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Mendeliome v0.2833 PACS1 Ain Roesley reviewed gene: PACS1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 26842493, 23159249; Phenotypes: Schuurs-Hoeijmakers syndrome (MIM# 615009); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2833 SLC15A4 Naomi Baker reviewed gene: SLC15A4: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 25238095; Phenotypes: ; Mode of inheritance: None
Joubert syndrome and other neurological ciliopathies v0.70 ZSWIM6 Crystle Lee gene: ZSWIM6 was added
gene: ZSWIM6 was added to Joubert syndrome and other neurological ciliopathies. Sources: Expert Review
Mode of inheritance for gene: ZSWIM6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ZSWIM6 were set to 25105228; 28213462; 29198722
Phenotypes for gene: ZSWIM6 were set to Acromelic frontonasal dysostosis (MIM#603671)
Review for gene: ZSWIM6 was set to AMBER
Added comment: There are some phenotypic overlap, primarily skeletal abnormalities.

PMID: 25105228: 4 pts with AFND (Arg1163Trp)

PMID: 28213462; AFND caused by this gene was classified as "Likely ciliopathy"

PMID: 29198722; Reported 7 unrelated individuals with a recurrent truncating variant. This patients were "Neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features". No functional studies performed but postulated to be dominant-negative.
Sources: Expert Review
Hereditary Haemorrhagic Telangiectasia v0.8 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Ciliopathies v0.161 UMOD Crystle Lee reviewed gene: UMOD: Rating: GREEN; Mode of pathogenicity: None; Publications: 20172860, 31068150; Phenotypes: Glomerulocystic kidney disease with hyperuricemia and isosthenuria (MIM#609886), Hyperuricemic nephropathy, familial juvenile 1 (MIM#162000), Medullary cystic kidney disease 2 (MIM#603860); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Ichthyosis and Porokeratosis v0.73 FLG Elena Savva reviewed gene: FLG: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 17291859, 30681730; Phenotypes: Ichthyosis vulgaris 146700, {Dermatitis, atopic, susceptibility to, 2} 605803; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Ciliopathies v0.161 PIK3C2A Elena Savva gene: PIK3C2A was added
gene: PIK3C2A was added to Ciliopathies. Sources: Expert list
Mode of inheritance for gene: PIK3C2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIK3C2A were set to PMID: 31034465
Phenotypes for gene: PIK3C2A were set to Oculoskeletodental syndrome 618440
Review for gene: PIK3C2A was set to GREEN
Added comment: Function: catalyzes the phosphorylation of the lipids that are essential for a variety of cellular processes including cilia formation and vesicle trafficking.

PMID: 31034465 - 3 unrelated families (5 patients) with cataracts, skeletal abnormalities, hearing loss, nephrocalcinosis, visual defects etc. Variants included a nonsense, canonical splice causing a large inframe deletion-insertion and intragenic CNV.
MRIs revealed multiple forntal and periventricular lacunar infarcts, lesions of white matter. No mention of MTS or cerebellar atrophy.
Functional assays on patents fibroblasts showed reduced accumulation of PI(3)P (a downstream target of this gene) at the base of cilia and reduced cilia length.
Sources: Expert list
Skeletal Ciliopathies v0.14 EVC Elena Savva reviewed gene: EVC: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 23220543; Phenotypes: Ellis-van Creveld syndrome 225500, ?Weyers acrofacial dysostosis 193530; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Haemorrhagic Telangiectasia v0.7 GDF2 Bryony Thompson Classified gene: GDF2 as Red List (low evidence)
Hereditary Haemorrhagic Telangiectasia v0.7 GDF2 Bryony Thompson Added comment: Comment on list classification: No adequate replication studies exist for this gene, since the initial publication in 2013.
Hereditary Haemorrhagic Telangiectasia v0.7 GDF2 Bryony Thompson Gene: gdf2 has been classified as Red List (Low Evidence).
Mendeliome v0.2833 STARD7 Zornitza Stark Marked gene: STARD7 as ready
Mendeliome v0.2833 STARD7 Zornitza Stark Gene: stard7 has been classified as Green List (High Evidence).
