes for gene: COX6B1 were changed from to Mitochondrial complex IV deficiency, nuclear type 7, MIM# 619051
Mendeliome v0.5104 COX6B1 Zornitza Stark Publications for gene: COX6B1 were set to
Mendeliome v0.5103 COX6B1 Zornitza Stark Mode of inheritance for gene: COX6B1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5102 COX6B1 Zornitza Stark reviewed gene: COX6B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18499082, 24781756; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 7, MIM# 619051; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5102 PRKACB Konstantinos Varvagiannis gene: PRKACB was added
gene: PRKACB was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PRKACB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PRKACB were set to 33058759
Phenotypes for gene: PRKACB were set to Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability
Penetrance for gene: PRKACB were set to unknown
Mode of pathogenicity for gene: PRKACB 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: PRKACB was set to GREEN
Added comment: Palencia-Campos et al (2020 - PMID: 33058759) report on the phenotype of 3 individuals heterozygous for PRKACA and 4 individuals heterozygous for PRKACB pathogenic variants.

The most characteristic features in all individuals with PRKACA/PRKACB mutation, included postaxial polydactyly of hands (6/7 bilateral, 1/7 unilateral) and feet (4/7 bilateral, 1/7 unilateral), brachydactyly and congenital heart defects (CHD 5/7) namely a common atrium or AVSD. Two individuals with PRKACA variant who did not have CHD had offspring with the same variant and an AVSD.

Other variably occurring features included short stature, limbs, narrow chest, abnormal teeth, oral frenula, nail dysplasia. One individual with PRKACB variant presented tumors.

Intellectual disability was reported in 2/4 individuals with PRKACB variant (1/4: mild, 1/4: severe). The 3 individuals with PRKACA variant did not present ID.

As the phenotype was overall suggestive of Ellis-van Creveld syndrome (or the allelic Weyers acrofacial dysostosis), although these diagnoses were ruled out following analysis of EVC and EVC2 genes.

WES was carried out in all.

PRKACA : A single heterozygous missense variant was identified in 3 individuals from 3 families (NM_002730.4:c.409G>A / p.Gly137Arg) with 1 of the probands harboring the variant in mosaic state (28% of reads) and having 2 similarly affected offspring. The variant was de novo in one individual and inherited in a third one having a similarly affected fetus (narrow thorax, postaxial polyd, AVSD).

PRKACB : 4 different variants were identified (NM_002731.3: p.His88Arg/Asn, p.Gly235Arg, c.161C>T - p.Ser54Leu). One of the individuals was mosaic for the latter variant, while in all other cases the variant had occurred de novo.

Protein kinase A (PKA) is a tetrameric holoenzyme formed by the association of 2 catalytic (C) subunits with a regulatory (R) subunit dimer. Activation of PKA is achieved through binding of 2 cAMP molecules to each R-subunit, and unleashing(/dissociation) of C-subunits to engage substrates. PRKACA/B genes encode the Cα- and Cβ-subunits while the 4 functionally non-redundant regulatory subunits are encoded by PRKAR1A/1B/2A/2B genes.

The authors provide evidence that the variants confer increased sensitivity of PKA holoenzymes to activation by cAMP (compared to wt).

By performing ectopic expression of wt or mt PRKACA/B (variants studied : PRKACA p.Gly137Arg / PRKACB p.Gly235Arg) in NIH 3T3 fibroblasts, the authors demonstrate that inhibition of hedgehog signaling likely underlyies the developmental defects observed in affected individuals.

As for PRKACA, the authors cite another study where a 31-month old female with EvC syndrome diagnosis was found to harbor the aforementioned variant (NM_001304349.1:c.637G>A:p.Gly213Arg corresponding to NM_002730.4:c.409G>A / p.Gly137Arg) as a de novo event. Without additional evidence at the time, the variant was considered to be a candidate for this subject's phenotype (Monies et al 2019 – PMID: 31130284).
Sources: Literature
Mendeliome v0.5102 PRKACA Konstantinos Varvagiannis gene: PRKACA was added
gene: PRKACA was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PRKACA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PRKACA were set to 33058759; 31130284
Phenotypes for gene: PRKACA were set to Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability
Penetrance for gene: PRKACA were set to unknown
Mode of pathogenicity for gene: PRKACA 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: PRKACA was set to GREEN
Added comment: Palencia-Campos et al (2020 - PMID: 33058759) report on the phenotype of 3 individuals heterozygous for PRKACA and 4 individuals heterozygous for PRKACB pathogenic variants.

The most characteristic features in all individuals with PRKACA/PRKACB mutation, included postaxial polydactyly of hands (6/7 bilateral, 1/7 unilateral) and feet (4/7 bilateral, 1/7 unilateral), brachydactyly and congenital heart defects (CHD 5/7) namely a common atrium or AVSD. Two individuals with PRKACA variant who did not have CHD had offspring with the same variant and an AVSD.

Other variably occurring features included short stature, limbs, narrow chest, abnormal teeth, oral frenula, nail dysplasia. One individual with PRKACB variant presented tumors.

Intellectual disability was reported in 2/4 individuals with PRKACB variant (1/4: mild, 1/4: severe). The 3 individuals with PRKACA variant did not present ID.

As the phenotype was overall suggestive of Ellis-van Creveld syndrome (or the allelic Weyers acrofacial dysostosis), although these diagnoses were ruled out following analysis of EVC and EVC2 genes.

WES was carried out in all.

PRKACA : A single heterozygous missense variant was identified in 3 individuals from 3 families (NM_002730.4:c.409G>A / p.Gly137Arg) with 1 of the probands harboring the variant in mosaic state (28% of reads) and having 2 similarly affected offspring. The variant was de novo in one individual and inherited in a third one having a similarly affected fetus (narrow thorax, postaxial polyd, AVSD).

PRKACB : 4 different variants were identified (NM_002731.3: p.His88Arg/Asn, p.Gly235Arg, c.161C>T - p.Ser54Leu). One of the individuals was mosaic for the latter variant, while in all other cases the variant had occurred de novo.

Protein kinase A (PKA) is a tetrameric holoenzyme formed by the association of 2 catalytic (C) subunits with a regulatory (R) subunit dimer. Activation of PKA is achieved through binding of 2 cAMP molecules to each R-subunit, and unleashing(/dissociation) of C-subunits to engage substrates. PRKACA/B genes encode the Cα- and Cβ-subunits while the 4 functionally non-redundant regulatory subunits are encoded by PRKAR1A/1B/2A/2B genes.

The authors provide evidence that the variants confer increased sensitivity of PKA holoenzymes to activation by cAMP (compared to wt).

By performing ectopic expression of wt or mt PRKACA/B (variants studied : PRKACA p.Gly137Arg / PRKACB p.Gly235Arg) in NIH 3T3 fibroblasts, the authors demonstrate that inhibition of hedgehog signaling likely underlyies the developmental defects observed in affected individuals.

As for PRKACA, the authors cite another study where a 31-month old female with EvC syndrome diagnosis was found to harbor the aforementioned variant (NM_001304349.1:c.637G>A:p.Gly213Arg corresponding to NM_002730.4:c.409G>A / p.Gly137Arg) as a de novo event. Without additional evidence at the time, the variant was considered to be a candidate for this subject's phenotype (Monies et al 2019 – PMID: 31130284).
Sources: Literature
Mendeliome v0.5102 SCO1 Zornitza Stark Gene: sco1 has been classified as Green List (High Evidence).
Mendeliome v0.5102 SCO1 Zornitza Stark Phenotypes for gene: SCO1 were changed from to Mitochondrial complex IV deficiency, nuclear type 4, MIM# 619048
Mendeliome v0.5101 SCO1 Zornitza Stark Publications for gene: SCO1 were set to
Mendeliome v0.5100 SCO1 Zornitza Stark Mode of inheritance for gene: SCO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5099 SCO1 Zornitza Stark reviewed gene: SCO1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11013136, 19295170, 31352446, 23878101; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 4, MIM# 619048; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5099 COX10 Zornitza Stark Gene: cox10 has been classified as Green List (High Evidence).
Mendeliome v0.5099 COX10 Zornitza Stark Phenotypes for gene: COX10 were changed from to Mitochondrial complex IV deficiency, nuclear type 3, MIM# 619046
Mendeliome v0.5098 COX10 Zornitza Stark Publications for gene: COX10 were set to
Mendeliome v0.5097 COX10 Zornitza Stark Mode of inheritance for gene: COX10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5096 COX10 Zornitza Stark reviewed gene: COX10: Rating: GREEN; Mode of pathogenicity: None; Publications: 10767350, 12928484, 15455402, 27290639; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 3, MIM# 619046; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5096 GFPT1 Zornitza Stark Marked gene: GFPT1 as ready
Mendeliome v0.5096 GFPT1 Zornitza Stark Gene: gfpt1 has been classified as Green List (High Evidence).
Mendeliome v0.5096 GFPT1 Zornitza Stark Phenotypes for gene: GFPT1 were changed from to Myasthenia, congenital, 12, with tubular aggregates, 610542; Limb-girdle congenital myasthenic syndrome; Leukoencephalopathy
Mendeliome v0.5095 GFPT1 Zornitza Stark Publications for gene: GFPT1 were set to
Mendeliome v0.5094 GFPT1 Zornitza Stark Mode of inheritance for gene: GFPT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5093 GFPT1 Zornitza Stark reviewed gene: GFPT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21310273, 30635494; Phenotypes: Myasthenia, congenital, 12, with tubular aggregates, 610542, Limb-girdle congenital myasthenic syndrome, Leukoencephalopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5093 BMP7 Zornitza Stark Gene: bmp7 has been classified as Red List (Low Evidence).
Mendeliome v0.5093 BMP7 Zornitza Stark gene: BMP7 was added
gene: BMP7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BMP7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BMP7 were set to 32266521; 24429398
Phenotypes for gene: BMP7 were set to Non-syndromic metopic craniosynostosis
Mode of pathogenicity for gene: BMP7 was set to Other
Review for gene: BMP7 was set to RED
Added comment: Non-syndromic metopic craniosynostosis: PMID 32266521 reports rs6127972 as a susceptibility SNP for non-syndromic metopic craniosynostosis

CAKUT: PMID 24429398 1 family with mouse model in large cohort of CAKUT.
Sources: Literature
Mendeliome v0.5092 SMARCC1 Zornitza Stark Publications for gene: SMARCC1 were set to 33077954
Mendeliome v0.5091 SMARCC1 Zornitza Stark changed review comment from: Three de novo variants, two LOF, one missense, reported in this hydrocephalus cohort.
Sources: Literature; to: Three de novo variants, two LOF, one missense, reported in this hydrocephalus cohort. Supportive mouse model.
Sources: Literature
Mendeliome v0.5091 SMARCC1 Zornitza Stark edited their review of gene: SMARCC1: Changed publications: 33077954, 24170322
Mendeliome v0.5091 SMARCC1 Zornitza Stark Gene: smarcc1 has been classified as Green List (High Evidence).
Mendeliome v0.5091 SMARCC1 Zornitza Stark Classified gene: SMARCC1 as Green List (high evidence)
Mendeliome v0.5091 SMARCC1 Zornitza Stark Gene: smarcc1 has been classified as Green List (High Evidence).
Mendeliome v0.5090 SMARCC1 Zornitza Stark gene: SMARCC1 was added
gene: SMARCC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SMARCC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMARCC1 were set to 33077954
Phenotypes for gene: SMARCC1 were set to Congenital hydrocephalus
Review for gene: SMARCC1 was set to GREEN
Added comment: Three de novo variants, two LOF, one missense, reported in this hydrocephalus cohort.
Sources: Literature
Mendeliome v0.5089 SLC18A3 Zornitza Stark Gene: slc18a3 has been classified as Green List (High Evidence).
Mendeliome v0.5089 SLC18A3 Zornitza Stark Phenotypes for gene: SLC18A3 were changed from to Myasthenic syndrome, congenital, 21, presynaptic, MIM#617239
Mendeliome v0.5088 SLC18A3 Zornitza Stark Publications for gene: SLC18A3 were set to
Mendeliome v0.5087 SLC18A3 Zornitza Stark Mode of inheritance for gene: SLC18A3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5086 SLC18A3 Zornitza Stark reviewed gene: SLC18A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 27590285, 20123977, 28188302, 31059209; Phenotypes: Myasthenic syndrome, congenital, 21, presynaptic, MIM#617239; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5086 SYT2 Zornitza Stark Publications for gene: SYT2 were set to 25192047; 32776697; 32250532
Mendeliome v0.5085 SYT2 Zornitza Stark changed review comment from: Mono-allelic disease, PMID 25192047: dominant missense variants in SYT2 reported as a rare cause of distal motor neuropathy and myasthenic syndrome, manifesting with stable or slowly progressive distal weakness of variable severity along with presynaptic NMJ impairment in two families. These variants are thought to have a dominant-negative effect on synaptic vesicle exocytosis, although the precise pathomechanism remains to be elucidated.

Bi-allelic disease: 32250532 and 32776697, 8 individuals from 6 families, with biallelic loss of function variants in SYT2, clinically manifesting with severe congenital onset hypotonia and weakness, with variable degrees of respiratory involvement. Electrodiagnostic findings consistent with a presynaptic congenital myasthenic syndrome (CMS) in some. Treatment with an acetylcholinesterase inhibitor pursued in 4 indviduals showed clinical improvement with increased strength and function.; to: Mono-allelic disease, PMID 25192047 and 30533528: dominant missense variants in SYT2 reported as a rare cause of distal motor neuropathy and myasthenic syndrome, manifesting with stable or slowly progressive distal weakness of variable severity along with presynaptic NMJ impairment in three families. These variants are thought to have a dominant-negative effect on synaptic vesicle exocytosis, although the precise pathomechanism remains to be elucidated.

Bi-allelic disease: 32250532 and 32776697, 8 individuals from 6 families, with biallelic loss of function variants in SYT2, clinically manifesting with severe congenital onset hypotonia and weakness, with variable degrees of respiratory involvement. Electrodiagnostic findings consistent with a presynaptic congenital myasthenic syndrome (CMS) in some. Treatment with an acetylcholinesterase inhibitor pursued in 4 indviduals showed clinical improvement with increased strength and function.
Mendeliome v0.5085 SYT2 Zornitza Stark edited their review of gene: SYT2: Changed publications: 25192047, 32776697, 32250532, 30533528
Mendeliome v0.5085 SYT2 Zornitza Stark Marked gene: SYT2 as ready
Mendeliome v0.5085 SYT2 Zornitza Stark Gene: syt2 has been classified as Green List (High Evidence).
Mendeliome v0.5085 SYT2 Zornitza Stark Phenotypes for gene: SYT2 were changed from to Myasthenic syndrome, congenital, 7, presynaptic, MIM# 616040
Mendeliome v0.5084 SYT2 Zornitza Stark Publications for gene: SYT2 were set to
Mendeliome v0.5083 SYT2 Zornitza Stark Mode of inheritance for gene: SYT2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5082 SYT2 Zornitza Stark reviewed gene: SYT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25192047, 32776697, 32250532; Phenotypes: Myasthenic syndrome, congenital, 7, presynaptic, MIM# 616040; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5082 CHAT Zornitza Stark Marked gene: CHAT as ready
Mendeliome v0.5082 CHAT Zornitza Stark Gene: chat has been classified as Green List (High Evidence).
Mendeliome v0.5082 CHAT Zornitza Stark Phenotypes for gene: CHAT were changed from to Congenital myasthenics syndrome associated with episodic apnea; Myasthenic syndrome, congenital, 6, presynaptic, 254210
Mendeliome v0.5081 CHAT Zornitza Stark Publications for gene: CHAT were set to
Mendeliome v0.5080 CHAT Zornitza Stark Mode of inheritance for gene: CHAT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5079 CHAT Zornitza Stark reviewed gene: CHAT: Rating: GREEN; Mode of pathogenicity: None; Publications: 11172068, 12756141, 31192527, 29518833, 29189923; Phenotypes: Congenital myasthenics syndrome associated with episodic apnea, Myasthenic syndrome, congenital, 6, presynaptic, 254210; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5079 ALG2 Zornitza Stark Tag founder tag was added to gene: ALG2.
Mendeliome v0.5079 ALG2 Zornitza Stark Gene: alg2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5079 ALG2 Zornitza Stark Phenotypes for gene: ALG2 were changed from to Myasthenic syndrome, congenital, 14, with tubular aggregates, MIM# 616228; Congenital disorder of glycosylation, type Ii, MIM# 607906
Mendeliome v0.5078 ALG2 Zornitza Stark Publications for gene: ALG2 were set to
Mendeliome v0.5077 ALG2 Zornitza Stark Mode of inheritance for gene: ALG2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5076 ALG2 Zornitza Stark Classified gene: ALG2 as Amber List (moderate evidence)
Mendeliome v0.5076 ALG2 Zornitza Stark Gene: alg2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5075 ALG2 Zornitza Stark reviewed gene: ALG2: Rating: AMBER; Mode of pathogenicity: None; Publications: 23404334, 24461433, 12684507; Phenotypes: Myasthenic syndrome, congenital, 14, with tubular aggregates, MIM# 616228, Congenital disorder of glycosylation, type Ii, MIM# 607906; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5075 AGRN Zornitza Stark Gene: agrn has been classified as Green List (High Evidence).
Mendeliome v0.5075 AGRN Zornitza Stark Phenotypes for gene: AGRN were changed from to Myasthenic syndrome, congenital, 8, with pre- and postsynaptic defects, MIM# 615120
Mendeliome v0.5074 AGRN Zornitza Stark Publications for gene: AGRN were set to
Mendeliome v0.5073 AGRN Zornitza Stark Mode of inheritance for gene: AGRN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5072 AGRN Zornitza Stark reviewed gene: AGRN: Rating: GREEN; Mode of pathogenicity: None; Publications: 19631309, 22205389, 32221959; Phenotypes: Myasthenic syndrome, congenital, 8, with pre- and postsynaptic defects, MIM# 615120; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5072 DPH1 Zornitza Stark Gene: dph1 has been classified as Green List (High Evidence).
Mendeliome v0.5072 DPH1 Zornitza Stark Phenotypes for gene: DPH1 were changed from to Developmental delay with short stature, dysmorphic facial features, and sparse hair, MIM# 616901
Mendeliome v0.5071 DPH1 Zornitza Stark Publications for gene: DPH1 were set to
Mendeliome v0.5070 DPH1 Zornitza Stark Mode of inheritance for gene: DPH1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5069 DPH1 Zornitza Stark edited their review of gene: DPH1: Changed publications: 29362492, 29410513, 25558065, 26220823
Mendeliome v0.5069 DPH1 Zornitza Stark reviewed gene: DPH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29362492, 29410513, 25558065, 26220823]; Phenotypes: Developmental delay with short stature, dysmorphic facial features, and sparse hair, MIM# 616901; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5069 PTCD3 Zornitza Stark Phenotypes for gene: PTCD3 were changed from Intellectual disability; optic atrophy; Leigh-like syndrome to Combined oxidative phosphorylation deficiency-51, MIM#619057; Intellectual disability; optic atrophy; Leigh-like syndrome
Mendeliome v0.5068 PTCD3 Zornitza Stark edited their review of gene: PTCD3: Changed phenotypes: Combined oxidative phosphorylation deficiency-51, MIM#619057, Intellectual disability, optic atrophy, Leigh-like syndrome
Mendeliome v0.5068 LRP8 Bryony Thompson Gene: lrp8 has been classified as Red List (Low Evidence).
Mendeliome v0.5068 LRP8 Bryony Thompson Classified gene: LRP8 as Red List (low evidence)
Mendeliome v0.5068 LRP8 Bryony Thompson Gene: lrp8 has been classified as Red List (Low Evidence).
Mendeliome v0.5067 LRP8 Bryony Thompson reviewed gene: LRP8: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Myocardial infarction, susceptibility to MIM#608446; Mode of inheritance: Unknown
Mendeliome v0.5067 TCF21 Bryony Thompson Marked gene: TCF21 as ready
Mendeliome v0.5067 TCF21 Bryony Thompson Gene: tcf21 has been classified as Red List (Low Evidence).
Mendeliome v0.5067 TCF21 Bryony Thompson Classified gene: TCF21 as Red List (low evidence)
Mendeliome v0.5067 TCF21 Bryony Thompson Gene: tcf21 has been classified as Red List (Low Evidence).
Mendeliome v0.5066 TCF21 Bryony Thompson reviewed gene: TCF21: Rating: RED; Mode of pathogenicity: None; Publications: 16156022, 10769282, 24875298; Phenotypes: Sensorineural hearing loss, dilated cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.5066 SETD1A Zornitza Stark changed review comment from: OMIM has assigned a second phenotype in relation to the syndromic ID cohort reported in PMID 32346159. All variants were predicted to disrupt or delete the SET catalytic domain, and LOF is the established mechanism.

In addition, there are 3 families reported with a predominantly seizure phenotype without ID, PMID 31197650. All the variants are missense and mechanism of pathogenicity is not clearly established, hence it is difficult to know whether these are two distinct conditions or part of a spectrum of severity for SETD1A-related disorders.; to: OMIM has assigned a second phenotype in relation to the syndromic ID cohort reported in PMID 32346159. All variants were predicted to disrupt or delete the SET catalytic domain, and LOF is the established mechanism.

In addition, there are 4 families reported with a predominantly seizure phenotype without ID, PMID 31197650. All the variants are missense and mechanism of pathogenicity is not clearly established, hence it is difficult to know whether these are two distinct conditions or part of a spectrum of severity for SETD1A-related disorders.
Mendeliome v0.5066 SETD1A Zornitza Stark Phenotypes for gene: SETD1A were changed from Epilepsy, early-onset, with or without developmental delay, MIM# 618832 to Epilepsy, early-onset, with or without developmental delay, MIM# 618832; Neurodevelopmental disorder with speech impairment and dysmorphic facies, MIM# 619056
Mendeliome v0.5065 SETD1A Zornitza Stark edited their review of gene: SETD1A: Added comment: OMIM has assigned a second phenotype in relation to the syndromic ID cohort reported in PMID 32346159. All variants were predicted to disrupt or delete the SET catalytic domain, and LOF is the established mechanism.

In addition, there are 3 families reported with a predominantly seizure phenotype without ID, PMID 31197650. All the variants are missense and mechanism of pathogenicity is not clearly established, hence it is difficult to know whether these are two distinct conditions or part of a spectrum of severity for SETD1A-related disorders.; Changed phenotypes: Epilepsy, early-onset, with or without developmental delay, MIM# 618832, Neurodevelopmental disorder with speech impairment and dysmorphic facies, MIM# 619056
Mendeliome v0.5065 JARID2 Zornitza Stark Publications for gene: JARID2 were set to 23294540
Mendeliome v0.5064 JARID2 Zornitza Stark Classified gene: JARID2 as Green List (high evidence)
Mendeliome v0.5064 JARID2 Zornitza Stark Gene: jarid2 has been classified as Green List (High Evidence).
Mendeliome v0.5063 JARID2 Zornitza Stark edited their review of gene: JARID2: Added comment: 13 additional individuals reported, note CNVs common but LOF sequence variants identified too.; Changed rating: GREEN; Changed publications: 23294540, 33077894
Mendeliome v0.5063 NUDT2 Zornitza Stark Phenotypes for gene: NUDT2 were changed from Muscular hypotonia; Global developmental delay; Intellectual disability to Muscular hypotonia; Global developmental delay; Intellectual disability; Polyneuropathy
Mendeliome v0.5062 NUDT2 Zornitza Stark Publications for gene: NUDT2 were set to 27431290; 30059600
Mendeliome v0.5061 NUDT2 Zornitza Stark Classified gene: NUDT2 as Green List (high evidence)
Mendeliome v0.5061 NUDT2 Zornitza Stark Gene: nudt2 has been classified as Green List (High Evidence).
Mendeliome v0.5060 NUDT2 Zornitza Stark edited their review of gene: NUDT2: Added comment: Three individuals from two additional families reported with a different homozygous variant and ID/polyneuropathy phenotype. Upgrade to Green.; Changed rating: GREEN; Changed publications: 27431290, 30059600, 33058507
Mendeliome v0.5060 AFF2 Zornitza Stark changed review comment from: This is classically a triplet expansion disorder. Note one report of an intragenic deletion which segregated with ID in a family, and two truncating variants classified as pathogenic by laboratories in ClinVar.; to: This is classically a triplet expansion disorder. Note one report of an intragenic deletion which segregated with ID in a family, and two truncating variants classified as pathogenic by laboratories in ClinVar. Missense variants found to be over-represented in an autism cohort.
Mendeliome v0.5060 AFF2 Zornitza Stark edited their review of gene: AFF2: Changed publications: 8334699, 21739600, 22773736
Mendeliome v0.5060 AFF2 Zornitza Stark Tag SV/CNV tag was added to gene: AFF2.
Tag STR tag was added to gene: AFF2.
Mendeliome v0.5060 AFF2 Zornitza Stark Gene: aff2 has been classified as Green List (High Evidence).
Mendeliome v0.5060 AFF2 Zornitza Stark Phenotypes for gene: AFF2 were changed from to Mental retardation, X-linked, FRAXE type 309548
Mendeliome v0.5059 AFF2 Zornitza Stark Publications for gene: AFF2 were set to
Mendeliome v0.5058 AFF2 Zornitza Stark Mode of inheritance for gene: AFF2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5057 AFF2 Zornitza Stark commented on gene: AFF2: This is classically a triplet expansion disorder. Note one report of an intragenic deletion which segregated with ID in a family, and two truncating variants classified as pathogenic by laboratories in ClinVar.
Mendeliome v0.5057 AFF2 Zornitza Stark reviewed gene: AFF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 8334699, 21739600; Phenotypes: Mental retardation, X-linked, FRAXE type 309548; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5057 AUTS2 Zornitza Stark Marked gene: AUTS2 as ready
Mendeliome v0.5057 AUTS2 Zornitza Stark Gene: auts2 has been classified as Green List (High Evidence).
Mendeliome v0.5057 AUTS2 Zornitza Stark Phenotypes for gene: AUTS2 were changed from to Mental retardation, autosomal dominant 26, MIM#615834
Mendeliome v0.5056 AUTS2 Zornitza Stark Publications for gene: AUTS2 were set to
Mendeliome v0.5055 AUTS2 Zornitza Stark Mode of inheritance for gene: AUTS2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5055 AUTS2 Zornitza Stark Mode of inheritance for gene: AUTS2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5054 AUTS2 Zornitza Stark Tag SV/CNV tag was added to gene: AUTS2.
Mendeliome v0.5054 AUTS2 Zornitza Stark reviewed gene: AUTS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23332918, 25205402, 31474318; Phenotypes: Mental retardation, autosomal dominant 26, MIM#615834; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5054 ZEB2 Zornitza Stark Phenotypes for gene: ZEB2 were changed from to Mowat-Wilson syndrome (MIM#235730)
Mendeliome v0.5053 ZEB2 Zornitza Stark Publications for gene: ZEB2 were set to
Mendeliome v0.5052 ZEB2 Zornitza Stark Mode of inheritance for gene: ZEB2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5051 ITSN2 Zornitza Stark Marked gene: ITSN2 as ready
Mendeliome v0.5051 ITSN2 Zornitza Stark Gene: itsn2 has been classified as Green List (High Evidence).
Mendeliome v0.5051 ITSN2 Zornitza Stark Classified gene: ITSN2 as Green List (high evidence)
Mendeliome v0.5051 ITSN2 Zornitza Stark Gene: itsn2 has been classified as Green List (High Evidence).
Mendeliome v0.5050 ZEB2 Ain Roesley reviewed gene: ZEB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29300384; Phenotypes: Mowat-Wilson syndrome (MIM#235730); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5050 ITSN2 Elena Savva gene: ITSN2 was added
gene: ITSN2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ITSN2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ITSN2 were set to PMID: 29773874
Phenotypes for gene: ITSN2 were set to Nephrotic syndrome
Review for gene: ITSN2 was set to GREEN
Added comment: PMID: 29773874: 2 families (3 patients) with homozygous missense or chet missense/PTC + null mice recapitulating the human phenotype.
Functional analysis of all variants shows an inability for Cdc42 activation as shown by wildtype overexpression
Sources: Literature
Mendeliome v0.5050 PI4K2A Zornitza Stark Gene: pi4k2a has been classified as Red List (Low Evidence).
Mendeliome v0.5050 PI4K2A Zornitza Stark gene: PI4K2A was added
gene: PI4K2A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PI4K2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PI4K2A were set to 32418222
Phenotypes for gene: PI4K2A were set to Cutis laxa, intellectual disability, movement disorder
Review for gene: PI4K2A was set to RED
Added comment: Single individual reported with homozygous missense variant and functional data including mouse model.
Sources: Literature
Mendeliome v0.5049 NR5A1 Zornitza Stark Gene: nr5a1 has been classified as Green List (High Evidence).
Mendeliome v0.5049 NR5A1 Zornitza Stark Phenotypes for gene: NR5A1 were changed from to Adrenocortical insufficiency, (MIM#612964); 46, XX sex reversal 4, (MIM# 617480); Premature ovarian failure 7, (MIM#612964); Spermatogenic failure 8, (MIM#613957); 46XY sex reversal 3, (MIM#612965)
Mendeliome v0.5048 NR5A1 Zornitza Stark Publications for gene: NR5A1 were set to
Mendeliome v0.5047 NR5A1 Zornitza Stark Mode of inheritance for gene: NR5A1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5046 NR5A1 Zornitza Stark reviewed gene: NR5A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31513305; Phenotypes: Adrenocortical insufficiency, (MIM#612964), 46, XX sex reversal 4, (MIM# 617480), Premature ovarian failure 7, (MIM#612964), Spermatogenic failure 8, (MIM#613957), 46XY sex reversal 3, (MIM#612965); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5046 HECW2 Zornitza Stark Gene: hecw2 has been classified as Green List (High Evidence).
Mendeliome v0.5046 HECW2 Zornitza Stark Publications for gene: HECW2 were set to
Mendeliome v0.5045 HECW2 Zornitza Stark Phenotypes for gene: HECW2 were changed from to Neurodevelopmental disorder with hypotonia, seizures, and absent language, MIM# 617268; intellectual disability; epilepsy; regression; microcephaly
Mendeliome v0.5044 HECW2 Zornitza Stark Mode of pathogenicity for gene: HECW2 was changed from to Other
Mendeliome v0.5043 HECW2 Zornitza Stark Mode of inheritance for gene: HECW2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5042 HECW2 Natasha Brown reviewed gene: HECW2: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 29807643, 29395664, 27334371, 27389779; Phenotypes: intellectual disability, epilepsy, regression, microcephaly; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5042 ARHGEF9 Zornitza Stark Mode of inheritance for gene: ARHGEF9 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.5041 ARHGEF9 Zornitza Stark edited their review of gene: ARHGEF9: Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.5041 ZMYND10 Zornitza Stark Gene: zmynd10 has been classified as Green List (High Evidence).
Mendeliome v0.5041 ZMYND10 Zornitza Stark Phenotypes for gene: ZMYND10 were changed from to Ciliary dyskinesia, primary, 22, MIM#615444
Mendeliome v0.5040 ZMYND10 Zornitza Stark Publications for gene: ZMYND10 were set to
Mendeliome v0.5039 ZMYND10 Zornitza Stark Mode of inheritance for gene: ZMYND10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5038 ZMYND10 Zornitza Stark reviewed gene: ZMYND10: Rating: GREEN; Mode of pathogenicity: None; Publications: 23891471, 23891469; Phenotypes: Ciliary dyskinesia, primary, 22, MIM#615444; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5038 SPAG1 Zornitza Stark Gene: spag1 has been classified as Green List (High Evidence).
Mendeliome v0.5038 SPAG1 Zornitza Stark Phenotypes for gene: SPAG1 were changed from to Ciliary dyskinesia, primary, 28 (MIM#615505)
Mendeliome v0.5037 SPAG1 Zornitza Stark Publications for gene: SPAG1 were set to
Mendeliome v0.5036 SPAG1 Zornitza Stark Mode of inheritance for gene: SPAG1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5035 SPAG1 Zornitza Stark reviewed gene: SPAG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32622824, 32502479, 24055112; Phenotypes: Ciliary dyskinesia, primary, 28 (MIM#615505); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5035 MMP21 Zornitza Stark Gene: mmp21 has been classified as Green List (High Evidence).
Mendeliome v0.5035 MMP21 Zornitza Stark Phenotypes for gene: MMP21 were changed from to Heterotaxy, visceral, 7, autosomal,MIM# 616749
Mendeliome v0.5034 MMP21 Zornitza Stark Publications for gene: MMP21 were set to
Mendeliome v0.5033 MMP21 Zornitza Stark Mode of inheritance for gene: MMP21 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5032 MMP21 Zornitza Stark reviewed gene: MMP21: Rating: GREEN; Mode of pathogenicity: None; Publications: 26429889, 26437028, 26437029; Phenotypes: Heterotaxy, visceral, 7, autosomal,MIM# 616749; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5032 DNAAF1 Zornitza Stark Gene: dnaaf1 has been classified as Green List (High Evidence).
Mendeliome v0.5032 DNAAF1 Zornitza Stark Phenotypes for gene: DNAAF1 were changed from to Ciliary dyskinesia, primary, 13, MIM# 613193
Mendeliome v0.5031 DNAAF1 Zornitza Stark Publications for gene: DNAAF1 were set to
Mendeliome v0.5030 DNAAF1 Zornitza Stark Mode of inheritance for gene: DNAAF1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5029 DNAAF1 Zornitza Stark reviewed gene: DNAAF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19944400, 19944405, 32502479, 29228333, 27261005; Phenotypes: Ciliary dyskinesia, primary, 13, MIM# 613193; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5029 LRRC6 Zornitza Stark Gene: lrrc6 has been classified as Green List (High Evidence).
Mendeliome v0.5029 LRRC6 Zornitza Stark Phenotypes for gene: LRRC6 were changed from to Ciliary dyskinesia, primary, 19, MIM# 614935
Mendeliome v0.5028 LRRC6 Zornitza Stark Publications for gene: LRRC6 were set to
Mendeliome v0.5027 LRRC6 Zornitza Stark Mode of inheritance for gene: LRRC6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5026 LRRC6 Zornitza Stark reviewed gene: LRRC6: Rating: GREEN; Mode of pathogenicity: None; Publications: 23122589, 23891469, 32622824, 29511670; Phenotypes: Ciliary dyskinesia, primary, 19, MIM# 614935; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5026 GAS8 Zornitza Stark Gene: gas8 has been classified as Green List (High Evidence).
Mendeliome v0.5026 GAS8 Zornitza Stark Phenotypes for gene: GAS8 were changed from to Ciliary dyskinesia, primary, 33, MIM#616726
Mendeliome v0.5025 GAS8 Zornitza Stark Publications for gene: GAS8 were set to
Mendeliome v0.5024 GAS8 Zornitza Stark Mode of inheritance for gene: GAS8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5023 GAS8 Zornitza Stark reviewed gene: GAS8: Rating: GREEN; Mode of pathogenicity: None; Publications: 26387594, 27120127; Phenotypes: Ciliary dyskinesia, primary, 33, mIM# 616726; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5023 DNAI2 Zornitza Stark Gene: dnai2 has been classified as Green List (High Evidence).
Mendeliome v0.5023 DNAI2 Zornitza Stark Phenotypes for gene: DNAI2 were changed from to Ciliary dyskinesia, primary, 9, with or without situs inversus, MIM# 612444
Mendeliome v0.5022 DNAI2 Zornitza Stark Publications for gene: DNAI2 were set to
Mendeliome v0.5021 DNAI2 Zornitza Stark Mode of inheritance for gene: DNAI2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5020 DNAI2 Zornitza Stark reviewed gene: DNAI2: Rating: GREEN; Mode of pathogenicity: None; Publications: 18950741, 23261302; Phenotypes: Ciliary dyskinesia, primary, 9, with or without situs inversus, MIM# 612444; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5020 DNAI1 Zornitza Stark Gene: dnai1 has been classified as Green List (High Evidence).
Mendeliome v0.5020 DNAI1 Zornitza Stark Phenotypes for gene: DNAI1 were changed from to Ciliary dyskinesia, primary, 1, with or without situs inversus, MIM# 244400
Mendeliome v0.5019 DNAI1 Zornitza Stark Publications for gene: DNAI1 were set to
Mendeliome v0.5018 DNAI1 Zornitza Stark Mode of inheritance for gene: DNAI1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5017 DNAI1 Zornitza Stark reviewed gene: DNAI1: Rating: GREEN; Mode of pathogenicity: None; Publications: 10577904, 11231901, 32502479, 31765523, 30622330; Phenotypes: Ciliary dyskinesia, primary, 1, with or without situs inversus, MIM# 244400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5017 DNAH11 Zornitza Stark Publications for gene: DNAH11 were set to
Mendeliome v0.5016 DNAH11 Zornitza Stark reviewed gene: DNAH11: Rating: GREEN; Mode of pathogenicity: None; Publications: 12142464, 18022865, 22102620, 32633470, 31879361, 31765523, 31040315; Phenotypes: Ciliary dyskinesia, primary, 7, with or without situs inversus, MIM#611884; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5016 DNAAF5 Zornitza Stark Gene: dnaaf5 has been classified as Green List (High Evidence).
Mendeliome v0.5016 DNAAF5 Zornitza Stark Phenotypes for gene: DNAAF5 were changed from to Ciliary dyskinesia, primary, 18, MIM# 614874
Mendeliome v0.5015 DNAAF5 Zornitza Stark Publications for gene: DNAAF5 were set to
Mendeliome v0.5014 DNAAF5 Zornitza Stark Mode of inheritance for gene: DNAAF5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5013 DNAAF5 Zornitza Stark reviewed gene: DNAAF5: Rating: GREEN; Mode of pathogenicity: None; Publications: 23040496, 29363216, 25232951; Phenotypes: Ciliary dyskinesia, primary, 18, MIM# 614874; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5013 DNAAF3 Zornitza Stark Gene: dnaaf3 has been classified as Green List (High Evidence).
Mendeliome v0.5013 DNAAF3 Zornitza Stark Phenotypes for gene: DNAAF3 were changed from to Ciliary dyskinesia, primary, 2, MIM# 606763
Mendeliome v0.5012 DNAAF3 Zornitza Stark Publications for gene: DNAAF3 were set to
Mendeliome v0.5011 DNAAF3 Zornitza Stark Mode of inheritance for gene: DNAAF3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5010 DNAAF3 Zornitza Stark reviewed gene: DNAAF3: Rating: GREEN; Mode of pathogenicity: None; Publications: 22387996, 32622824, 31186518; Phenotypes: Ciliary dyskinesia, primary, 2, MIM# 606763; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5010 RAB27A Zornitza Stark Gene: rab27a has been classified as Green List (High Evidence).
Mendeliome v0.5010 RAB27A Zornitza Stark Phenotypes for gene: RAB27A were changed from to Griscelli syndrome, type 2, MIM# 607624
Mendeliome v0.5009 RAB27A Zornitza Stark Publications for gene: RAB27A were set to
Mendeliome v0.5008 RAB27A Zornitza Stark Mode of inheritance for gene: RAB27A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5007 RAB27A Zornitza Stark reviewed gene: RAB27A: Rating: GREEN; Mode of pathogenicity: None; Publications: 10835631, 10704277, 19030707, 15163896, 12058346, 10859366; Phenotypes: Griscelli syndrome, type 2, MIM# 607624; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5007 DNAAF2 Zornitza Stark Gene: dnaaf2 has been classified as Green List (High Evidence).
Mendeliome v0.5007 DNAAF2 Zornitza Stark Phenotypes for gene: DNAAF2 were changed from to Ciliary dyskinesia, primary, 10, MIM# 612518
Mendeliome v0.5006 DNAAF2 Zornitza Stark Publications for gene: DNAAF2 were set to
Mendeliome v0.5005 DNAAF2 Zornitza Stark Mode of inheritance for gene: DNAAF2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5004 DNAAF2 Zornitza Stark reviewed gene: DNAAF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 19052621, 32638265, 31107948; Phenotypes: Ciliary dyskinesia, primary, 10, MIM# 612518; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5004 PPP1R13L Zornitza Stark Gene: ppp1r13l has been classified as Green List (High Evidence).
Mendeliome v0.5004 PPP1R13L Zornitza Stark Classified gene: PPP1R13L as Green List (high evidence)
Mendeliome v0.5004 PPP1R13L Zornitza Stark Gene: ppp1r13l has been classified as Green List (High Evidence).
Mendeliome v0.5003 PPP1R13L Zornitza Stark gene: PPP1R13L was added
gene: PPP1R13L was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PPP1R13L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPP1R13L were set to 32666529; 28864777
Phenotypes for gene: PPP1R13L were set to Dilated cardiomyopathy, onset in infancy
Review for gene: PPP1R13L was set to GREEN
Added comment: Four families reported in PMID 28864777, but same homozygous variant, identity by descent. Five unrelated families reported in PMID 32666529. Severe progressive DCM with onset in infancy.
Sources: Expert list
Mendeliome v0.5002 CCNO Zornitza Stark Gene: ccno has been classified as Green List (High Evidence).
Mendeliome v0.5002 CCNO Zornitza Stark Phenotypes for gene: CCNO were changed from to Ciliary dyskinesia, primary, 29, MIM# 615872
Mendeliome v0.5001 CCNO Zornitza Stark Publications for gene: CCNO were set to
Mendeliome v0.5000 CCNO Zornitza Stark Mode of inheritance for gene: CCNO was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4999 CCNO Zornitza Stark reviewed gene: CCNO: Rating: GREEN; Mode of pathogenicity: None; Publications: 24747639, 31765523, 28801648; Phenotypes: Ciliary dyskinesia, primary, 29, MIM# 615872; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4999 CSNK1G1 Zornitza Stark Gene: csnk1g1 has been classified as Green List (High Evidence).
Mendeliome v0.4999 CSNK1G1 Zornitza Stark Classified gene: CSNK1G1 as Green List (high evidence)
Mendeliome v0.4999 CSNK1G1 Zornitza Stark Gene: csnk1g1 has been classified as Green List (High Evidence).
Mendeliome v0.4998 CSNK1G1 Zornitza Stark gene: CSNK1G1 was added
gene: CSNK1G1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CSNK1G1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CSNK1G1 were set to 33009664
Phenotypes for gene: CSNK1G1 were set to Global developmental delay; Intellectual disability; Autism; Seizures
Review for gene: CSNK1G1 was set to GREEN
Added comment: Borderline Green/Amber rating.

Gold et al (2020 - PMID: 33009664) report 5 individuals with CSNK1G1 variants, including updated information on a previously reported subject (Martin et al 2014 - PMID: 24463883).

Features included DD (5/5) with associated expressive language delay, ASD (in at least 3/5), seizures (2/5), dysmorphic facial features (4/5 arched eyebrows, 3/5 prominent central incisors, 2/5 epicanthus) and limb anomalies (2/5 - proximally placed thumb, 5th f. clinodactyly, asymmetric overgrowth - the other individual had tapering fingers). GI problems were observed in 4/5. Two individuals had macrocephaly and one had microcephaly. There was no formal developmental assessment although ID might be implied in at least 3 individuals (p1: 20y - single words/regression in walking following a seizure episode, p2: 8y - first words at 5y, assistance to feed, dress and bathe, ASD, p4: 13y - regression, assistance to feed and dress).

CSNK1G1 encodes the gamma-1 isoform of casein kinase 1, a protein involved in growth and cell morphogenesis. The gene has ubiquitous expression, incl. brain. As commented, in brain it regulates phosphorylation of NMDA receptors, playing a role in synaptic transmission (4 articles cited).

One individual had a 1.2 kb deletion spanning exon 3 of CSNK1G1 [chr15:64550952-64552120 - GRCh37]. Parental samples were unavailable for this individual. Four individuals were found to harbor de novo CSNK1G1 variants [NM_022048.3: c.688C>T - p.(Arg230Trp) dn | c.1255C>T - p.(Gln419*) dn | c.1214+5G>A dn with in silico predictions in favor of splice disruption | c.419C>T - p.(Thr140Met) dn].

Arg230Trp is however present once in gnomAD. The stopgain variant is located in the last exon and predicted to skip NMD.

There were no variant studies performed.

The Drosophila gish gene encodes a CK1γ homolog with preferential expression in the mushroom body. Heterozygous and homozygous mutants exhibit impairment in memory retention, more severe in homozygous flies. gish was also identified as a seizure modifier in a fly epilepsy model (heterozygous para mt flies).
Sources: Literature
Mendeliome v0.4997 LMNB2 Zornitza Stark Gene: lmnb2 has been classified as Green List (High Evidence).
Mendeliome v0.4997 LMNB2 Zornitza Stark Phenotypes for gene: LMNB2 were changed from to {Lipodystrophy, partial, acquired, susceptibility to} 608709; Congenital microcephaly, Intellectual disability
Mendeliome v0.4996 LMNB2 Zornitza Stark Publications for gene: LMNB2 were set to
Mendeliome v0.4995 LMNB2 Zornitza Stark Mode of inheritance for gene: LMNB2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4994 LMNB2 Zornitza Stark reviewed gene: LMNB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 16826530, 22768673, 33033404; Phenotypes: {Lipodystrophy, partial, acquired, susceptibility to} 608709, Congenital microcephaly, Intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4994 LMNB1 Zornitza Stark Publications for gene: LMNB1 were set to 32910914; 16951681; 19151023
Mendeliome v0.4993 LMNB1 Zornitza Stark edited their review of gene: LMNB1: Added comment: Additional study PMID 33033404 reporting 7 individuals with recurrent missense variants in this gene and ID/microcephaly phenotype.; Changed publications: 32910914, 16951681, 19151023, 33033404
Mendeliome v0.4993 SREBF1 Zornitza Stark Phenotypes for gene: SREBF1 were changed from IFAP (ichthyosis follicularis, atrichia, and photophobia) syndrome 2, MIM619016 to IFAP (ichthyosis follicularis, atrichia, and photophobia) syndrome 2, MIM619016; Mucoepithelial dysplasia, hereditary, MIM#158310
Mendeliome v0.4992 SREBF1 Zornitza Stark Publications for gene: SREBF1 were set to 32497488
Mendeliome v0.4991 SREBF1 Zornitza Stark edited their review of gene: SREBF1: Added comment: HMD phenotype: 5 unrelated families reported with heterozygous variants at same residue (p.Arg557Cys and p.Arg557His) and a panepithelial defect involving the oral, nasal, conjunctival, vaginal, cervical, perineal, urethral, and bladder mucosa. Individuals developed cataracts, blindness, nonscarring alopecia, perineal psoriasiform lesions, and follicular keratoses.; Changed publications: 32497488, 31790666, 32902915; Changed phenotypes: IFAP (ichthyosis follicularis, atrichia, and photophobia) syndrome 2, MIM619016, Mucoepithelial dysplasia, hereditary, MIM#158310
Mendeliome v0.4991 CCDC40 Zornitza Stark Gene: ccdc40 has been classified as Green List (High Evidence).
Mendeliome v0.4991 CCDC40 Zornitza Stark Phenotypes for gene: CCDC40 were changed from to Ciliary dyskinesia, primary, 15, MIM#613808
Mendeliome v0.4990 CCDC40 Zornitza Stark Publications for gene: CCDC40 were set to
Mendeliome v0.4989 CCDC40 Zornitza Stark Mode of inheritance for gene: CCDC40 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4988 CCDC40 Zornitza Stark reviewed gene: CCDC40: Rating: GREEN; Mode of pathogenicity: None; Publications: 21131974, 23255504, 31879361, 31765523, 31650533; Phenotypes: Ciliary dyskinesia, primary, 15, MIM#613808; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4988 CCDC39 Zornitza Stark Gene: ccdc39 has been classified as Green List (High Evidence).
Mendeliome v0.4988 CCDC39 Zornitza Stark Phenotypes for gene: CCDC39 were changed from to Ciliary dyskinesia, primary, 14, MIM# 613807
Mendeliome v0.4987 CCDC39 Zornitza Stark Publications for gene: CCDC39 were set to
Mendeliome v0.4986 CCDC39 Zornitza Stark Mode of inheritance for gene: CCDC39 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4985 CCDC39 Zornitza Stark reviewed gene: CCDC39: Rating: GREEN; Mode of pathogenicity: None; Publications: 21131972, 23255504; Phenotypes: Ciliary dyskinesia, primary, 14, MIM# 613807; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4985 CCDC151 Zornitza Stark Gene: ccdc151 has been classified as Green List (High Evidence).
Mendeliome v0.4985 CCDC151 Zornitza Stark Phenotypes for gene: CCDC151 were changed from to Ciliary dyskinesia, primary, 30, MIM# 616037
Mendeliome v0.4984 CCDC151 Zornitza Stark Publications for gene: CCDC151 were set to
Mendeliome v0.4983 CCDC151 Zornitza Stark Mode of inheritance for gene: CCDC151 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4982 CCDC151 Zornitza Stark reviewed gene: CCDC151: Rating: GREEN; Mode of pathogenicity: None; Publications: 25192045, 25224326, 32490514, 32286033, 30504913; Phenotypes: Ciliary dyskinesia, primary, 30, MIM# 616037; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4982 CCDC114 Zornitza Stark Gene: ccdc114 has been classified as Green List (High Evidence).
Mendeliome v0.4982 CCDC114 Zornitza Stark Phenotypes for gene: CCDC114 were changed from to Ciliary dyskinesia, primary, 20, MIM# 615067
Mendeliome v0.4981 CCDC114 Zornitza Stark Publications for gene: CCDC114 were set to
Mendeliome v0.4980 CCDC114 Zornitza Stark Mode of inheritance for gene: CCDC114 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4979 CCDC114 Zornitza Stark reviewed gene: CCDC114: Rating: GREEN; Mode of pathogenicity: None; Publications: 23261303, 23261302, 32855706, 23506398; Phenotypes: Ciliary dyskinesia, primary, 20, MIM# 615067; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4979 CCDC103 Zornitza Stark Gene: ccdc103 has been classified as Green List (High Evidence).
Mendeliome v0.4979 CCDC103 Zornitza Stark Phenotypes for gene: CCDC103 were changed from to Ciliary dyskinesia, primary, 17, MIM# 614679
Mendeliome v0.4978 CCDC103 Zornitza Stark Publications for gene: CCDC103 were set to
Mendeliome v0.4977 CCDC103 Zornitza Stark Mode of inheritance for gene: CCDC103 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4976 CCDC103 Zornitza Stark Tag founder tag was added to gene: CCDC103.
Mendeliome v0.4976 CCDC103 Zornitza Stark reviewed gene: CCDC103: Rating: GREEN; Mode of pathogenicity: None; Publications: 22581229, 32447765, 31858719, 28790179; Phenotypes: Ciliary dyskinesia, primary, 17, MIM# 614679; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4976 GARS Zornitza Stark Gene: gars has been classified as Green List (High Evidence).
Mendeliome v0.4976 GARS Zornitza Stark Phenotypes for gene: GARS were changed from to Spinal muscular atrophy, infantile, James type, MIM# 619042; Charcot-Marie-Tooth disease, type 2D, MIM# 601472; Neuronopathy, distal hereditary motor, type VA, MIM# 600794; Multi-system mitochondrial disorder
Mendeliome v0.4975 GARS Zornitza Stark Publications for gene: GARS were set to
Mendeliome v0.4974 GARS Zornitza Stark Mode of inheritance for gene: GARS was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4973 GARS Zornitza Stark Tag new gene name tag was added to gene: GARS.
Mendeliome v0.4973 GARS Zornitza Stark reviewed gene: GARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 17101916, 22462675, 31985473, 32181591, 12690580, 25168514, 26503042, 29648643, 16982418, 24669931, 28594869; Phenotypes: Spinal muscular atrophy, infantile, James type, MIM# 619042, Charcot-Marie-Tooth disease, type 2D, MIM# 601472, Neuronopathy, distal hereditary motor, type VA, MIM# 600794, Multi-system mitochondrial disorder; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4973 SELENON Zornitza Stark Gene: selenon has been classified as Green List (High Evidence).
Mendeliome v0.4973 SELENON Zornitza Stark Phenotypes for gene: SELENON were changed from to Myopathy, congenital, with fiber-type disproportion, MIM# 255310; Muscular dystrophy, rigid spine, 1, MIM# 602771
Mendeliome v0.4972 SELENON Zornitza Stark Publications for gene: SELENON were set to
Mendeliome v0.4971 SELENON Zornitza Stark Mode of inheritance for gene: SELENON was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4970 SELENON Zornitza Stark reviewed gene: SELENON: Rating: GREEN; Mode of pathogenicity: None; Publications: 11528383, 12192640, 16365872, 21131290, 21131290, 32154989, 32796131; Phenotypes: Myopathy, congenital, with fiber-type disproportion, MIM# 255310, Muscular dystrophy, rigid spine, 1, MIM# 602771; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4970 TNNT1 Zornitza Stark Marked gene: TNNT1 as ready
Mendeliome v0.4970 TNNT1 Zornitza Stark Gene: tnnt1 has been classified as Green List (High Evidence).
Mendeliome v0.4970 TNNT1 Zornitza Stark Phenotypes for gene: TNNT1 were changed from to Nemaline myopathy 5, Amish type, MIM# 605355
Mendeliome v0.4969 TNNT1 Zornitza Stark Mode of inheritance for gene: TNNT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4968 TNNT1 Zornitza Stark reviewed gene: TNNT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 10952871, 32994279, 32819427, 31970803, 31604653, 29931346, 29178646; Phenotypes: Nemaline myopathy 5, Amish type, MIM# 605355; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4968 TNNT3 Zornitza Stark Marked gene: TNNT3 as ready
Mendeliome v0.4968 TNNT3 Zornitza Stark Gene: tnnt3 has been classified as Green List (High Evidence).
Mendeliome v0.4968 TNNT3 Zornitza Stark Phenotypes for gene: TNNT3 were changed from to Arthrogryposis, distal, type 2B2, MIM# 618435
Mendeliome v0.4967 TNNT3 Zornitza Stark Publications for gene: TNNT3 were set to
Mendeliome v0.4966 TNNT3 Zornitza Stark Mode of pathogenicity for gene: TNNT3 was changed from to Other
Mendeliome v0.4965 TNNT3 Zornitza Stark Mode of inheritance for gene: TNNT3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4964 TNNT3 Zornitza Stark reviewed gene: TNNT3: Rating: GREEN; Mode of pathogenicity: Other; Publications: 12865991, 19142688, 21402185, 25337069, 17194691; Phenotypes: Arthrogryposis, distal, type 2B2, MIM# 618435; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4964 STAC3 Zornitza Stark Marked gene: STAC3 as ready
Mendeliome v0.4964 STAC3 Zornitza Stark Gene: stac3 has been classified as Green List (High Evidence).
Mendeliome v0.4964 STAC3 Zornitza Stark Tag founder tag was added to gene: STAC3.
Mendeliome v0.4964 STAC3 Zornitza Stark Phenotypes for gene: STAC3 were changed from to Myopathy, congenital, Baily-Bloch, MIM# 255995
Mendeliome v0.4963 STAC3 Zornitza Stark Publications for gene: STAC3 were set to
Mendeliome v0.4962 STAC3 Zornitza Stark Mode of inheritance for gene: STAC3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4961 STAC3 Zornitza Stark reviewed gene: STAC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 23736855, 28411587, 28777491, 30168660; Phenotypes: Myopathy, congenital, Baily-Bloch, MIM# 255995; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4961 SPEG Zornitza Stark Gene: speg has been classified as Green List (High Evidence).
Mendeliome v0.4961 SPEG Zornitza Stark Phenotypes for gene: SPEG were changed from to Centronuclear myopathy 5, MIM# 615959
Mendeliome v0.4960 SPEG Zornitza Stark Publications for gene: SPEG were set to
Mendeliome v0.4959 SPEG Zornitza Stark Mode of inheritance for gene: SPEG was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4958 SPEG Zornitza Stark reviewed gene: SPEG: Rating: GREEN; Mode of pathogenicity: None; Publications: 25087613, 31625632, 30412272, 30157964, 29614691, 29474540, 28624463, 26578207, 25087613; Phenotypes: Centronuclear myopathy 5, MIM# 615959; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4958 TPM3 Zornitza Stark Marked gene: TPM3 as ready
Mendeliome v0.4958 TPM3 Zornitza Stark Gene: tpm3 has been classified as Green List (High Evidence).
Mendeliome v0.4958 TPM3 Zornitza Stark Phenotypes for gene: TPM3 were changed from to CAP myopathy 1, MIM# 609284; Myopathy, congenital, with fiber-type disproportion, MIM# 255310; Nemaline myopathy 1, autosomal dominant or recessive, MIM# 609284; Congenital muscle stiffness
Mendeliome v0.4957 TPM3 Zornitza Stark Publications for gene: TPM3 were set to
Mendeliome v0.4956 TPM3 Zornitza Stark Mode of pathogenicity for gene: TPM3 was changed from to Other
Mendeliome v0.4955 TPM3 Zornitza Stark Mode of inheritance for gene: TPM3 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4954 TPM3 Zornitza Stark reviewed gene: TPM3: Rating: GREEN; Mode of pathogenicity: Other; Publications: 26418456, 7704029, 17376686, 18382475, 19487656; Phenotypes: CAP myopathy 1, MIM# 609284, Myopathy, congenital, with fiber-type disproportion, MIM# 255310, Nemaline myopathy 1, autosomal dominant or recessive, MIM# 609284, Congenital muscle stiffness; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4954 MICU1 Zornitza Stark Tag founder tag was added to gene: MICU1.
Mendeliome v0.4954 MICU1 Zornitza Stark Gene: micu1 has been classified as Green List (High Evidence).
Mendeliome v0.4954 MICU1 Zornitza Stark Phenotypes for gene: MICU1 were changed from to Myopathy with extrapyramidal signs, MIM# 615673
Mendeliome v0.4953 MICU1 Zornitza Stark Publications for gene: MICU1 were set to
Mendeliome v0.4952 MICU1 Zornitza Stark Mode of inheritance for gene: MICU1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4951 MICU1 Zornitza Stark reviewed gene: MICU1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24336167, 29721912, 32395406; Phenotypes: Myopathy with extrapyramidal signs, MIM# 615673; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4951 LMOD3 Zornitza Stark Gene: lmod3 has been classified as Green List (High Evidence).
Mendeliome v0.4951 LMOD3 Zornitza Stark Phenotypes for gene: LMOD3 were changed from to Nemaline myopathy 10, MIM# 616165
Mendeliome v0.4950 LMOD3 Zornitza Stark Publications for gene: LMOD3 were set to
Mendeliome v0.4949 LMOD3 Zornitza Stark Mode of inheritance for gene: LMOD3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4948 LMOD3 Zornitza Stark reviewed gene: LMOD3: Rating: GREEN; Mode of pathogenicity: None; Publications: 25250574, 30291184, 28815944, 30642739; Phenotypes: Nemaline myopathy 10, MIM# 616165; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4948 PIBF1 Zornitza Stark Publications for gene: PIBF1 were set to 26167768; 30858804; 29695797
Mendeliome v0.4947 PIBF1 Sarah Righetti reviewed gene: PIBF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33004012; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.4947 MYH2 Zornitza Stark Gene: myh2 has been classified as Green List (High Evidence).
Mendeliome v0.4947 MYH2 Zornitza Stark Phenotypes for gene: MYH2 were changed from to Proximal myopathy and ophthalmoplegia, MIM# 605637
Mendeliome v0.4946 MYH2 Zornitza Stark Publications for gene: MYH2 were set to
Mendeliome v0.4945 MYH2 Zornitza Stark Mode of inheritance for gene: MYH2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4944 MYH2 Zornitza Stark reviewed gene: MYH2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20418530, 15548556, 24193343, 11114175, 23489661, 32578970, 29934118, 28729039, 27490141, 27177998; Phenotypes: Proximal myopathy and ophthalmoplegia, MIM# 605637; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4944 KLHL41 Zornitza Stark Gene: klhl41 has been classified as Green List (High Evidence).
Mendeliome v0.4944 KLHL41 Zornitza Stark Phenotypes for gene: KLHL41 were changed from to Nemaline myopathy 9, MIM# 615731
Mendeliome v0.4943 KLHL41 Zornitza Stark Publications for gene: KLHL41 were set to
Mendeliome v0.4942 KLHL41 Zornitza Stark Mode of inheritance for gene: KLHL41 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4941 KLHL41 Zornitza Stark reviewed gene: KLHL41: Rating: GREEN; Mode of pathogenicity: None; Publications: 24268659, 30986853, 28939701, 28826497; Phenotypes: Nemaline myopathy 9, MIM# 615731; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4941 KLHL40 Zornitza Stark Tag founder tag was added to gene: KLHL40.
Mendeliome v0.4941 KLHL40 Zornitza Stark Gene: klhl40 has been classified as Green List (High Evidence).
Mendeliome v0.4941 KLHL40 Zornitza Stark Phenotypes for gene: KLHL40 were changed from to Nemaline myopathy 8, autosomal recessive, MIM# 615348
Mendeliome v0.4940 KLHL40 Zornitza Stark Publications for gene: KLHL40 were set to
Mendeliome v0.4939 KLHL40 Zornitza Stark Mode of inheritance for gene: KLHL40 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4938 KLHL40 Zornitza Stark reviewed gene: KLHL40: Rating: GREEN; Mode of pathogenicity: None; Publications: 23746549, 24960163, 32352246, 31908664, 27528495; Phenotypes: Nemaline myopathy 8, autosomal recessive, MIM# 615348; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4938 MYO18B Zornitza Stark Gene: myo18b has been classified as Green List (High Evidence).
Mendeliome v0.4938 MYO18B Zornitza Stark Phenotypes for gene: MYO18B were changed from to Klippel-Feil syndrome 4, autosomal recessive, with myopathy and facial dysmorphism, MIM# 616549
Mendeliome v0.4937 MYO18B Zornitza Stark Publications for gene: MYO18B were set to
Mendeliome v0.4936 MYO18B Zornitza Stark Mode of inheritance for gene: MYO18B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4935 MYO18B Zornitza Stark reviewed gene: MYO18B: Rating: GREEN; Mode of pathogenicity: None; Publications: 25748484, 27858739, 32637634, 32184166, 27879346; Phenotypes: Klippel-Feil syndrome 4, autosomal recessive, with myopathy and facial dysmorphism, MIM# 616549; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4935 MEGF10 Zornitza Stark Gene: megf10 has been classified as Green List (High Evidence).
Mendeliome v0.4935 MEGF10 Zornitza Stark Phenotypes for gene: MEGF10 were changed from to Myopathy, areflexia, respiratory distress, and dysphagia, early-onset, MIM# 614399
Mendeliome v0.4934 MEGF10 Zornitza Stark Publications for gene: MEGF10 were set to
Mendeliome v0.4933 MEGF10 Zornitza Stark Mode of inheritance for gene: MEGF10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4932 MEGF10 Zornitza Stark reviewed gene: MEGF10: Rating: GREEN; Mode of pathogenicity: None; Publications: 22101682, 22371254, 30802937; Phenotypes: Myopathy, areflexia, respiratory distress, and dysphagia, early-onset, MIM# 614399; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4932 WDPCP Zornitza Stark Publications for gene: WDPCP were set to 20671153; 25427950
Mendeliome v0.4931 WDPCP Zornitza Stark Classified gene: WDPCP as Green List (high evidence)
Mendeliome v0.4931 WDPCP Zornitza Stark Gene: wdpcp has been classified as Green List (High Evidence).
Mendeliome v0.4930 WDPCP Zornitza Stark commented on gene: WDPCP: Four families reported with ciliopathy phenotypes, including BBS, OFD, syndromic retinopathy.
Mendeliome v0.4930 WDPCP Zornitza Stark edited their review of gene: WDPCP: Changed rating: GREEN; Changed publications: 20671153, 25427950, 32055034, 29588463, 28289185; Changed phenotypes: Bardet-Biedl syndrome 15, MIM# 615992, OFD, Congenital heart defects, hamartomas of tongue, and polysyndactyly, 217085
Mendeliome v0.4930 WDPCP Zornitza Stark Gene: wdpcp has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4930 WDPCP Zornitza Stark Phenotypes for gene: WDPCP were changed from Bardet-Biedl syndrome 15, MIM# 615992; OFD; Congenital heart defects, hamartomas of tongue, and polysyndactyly, 217085 to Bardet-Biedl syndrome 15, MIM# 615992; OFD; Congenital heart defects, hamartomas of tongue, and polysyndactyly, 217085
Mendeliome v0.4930 WDPCP Zornitza Stark Phenotypes for gene: WDPCP were changed from to Bardet-Biedl syndrome 15, MIM# 615992; OFD; Congenital heart defects, hamartomas of tongue, and polysyndactyly, 217085
Mendeliome v0.4929 WDPCP Zornitza Stark Publications for gene: WDPCP were set to
Mendeliome v0.4928 WDPCP Zornitza Stark Mode of inheritance for gene: WDPCP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4927 WDPCP Zornitza Stark Classified gene: WDPCP as Amber List (moderate evidence)
Mendeliome v0.4927 WDPCP Zornitza Stark Gene: wdpcp has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4926 WDPCP Zornitza Stark reviewed gene: WDPCP: Rating: AMBER; Mode of pathogenicity: None; Publications: 20671153, 25427950; Phenotypes: Bardet-Biedl syndrome 15, MIM# 615992, OFD; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4926 TUBGCP4 Zornitza Stark Marked gene: TUBGCP4 as ready
Mendeliome v0.4926 TUBGCP4 Zornitza Stark Gene: tubgcp4 has been classified as Green List (High Evidence).
Mendeliome v0.4926 TUBGCP4 Zornitza Stark Phenotypes for gene: TUBGCP4 were changed from to Microcephaly and chorioretinopathy, autosomal recessive, 3, MIM# 616335
Mendeliome v0.4925 TUBGCP4 Zornitza Stark Publications for gene: TUBGCP4 were set to
Mendeliome v0.4924 TUBGCP4 Zornitza Stark Mode of inheritance for gene: TUBGCP4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4923 TUBGCP4 Zornitza Stark reviewed gene: TUBGCP4: Rating: GREEN; Mode of pathogenicity: None; Publications: 25817018, 32270730; Phenotypes: Microcephaly and chorioretinopathy, autosomal recessive, 3, MIM# 616335; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4923 DYNC2LI1 Zornitza Stark Gene: dync2li1 has been classified as Green List (High Evidence).
Mendeliome v0.4923 DYNC2LI1 Zornitza Stark Phenotypes for gene: DYNC2LI1 were changed from to Short-rib thoracic dysplasia 15 with polydactyly (MIM#617088)
Mendeliome v0.4922 DYNC2LI1 Zornitza Stark Publications for gene: DYNC2LI1 were set to
Mendeliome v0.4921 DYNC2LI1 Zornitza Stark Mode of inheritance for gene: DYNC2LI1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4920 SLC20A2 Zornitza Stark Phenotypes for gene: SLC20A2 were changed from Basal ganglia calcification, idiopathic, 1, MIM# 213600 to Basal ganglia calcification, idiopathic, 1, MIM# 213600; ?hereditary multiple exostoses
Mendeliome v0.4919 SLC20A2 Zornitza Stark Publications for gene: SLC20A2 were set to 22327515; 23334463
Mendeliome v0.4918 TRAPPC9 Zornitza Stark Publications for gene: TRAPPC9 were set to 22549410; 20004765; 20004763; 30853973
Mendeliome v0.4917 TRAPPC9 Zornitza Stark Tag SV/CNV tag was added to gene: TRAPPC9.
Mendeliome v0.4917 DYNC2LI1 Ain Roesley reviewed gene: DYNC2LI1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33030252; Phenotypes: Short-rib thoracic dysplasia 15 with polydactyly (MIM#617088); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4917 SLC20A2 Elena Savva reviewed gene: SLC20A2: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID 24209445, 23437308, 32705272, 27943094; Phenotypes: Basal ganglia calcification, idiopathic, 1213600, ?hereditary multiple exostoses; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.4917 TRAPPC9 Elena Savva edited their review of gene: TRAPPC9: Added comment: PMID: 29187737 - multiple intragenic CNVs reported for this gene; Changed publications: PMID: 29187737
Mendeliome v0.4917 GPC6 Zornitza Stark Publications for gene: GPC6 were set to 19481194
Mendeliome v0.4916 GPC6 Elena Savva reviewed gene: GPC6: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 19481194, 32655339; Phenotypes: Omodysplasia 1 MIM#258315; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4916 FKBP14 Zornitza Stark Gene: fkbp14 has been classified as Green List (High Evidence).
Mendeliome v0.4916 FKBP14 Zornitza Stark Phenotypes for gene: FKBP14 were changed from to Ehlers-Danlos syndrome, kyphoscoliotic type, 2, MIM# 614557
Mendeliome v0.4915 FKBP14 Zornitza Stark Publications for gene: FKBP14 were set to
Mendeliome v0.4914 FKBP14 Zornitza Stark Mode of inheritance for gene: FKBP14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4913 FKBP14 Zornitza Stark reviewed gene: FKBP14: Rating: GREEN; Mode of pathogenicity: None; Publications: 22265013, 24773188, 27149304, 31132235, 30561154, 28617417; Phenotypes: Ehlers-Danlos syndrome, kyphoscoliotic type, 2, MIM# 614557; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4913 EPG5 Zornitza Stark Gene: epg5 has been classified as Green List (High Evidence).
Mendeliome v0.4913 EPG5 Zornitza Stark Phenotypes for gene: EPG5 were changed from to Vici syndrome, MIM# 242840
Mendeliome v0.4912 EPG5 Zornitza Stark Publications for gene: EPG5 were set to
Mendeliome v0.4911 EPG5 Zornitza Stark Mode of inheritance for gene: EPG5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4910 EPG5 Zornitza Stark reviewed gene: EPG5: Rating: GREEN; Mode of pathogenicity: None; Publications: 23222957, 26917586; Phenotypes: Vici syndrome, MIM# 242840, vacuolar myopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4910 LMX1B Zornitza Stark Gene: lmx1b has been classified as Green List (High Evidence).
Mendeliome v0.4910 LMX1B Zornitza Stark Phenotypes for gene: LMX1B were changed from to Nail-patella syndrome (MIM#161200); LMX1B-related nephropathy
Mendeliome v0.4909 LMX1B Zornitza Stark Publications for gene: LMX1B were set to
Mendeliome v0.4908 LMX1B Zornitza Stark Mode of inheritance for gene: LMX1B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4907 SEMA4A Zornitza Stark Gene: sema4a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4907 SEMA4A Zornitza Stark Phenotypes for gene: SEMA4A were changed from to Cone-rod dystrophy 10, 610283; Retinitis pigmentosa 35, 610282
Mendeliome v0.4906 SEMA4A Zornitza Stark Publications for gene: SEMA4A were set to
Mendeliome v0.4905 SEMA4A Zornitza Stark Mode of inheritance for gene: SEMA4A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4904 SEMA4A Zornitza Stark Classified gene: SEMA4A as Amber List (moderate evidence)
Mendeliome v0.4904 SEMA4A Zornitza Stark Gene: sema4a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4903 SEMA4A Zornitza Stark reviewed gene: SEMA4A: Rating: AMBER; Mode of pathogenicity: None; Publications: 16199541, 28805479, 23360997, 15277503; Phenotypes: Cone-rod dystrophy 10, 610283, Retinitis pigmentosa 35, 610282; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4903 LMX1B Teresa Zhao reviewed gene: LMX1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 27450397; Phenotypes: Nail-patella syndrome (MIM#161200), LMX1B-related nephropathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.4903 JPH2 Zornitza Stark Gene: jph2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4903 JPH2 Zornitza Stark Phenotypes for gene: JPH2 were changed from to Cardiomyopathy, hypertrophic, MIM#613873; dilated cardiomyopathy
Mendeliome v0.4902 JPH2 Zornitza Stark Publications for gene: JPH2 were set to
Mendeliome v0.4901 JPH2 Zornitza Stark Mode of inheritance for gene: JPH2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4900 JPH2 Zornitza Stark Classified gene: JPH2 as Amber List (moderate evidence)
Mendeliome v0.4900 JPH2 Zornitza Stark Gene: jph2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4899 JPH2 Zornitza Stark reviewed gene: JPH2: Rating: AMBER; Mode of pathogenicity: None; Publications: 30681346, 17509612, 23973696, 26869393, 28393127, 30235249, 31227780; Phenotypes: Cardiomyopathy, hypertrophic, MIM#613873, dilated cardiomyopathy; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4899 RGR Zornitza Stark Tag disputed tag was added to gene: RGR.
Mendeliome v0.4899 RGR Zornitza Stark Gene: rgr has been classified as Red List (Low Evidence).
Mendeliome v0.4899 RGR Zornitza Stark Phenotypes for gene: RGR were changed from to Retinitis pigmentosa 44, MIM# 613769
Mendeliome v0.4898 RGR Zornitza Stark Publications for gene: RGR were set to
Mendeliome v0.4897 RGR Zornitza Stark Mode of inheritance for gene: RGR was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4896 RGR Zornitza Stark Classified gene: RGR as Red List (low evidence)
Mendeliome v0.4896 RGR Zornitza Stark Gene: rgr has been classified as Red List (Low Evidence).
Mendeliome v0.4895 RGR Zornitza Stark reviewed gene: RGR: Rating: RED; Mode of pathogenicity: None; Publications: 10581022, 30347075, 27748892, 27623334; Phenotypes: Retinitis pigmentosa 44, MIM# 613769; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4895 RDH11 Zornitza Stark Gene: rdh11 has been classified as Red List (Low Evidence).
Mendeliome v0.4895 RDH11 Zornitza Stark gene: RDH11 was added
gene: RDH11 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: RDH11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RDH11 were set to 24916380; 15634683; 30731079; 18326732
Phenotypes for gene: RDH11 were set to Retinal dystrophy, juvenile cataracts, and short stature syndrome, MIM# 616108
Review for gene: RDH11 was set to RED
Added comment: Single family reported with compound heterozygous LOF variants segregating with disease in three siblings. Some functional data, but note mouse KO did not have eye phenotype.
Sources: Expert list
Mendeliome v0.4894 CEP112 Zornitza Stark Gene: cep112 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4894 CEP112 Zornitza Stark Phenotypes for gene: CEP112 were changed from Acephalic spermatozoa; infertility to Spermatogenic failure 44, MIM#619044; Acephalic spermatozoa; infertility
Mendeliome v0.4893 CEP112 Zornitza Stark reviewed gene: CEP112: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Spermatogenic failure 44, MIM#619044; Mode of inheritance: None
Mendeliome v0.4893 SVIL Zornitza Stark Phenotypes for gene: SVIL were changed from myopathy to Myofibrillar myopathy, MIM#619040
Mendeliome v0.4892 SVIL Zornitza Stark edited their review of gene: SVIL: Changed rating: AMBER; Changed phenotypes: Myofibrillar myopathy, MIM#619040
Mendeliome v0.4892 PRDM13 Zornitza Stark Tag SV/CNV tag was added to gene: PRDM13.
Tag 5'UTR tag was added to gene: PRDM13.
Mendeliome v0.4892 GPC6 Zornitza Stark Gene: gpc6 has been classified as Green List (High Evidence).
Mendeliome v0.4892 GPC6 Zornitza Stark Tag SV/CNV tag was added to gene: GPC6.
Mendeliome v0.4892 GPC6 Zornitza Stark Phenotypes for gene: GPC6 were changed from to Omodysplasia 1 (MIM#258315), AR
Mendeliome v0.4891 GPC6 Zornitza Stark Publications for gene: GPC6 were set to
Mendeliome v0.4890 GPC6 Zornitza Stark Mode of inheritance for gene: GPC6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4889 GPC6 Kristin Rigbye reviewed gene: GPC6: Rating: GREEN; Mode of pathogenicity: None; Publications: 19481194; Phenotypes: Omodysplasia 1 (MIM#258315), AR; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4889 SPATA7 Zornitza Stark Marked gene: SPATA7 as ready
Mendeliome v0.4889 SPATA7 Zornitza Stark Gene: spata7 has been classified as Green List (High Evidence).
Mendeliome v0.4889 SPATA7 Zornitza Stark Phenotypes for gene: SPATA7 were changed from to Leber congenital amaurosis 3, MIM#604232; Autosomal recessive juvenile retinitis pigmentosa, MIM#604232
Mendeliome v0.4888 SPATA7 Zornitza Stark Publications for gene: SPATA7 were set to
Mendeliome v0.4887 SPATA7 Zornitza Stark Mode of inheritance for gene: SPATA7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4886 SPATA7 Chern Lim reviewed gene: SPATA7: Rating: GREEN; Mode of pathogenicity: None; Publications: 31908400, 32799588; Phenotypes: Leber congenital amaurosis 3, MIM#604232, Autosomal recessive juvenile retinitis pigmentosa, MIM#604232; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.4886 KIRREL3 Zornitza Stark Gene: kirrel3 has been classified as Red List (Low Evidence).
Mendeliome v0.4886 KIRREL3 Zornitza Stark gene: KIRREL3 was added
gene: KIRREL3 was added to Mendeliome. Sources: Expert list
refuted tags were added to gene: KIRREL3.
Mode of inheritance for gene: KIRREL3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIRREL3 were set to 19012874
Phenotypes for gene: KIRREL3 were set to Intellectual disability
Review for gene: KIRREL3 was set to RED
Added comment: Variants associated with ID have now been re-classified based on population frequency.
Sources: Expert list
Mendeliome v0.4885 NEUROD1 Zornitza Stark Gene: neurod1 has been classified as Green List (High Evidence).
Mendeliome v0.4885 NEUROD1 Zornitza Stark Phenotypes for gene: NEUROD1 were changed from to Maturity-onset diabetes of the young 6, MIM#606394; Retinitis pigmentosa, retinopathy, permanent neonatal diabetes
Mendeliome v0.4884 NEUROD1 Zornitza Stark Publications for gene: NEUROD1 were set to
Mendeliome v0.4883 NEUROD1 Zornitza Stark Mode of inheritance for gene: NEUROD1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4882 NEUROD1 Zornitza Stark reviewed gene: NEUROD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25477324, 25684977, 22784109, 29521454; Phenotypes: Maturity-onset diabetes of the young 6, MIM#606394, Retinitis pigmentosa, retinopathy, permanent neonatal diabetes; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4882 DNAAF4 Zornitza Stark Tag SV/CNV tag was added to gene: DNAAF4.
Tag founder tag was added to gene: DNAAF4.
Mendeliome v0.4882 DNAAF4 Zornitza Stark Gene: dnaaf4 has been classified as Green List (High Evidence).
Mendeliome v0.4882 DNAAF4 Zornitza Stark Phenotypes for gene: DNAAF4 were changed from to Ciliary dyskinesia, primary, 25, MIM# 615482
Mendeliome v0.4881 DNAAF4 Zornitza Stark Publications for gene: DNAAF4 were set to
Mendeliome v0.4880 DNAAF4 Zornitza Stark Mode of inheritance for gene: DNAAF4 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4880 DNAAF4 Zornitza Stark Mode of inheritance for gene: DNAAF4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4879 DNAAF4 Zornitza Stark reviewed gene: DNAAF4: Rating: GREEN; Mode of pathogenicity: None; Publications: 23872636; Phenotypes: Ciliary dyskinesia, primary, 25, MIM# 615482; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4879 MAG Zornitza Stark Phenotypes for gene: MAG were changed from Spastic paraplegia 75, autosomal recessive, MIM# 616680 to Spastic paraplegia 75, autosomal recessive, MIM# 616680; Cerebellar ataxia
Mendeliome v0.4878 MAG Zornitza Stark changed review comment from: Spastic paraplegia-75 is an autosomal recessive, slowly progressive neurodegenerative disorder characterized by onset of spastic paraplegia and cognitive impairment in childhood. Eight unrelated families reported.; to: Spastic paraplegia-75 is an autosomal recessive, slowly progressive neurodegenerative disorder characterized by onset of spastic paraplegia and cognitive impairment in childhood. Eight unrelated families reported with variable combinations of psychomotor delay, ataxia, eye movement abnormalities, spasticity, dystonia, and neuropathic symptoms.
Mendeliome v0.4878 GZF1 Zornitza Stark Gene: gzf1 has been classified as Green List (High Evidence).
Mendeliome v0.4878 GZF1 Zornitza Stark Phenotypes for gene: GZF1 were changed from to Joint laxity, short stature, and myopia, MIM# 617662; Larsen-like syndrome
Mendeliome v0.4877 GZF1 Zornitza Stark Publications for gene: GZF1 were set to
Mendeliome v0.4876 GZF1 Zornitza Stark Mode of inheritance for gene: GZF1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4875 GZF1 Zornitza Stark reviewed gene: GZF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33009817, 28475863; Phenotypes: Joint laxity, short stature, and myopia, MIM# 617662, Larsen-like syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4875 ITFG2 Zornitza Stark Marked gene: ITFG2 as ready
Mendeliome v0.4875 ITFG2 Zornitza Stark Gene: itfg2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4875 ITFG2 Zornitza Stark Classified gene: ITFG2 as Amber List (moderate evidence)
Mendeliome v0.4875 ITFG2 Zornitza Stark Gene: itfg2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4874 ITFG2 Zornitza Stark gene: ITFG2 was added
gene: ITFG2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ITFG2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ITFG2 were set to 28397838; https://doi.org/10.1038/s41525-020-00150-z
Phenotypes for gene: ITFG2 were set to Neurodevelopmental abnormality; Intellectual disability; Developmental regression; Ataxia
Review for gene: ITFG2 was set to AMBER
Added comment: ITFG2 was suggested to be a candidate gene for autosomal recessive ID in the study by Harripaul et al (2018 - PMID: 28397838). The authors performed microarray and exome sequencing in 192 consanguineous families and identified a homozygous ITGF2 stopgain variant (NM_018463.3:c.472G>T / p.Glu158*) along with 3 additional variants segregating with ID within an investigated family (PK51). Cheema et al (2020 - https://doi.org/10.1038/s41525-020-00150-z) report briefly on a male, born to consanguineous parents presenting with NDD, seizures, regression and ataxia. There was a similarly affected female sibling. Evaluation of ROH revealed a homozygous ITFG2 nonsense variant [NM_018463.3:c.361C>T / p.(Gln121*)]. Families in this study were investigated by trio WES or WGS. Evaluation of data of the same lab revealed 3 additional unrelated subjects with overlapping phenotypes, notably NDD and ataxia. These individuals were - each - homozygous for pLoF variants [NM_018463.3:c.848-1G>A; NM_018463.3:c.704dupC, p.(Ala236fs), NM_018463.3:c.1000_1001delAT, p.(Ile334fs)]. As discussed in OMIM, ITFG2 encodes a subunit of the KICSTOR protein complex, having a role in regulating nutrient sensing by MTOR complex-1 (Wolfson et al 2017 - PMID : 28199306).