Mendeliome v0.2833 STARD7 Zornitza Stark Classified gene: STARD7 as Green List (high evidence)
Mendeliome v0.2833 STARD7 Zornitza Stark Gene: stard7 has been classified as Green List (High Evidence).
Mendeliome v0.2832 STARD7 Zornitza Stark gene: STARD7 was added
gene: STARD7 was added to Mendeliome. Sources: Expert list
STR tags were added to gene: STARD7.
Mode of inheritance for gene: STARD7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: STARD7 were set to 11701600; 24114805; 31664034
Phenotypes for gene: STARD7 were set to Epilepsy, familial adult myoclonic, 2, 607876
Mode of pathogenicity for gene: STARD7 was set to Other
Review for gene: STARD7 was set to GREEN
Added comment: 158 individuals from 22 families reported with heterozygous 5-bp repeat expansion (ATTTC)n in intron 1 of the STARD7 gene.
Sources: Expert list
Genetic Epilepsy v0.705 STARD7 Zornitza Stark Marked gene: STARD7 as ready
Genetic Epilepsy v0.705 STARD7 Zornitza Stark Gene: stard7 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.705 STARD7 Zornitza Stark Classified gene: STARD7 as Green List (high evidence)
Genetic Epilepsy v0.705 STARD7 Zornitza Stark Gene: stard7 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.704 STARD7 Zornitza Stark gene: STARD7 was added
gene: STARD7 was added to Genetic Epilepsy. Sources: Literature
STR tags were added to gene: STARD7.
Mode of inheritance for gene: STARD7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: STARD7 were set to 11701600; 24114805; 31664034
Phenotypes for gene: STARD7 were set to Epilepsy, familial adult myoclonic, 2, 607876
Mode of pathogenicity for gene: STARD7 was set to Other
Review for gene: STARD7 was set to GREEN
Added comment: 158 individuals from 22 families reported with heterozygous 5-bp repeat expansion (ATTTC)n in intron 1 of the STARD7 gene.
Sources: Literature
Hereditary Haemorrhagic Telangiectasia v0.6 RASA1 Naomi Baker reviewed gene: RASA1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27081547, 29891884, 30507091; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Lissencephaly and Band Heterotopia v0.39 GMPPB Zornitza Stark Marked gene: GMPPB as ready
Lissencephaly and Band Heterotopia v0.39 GMPPB Zornitza Stark Gene: gmppb has been classified as Amber List (Moderate Evidence).
Lissencephaly and Band Heterotopia v0.39 GMPPB Zornitza Stark Phenotypes for gene: GMPPB were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 (MIM# 615350); Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 14 (MIM# 615351); Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 (MIM# 615352)
Lissencephaly and Band Heterotopia v0.38 GMPPB Zornitza Stark Publications for gene: GMPPB were set to
Lissencephaly and Band Heterotopia v0.37 GMPPB Zornitza Stark Mode of inheritance for gene: GMPPB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Lissencephaly and Band Heterotopia v0.36 GMPPB Zornitza Stark Classified gene: GMPPB as Amber List (moderate evidence)
Lissencephaly and Band Heterotopia v0.36 GMPPB Zornitza Stark Gene: gmppb has been classified as Amber List (Moderate Evidence).