Rated Amber as Cheema et al report on diagnostic outcomes and multiple candidate genes as part of a heterogenous cohort and details are therefore limited.
Sources: Literature
Mendeliome v0.4873 SHMT2 Zornitza Stark Marked gene: SHMT2 as ready
Mendeliome v0.4873 SHMT2 Zornitza Stark Gene: shmt2 has been classified as Green List (High Evidence).
Mendeliome v0.4873 SHMT2 Zornitza Stark Classified gene: SHMT2 as Green List (high evidence)
Mendeliome v0.4873 SHMT2 Zornitza Stark Gene: shmt2 has been classified as Green List (High Evidence).
Mendeliome v0.4872 SHMT2 Zornitza Stark gene: SHMT2 was added
gene: SHMT2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SHMT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SHMT2 were set to 33015733
Phenotypes for gene: SHMT2 were set to Congenital microcephaly; Infantile axial hypotonia; Spastic paraparesis; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum; Abnormal cortical gyration; Hypertrophic cardiomyopathy; Abnormality of the face; Proximal placement of thumb; 2-3 toe syndactyly
Review for gene: SHMT2 was set to GREEN
Added comment: García‑Cazorla et al. (2020 - PMID: 33015733) report 5 individuals (from 4 families) with a novel brain and heart developmental syndrome caused by biallelic SHMT2 pathogenic variants.

All affected subjects presented similar phenotype incl. microcephaly at birth (5/5 with OFC < -2 SD though in 2/5 cases N OFC was observed later), DD and ID (1/5 mild-moderate, 1/5 moderate, 3/5 severe), motor dysfunction in the form of spastic (5/5) paraparesis, ataxia/dysmetria (3/4), intention tremor (in 3/?) and/or peripheral neuropathy (2 sibs). They exhibited corpus callosum hypoplasia (5/5) and perisylvian microgyria-like pattern (4/5). Cardiac problems were reported in all, with hypertrophic cardiomyopathy in 4/5 (from 3 families) and atrial-SD in the 5th individual (1/5). Common dysmorphic features incl. long palpebral/fissures, eversion of lateral third of lower eylids, arched eyebrows, long eyelashes, thin upper lip, short Vth finger, fetal pads, mild 2-3 toe syndactyly, proximally placed thumbs.

Biallelic variants were identified following exome sequencing in all (other investigations not mentioned). Identified variants were in all cases missense SNVs or in-frame del, which together with evidence from population databases and mouse model might suggest a hypomorphic effect of variants and intolerance/embryonic lethality for homozygous LoF ones.

SHMT2 encodes the mitohondrial form of serine hydroxymethyltransferase. The enzyme transfers one-carbon units from serine to tetrahydrofolate (THF) and generates glycine and 5,10,methylene-THF.

Mitochondrial defect was suggested by presence of ragged red fibers in myocardial biopsy of one patient. Quadriceps and myocardial biopsies of the same individual were overall suggestive of myopathic changes.

While plasma metabolites were within N range and SHMT2 protein levels not significantly altered in patient fibroblasts, the authors provide evidence for impaired enzymatic function eg. presence of the SHMT2 substrate (THF) in patient but not control (mitochondria-enriched) fibroblasts , decrease in glycine/serine ratios, impared folate metabolism. Patient fibroblasts displayed impaired oxidative capacity (reduced ATP levels in a medium without glucose, diminished oxygen consumption rates). Mitochondrial membrane potential and ROS levels were also suggestive of redox malfunction.

Shmt2 ko in mice was previously shown to be embryonically lethal attributed to severe mitochondrial respiration defects, although there was no observed brain metabolic defect.

The authors performed Shmt2 knockdown in motoneurons in Drosophila, demonstrating neuromuscular junction (# of satellite boutons) and motility defects (climbing distance/velocity).
Sources: Literature
Mendeliome v0.4871 DHX38 Zornitza Stark Gene: dhx38 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4871 DHX38 Zornitza Stark Phenotypes for gene: DHX38 were changed from to Retinitis pigmentosa 84, MIM# 618220
Mendeliome v0.4870 DHX38 Zornitza Stark Publications for gene: DHX38 were set to
Mendeliome v0.4869 DHX38 Zornitza Stark Mode of inheritance for gene: DHX38 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4868 DHX38 Zornitza Stark Classified gene: DHX38 as Amber List (moderate evidence)
Mendeliome v0.4868 DHX38 Zornitza Stark Gene: dhx38 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4867 DHX38 Zornitza Stark reviewed gene: DHX38: Rating: AMBER; Mode of pathogenicity: None; Publications: 24737827, 30208423; Phenotypes: Retinitis pigmentosa 84, MIM# 618220; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4867 CCT2 Zornitza Stark Marked gene: CCT2 as ready
Mendeliome v0.4867 CCT2 Zornitza Stark Gene: cct2 has been classified as Red List (Low Evidence).
Mendeliome v0.4867 CCT2 Zornitza Stark gene: CCT2 was added
gene: CCT2 was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: CCT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCT2 were set to 27645772; 29450543
Phenotypes for gene: CCT2 were set to Leber's congenital amaurosis
Review for gene: CCT2 was set to RED
Added comment: Single family reported with compound het missense variants, functional data, including animal model.
Sources: NHS GMS
Mendeliome v0.4866 CA4 Zornitza Stark Gene: ca4 has been classified as Red List (Low Evidence).
Mendeliome v0.4866 CA4 Zornitza Stark Phenotypes for gene: CA4 were changed from to Retinitis pigmentosa 17, MIM# 600852
Mendeliome v0.4865 CA4 Zornitza Stark Publications for gene: CA4 were set to
Mendeliome v0.4864 CA4 Zornitza Stark Mode of inheritance for gene: CA4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4863 CA4 Zornitza Stark Classified gene: CA4 as Red List (low evidence)
Mendeliome v0.4863 CA4 Zornitza Stark Gene: ca4 has been classified as Red List (Low Evidence).
Mendeliome v0.4862 CA4 Zornitza Stark reviewed gene: CA4: Rating: RED; Mode of pathogenicity: None; Publications: 15563508, 15090652, 17652713, 16260723; Phenotypes: Retinitis pigmentosa 17, MIM# 600852; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4862 VPS41 Zornitza Stark Gene: vps41 has been classified as Red List (Low Evidence).
Mendeliome v0.4862 VPS41 Zornitza Stark gene: VPS41 was added
gene: VPS41 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: VPS41 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS41 were set to 32808683
Phenotypes for gene: VPS41 were set to Dystonia; intellectual disability
Review for gene: VPS41 was set to RED
Added comment: Single individual reported with homozygous canonical splice site variant resulting in exon 7 skipping, and global developmental delay and generalized dystonia. He attained a few words and voluntary limb movements but never sat unsupported. He had pale optic discs and an axonal neuropathy. From 6 years of age, his condition began to deteriorate, with reduced motor abilities and alertness. An MRI of the brain showed atrophy of the superior cerebellar vermis and slimming of the posterior limb of the corpus callosum. VPS41 is component of the HOPS complex and other genes in the complex have been implicated in movement disorders.
Sources: Literature
Mendeliome v0.4861 VPS16 Zornitza Stark edited their review of gene: VPS16: Changed rating: GREEN
Mendeliome v0.4861 VPS16 Zornitza Stark Gene: vps16 has been classified as Green List (High Evidence).
Mendeliome v0.4861 VPS16 Zornitza Stark Classified gene: VPS16 as Green List (high evidence)
Mendeliome v0.4861 VPS16 Zornitza Stark Gene: vps16 has been classified as Green List (High Evidence).
Mendeliome v0.4860 VPS16 Zornitza Stark gene: VPS16 was added
gene: VPS16 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: VPS16 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VPS16 were set to 32808683
Phenotypes for gene: VPS16 were set to Dystonia
Added comment: 18 individuals reported with high-impact variants in VPS16 and a progressive early onset dystonia (median age 12 years, range 3–50 years), with prominent oromandibular, bulbar, cervical, and upper limb involvement. Progressive generalization ensued, although most remained ambulant, and only a minority (16%) lost the ability to walk in adulthood. Additional clinical features of mild to moderate intellectual disability and neuropsychiatric symptoms were present in approximately one‐third. In 4 individuals, magnetic resonance imaging (MRI) showed bilateral and symmetrical hypointensity of the globi pallidi and sometimes also the midbrain and dentate nuclei, suggestive of iron deposition. Mild generalized cerebral atrophy was also apparent in 4 individuals.
Sources: Literature
Mendeliome v0.4859 KRIT1 Zornitza Stark Tag founder tag was added to gene: KRIT1.
Mendeliome v0.4859 KRIT1 Zornitza Stark Marked gene: KRIT1 as ready
Mendeliome v0.4859 KRIT1 Zornitza Stark Gene: krit1 has been classified as Green List (High Evidence).
Mendeliome v0.4859 KRIT1 Zornitza Stark Phenotypes for gene: KRIT1 were changed from to Cavernous malformations of CNS and retina, 116860; Cerebral cavernous malformations-1, 116860; Hyperkeratotic cutaneous capillary-venous malformations associated with cerebral capillary malformations, 116860
Mendeliome v0.4858 KRIT1 Zornitza Stark Publications for gene: KRIT1 were set to
Mendeliome v0.4857 KRIT1 Zornitza Stark Mode of inheritance for gene: KRIT1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4856 SH3TC2 Zornitza Stark Marked gene: SH3TC2 as ready
Mendeliome v0.4856 SH3TC2 Zornitza Stark Gene: sh3tc2 has been classified as Green List (High Evidence).
Mendeliome v0.4856 SH3TC2 Zornitza Stark Phenotypes for gene: SH3TC2 were changed from to Charcot-Marie-Tooth disease, type 4C MIM#601596, Mononeuropathy of the median nerve, mild MIM#613353
Mendeliome v0.4855 SH3TC2 Zornitza Stark Publications for gene: SH3TC2 were set to
Mendeliome v0.4854 SH3TC2 Zornitza Stark Mode of inheritance for gene: SH3TC2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4853 SH3TC2 Zornitza Stark reviewed gene: SH3TC2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4853 ABCC6 Zornitza Stark Added comment: Comment when marking as ready: Evidence for mono-allelic variants causing disease is limited.
Mendeliome v0.4853 ABCC6 Zornitza Stark Gene: abcc6 has been classified as Green List (High Evidence).
Mendeliome v0.4853 ABCC6 Zornitza Stark Tag SV/CNV tag was added to gene: ABCC6.
Mendeliome v0.4853 CAPN3 Zornitza Stark Gene: capn3 has been classified as Green List (High Evidence).
Mendeliome v0.4853 CAPN3 Zornitza Stark Phenotypes for gene: CAPN3 were changed from to Muscular dystrophy, limb-girdle, autosomal dominant 4, MIM# 618129; Muscular dystrophy, limb-girdle, autosomal recessive 1, MIM# 253600
Mendeliome v0.4852 CAPN3 Zornitza Stark Publications for gene: CAPN3 were set to
Mendeliome v0.4851 CAPN3 Zornitza Stark Mode of inheritance for gene: CAPN3 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.4850 CAPN3 Zornitza Stark reviewed gene: CAPN3: Rating: GREEN; Mode of pathogenicity: None; Publications: 31937337, 28881388, 32342993, 32557990; Phenotypes: Muscular dystrophy, limb-girdle, autosomal dominant 4, MIM# 618129, Muscular dystrophy, limb-girdle, autosomal recessive 1, MIM# 253600; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.4850 SLC6A5 Zornitza Stark Gene: slc6a5 has been classified as Green List (High Evidence).
Mendeliome v0.4850 SLC6A5 Zornitza Stark Phenotypes for gene: SLC6A5 were changed from to Hyperekplexia 3, MIM# 614618
Mendeliome v0.4849 KRIT1 Elena Savva reviewed gene: KRIT1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 16571644, 29593473; Phenotypes: Cavernous malformations of CNS and retina, 116860, Cerebral cavernous malformations-1, 116860, Hyperkeratotic cutaneous capillary-venous malformations associated with cerebral capillary malformations, 116860; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.4849 SLC6A5 Zornitza Stark Publications for gene: SLC6A5 were set to
Mendeliome v0.4848 SLC6A5 Zornitza Stark Mode of pathogenicity for gene: SLC6A5 was changed from to Other
Mendeliome v0.4847 SLC6A5 Zornitza Stark Mode of inheritance for gene: SLC6A5 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4846 SLC6A5 Zornitza Stark reviewed gene: SLC6A5: Rating: GREEN; Mode of pathogenicity: None; Publications: 31604777, 30847549, 29859229, 16751771; Phenotypes: Hyperekplexia 3, MIM# 614618; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4846 ARX Zornitza Stark Gene: arx has been classified as Green List (High Evidence).
Mendeliome v0.4846 ARX Zornitza Stark Phenotypes for gene: ARX were changed from to Epileptic encephalopathy, early infantile, 1 MIM#308350; Hydranencephaly with abnormal genitalia MIM#300215; Lissencephaly, X-linked 2 MIM#300215; Mental retardation, X-linked 29 and others MIM#300419; Partington syndrome MIM#309510; Proud syndrome MIM#300004
Mendeliome v0.4845 ARX Zornitza Stark Publications for gene: ARX were set to
Mendeliome v0.4844 ARX Zornitza Stark Mode of inheritance for gene: ARX was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.4843 SH3TC2 Elena Savva reviewed gene: SH3TC2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 19744956, 20220177, 19744956, 20028792; Phenotypes: Charcot-Marie-Tooth disease, type 4C MIM#601596, Mononeuropathy of the median nerve, mild MIM#613353; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4843 ABCC6 Kristin Rigbye changed review comment from: All conditions are regarded as a single disorder at variable ends of the phenotypic spectrum. The same variants have been reported in all three conditions, however reports for AD PE are consistently from older papers (pre-2005) and may have missed a 2nd hit (OMIM). More recent papers consistently report this condition as autosomal recessive (PMID: 28102862).; to: All conditions are regarded as a single disorder at variable ends of the phenotypic spectrum. The same variants have been reported in all three conditions, however reports for AD PXE are consistently from older papers (pre-2005) and may have missed a 2nd hit (OMIM). More recent papers consistently report this condition as autosomal recessive (PMID: 28102862).

In addition to missense, PTCs and splice variants, deletions and duplications in this gene comprise a significant proportion of variants and are a recognised mechanism / cause of PXE.
Mendeliome v0.4843 SLC6A5 Elena Savva reviewed gene: SLC6A5: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 16751771; Phenotypes: Hyperekplexia 3 MIM#614618; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4843 ARX Elena Savva reviewed gene: ARX: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 14722918, 19738637, 32519823, 28150386, 21496008; Phenotypes: Epileptic encephalopathy, early infantile, 1 MIM#308350, Hydranencephaly with abnormal genitalia MIM#300215, Lissencephaly, X-linked 2 MIM#300215, Mental retardation, X-linked 29 and others MIM#300419, Partington syndrome MIM#309510, Proud syndrome MIM#300004; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males); Current diagnostic: yes
Mendeliome v0.4843 TBL1Y Zornitza Stark Phenotypes for gene: TBL1Y were changed from Hearing loss to Deafness, Y-linked 2, MIM# 400047
Mendeliome v0.4842 TBL1Y Zornitza Stark edited their review of gene: TBL1Y: Changed rating: RED; Changed phenotypes: Deafness, Y-linked 2, MIM# 400047
Mendeliome v0.4842 MCM2 Zornitza Stark Gene: mcm2 has been classified as Red List (Low Evidence).
Mendeliome v0.4842 MCM2 Zornitza Stark gene: MCM2 was added
gene: MCM2 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: MCM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MCM2 were set to 26196677
Phenotypes for gene: MCM2 were set to Deafness, autosomal dominant 70, MIM# 616968
Review for gene: MCM2 was set to RED
Added comment: One family, expression studies.
Sources: Expert Review
Mendeliome v0.4841 ATP1A4 Zornitza Stark Marked gene: ATP1A4 as ready
Mendeliome v0.4841 ATP1A4 Zornitza Stark Gene: atp1a4 has been classified as Red List (Low Evidence).
Mendeliome v0.4841 ATP1A4 Zornitza Stark gene: ATP1A4 was added
gene: ATP1A4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATP1A4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP1A4 were set to 32549268
Phenotypes for gene: ATP1A4 were set to Hemiplegic migraine
Review for gene: ATP1A4 was set to RED
Added comment: Single family reported where missense variant segregated with hemiplegic migraine in four affected individuals.
Sources: Literature
Mendeliome v0.4840 BSND Zornitza Stark Gene: bsnd has been classified as Green List (High Evidence).
Mendeliome v0.4840 BSND Zornitza Stark Phenotypes for gene: BSND were changed from to Bartter syndrome, type 4a, MIM#602522
Mendeliome v0.4839 BSND Zornitza Stark Publications for gene: BSND were set to
Mendeliome v0.4838 BSND Zornitza Stark Mode of inheritance for gene: BSND was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4837 BSND Zornitza Stark changed review comment from: Some individuals with severe Bartter syndrome have been described as having intellectual disability, whereas others with milder symptoms have normal intellect.
Sources: Expert list; to: Well established gene-disease association.
Sources: Expert list
Mendeliome v0.4837 BSND Zornitza Stark edited their review of gene: BSND: Changed publications: 11687798, 12574213, 30174009, 21269598
Mendeliome v0.4837 LTBP2 Zornitza Stark Marked gene: LTBP2 as ready
Mendeliome v0.4837 LTBP2 Zornitza Stark Gene: ltbp2 has been classified as Green List (High Evidence).
Mendeliome v0.4837 LTBP2 Zornitza Stark Phenotypes for gene: LTBP2 were changed from to Glaucoma 3, primary congenital, D 613086; Microspherophakia and/or megalocornea, with ectopia lentis and with or without secondary glaucoma, MIM# 251750
Mendeliome v0.4836 LTBP2 Zornitza Stark Publications for gene: LTBP2 were set to
Mendeliome v0.4835 LTBP2 Zornitza Stark Mode of inheritance for gene: LTBP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4834 LTBP2 Zornitza Stark reviewed gene: LTBP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 19656777, 19361779, 20617341, 32165823, 30380740, 30565850; Phenotypes: Glaucoma 3, primary congenital, D 613086, Microspherophakia and/or megalocornea, with ectopia lentis and with or without secondary glaucoma, MIM# 251750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4834 CYP1B1 Zornitza Stark Publications for gene: CYP1B1 were set to 21730847; 27243976
Mendeliome v0.4833 CYP1B1 Zornitza Stark reviewed gene: CYP1B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9463332, 10655546, 12372064, 21081970; Phenotypes: Glaucoma 3A, primary open angle, congenital, juvenile, or adult onset, MIM# 231300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4833 IFT122 Zornitza Stark Publications for gene: IFT122 were set to 26792575; 28370949; 29037998
Mendeliome v0.4832 IFT122 Zornitza Stark edited their review of gene: IFT122: Changed publications: 29037998, 20493458, 23826986, 26792575, 29220510, 28370949, 27681595, 27681595
Mendeliome v0.4832 NEK9 Zornitza Stark Phenotypes for gene: NEK9 were changed from Lethal congenital contracture syndrome 10, MIM# 617022; Skeletal dysplasia to Lethal congenital contracture syndrome 10, MIM# 617022; Arthrogryposis, Perthes disease, and upward gaze palsy, MIM# 614262; Skeletal dysplasia
Mendeliome v0.4831 NEK9 Zornitza Stark Publications for gene: NEK9 were set to 26908619
Mendeliome v0.4830 NEK9 Zornitza Stark Classified gene: NEK9 as Amber List (moderate evidence)
Mendeliome v0.4830 NEK9 Zornitza Stark Gene: nek9 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4829 NEK9 Zornitza Stark edited their review of gene: NEK9: Changed rating: AMBER
Mendeliome v0.4829 NEK9 Zornitza Stark edited their review of gene: NEK9: Added comment: Another Saudi family described with which 2 sisters and a female cousin who had a similar disorder characterised by arthrogryposis apparent since early childhood, avascular necrosis of the hip (Perthes disease), and upward gaze palsy. Homozygous missense variant segregated with the phenotype. Given the small number of reports, it is unclear whether this represents a distinct association is part of a spectrum with includes the more severe phenotype described in the Irish traveller families.; Changed publications: 26908619, 21271645; Changed phenotypes: Lethal congenital contracture syndrome 10, MIM# 617022, Arthrogryposis, Perthes disease, and upward gaze palsy, MIM# 614262, Skeletal dysplasia
Mendeliome v0.4829 TRPM7 Eleanor Williams Deleted their comment
Mendeliome v0.4829 IL11RA Zornitza Stark Gene: il11ra has been classified as Green List (High Evidence).
Mendeliome v0.4829 IL11RA Zornitza Stark Phenotypes for gene: IL11RA were changed from to Craniosynostosis and dental anomalies, MIM# 614188
Mendeliome v0.4828 IL11RA Zornitza Stark Publications for gene: IL11RA were set to
Mendeliome v0.4827 IL11RA Zornitza Stark Mode of inheritance for gene: IL11RA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4826 IL11RA Zornitza Stark reviewed gene: IL11RA: Rating: GREEN; Mode of pathogenicity: None; Publications: 21741611, 32277509, 30811827, 29926465, 24498618; Phenotypes: Craniosynostosis and dental anomalies, MIM# 614188; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4826 ABCC6 Zornitza Stark Publications for gene: ABCC6 were set to 11536079
Mendeliome v0.4825 EFNB1 Zornitza Stark Gene: efnb1 has been classified as Green List (High Evidence).
Mendeliome v0.4825 EFNB1 Zornitza Stark Phenotypes for gene: EFNB1 were changed from to Craniofrontonasal dysplasia, MIM# 304110
Mendeliome v0.4824 EFNB1 Zornitza Stark Publications for gene: EFNB1 were set to
Mendeliome v0.4823 EFNB1 Zornitza Stark Mode of inheritance for gene: EFNB1 was changed from Unknown to Other
Mendeliome v0.4822 EFNB1 Zornitza Stark reviewed gene: EFNB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15166289, 18627045, 23335590; Phenotypes: Craniofrontonasal dysplasia, MIM# 304110; Mode of inheritance: Other
Mendeliome v0.4822 ABCC6 Kristin Rigbye reviewed gene: ABCC6: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28102862; Phenotypes: Pseudoxanthoma elasticum (MIM#264800), AR; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4822 AGAP1 Zornitza Stark Gene: agap1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4822 AGAP1 Zornitza Stark Classified gene: AGAP1 as Amber List (moderate evidence)
Mendeliome v0.4822 AGAP1 Zornitza Stark Gene: agap1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4821 AGAP1 Zornitza Stark gene: AGAP1 was added
gene: AGAP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AGAP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AGAP1 were set to 31700678; 25666757; 30472483
Phenotypes for gene: AGAP1 were set to Cerebral palsy
Review for gene: AGAP1 was set to AMBER
Added comment: Two individuals reported with de novo variants in this gene and a CP phenotype. Rare variants over-represented in a case-control study. Supportive zebrafish model. Another individual with a deletion (+1 other gene) reported with ID and autism.
Sources: Literature
Mendeliome v0.4820 SMN1 Zornitza Stark Gene: smn1 has been classified as Green List (High Evidence).
Mendeliome v0.4820 SMN1 Zornitza Stark Phenotypes for gene: SMN1 were changed from to Spinal muscular atrophy-1, MIM# 253300
Mendeliome v0.4819 SMN1 Zornitza Stark Publications for gene: SMN1 were set to
Mendeliome v0.4818 SMN1 Zornitza Stark Mode of inheritance for gene: SMN1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4817 SMN1 Zornitza Stark Tag SV/CNV tag was added to gene: SMN1.
Mendeliome v0.4817 SMN1 Zornitza Stark reviewed gene: SMN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 7813012; Phenotypes: Spinal muscular atrophy-1, MIM# 253300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4817 BUB1B Zornitza Stark Gene: bub1b has been classified as Green List (High Evidence).
Mendeliome v0.4817 BUB1B Zornitza Stark Phenotypes for gene: BUB1B were changed from to Mosaic variegated aneuploidy syndrome 1, MIM# 257300; Premature ovarian failure
Mendeliome v0.4816 BUB1B Zornitza Stark Publications for gene: BUB1B were set to
Mendeliome v0.4815 BUB1B Zornitza Stark Mode of inheritance for gene: BUB1B was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4814 BUB1B Zornitza Stark reviewed gene: BUB1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 32716490, 18548531; Phenotypes: Mosaic variegated aneuploidy syndrome 1, MIM# 257300, Premature ovarian failure; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4814 ROM1 Zornitza Stark Gene: rom1 has been classified as Green List (High Evidence).
Mendeliome v0.4814 ROM1 Zornitza Stark Phenotypes for gene: ROM1 were changed from to Retinitis pigmentosa 7, digenic form, MIM# 608133
Mendeliome v0.4813 ROM1 Zornitza Stark Publications for gene: ROM1 were set to
Mendeliome v0.4812 ROM1 Zornitza Stark Mode of inheritance for gene: ROM1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4811 ROM1 Zornitza Stark reviewed gene: ROM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32036094, 8202715, 30630813, 24618324, 20300562; Phenotypes: Retinitis pigmentosa 7, digenic form, MIM# 608133; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4811 FOXC1 Zornitza Stark changed review comment from: Well established gene-disease association.; to: Well established gene-disease association supported by case-level data and experimental data, including animal models.
Mendeliome v0.4811 FOXC1 Zornitza Stark Gene: foxc1 has been classified as Green List (High Evidence).
Mendeliome v0.4811 FOXC1 Zornitza Stark Phenotypes for gene: FOXC1 were changed from to Axenfeld-Rieger syndrome, type 3, MIM# 602482
Mendeliome v0.4810 FOXC1 Zornitza Stark Publications for gene: FOXC1 were set to
Mendeliome v0.4809 FOXC1 Zornitza Stark Mode of inheritance for gene: FOXC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4808 FOXC1 Zornitza Stark reviewed gene: FOXC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9792859, 10713890, 19668217; Phenotypes: Axenfeld-Rieger syndrome, type 3, MIM# 602482; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4808 ALG14 Zornitza Stark Phenotypes for gene: ALG14 were changed from Myasthenic syndrome, congenital, 15, without tubular aggregates 616227; Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies (IDDEBF), MIM#619031; Disorder of N-glycosylation to Myasthenic syndrome, congenital, 15, without tubular aggregates 616227; Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies (IDDEBF), MIM#619031; Myopathy, epilepsy, and progressive cerebral atrophy, MIM# 619036; Disorder of N-glycosylation
Mendeliome v0.4807 ALG14 Zornitza Stark changed review comment from: 5 individuals from unrelated families described in the literature: one with myasthenic syndrome, no report of ID; second with predominantly ID phenotype; and three more with a neurodegenerative phenotype. ALG14 is part of the UDP-GlcNAc transferase, which catalyzes a key step in endoplasmic reticulum N-linked glycosylation; to: 5 individuals from unrelated families described in the literature: one with myasthenic syndrome, no report of ID; second with predominantly ID phenotype; and three more with a neurodegenerative phenotype. ALG14 is part of the UDP-GlcNAc transferase, which catalyzes a key step in endoplasmic reticulum N-linked glycosylation. The three OMIM disorders may represent a spectrum of severity for CDG.
Mendeliome v0.4807 ALG14 Zornitza Stark edited their review of gene: ALG14: Changed phenotypes: Myasthenic syndrome, congenital, 15, without tubular aggregates 616227, Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies (IDDEBF), MIM#619031, Myopathy, epilepsy, and progressive cerebral atrophy, MIM# 619036, Disorder of N-glycosylation
Mendeliome v0.4807 FOXC1 Eleanor Williams reviewed gene: FOXC1: Rating: ; Mode of pathogenicity: None; Publications: 32720677; Phenotypes: eye and vascular development; Mode of inheritance: None
Mendeliome v0.4807 ROM1 Eleanor Williams reviewed gene: ROM1: Rating: ; Mode of pathogenicity: None; Publications: 32716032; Phenotypes: retinal degeneration; Mode of inheritance: None
Mendeliome v0.4807 BUB1B Eleanor Williams reviewed gene: BUB1B: Rating: ; Mode of pathogenicity: None; Publications: 32716490; Phenotypes: premature ovarian insufficiency; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.4807 SMN1 Eleanor Williams reviewed gene: SMN1: Rating: ; Mode of pathogenicity: None; Publications: 32644125, 32644120; Phenotypes: Spinal muscular atrophy; Mode of inheritance: None
Mendeliome v0.4807 ACER3 Zornitza Stark Gene: acer3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4807 ACER3 Zornitza Stark Phenotypes for gene: ACER3 were changed from to Leukodystrophy
Mendeliome v0.4806 ACER3 Zornitza Stark Publications for gene: ACER3 were set to
Mendeliome v0.4805 ACER3 Zornitza Stark Mode of inheritance for gene: ACER3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4804 ACER3 Zornitza Stark Classified gene: ACER3 as Amber List (moderate evidence)
Mendeliome v0.4804 ACER3 Zornitza Stark Gene: acer3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4803 ACER3 Zornitza Stark edited their review of gene: ACER3: Changed phenotypes: Leukodystrophy
Mendeliome v0.4803 ACER3 Zornitza Stark reviewed gene: ACER3: Rating: AMBER; Mode of pathogenicity: None; Publications: 32816236, 26792856; Phenotypes: Leukodystrphy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4803 TRPV1 Bryony Thompson Publications for gene: TRPV1 were set to 29930394
Mendeliome v0.4802 TRPV1 Bryony Thompson Classified gene: TRPV1 as Amber List (moderate evidence)
Mendeliome v0.4802 TRPV1 Bryony Thompson Gene: trpv1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4800 NUAK2 Zornitza Stark commented on gene: NUAK2: no OMIM# yet
Mendeliome v0.4800 NUAK2 Zornitza Stark edited their review of gene: NUAK2: Changed phenotypes: Anencephaly
Mendeliome v0.4800 NUAK2 Zornitza Stark Phenotypes for gene: NUAK2 were changed from ANENCEPHALY (OMIM#206500) to Anencephaly
Mendeliome v0.4799 NUAK2 Zornitza Stark Mode of inheritance for gene: NUAK2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4798 NUAK2 Zornitza Stark reviewed gene: NUAK2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4798 GOLGA3 Zornitza Stark Publications for gene: GOLGA3 were set to PMID: 23495255
Mendeliome v0.4797 GOLGA3 Zornitza Stark reviewed gene: GOLGA3: Rating: RED; Mode of pathogenicity: None; Publications: 32367404; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.4797 ANGPT2 Zornitza Stark Publications for gene: ANGPT2 were set to https://stm.sciencemag.org/content/12/560/eaax8013
Mendeliome v0.4796 ANGPT2 Zornitza Stark edited their review of gene: ANGPT2: Changed publications: 32908006
Mendeliome v0.4796 AP1S1 Zornitza Stark Gene: ap1s1 has been classified as Green List (High Evidence).
Mendeliome v0.4796 AP1S1 Zornitza Stark Phenotypes for gene: AP1S1 were changed from to MEDNIK syndrome 609313; non-syndromic congenital intestinal failure
Mendeliome v0.4795 AP1S1 Zornitza Stark Publications for gene: AP1S1 were set to
Mendeliome v0.4794 AP1S1 Zornitza Stark Mode of inheritance for gene: AP1S1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4793 AP1S1 Zornitza Stark reviewed gene: AP1S1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: MEDNIK syndrome 609313; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4793 Zornitza Stark removed gene:NOTCH3 from the panel
Mendeliome v0.4792 Zornitza Stark removed gene:ALS2 from the panel
Mendeliome v0.4791 AP1S1 Ee Ming Wong changed review comment from: - Established green gene in Ichthyosis, Palmoplantar Keratoderma and Erythrokeratoderma, ID and Hereditary Neuropathy (complex) panels associated with MEDNIK syndrome
- PMID: 32306098 propose a clinical and genetic expansion for AP1S1-associated disease

- 2 consanguineous families, each carrying a homozygous missense AP1S1 variant
- AP1S1 knockout cell line demonstrated tight-junction and polarity abnormalities that were rescued by WT AP1S1, but not the AP1S1 missense mutants; to: - Established green gene in Ichthyosis, Palmoplantar Keratoderma and Erythrokeratoderma, ID and Hereditary Neuropathy (complex) panels associated with MEDNIK syndrome
- PMID: 32306098 propose a clinical and genetic expansion for AP1S1-associated disease

- 2 consanguineous families, each carrying a homozygous missense AP1S1 variant
- AP1S1 knockout cell line demonstrated tight-junction and polarity abnormalities that were rescued by WT AP1S1, but not the AP1S1 missense mutants
Mendeliome v0.4791 AP1S1 Ee Ming Wong changed review comment from: - 2 consanguineous families, each carrying a homozygous missense AP1S1 variant
- AP1S1 knockout cell line demonstrated tight-junction and polarity abnormalities that were rescued by WT AP1S1, but not the AP1S1 missense mutants; to: - Established green gene in Ichthyosis, Palmoplantar Keratoderma and Erythrokeratoderma, ID and Hereditary Neuropathy (complex) panels associated with MEDNIK syndrome
- PMID: 32306098 propose a clinical and genetic expansion for AP1S1-associated disease

- 2 consanguineous families, each carrying a homozygous missense AP1S1 variant
- AP1S1 knockout cell line demonstrated tight-junction and polarity abnormalities that were rescued by WT AP1S1, but not the AP1S1 missense mutants
Mendeliome v0.4791 AKNA Seb Lunke Gene: akna has been classified as Red List (Low Evidence).
Mendeliome v0.4791 GOLGA3 Zornitza Stark Gene: golga3 has been classified as Red List (Low Evidence).
Mendeliome v0.4791 GOLGA3 Zornitza Stark Classified gene: GOLGA3 as Red List (low evidence)
Mendeliome v0.4791 GOLGA3 Zornitza Stark Gene: golga3 has been classified as Red List (Low Evidence).
Mendeliome v0.4790 AKNA Seb Lunke Classified gene: AKNA as Red List (low evidence)
Mendeliome v0.4790 AKNA Seb Lunke Gene: akna has been classified as Red List (Low Evidence).
Mendeliome v0.4789 THOC1 Melanie Marty changed review comment from: Missense variant identified and segregated with adult-onset hearing loss in 9 affected family members. 12 unaffected individuals also tested.
Functional studies showed THOC1 was expressed in mouse and zebrafish hair cells. Furthermore, thoc1 deficiency caused the reduction of hair cell numbers in zebrafish and in mouse it induced hair cell apoptosis.
Sources: Literature; to: Missense variant identified and segregated with adult-onset hearing loss in 9 affected family members. 12 unaffected individuals also tested.
Functional studies showed THOC1 was expressed in mouse and zebrafish hair cells. Furthermore, thoc1 deficiency caused the reduction of hair cell numbers in zebrafish and the hypomorphic thoc1 in mouse induced hair cell apoptosis.
Sources: Literature
Mendeliome v0.4789 GOLGA3 Elena Savva gene: GOLGA3 was added
gene: GOLGA3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GOLGA3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GOLGA3 were set to PMID: 23495255
Phenotypes for gene: GOLGA3 were set to Primary ciliary dyskinesia
Review for gene: GOLGA3 was set to RED
Added comment: https://link.springer.com/article/10.1007/s00439-020-02170-2
Two siblings with a homozygous missense and PCD

PMID: 23495255; null mice have failed spermatogenesis
Sources: Literature
Mendeliome v0.4789 PRICKLE3 Seb Lunke Gene: prickle3 has been classified as Red List (Low Evidence).
Mendeliome v0.4789 PRICKLE3 Seb Lunke Classified gene: PRICKLE3 as Red List (low evidence)
Mendeliome v0.4789 PRICKLE3 Seb Lunke Added comment: Comment on list classification: Single variant only and questionable association due to uncertainty of role around ND4.
Mendeliome v0.4789 PRICKLE3 Seb Lunke Gene: prickle3 has been classified as Red List (Low Evidence).
Mendeliome v0.4788 AKNA Elena Savva gene: AKNA was added
gene: AKNA was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AKNA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AKNA were set to PMID: 21606955
Phenotypes for gene: AKNA were set to Primary ciliary dyskinesia
Review for gene: AKNA was set to RED
Added comment: https://link.springer.com/article/10.1007/s00439-020-02170-2
Two siblings with homozygous PTCs with PCD. Carrier parents and mutation negative siblings (5) was normal.

PMID: 21606955: Null mice have neonatal death with systemic inflammation and alveolar loss
Sources: Literature
Mendeliome v0.4788 THOC1 Zornitza Stark Marked gene: THOC1 as ready
Mendeliome v0.4788 THOC1 Zornitza Stark Gene: thoc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4788 THOC1 Zornitza Stark Classified gene: THOC1 as Amber List (moderate evidence)
Mendeliome v0.4788 THOC1 Zornitza Stark Gene: thoc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4787 GBF1 Seb Lunke Gene: gbf1 has been classified as Green List (High Evidence).
Mendeliome v0.4787 GBF1 Seb Lunke Classified gene: GBF1 as Green List (high evidence)
Mendeliome v0.4787 GBF1 Seb Lunke Gene: gbf1 has been classified as Green List (High Evidence).
Mendeliome v0.4786 THOC1 Melanie Marty changed review comment from: Missense variant identified and segregated with adult-onset hearing loss in 9 affected family members. 12 unaffected individuals also tested.
Functional studies showed THOC1 was expressed in mouse and zebrafish hair cells. Furthermore, thoc1 deficiency caused the reduction of hair cell numbers in zebrafish and the induced hair cell apoptosis.
Sources: Literature; to: Missense variant identified and segregated with adult-onset hearing loss in 9 affected family members. 12 unaffected individuals also tested.
Functional studies showed THOC1 was expressed in mouse and zebrafish hair cells. Furthermore, thoc1 deficiency caused the reduction of hair cell numbers in zebrafish and in mouse it induced hair cell apoptosis.
Sources: Literature
Mendeliome v0.4786 AP1S1 Ee Ming Wong reviewed gene: AP1S1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 32306098; Phenotypes: non-syndromic congenital intestinal failure; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.4786 NUAK2 Seb Lunke Classified gene: NUAK2 as Amber List (moderate evidence)
Mendeliome v0.4786 NUAK2 Seb Lunke Gene: nuak2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4785 RNPC3 Zornitza Stark Gene: rnpc3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4785 RNPC3 Zornitza Stark Classified gene: RNPC3 as Amber List (moderate evidence)
Mendeliome v0.4785 RNPC3 Zornitza Stark Gene: rnpc3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4784 RNPC3 Zornitza Stark gene: RNPC3 was added
gene: RNPC3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RNPC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNPC3 were set to 29866761; 32462814
Phenotypes for gene: RNPC3 were set to Growth hormone deficiency
Review for gene: RNPC3 was set to AMBER
Added comment: Two families reported. PMID 29866761: isolated growth deficiency and pituitary hypoplasia. PMID 32462814: growth hormone deficiency, central congenital hypothyroidism, congenital cataract, developmental delay/intellectual deficiency and delayed puberty. Full spectrum of phenotype unclear at present.
Sources: Literature
Mendeliome v0.4783 THOC1 Melanie Marty changed review comment from: Missense variant identified and segregated with adulthood-onset hearing loss in 9 affected family members. 12 unaffected individuals also tested.
Functional studies showed THOC1 was expressed in mouse and zebrafish hair cells. Furthermore, thoc1 deficiency caused the reduction of hair cell numbers in zebrafish and the induced hair cell apoptosis.
Sources: Literature; to: Missense variant identified and segregated with adult-onset hearing loss in 9 affected family members. 12 unaffected individuals also tested.
Functional studies showed THOC1 was expressed in mouse and zebrafish hair cells. Furthermore, thoc1 deficiency caused the reduction of hair cell numbers in zebrafish and the induced hair cell apoptosis.
Sources: Literature
Mendeliome v0.4783 PRICKLE3 Teresa Zhao gene: PRICKLE3 was added
gene: PRICKLE3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PRICKLE3 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: PRICKLE3 were set to 32516135
Phenotypes for gene: PRICKLE3 were set to Leber’s hereditary optic neuropathy MIM#535000
Review for gene: PRICKLE3 was set to AMBER
Added comment: Reported as X-linked LHON modifier (c.157C>T, p.Arg53Trp) in PRICKLE3 in 3 Chinese families. All affected individuals carried both ND4 11778G>A and p.Arg53Trp mutations, while subjects bearing only a single mutation exhibited normal vision.

Defective assembly, stability, and function of ATP synthase observed using Lymphoblastoid cell lines from one of the families.

This finding indicated that the p.Arg53Trp mutation acted in synergy with the m.11778G>A mutation and deteriorated mitochondrial dysfunctions necessary for the expression of LHON.

Prickle3-deficient mice exhibited pronounced ATPase deficiencies.
Sources: Literature
Mendeliome v0.4783 NUAK2 Seb Lunke Gene: nuak2 has been classified as Red List (Low Evidence).
Mendeliome v0.4783 GBF1 Paul De Fazio changed review comment from: Four unrelated families with individuals affected by sporadic or dominant Distal hereditary motor neuropathies (HMNs) or axonal Charcot-Marie-Tooth neuropathy (CMT2). 3 missense variants (1 de novo) and 1 nonsense variant (de novo). Authors observed marked increase in Golgi fragmentation in primary fibroblasts derived from all affected individuals.
Sources: Literature; to: Four unrelated families with individuals affected by sporadic or dominant Distal hereditary motor neuropathies (HMNs) or axonal Charcot-Marie-Tooth neuropathy (CMT2). 3 missense variants (1 de novo) and 1 nonsense variant (de novo).

Age of onset varied from childhood (nonsense variant) to 50s. Authors observed marked increase in Golgi fragmentation in primary fibroblasts derived from all affected individuals.
Sources: Literature
Mendeliome v0.4783 NUAK2 Seb Lunke gene: NUAK2 was added
gene: NUAK2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NUAK2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: NUAK2 were set to 32845958
Phenotypes for gene: NUAK2 were set to ANENCEPHALY (OMIM#206500)
Review for gene: NUAK2 was set to AMBER
Added comment: Novel gene described in single consanguineous family with three FDIU and extensive anencephaly. Hom inframe del affecting functional kinase domain, parents confirmed carriers. Good functional data showing loss of enzyme function and mouse model with 40% anencephaly after knock-out.
Sources: Literature
Mendeliome v0.4782 THOC1 Melanie Marty gene: THOC1 was added
gene: THOC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: THOC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: THOC1 were set to 32776944
Phenotypes for gene: THOC1 were set to Nonsyndromic hearing loss
Review for gene: THOC1 was set to AMBER
Added comment: Missense variant identified and segregated with adulthood-onset hearing loss in 9 affected family members. 12 unaffected individuals also tested.
Functional studies showed THOC1 was expressed in mouse and zebrafish hair cells. Furthermore, thoc1 deficiency caused the reduction of hair cell numbers in zebrafish and the induced hair cell apoptosis.
Sources: Literature
Mendeliome v0.4782 MBTPS1 Zornitza Stark Marked gene: MBTPS1 as ready
Mendeliome v0.4782 MBTPS1 Zornitza Stark Gene: mbtps1 has been classified as Green List (High Evidence).
Mendeliome v0.4782 MBTPS1 Zornitza Stark Classified gene: MBTPS1 as Green List (high evidence)
Mendeliome v0.4782 MBTPS1 Zornitza Stark Gene: mbtps1 has been classified as Green List (High Evidence).
Mendeliome v0.4781 MBTPS1 Zornitza Stark gene: MBTPS1 was added
gene: MBTPS1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MBTPS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MBTPS1 were set to 32857899; 32420688; 30046013
Phenotypes for gene: MBTPS1 were set to Skeletal dysplasia
Review for gene: MBTPS1 was set to GREEN
Added comment: Three unrelated individuals reported with bi-allelic variants in this gene and a skeletal dysplasia, one described with SRS-like features. Elevated blood lysosomal enzymes are also a feature.
Sources: Literature
Mendeliome v0.4780 GBF1 Paul De Fazio gene: GBF1 was added
gene: GBF1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GBF1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: GBF1 were set to 32937143
Phenotypes for gene: GBF1 were set to Axonal Neuropathy
Review for gene: GBF1 was set to GREEN
gene: GBF1 was marked as current diagnostic
Added comment: Four unrelated families with individuals affected by sporadic or dominant Distal hereditary motor neuropathies (HMNs) or axonal Charcot-Marie-Tooth neuropathy (CMT2). 3 missense variants (1 de novo) and 1 nonsense variant (de novo). Authors observed marked increase in Golgi fragmentation in primary fibroblasts derived from all affected individuals.
Sources: Literature
Mendeliome v0.4780 ALS2 Ain Roesley gene: ALS2 was added
gene: ALS2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ALS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALS2 were set to 32214227
Phenotypes for gene: ALS2 were set to Tetraparesis with affection of upper and lower motor neuron
Penetrance for gene: ALS2 were set to unknown
Review for gene: ALS2 was set to RED
Added comment: In a cohort of Palestinian and Israeli Arabs with neurological disorders, a family with 2 affecteds were homozygous for a nonsense variant. Authors classified as likely path by ACMG guidelines
Sources: Literature
Mendeliome v0.4780 QRICH1 Zornitza Stark Gene: qrich1 has been classified as Green List (High Evidence).
Mendeliome v0.4780 QRICH1 Zornitza Stark Phenotypes for gene: QRICH1 were changed from to Ververi-Brady syndrome, MIM#617982
Mendeliome v0.4779 QRICH1 Zornitza Stark Publications for gene: QRICH1 were set to
Mendeliome v0.4778 QRICH1 Zornitza Stark Mode of inheritance for gene: QRICH1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4777 QRICH1 Zornitza Stark reviewed gene: QRICH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28692176, 30281152, 33009816; Phenotypes: Ververi-Brady syndrome, MIM#617982; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4777 GREB1L Zornitza Stark Gene: greb1l has been classified as Green List (High Evidence).
Mendeliome v0.4777 GREB1L Zornitza Stark Phenotypes for gene: GREB1L were changed from to Renal hypodysplasia/aplasia 3, OMIM# 617805
Mendeliome v0.4776 GREB1L Zornitza Stark Publications for gene: GREB1L were set to
Mendeliome v0.4775 GREB1L Zornitza Stark Mode of inheritance for gene: GREB1L was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4774 GREB1L Zornitza Stark reviewed gene: GREB1L: Rating: GREEN; Mode of pathogenicity: None; Publications: 29100091; Phenotypes: Renal hypodysplasia/aplasia 3, OMIM# 617805; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4774 IL1RAP Zornitza Stark Gene: il1rap has been classified as Red List (Low Evidence).
Mendeliome v0.4774 IL1RAP Zornitza Stark gene: IL1RAP was added
gene: IL1RAP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: IL1RAP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL1RAP were set to 31954058
Phenotypes for gene: IL1RAP were set to Steroid-sensitive nephrotic syndrome
Review for gene: IL1RAP was set to RED
Added comment: A pair of siblings with compound heterozygous variants in this gene and steroid-sensitive nephrotic syndrome. Functional effect of variants demonstrated but mouse model does not have proteinuria.
Sources: Literature
Mendeliome v0.4773 MRAS Zornitza Stark Publications for gene: MRAS were set to 28289718
Mendeliome v0.4772 MRAS Zornitza Stark Phenotypes for gene: MRAS were changed from Noonan syndrome to Noonan syndrome 11, MIM#618499
Mendeliome v0.4771 MRAS Zornitza Stark edited their review of gene: MRAS: Changed phenotypes: Noonan syndrome 11, MIM#618499
Mendeliome v0.4771 NEMF Zornitza Stark Mode of inheritance for gene: NEMF was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4770 NEMF Zornitza Stark changed review comment from: Nine individuals from 7 unrelated families reported with a mixed CNS/PNS phenotype. 7/9 had ID, 4/9 had formal assessments demonstrating axonal neuropathy, 3/9 had ataxia; muscular atrophy, hypotonia, respiratory distress, scoliosis also described in some. Three independently generated mouse models had progressive motor neuron degeneration.
Sources: Literature; to: Nine individuals from 7 unrelated families reported with a mixed CNS/PNS phenotype. 7/9 had ID, 4/9 had formal assessments demonstrating axonal neuropathy, 3/9 had ataxia; muscular atrophy, hypotonia, respiratory distress, scoliosis also described in some. Three independently generated mouse models had progressive motor neuron degeneration.

Single individual with de novo variant reported, postulated dominant negative effect. Evidence for mono allelic variants causing disease is limited.
Sources: Literature
Mendeliome v0.4770 NEMF Zornitza Stark edited their review of gene: NEMF: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4770 PLS1 Zornitza Stark Phenotypes for gene: PLS1 were changed from Deafness to Deafness, autosomal dominant 76, MIM# 618787
Mendeliome v0.4769 PLS1 Zornitza Stark edited their review of gene: PLS1: Changed phenotypes: Deafness, autosomal dominant 76, MIM# 618787
Mendeliome v0.4769 HOMER2 Zornitza Stark Gene: homer2 has been classified as Green List (High Evidence).
Mendeliome v0.4769 HOMER2 Zornitza Stark Phenotypes for gene: HOMER2 were changed from to Deafness, autosomal dominant 68, MIM# 616707
Mendeliome v0.4768 HOMER2 Zornitza Stark Publications for gene: HOMER2 were set to
Mendeliome v0.4767 HOMER2 Zornitza Stark Mode of inheritance for gene: HOMER2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4766 HOMER2 Zornitza Stark reviewed gene: HOMER2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25816005, 30047143, 25816005; Phenotypes: Deafness, autosomal dominant 68, MIM# 616707; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4766 TPRN Zornitza Stark Marked gene: TPRN as ready
Mendeliome v0.4766 TPRN Zornitza Stark Gene: tprn has been classified as Green List (High Evidence).
Mendeliome v0.4766 TPRN Zornitza Stark Phenotypes for gene: TPRN were changed from to Deafness, autosomal recessive 79, MIM# 613307
Mendeliome v0.4765 TPRN Zornitza Stark Publications for gene: TPRN were set to
Mendeliome v0.4764 TPRN Zornitza Stark Mode of inheritance for gene: TPRN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4763 TPRN Zornitza Stark reviewed gene: TPRN: Rating: GREEN; Mode of pathogenicity: None; Publications: 19603065, 20170898, 20170899, 23340767, 25129962, 20170899, 20170899, 27693694, 24285636; Phenotypes: Deafness, autosomal recessive 79, MIM# 613307; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4763 TMC1 Zornitza Stark Marked gene: TMC1 as ready
Mendeliome v0.4763 TMC1 Zornitza Stark Gene: tmc1 has been classified as Green List (High Evidence).
Mendeliome v0.4763 TMC1 Zornitza Stark Phenotypes for gene: TMC1 were changed from to Deafness, autosomal dominant 36, MIM# 606705; Deafness, autosomal recessive 7, MIM# 600974
Mendeliome v0.4762 TMC1 Zornitza Stark Publications for gene: TMC1 were set to
Mendeliome v0.4761 TMC1 Zornitza Stark Mode of inheritance for gene: TMC1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4760 TMC1 Zornitza Stark reviewed gene: TMC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11850618, 17250663, 18616530, 24827932, 11850623, 22105175; Phenotypes: Deafness, autosomal dominant 36, MIM# 606705, Deafness, autosomal recessive 7, MIM# 600974; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4760 TMIE Zornitza Stark Marked gene: TMIE as ready
Mendeliome v0.4760 TMIE Zornitza Stark Gene: tmie has been classified as Green List (High Evidence).
Mendeliome v0.4760 TMIE Zornitza Stark Phenotypes for gene: TMIE were changed from to Deafness, autosomal recessive 6, MIM# 600971
Mendeliome v0.4759 TMIE Zornitza Stark Mode of inheritance for gene: TMIE was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4758 TMIE Zornitza Stark Publications for gene: TMIE were set to
Mendeliome v0.4757 TMIE Zornitza Stark reviewed gene: TMIE: Rating: GREEN; Mode of pathogenicity: None; Publications: 12145746, 19438934, 24416283, 25467981, 25475183, 19934034, 12140191; Phenotypes: Deafness, autosomal recessive 6, MIM# 600971; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4757 TRIOBP Zornitza Stark Marked gene: TRIOBP as ready
Mendeliome v0.4757 TRIOBP Zornitza Stark Gene: triobp has been classified as Green List (High Evidence).
Mendeliome v0.4757 TRIOBP Zornitza Stark Phenotypes for gene: TRIOBP were changed from to Deafness, autosomal recessive 28, MIM# 609823
Mendeliome v0.4756 TRIOBP Zornitza Stark Publications for gene: TRIOBP were set to
Mendeliome v0.4755 TRIOBP Zornitza Stark Mode of inheritance for gene: TRIOBP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4754 TRIOBP Zornitza Stark reviewed gene: TRIOBP: Rating: GREEN; Mode of pathogenicity: None; Publications: 16385458, 16385457, 23226338, 27014650, 24853665, 27344577, 20510926; Phenotypes: Deafness, autosomal recessive 28, MIM# 609823; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4754 STRC Zornitza Stark Marked gene: STRC as ready
Mendeliome v0.4754 STRC Zornitza Stark Gene: strc has been classified as Green List (High Evidence).
Mendeliome v0.4754 STRC Zornitza Stark Phenotypes for gene: STRC were changed from to Deafness, autosomal recessive 16, MIM# 603720
Mendeliome v0.4753 STRC Zornitza Stark Publications for gene: STRC were set to
Mendeliome v0.4752 STRC Zornitza Stark Mode of inheritance for gene: STRC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4751 STRC Zornitza Stark reviewed gene: STRC: Rating: GREEN; Mode of pathogenicity: None; Publications: 11687802, 26011646, 26746617, 20301780; Phenotypes: Deafness, autosomal recessive 16, MIM# 603720; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4751 NUP188 Zornitza Stark Phenotypes for gene: NUP188 were changed from microcephaly; ID; cataract; structural brain abnormalities; hypoventilation to Sandestig-Stefanova syndrome, 618804; microcephaly; ID; cataract; structural brain abnormalities; hypoventilation
Mendeliome v0.4750 NUP188 Zornitza Stark edited their review of gene: NUP188: Changed phenotypes: Sandestig-Stefanova syndrome, 618804, microcephaly, ID, cataract, structural brain abnormalities, hypoventilation
Mendeliome v0.4750 SETD1A Zornitza Stark Marked gene: SETD1A as ready
Mendeliome v0.4750 SETD1A Zornitza Stark Gene: setd1a has been classified as Green List (High Evidence).
Mendeliome v0.4750 SETD1A Zornitza Stark Classified gene: SETD1A as Green List (high evidence)
Mendeliome v0.4750 SETD1A Zornitza Stark Gene: setd1a has been classified as Green List (High Evidence).
Mendeliome v0.4749 SETD1A Zornitza Stark gene: SETD1A was added
gene: SETD1A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SETD1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SETD1A were set to 31197650; 32346159
Phenotypes for gene: SETD1A were set to Epilepsy, early-onset, with or without developmental delay, MIM# 618832
Review for gene: SETD1A was set to GREEN
Added comment: 19 unrelated individuals reported with de novo variants in this gene and a neurodevelopmental phenotype, primarily manifesting and ID and seizures. LOF mechanism supported by functional data. Three mouse models. SNPs in this gene have also been associated with risk of developing schizophrenia.
Sources: Literature
Mendeliome v0.4748 HPDL Zornitza Stark Phenotypes for gene: HPDL were changed from Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (NEDSWMA), MIM#619026; Progressive neurological disorder; Leigh-like syndrome to Spastic paraplegia-83 (SPG83), MIM#619027; Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (NEDSWMA), MIM#619026; Progressive neurological disorder; Leigh-like syndrome
Mendeliome v0.4747 HPDL Zornitza Stark edited their review of gene: HPDL: Added comment: Although two distinct distinct disease associations have been assigned by OMIM, these clinical presentations likely represent a continuum of severity for an underlying mitochondrial disorder.; Changed phenotypes: Spastic paraplegia-83 (SPG83), MIM#619027, Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (NEDSWMA), MIM#619026
Mendeliome v0.4747 HPDL Zornitza Stark commented on gene: HPDL: 17 individuals from 13 families, with a spectrum of neurologic impairment ranging from a severe congenital form without any neurological development (n = 2/17, 12%) to infantile-onset presentations (n = 10/17, 59%) with moderate to severe neurodevelopmental issues, partly with a pathology reminiscent of mitochondrial disease (Leigh-like syndrome), to juvenile-onset spastic paraplegia (n = 5/17, 29%).

Frequently observed clinical findings included chronic progression of neurological signs (n = 16/17, 94%), motor developmental delay (n = 12/17, 71%), intellectual impairment (n = 11/17, 65%), microcephaly (n = 9/16, 56%), and seizures/epilepsy (n = 9/17, 53%). Other relevant clinical findings were visual disturbances/strabismus (n = 9/17, 53%) and loss of developmental milestones (n = 6/17, 35%).

Acute central respiratory failure leading to life-threatening events requiring partly mechanically assisted ventilation occurred in half of individuals with infantile presentation (n = 5/10, 50%), respectively one third of all individuals (n = 5/17, 29%).

Demyelinating neuropathy was present in three individuals (n = 3/11, 27%), with reduced sensory nerve conduction velocity (NCV) in all and severely reduced motor NCV in one.
Mendeliome v0.4747 HPDL Zornitza Stark Phenotypes for gene: HPDL were changed from Progressive neurological disorder; Leigh-like syndrome to Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (NEDSWMA), MIM#619026; Progressive neurological disorder; Leigh-like syndrome
Mendeliome v0.4746 HPDL Zornitza Stark edited their review of gene: HPDL: Changed rating: GREEN
Mendeliome v0.4746 HPDL Zornitza Stark reviewed gene: HPDL: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (NEDSWMA), MIM#619026; Mode of inheritance: None
Mendeliome v0.4746 SCN1A Zornitza Stark Publications for gene: SCN1A were set to 30368457; 12754708; 25754450; 32928894
Mendeliome v0.4745 SCN1A Zornitza Stark edited their review of gene: SCN1A: Changed publications: 29543227
Mendeliome v0.4745 SCN1A Zornitza Stark Phenotypes for gene: SCN1A were changed from Epileptic encephalopathy, early infantile, 6 (Dravet syndrome), MIM# 607208 to Epileptic encephalopathy, early infantile, 6 (Dravet syndrome), MIM# 607208; Genetic Epilepsy Febrile Seizures plus (GEFS+) Syndrome; Febrile seizures; Arthrogryposis multiplex congenita
Mendeliome v0.4744 SCN1A Zornitza Stark Publications for gene: SCN1A were set to 30368457; 12754708; 25754450
Mendeliome v0.4743 SCN1A Zornitza Stark edited their review of gene: SCN1A: Added comment: Note we have reported the association with AMC previously in PMID 29543227 (Supplementary info) in an infant presenting with AMC and severe EE, and de novo p.(Ile1347Asn) variant which at the time was thought to only partially explain the phenotype, but in light of this new report, likely fully explains the phenotype. Given the presence of severe seizure disorder in the two infants who were phenotyped in the newborn period, this likely represents the severe end of the spectrum of SCN1A-related disorders rather than a distinct association.; Changed phenotypes: Epileptic encephalopathy, early infantile, 6 (Dravet syndrome), MIM# 607208, Genetic Epilepsy Febrile Seizures plus (GEFS+) Syndrome, Febrile seizures, Arthrogryposis multiplex congenita
Mendeliome v0.4743 SCN1A Zornitza Stark Deleted their comment
Mendeliome v0.4743 PRKD1 Zornitza Stark changed review comment from: PMID: 32817298 (2020) - Two additional unrelated cases with de novo variants, c.1774G>C and c.1808G>A, and telangiectasia, ectodermal dysplasia, brachydactyly and congenital heart disease. Functional analysis using in vitro kinase assays with recombinant proteins showed that the c.1808G>A, p.(Arg603His) variant represents a gain-of-function mutation encoding an enzyme with a constitutive, lipid-independent catalytic activity. The c.1774G>C, p.(Gly592Arg) variant in contrast shows a defect in substrate phosphorylation representing a loss-of-function mutation.

c.1774G>C, p.(Gly592Arg) is recurrent, reported in 3/5 individuals.; to: PMID: 27479907 (2016): three individuals reported, two with the c.1774G>A variant and one with the c.896T>G variant. All had congenital heart disease, two had some developmental delay, and two had variable features of ectodermal dysplasia, including sparse hair, dry skin, thin skin, fragile nails, premature loss of primary teeth, and small widely spaced teeth; the third individuals had a 'disorganized eyebrow.'

PMID: 32817298 (2020) - Two additional unrelated cases with de novo variants, c.1774G>C and c.1808G>A, and telangiectasia, ectodermal dysplasia, brachydactyly and congenital heart disease. Functional analysis using in vitro kinase assays with recombinant proteins showed that the c.1808G>A, p.(Arg603His) variant represents a gain-of-function mutation encoding an enzyme with a constitutive, lipid-independent catalytic activity. The c.1774G>C, p.(Gly592Arg) variant in contrast shows a defect in substrate phosphorylation representing a loss-of-function mutation.

c.1774G>C, p.(Gly592Arg) is recurrent, reported in 3/5 individuals.
Mendeliome v0.4743 PRKD1 Zornitza Stark Publications for gene: PRKD1 were set to 27479907
Mendeliome v0.4742 PRKD1 Zornitza Stark reviewed gene: PRKD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27479907, 32817298; Phenotypes: Congenital heart defects and ectodermal dysplasia, 617364; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4742 SCN1A Arina Puzriakova reviewed gene: SCN1A: Rating: AMBER; Mode of pathogenicity: None; Publications: 32928894; Phenotypes: Arthrogryposis multiplex congenita; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.4742 SIX1 Zornitza Stark Gene: six1 has been classified as Green List (High Evidence).
Mendeliome v0.4742 SIX1 Zornitza Stark Phenotypes for gene: SIX1 were changed from to Deafness, autosomal dominant 23, MIM# 605192; Branchiootic syndrome 3, MIM# 608389
Mendeliome v0.4741 SIX1 Zornitza Stark Publications for gene: SIX1 were set to
Mendeliome v0.4740 SIX1 Zornitza Stark Mode of inheritance for gene: SIX1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4739 SIX1 Zornitza Stark reviewed gene: SIX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15141091, 18330911, 21254961, 17637804, 29500469, 21700001, 24164807; Phenotypes: Deafness, autosomal dominant 23, MIM# 605192, Branchiootic syndrome 3, MIM# 608389; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4739 PTPRQ Zornitza Stark Marked gene: PTPRQ as ready
Mendeliome v0.4739 PTPRQ Zornitza Stark Gene: ptprq has been classified as Green List (High Evidence).
Mendeliome v0.4739 PTPRQ Zornitza Stark Phenotypes for gene: PTPRQ were changed from to Deafness, autosomal recessive 84A, MIM# 613391; Deafness, autosomal dominant 73, MIM# 617663
Mendeliome v0.4738 PTPRQ Zornitza Stark Publications for gene: PTPRQ were set to
Mendeliome v0.4737 PTPRQ Zornitza Stark Mode of inheritance for gene: PTPRQ was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4736 PTPRQ Zornitza Stark reviewed gene: PTPRQ: Rating: GREEN; Mode of pathogenicity: None; Publications: 20346435, 20472657, 25919374, 14534255, 22357859, 29849575, 29309402, 31655630; Phenotypes: Deafness, autosomal recessive 84A, MIM# 613391, Deafness, autosomal dominant 73, MIM# 617663; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4736 POU4F3 Zornitza Stark Gene: pou4f3 has been classified as Green List (High Evidence).
Mendeliome v0.4736 POU4F3 Zornitza Stark Phenotypes for gene: POU4F3 were changed from to Deafness, autosomal dominant 15, MIM# 602459
Mendeliome v0.4735 POU4F3 Zornitza Stark Publications for gene: POU4F3 were set to
Mendeliome v0.4734 POU4F3 Zornitza Stark Mode of inheritance for gene: POU4F3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4733 POU4F3 Zornitza Stark reviewed gene: POU4F3: Rating: GREEN; Mode of pathogenicity: None; Publications: 18228599, 9506947, 20434433, 28545070, 15254021, 8637595; Phenotypes: Deafness, autosomal dominant 15, MIM# 602459; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4733 KPTN Zornitza Stark Marked gene: KPTN as ready
Mendeliome v0.4733 KPTN Zornitza Stark Gene: kptn has been classified as Green List (High Evidence).
Mendeliome v0.4733 KPTN Zornitza Stark Phenotypes for gene: KPTN were changed from to Mental retardation, autosomal recessive 41 (MIM#615637)
Mendeliome v0.4732 KPTN Zornitza Stark Publications for gene: KPTN were set to
Mendeliome v0.4731 KPTN Zornitza Stark Mode of inheritance for gene: KPTN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4730 NPHS1 Zornitza Stark Gene: nphs1 has been classified as Green List (High Evidence).
Mendeliome v0.4730 NPHS1 Zornitza Stark Phenotypes for gene: NPHS1 were changed from to Nephrotic syndrome, type 1, MIM# 256300
Mendeliome v0.4729 NPHS1 Zornitza Stark Mode of inheritance for gene: NPHS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4728 TTI2 Zornitza Stark Marked gene: TTI2 as ready
Mendeliome v0.4728 TTI2 Zornitza Stark Gene: tti2 has been classified as Green List (High Evidence).
Mendeliome v0.4728 TTI2 Zornitza Stark Phenotypes for gene: TTI2 were changed from to Mental retardation, autosomal recessive 39, MIM#615541
Mendeliome v0.4727 TTI2 Zornitza Stark Publications for gene: TTI2 were set to
Mendeliome v0.4726 TTI2 Zornitza Stark Mode of inheritance for gene: TTI2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4725 TTI2 Zornitza Stark reviewed gene: TTI2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32061250, 23956177, 31737043; Phenotypes: Mental retardation, autosomal recessive 39, MIM#615541; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4725 IGSF10 Bryony Thompson Gene: igsf10 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4725 IGSF10 Bryony Thompson Classified gene: IGSF10 as Amber List (moderate evidence)
Mendeliome v0.4725 IGSF10 Bryony Thompson Gene: igsf10 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4724 IGSF10 Bryony Thompson gene: IGSF10 was added
gene: IGSF10 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: IGSF10 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: IGSF10 were set to 27137492; 31042289
Phenotypes for gene: IGSF10 were set to delayed puberty; hypogonadotropic hypogonadism; primary ovary insufficiency
Review for gene: IGSF10 was set to AMBER
Added comment: PMID: 27137492 - 4 Finnish families segregating p.Glu161Lys, but Finnish MAF in ExAC is 2%. Another six additional families with a possible missense, but variants are seen in ExAC suggesting incomplete penetrance. Supporting in vitro functional assays and zebrafish model. PMID: 31042289 - 2 unrelated consanguineous families with homozygous variants and family with a heterozygous frameshift and apparent incomplete penetrance.
Sources: Literature
Mendeliome v0.4723 KPTN Melanie Marty reviewed gene: KPTN: Rating: GREEN; Mode of pathogenicity: None; Publications: 24239382, 32358097, 32808430; Phenotypes: Mental retardation, autosomal recessive 41 (MIM#615637); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4723 NPHS1 Elena Savva reviewed gene: NPHS1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Nephrotic syndrome, type 1 256300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4723 PFN1 Zornitza Stark Gene: pfn1 has been classified as Green List (High Evidence).
Mendeliome v0.4723 PFN1 Zornitza Stark Publications for gene: PFN1 were set to
Mendeliome v0.4722 PFN1 Zornitza Stark Phenotypes for gene: PFN1 were changed from to Amyotrophic lateral sclerosis 18 (MIM# 614808); Paget’s disease of bone
Mendeliome v0.4721 PFN1 Zornitza Stark Mode of inheritance for gene: PFN1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4720 PFN1 Zornitza Stark reviewed gene: PFN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31802421, 31611772, 31401564, 30203378, 28040732, 22801503; Phenotypes: Amyotrophic lateral sclerosis 18, MIM# 614808; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4720 PCDH15 Zornitza Stark Gene: pcdh15 has been classified as Green List (High Evidence).
Mendeliome v0.4720 PCDH15 Zornitza Stark Phenotypes for gene: PCDH15 were changed from to Usher syndrome, type 1F, MIM# 602083; Deafness, autosomal recessive 23, MIM# 609533
Mendeliome v0.4719 PCDH15 Zornitza Stark Publications for gene: PCDH15 were set to
Mendeliome v0.4718 PCDH15 Zornitza Stark Mode of inheritance for gene: PCDH15 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4717 PCDH15 Zornitza Stark reviewed gene: PCDH15: Rating: GREEN; Mode of pathogenicity: None; Publications: 11398101, 11487575, 11138007, 12782354, 16260500, 14570705, 25930172, 28281779; Phenotypes: Usher syndrome, type 1F, MIM# 602083, Deafness, autosomal recessive 23, MIM# 609533; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4717 PFN1 Melanie Marty reviewed gene: PFN1: Rating: AMBER; Mode of pathogenicity: None; Publications: 32392277, 31991009, 31346562, 32589291, 22801503; Phenotypes: Paget’s disease of bone; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4717 WHRN Zornitza Stark Gene: whrn has been classified as Green List (High Evidence).
Mendeliome v0.4717 WHRN Zornitza Stark Phenotypes for gene: WHRN were changed from to Usher syndrome, type 2D, MIM# 611383; Deafness, autosomal recessive 31, MIM# 607084
Mendeliome v0.4716 WHRN Zornitza Stark Publications for gene: WHRN were set to
Mendeliome v0.4715 WHRN Zornitza Stark Mode of inheritance for gene: WHRN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4714 WHRN Zornitza Stark reviewed gene: WHRN: Rating: GREEN; Mode of pathogenicity: None; Publications: 17171570, 21738389, 22147658, 26338283, 12833159, 20502675, 28254438, 27117407, 12833159, 29270100, 15841483; Phenotypes: Usher syndrome, type 2D, MIM# 611383, Deafness, autosomal recessive 31, MIM# 607084; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4714 PFN1 Ain Roesley reviewed gene: PFN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23141414, 22801503, 25499087, 24309268, 22801503, 26908597; Phenotypes: Amyotrophic lateral sclerosis 18 (MIM# 614808); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4714 OTOGL Zornitza Stark Marked gene: OTOGL as ready
Mendeliome v0.4714 OTOGL Zornitza Stark Gene: otogl has been classified as Green List (High Evidence).
Mendeliome v0.4714 OTOGL Zornitza Stark Phenotypes for gene: OTOGL were changed from to Deafness, autosomal recessive 84B, MIM# 614944
Mendeliome v0.4713 OTOGL Zornitza Stark Publications for gene: OTOGL were set to
Mendeliome v0.4712 OTOGL Zornitza Stark Mode of inheritance for gene: OTOGL was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4711 OTOGL Zornitza Stark reviewed gene: OTOGL: Rating: GREEN; Mode of pathogenicity: None; Publications: 23122586, 23850727, 25829320, ​25719458, 28426234; Phenotypes: Deafness, autosomal recessive 84B, MIM# 614944; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4711 RDX Zornitza Stark Gene: rdx has been classified as Green List (High Evidence).
Mendeliome v0.4711 RDX Zornitza Stark Phenotypes for gene: RDX were changed from to Deafness, autosomal recessive 24, MIM# 611022
Mendeliome v0.4710 RDX Zornitza Stark Publications for gene: RDX were set to
Mendeliome v0.4709 RDX Zornitza Stark Mode of inheritance for gene: RDX was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4708 RDX Zornitza Stark reviewed gene: RDX: Rating: GREEN; Mode of pathogenicity: None; Publications: 17226784, 19215054, 22567349, 26226137, 15314067; Phenotypes: Deafness, autosomal recessive 24, MIM# 611022; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4708 OTOA Zornitza Stark Marked gene: OTOA as ready
Mendeliome v0.4708 OTOA Zornitza Stark Gene: otoa has been classified as Green List (High Evidence).
Mendeliome v0.4708 OTOA Zornitza Stark Phenotypes for gene: OTOA were changed from to Deafness, autosomal recessive 22, MIM# 607039
Mendeliome v0.4707 OTOA Zornitza Stark Publications for gene: OTOA were set to
Mendeliome v0.4706 OTOA Zornitza Stark Mode of inheritance for gene: OTOA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4705 OTOA Zornitza Stark reviewed gene: OTOA: Rating: GREEN; Mode of pathogenicity: None; Publications: 11972037, 19888295, 23173898, 16460646, 26029705, 26969326, 23129639; Phenotypes: Deafness, autosomal recessive 22, MIM# 607039; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4705 MYO7A Zornitza Stark Gene: myo7a has been classified as Green List (High Evidence).
Mendeliome v0.4705 MYO7A Zornitza Stark Phenotypes for gene: MYO7A were changed from to Deafness, autosomal dominant 11, MIM# 601317; Deafness, autosomal recessive 2, 600060; Usher syndrome, type 1B, MIM# 276900
Mendeliome v0.4704 MYO7A Zornitza Stark Publications for gene: MYO7A were set to
Mendeliome v0.4703 MYO7A Zornitza Stark Mode of inheritance for gene: MYO7A was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4702 MYO7A Zornitza Stark reviewed gene: MYO7A: Rating: GREEN; Mode of pathogenicity: None; Publications: 9354784, 15300860, 15121790, 15221449, 16449806, 21150918, 23451214, 23383098, 28802369, 29400105, 23559863, 18181211, 25211151; Phenotypes: Deafness, autosomal dominant 11, MIM# 601317, Deafness, autosomal recessive 2, 600060, Usher syndrome, type 1B, MIM# 276900; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4702 SMPX Zornitza Stark Gene: smpx has been classified as Green List (High Evidence).
Mendeliome v0.4702 SMPX Zornitza Stark Phenotypes for gene: SMPX were changed from to Deafness, X-linked 4, MIM# 300066
Mendeliome v0.4701 SMPX Zornitza Stark Publications for gene: SMPX were set to
Mendeliome v0.4700 SMPX Zornitza Stark Mode of inheritance for gene: SMPX was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.4699 SMPX Zornitza Stark reviewed gene: SMPX: Rating: GREEN; Mode of pathogenicity: None; Publications: 21549342, 21549336, 21893181, 22911656, 28542515; Phenotypes: Deafness, X-linked 4, MIM# 300066; 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 v0.4699 MYO6 Zornitza Stark Gene: myo6 has been classified as Green List (High Evidence).
Mendeliome v0.4699 MYO6 Zornitza Stark Phenotypes for gene: MYO6 were changed from to Deafness, autosomal dominant 22, MIM# 606346; Deafness, autosomal recessive 37, MIM# 607821
Mendeliome v0.4698 MYO6 Zornitza Stark Publications for gene: MYO6 were set to
Mendeliome v0.4697 MYO6 Zornitza Stark Mode of inheritance for gene: MYO6 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.4696 MYO6 Zornitza Stark reviewed gene: MYO6: Rating: GREEN; Mode of pathogenicity: None; Publications: 24105371, 11468689, 25999546, 25227905, 18348273, 27171474; Phenotypes: Deafness, autosomal dominant 22, MIM# 606346, Deafness, autosomal recessive 37, MIM# 607821; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.4696 MYO15A Zornitza Stark Gene: myo15a has been classified as Green List (High Evidence).
Mendeliome v0.4696 MYO15A Zornitza Stark Phenotypes for gene: MYO15A were changed from to Deafness, autosomal recessive 3, MIM# 600316
Mendeliome v0.4695 MYO15A Zornitza Stark Publications for gene: MYO15A were set to
Mendeliome v0.4694 MYO15A Zornitza Stark Mode of inheritance for gene: MYO15A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4693 MYO15A Zornitza Stark reviewed gene: MYO15A: Rating: GREEN; Mode of pathogenicity: None; Publications: 27375115, 26226137, 23208854, 19309289, 9603735, 10915760; Phenotypes: Deafness, autosomal recessive 3, MIM# 600316; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4693 MYH9 Zornitza Stark Gene: myh9 has been classified as Green List (High Evidence).
Mendeliome v0.4693 MYH9 Zornitza Stark Phenotypes for gene: MYH9 were changed from to Deafness, autosomal dominant 17, MIM# 603622; Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss, MIM# 155100; MYH9-related disorders
Mendeliome v0.4692 MYH9 Zornitza Stark Publications for gene: MYH9 were set to
Mendeliome v0.4691 MYH9 Zornitza Stark Mode of inheritance for gene: MYH9 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4690 MYH9 Zornitza Stark reviewed gene: MYH9: Rating: GREEN; Mode of pathogenicity: None; Publications: 9390828, 24890873, 17146397, 25505834, 16630581, 16162639, 23976996, 21908426; Phenotypes: Deafness, autosomal dominant 17, MIM# 603622, Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss, MIM# 155100, MYH9-related disorders; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4690 MARVELD2 Zornitza Stark Gene: marveld2 has been classified as Green List (High Evidence).
Mendeliome v0.4690 MARVELD2 Zornitza Stark Phenotypes for gene: MARVELD2 were changed from to Deafness, autosomal recessive 49, MIM# 610153
Mendeliome v0.4689 MARVELD2 Zornitza Stark Publications for gene: MARVELD2 were set to
Mendeliome v0.4688 MARVELD2 Zornitza Stark Mode of inheritance for gene: MARVELD2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4687 MARVELD2 Zornitza Stark reviewed gene: MARVELD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 17186462, 18084694, 22903915, 27344577, 26677943, 23979167; Phenotypes: Deafness, autosomal recessive 49, MIM# 610153; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4687 RPL9 Zornitza Stark Added comment: Comment when marking as ready: Second individual reported with same c.-2+1G>C variant in the 5′UTR of RPL9, deleterious effect demonstrated, functional data, upgrade to Amber.
Mendeliome v0.4687 RPL9 Zornitza Stark Gene: rpl9 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4687 RPL9 Zornitza Stark Publications for gene: RPL9 were set to 29114930; 20116044
Mendeliome v0.4686 RPL9 Zornitza Stark Classified gene: RPL9 as Amber List (moderate evidence)
Mendeliome v0.4686 RPL9 Zornitza Stark Gene: rpl9 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4685 RPL9 Arina Puzriakova changed review comment from: PMID: 31799629 (2020) - One individual diagnosed with Diamond Blackfan anaemia carrying a de novo variant (c.-2+1G>C) in the 5′UTR of RPL9, predicted to affect the donor splice site of exon 1. Functional studies showed the variant impairs processing of pre-rRNA during ribosome biogenesis, stabilises TP53 and impairs the proliferation and differentiation of erythroid cells. Zebrafish models of RPL9 LoF recapitulate the anaemia phenotype.; to: PMID: 31799629 (2020) - Female infant diagnosed with Diamond-Blackfan anaemia carrying a de novo variant (c.-2+1G>C) in the 5′UTR of RPL9, predicted to affect the donor splice site of exon 1. Phenotypic overlap can be seen with the previously reported case with the same variant, including colitis, thumb anomaly, and microcephaly. Functional studies showed the variant impairs processing of pre-rRNA during ribosome biogenesis, stabilises TP53 and impairs the proliferation and differentiation of erythroid cells. Zebrafish models of RPL9 LoF recapitulate the anaemia phenotype.
Mendeliome v0.4685 RPL9 Arina Puzriakova reviewed gene: RPL9: Rating: AMBER; Mode of pathogenicity: None; Publications: 31799629; Phenotypes: Diamond Blackfan anaemia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.4685 LRTOMT Zornitza Stark Marked gene: LRTOMT as ready
Mendeliome v0.4685 LRTOMT Zornitza Stark Gene: lrtomt has been classified as Green List (High Evidence).
Mendeliome v0.4685 LRTOMT Zornitza Stark Phenotypes for gene: LRTOMT were changed from to Deafness, autosomal recessive 63, MIM# 611451
Mendeliome v0.4684 LRTOMT Zornitza Stark Publications for gene: LRTOMT were set to
Mendeliome v0.4683 LRTOMT Zornitza Stark Mode of inheritance for gene: LRTOMT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4682 LRTOMT Zornitza Stark reviewed gene: LRTOMT: Rating: GREEN; Mode of pathogenicity: None; Publications: 18953341, 18794526, 21739586, 18794526; Phenotypes: Deafness, autosomal recessive 63, MIM# 611451; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4682 LHFPL5 Zornitza Stark Gene: lhfpl5 has been classified as Green List (High Evidence).
Mendeliome v0.4682 LHFPL5 Zornitza Stark Phenotypes for gene: LHFPL5 were changed from to Deafness, autosomal recessive 67, MIM# 610265
Mendeliome v0.4681 LHFPL5 Zornitza Stark Publications for gene: LHFPL5 were set to
Mendeliome v0.4680 LHFPL5 Zornitza Stark Mode of inheritance for gene: LHFPL5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4679 LHFPL5 Zornitza Stark reviewed gene: LHFPL5: Rating: GREEN; Mode of pathogenicity: None; Publications: 16459341, 16752389, 21816241, 19888295, 26437881, 26029705, 15905332, 19102128, 25550511; Phenotypes: Deafness, autosomal recessive 67, MIM# 610265; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4679 GYS1 Zornitza Stark Gene: gys1 has been classified as Green List (High Evidence).
Mendeliome v0.4679 GYS1 Zornitza Stark Phenotypes for gene: GYS1 were changed from to Glycogen storage disease 0, muscle, MIM# 611556
Mendeliome v0.4678 GYS1 Zornitza Stark Publications for gene: GYS1 were set to
Mendeliome v0.4677 GYS1 Zornitza Stark Mode of inheritance for gene: GYS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4676 GYS1 Zornitza Stark reviewed gene: GYS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 17928598, 19699667, 21958591; Phenotypes: Glycogen storage disease 0, muscle, MIM# 611556; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4676 PIGT Zornitza Stark Marked gene: PIGT as ready
Mendeliome v0.4676 PIGT Zornitza Stark Gene: pigt has been classified as Green List (High Evidence).
Mendeliome v0.4676 PIGT Zornitza Stark Phenotypes for gene: PIGT were changed from Multiple congenital anomalies-hypotonia-seizures syndrome 3, MIM# 615398 to Multiple congenital anomalies-hypotonia-seizures syndrome 3, MIM# 615398
Mendeliome v0.4675 PIGT Zornitza Stark Phenotypes for gene: PIGT were changed from to Multiple congenital anomalies-hypotonia-seizures syndrome 3, MIM# 615398
Mendeliome v0.4674 PIGT Zornitza Stark Publications for gene: PIGT were set to
Mendeliome v0.4673 PIGT Zornitza Stark Mode of inheritance for gene: PIGT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4672 PIGT Zornitza Stark reviewed gene: PIGT: Rating: GREEN; Mode of pathogenicity: None; Publications: 30976099, 25943031, 24906948, 24906948, 24906948, 28728837, 28728837, 28728837; Phenotypes: Multiple congenital anomalies-hypotonia-seizures syndrome 3, MIM# 615398; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4672 ALG13 Zornitza Stark Gene: alg13 has been classified as Green List (High Evidence).
Mendeliome v0.4672 ALG13 Zornitza Stark Phenotypes for gene: ALG13 were changed from to Congenital disorder of glycosylation, type Is (MIM# 300884)
Mendeliome v0.4671 ALG13 Zornitza Stark Publications for gene: ALG13 were set to
Mendeliome v0.4670 ALG13 Zornitza Stark Mode of inheritance for gene: ALG13 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.4669 ALG13 Zornitza Stark reviewed gene: ALG13: Rating: GREEN; Mode of pathogenicity: None; Publications: 23033978, 23934111, 24781210, 24896178, 25732998, 26138355, 26482601, 28940310, 32238909; Phenotypes: Congenital disorder of glycosylation, type Is (MIM# 300884); 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 v0.4669 BLOC1S5 Zornitza Stark Gene: bloc1s5 has been classified as Green List (High Evidence).
Mendeliome v0.4669 BLOC1S5 Zornitza Stark Classified gene: BLOC1S5 as Green List (high evidence)
Mendeliome v0.4669 BLOC1S5 Zornitza Stark Gene: bloc1s5 has been classified as Green List (High Evidence).
Mendeliome v0.4668 BLOC1S5 Zornitza Stark gene: BLOC1S5 was added
gene: BLOC1S5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BLOC1S5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BLOC1S5 were set to 32565547
Phenotypes for gene: BLOC1S5 were set to Hermansky–Pudlak syndrome
Review for gene: BLOC1S5 was set to GREEN
Added comment: 2 unrelated patients with mild oculocutaneous albinism, moderate bleeding diathesis, platelet aggregation deficit, and a dramatically decreased number of platelet dense granules, all signs compatible with HPS. Identified distinct homozygous variants in the BLOC1S5 gene (patient 1: deletion of exons 3 and 4, patient 2: 1-bp deletion in exon 4). Parental segregation confirmatory in patient 1, quantitative PCR analysis confirmatory in patient 2). Functional tests performed on platelets of one patient displayed an absence of the obligate multisubunit complex BLOC-1, showing that the variant disrupts BLOC1S5 function and impairs BLOC-1 assembly. Expression of the patient-derived BLOC1S5 deletion in nonpigmented murine Bloc1s5-/- melan-mu melanocytes failed to rescue pigmentation, the assembly of a functional BLOC-1 complex, and melanosome cargo trafficking, unlike the wild-type allele. Pathogenic variants in the genes encoding three other BLOC-1 subunits (DTNBP1, BLOC1S3, and BLOC1S6) underlie HPS types 7, 8, and 9 respectively.
Sources: Literature
Mendeliome v0.4667 FOXL2 Zornitza Stark Gene: foxl2 has been classified as Green List (High Evidence).
Mendeliome v0.4667 FOXL2 Zornitza Stark Phenotypes for gene: FOXL2 were changed from to Blepharophimosis, epicanthus inversus, and ptosis, type 1 with premature ovarian insufficiency (POI) and type II without POI (MIM# 110100)
Mendeliome v0.4666 FOXL2 Zornitza Stark Publications for gene: FOXL2 were set to
Mendeliome v0.4665 FOXL2 Zornitza Stark Mode of inheritance for gene: FOXL2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4664 FOXL2 Ain Roesley changed review comment from: PMID: 31077882; 19x probands reported, AD.