Hereditary Haemorrhagic Telangiectasia v0.6 GDF2 Zornitza Stark reviewed gene: GDF2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Telangiectasia, hereditary hemorrhagic, type 5, MIM# 615506; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Lissencephaly and Band Heterotopia v0.35 GMPPB Lauren Akesson reviewed gene: GMPPB: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 23768512, 30257713, 26310427, 24780531; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 (MIM# 615350), Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 14 (MIM# 615351), Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 (MIM# 615352); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Haemorrhagic Telangiectasia v0.6 GDF2 Naomi Baker reviewed gene: GDF2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 23972370, 27081547, 25674101.; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Retinal Disorders Superpanel v0.22 Bryony Thompson Changed child panels to: Autosomal Recessive/X-Linked Retinitis Pigmentosa; Macular Dystrophy/Stargardt Disease; Syndromic Retinopathy; Autosomal Dominant Retinitis Pigmentosa; Vitreoretinopathy; Usher Syndrome; Stickler Syndrome; Cone-rod Dystrophy; Congenital Stationary Night Blindness
Syndromic Retinopathy v0.8 ACBD5 Bryony Thompson Publications for gene: ACBD5 were set to
Cone-rod Dystrophy v0.1 UNC119 Bryony Thompson reviewed gene: UNC119: Rating: GREEN; Mode of pathogenicity: None; Publications: 11006213, 23563732, 27079236; Phenotypes: Cone-rod dystrophy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cone-rod Dystrophy v0.1 Bryony Thompson Panel name changed from Cone-rod Dystrophies to Cone-rod Dystrophy
Panel status changed from internal to public
Panel types changed to Royal Melbourne Hospital; Rare Disease
Cone-rod Dystrophy v0.0 UNC119 Bryony Thompson gene: UNC119 was added
gene: UNC119 was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: UNC119 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: UNC119 were set to 30679166
Phenotypes for gene: UNC119 were set to ?Cone-rod dystrophy
Cone-rod Dystrophy v0.0 TTLL5 Bryony Thompson gene: TTLL5 was added
gene: TTLL5 was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: TTLL5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTLL5 were set to 30679166
Phenotypes for gene: TTLL5 were set to Cone-rod dystrophy 19,615860
Cone-rod Dystrophy v0.0 SEMA4A Bryony Thompson gene: SEMA4A was added
gene: SEMA4A was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: SEMA4A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SEMA4A were set to 30679166
Phenotypes for gene: SEMA4A were set to Cone-rod dystrophy 10, 610283
Cone-rod Dystrophy v0.0 RPGRIP1 Bryony Thompson gene: RPGRIP1 was added
gene: RPGRIP1 was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: RPGRIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RPGRIP1 were set to 30679166
Phenotypes for gene: RPGRIP1 were set to Cone-rod dystrophy 13, 608194
Cone-rod Dystrophy v0.0 RPGR Bryony Thompson gene: RPGR was added
gene: RPGR was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: RPGR 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: RPGR were set to 30679166
Phenotypes for gene: RPGR were set to Cone-rod dystrophy, X-linked, 1, 304020
Cone-rod Dystrophy v0.0 RIMS1 Bryony Thompson gene: RIMS1 was added
gene: RIMS1 was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: RIMS1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RIMS1 were set to 30679166
Phenotypes for gene: RIMS1 were set to Cone-rod dystrophy 7, 603649
Cone-rod Dystrophy v0.0 RAX2 Bryony Thompson gene: RAX2 was added
gene: RAX2 was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: RAX2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RAX2 were set to 30679166
Phenotypes for gene: RAX2 were set to Cone-rod dystrophy 11
Cone-rod Dystrophy v0.0 RAB28 Bryony Thompson gene: RAB28 was added
gene: RAB28 was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: RAB28 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAB28 were set to 30679166
Phenotypes for gene: RAB28 were set to Cone-rod dystrophy 18, 615374
Cone-rod Dystrophy v0.0 PRPH2 Bryony Thompson gene: PRPH2 was added
gene: PRPH2 was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: PRPH2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PRPH2 were set to 30679166
Phenotypes for gene: PRPH2 were set to Choroidal dystrophy, central areolar 2 MIM#613105
Cone-rod Dystrophy v0.0 PROM1 Bryony Thompson gene: PROM1 was added
gene: PROM1 was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: PROM1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: PROM1 were set to 30679166
Phenotypes for gene: PROM1 were set to Cone-rod dystrophy 12, 612657
Cone-rod Dystrophy v0.0 POC1B Bryony Thompson gene: POC1B was added
gene: POC1B was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: POC1B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POC1B were set to 30679166
Phenotypes for gene: POC1B were set to Cone-rod dystrophy 20, 615973
Cone-rod Dystrophy v0.0 PITPNM3 Bryony Thompson gene: PITPNM3 was added
gene: PITPNM3 was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: PITPNM3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PITPNM3 were set to 30679166; 17377520; 22405330
Phenotypes for gene: PITPNM3 were set to Cone-rod dystrophy 5, 600977
Cone-rod Dystrophy v0.0 PDE6H Bryony Thompson gene: PDE6H was added
gene: PDE6H was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: PDE6H was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDE6H were set to 30679166
Phenotypes for gene: PDE6H were set to Retinal Cone Dystrophy 3, 610024; Achromatopsia 6, 610024
Cone-rod Dystrophy v0.0 PDE6C Bryony Thompson gene: PDE6C was added
gene: PDE6C was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: PDE6C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDE6C were set to 30679166
Phenotypes for gene: PDE6C were set to Cone dystrophy 4 MIM#613093
Cone-rod Dystrophy v0.0 OPN1MW Bryony Thompson gene: OPN1MW was added
gene: OPN1MW was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: OPN1MW was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: OPN1MW were set to 30679166
Phenotypes for gene: OPN1MW were set to Blue cone monochromacy MIM#303700; Colorblindness, deutan MIM#303800
Cone-rod Dystrophy v0.0 OPN1LW Bryony Thompson gene: OPN1LW was added
gene: OPN1LW was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: OPN1LW was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: OPN1LW were set to 30679166
Phenotypes for gene: OPN1LW were set to Blue cone monochromacy MIM#303700; Colorblindness, protan MIM#303900
Cone-rod Dystrophy v0.0 KCNV2 Bryony Thompson gene: KCNV2 was added
gene: KCNV2 was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: KCNV2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KCNV2 were set to 30679166
Phenotypes for gene: KCNV2 were set to Retinal cone dystrophy 3B MIM#610356
Cone-rod Dystrophy v0.0 GUCY2D Bryony Thompson gene: GUCY2D was added
gene: GUCY2D was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: GUCY2D was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: GUCY2D were set to 30679166
Phenotypes for gene: GUCY2D were set to Cone-rod dystrophy 6 MIM#601777
Cone-rod Dystrophy v0.0 GUCA1A Bryony Thompson gene: GUCA1A was added
gene: GUCA1A was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: GUCA1A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: GUCA1A were set to 30679166
Phenotypes for gene: GUCA1A were set to Cone dystrophy-3, 602093
Cone-rod Dystrophy v0.0 CRX Bryony Thompson gene: CRX was added
gene: CRX was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: CRX was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CRX were set to 30679166
Phenotypes for gene: CRX were set to Cone-rod retinal dystrophy-2, 120970
Cone-rod Dystrophy v0.0 CNGB3 Bryony Thompson gene: CNGB3 was added
gene: CNGB3 was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: CNGB3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CNGB3 were set to 30679166
Phenotypes for gene: CNGB3 were set to Achromatopsia-3, 262300
Cone-rod Dystrophy v0.0 CNGA3 Bryony Thompson gene: CNGA3 was added
gene: CNGA3 was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: CNGA3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CNGA3 were set to 30679166
Phenotypes for gene: CNGA3 were set to Achromatopsia 2MIM#216900
Cone-rod Dystrophy v0.0 CERKL Bryony Thompson gene: CERKL was added
gene: CERKL was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: CERKL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CERKL were set to 30679166
Phenotypes for gene: CERKL were set to Cone-rod dystrophy
Cone-rod Dystrophy v0.0 CEP78 Bryony Thompson gene: CEP78 was added
gene: CEP78 was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: CEP78 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP78 were set to 30679166
Phenotypes for gene: CEP78 were set to Cone-Rod Dystrophy and Hearing Loss; CRDHL; OMIM: 617236