PMID: 18642388;
BPES type I : Mutations predicted to result in proteins with truncation before the poly-Ala tract
BPES type II: poly-Ala expansions (WT poly-Ala is between aa 221-234)
Exceptions: Truncated proteins with complete forkhead and poly-Ala domains, can be either Type I and II

NOTE: only 1 family reported for AR (PMID: 17089161); to: PMID: 31077882; >100 probands reported, AD.

PMID: 18642388;
BPES type I : Mutations predicted to result in proteins with truncation before the poly-Ala tract
BPES type II: poly-Ala expansions (WT poly-Ala is between aa 221-234)
Exceptions: Truncated proteins with complete forkhead and poly-Ala domains, can be either Type I and II

NOTE: only 1 family reported for AR (PMID: 17089161)
Mendeliome v0.4664 FOXL2 Ain Roesley reviewed gene: FOXL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31077882, 18642388, 17089161; Phenotypes: Blepharophimosis, epicanthus inversus, and ptosis, type 1 with premature ovarian insufficiency (POI) and type II without POI (MIM# 110100); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4664 ILDR1 Zornitza Stark Gene: ildr1 has been classified as Green List (High Evidence).
Mendeliome v0.4664 ILDR1 Zornitza Stark Phenotypes for gene: ILDR1 were changed from to Deafness, autosomal recessive 42, MIM# 609646
Mendeliome v0.4663 ILDR1 Zornitza Stark Publications for gene: ILDR1 were set to
Mendeliome v0.4662 ILDR1 Zornitza Stark Mode of inheritance for gene: ILDR1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4661 ILDR1 Zornitza Stark reviewed gene: ILDR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21255762, 23226338, 22903915, 27344577, 21255762, 23239027, 25822906, 25819842, 24990150; Phenotypes: Deafness, autosomal recessive 42, MIM# 609646; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4661 HOXA2 Zornitza Stark Gene: hoxa2 has been classified as Green List (High Evidence).
Mendeliome v0.4661 HOXA2 Zornitza Stark Phenotypes for gene: HOXA2 were changed from to Microtia with or without hearing impairment, MIM# 612290
Mendeliome v0.4660 HOXA2 Zornitza Stark Publications for gene: HOXA2 were set to
Mendeliome v0.4659 HOXA2 Zornitza Stark Mode of inheritance for gene: HOXA2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4658 HOXA2 Zornitza Stark reviewed gene: HOXA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 18394579, 23775976, 27503514, 32649979, 31567444; Phenotypes: Microtia with or without hearing impairment, MIM# 612290; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4658 GRXCR1 Zornitza Stark Gene: grxcr1 has been classified as Green List (High Evidence).
Mendeliome v0.4658 GRXCR1 Zornitza Stark Phenotypes for gene: GRXCR1 were changed from to Deafness, autosomal recessive 25, MIM# 613285
Mendeliome v0.4657 GRXCR1 Zornitza Stark Publications for gene: GRXCR1 were set to
Mendeliome v0.4656 GRXCR1 Zornitza Stark Mode of inheritance for gene: GRXCR1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4655 GRXCR1 Zornitza Stark reviewed gene: GRXCR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20137778, 25802247, 26226137, 26445815, 26969326, 20137774; Phenotypes: Deafness, autosomal recessive 25, MIM# 613285; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4655 GPSM2 Zornitza Stark Gene: gpsm2 has been classified as Green List (High Evidence).
Mendeliome v0.4655 GPSM2 Zornitza Stark Phenotypes for gene: GPSM2 were changed from to Chudley-McCullough syndrome, MIM# 604213
Mendeliome v0.4654 GPSM2 Zornitza Stark Publications for gene: GPSM2 were set to
Mendeliome v0.4653 GPSM2 Zornitza Stark Mode of inheritance for gene: GPSM2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4652 GPSM2 Zornitza Stark reviewed gene: GPSM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20602914, 22578326, 28387217, 27180139, 27064331; Phenotypes: Chudley-McCullough syndrome, MIM# 604213; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4652 GIPC3 Zornitza Stark Gene: gipc3 has been classified as Green List (High Evidence).
Mendeliome v0.4652 GIPC3 Zornitza Stark Phenotypes for gene: GIPC3 were changed from to Deafness, autosomal recessive 15, MIM# 601869
Mendeliome v0.4651 GIPC3 Zornitza Stark Publications for gene: GIPC3 were set to
Mendeliome v0.4650 GIPC3 Zornitza Stark Mode of inheritance for gene: GIPC3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4649 GIPC3 Zornitza Stark reviewed gene: GIPC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 21326233, 21660509; Phenotypes: Deafness, autosomal recessive 15, MIM# 601869; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4649 COCH Zornitza Stark Phenotypes for gene: COCH were changed from Deafness, autosomal dominant 9, MIM# 601369 to Deafness, autosomal dominant 9, MIM# 601369; Deafness, autosomal recessive 110, MIM# 618094
Mendeliome v0.4648 COCH Zornitza Stark Publications for gene: COCH were set to 16151338; 28116169; 28099493; 9806553; 17561763; 21046548; 26256111; 22931125; 22610276; 18312449; 28733840; 18697796; 29449721
Mendeliome v0.4647 COCH Zornitza Stark changed review comment from: Mono-allelic variants: Over 50 affected individuals from more than 10 families reported, mouse model. Dominant negative effect postulated.

Bi-allelic variants: three families reported with bi-allelic variants in this gene and deafness. All variants are LOF, some functional data. PMIDs 29449721, 32939038, 32562050.; to: Mono-allelic variants: Over 50 affected individuals from more than 10 families reported, mouse model. Dominant negative effect postulated.

Bi-allelic variants: three families reported with bi-allelic variants in this gene and deafness. All variants are LOF, some functional data. PMIDs 29449721, 32939038, 32562050.
Mendeliome v0.4647 COCH Zornitza Stark changed review comment from: Over 50 affected individuals from more than 10 families reported, mouse model. Single family with two siblings reported with bi-allelic variants in this gene and deafness (homozygous LOF) in PMID 29449721, evidence for bi-allelic disease is limited.; to: Mono-allelic variants: Over 50 affected individuals from more than 10 families reported, mouse model. Dominant negative effect postulated.

Bi-allelic variants: three families reported with bi-allelic variants in this gene and deafness. All variants are LOF, some functional data. PMIDs 29449721, 32939038, 32562050.
Mendeliome v0.4647 COCH Zornitza Stark edited their review of gene: COCH: Changed publications: 16151338, 28116169, 28099493, 9806553, 17561763, 21046548, 26256111, 22931125, 22610276, 18312449, 28733840, 18697796, 29449721, 32939038, 32562050
Mendeliome v0.4647 COCH Zornitza Stark edited their review of gene: COCH: Changed phenotypes: Deafness, autosomal dominant 9, MIM# 601369, Deafness, autosomal recessive 110, MIM# 618094
Mendeliome v0.4647 CNOT1 Zornitza Stark Phenotypes for gene: CNOT1 were changed from Holoprosencephaly 12, with or without pancreatic agenesis; OMIM# 618500 to Vissers-Bodmer syndrome, MIM#619033; Holoprosencephaly 12, with or without pancreatic agenesis; OMIM# 618500
Mendeliome v0.4646 CNOT1 Zornitza Stark Publications for gene: CNOT1 were set to PMID: 31006513
Mendeliome v0.4645 CNOT1 Zornitza Stark Mode of inheritance for gene: CNOT1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4644 CNOT1 Zornitza Stark reviewed gene: CNOT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Vissers-Bodmer syndrome, MIM#619033; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4644 COQ5 Zornitza Stark Phenotypes for gene: COQ5 were changed from Cerebellar ataxia; encephalopathy; generalized tonic-clonic seizures; intellectual disability to Coenzyme Q10 deficiency, primary 9, MIM#619028; Cerebellar ataxia; encephalopathy; generalized tonic-clonic seizures; intellectual disability
Mendeliome v0.4643 COQ5 Zornitza Stark edited their review of gene: COQ5: Changed phenotypes: Coenzyme Q10 deficiency, primary 9, MIM#619028, Cerebellar ataxia, encephalopathy, generalized tonic-clonic seizures, intellectual disability
Mendeliome v0.4643 GATA3 Zornitza Stark Marked gene: GATA3 as ready
Mendeliome v0.4643 GATA3 Zornitza Stark Gene: gata3 has been classified as Green List (High Evidence).
Mendeliome v0.4643 GATA3 Zornitza Stark Phenotypes for gene: GATA3 were changed from to Hypoparathyroidism, sensorineural deafness, and renal dysplasia, MIM# 146255
Mendeliome v0.4642 GATA3 Zornitza Stark Publications for gene: GATA3 were set to
Mendeliome v0.4641 GATA3 Zornitza Stark Mode of inheritance for gene: GATA3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4640 GATA3 Zornitza Stark reviewed gene: GATA3: Rating: GREEN; Mode of pathogenicity: None; Publications: 10935639, 11389161, 21120445, 26316437, 25771973, 27387476, 30396722; Phenotypes: Hypoparathyroidism, sensorineural deafness, and renal dysplasia, MIM# 146255; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4640 FGF3 Zornitza Stark Publications for gene: FGF3 were set to
Mendeliome v0.4639 FGF3 Zornitza Stark reviewed gene: FGF3: Rating: GREEN; Mode of pathogenicity: None; Publications: 21480479, 21306635, 18435799, 17236138, 21306635, 18701883, 8223243, 26995070, 29902227, 30504125; Phenotypes: Deafness, congenital with inner ear agenesis, microtia, and microdontia, MIM# 610706; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4639 EYA4 Zornitza Stark Phenotypes for gene: EYA4 were changed from to Deafness, autosomal dominant 10, MIM# 601316; Cardiomyopathy, dilated, 1J, MIM# 605362
Mendeliome v0.4638 EYA4 Zornitza Stark Publications for gene: EYA4 were set to
Mendeliome v0.4637 EYA4 Zornitza Stark Mode of inheritance for gene: EYA4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4636 EYA4 Zornitza Stark reviewed gene: EYA4: Rating: GREEN; Mode of pathogenicity: None; Publications: 11159937, ​17568404, 25681523, 25963406, 25242383, 26331839, 18219393, 27545760, 15735644, 10769282, 30155266; Phenotypes: Deafness, autosomal dominant 10, MIM# 601316, Cardiomyopathy, dilated, 1J, MIM# 605362; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4636 ESPN Zornitza Stark Gene: espn has been classified as Green List (High Evidence).
Mendeliome v0.4636 ESPN Zornitza Stark Phenotypes for gene: ESPN were changed from to Deafness, autosomal recessive 36, MIM# 609006; Deafness, neurosensory, without vestibular involvement, autosomal dominant, MIM# 609006
Mendeliome v0.4635 ESPN Zornitza Stark Publications for gene: ESPN were set to
Mendeliome v0.4634 ESPN Zornitza Stark Mode of inheritance for gene: ESPN was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4633 ESPN Zornitza Stark reviewed gene: ESPN: Rating: GREEN; Mode of pathogenicity: None; Publications: 15286153, 18973245, 26445815, 28281779, 10975527, 15930085; Phenotypes: Deafness, autosomal recessive 36, MIM# 609006, Deafness, neurosensory, without vestibular involvement, autosomal dominant, MIM# 609006; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4633 PRIMPOL Zornitza Stark edited their review of gene: PRIMPOL: Changed rating: RED
Mendeliome v0.4633 PRIMPOL Seb Lunke commented on gene: PRIMPOL
Mendeliome v0.4633 DFNB59 Zornitza Stark Gene: dfnb59 has been classified as Green List (High Evidence).
Mendeliome v0.4633 DFNB59 Zornitza Stark Phenotypes for gene: DFNB59 were changed from to Deafness, autosomal recessive 59, MIM# 610220
Mendeliome v0.4632 DFNB59 Zornitza Stark Publications for gene: DFNB59 were set to
Mendeliome v0.4631 DFNB59 Zornitza Stark Mode of inheritance for gene: DFNB59 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4630 DFNB59 Zornitza Stark reviewed gene: DFNB59: Rating: GREEN; Mode of pathogenicity: None; Publications: 16804542, 26166082, 22617256, 28964305, 17373699, 25631766, 28209736; Phenotypes: Deafness, autosomal recessive 59, MIM# 610220; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4630 DFNA5 Zornitza Stark Gene: dfna5 has been classified as Green List (High Evidence).
Mendeliome v0.4630 DFNA5 Zornitza Stark Phenotypes for gene: DFNA5 were changed from to Deafness, autosomal dominant 5, MIM# 600994
Mendeliome v0.4629 DFNA5 Zornitza Stark Publications for gene: DFNA5 were set to
Mendeliome v0.4628 DFNA5 Zornitza Stark Mode of inheritance for gene: DFNA5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4627 DFNA5 Zornitza Stark Tag new gene name tag was added to gene: DFNA5.
Mendeliome v0.4627 DFNA5 Zornitza Stark reviewed gene: DFNA5: Rating: GREEN; Mode of pathogenicity: None; Publications: 9771715, 14676472, ​14559215, 24933359, 17868390, 24506266, 12853124, 14736743, 22848872; Phenotypes: Deafness, autosomal dominant 5, MIM# 600994; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4627 RIC3 Bryony Thompson Gene: ric3 has been classified as Red List (Low Evidence).
Mendeliome v0.4627 RIC3 Bryony Thompson Classified gene: RIC3 as Red List (low evidence)
Mendeliome v0.4627 RIC3 Bryony Thompson Gene: ric3 has been classified as Red List (Low Evidence).
Mendeliome v0.4626 RIC3 Bryony Thompson reviewed gene: RIC3: Rating: RED; Mode of pathogenicity: None; Publications: 27055476, 28153381, 28606768, 32794657; Phenotypes: Parkinson disease; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4626 PRIMPOL Zornitza Stark Tag disputed tag was added to gene: PRIMPOL.
Mendeliome v0.4626 PRIMPOL Zornitza Stark Classified gene: PRIMPOL as Red List (low evidence)
Mendeliome v0.4626 PRIMPOL Zornitza Stark Gene: primpol has been classified as Red List (Low Evidence).
Mendeliome v0.4625 MIEF2 Zornitza Stark Phenotypes for gene: MIEF2 were changed from Progressive muscle weakness; Exercise intolerance; Ragged red and COX negative fibres; Complex I and IV deficiency to Combined oxidative phosphorylation deficiency 49, MIM# 619024; Progressive muscle weakness; Exercise intolerance; Ragged red and COX negative fibres; Complex I and IV deficiency
Mendeliome v0.4624 MRPS25 Zornitza Stark Phenotypes for gene: MRPS25 were changed from Dyskinetic cerebral palsy; Mitochondrial myopathy; Partial agenesis of the corpus callosum to Combined oxidative phosphorylation deficiency 50, MIM# 619025; Dyskinetic cerebral palsy; Mitochondrial myopathy; Partial agenesis of the corpus callosum
Mendeliome v0.4623 MRPS25 Zornitza Stark edited their review of gene: MRPS25: Changed phenotypes: Combined oxidative phosphorylation deficiency 50, MIM# 619025, Dyskinetic cerebral palsy, Mitochondrial myopathy, Partial agenesis of the corpus callosum
Mendeliome v0.4623 MIEF2 Zornitza Stark edited their review of gene: MIEF2: Changed phenotypes: Combined oxidative phosphorylation deficiency 49, MIM# 619024, Progressive muscle weakness, Exercise intolerance, Ragged red and COX negative fibres, Complex I and IV deficiency
Mendeliome v0.4623 PRIMPOL Sebastian Lunke reviewed gene: PRIMPOL: Rating: RED; Mode of pathogenicity: None; Publications: 23579484, 32375772, 25262353, 27230014, 25680975, 31560770; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4623 COL4A5 Zornitza Stark Gene: col4a5 has been classified as Green List (High Evidence).
Mendeliome v0.4623 COL4A5 Zornitza Stark Phenotypes for gene: COL4A5 were changed from to Alport syndrome 1, X-linked, MIM# 301050
Mendeliome v0.4622 COL4A5 Zornitza Stark Mode of inheritance for gene: COL4A5 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.4621 COL4A5 Zornitza Stark reviewed gene: COL4A5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Alport syndrome 1, X-linked, MIM# 301050; 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 v0.4621 COCH Zornitza Stark Gene: coch has been classified as Green List (High Evidence).
Mendeliome v0.4621 COCH Zornitza Stark Phenotypes for gene: COCH were changed from to Deafness, autosomal dominant 9, MIM# 601369
Mendeliome v0.4620 COCH Zornitza Stark Publications for gene: COCH were set to
Mendeliome v0.4619 COCH Zornitza Stark Mode of inheritance for gene: COCH was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4618 COCH Zornitza Stark reviewed gene: COCH: Rating: GREEN; Mode of pathogenicity: None; Publications: 16151338, 28116169, 28099493, 9806553, 17561763, 21046548, 26256111, 22931125, 22610276, 18312449, 28733840, 18697796, 29449721; Phenotypes: Deafness, autosomal dominant 9, MIM# 601369; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4618 CLRN1 Zornitza Stark Gene: clrn1 has been classified as Green List (High Evidence).
Mendeliome v0.4618 CLRN1 Zornitza Stark Phenotypes for gene: CLRN1 were changed from to Usher syndrome, type 3A, MIM# 276902
Mendeliome v0.4617 CLRN1 Zornitza Stark Publications for gene: CLRN1 were set to
Mendeliome v0.4616 CLRN1 Zornitza Stark Mode of inheritance for gene: CLRN1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4615 CLRN1 Zornitza Stark reviewed gene: CLRN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11524702, 24596593, 22135276, 21675857, 19753315, 27110679, 26943149, 22787034; Phenotypes: Usher syndrome, type 3A, MIM# 276902; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4615 CLPP Zornitza Stark Gene: clpp has been classified as Green List (High Evidence).
Mendeliome v0.4615 CLPP Zornitza Stark Phenotypes for gene: CLPP were changed from to Perrault syndrome 3, MIM# 614129
Mendeliome v0.4614 CLPP Zornitza Stark Publications for gene: CLPP were set to
Mendeliome v0.4613 CLPP Zornitza Stark Mode of inheritance for gene: CLPP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4612 CLPP Zornitza Stark reviewed gene: CLPP: Rating: GREEN; Mode of pathogenicity: None; Publications: 23541340, 27087618, 27899912, 25254289; Phenotypes: Perrault syndrome 3, MIM# 614129; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4612 CLDN14 Zornitza Stark Gene: cldn14 has been classified as Green List (High Evidence).
Mendeliome v0.4612 CLDN14 Zornitza Stark Phenotypes for gene: CLDN14 were changed from to Deafness, autosomal recessive 29, MIM# 614035
Mendeliome v0.4611 CLDN14 Zornitza Stark Publications for gene: CLDN14 were set to
Mendeliome v0.4610 CLDN14 Zornitza Stark Mode of inheritance for gene: CLDN14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4609 CLDN14 Zornitza Stark reviewed gene: CLDN14: Rating: GREEN; Mode of pathogenicity: None; Publications: 11163249, 20811388, 22246673, 23235333, 27870113, 27838790, 12913076; Phenotypes: Deafness, autosomal recessive 29, MIM# 614035; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4609 CIB2 Zornitza Stark Gene: cib2 has been classified as Green List (High Evidence).
Mendeliome v0.4609 CIB2 Zornitza Stark Phenotypes for gene: CIB2 were changed from to Deafness, autosomal recessive 48, MIM# 609439
Mendeliome v0.4608 CIB2 Zornitza Stark Publications for gene: CIB2 were set to
Mendeliome v0.4607 CIB2 Zornitza Stark Mode of inheritance for gene: CIB2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4606 CIB2 Zornitza Stark reviewed gene: CIB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23023331, 23023331, 26173970, 26473954, 27344577, 26226137, 26445815; Phenotypes: Deafness, autosomal recessive 48, MIM# 609439; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4606 GCM2 Zornitza Stark Gene: gcm2 has been classified as Green List (High Evidence).
Mendeliome v0.4606 GCM2 Zornitza Stark Phenotypes for gene: GCM2 were changed from to Hyperparathyroidism 4, OMIM #617343
Mendeliome v0.4605 GCM2 Zornitza Stark Publications for gene: GCM2 were set to
Mendeliome v0.4604 GCM2 Zornitza Stark Mode of pathogenicity for gene: GCM2 was changed from to Other
Mendeliome v0.4603 GCM2 Zornitza Stark Mode of inheritance for gene: GCM2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4602 GCM2 Zornitza Stark edited their review of gene: GCM2: Changed mode of pathogenicity: Other
Mendeliome v0.4602 GCM2 Zornitza Stark reviewed gene: GCM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 27745835; Phenotypes: Hyperparathyroidism 4, OMIM #617343; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4602 SECISBP2 Zornitza Stark Gene: secisbp2 has been classified as Green List (High Evidence).
Mendeliome v0.4602 SECISBP2 Zornitza Stark Phenotypes for gene: SECISBP2 were changed from to Thyroid hormone metabolism, abnormal, MIM# 609698
Mendeliome v0.4601 SECISBP2 Zornitza Stark Publications for gene: SECISBP2 were set to
Mendeliome v0.4600 SECISBP2 Zornitza Stark Mode of inheritance for gene: SECISBP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4599 SECISBP2 Zornitza Stark reviewed gene: SECISBP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 16228000, 19602558, 21084748, 22247018; Phenotypes: Thyroid hormone metabolism, abnormal, MIM# 609698; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4599 UBA1 Zornitza Stark Gene: uba1 has been classified as Green List (High Evidence).
Mendeliome v0.4599 UBA1 Zornitza Stark Phenotypes for gene: UBA1 were changed from to Spinal muscular atrophy, X-linked 2, infantile, MIM# 301830
Mendeliome v0.4598 UBA1 Zornitza Stark Publications for gene: UBA1 were set to
Mendeliome v0.4597 UBA1 Zornitza Stark Mode of inheritance for gene: UBA1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.4596 UBA1 Zornitza Stark reviewed gene: UBA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18179898, 32181232, 31932168, 29034082, 27699224, 26028276, 23518311; Phenotypes: Spinal muscular atrophy, X-linked 2, infantile, MIM# 301830; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.4596 TRIP4 Zornitza Stark Marked gene: TRIP4 as ready
Mendeliome v0.4596 TRIP4 Zornitza Stark Gene: trip4 has been classified as Green List (High Evidence).
Mendeliome v0.4596 TRIP4 Zornitza Stark Phenotypes for gene: TRIP4 were changed from to Spinal muscular atrophy with congenital bone fractures 1, MIM# 616866; Muscular dystrophy, congenital, Davignon-Chauveau type 617066
Mendeliome v0.4595 TRIP4 Zornitza Stark Publications for gene: TRIP4 were set to
Mendeliome v0.4594 TRIP4 Zornitza Stark Mode of inheritance for gene: TRIP4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4593 TRIP4 Zornitza Stark reviewed gene: TRIP4: Rating: GREEN; Mode of pathogenicity: None; Publications: 26924529, 31794073; Phenotypes: Spinal muscular atrophy with congenital bone fractures 1, MIM# 616866, Muscular dystrophy, congenital, Davignon-Chauveau type 617066; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4593 EXOSC9 Zornitza Stark Gene: exosc9 has been classified as Green List (High Evidence).
Mendeliome v0.4593 EXOSC9 Zornitza Stark Phenotypes for gene: EXOSC9 were changed from to Pontocerebellar hypoplasia, type 1D, MIM# 618065
Mendeliome v0.4592 EXOSC9 Zornitza Stark Publications for gene: EXOSC9 were set to
Mendeliome v0.4591 EXOSC9 Zornitza Stark Mode of inheritance for gene: EXOSC9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4590 EXOSC9 Zornitza Stark reviewed gene: EXOSC9: Rating: GREEN; Mode of pathogenicity: None; Publications: 30690203, 29727687; Phenotypes: Pontocerebellar hypoplasia, type 1D, MIM# 618065; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4590 SLC7A14 Zornitza Stark Gene: slc7a14 has been classified as Red List (Low Evidence).
Mendeliome v0.4590 SLC7A14 Zornitza Stark Phenotypes for gene: SLC7A14 were changed from to Retinitis pigmentosa 68, MIM# MIM#615725
Mendeliome v0.4589 SLC7A14 Zornitza Stark Publications for gene: SLC7A14 were set to
Mendeliome v0.4588 SLC7A14 Zornitza Stark Mode of inheritance for gene: SLC7A14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4587 SLC7A14 Zornitza Stark Classified gene: SLC7A14 as Red List (low evidence)
Mendeliome v0.4587 SLC7A14 Zornitza Stark Gene: slc7a14 has been classified as Red List (Low Evidence).
Mendeliome v0.4586 SLC7A14 Zornitza Stark Tag disputed tag was added to gene: SLC7A14.
Mendeliome v0.4586 SLC7A14 Zornitza Stark reviewed gene: SLC7A14: Rating: RED; Mode of pathogenicity: None; Publications: 31921845, 30924391, 24670872; Phenotypes: Retinitis pigmentosa 68, MIM# MIM#615725; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4586 ATP6V1B1 Zornitza Stark Marked gene: ATP6V1B1 as ready
Mendeliome v0.4586 ATP6V1B1 Zornitza Stark Gene: atp6v1b1 has been classified as Green List (High Evidence).
Mendeliome v0.4586 ATP6V1B1 Zornitza Stark Phenotypes for gene: ATP6V1B1 were changed from to Distal renal tubular acidosis 2 with progressive sensorineural hearing loss, MIM# 267300
Mendeliome v0.4585 ATP6V1B1 Zornitza Stark Publications for gene: ATP6V1B1 were set to
Mendeliome v0.4584 ATP6V1B1 Zornitza Stark Mode of inheritance for gene: ATP6V1B1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4583 ATP6V1B1 Zornitza Stark reviewed gene: ATP6V1B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9916796, 12414817, 16611712, 18798332; Phenotypes: Distal renal tubular acidosis 2 with progressive sensorineural hearing loss, MIM# 267300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4583 ATP2B2 Zornitza Stark reviewed gene: ATP2B2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30535804, 15829536; Phenotypes: Dominant progressive sensorineural deafness, {Deafness, autosomal recessive 12, modifier of}, MIM# 601386; Mode of inheritance: None
Mendeliome v0.4583 C1orf194 Zornitza Stark Phenotypes for gene: C1orf194 were changed from Charcot-Marie-Tooth to Charcot-Marie-Tooth disease, intermediate or demyelinating
Mendeliome v0.4582 C1orf194 Zornitza Stark Publications for gene: C1orf194 were set to PMID: 31199454
Mendeliome v0.4581 ALB Zornitza Stark Gene: alb has been classified as Green List (High Evidence).
Mendeliome v0.4581 ALB Zornitza Stark Phenotypes for gene: ALB were changed from to Familial dysalbuminaemic hyperthyroxinaemia; [Dysalbuminemic hyperthyroxinemia], 615999; Analbuminemia, MIM# 616000
Mendeliome v0.4580 ALB Zornitza Stark Publications for gene: ALB were set to
Mendeliome v0.4579 ALB Zornitza Stark Mode of inheritance for gene: ALB was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4578 ALB Zornitza Stark reviewed gene: ALB: Rating: GREEN; Mode of pathogenicity: None; Publications: 29163366, 24646103, 8064810, 27834068, 32635414; Phenotypes: Familial dysalbuminaemic hyperthyroxinaemia, [Dysalbuminemic hyperthyroxinemia], 615999, Analbuminemia, MIM# 616000; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4578 TREM2 Zornitza Stark Marked gene: TREM2 as ready
Mendeliome v0.4578 TREM2 Zornitza Stark Gene: trem2 has been classified as Green List (High Evidence).
Mendeliome v0.4578 TREM2 Zornitza Stark Phenotypes for gene: TREM2 were changed from to Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2, MIM# 618193
Mendeliome v0.4577 TREM2 Zornitza Stark Publications for gene: TREM2 were set to
Mendeliome v0.4576 TREM2 Zornitza Stark Mode of inheritance for gene: TREM2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4575 TREM2 Zornitza Stark reviewed gene: TREM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 12080485, 15883308; Phenotypes: Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2, MIM# 618193; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4575 SPG21 Zornitza Stark Gene: spg21 has been classified as Green List (High Evidence).
Mendeliome v0.4575 SPG21 Zornitza Stark Phenotypes for gene: SPG21 were changed from to Mast syndrome, MIM# 248900
Mendeliome v0.4574 SPG21 Zornitza Stark Publications for gene: SPG21 were set to
Mendeliome v0.4573 SPG21 Zornitza Stark Mode of inheritance for gene: SPG21 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4572 SPG21 Zornitza Stark Tag new gene name tag was added to gene: SPG21.
Mendeliome v0.4572 SPG21 Zornitza Stark reviewed gene: SPG21: Rating: GREEN; Mode of pathogenicity: None; Publications: 14564668, 24451228, 28752238, 26978163; Phenotypes: Mast syndrome, MIM# 248900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4572 LMX1A Zornitza Stark Gene: lmx1a has been classified as Green List (High Evidence).
Mendeliome v0.4572 LMX1A Zornitza Stark Phenotypes for gene: LMX1A were changed from to Deafness, autosomal dominant 7 MIM#601412; non-syndromic hearing loss
Mendeliome v0.4571 LMX1A Zornitza Stark Publications for gene: LMX1A were set to
Mendeliome v0.4570 LMX1A Zornitza Stark Mode of inheritance for gene: LMX1A was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4569 LMX1A Zornitza Stark reviewed gene: LMX1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 29754270, 32840933, 29971487; Phenotypes: Deafness, autosomal dominant 7 MIM#601412, non-syndromic hearing loss; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4569 RPS20 Bryony Thompson Gene: rps20 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4569 RPS20 Bryony Thompson Classified gene: RPS20 as Amber List (moderate evidence)
Mendeliome v0.4569 RPS20 Bryony Thompson Gene: rps20 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4568 RPS20 Bryony Thompson gene: RPS20 was added
gene: RPS20 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RPS20 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPS20 were set to 32790018
Phenotypes for gene: RPS20 were set to Diamond Blackfan anaemia
Mode of pathogenicity for gene: RPS20 was set to Other
Review for gene: RPS20 was set to AMBER
Added comment: Two unrelated cases where a de novo variant involving Ile84 (Ile84Ser and Ile84Asn), and reduce the RPS20 protein level in patient cells. Yeast models with mutation of the cognate residue resulted in defects in growth, ribosome biogenesis, and polysome formation. Loss of function may not be the mechanism of disease, because loss of function variants appear to be exclusively associated with familial colorectal cancer without the DBA phenotype.
Sources: Literature
Mendeliome v0.4567 ABHD12 Zornitza Stark Publications for gene: ABHD12 were set to
Mendeliome v0.4566 ABHD12 Zornitza Stark reviewed gene: ABHD12: Rating: GREEN; Mode of pathogenicity: None; Publications: 20797687, 24697911; Phenotypes: Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract, MIM# 612674; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4566 SPAST Zornitza Stark Marked gene: SPAST as ready
Mendeliome v0.4566 SPAST Zornitza Stark Gene: spast has been classified as Green List (High Evidence).
Mendeliome v0.4566 SPAST Zornitza Stark Phenotypes for gene: SPAST were changed from to Spastic paraplegia 4, autosomal dominant (MIM#182601), AD
Mendeliome v0.4565 SPAST Zornitza Stark Publications for gene: SPAST were set to
Mendeliome v0.4564 SPAST Zornitza Stark Mode of inheritance for gene: SPAST was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4563 TRRAP Zornitza Stark Marked gene: TRRAP as ready
Mendeliome v0.4563 TRRAP Zornitza Stark Gene: trrap has been classified as Green List (High Evidence).
Mendeliome v0.4563 TRRAP Zornitza Stark Publications for gene: TRRAP were set to
Mendeliome v0.4562 TRRAP Zornitza Stark Phenotypes for gene: TRRAP were changed from to Developmental delay with or without dysmorphic facies and autism (MIM#618454)
Mendeliome v0.4561 TRRAP Zornitza Stark Mode of inheritance for gene: TRRAP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4560 TRRAP Chern Lim reviewed gene: TRRAP: Rating: GREEN; Mode of pathogenicity: None; Publications: 30827496, 31231791; Phenotypes: Developmental delay with or without dysmorphic facies and autism (MIM#618454), AD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.4560 TRRAP Chern Lim Deleted their review
Mendeliome v0.4560 SPAST Chern Lim reviewed gene: SPAST: Rating: GREEN; Mode of pathogenicity: None; Publications: 30476002, 30006150; Phenotypes: Spastic paraplegia 4, autosomal dominant (MIM#182601), AD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.4560 TRRAP Chern Lim reviewed gene: TRRAP: Rating: GREEN; Mode of pathogenicity: None; Publications: 30827496; Phenotypes: Developmental delay with or without dysmorphic facies and autism (MIM#618454), AD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.4560 UPF3B Zornitza Stark Gene: upf3b has been classified as Green List (High Evidence).
Mendeliome v0.4560 UPF3B Zornitza Stark Phenotypes for gene: UPF3B were changed from to Mental retardation, X-linked, syndromic 14, MIM# 300676
Mendeliome v0.4559 UPF3B Zornitza Stark Publications for gene: UPF3B were set to
Mendeliome v0.4558 UPF3B Zornitza Stark Mode of inheritance for gene: UPF3B was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.4557 UPF3B Zornitza Stark reviewed gene: UPF3B: Rating: GREEN; Mode of pathogenicity: None; Publications: 19377476, 17704778, 31737052, 28948974, 32667670; Phenotypes: Mental retardation, X-linked, syndromic 14, MIM# 300676; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.4557 C1orf194 Arina Puzriakova changed review comment from: PMID: 32592472 (2020) - Another knockout mouse model by same research group, demonstrating defects in motor and sensory functions, myelination abnormalities, peripheral nerve loss and muscle atrophy.; to: PMID: 32592472 (2020) - An additional knockout mouse model by same research group, demonstrating defects in motor and sensory functions, myelination abnormalities, peripheral nerve loss and muscle atrophy.
Mendeliome v0.4557 C1orf194 Arina Puzriakova reviewed gene: C1orf194: Rating: ; Mode of pathogenicity: None; Publications: 32592472; Phenotypes: Charcot-Marie-Tooth; Mode of inheritance: None
Mendeliome v0.4557 MECP2 Arina Puzriakova reviewed gene: MECP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32469049; Phenotypes: Rett syndrome, 312750; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.4557 XPR1 Zornitza Stark Gene: xpr1 has been classified as Green List (High Evidence).
Mendeliome v0.4557 XPR1 Zornitza Stark Phenotypes for gene: XPR1 were changed from to Basal ganglia calcification, idiopathic, 6, MIM# 616413
Mendeliome v0.4556 XPR1 Zornitza Stark Publications for gene: XPR1 were set to
Mendeliome v0.4555 XPR1 Zornitza Stark Mode of inheritance for gene: XPR1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4554 XPR1 Zornitza Stark reviewed gene: XPR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25938945; Phenotypes: Basal ganglia calcification, idiopathic, 6, MIM# 616413; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4554 VPS13C Zornitza Stark Gene: vps13c has been classified as Green List (High Evidence).
Mendeliome v0.4554 VPS13C Zornitza Stark Phenotypes for gene: VPS13C were changed from to Early-onset Parkinson disease-23, MIM# 616840
Mendeliome v0.4553 VPS13C Zornitza Stark Publications for gene: VPS13C were set to
Mendeliome v0.4552 VPS13C Zornitza Stark Mode of inheritance for gene: VPS13C was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4551 VPS13C Zornitza Stark reviewed gene: VPS13C: Rating: GREEN; Mode of pathogenicity: None; Publications: 26942284 30452786 28862745; Phenotypes: Early-onset Parkinson disease-23, MIM# 616840; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4551 KIAA1161 Zornitza Stark Phenotypes for gene: KIAA1161 were changed from Basal ganglia calcification, idiopathic, 7, autosomal recessive; OMIM #618317; primary familial brain calcifications (PFBC); ataxia; dysarthria; cerebellar atrophy; akinetic-hypertonic syndrome to Basal ganglia calcification, idiopathic, 7, MIM #618317; primary familial brain calcifications (PFBC); ataxia; dysarthria; cerebellar atrophy; akinetic-hypertonic syndrome
Mendeliome v0.4550 KIAA1161 Zornitza Stark Publications for gene: KIAA1161 were set to 30656188; 30649222; 30460687; 29910000; 31009047
Mendeliome v0.4549 KIAA1161 Zornitza Stark Mode of inheritance for gene: KIAA1161 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4548 KIAA1161 Zornitza Stark Tag new gene name tag was added to gene: KIAA1161.
Mendeliome v0.4548 KIAA1161 Zornitza Stark edited their review of gene: KIAA1161: Added comment: In a cohort study comprising 435 individuals with primary brain calcification, 38 individuals identified with mono-allelic variants in this gene, in addition to 14 with bi-allelic variants. Clinical and imaging penetrance of individuals with bi-allelic variants were 100%, whereas among individuals with heterozygous variants, penetrance of imaging phenotype was reduced to 73.7% (28 of 38) and clinical penetrance was much lower. Most (34 of 38) remained asymptomatic whereas 4 had symptoms of uncertain clinical significance (nonspecific depression, epilepsy and late-onset parkinsonism). Compared with individuals with biallelic MYORG variants, individuals with heterozygous variants had brain calcifications with much lower calcification scores (P < 2e-16). HGNC approved name is MYORG.; Changed publications: 30656188, 30649222, 30460687, 29910000, 31951047; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4548 ALG14 Zornitza Stark Gene: alg14 has been classified as Green List (High Evidence).
Mendeliome v0.4548 ALG14 Zornitza Stark Phenotypes for gene: ALG14 were changed from to Myasthenic syndrome, congenital, 15, without tubular aggregates 616227; Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies (IDDEBF), MIM#619031; Disorder of N-glycosylation
Mendeliome v0.4547 ALG14 Zornitza Stark Publications for gene: ALG14 were set to
Mendeliome v0.4546 ALG14 Zornitza Stark Mode of inheritance for gene: ALG14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4545 ALG14 Zornitza Stark reviewed gene: ALG14: Rating: GREEN; Mode of pathogenicity: None; Publications: 30221345, 23404334, 28733338; Phenotypes: Myasthenic syndrome, congenital, 15, without tubular aggregates 616227, Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies (IDDEBF), MIM#619031, Disorder of N-glycosylation; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4545 TCF12 Zornitza Stark Marked gene: TCF12 as ready
Mendeliome v0.4545 TCF12 Zornitza Stark Gene: tcf12 has been classified as Green List (High Evidence).
Mendeliome v0.4545 TCF12 Zornitza Stark Phenotypes for gene: TCF12 were changed from to Craniosynostosis 3, MIM# 615314; Kallman syndrome
Mendeliome v0.4544 TCF12 Zornitza Stark Publications for gene: TCF12 were set to
Mendeliome v0.4543 TCF12 Zornitza Stark Mode of inheritance for gene: TCF12 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4542 TCF12 Zornitza Stark reviewed gene: TCF12: Rating: GREEN; Mode of pathogenicity: None; Publications: 23354436, 32620954; Phenotypes: Craniosynostosis 3, MIM# 615314, Kallman syndrome; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4542 TCF12 Arina Puzriakova reviewed gene: TCF12: Rating: AMBER; Mode of pathogenicity: None; Publications: 32620954; Phenotypes: Kallmann syndrome; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4542 RP1L1 Zornitza Stark Gene: rp1l1 has been classified as Green List (High Evidence).
Mendeliome v0.4542 RP1L1 Zornitza Stark Phenotypes for gene: RP1L1 were changed from to Occult macular dystrophy (MIM#613587) AD; Retinitis pigmentosa 88 (MIM#618826) AR
Mendeliome v0.4541 RP1L1 Zornitza Stark Publications for gene: RP1L1 were set to
Mendeliome v0.4540 RP1L1 Zornitza Stark Mode of inheritance for gene: RP1L1 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.4539 CYP11B2 Zornitza Stark Gene: cyp11b2 has been classified as Green List (High Evidence).
Mendeliome v0.4539 CYP11B2 Zornitza Stark Phenotypes for gene: CYP11B2 were changed from to Hypoaldosteronism, congenital, due to CMO I deficiency (MIM#203400) or due to CMO II deficiency (MIM#610600).
Mendeliome v0.4538 CYP11B2 Zornitza Stark Publications for gene: CYP11B2 were set to
Mendeliome v0.4537 CYP11B2 Zornitza Stark Mode of inheritance for gene: CYP11B2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4536 HPS5 Zornitza Stark Gene: hps5 has been classified as Green List (High Evidence).
Mendeliome v0.4536 HPS5 Zornitza Stark Phenotypes for gene: HPS5 were changed from to Hermansky-Pudlak syndrome 5 (MIM#614074)
Mendeliome v0.4535 HPS5 Zornitza Stark Publications for gene: HPS5 were set to
Mendeliome v0.4534 HPS5 Zornitza Stark Mode of inheritance for gene: HPS5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4533 HPS5 Zornitza Stark reviewed gene: HPS5: Rating: GREEN; Mode of pathogenicity: None; Publications: 28296950, 32725903; Phenotypes: Hermansky-Pudlak syndrome 5 (MIM#614074); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4533 IBA57 Zornitza Stark Phenotypes for gene: IBA57 were changed from Multiple mitochondrial dysfunctions syndrome 3, MIM#615330 to Multiple mitochondrial dysfunctions syndrome 3, MIM#615330; Spastic paraplegia 74, autosomal recessive MIM#616451
Mendeliome v0.4532 IBA57 Zornitza Stark Publications for gene: IBA57 were set to 23462291; 25971455; 27785568; 28671726; 28913435
Mendeliome v0.4531 IBA57 Zornitza Stark changed review comment from: More than 15 families reported with bi-allelic variants in this gene and a severe neurodegenerative disorder characterised by loss of previously acquired developmental milestones in the first months or years of life. Some affected individuals have normal development in early infancy before the onset of symptoms, whereas others show delays from birth. Features included loss of motor function, spasticity, pyramidal signs, loss of speech, and cognitive impairment. The disease course is highly variable: some individuals die of respiratory failure early in childhood, whereas some survive but may be bedridden with a feeding tube. Less commonly, some individuals may survive and have a stable course with motor deficits and mild or even absent cognitive impairment, although there may be fluctuating symptoms, often in response to infection. Other variable features include visual problems and seizures. Brain imaging shows diffuse leukodystrophy in the subcortical region, brainstem, cerebellum, and spinal cord. Laboratory studies tend to show increased lactate and CSF glycine, and decreased activity of mitochondrial complexes I and II, although these findings are also variable.; to: MMDS3: More than 15 families reported with bi-allelic variants in this gene and a severe neurodegenerative disorder characterised by loss of previously acquired developmental milestones in the first months or years of life. Some affected individuals have normal development in early infancy before the onset of symptoms, whereas others show delays from birth. Features included loss of motor function, spasticity, pyramidal signs, loss of speech, and cognitive impairment. The disease course is highly variable: some individuals die of respiratory failure early in childhood, whereas some survive but may be bedridden with a feeding tube. Less commonly, some individuals may survive and have a stable course with motor deficits and mild or even absent cognitive impairment, although there may be fluctuating symptoms, often in response to infection. Other variable features include visual problems and seizures. Brain imaging shows diffuse leukodystrophy in the subcortical region, brainstem, cerebellum, and spinal cord. Laboratory studies tend to show increased lactate and CSF glycine, and decreased activity of mitochondrial complexes I and II, although these findings are also variable.

SPG74: Three families with spastic paraparesis as a feature of the condition.
Mendeliome v0.4531 IBA57 Zornitza Stark edited their review of gene: IBA57: Changed phenotypes: Multiple mitochondrial dysfunctions syndrome 3, MIM#615330, Spastic paraplegia 74, autosomal recessive MIM#616451
Mendeliome v0.4531 IBA57 Zornitza Stark edited their review of gene: IBA57: Changed publications: 23462291, 25971455, 27785568, 28671726, 28913435, 25609768 30258207
Mendeliome v0.4531 IBA57 Zornitza Stark Gene: iba57 has been classified as Green List (High Evidence).
Mendeliome v0.4531 IBA57 Zornitza Stark Phenotypes for gene: IBA57 were changed from to Multiple mitochondrial dysfunctions syndrome 3, MIM#615330
Mendeliome v0.4530 IBA57 Zornitza Stark Publications for gene: IBA57 were set to
Mendeliome v0.4529 IBA57 Zornitza Stark Mode of inheritance for gene: IBA57 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4528 IBA57 Zornitza Stark reviewed gene: IBA57: Rating: GREEN; Mode of pathogenicity: None; Publications: 23462291, 25971455, 27785568, 28671726, 28913435; Phenotypes: Multiple mitochondrial dysfunctions syndrome 3, MIM#615330; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4528 RP1L1 Teresa Zhao reviewed gene: RP1L1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23281133, 30025130, 32360662; Phenotypes: Occult macular dystrophy (MIM#613587) AD, Retinitis pigmentosa 88 (MIM#618826) AR; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.4528 CYP11B2 Paul De Fazio reviewed gene: CYP11B2: Rating: GREEN; Mode of pathogenicity: None; Publications: 8439335, 9360501, 15240589, 9814506, 12788848, 8772616; Phenotypes: Hypoaldosteronism, congenital, due to CMO I deficiency (MIM#203400) or due to CMO II deficiency (MIM#610600).; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.4528 NSUN3 Zornitza Stark Phenotypes for gene: NSUN3 were changed from combined mitochondrial respiratory chain complex deficiency to Combined oxidative phosphorylation deficiency 48, MIM# 619012
Mendeliome v0.4527 NSUN3 Zornitza Stark Publications for gene: NSUN3 were set to 27356879
Mendeliome v0.4526 NSUN3 Zornitza Stark edited their review of gene: NSUN3: Added comment: Second family reported with early-onset mitochondrial encephalomyopathy and seizures.; Changed publications: 27356879, 32488845; Changed phenotypes: Combined oxidative phosphorylation deficiency 48, MIM# 619012
Mendeliome v0.4526 LIFR Zornitza Stark Publications for gene: LIFR were set to 28334964
Mendeliome v0.4525 LIFR Zornitza Stark edited their review of gene: LIFR: Added comment: Bi-allelic variants: At least 28 unique variants (nonsense, frameshift, splicing, missense, gross deletions) have been reported in individuals with Stuve-Wiedemann syndrome/Schwartz-Jampel type 2 syndrome, 22 of which are predicted to cause LOF, suggesting homozygous LOF is the mechanism of disease for this gene. Variants in this gene have been reported in at least 22 probands in four publications.

Mono-allelic variants: associated with CAKUT in 4 individuals, mouse model recapitulates phenotype.; Changed rating: GREEN; Changed publications: 14740318, 20447141, 24988918, 29620724, 28334964; Changed phenotypes: Stuve-Wiedemann syndrome/Schwartz-Jampel type 2 syndrome, MIM# 601559, CAKUT; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4525 PAX7 Zornitza Stark Gene: pax7 has been classified as Green List (High Evidence).
Mendeliome v0.4525 PAX7 Zornitza Stark Phenotypes for gene: PAX7 were changed from to Myopathy, congenital, progressive, with scoliosis, MIM# 618578
Mendeliome v0.4524 PAX7 Zornitza Stark Publications for gene: PAX7 were set to
Mendeliome v0.4523 PAX7 Zornitza Stark Mode of inheritance for gene: PAX7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4522 PAX7 Zornitza Stark reviewed gene: PAX7: Rating: GREEN; Mode of pathogenicity: None; Publications: 31092906, 11030621, 24065826, 31092906, 8631261, 11030621, 24065826; Phenotypes: Myopathy, congenital, progressive, with scoliosis, MIM# 618578; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4522 MADD Zornitza Stark Phenotypes for gene: MADD were changed from Intellectual disability; seizures; autonomic dysfunction; endocrine dysfunction to DEEAH syndrome, MIM#619004 (Developmental Delay With Endocrine, Exocrine, Autonomic, and Hematologic Abnormalities); Neurodevelopmental disorder with dysmorphic facies, impaired speech and hypotonia (NEDDISH), MIM# 619005
Mendeliome v0.4521 MADD Zornitza Stark edited their review of gene: MADD: Added comment: OMIM have assigned two disease entities to this gene.

DEEAH syndrome: 12 families.
NEDDISH syndrome: 8 families.; Changed phenotypes: DEEAH syndrome, MIM#619004 (Developmental Delay With Endocrine, Exocrine, Autonomic, and Hematologic Abnormalities), Neurodevelopmental disorder with dysmorphic facies, impaired speech and hypotonia (NEDDISH), MIM# 619005
Mendeliome v0.4521 SLC12A2 Zornitza Stark Publications for gene: SLC12A2 were set to 30740830; 32294086
Mendeliome v0.4520 SLC12A2 Zornitza Stark edited their review of gene: SLC12A2: Added comment: Monoallelic :
DD/ID was a feature in >= 6 individuals with monoallelic de novo SLC12A2. An individual with an exon 22 truncating variant was reported to have normal milestones and cognitive function. Exon 21 variants have been described in individuals with rather isolated hearing impairment (possibly some associated motor delay, but normal cognition). Hearing impairment was also reported in 2/6 patients with variants in other exons (1 missense / 1 frameshift).

Biallelic :
DD/ID was reported in at least 3 individuals in literature. Hearing impairment has been reported on 2 occasions (although this was not probably evaluated in all subjects).

---

Monoallelic SLC12A2 mutations :

► Individuals with de novo mutations and developmental disorder were first identified by the DDD study (2017 - PMID: 28135719). 5 of them have been reported in detail by McNeill et al (below).

► McNeill et al (2020 - PMID: 32658972) report on 6 individuals with neurodevelopmental disorder due to de novo SLC12A2 mutation. All presented DD or ID ranging from mild to severe. ASD was reported in 3/6. Sensorineural hearing loss was a feature in 2/6 with the remaining having normal formal evaluations. Brain, cardiac and/or additional malformations were reported in a single individual. Following non-diagnostic prior work-up (CMA, FMR1 or other investigations) trio exome sequencing revealed missense (4/6) or truncating variants (2/6).

Three additional individuals (incl. a father and his son) with missense variants in exon 21 (NM_001046.3 / p.Glu979Lys and p.Glu980Lys) presented with bilateral sensorineural hearing loss. Speech and/or motor delay reported in these cases were attributed to the hearing impairment/vestibular arreflexia (cognitive abilities not tested).

SLC12A2 encodes sodium-potassium-chloride transporter 1 (also NKCC1).

The GTEx project has identified 8 isoforms. In brain both exon 21-containing/deleted isoforms are expressed (cited Morita et al 2014 - PMID: 24695712). As the authors discuss, RNA-seq of the developing mouse cochlea suggests that the exon 21 containing isoform is the single transcript expressed. Evidence from RNA-seq data (BrainSpan project) and literature suggests that the significant amounts of exon 21 lacking isoforms in fetal brain compensate for the deleterious effects of exon 21 variants and explain the lack of NDD in relevant patients.

Slc12a2 (NKCC1) null mouse model has demonstrated that the transporter plays a role in accumulation of the potassium rich endolymph in the inner ear, with NKCC1 absence causing sensorineural deafness and imbalance. Slc12a2 display cochlear malformations, loss of hair cells and hearing impairment (cited Delpire et al 1999 - PMID: 10369265). The brain phenotype has not been studied extensively, although loss of Slc12a2 has been shown to inhibit neurogenesis (cited: Magalhães and Rivera et al. - PMID: 27582690).

Slc12a2 null zebrafish display a collapse of the otic vesicle and reduced endolymph (Abbas and Whitfield, 2009 - PMID: 19633174) relevant to the human hearing disorder.

In vitro assessment of NKCC1 ion transporter function in Xenopus laevis, supported the deleterious effect of the identified variants (significant reduction in K+ influx). Using available single cell RNA-seq data the authors further demonstrated that SLC12A2 expressing cells display transcriptomic profiles reflective of active neurogenesis.

► Delpire et al (2016 - PMID: 27900370 - not reviewed in detail) described a 13 y.o. girl harboring a de novo 11-bp deletion in SLC12A2 exon 22. This individual reached developmental milestones on time and had a NORMAL cognitive function. Hearing was seemingly normal. Features included orthostatic intolerance, respiratory weakness, multiple endocrine abnormalities, pancreatic insufficiency and multiorgan failure incl. gut and bladder. Exome in the proband, parents and 3 unaffected sibs suggested SLC12A2 as the only candidate for her phenotype. Functional analyses in Xenopus laevis oocytes suggested that a non functional transporter was expressed and trafficked to the membrane as the wt. Detection of the truncated protein at higher molecular sizes suggested either enhanced dimerization or misfolded aggregate. There was no dominant-negative effect of mutant NKCC1. In patient fibroblasts a reduced total and NKCC1-mediated K+ influx.

► Mutai et al (2020 - PMID: 32294086) report on several individuals from 4 families, harboring variants within exon 21 or - in one case - at it's 3' splice-site (leading to skipping oe this exon at the mRNA level). All subjects were investigated for severe/profound hearing loss (in line with the role of exon 21-included isoforms in cochlea. The variant segregated with hearing impairment in 3 generations of a family while in all other subjects the variant had occured as de novo event. Despite motor delays (e.g. the subject from fam2 could not hold head or sit at the age of 10m / the proband in Fam3 was able to hold his head and walk at 6 and 20 m respectively) behavior and cognition were commented to be within normal range.


-----

Biallelic SLC12A2 mutations:

► Anazi et al (2017 - PMID: 29288388) briefly reported on a 3 y.o. boy (17DG0776) with central hypotonia, neonatal respiratory distress, failure to thrive, global DD and microcephaly and a skeletal survey suggestive of osteopenia. After non-diagnostic prior investigations (CMA revealing a 1p duplication classified as VUS, extensive metabolic workup), WES revealed a homozygous SLC12A2 splicing variant [NM_001046.2:c.2617-2A>G].

► Macnamara et al (2019 - PMID: 30740830) described a 5.5 y.o. male with sensorineural hearing loss, profound delays in all developmental areas among several other features (choanal atresia, failure to thrive, respiratory problems, absent sweat and tear production or salivation, GI abnormalities). Genetic testing for several disorders considered (cystic fibrosis, spinal muscular atrophy, sequencing and del/dup analysis of mtDNA) was normal. CMA revealed paternal uniparental isodisomy for chr. 5 and WGS a homozygous 22kb deletion in SLC12A2. This was followed by confirmation of homozygosity in the proband, heterozygosity of the unaffected father, delineation of breakpoints (chr5:127441491-127471419). mRNA studies in patient fibroblasts confirmed deletion of ex2-7, splicing of ex1 directly to ex8 and introduction of a premature stop codon in ex9. qRT-PCR confirmed that mRNA is likely subjected to NMD (expression ~80% of control). Western blot confirmed absence of the protein in the patient's fibroblasts. Again mouse models are thought to recapitulate the hearing defect but also the deficient saliva production (cited Evans et al 2000 - PMID: 10831596). Again the authors speculate a role of SLC12A2 in brain development based on evidence from murine models (migration, dendritic growth, increse in neuron density through regulation of GABAergic signalling (Young et al 2012 - PMID: 23015452). Hypotheses are also made on a regulatory relationship between NKCC1 and CFTR based on mRNA data from the ko mouse model.

► Stödberg et al (2020 - PMID: 32754646) reported 2 sibs with a complex neurodevelopmental disorder due to compound heterozygosity for a frameshift SLC12A2 variant and a splicing one (NM_001046:c.1431delT and c.2006-1G>A). Both presented hypotonia, neonatal S. aureus parotitis and respiratory problems (incl. apneas). While the older sib died at the age of 22 days, the younger one had persistent respiratory issues incl. a dry respiratory mucosa motivating metabolic, immunology investigations and testing for CF. She displayed microcephaly (OFC -2.5 SD, H was also -3.5SD), severe intellectual disability. MRI was suggestive of white matter and basal ganglia abnormalities. Other features incl. hearing impairment, and lack of tears,saliva and sweat, constipation and intestinal malrotation. There was facial dysmorphism. The variants were the only retained following WGS of the 2 affected sisters, parents and an unaffected brother. The splicing variant was shown to result in skipping of exon 13, while the indel in NMD. Again the authors discuss that the deficient saliva production, impaired hearing and GI problems are recapitulated in the mouse model (several refs provided).; Changed rating: GREEN; Changed publications: 28135719, 32658972, 27900370, 32294086, 29288388, 30740830, 32754646; Changed phenotypes: Kilquist syndrome, deafness, intellectual disability, dysmorphic features, absent salivation, ectodermal dysplasia, constipation, intestinal malrotation, multiple congenital anomalies; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4520 VPS37A Zornitza Stark Gene: vps37a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4520 VPS37A Zornitza Stark Phenotypes for gene: VPS37A were changed from to Spastic paraplegia 53, autosomal recessive, MIM# 614898
Mendeliome v0.4519 VPS37A Zornitza Stark Publications for gene: VPS37A were set to
Mendeliome v0.4518 VPS37A Zornitza Stark Mode of inheritance for gene: VPS37A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4517 VPS37A Zornitza Stark Classified gene: VPS37A as Amber List (moderate evidence)
Mendeliome v0.4517 VPS37A Zornitza Stark Gene: vps37a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4516 VPS37A Zornitza Stark reviewed gene: VPS37A: Rating: AMBER; Mode of pathogenicity: None; Publications: 22717650; Phenotypes: Spastic paraplegia 53, autosomal recessive, MIM# 614898; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4516 TECPR2 Zornitza Stark Marked gene: TECPR2 as ready
Mendeliome v0.4516 TECPR2 Zornitza Stark Gene: tecpr2 has been classified as Green List (High Evidence).
Mendeliome v0.4516 TECPR2 Zornitza Stark Phenotypes for gene: TECPR2 were changed from to Spastic paraplegia 49, autosomal recessive, MIM# 615031; Autonomic-sensory neuropathy
Mendeliome v0.4515 TECPR2 Zornitza Stark Publications for gene: TECPR2 were set to
Mendeliome v0.4514 TECPR2 Zornitza Stark Mode of inheritance for gene: TECPR2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4513 TECPR2 Zornitza Stark reviewed gene: TECPR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23176824, 26542466; Phenotypes: Spastic paraplegia 49, autosomal recessive, MIM# 615031, Autonomic-sensory neuropathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4513 SMOC2 Zornitza Stark Gene: smoc2 has been classified as Green List (High Evidence).
Mendeliome v0.4513 SMOC2 Zornitza Stark Phenotypes for gene: SMOC2 were changed from to Dentin dysplasia, type I, with microdontia and misshapen teeth, MIM# 125400
Mendeliome v0.4512 SMOC2 Zornitza Stark Publications for gene: SMOC2 were set to
Mendeliome v0.4511 SMOC2 Zornitza Stark Mode of inheritance for gene: SMOC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4510 SMOC2 Zornitza Stark reviewed gene: SMOC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22152679, 23317772, 32908163; Phenotypes: Dentin dysplasia, type I, with microdontia and misshapen teeth, MIM# 125400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4510 MAG Zornitza Stark Gene: mag has been classified as Green List (High Evidence).
Mendeliome v0.4510 MAG Zornitza Stark Phenotypes for gene: MAG were changed from to Spastic paraplegia 75, autosomal recessive, MIM# 616680
Mendeliome v0.4509 MAG Zornitza Stark Publications for gene: MAG were set to
Mendeliome v0.4508 MAG Zornitza Stark Mode of inheritance for gene: MAG was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4507 MAG Zornitza Stark reviewed gene: MAG: Rating: GREEN; Mode of pathogenicity: None; Publications: 24482476, 26179919, 31402626, 32629324; Phenotypes: Spastic paraplegia 75, autosomal recessive, MIM# 616680; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4507 DSTYK Zornitza Stark Tag SV/CNV tag was added to gene: DSTYK.
Mendeliome v0.4507 DSTYK Zornitza Stark Marked gene: DSTYK as ready
Mendeliome v0.4507 DSTYK Zornitza Stark Gene: dstyk has been classified as Green List (High Evidence).
Mendeliome v0.4507 DSTYK Zornitza Stark Phenotypes for gene: DSTYK were changed from to Congenital anomalies of kidney and urinary tract 1, MIM# 610805; Spastic paraplegia 23, MIM# 270750
Mendeliome v0.4506 DSTYK Zornitza Stark Publications for gene: DSTYK were set to
Mendeliome v0.4505 DSTYK Zornitza Stark Mode of inheritance for gene: DSTYK was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4504 DSTYK Zornitza Stark reviewed gene: DSTYK: Rating: GREEN; Mode of pathogenicity: None; Publications: 23862974, 23862974, 28618409, 28157540, 23862974; Phenotypes: Congenital anomalies of kidney and urinary tract 1, MIM# 610805, Spastic paraplegia 23, MIM# 270750; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4504 ZMYM2 Zornitza Stark Gene: zmym2 has been classified as Green List (High Evidence).
Mendeliome v0.4504 ZMYM2 Zornitza Stark Classified gene: ZMYM2 as Green List (high evidence)
Mendeliome v0.4504 ZMYM2 Zornitza Stark Gene: zmym2 has been classified as Green List (High Evidence).
Mendeliome v0.4503 ZMYM2 Zornitza Stark gene: ZMYM2 was added
gene: ZMYM2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZMYM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZMYM2 were set to 32891193
Phenotypes for gene: ZMYM2 were set to Congenital anomalies of kidney and urinary tract; Neurodevelopmental disorder
Review for gene: ZMYM2 was set to GREEN
Added comment: Heterozygous pathogenic (pLoF) ZMYM2 variants have been reported in individuals with syndromic presentation including CAKUT (in several cases) and variable neurological manifestations among extra-renal features.

--

Connaughton et al (2020 - PMID: 32891193) report on 19 individuals (from 15 unrelated families) with heterozygous pathogenic ZMYM2 variants.

Affected individuals from 7 families presented with CAKUT while all of them displayed extra-renal features. Neurological manifestations were reported in 16 individuals from 14 families (data not available for 1 fam), among others hypotonia (3/14 fam), speech delay (4/14 fam), global DD (9/14 fam), ID (4/14 fam), microcephaly (4/14 fam). ASD was reported in 4 fam (4 indiv). Seizures were reported in 2 fam (2 indiv). Variable other features included cardiac defects, facial dysmorphisms, small hands and feet with dys-/hypo-plastic nails and clinodactyly.

14 pLoF variants were identified, in most cases as de novo events (8 fam). In 2 families the variant was inherited from an affected parent. Germline mosaicism occurred in 1 family.

The human disease features were recapitulated in a X. tropicalis morpholino knockdown, with expression of truncating variants failing to rescue renal and craniofacial defects. Heterozygous Zmym2-deficient mice also recapitulated the features of CAKUT.

ZMYM2 (previously ZNF198) encodes a nuclear zinc finger protein localizing to the nucleus (and PML nuclear body).

It has previously been identified as transcriptional corepressor interacting with nuclear receptors and the LSD1-CoREST-HDAC1 complex. It has also been shown to interact with FOXP transcription factors.

The authors provide evidence for loss of interaction of the truncated ZMYM2 with FOXP1 (mutations in the latter having recently been reported in syndromic CAKUT).
Sources: Literature
Mendeliome v0.4502 MTX2 Zornitza Stark Marked gene: MTX2 as ready
Mendeliome v0.4502 MTX2 Zornitza Stark Gene: mtx2 has been classified as Green List (High Evidence).
Mendeliome v0.4502 MTX2 Zornitza Stark Classified gene: MTX2 as Green List (high evidence)
Mendeliome v0.4502 MTX2 Zornitza Stark Gene: mtx2 has been classified as Green List (High Evidence).
Mendeliome v0.4501 MTX2 Zornitza Stark gene: MTX2 was added
gene: MTX2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MTX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTX2 were set to 32917887
Phenotypes for gene: MTX2 were set to Mandibuloacral dysplasia; lipodystrophy; arterial calcification
Review for gene: MTX2 was set to GREEN
Added comment: Seven individuals from 5 unrelated families reported with severe progeroid form of MAD with growth retardation, small viscerocranium with mandibular underdevelopment, distal acro-osteolyses, lipodystrophy, altered skin pigmentation, renal focal glomerulosclerosis, and extremely severe hypertension in most cases, eventually associated with disseminated arterial calcification. Loss of MTX2 in patients' primary fibroblasts led to loss of Metaxin-1 (MTX1) and mitochondrial dysfunction, including network fragmentation and oxidative phosphorylation impairment. Furthermore, patients' fibroblasts were resistant to induced apoptosis, leading to increased cell senescence and mitophagy and reduced proliferation.
Sources: Literature
Mendeliome v0.4500 RREB1 Zornitza Stark Gene: rreb1 has been classified as Red List (Low Evidence).
Mendeliome v0.4500 RREB1 Zornitza Stark gene: RREB1 was added
gene: RREB1 was added to Mendeliome. Sources: Literature
SV/CNV tags were added to gene: RREB1.
Mode of inheritance for gene: RREB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RREB1 were set to 32938917
Phenotypes for gene: RREB1 were set to Noonan syndrome-like disorder
Review for gene: RREB1 was set to RED
Added comment: Single individual reported with Noonan syndrome-like features and a deletion encompassing RREB1. Overlapping deletions in publicly reported databases examined, and RREB1 postulated to be the key gene. Rreb1 hemizygous mice display orbital hypertelorism and age dependent cardiac hypertrophy. RREB1 recruits SIN3A and KDM1A to an RRE in target promoters in human and murine cells to control histone H3K4 methylation of MAPK pathway genes.

In summary, single well phenotyped individual with a CNV and experimental data to support gene-disease association.
Sources: Literature
Mendeliome v0.4499 FNIP1 Zornitza Stark Gene: fnip1 has been classified as Green List (High Evidence).
Mendeliome v0.4499 FNIP1 Zornitza Stark Classified gene: FNIP1 as Green List (high evidence)
Mendeliome v0.4499 FNIP1 Zornitza Stark Gene: fnip1 has been classified as Green List (High Evidence).
Mendeliome v0.4498 NEMF Zornitza Stark Gene: nemf has been classified as Green List (High Evidence).
Mendeliome v0.4498 NEMF Zornitza Stark Classified gene: NEMF as Green List (high evidence)
Mendeliome v0.4498 NEMF Zornitza Stark Gene: nemf has been classified as Green List (High Evidence).
Mendeliome v0.4497 NEMF Zornitza Stark gene: NEMF was added
gene: NEMF was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NEMF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NEMF were set to 32934225
Phenotypes for gene: NEMF were set to Intellectual disability; neuropathy
Review for gene: NEMF was set to GREEN
Added comment: Nine individuals from 7 unrelated families reported with a mixed CNS/PNS phenotype. 7/9 had ID, 4/9 had formal assessments demonstrating axonal neuropathy, 3/9 had ataxia; muscular atrophy, hypotonia, respiratory distress, scoliosis also described in some. Three independently generated mouse models had progressive motor neuron degeneration.
Sources: Literature
Mendeliome v0.4496 FNIP1 Arina Puzriakova gene: FNIP1 was added
gene: FNIP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FNIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FNIP1 were set to 32181500; 32905580
Phenotypes for gene: FNIP1 were set to Hypertrophic Cardiomyopathy; Primary Immunodeficiency; Agammaglobulinemia; Neutropenia
Review for gene: FNIP1 was set to GREEN
Added comment: - PMID: 32181500 (2020) - Three patients from two independent consanguineous families with homozygous variants (c.3353G>A, p.Ser1118Asn and c.1289delA, p.His430Profs7*) in the FNIP1 gene. Both variants segregated with the disease phenotype in each family. Clinically, patients presented with combined immunodeficiency, cardiac findings (hypertrophic cardiomyopathy, Wolff‐Parkinson‐White syndrome), and myopathy of skeletal muscles with motor DD. Authors note phenotypic overlap with the murine model of FNIP1 deficiency, but no functional analyses of the variants or patient cells were performed.

- PMID: 32905580 (2020) - Three cases from unrelated families, all harbouring novel biallelic variants in FNIP1. Clinical manifestations in all patients include hypertrophic cardiomyopathy, severe and/or recurrent infections, absent circulating B-cells, and agammaglobulinemia; as well as either severe or intermittent neutropenia in two cases. Functional studies showed impairment of B-cell metabolism, including disruptions to mitochondrial numbers/activity and the PI3K/AKT pathway.
Sources: Literature
Mendeliome v0.4496 TAOK1 Zornitza Stark Marked gene: TAOK1 as ready
Mendeliome v0.4496 TAOK1 Zornitza Stark Gene: taok1 has been classified as Green List (High Evidence).
Mendeliome v0.4496 TAOK1 Zornitza Stark Phenotypes for gene: TAOK1 were changed from to TAOK1-related neurodevelopmental disorder
Mendeliome v0.4495 TAOK1 Zornitza Stark Publications for gene: TAOK1 were set to
Mendeliome v0.4494 TAOK1 Zornitza Stark Mode of inheritance for gene: TAOK1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4493 TAOK1 Zornitza Stark changed review comment from: Monoallelic de novo variants reported in 8 individuals with nonspecific phenotype of intellectual disability and hypotonia. Most were LOF, 2 missense. 3 had macrocephaly.; to: Monoallelic de novo variants reported in 8 individuals with nonspecific phenotype of intellectual disability and hypotonia; 3 had macrocephaly.
Mendeliome v0.4493 TAOK1 Zornitza Stark reviewed gene: TAOK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31230721; Phenotypes: TAOK1-related neurodevelopmental disorder; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4493 CSF1R Zornitza Stark Gene: csf1r has been classified as Green List (High Evidence).
Mendeliome v0.4493 CSF1R Zornitza Stark Phenotypes for gene: CSF1R were changed from to Brain abnormalities, neurodegeneration, and dysosteosclerosis, (MIM#618476); Leukoencephalopathy, diffuse hereditary, with spheroids, (MIM#221820)
Mendeliome v0.4492 CSF1R Zornitza Stark Publications for gene: CSF1R were set to
Mendeliome v0.4491 CSF1R Zornitza Stark Mode of pathogenicity for gene: CSF1R was changed from to Other
Mendeliome v0.4490 CSF1R Zornitza Stark Mode of inheritance for gene: CSF1R was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4489 TAOK1 Elena Savva reviewed gene: TAOK1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31230721; Phenotypes: Neurodevelopmental disorder; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.4489 L2HGDH Zornitza Stark Gene: l2hgdh has been classified as Green List (High Evidence).
Mendeliome v0.4489 L2HGDH Zornitza Stark Phenotypes for gene: L2HGDH were changed from to L-2-hydroxyglutaric aciduria, MIM#236792
Mendeliome v0.4488 L2HGDH Zornitza Stark Publications for gene: L2HGDH were set to
Mendeliome v0.4487 L2HGDH Zornitza Stark Mode of inheritance for gene: L2HGDH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4486 L2HGDH Zornitza Stark reviewed gene: L2HGDH: Rating: GREEN; Mode of pathogenicity: None; Publications: 15385440; Phenotypes: L-2-hydroxyglutaric aciduria, MIM#236792; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4486 CSF1R Elena Savva reviewed gene: CSF1R: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 31330095, 24336230; Phenotypes: Brain abnormalities, neurodegeneration, and dysosteosclerosis, (MIM#618476), Leukoencephalopathy, diffuse hereditary, with spheroids, (MIM#221820); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4486 LMNB1 Zornitza Stark Gene: lmnb1 has been classified as Green List (High Evidence).
Mendeliome v0.4486 LMNB1 Zornitza Stark Mode of inheritance for gene: LMNB1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4485 LMNB1 Zornitza Stark Mode of pathogenicity for gene: LMNB1 was changed from to Other
Mendeliome v0.4484 LMNB1 Zornitza Stark Publications for gene: LMNB1 were set to
Mendeliome v0.4483 LMNB1 Zornitza Stark Phenotypes for gene: LMNB1 were changed from to Global developmental delay, Intellectual disability, Microcephaly, Short stature, Seizures, Abnormality of the corpus callosum, Cortical gyral simplification, Feeding difficulties, Scoliosis; Leukodystrophy, adult-onset, autosomal dominant, MIM#169500
Mendeliome v0.4482 LMNB1 Zornitza Stark Tag SV/CNV tag was added to gene: LMNB1.
Mendeliome v0.4482 LMNB1 Zornitza Stark reviewed gene: LMNB1: Rating: GREEN; Mode of pathogenicity: Other; Publications: 32910914, 16951681, 19151023; Phenotypes: Global developmental delay, Intellectual disability, Microcephaly, Short stature, Seizures, Abnormality of the corpus callosum, Cortical gyral simplification, Feeding difficulties, Scoliosis, Leukodystrophy, adult-onset, autosomal dominant, MIM#169500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4482 L2HGDH Elena Savva reviewed gene: L2HGDH: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20052767; Phenotypes: L-2-hydroxyglutaric aciduria MIM#236792; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4482 MAPK8 Zornitza Stark reviewed gene: MAPK8: Rating: AMBER; Mode of pathogenicity: None; Publications: 31784499; Phenotypes: Chronic mucocutaneous candidiasis, Connective tissue disorders; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4482 MAPK8 Zornitza Stark Gene: mapk8 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4482 MAPK8 Zornitza Stark Classified gene: MAPK8 as Amber List (moderate evidence)
Mendeliome v0.4482 MAPK8 Zornitza Stark Gene: mapk8 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4481 CTNNBL1 Zornitza Stark Marked gene: CTNNBL1 as ready
Mendeliome v0.4481 CTNNBL1 Zornitza Stark Gene: ctnnbl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4481 CTNNBL1 Zornitza Stark Classified gene: CTNNBL1 as Amber List (moderate evidence)
Mendeliome v0.4481 CTNNBL1 Zornitza Stark Gene: ctnnbl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4480 MAPK8 Arina Puzriakova gene: MAPK8 was added
gene: MAPK8 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MAPK8 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MAPK8 were set to 31784499
Phenotypes for gene: MAPK8 were set to Chronic mucocutaneous candidiasis; Connective tissue disorders
Added comment: PMID: 31784499 (2020) - Three cases in a single family with chronic mucocutaneous candidiasis and a connective tissue disorder that clinically overlaps with hEDS. WES revealed a splice-site variant (c.311+1G>A) in the MAPK8 gene that segregated with the disorder. Includes supportive functional data using patient-derived fibroblasts, showing that the variant impairs IL-17A/F immunity and the development of Th17 cells.
Sources: Literature
Mendeliome v0.4480 CTNNBL1 Arina Puzriakova gene: CTNNBL1 was added
gene: CTNNBL1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CTNNBL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTNNBL1 were set to 32484799
Phenotypes for gene: CTNNBL1 were set to Primary Immunodeficiency; Autoimmune Cytopenias; Common variable immunodeficiency
Added comment: PMID: 32484799 (2020) - One patient with common variable immunodeficiency associated with autoimmune cytopenia (CVID+AIC), associated with a homozygous missense M466V variant in the CTNNBL1 gene. Functional studies showed that the variant impaired interaction with AID, in turn disrupting AID-mediated antibody diversification in activated B-cells.
Sources: Literature
Mendeliome v0.4480 PDIA5 Zornitza Stark Gene: pdia5 has been classified as Red List (Low Evidence).
Mendeliome v0.4480 PDIA5 Zornitza Stark Classified gene: PDIA5 as Red List (low evidence)
Mendeliome v0.4480 PDIA5 Zornitza Stark Gene: pdia5 has been classified as Red List (Low Evidence).
Mendeliome v0.4479 TNNI2 Zornitza Stark Marked gene: TNNI2 as ready
Mendeliome v0.4479 TNNI2 Zornitza Stark Gene: tnni2 has been classified as Green List (High Evidence).
Mendeliome v0.4479 TNNI2 Zornitza Stark Phenotypes for gene: TNNI2 were changed from to Arthrogryposis, distal, type 2B1 (MIM#601680)
Mendeliome v0.4478 TNNI2 Zornitza Stark Publications for gene: TNNI2 were set to
Mendeliome v0.4477 TNNI2 Zornitza Stark Mode of pathogenicity for gene: TNNI2 was changed from to Other
Mendeliome v0.4476 TNNI2 Zornitza Stark Mode of inheritance for gene: TNNI2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4475 MEIS2 Michelle Torres reviewed gene: MEIS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25712757; Phenotypes: Cleft palate, cardiac defects, and mental retardation (MIM#600987); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4475 TNNI2 Michelle Torres changed review comment from: Only a handful of variants reported, with a cluster of pathogenic missense in the C-terminal (between p.165 and 175). Missense, nonsense (not NMD) and an inframe-deletion have been shown to result in gain of function.; to: Only a handful of variants reported, with a cluster of pathogenic missense in the C-terminal (between p.165 and 175). Missense, nonsense (not NMD) and an inframe-deletion have been shown to result in gain of function (PMIDs: 17194691, 25340332).
Mendeliome v0.4475 PDIA5 Ain Roesley reviewed gene: PDIA5: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.4475 TNNI2 Michelle Torres reviewed gene: TNNI2: Rating: GREEN; Mode of pathogenicity: Other; Publications: 17194691, 25340332; Phenotypes: Arthrogryposis, distal, type 2B1 (MIM#601680); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4475 MMP23A Bryony Thompson Gene: mmp23a has been classified as Red List (Low Evidence).
Mendeliome v0.4475 MMP23A Bryony Thompson Classified gene: MMP23A as Red List (low evidence)
Mendeliome v0.4475 MMP23A Bryony Thompson Gene: mmp23a has been classified as Red List (Low Evidence).
Mendeliome v0.4474 MMP23A Bryony Thompson reviewed gene: MMP23A: Rating: RED; Mode of pathogenicity: None; Publications: 15483646, 18924166; Phenotypes: Craniosynostosis; Mode of inheritance: Unknown
Mendeliome v0.4474 TAF2 Zornitza Stark Publications for gene: TAF2 were set to 21937992; 22633631; 26350204
Mendeliome v0.4473 TAF2 Zornitza Stark edited their review of gene: TAF2: Added comment: Evidence for gene-disease association is limited. Families reported as part of large cohorts with limited phenotypic data, and variants are homozygous missense without functional validation. Borderline Amber/Green.; Changed publications: 21937992, 22633631, 26350204, 24084144
Mendeliome v0.4473 TAF2 Elena Savva reviewed gene: TAF2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 24084144, 21937992, 22633631, 26350204; Phenotypes: Mental retardation, autosomal recessive 40 615599; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4473 VPS11 Zornitza Stark Gene: vps11 has been classified as Green List (High Evidence).
Mendeliome v0.4473 VPS11 Zornitza Stark Phenotypes for gene: VPS11 were changed from to Leukodystrophy, hypomyelinating, 12, MIM# 616683
Mendeliome v0.4472 VPS11 Zornitza Stark Publications for gene: VPS11 were set to
Mendeliome v0.4471 VPS11 Zornitza Stark Mode of inheritance for gene: VPS11 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4470 VPS11 Zornitza Stark Tag founder tag was added to gene: VPS11.
Mendeliome v0.4470 VPS11 Zornitza Stark reviewed gene: VPS11: Rating: GREEN; Mode of pathogenicity: None; Publications: 27120463, 26307567, 27473128; Phenotypes: Leukodystrophy, hypomyelinating, 12, MIM# 616683; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4470 GGT1 Zornitza Stark Marked gene: GGT1 as ready
Mendeliome v0.4470 GGT1 Zornitza Stark Gene: ggt1 has been classified as Red List (Low Evidence).
Mendeliome v0.4470 GGT1 Zornitza Stark Phenotypes for gene: GGT1 were changed from to ?Glutathioninuria 231950
Mendeliome v0.4469 GGT1 Zornitza Stark Publications for gene: GGT1 were set to
Mendeliome v0.4468 GGT1 Zornitza Stark Mode of inheritance for gene: GGT1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4467 GGT1 Zornitza Stark Classified gene: GGT1 as Red List (low evidence)
Mendeliome v0.4467 GGT1 Zornitza Stark Gene: ggt1 has been classified as Red List (Low Evidence).
Mendeliome v0.4466 GGT1 Elena Savva edited their review of gene: GGT1: Added comment: PMID: 29483667 - 1 family (2 sibs) w/ a homozygous 16.9kb deletion spanning part of the gene and no others. Carrier parents were normal.

PMID: 23615310 - homozygous mutant mouse model have dwarfism, cataracts and coat colour abnormalities. Protein activity reduced to 4% of wildtype. Noted it was for use as a GGT deficiency model.

PMID: 31520399 - 2 families with AD inheritance showing GGT1 deficiency but NO clinical symptoms. Authors call GGTemia a benign condition.; Changed publications: PMID: 29483667, 23615310, 31520399
Mendeliome v0.4466 NAXE Zornitza Stark Gene: naxe has been classified as Green List (High Evidence).
Mendeliome v0.4466 NAXE Zornitza Stark Phenotypes for gene: NAXE were changed from to Encephalopathy, progressive, early-onset, with brain oedema and/or leukoencephalopathy, MIM# 617186
Mendeliome v0.4465 NAXE Zornitza Stark Publications for gene: NAXE were set to
Mendeliome v0.4464 NAXE Zornitza Stark Mode of inheritance for gene: NAXE was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4463 NAXE Zornitza Stark changed review comment from: Early-onset progressive encephalopathy with brain edema and/or leukoencephalopathy-1 (PEBEL1) is an autosomal recessive severe neurometabolic disorder characterized by rapidly progressive neurologic deterioration that is usually associated with a febrile illness. Affected infants tend to show normal early development followed by acute psychomotor regression with ataxia, hypotonia, respiratory insufficiency, and seizures, resulting in coma and death in the first years of life. Brain imaging shows multiple abnormalities, including brain edema and signal abnormalities in the cortical and subcortical regions. More than 5 unrelated families reported.; to: Early-onset progressive encephalopathy with brain oedema and/or leukoencephalopathy-1 (PEBEL1) is an autosomal recessive severe neurometabolic disorder characterized by rapidly progressive neurologic deterioration that is usually associated with a febrile illness. Affected infants tend to show normal early development followed by acute psychomotor regression with ataxia, hypotonia, respiratory insufficiency, and seizures, resulting in coma and death in the first years of life. Brain imaging shows multiple abnormalities, including brain edema and signal abnormalities in the cortical and subcortical regions. More than 5 unrelated families reported.
Mendeliome v0.4463 NAXE Zornitza Stark reviewed gene: NAXE: Rating: GREEN; Mode of pathogenicity: None; Publications: 27122014, 27616477, 31758406; Phenotypes: Encephalopathy, progressive, early-onset, with brain oedema and/or leukoencephalopathy, MIM# 617186; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4463 NAXD Zornitza Stark Gene: naxd has been classified as Green List (High Evidence).
Mendeliome v0.4463 NAXD Zornitza Stark Phenotypes for gene: NAXD were changed from to Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 2 MIM#618321
Mendeliome v0.4462 NAXD Zornitza Stark Publications for gene: NAXD were set to
Mendeliome v0.4461 NAXD Zornitza Stark Mode of inheritance for gene: NAXD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4460 NAXD Zornitza Stark reviewed gene: NAXD: Rating: GREEN; Mode of pathogenicity: None; Publications: 30576410, 31755961, 32462209; Phenotypes: Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 2 MIM#618321; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4460 ISCA2 Zornitza Stark Gene: isca2 has been classified as Green List (High Evidence).
Mendeliome v0.4460 ISCA2 Zornitza Stark Phenotypes for gene: ISCA2 were changed from to Multiple mitochondrial dysfunctions syndrome 4, MIM# 616370
Mendeliome v0.4459 ISCA2 Zornitza Stark Publications for gene: ISCA2 were set to
Mendeliome v0.4458 ISCA2 Zornitza Stark Mode of inheritance for gene: ISCA2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4457 ISCA2 Zornitza Stark reviewed gene: ISCA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25539947, 29297947, 29122497, 29359243; Phenotypes: Multiple mitochondrial dysfunctions syndrome 4, MIM# 616370; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4457 PRIMPOL Zornitza Stark Gene: primpol has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4457 PRIMPOL Zornitza Stark Phenotypes for gene: PRIMPOL were changed from to Myopia 22, autosomal dominant, MIM# 615420
Mendeliome v0.4456 PRIMPOL Zornitza Stark Publications for gene: PRIMPOL were set to
Mendeliome v0.4455 PRIMPOL Zornitza Stark Mode of inheritance for gene: PRIMPOL was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4454 PRIMPOL Zornitza Stark Classified gene: PRIMPOL as Amber List (moderate evidence)
Mendeliome v0.4454 PRIMPOL Zornitza Stark Gene: primpol has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4453 PRIMPOL Zornitza Stark reviewed gene: PRIMPOL: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Myopia 22, autosomal dominant, MIM# 615420; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4453 PRIMPOL Teresa Zhao reviewed gene: PRIMPOL: Rating: GREEN; Mode of pathogenicity: None; Publications: 23579484, 25262353, 27230014, 32375772; Phenotypes: Myopia 22 (MIM#615420) AD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4453 KCNN4 Zornitza Stark Gene: kcnn4 has been classified as Green List (High Evidence).
Mendeliome v0.4453 KCNN4 Zornitza Stark Classified gene: KCNN4 as Green List (high evidence)
Mendeliome v0.4453 KCNN4 Zornitza Stark Gene: kcnn4 has been classified as Green List (High Evidence).
Mendeliome v0.4452 KCNN4 Zornitza Stark gene: KCNN4 was added
gene: KCNN4 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: KCNN4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNN4 were set to 26148990; 26198474; 26178367
Phenotypes for gene: KCNN4 were set to Dehydrated hereditary stomatocytosis 2, MIM# 616689
Review for gene: KCNN4 was set to GREEN
Added comment: At least three families reported.
Sources: Expert list
Mendeliome v0.4451 C15orf41 Zornitza Stark Gene: c15orf41 has been classified as Green List (High Evidence).
Mendeliome v0.4451 C15orf41 Zornitza Stark Classified gene: C15orf41 as Green List (high evidence)
Mendeliome v0.4451 C15orf41 Zornitza Stark Gene: c15orf41 has been classified as Green List (High Evidence).
Mendeliome v0.4450 C15orf41 Zornitza Stark gene: C15orf41 was added
gene: C15orf41 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: C15orf41 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C15orf41 were set to 23716552; 32293259; 31191338; 29885034
Phenotypes for gene: C15orf41 were set to Dyserythropoietic anemia, congenital, type Ib, MIM# 615631
Review for gene: C15orf41 was set to GREEN
Added comment: At least 6 families reported, functional data.
Sources: Expert list
Mendeliome v0.4449 XRCC2 Zornitza Stark Gene: xrcc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4449 XRCC2 Zornitza Stark Phenotypes for gene: XRCC2 were changed from to Fanconi anemia, complementation group U, MIM# 617247
Mendeliome v0.4448 XRCC2 Zornitza Stark Publications for gene: XRCC2 were set to
Mendeliome v0.4447 XRCC2 Zornitza Stark Mode of inheritance for gene: XRCC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4446 XRCC2 Zornitza Stark Classified gene: XRCC2 as Amber List (moderate evidence)
Mendeliome v0.4446 XRCC2 Zornitza Stark Gene: xrcc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4445 XRCC2 Zornitza Stark reviewed gene: XRCC2: Rating: AMBER; Mode of pathogenicity: None; Publications: 27208205, 22232082, 11118202; Phenotypes: Fanconi anemia, complementation group U, MIM# 617247; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4445 TSR2 Zornitza Stark Marked gene: TSR2 as ready
Mendeliome v0.4445 TSR2 Zornitza Stark Gene: tsr2 has been classified as Red List (Low Evidence).
Mendeliome v0.4445 TSR2 Zornitza Stark Phenotypes for gene: TSR2 were changed from to Diamond-Blackfan anemia 14 with mandibulofacial dysostosis, MIM# 300946
Mendeliome v0.4444 TSR2 Zornitza Stark Publications for gene: TSR2 were set to
Mendeliome v0.4443 TSR2 Zornitza Stark Mode of inheritance for gene: TSR2 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.4442 TSR2 Zornitza Stark Classified gene: TSR2 as Red List (low evidence)
Mendeliome v0.4442 TSR2 Zornitza Stark Gene: tsr2 has been classified as Red List (Low Evidence).
Mendeliome v0.4441 TSR2 Zornitza Stark reviewed gene: TSR2: Rating: RED; Mode of pathogenicity: None; Publications: 24942156; Phenotypes: Diamond-Blackfan anemia 14 with mandibulofacial dysostosis, MIM# 300946; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.4441 SRP72 Zornitza Stark Tag disputed tag was added to gene: SRP72.
Mendeliome v0.4441 SRP72 Zornitza Stark Gene: srp72 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4441 SRP72 Zornitza Stark Phenotypes for gene: SRP72 were changed from to Bone marrow failure syndrome 1, MIM# 614675
Mendeliome v0.4440 SRP72 Zornitza Stark Publications for gene: SRP72 were set to
Mendeliome v0.4439 SRP72 Zornitza Stark Mode of inheritance for gene: SRP72 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4438 SRP72 Zornitza Stark Classified gene: SRP72 as Amber List (moderate evidence)
Mendeliome v0.4438 SRP72 Zornitza Stark Gene: srp72 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4437 SRP72 Zornitza Stark reviewed gene: SRP72: Rating: AMBER; Mode of pathogenicity: None; Publications: 22541560, 31254415; Phenotypes: Bone marrow failure syndrome 1, MIM# 614675; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4437 SLC25A38 Zornitza Stark Gene: slc25a38 has been classified as Green List (High Evidence).
Mendeliome v0.4437 SLC25A38 Zornitza Stark Phenotypes for gene: SLC25A38 were changed from to Anemia, sideroblastic, 2, pyridoxine-refractory, MIM# 205950
Mendeliome v0.4436 SLC25A38 Zornitza Stark Publications for gene: SLC25A38 were set to
Mendeliome v0.4435 SLC25A38 Zornitza Stark Mode of inheritance for gene: SLC25A38 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4434 SLC25A38 Zornitza Stark reviewed gene: SLC25A38: Rating: GREEN; Mode of pathogenicity: None; Publications: 19412178; Phenotypes: Anemia, sideroblastic, 2, pyridoxine-refractory, MIM# 205950; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4434 SLC19A2 Zornitza Stark Gene: slc19a2 has been classified as Green List (High Evidence).
Mendeliome v0.4434 SLC19A2 Zornitza Stark Phenotypes for gene: SLC19A2 were changed from to Thiamine-responsive megaloblastic anemia syndrome, MIM# 249270
Mendeliome v0.4433 SLC19A2 Zornitza Stark Publications for gene: SLC19A2 were set to
Mendeliome v0.4432 SLC19A2 Zornitza Stark Mode of inheritance for gene: SLC19A2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4431 SLC19A2 Zornitza Stark reviewed gene: SLC19A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 10391221, 10978358; Phenotypes: Thiamine-responsive megaloblastic anemia syndrome, MIM# 249270; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4431 SEC23B Zornitza Stark Gene: sec23b has been classified as Green List (High Evidence).
Mendeliome v0.4431 SEC23B Zornitza Stark Phenotypes for gene: SEC23B were changed from to Dyserythropoietic anemia, congenital, type II , MIM#224100
Mendeliome v0.4430 SEC23B Zornitza Stark Publications for gene: SEC23B were set to
Mendeliome v0.4429 SEC23B Zornitza Stark Mode of inheritance for gene: SEC23B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4428 SEC23B Zornitza Stark commented on gene: SEC23B: Over 20 families reported.
Mendeliome v0.4428 SEC23B Zornitza Stark reviewed gene: SEC23B: Rating: GREEN; Mode of pathogenicity: None; Publications: 19561605, 19621418; Phenotypes: Dyserythropoietic anemia, congenital, type II , MIM#224100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4428 RPS27 Zornitza Stark Gene: rps27 has been classified as Red List (Low Evidence).
Mendeliome v0.4428 RPS27 Zornitza Stark Phenotypes for gene: RPS27 were changed from to Diamond-Blackfan anemia 17, MIM# 617409
Mendeliome v0.4427 RPS27 Zornitza Stark Publications for gene: RPS27 were set to
Mendeliome v0.4426 RPS27 Zornitza Stark Mode of inheritance for gene: RPS27 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4425 RPS27 Zornitza Stark Classified gene: RPS27 as Red List (low evidence)
Mendeliome v0.4425 RPS27 Zornitza Stark Gene: rps27 has been classified as Red List (Low Evidence).
Mendeliome v0.4424 RPS27 Zornitza Stark reviewed gene: RPS27: Rating: RED; Mode of pathogenicity: None; Publications: 25424902; Phenotypes: Diamond-Blackfan anemia 17, MIM# 617409; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4424 RPS17 Zornitza Stark Gene: rps17 has been classified as Green List (High Evidence).
Mendeliome v0.4424 RPS17 Zornitza Stark Phenotypes for gene: RPS17 were changed from to Diamond-Blackfan anemia 4, MIM# 612527
Mendeliome v0.4423 RPS17 Zornitza Stark Publications for gene: RPS17 were set to
Mendeliome v0.4422 RPS17 Zornitza Stark Mode of inheritance for gene: RPS17 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4421 RPS17 Zornitza Stark reviewed gene: RPS17: Rating: GREEN; Mode of pathogenicity: None; Publications: 17647292, 19061985, 23812780, 23718193; Phenotypes: Diamond-Blackfan anemia 4, MIM# 612527; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4421 RPL9 Zornitza Stark Gene: rpl9 has been classified as Red List (Low Evidence).
Mendeliome v0.4421 RPL9 Zornitza Stark gene: RPL9 was added
gene: RPL9 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: RPL9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPL9 were set to 29114930; 20116044
Phenotypes for gene: RPL9 were set to Diamond Blackfan anaemia
Review for gene: RPL9 was set to RED
Added comment: PMID: 29114930, de novo splice site variant, c.-2+1G>C, functional impact of this variant is likely deleterious but not proven. Inherited missense variant reported in PMID 20116044, p.Arg125Ser is present in 31 hets in gnomad.
Sources: Expert list
Mendeliome v0.4420 RPL31 Zornitza Stark Gene: rpl31 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4420 RPL31 Zornitza Stark Phenotypes for gene: RPL31 were changed from to Diamond Blackfan anaemia
Mendeliome v0.4419 RPL31 Zornitza Stark Publications for gene: RPL31 were set to
Mendeliome v0.4418 RPL31 Zornitza Stark Mode of inheritance for gene: RPL31 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4417 RPL31 Zornitza Stark Classified gene: RPL31 as Amber List (moderate evidence)
Mendeliome v0.4417 RPL31 Zornitza Stark Gene: rpl31 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4416 RPL31 Zornitza Stark reviewed gene: RPL31: Rating: AMBER; Mode of pathogenicity: None; Publications: 25042156, 25424902; Phenotypes: Diamond Blackfan anaemia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4416 PUS1 Zornitza Stark Gene: pus1 has been classified as Green List (High Evidence).
Mendeliome v0.4416 PUS1 Zornitza Stark Phenotypes for gene: PUS1 were changed from to Myopathy, lactic acidosis, and sideroblastic anemia 1, MIM# 600462
Mendeliome v0.4415 PUS1 Zornitza Stark Publications for gene: PUS1 were set to
Mendeliome v0.4414 PUS1 Zornitza Stark Mode of inheritance for gene: PUS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4413 PUS1 Zornitza Stark reviewed gene: PUS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25227147, 17056637, 15108122, 32287105, 31641589, 28832011; Phenotypes: Myopathy, lactic acidosis, and sideroblastic anemia 1, MIM# 600462; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4413 OXSR1 Zornitza Stark Gene: oxsr1 has been classified as Red List (Low Evidence).
Mendeliome v0.4413 OXSR1 Zornitza Stark Classified gene: OXSR1 as Red List (low evidence)
Mendeliome v0.4413 OXSR1 Zornitza Stark Gene: oxsr1 has been classified as Red List (Low Evidence).
Mendeliome v0.4412 OXSR1 Zornitza Stark reviewed gene: OXSR1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.4412 NHP2 Zornitza Stark Gene: nhp2 has been classified as Green List (High Evidence).
Mendeliome v0.4412 NHP2 Zornitza Stark Phenotypes for gene: NHP2 were changed from to Dyskeratosis congenita, autosomal recessive 2, MIM# 613987
Mendeliome v0.4411 NHP2 Zornitza Stark Publications for gene: NHP2 were set to
Mendeliome v0.4410 NHP2 Zornitza Stark Mode of inheritance for gene: NHP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4409 NHP2 Zornitza Stark reviewed gene: NHP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 18523010, 31985013; Phenotypes: Dyskeratosis congenita, autosomal recessive 2, MIM# 613987; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4409 GGT1 Elena Savva reviewed gene: GGT1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 29483667, 23615310; Phenotypes: ?Glutathioninuria 231950; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4409 JPT1 Elena Savva reviewed gene: JPT1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.4409 LIG4 Zornitza Stark Gene: lig4 has been classified as Green List (High Evidence).
Mendeliome v0.4409 LIG4 Zornitza Stark Phenotypes for gene: LIG4 were changed from to LIG4 syndrome, MIM# 606593
Mendeliome v0.4408 LIG4 Zornitza Stark Publications for gene: LIG4 were set to
Mendeliome v0.4407 LIG4 Zornitza Stark Mode of inheritance for gene: LIG4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4406 LIG4 Zornitza Stark reviewed gene: LIG4: Rating: GREEN; Mode of pathogenicity: None; Publications: 11779494, 16088910, 15333585, 20133615; Phenotypes: LIG4 syndrome, MIM# 606593; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4406 HOXA11 Zornitza Stark Gene: hoxa11 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4406 HOXA11 Zornitza Stark Phenotypes for gene: HOXA11 were changed from to Radioulnar synostosis with amegakaryocytic thrombocytopenia 1, MIM# 605432
Mendeliome v0.4405 HOXA11 Zornitza Stark Publications for gene: HOXA11 were set to
Mendeliome v0.4404 HOXA11 Zornitza Stark Mode of inheritance for gene: HOXA11 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4403 HOXA11 Zornitza Stark Classified gene: HOXA11 as Amber List (moderate evidence)
Mendeliome v0.4403 HOXA11 Zornitza Stark Gene: hoxa11 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4402 HOXA11 Zornitza Stark reviewed gene: HOXA11: Rating: AMBER; Mode of pathogenicity: None; Publications: 11101832, 16765069; Phenotypes: Radioulnar synostosis with amegakaryocytic thrombocytopenia 1, MIM# 605432; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4402 TGM6 Zornitza Stark Marked gene: TGM6 as ready
Mendeliome v0.4402 TGM6 Zornitza Stark Gene: tgm6 has been classified as Red List (Low Evidence).
Mendeliome v0.4402 TGM6 Zornitza Stark Phenotypes for gene: TGM6 were changed from to Spinocerebellar ataxia 35, MIM# 613908
Mendeliome v0.4401 TGM6 Zornitza Stark Publications for gene: TGM6 were set to
Mendeliome v0.4400 TGM6 Zornitza Stark Mode of inheritance for gene: TGM6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4399 TGM6 Zornitza Stark Classified gene: TGM6 as Red List (low evidence)
Mendeliome v0.4399 TGM6 Zornitza Stark Gene: tgm6 has been classified as Red List (Low Evidence).
Mendeliome v0.4398 TGM6 Zornitza Stark Tag refuted tag was added to gene: TGM6.
Mendeliome v0.4398 TGM6 Zornitza Stark Deleted their comment
Mendeliome v0.4398 TGM6 Zornitza Stark reviewed gene: TGM6: Rating: RED; Mode of pathogenicity: None; Publications: 30670339, 32426513; Phenotypes: Spinocerebellar ataxia 35, MIM# 613908; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4398 SVBP Zornitza Stark Tag founder tag was added to gene: SVBP.
Mendeliome v0.4398 SVBP Zornitza Stark changed review comment from: 5 unrelated families with homozygous mutations in SVBP. The mutations segregated with the disorder in all families. In vitro functional cellular expression studies showed that protein levels of the SVBP mutants were barely detectable, suggesting instability, and that the mutant proteins had lost VASH/SVBP catalytic detyrosination activity toward tubulin. Knockdown of about 50% Svbp expression using shRNA in rat hippocampal neurons impaired the formation of excitatory synapses compared to controls.
Sources: Literature; to: 5 unrelated families with homozygous mutations in SVBP. Some shared the same founder variant, p.Q28*. The mutations segregated with the disorder in all families. In vitro functional cellular expression studies showed that protein levels of the SVBP mutants were barely detectable, suggesting instability, and that the mutant proteins had lost VASH/SVBP catalytic detyrosination activity toward tubulin. Knockdown of about 50% Svbp expression using shRNA in rat hippocampal neurons impaired the formation of excitatory synapses compared to controls.
Sources: Literature
Mendeliome v0.4398 SQSTM1 Zornitza Stark Marked gene: SQSTM1 as ready
Mendeliome v0.4398 SQSTM1 Zornitza Stark Gene: sqstm1 has been classified as Green List (High Evidence).
Mendeliome v0.4398 SQSTM1 Zornitza Stark Phenotypes for gene: SQSTM1 were changed from to Neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset, MIM# 617145
Mendeliome v0.4397 SQSTM1 Zornitza Stark Publications for gene: SQSTM1 were set to
Mendeliome v0.4396 SQSTM1 Zornitza Stark Mode of inheritance for gene: SQSTM1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4395 SQSTM1 Zornitza Stark changed review comment from: Four unrelated families, presenting feature of this progressive neurological disorder was ataxia.; to: Nine individuals from four unrelated families.
Mendeliome v0.4395 SLC25A46 Zornitza Stark Gene: slc25a46 has been classified as Green List (High Evidence).
Mendeliome v0.4395 SLC25A46 Zornitza Stark Phenotypes for gene: SLC25A46 were changed from to Neuropathy, hereditary motor and sensory, type VIB, MIM# 616505
Mendeliome v0.4394 SLC25A46 Zornitza Stark Publications for gene: SLC25A46 were set to
Mendeliome v0.4393 SLC25A46 Zornitza Stark Mode of inheritance for gene: SLC25A46 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4392 SLC25A46 Zornitza Stark changed review comment from: Age of onset is variable, but childhood onset described. Ataxia is a feature.; to: Hereditary motor and sensory neuropathy type VIB is an autosomal recessive complex progressive neurologic disorder characterized mainly by early-onset optic atrophy resulting in progressive visual loss and peripheral axonal sensorimotor neuropathy with highly variable age at onset and severity. Affected individuals also have cerebellar or pontocerebellar atrophy on brain imaging, and they show abnormal movements, such as ataxia, dysmetria, and myoclonus.

At least 10 unrelated families reported, supportive functional data.
Mendeliome v0.4392 SLC25A46 Zornitza Stark edited their review of gene: SLC25A46: Changed publications: 30178502, 26168012, 27543974, 27430653, 27390132, 28934388, 28558379
Mendeliome v0.4392 RORA Zornitza Stark Gene: rora has been classified as Green List (High Evidence).
Mendeliome v0.4392 RORA Zornitza Stark Phenotypes for gene: RORA were changed from to Intellectual developmental disorder with or without epilepsy or cerebellar ataxia, MIM# 618060
Mendeliome v0.4391 RORA Zornitza Stark Publications for gene: RORA were set to
Mendeliome v0.4390 RORA Zornitza Stark Mode of inheritance for gene: RORA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4389 RORA Zornitza Stark reviewed gene: RORA: Rating: GREEN; Mode of pathogenicity: None; Publications: 29656859; Phenotypes: Intellectual developmental disorder with or without epilepsy or cerebellar ataxia, MIM# 618060; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4389 MAPK8IP3 Zornitza Stark Deleted their comment
Mendeliome v0.4389 MAPK8IP3 Zornitza Stark edited their review of gene: MAPK8IP3: Added comment: 18 unrelated individuals reported with de novo variants and a neurodevelopmental disorder characterised by global developmental delay, variably impaired intellectual development, and poor or absent speech. Additional features may include hypotonia, spasticity, or ataxia. About half have abnormal findings on brain imaging, including cerebral or cerebellar atrophy, loss of white matter volume, thin corpus callosum, and perisylvian polymicrogyria. Seizures are not a prominent finding, and nonspecific dysmorphic facial features are described.; Changed publications: 30612693, 30945334
Mendeliome v0.4389 LARS2 Zornitza Stark Gene: lars2 has been classified as Green List (High Evidence).
Mendeliome v0.4389 LARS2 Zornitza Stark Phenotypes for gene: LARS2 were changed from to Perrault syndrome 4; Hydrops, lactic acidosis, and sideroblastic anemia, MIM# 617021; Leukodystrophy
Mendeliome v0.4388 LARS2 Zornitza Stark Publications for gene: LARS2 were set to
Mendeliome v0.4387 LARS2 Zornitza Stark Mode of inheritance for gene: LARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4386 LARS2 Zornitza Stark reviewed gene: LARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29205794, 32423379, 30737337, 26537577, 23541342; Phenotypes: Perrault syndrome 4, Hydrops, lactic acidosis, and sideroblastic anemia, MIM# 617021, Leukodystrophy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4386 LAMA1 Zornitza Stark Gene: lama1 has been classified as Green List (High Evidence).
Mendeliome v0.4386 LAMA1 Zornitza Stark Phenotypes for gene: LAMA1 were changed from to Cerebellar ataxia, intellectual disability, oculomotor apraxia, cerebellar cysts; Poretti Boltshauser syndrome MIM#615960
Mendeliome v0.4385 LAMA1 Zornitza Stark Publications for gene: LAMA1 were set to
Mendeliome v0.4384 LAMA1 Zornitza Stark Mode of inheritance for gene: LAMA1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4383 LAMA1 Zornitza Stark edited their review of gene: LAMA1: Changed publications: 25105227
Mendeliome v0.4383 LAMA1 Zornitza Stark changed review comment from: Ataxia is part of the phenotype.
Sources: Expert list; to: Five unrelated families reported.
Sources: Expert list
Mendeliome v0.4383 KCNA2 Zornitza Stark Gene: kcna2 has been classified as Green List (High Evidence).
Mendeliome v0.4383 KCNA2 Zornitza Stark Phenotypes for gene: KCNA2 were changed from to Early infantile encephalopathy 32, MIM#616366
Mendeliome v0.4382 KCNA2 Zornitza Stark Publications for gene: KCNA2 were set to
Mendeliome v0.4381 KCNA2 Zornitza Stark Mode of inheritance for gene: KCNA2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4380 KCNA2 Zornitza Stark Deleted their comment
Mendeliome v0.4380 KCNA2 Zornitza Stark commented on gene: KCNA2: Review of 23 affected individuals in PMID 29050392: some variants are LoF and others GoF, and some genotype-phenotype correlations made. The main differences were (i) predominant focal (loss-of-function) versus generalized (gain-of-function) seizures and corresponding epileptic discharges with prominent sleep activation in most cases with loss-of-function mutations; (ii) more severe epilepsy, developmental problems and ataxia, and atrophy of the cerebellum or even the whole brain in about half of the patients with gain-of-function mutations; and (iii) most severe early-onset phenotypes, occasionally with neonatal onset epilepsy and developmental impairment, as well as generalised and focal seizures and EEG abnormalities for patients with gain- and loss-of-function mutations.
Mendeliome v0.4380 HARS2 Zornitza Stark Gene: hars2 has been classified as Green List (High Evidence).
Mendeliome v0.4380 HARS2 Zornitza Stark Phenotypes for gene: HARS2 were changed from to Perrault syndrome 2, MIM# 614926
Mendeliome v0.4379 HARS2 Zornitza Stark Publications for gene: HARS2 were set to
Mendeliome v0.4378 HARS2 Zornitza Stark Mode of inheritance for gene: HARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4377 HARS2 Zornitza Stark reviewed gene: HARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31827252; Phenotypes: Perrault syndrome 2, MIM# 614926; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4377 ELOVL5 Zornitza Stark reviewed gene: ELOVL5: Rating: GREEN; Mode of pathogenicity: None; Publications: 25065913; Phenotypes: Spinocerebellar ataxia 38, MIM# 615957; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4377 EBF3 Zornitza Stark Gene: ebf3 has been classified as Green List (High Evidence).
Mendeliome v0.4377 EBF3 Zornitza Stark Phenotypes for gene: EBF3 were changed from to Hypotonia, ataxia, and delayed development syndrome, MIM# 617330
Mendeliome v0.4376 EBF3 Zornitza Stark Publications for gene: EBF3 were set to
Mendeliome v0.4375 EBF3 Zornitza Stark Mode of inheritance for gene: EBF3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4374 EBF3 Zornitza Stark reviewed gene: EBF3: Rating: GREEN; Mode of pathogenicity: None; Publications: 28017373, 28017372, 28017370, 32366537; Phenotypes: Hypotonia, ataxia, and delayed development syndrome, MIM# 617330; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4374 DOCK3 Zornitza Stark Gene: dock3 has been classified as Green List (High Evidence).
Mendeliome v0.4374 DOCK3 Zornitza Stark Phenotypes for gene: DOCK3 were changed from to Neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia, MIM#618292
Mendeliome v0.4373 DOCK3 Zornitza Stark Publications for gene: DOCK3 were set to
Mendeliome v0.4372 DOCK3 Zornitza Stark Mode of inheritance for gene: DOCK3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4371 DOCK3 Zornitza Stark reviewed gene: DOCK3: Rating: GREEN; Mode of pathogenicity: None; Publications: 28195318, 29130632, 30976111; Phenotypes: Neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia, MIM#618292; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4371 ATP8A2 Zornitza Stark Marked gene: ATP8A2 as ready
Mendeliome v0.4371 ATP8A2 Zornitza Stark Gene: atp8a2 has been classified as Green List (High Evidence).
Mendeliome v0.4371 ATP8A2 Zornitza Stark Phenotypes for gene: ATP8A2 were changed from to Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 4, MIM#615268
Mendeliome v0.4370 ATP8A2 Zornitza Stark Publications for gene: ATP8A2 were set to
Mendeliome v0.4369 ATP8A2 Zornitza Stark Mode of inheritance for gene: ATP8A2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4368 ATP8A2 Zornitza Stark changed review comment from: Multiple individuals from unrelated families reported with bi-allelic variants in this gene and neurological phenotypes including intellectual disability.
Sources: Expert list; to: 10 individuals from six unrelated families reported with bi-allelic variants in this gene and neurological phenotypes including intellectual disability.
Sources: Expert list
Mendeliome v0.4368 ADPRHL2 Zornitza Stark Added comment: Comment when marking as ready: New HGNC approved name is ADPRS.
Mendeliome v0.4368 ADPRHL2 Zornitza Stark Gene: adprhl2 has been classified as Green List (High Evidence).
Mendeliome v0.4368 ADPRHL2 Zornitza Stark Tag new gene name tag was added to gene: ADPRHL2.
Mendeliome v0.4368 CNGB3 Zornitza Stark Gene: cngb3 has been classified as Green List (High Evidence).
Mendeliome v0.4368 CNGB3 Zornitza Stark Phenotypes for gene: CNGB3 were changed from to Achromatopsia 3, MIM# 262300
Mendeliome v0.4367 CNGB3 Zornitza Stark Publications for gene: CNGB3 were set to
Mendeliome v0.4366 CNGB3 Zornitza Stark Mode of inheritance for gene: CNGB3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4365 CNGB3 Zornitza Stark reviewed gene: CNGB3: Rating: GREEN; Mode of pathogenicity: None; Publications: 17265047; Phenotypes: Achromatopsia 3, MIM# 262300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4365 CNGA3 Zornitza Stark Gene: cnga3 has been classified as Green List (High Evidence).
Mendeliome v0.4365 CNGA3 Zornitza Stark Phenotypes for gene: CNGA3 were changed from to Achromatopsia 2, MIM# 216900
Mendeliome v0.4364 CNGA3 Zornitza Stark Publications for gene: CNGA3 were set to
Mendeliome v0.4363 CNGA3 Zornitza Stark Mode of inheritance for gene: CNGA3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4362 CNGA3 Zornitza Stark reviewed gene: CNGA3: Rating: GREEN; Mode of pathogenicity: None; Publications: 9662398, 11536077, 17265047; Phenotypes: Achromatopsia 2, MIM# 216900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4362 SPRED1 Zornitza Stark Gene: spred1 has been classified as Green List (High Evidence).
Mendeliome v0.4362 SPRED1 Zornitza Stark Phenotypes for gene: SPRED1 were changed from to Legius syndrome, MIM# 611431
Mendeliome v0.4361 SPRED1 Zornitza Stark Publications for gene: SPRED1 were set to
Mendeliome v0.4360 SPRED1 Zornitza Stark Mode of inheritance for gene: SPRED1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4359 SPRED1 Zornitza Stark reviewed gene: SPRED1: Rating: GREEN; Mode of pathogenicity: None; Publications: 17704776, 19366998, 21548021; Phenotypes: Legius syndrome, MIM# 611431; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4359 SOS2 Zornitza Stark Publications for gene: SOS2 were set to 26173643
Mendeliome v0.4358 SOS2 Zornitza Stark Publications for gene: SOS2 were set to 26173643
Mendeliome v0.4357 SOS2 Zornitza Stark Mode of pathogenicity for gene: SOS2 was changed from Other to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Mendeliome v0.4356 SOS2 Zornitza Stark reviewed gene: SOS2: 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: 25795793, 32788663; Phenotypes: Noonan syndrome 9, MIM# 616559; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4356 SOS1 Zornitza Stark Publications for gene: SOS1 were set to 25062969; 17143285; 17143282
Mendeliome v0.4355 SOS1 Zornitza Stark edited their review of gene: SOS1: Added comment: Over 50 individuals reported with SOS1 variants and a Noonan syndrome phenotype. Pulmonic stenosis tends to be more frequent compared to those with PTPN11 mutations, and atrial septal defect is relatively rare. Ectodermal features including keratosis pilaris and curly hair are significantly more prevalent compared with the general Noonan population. Height below the third percentile and learning disability are observed in fewer individuals compared with Noonan syndrome in general. In contrast, macrocephaly is overrepresented among those with SOS1 mutations.; Changed rating: GREEN; Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Changed publications: 17143285, 17143282, 28884940, 17586837; Changed phenotypes: Noonan syndrome 4, MIM# 610733; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4355 SHOC2 Zornitza Stark Gene: shoc2 has been classified as Green List (High Evidence).
Mendeliome v0.4355 SHOC2 Zornitza Stark Phenotypes for gene: SHOC2 were changed from to Noonan syndrome-like with loose anagen hair 1, MIM# 607721
Mendeliome v0.4354 SHOC2 Zornitza Stark Publications for gene: SHOC2 were set to
Mendeliome v0.4353 SHOC2 Zornitza Stark Mode of pathogenicity for gene: SHOC2 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Mendeliome v0.4352 SHOC2 Zornitza Stark Mode of inheritance for gene: SHOC2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4351 SHOC2 Zornitza Stark reviewed gene: SHOC2: 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: 19684605, 23918763, 20882035; Phenotypes: Noonan syndrome-like with loose anagen hair 1, MIM# 607721; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4351 RIT1 Zornitza Stark Marked gene: RIT1 as ready
Mendeliome v0.4351 RIT1 Zornitza Stark Gene: rit1 has been classified as Green List (High Evidence).
Mendeliome v0.4351 RIT1 Zornitza Stark Phenotypes for gene: RIT1 were changed from to Noonan syndrome 8, MIM# 615355
Mendeliome v0.4350 RIT1 Zornitza Stark Publications for gene: RIT1 were set to
Mendeliome v0.4349 RIT1 Zornitza Stark Mode of pathogenicity for gene: RIT1 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Mendeliome v0.4348 RIT1 Zornitza Stark Mode of inheritance for gene: RIT1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4347 RIT1 Zornitza Stark reviewed gene: RIT1: 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: 23791108, 25124994, 24939608, 27101134; Phenotypes: Noonan syndrome 8, MIM# 615355; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4347 NRAS Zornitza Stark Gene: nras has been classified as Green List (High Evidence).
Mendeliome v0.4347 NRAS Zornitza Stark Phenotypes for gene: NRAS were changed from to Noonan syndrome 6, MIM# 613224
Mendeliome v0.4346 NRAS Zornitza Stark Publications for gene: NRAS were set to
Mendeliome v0.4345 NRAS Zornitza Stark Mode of pathogenicity for gene: NRAS was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Mendeliome v0.4344 NRAS Zornitza Stark Mode of inheritance for gene: NRAS was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4343 NRAS Zornitza Stark reviewed gene: NRAS: 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: 19966803, 26467218, 28594414; Phenotypes: Noonan syndrome 6, MIM# 613224; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4343 MAP2K2 Zornitza Stark Gene: map2k2 has been classified as Green List (High Evidence).
Mendeliome v0.4343 MAP2K2 Zornitza Stark Phenotypes for gene: MAP2K2 were changed from to Cardiofaciocutaneous syndrome 4, MIM# 615280
Mendeliome v0.4342 MAP2K2 Zornitza Stark Publications for gene: MAP2K2 were set to
Mendeliome v0.4341 MAP2K2 Zornitza Stark Mode of pathogenicity for gene: MAP2K2 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Mendeliome v0.4340 MAP2K2 Zornitza Stark Mode of inheritance for gene: MAP2K2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4339 MAP2K2 Zornitza Stark reviewed gene: MAP2K2: 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: 20358587, 16439621, 18042262; Phenotypes: Cardiofaciocutaneous syndrome 4, MIM# 615280; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4339 MAP2K1 Zornitza Stark Gene: map2k1 has been classified as Green List (High Evidence).
Mendeliome v0.4339 MAP2K1 Zornitza Stark Phenotypes for gene: MAP2K1 were changed from to Cardiofaciocutaneous syndrome 3, MIM# 615279
Mendeliome v0.4338 MAP2K1 Zornitza Stark Publications for gene: MAP2K1 were set to
Mendeliome v0.4337 MAP2K1 Zornitza Stark Mode of pathogenicity for gene: MAP2K1 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Mendeliome v0.4336 MAP2K1 Zornitza Stark Mode of inheritance for gene: MAP2K1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4335 MAP2K1 Zornitza Stark reviewed gene: MAP2K1: 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: 16439621, 17551924, 18042262, 20301365; Phenotypes: Cardiofaciocutaneous syndrome 3, MIM# 615279; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4335 HRAS Zornitza Stark Gene: hras has been classified as Green List (High Evidence).
Mendeliome v0.4335 HRAS Zornitza Stark Phenotypes for gene: HRAS were changed from to Costello syndrome, MIM# 218040
Mendeliome v0.4334 HRAS Zornitza Stark Publications for gene: HRAS were set to
Mendeliome v0.4333 HRAS Zornitza Stark Mode of pathogenicity for gene: HRAS was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Mendeliome v0.4332 HRAS Zornitza Stark Mode of inheritance for gene: HRAS was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4331 HRAS Zornitza Stark reviewed gene: HRAS: 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: 16329078, 16372351, 16443854; Phenotypes: Costello syndrome, MIM# 218040; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4331 CBL Zornitza Stark Gene: cbl has been classified as Green List (High Evidence).
Mendeliome v0.4331 CBL Zornitza Stark Phenotypes for gene: CBL were changed from to Noonan syndrome-like disorder with or without juvenile myelomonocytic leukaemia, MIM# 613563
Mendeliome v0.4330 CBL Zornitza Stark Publications for gene: CBL were set to
Mendeliome v0.4329 CBL Zornitza Stark Mode of pathogenicity for gene: CBL was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Mendeliome v0.4328 CBL Zornitza Stark Mode of inheritance for gene: CBL was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4327 CBL Zornitza Stark reviewed gene: CBL: 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: 25358541, 20619386, 20543203, 20694012; Phenotypes: Noonan syndrome-like disorder with or without juvenile myelomonocytic leukaemia, MIM# 613563; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4327 CSNK1D Zornitza Stark Gene: csnk1d has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4327 CSNK1D Zornitza Stark Phenotypes for gene: CSNK1D were changed from to Advanced sleep-phase syndrome, familial, 2, MIM# 615224
Mendeliome v0.4326 CSNK1D Zornitza Stark Publications for gene: CSNK1D were set to
Mendeliome v0.4325 CSNK1D Zornitza Stark Mode of inheritance for gene: CSNK1D was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4324 CSNK1D Zornitza Stark Classified gene: CSNK1D as Amber List (moderate evidence)
Mendeliome v0.4324 CSNK1D Zornitza Stark Gene: csnk1d has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4323 CSNK1D Zornitza Stark reviewed gene: CSNK1D: Rating: AMBER; Mode of pathogenicity: None; Publications: 15800623, 23636092; Phenotypes: Advanced sleep-phase syndrome, familial, 2, MIM# 615224; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4323 CACNA1E Zornitza Stark Gene: cacna1e has been classified as Green List (High Evidence).
Mendeliome v0.4323 CACNA1E Zornitza Stark Phenotypes for gene: CACNA1E were changed from to Epileptic encephalopathy, early infantile, 69, MIM#618285
Mendeliome v0.4322 CACNA1E Zornitza Stark Publications for gene: CACNA1E were set to
Mendeliome v0.4321 CACNA1E Zornitza Stark Mode of inheritance for gene: CACNA1E was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4320 CACNA1E Zornitza Stark changed review comment from: At least 30 unrelated patients reported with heterozygous variants in this gene; primarily a seizure disorder, often with profound intellectual disability.; to: At least 30 unrelated patients reported with heterozygous variants in this gene; primarily a seizure disorder, often with profound intellectual disability. Additional common features included spastic quadriplegia, hyperreflexia, hyperkinetic movements, dystonia, myoclonus, clonus, poor or absent eye contact, nystagmus, cortical visual impairment, and loss of head control. Thirteen patients had congenital contractures and 13 had macrocephaly.
Mendeliome v0.4320 ATAD1 Zornitza Stark Marked gene: ATAD1 as ready
Mendeliome v0.4320 ATAD1 Zornitza Stark Gene: atad1 has been classified as Green List (High Evidence).
Mendeliome v0.4320 ATAD1 Zornitza Stark Phenotypes for gene: ATAD1 were changed from to Hyperekplexia 4, MIM#618011
Mendeliome v0.4319 ATAD1 Zornitza Stark Publications for gene: ATAD1 were set to
Mendeliome v0.4318 ATAD1 Zornitza Stark Mode of inheritance for gene: ATAD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4317 ATAD1 Zornitza Stark changed review comment from: Severe progressive neurological disorder, severe/profound intellectual disability is a feature; to: Hyperekplexia-4 is an autosomal recessive severe neurologic disorder apparent at birth. Three unrelated families reported. Affected infants have extreme hypertonia and appear stiff and rigid. They have little if any development, poor or absent visual contact, and no spontaneous movement, consistent with an encephalopathy. Some patients have early-onset refractory seizures. Severe progressive neurological disorder, severe/profound intellectual disability is a feature.
Mendeliome v0.4317 ATAD1 Zornitza Stark edited their review of gene: ATAD1: Changed publications: 28180185, 29390050, 29659736
Mendeliome v0.4317 Zornitza Stark removed gene:ADAT1 from the panel
Mendeliome v0.4316 ADAT1 Zornitza Stark Marked gene: ADAT1 as ready
Mendeliome v0.4316 ADAT1 Zornitza Stark Gene: adat1 has been classified as Green List (High Evidence).
Mendeliome v0.4316 ADAT1 Zornitza Stark Classified gene: ADAT1 as Green List (high evidence)
Mendeliome v0.4316 ADAT1 Zornitza Stark Gene: adat1 has been classified as Green List (High Evidence).
Mendeliome v0.4315 ADAT1 Zornitza Stark gene: ADAT1 was added
gene: ADAT1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ADAT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAT1 were set to 28180185; 29390050; 29659736
Phenotypes for gene: ADAT1 were set to Hyperekplexia 4, MIM#618011
Review for gene: ADAT1 was set to GREEN
Added comment: Hyperekplexia-4 is an autosomal recessive severe neurologic disorder apparent at birth. Three unrelated families reported. Affected infants have extreme hypertonia and appear stiff and rigid. They have little if any development, poor or absent visual contact, and no spontaneous movement, consistent with an encephalopathy. Some patients have early-onset refractory seizures.
Sources: Expert list
Mendeliome v0.4314 OCA2 Zornitza Stark Phenotypes for gene: OCA2 were changed from [Skin/hair/eye pigmentation 1, blond/brown hair] 227220; [Skin/hair/eye pigmentation 1, blue/nonblue eyes] 227220; Albinism, brown oculocutaneous 203200; Albinism, oculocutaneous, type II 203200; autosomal dominant Albinism, oculocutaneous to Albinism, brown oculocutaneous 203200; Albinism, oculocutaneous, type II 203200; autosomal dominant Albinism, oculocutaneous
Mendeliome v0.4313 OCA2 Zornitza Stark Publications for gene: OCA2 were set to 32741191; 24518832
Mendeliome v0.4312 OCA2 Zornitza Stark Tag SV/CNV tag was added to gene: OCA2.
Mendeliome v0.4312 OCA2 Zornitza Stark Gene: oca2 has been classified as Green List (High Evidence).
Mendeliome v0.4312 OCA2 Zornitza Stark Phenotypes for gene: OCA2 were changed from to [Skin/hair/eye pigmentation 1, blond/brown hair] 227220; [Skin/hair/eye pigmentation 1, blue/nonblue eyes] 227220; Albinism, brown oculocutaneous 203200; Albinism, oculocutaneous, type II 203200; autosomal dominant Albinism, oculocutaneous
Mendeliome v0.4311 OCA2 Zornitza Stark Publications for gene: OCA2 were set to
Mendeliome v0.4310 OCA2 Zornitza Stark Mode of inheritance for gene: OCA2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4309 OCA2 Elena Savva changed review comment from: Single variant found causing AD OCA - p.G780S in two families (Lee, 2020) -> GOF suggested

Complete penetrance for oculocutaneous albininism but variable expressivity (PMID: 24518832). No variable expressivity or incomplete penetrance reported in GeneReviews.

Loss of function; to: Single variant found causing AD OCA - p.G780S in two families (Lee, 2020) -> GOF suggested

Complete penetrance for oculocutaneous albininism but variable expressivity (PMID: 24518832). No variable expressivity or incomplete penetrance reported in GeneReviews.

Loss of function

2.7kb deletion is very common in sub-Saharan African populations (GeneReviews)
Mendeliome v0.4309 OCA2 Elena Savva reviewed gene: OCA2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32741191, 24518832; Phenotypes: [Skin/hair/eye pigmentation 1, blond/brown hair] 227220, [Skin/hair/eye pigmentation 1, blue/nonblue eyes] 227220, Albinism, brown oculocutaneous 203200, Albinism, oculocutaneous, type II 203200, autosomal dominant Albinism, oculocutaneous; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.4309 ZSWIM6 Zornitza Stark changed review comment from: MIM #617865 (NEDMAGA): A recurrent de novo heterozygous truncating mutation in the ZSWIM6 gene (R913X)identified in 7 unrelated patients. Analysis of patient cells indicated that the mutant transcript escaped nonsense-mediated mRNA decay, and most likely produced a truncated protein, although antibody studies were unable to detect a truncated protein. Possible dominant-negative effect. NB a more proximal nonsense variant was also reported inherited in a family with an unaffected mother: loss of function variants may not cause a phenotype.
MIM#603671 (acromelic frontonasal dysplasia): recurrent missense identified in 6 unrelated families, p.Arg1163Trp; to: MIM #617865 (NEDMAGA): A recurrent de novo heterozygous truncating mutation in the ZSWIM6 gene (R913X) identified in 7 unrelated patients. Analysis of patient cells indicated that the mutant transcript escaped nonsense-mediated mRNA decay, and most likely produced a truncated protein, although antibody studies were unable to detect a truncated protein. Possible dominant-negative effect. NB a more proximal nonsense variant was also reported inherited in a family with an unaffected mother: loss of function variants may not cause a phenotype.
MIM#603671 (acromelic frontonasal dysplasia): recurrent missense identified in 6 unrelated families, p.Arg1163Trp
Mendeliome v0.4309 ZSWIM6 Zornitza Stark changed review comment from: MIM #617865 A recurrent de novo heterozygous truncating mutation in the ZSWIM6 gene (R913X)identified in 7 unrelated patients. Analysis of patient cells indicated that the mutant transcript escaped nonsense-mediated mRNA decay, and most likely produced a truncated protein, although antibody studies were unable to detect a truncated protein. Possible dominant-negative effect. NB a more proximal nonsense variant was also reported inherited in a family with an unaffected mother: loss of function variants may not cause a phenotype.
MIM#603671: recurrent missense identified in 6 unrelated families, p.Arg1163Trp; to: MIM #617865 (NEDMAGA): A recurrent de novo heterozygous truncating mutation in the ZSWIM6 gene (R913X)identified in 7 unrelated patients. Analysis of patient cells indicated that the mutant transcript escaped nonsense-mediated mRNA decay, and most likely produced a truncated protein, although antibody studies were unable to detect a truncated protein. Possible dominant-negative effect. NB a more proximal nonsense variant was also reported inherited in a family with an unaffected mother: loss of function variants may not cause a phenotype.
MIM#603671 (acromelic frontonasal dysplasia): recurrent missense identified in 6 unrelated families, p.Arg1163Trp
Mendeliome v0.4309 SREBF1 Zornitza Stark Phenotypes for gene: SREBF1 were changed from IFAP (ichthyosis follicularis, atrichia, and photophobia) syndrome to IFAP (ichthyosis follicularis, atrichia, and photophobia) syndrome 2, MIM619016
Mendeliome v0.4308 SREBF1 Zornitza Stark reviewed gene: SREBF1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: IFAP (ichthyosis follicularis, atrichia, and photophobia) syndrome 2, MIM619016; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4308 VPS13D Zornitza Stark Gene: vps13d has been classified as Green List (High Evidence).
Mendeliome v0.4308 VPS13D Zornitza Stark Phenotypes for gene: VPS13D were changed from to Spinocerebellar ataxia, autosomal recessive 4, MIM# 607317
Mendeliome v0.4307 VPS13D Zornitza Stark Publications for gene: VPS13D were set to
Mendeliome v0.4306 VPS13D Zornitza Stark Mode of inheritance for gene: VPS13D was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4305 VAMP2 Zornitza Stark Phenotypes for gene: VAMP2 were changed from Intellectual disability; Autism to Neurodevelopmental disorder with hypotonia and autistic features with or without hyperkinetic movements 618760; Intellectual disability; Autism
Mendeliome v0.4304 VAMP2 Zornitza Stark edited their review of gene: VAMP2: Changed phenotypes: Neurodevelopmental disorder with hypotonia and autistic features with or without hyperkinetic movements 618760, Intellectual disability, Autism
Mendeliome v0.4304 FARSA Zornitza Stark Gene: farsa has been classified as Red List (Low Evidence).
Mendeliome v0.4304 FARSA Zornitza Stark gene: FARSA was added
gene: FARSA was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: FARSA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FARSA were set to 31355908
Phenotypes for gene: FARSA were set to Rajab interstitial lung disease with brain calcifications 2, MIM# 619013
Review for gene: FARSA was set to RED
Added comment: Autosomal recessive disorder characterized by growth delay, interstitial lung disease, liver disease, and abnormal brain MRI findings, including brain calcifications and periventricular cysts. Single affected individual reported, but FARSA interacts with FARSB, which causes a similar disorder.
Sources: Expert list
Mendeliome v0.4303 SLC1A3 Zornitza Stark Gene: slc1a3 has been classified as Green List (High Evidence).
Mendeliome v0.4303 SLC1A3 Zornitza Stark Phenotypes for gene: SLC1A3 were changed from to Episodic ataxia, type 6, MIM# 612656
Mendeliome v0.4302 SLC1A3 Zornitza Stark Publications for gene: SLC1A3 were set to
Mendeliome v0.4301 SLC1A3 Zornitza Stark Mode of inheritance for gene: SLC1A3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4300 SLC1A3 Zornitza Stark reviewed gene: SLC1A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 19139306, 16116111, 29208948, 27829685; Phenotypes: Episodic ataxia, type 6, MIM# 612656; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4300 ANGPT2 Zornitza Stark Marked gene: ANGPT2 as ready
Mendeliome v0.4300 ANGPT2 Zornitza Stark Gene: angpt2 has been classified as Green List (High Evidence).
Mendeliome v0.4300 ANGPT2 Zornitza Stark Classified gene: ANGPT2 as Green List (high evidence)
Mendeliome v0.4300 ANGPT2 Zornitza Stark Gene: angpt2 has been classified as Green List (High Evidence).
Mendeliome v0.4299 ANGPT2 Zornitza Stark gene: ANGPT2 was added
gene: ANGPT2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ANGPT2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ANGPT2 were set to https://stm.sciencemag.org/content/12/560/eaax8013
Phenotypes for gene: ANGPT2 were set to Primary lymphoedema
Review for gene: ANGPT2 was set to GREEN
Added comment: Five unrelated individuals reported with primary lymphedema and variants in this gene, together with functional data.
Sources: Literature
Mendeliome v0.4298 UBR4 Zornitza Stark changed review comment from: Episodic ataxia reported in two families, but another molecular diagnosis present in the second, so suggested as a modifier. Only one individual reported with childhood-onset progressive neurological disorder as part of a large paper proposing multiple candidate genes.; to: Episodic ataxia reported in four families, but another molecular diagnosis present in the some, so suggested as a modifier. Variants are missense, with no supportive segregation or functional data, some are present at a low level in population databases. Only one individual reported with childhood-onset progressive neurological disorder as part of a large paper proposing multiple candidate genes.
Mendeliome v0.4298 SLC20A2 Zornitza Stark Gene: slc20a2 has been classified as Green List (High Evidence).
Mendeliome v0.4298 SLC20A2 Zornitza Stark Phenotypes for gene: SLC20A2 were changed from to Basal ganglia calcification, idiopathic, 1, MIM# 213600
Mendeliome v0.4297 SLC20A2 Zornitza Stark Publications for gene: SLC20A2 were set to
Mendeliome v0.4296 SLC20A2 Zornitza Stark Mode of inheritance for gene: SLC20A2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4295 SLC20A2 Zornitza Stark reviewed gene: SLC20A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22327515, 23334463; Phenotypes: Basal ganglia calcification, idiopathic, 1, MIM# 213600; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4295 SLC16A2 Zornitza Stark Gene: slc16a2 has been classified as Green List (High Evidence).
Mendeliome v0.4295 SLC16A2 Zornitza Stark Phenotypes for gene: SLC16A2 were changed from to Allan-Herndon-Dudley syndrome, MIM# 300523
Mendeliome v0.4294 SLC16A2 Zornitza Stark Publications for gene: SLC16A2 were set to
Mendeliome v0.4293 SLC16A2 Zornitza Stark Mode of inheritance for gene: SLC16A2 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.4292 SLC16A2 Zornitza Stark reviewed gene: SLC16A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 15980113, 31410843, 20301789; Phenotypes: Allan-Herndon-Dudley syndrome, MIM# 300523; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.4292 TRIP13 Zornitza Stark Tag founder tag was added to gene: TRIP13.
Mendeliome v0.4292 TRIP13 Zornitza Stark Phenotypes for gene: TRIP13 were changed from to Mosaic variegated aneuploidy syndrome 3, MIM# 617598; Oocyte maturation defect 9, MIM# 619011
Mendeliome v0.4291 TRIP13 Zornitza Stark Publications for gene: TRIP13 were set to
Mendeliome v0.4290 TRIP13 Zornitza Stark Mode of inheritance for gene: TRIP13 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4289 TRIP13 Zornitza Stark reviewed gene: TRIP13: Rating: GREEN; Mode of pathogenicity: None; Publications: 28553959, 32473092; Phenotypes: Mosaic variegated aneuploidy syndrome 3, MIM# 617598, Oocyte maturation defect 9, MIM# 619011; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4289 HSP90B2P Bryony Thompson changed review comment from: Cannot find any link to any disease at all. This is a pseudogene. It may have been included because its previous gene symbol is TRAP1; to: Cannot find any link to any disease at all. There is no OMIM entry for this pseudogene. It may have been included because its previous gene symbol is TRAP1.
Mendeliome v0.4289 HSP90B2P Bryony Thompson Gene: hsp90b2p has been classified as Red List (Low Evidence).
Mendeliome v0.4289 HSP90B2P Bryony Thompson Classified gene: HSP90B2P as Red List (low evidence)
Mendeliome v0.4289 HSP90B2P Bryony Thompson Gene: hsp90b2p has been classified as Red List (Low Evidence).
Mendeliome v0.4288 HSP90B2P Bryony Thompson reviewed gene: HSP90B2P: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: Unknown
Mendeliome v0.4288 NOBOX Zornitza Stark Gene: nobox has been classified as Green List (High Evidence).
Mendeliome v0.4288 NOBOX Zornitza Stark Phenotypes for gene: NOBOX were changed from to Premature ovarian failure 5,MIM#611548
Mendeliome v0.4287 NOBOX Zornitza Stark Publications for gene: NOBOX were set to
Mendeliome v0.4286 NOBOX Zornitza Stark Mode of inheritance for gene: NOBOX was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4285 NOBOX Zornitza Stark reviewed gene: NOBOX: Rating: GREEN; Mode of pathogenicity: None; Publications: 27836978, 21837770, 25514101, 17701902, 27798098, 29067606; Phenotypes: Premature ovarian failure 5,MIM#611548; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4285 Zornitza Stark removed gene:DNAJC7 from the panel
Mendeliome v0.4284 TET2 Zornitza Stark Phenotypes for gene: TET2 were changed from Dementia; Lymphoma/myeloid malignancy to Dementia; Lymphoma/myeloid malignancy; Immunodeficiency
Mendeliome v0.4283 TET2 Zornitza Stark Mode of inheritance for gene: TET2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4282 TET2 Zornitza Stark Classified gene: TET2 as Green List (high evidence)
Mendeliome v0.4282 TET2 Zornitza Stark Gene: tet2 has been classified as Green List (High Evidence).
Mendeliome v0.4281 TLR7 Zornitza Stark Marked gene: TLR7 as ready
Mendeliome v0.4281 TLR7 Zornitza Stark Gene: tlr7 has been classified as Green List (High Evidence).
Mendeliome v0.4281 TLR7 Zornitza Stark Phenotypes for gene: TLR7 were changed from to Immunodeficiency 74, COVID19-related, X-linked, MIM# 301051
Mendeliome v0.4280 TLR7 Zornitza Stark Publications for gene: TLR7 were set to
Mendeliome v0.4279 TLR7 Zornitza Stark Mode of inheritance for gene: TLR7 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.4278 EXOSC5 Zornitza Stark Gene: exosc5 has been classified as Green List (High Evidence).
Mendeliome v0.4278 EXOSC5 Zornitza Stark Phenotypes for gene: EXOSC5 were changed from to Short stature; Motor developmental delays; Cerebellar hypoplasia; Ataxia
Mendeliome v0.4277 EXOSC5 Zornitza Stark Publications for gene: EXOSC5 were set to
Mendeliome v0.4276 EXOSC5 Zornitza Stark Mode of inheritance for gene: EXOSC5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4275 EXOSC5 Arina Puzriakova changed review comment from: - PMID: 32504085 (2020) - Five patients from four families with biallelic variants in EXCOSC5. Clinical features included short stature (3/5), developmental delays that affect motor skills (3/5), hypotonia (4/5), ataxia (3/4), cerebellar hypoplasia/atrophy (4/5). Cognitive function was generally preserved, but included mild speech delays in one patient.
Cerebellar ataxia was described in two sibs and one singleton - all of whom were compound heterozygous for the p.Thr114Ile variant, inherited in trans with a frameshift variant (p.His30Thrfs*35) or deletion involving exons 5–6 of EXOSC5, respectively.

A LoF zebrafish model resulted in a variety of morphological defects including shortened and curved tails/bodies, reduced eye/head size and oedema. Functional studies of the variants in budding yeast and cultured cells showed some defects in RNA exosome function and interactions, that could not be explained by decrease in the steady-state level of EXOSC5.

- PMID: 29302074 (2019) - Three sibs with a homozygous EXCOSC5 variant (p.Thr114Ile), associated with mild motor delays, cerebellar ataxia, nystagmus, dysarthria, and moderate ID. The family is also described in PMID: 30950035. No functional studies of the variant were undertaken.; to: - PMID: 32504085 (2020) - Five patients from four families with biallelic variants in EXOSC5. Clinical features included short stature (3/5), developmental delays that affect motor skills (3/5), hypotonia (4/5), ataxia (3/4), cerebellar hypoplasia/atrophy (4/5). Cognitive function was generally preserved, but included mild speech delays in one patient.
Cerebellar ataxia was described in two sibs and one singleton - all of whom were compound heterozygous for the p.Thr114Ile variant, inherited in trans with a frameshift variant (p.His30Thrfs*35) or deletion involving exons 5–6 of EXOSC5, respectively.

A LoF zebrafish model resulted in a variety of morphological defects including shortened and curved tails/bodies, reduced eye/head size and oedema. Functional studies of the variants in budding yeast and cultured cells showed some defects in RNA exosome function and interactions, that could not be explained by decrease in the steady-state level of EXOSC5.

- PMID: 29302074 (2019) - Three sibs with a homozygous EXOSC5 variant (p.Thr114Ile), associated with mild motor delays, cerebellar ataxia, nystagmus, dysarthria, and moderate ID. The family is also described in PMID: 30950035. No functional studies of the variant were undertaken.
Mendeliome v0.4275 EXOSC5 Arina Puzriakova reviewed gene: EXOSC5: Rating: ; Mode of pathogenicity: None; Publications: 32504085, 29302074; Phenotypes: Short stature, Motor developmental delays, Cerebellar hypoplasia, Ataxia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4275 SLC20A1 Zornitza Stark Gene: slc20a1 has been classified as Green List (High Evidence).
Mendeliome v0.4275 SLC20A1 Zornitza Stark Phenotypes for gene: SLC20A1 were changed from to Bladder-Exstrophy-Epispadias Complex (BEEC)
Mendeliome v0.4274 SLC20A1 Zornitza Stark Publications for gene: SLC20A1 were set to
Mendeliome v0.4273 SLC20A1 Zornitza Stark Mode of inheritance for gene: SLC20A1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4272 SLC20A1 Zornitza Stark reviewed gene: SLC20A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32850778, 27013921; Phenotypes: Bladder-Exstrophy-Epispadias Complex (BEEC); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4272 PNPLA8 Zornitza Stark Gene: pnpla8 has been classified as Green List (High Evidence).
Mendeliome v0.4272 PNPLA8 Zornitza Stark Phenotypes for gene: PNPLA8 were changed from to Mitochondrial myopathy with lactic acidosis (MIM#251950), AR
Mendeliome v0.4271 PNPLA8 Zornitza Stark Publications for gene: PNPLA8 were set to
Mendeliome v0.4270 PNPLA8 Zornitza Stark Mode of inheritance for gene: PNPLA8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4269 NR2F1 Zornitza Stark Gene: nr2f1 has been classified as Green List (High Evidence).
Mendeliome v0.4269 NR2F1 Zornitza Stark Phenotypes for gene: NR2F1 were changed from to Bosch-Boonstra-Schaaf optic atrophy syndrome, MIM# 615722
Mendeliome v0.4268 NR2F1 Zornitza Stark Publications for gene: NR2F1 were set to
Mendeliome v0.4267 NR2F1 Zornitza Stark Mode of inheritance for gene: NR2F1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4266 NR2F1 Zornitza Stark reviewed gene: NR2F1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32275123; Phenotypes: Bosch-Boonstra-Schaaf optic atrophy syndrome, MIM# 615722; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4266 RAD50 Zornitza Stark Gene: rad50 has been classified as Green List (High Evidence).
Mendeliome v0.4266 RAD50 Zornitza Stark Phenotypes for gene: RAD50 were changed from to Nijmegen breakage syndrome-like disorder, MIM# 613078
Mendeliome v0.4265 RAD50 Zornitza Stark Publications for gene: RAD50 were set to
Mendeliome v0.4264 RAD50 Zornitza Stark Mode of inheritance for gene: RAD50 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4263 RAD50 Zornitza Stark reviewed gene: RAD50: Rating: GREEN; Mode of pathogenicity: None; Publications: 19409520, 32212377; Phenotypes: Nijmegen breakage syndrome-like disorder, MIM# 613078; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4263 KMT2D Zornitza Stark Publications for gene: KMT2D were set to 31949313
Mendeliome v0.4262 KMT2D Zornitza Stark edited their review of gene: KMT2D: Added comment: Four further individuals with KMT2D-associated neurodevelopmental syndrome reported. Features include: athelia (absent nipples), choanal atresia, hypoparathyroidism, delayed or absent pubertal development, and extreme short stature. Two of the four individuals had severe interstitial lung disease.; Changed publications: 31949313, 32083401
Mendeliome v0.4262 CFAP58 Zornitza Stark Phenotypes for gene: CFAP58 were changed from Multiple morphological abnormalities of the sperm flagella (MMAF) (PMID: 32791035) to Multiple morphological abnormalities of the sperm flagella (MMAF)
Mendeliome v0.4261 CFAP58 Zornitza Stark Gene: cfap58 has been classified as Green List (High Evidence).
Mendeliome v0.4261 CFAP58 Zornitza Stark Classified gene: CFAP58 as Green List (high evidence)
Mendeliome v0.4261 CFAP58 Zornitza Stark Gene: cfap58 has been classified as Green List (High Evidence).
Mendeliome v0.4260 WASHC4 Zornitza Stark Gene: washc4 has been classified as Green List (High Evidence).
Mendeliome v0.4260 WASHC4 Zornitza Stark Classified gene: WASHC4 as Green List (high evidence)
Mendeliome v0.4260 WASHC4 Zornitza Stark Gene: washc4 has been classified as Green List (High Evidence).
Mendeliome v0.4259 WASHC4 Zornitza Stark gene: WASHC4 was added
gene: WASHC4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: WASHC4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WASHC4 were set to 31953988; 21498477
Phenotypes for gene: WASHC4 were set to Mental retardation, autosomal recessive 43, MIM #615817
Review for gene: WASHC4 was set to GREEN
Added comment: Three unrelated families reported.
Sources: Literature
Mendeliome v0.4258 DNAJC7 Seb Lunke Gene: dnajc7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4258 DNAJC7 Seb Lunke Classified gene: DNAJC7 as Amber List (moderate evidence)
Mendeliome v0.4258 DNAJC7 Seb Lunke Gene: dnajc7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4257 DNAJC7 Seb Lunke gene: DNAJC7 was added
gene: DNAJC7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DNAJC7 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DNAJC7 were set to 31768050
Phenotypes for gene: DNAJC7 were set to amyotrophic lateral sclerosis
Review for gene: DNAJC7 was set to AMBER
Added comment: Two cohort studies in ALS patients identified 11 and 1 patient, respectively, with variants in DNAJC7. Seven of these are putative PTVs. However gene described as risk factor, unclear why.

DOI: https://doi.org/10.1212/NXG.0000000000000503
Sources: Literature
Mendeliome v0.4256 SVIL Melanie Marty Deleted their comment
Mendeliome v0.4256 SVIL Melanie Marty edited their review of gene: SVIL: Added comment: Four patients from two unrelated consanguineous families with a childhood/adolescence onset of a myopathy associated with homozygous loss-of-function mutations in SVIL. Wide neck, anteverted shoulders and prominent trapezius muscles together with variable contractures were characteristic features. Functional studies on muscle biopsies showed complete loss protein in muscle fibres by western blot.; Changed rating: AMBER
Mendeliome v0.4256 CFAP58 Crystle Lee edited their review of gene: CFAP58: Added comment: Biallelic variants reported in 5 unrelated males with nultiple morphological abnormalities of the sperm flagella (MMAF). Knockout mice were infertile.; Changed rating: GREEN; Changed publications: 32791035; Changed phenotypes: Multiple morphological abnormalities of the sperm flagella (MMAF) (PMID: 32791035); Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4256 CFAP58 Crystle Lee commented on gene: CFAP58
Mendeliome v0.4256 CFAP58 Crystle Lee Deleted their review
Mendeliome v0.4256 HSPA9 Zornitza Stark Gene: hspa9 has been classified as Green List (High Evidence).
Mendeliome v0.4256 HSPA9 Zornitza Stark Phenotypes for gene: HSPA9 were changed from to Anemia, sideroblastic, 4, MIM# 182170; Even-plus syndrome, MIM#616854; skeletal anomalies; congenital cardiac and renal anomalies: marked small nose
Mendeliome v0.4255 HSPA9 Zornitza Stark Publications for gene: HSPA9 were set to
Mendeliome v0.4254 HSPA9 Zornitza Stark Mode of inheritance for gene: HSPA9 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4253 HSPA9 Seb Lunke Mode of inheritance for gene: HSPA9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4252 SVIL Zornitza Stark Added comment: Comment when marking as ready: Two unrelated families only.
Mendeliome v0.4252 SVIL Zornitza Stark Gene: svil has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4252 SVIL Zornitza Stark Classified gene: SVIL as Amber List (moderate evidence)
Mendeliome v0.4252 SVIL Zornitza Stark Gene: svil has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4251 CFAP57 Zornitza Stark Mode of inheritance for gene: CFAP57 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4250 CFAP57 Zornitza Stark reviewed gene: CFAP57: Rating: AMBER; Mode of pathogenicity: None; Publications: 21574244, 32764743; Phenotypes: Van der Woude Syndrome, Primary ciliary dyskinesia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4250 HSPA9 Sue White reviewed gene: HSPA9: Rating: GREEN; Mode of pathogenicity: None; Publications: 26598328, 32869452; Phenotypes: https://www.omim.org/entry/616854, skeletal anomalies, congenital cardiac and renal anomalies: marked small nose; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4250 SVIL Melanie Marty gene: SVIL was added
gene: SVIL was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SVIL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SVIL were set to 32779703
Phenotypes for gene: SVIL were set to myopathy
Penetrance for gene: SVIL were set to unknown
Review for gene: SVIL was set to GREEN
Added comment: Four patients from two unrelated consanguineous families with a childhood/adolescence onset of a myopathy associated with homozygous loss-of-function mutations in SVIL. Wide neck, anteverted shoulders and prominent trapezius muscles together with variable contractures were characteristic features. Functional studies on muscle biopsies showed complete loss protein in muscle fibres by western blot.
Sources: Literature
Mendeliome v0.4250 HSPA9 Zornitza Stark edited their review of gene: HSPA9: Changed publications: 26491070
Mendeliome v0.4250 HSPA9 Zornitza Stark reviewed gene: HSPA9: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Anemia, sideroblastic, 4, MIM# 182170; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4250 CFAP58 Crystle Lee gene: CFAP58 was added
gene: CFAP58 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: CFAP58 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFAP58 were set to 32791035
Phenotypes for gene: CFAP58 were set to Multiple morphological abnormalities of the sperm flagella (MMAF) (PMID: 32791035)
Review for gene: CFAP58 was set to AMBER
Added comment: 5 unrelated males reported with biallelic loss of function variants. Knockout mice were infertile (Abstract only)
Sources: Expert Review
Mendeliome v0.4250 MYT1L Zornitza Stark Tag SV/CNV tag was added to gene: MYT1L.
Mendeliome v0.4250 MYT1L Zornitza Stark Publications for gene: MYT1L were set to 28859103
Mendeliome v0.4249 MYT1L Zornitza Stark edited their review of gene: MYT1L: Added comment: Over 50 individuals reported with deletions and SNVs affecting MYT1L, and variable phenotype comprising intellectual disability, obesity, and behavioral problems.; Changed publications: 28859103, 32065501
Mendeliome v0.4249 ARID1A Zornitza Stark Gene: arid1a has been classified as Green List (High Evidence).
Mendeliome v0.4249 ARID1A Zornitza Stark Phenotypes for gene: ARID1A were changed from to Coffin-Siris syndrome 2 (MIM#614607)
Mendeliome v0.4248 ARID1A Zornitza Stark Publications for gene: ARID1A were set to
Mendeliome v0.4247 ARID1A Zornitza Stark Mode of inheritance for gene: ARID1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4246 PDE10A Zornitza Stark Gene: pde10a has been classified as Green List (High Evidence).
Mendeliome v0.4246 PDE10A Zornitza Stark Phenotypes for gene: PDE10A were changed from to Dyskinesia, limb and orofacial, infantile-onset, MIM#616921; Striatal degeneration, autosomal dominant, MIM# 616922
Mendeliome v0.4245 PDE10A Zornitza Stark Publications for gene: PDE10A were set to
Mendeliome v0.4244 PDE10A Zornitza Stark Mode of inheritance for gene: PDE10A was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4243 PDE10A Zornitza Stark reviewed gene: PDE10A: Rating: GREEN; Mode of pathogenicity: None; Publications: 27058446, 27058447; Phenotypes: Dyskinesia, limb and orofacial, infantile-onset, MIM#616921, Striatal degeneration, autosomal dominant, MIM# 616922; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4243 MYSM1 Zornitza Stark Publications for gene: MYSM1 were set to 4288411; 28115216; 26220525
Mendeliome v0.4242 MYSM1 Zornitza Stark changed review comment from: early-onset anaemia, leukopaenia, and decreased B cells, may have thrombocytopaenia or variable additional non-haematologic features, such as facial dysmorphism, skeletal anomalies, and mild developmental delay
Sources: Expert list; to: Early-onset anaemia, leukopaenia, and decreased B cells, may have thrombocytopaenia or variable additional non-haematologic features, such as facial dysmorphism, skeletal anomalies, and mild developmental delay. At least 4 unrelated families reported.
Sources: Expert list
Mendeliome v0.4242 MYSM1 Zornitza Stark edited their review of gene: MYSM1: Changed publications: 4288411, 28115216, 26220525, 32640305
Mendeliome v0.4242 PNPLA8 Kristin Rigbye reviewed gene: PNPLA8: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29681094, 25512002; Phenotypes: Mitochondrial myopathy with lactic acidosis (MIM#251950), AR; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4242 ARID1A Crystle Lee reviewed gene: ARID1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 23929686, 22426308, 25168959; Phenotypes: Coffin-Siris syndrome 2 (MIM#614607); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.4242 BTG4 Zornitza Stark Phenotypes for gene: BTG4 were changed from Zygotic cleavage failure (ZCF) to Zygotic cleavage failure (ZCF); Oocyte maturation defect, MIM#619009
Mendeliome v0.4241 BTG4 Zornitza Stark reviewed gene: BTG4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Oocyte maturation defect, MIM#619009; Mode of inheritance: None
Mendeliome v0.4241 KIF1C Zornitza Stark Gene: kif1c has been classified as Green List (High Evidence).
Mendeliome v0.4241 KIF1C Zornitza Stark Phenotypes for gene: KIF1C were changed from to Spastic ataxia 2, autosomal recessive, MIM# 611302
Mendeliome v0.4240 KIF1C Zornitza Stark Publications for gene: KIF1C were set to
Mendeliome v0.4239 KIF1C Zornitza Stark Mode of inheritance for gene: KIF1C was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4238 KIF1C Zornitza Stark reviewed gene: KIF1C: Rating: GREEN; Mode of pathogenicity: None; Publications: 24482476, 24319291, 31413903, 29544888; Phenotypes: Spastic ataxia 2, autosomal recessive, MIM# 611302; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4238 GTPBP2 Zornitza Stark Marked gene: GTPBP2 as ready
Mendeliome v0.4238 GTPBP2 Zornitza Stark Gene: gtpbp2 has been classified as Green List (High Evidence).
Mendeliome v0.4238 GTPBP2 Zornitza Stark Phenotypes for gene: GTPBP2 were changed from to Jaberi-Elahi syndrome, MIM#617988
Mendeliome v0.4237 GTPBP2 Zornitza Stark Publications for gene: GTPBP2 were set to
Mendeliome v0.4236 GTPBP2 Zornitza Stark Mode of inheritance for gene: GTPBP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4235 GTPBP2 Zornitza Stark reviewed gene: GTPBP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26675814, 29449720, 30790272; Phenotypes: Jaberi-Elahi syndrome, MIM#617988; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4235 GNB1 Zornitza Stark Gene: gnb1 has been classified as Green List (High Evidence).
Mendeliome v0.4235 GNB1 Zornitza Stark Phenotypes for gene: GNB1 were changed from to Mental retardation, autosomal dominant 42, MIM# 616973
Mendeliome v0.4234 GNB1 Zornitza Stark Publications for gene: GNB1 were set to
Mendeliome v0.4233 GNB1 Zornitza Stark Mode of inheritance for gene: GNB1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4232 GNB1 Zornitza Stark reviewed gene: GNB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27108799, 30194818, 27668284, 31034681; Phenotypes: Mental retardation, autosomal dominant 42, MIM# 616973; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4232 NDUFB10 Zornitza Stark Phenotypes for gene: NDUFB10 were changed from fatal infantile lactic acidosis; cardiomyopathy to fatal infantile lactic acidosis; cardiomyopathy; Mitochondrial complex I deficiency nuclear type 35 (MC1DN35), MIM#619003
Mendeliome v0.4231 NDUFB10 Zornitza Stark edited their review of gene: NDUFB10: Changed phenotypes: fatal infantile lactic acidosis, cardiomyopathy, Mitochondrial complex I deficiency nuclear type 35 (MC1DN35), MIM#619003
Mendeliome v0.4231 SSBP1 Zornitza Stark Phenotypes for gene: SSBP1 were changed from Optic atrophy with or without extraocular phenotypes to Optic atrophy with or without extraocular phenotypes; Optic atrophy-13 with retinal and foveal abnormalities, MIM#165510
Mendeliome v0.4230 SSBP1 Zornitza Stark reviewed gene: SSBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Optic atrophy-13 with retinal and foveal abnormalities, MIM#165510; Mode of inheritance: None
Mendeliome v0.4230 MCM10 Zornitza Stark Gene: mcm10 has been classified as Red List (Low Evidence).
Mendeliome v0.4230 MCM10 Zornitza Stark gene: MCM10 was added
gene: MCM10 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MCM10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCM10 were set to 32865517
Phenotypes for gene: MCM10 were set to Susceptibility to CMV
Review for gene: MCM10 was set to RED
Added comment: Compound heterozygous variants in minichromosomal maintenance complex member 10 (MCM10) reported as a cause of NK-cell deficiency in a child with fatal susceptibility to CMV.
Sources: Literature
Mendeliome v0.4229 TET2 Zornitza Stark changed review comment from: 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.; to: Mono-allelic variants: 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 v0.4229 TET2 Zornitza Stark changed review comment from: Association study (PMID 32330418) found enrichment of non-coding and LoF TET2 variants in cohort of individuals with early onset dementia, unclear if this is monogenic or polygenic contribution.; to: Mono-allelic variants: Association study (PMID 32330418) found enrichment of non-coding and LoF TET2 variants in cohort of individuals with early onset dementia, unclear if this is monogenic or polygenic contribution.
Mendeliome v0.4229 TET2 Zornitza Stark changed review comment from: PMID 32518946: 3 children with an immune dysregulation syndrome of susceptibility to infection, lymphadenopathy, hepatosplenomegaly, developmental delay, autoimmunity, and lymphoma of B-cell (n = 2) or T-cell (n = 1) origin, and bi-allelic variants in TET2.; to: Bi-allelic variants PMID 32518946: 3 children with an immune dysregulation syndrome of susceptibility to infection, lymphadenopathy, hepatosplenomegaly, developmental delay, autoimmunity, and lymphoma of B-cell (n = 2) or T-cell (n = 1) origin, and bi-allelic variants in TET2.
Mendeliome v0.4229 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. Another French family reported with three sibs: frameshift variant and myeloid malignancies. Contribution of germline variants to malignancy risk to be established.; to: 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 v0.4229 TET2 Zornitza Stark edited their review of gene: TET2: Added comment: PMID 32518946: 3 children with an immune dysregulation syndrome of susceptibility to infection, lymphadenopathy, hepatosplenomegaly, developmental delay, autoimmunity, and lymphoma of B-cell (n = 2) or T-cell (n = 1) origin, and bi-allelic variants in TET2.; Changed rating: GREEN; Changed publications: 30890702, 31827242, 32330418, 32518946; Changed phenotypes: Dementia, Lymphoma/myeloid malignancy, Immunodeficiency; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4229 FDXR Zornitza Stark Gene: fdxr has been classified as Green List (High Evidence).