Cone-rod Dystrophy v0.0 CDHR1 Bryony Thompson gene: CDHR1 was added
gene: CDHR1 was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: CDHR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDHR1 were set to 30679166
Phenotypes for gene: CDHR1 were set to Cone-rod dystrophy 15, 613660
Cone-rod Dystrophy v0.0 CACNA2D4 Bryony Thompson gene: CACNA2D4 was added
gene: CACNA2D4 was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: CACNA2D4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CACNA2D4 were set to 30679166
Phenotypes for gene: CACNA2D4 were set to Retinal cone dystrophy 4, 610478
Cone-rod Dystrophy v0.0 CACNA1F Bryony Thompson gene: CACNA1F was added
gene: CACNA1F was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: CACNA1F 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: CACNA1F were set to 30679166
Phenotypes for gene: CACNA1F were set to Cone-rod dystropy, X-linked, 3, 300476
Cone-rod Dystrophy v0.0 C8orf37 Bryony Thompson gene: C8orf37 was added
gene: C8orf37 was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: C8orf37 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C8orf37 were set to 30679166
Phenotypes for gene: C8orf37 were set to Cone-rod dystrophy 16, 614500; Retinitis pigmentosa 64, 614500
Cone-rod Dystrophy v0.0 C21orf2 Bryony Thompson gene: C21orf2 was added
gene: C21orf2 was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: C21orf2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C21orf2 were set to 30679166
Phenotypes for gene: C21orf2 were set to Retinal dystrophy with macular staphyloma, 617547
Cone-rod Dystrophy v0.0 AIPL1 Bryony Thompson gene: AIPL1 was added
gene: AIPL1 was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: AIPL1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: AIPL1 were set to 30679166
Phenotypes for gene: AIPL1 were set to Leber congenital amaurosis 4, 604393; Cone-rod dystrophy, 604393; Retinitis pigmentosa, juvenile, 604393
Cone-rod Dystrophy v0.0 ADAM9 Bryony Thompson gene: ADAM9 was added
gene: ADAM9 was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: ADAM9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAM9 were set to 30679166
Phenotypes for gene: ADAM9 were set to Cone-rod dystrophy 9, 612775
Cone-rod Dystrophy v0.0 ABCA4 Bryony Thompson gene: ABCA4 was added
gene: ABCA4 was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: ABCA4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABCA4 were set to 30679166
Phenotypes for gene: ABCA4 were set to Cone-rod dystrophy 3, 604116
Cone-rod Dystrophy v0.0 Bryony Thompson Added panel Cone-rod Dystrophies
Retinitis pigmentosa v0.22 IDH3A Bryony Thompson Classified gene: IDH3A as Green List (high evidence)
Retinitis pigmentosa v0.22 IDH3A Bryony Thompson Gene: idh3a has been classified as Green List (High Evidence).
Retinitis pigmentosa v0.21 IDH3A Bryony Thompson gene: IDH3A was added
gene: IDH3A was added to Autosomal Recessive/X-Linked Retinitis Pigmentosa. Sources: NHS GMS
Mode of inheritance for gene: IDH3A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IDH3A were set to 31012789; 30478029; 30058936; 28412069
Phenotypes for gene: IDH3A were set to Retinitis pigmentosa; Leber congenital amaurosis
Mendeliome v0.2831 ERC1 Zornitza Stark Marked gene: ERC1 as ready
Mendeliome v0.2831 ERC1 Zornitza Stark Gene: erc1 has been classified as Red List (Low Evidence).
Mendeliome v0.2831 ERC1 Zornitza Stark Classified gene: ERC1 as Red List (low evidence)
Mendeliome v0.2831 ERC1 Zornitza Stark Gene: erc1 has been classified as Red List (Low Evidence).
Mendeliome v0.2830 ERC1 Chloe Stutterd reviewed gene: ERC1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Cerebral vascular malformations v0.1 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Rare Disease
Cerebral vascular malformations v0.0 WDR62 Zornitza Stark gene: WDR62 was added
gene: WDR62 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: WDR62 was set to
Phenotypes for gene: WDR62 were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 VLDLR Zornitza Stark gene: VLDLR was added
gene: VLDLR was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: VLDLR was set to
Phenotypes for gene: VLDLR were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 TUBG1 Zornitza Stark gene: TUBG1 was added
gene: TUBG1 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: TUBG1 was set to
Phenotypes for gene: TUBG1 were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 TUBB3 Zornitza Stark gene: TUBB3 was added
gene: TUBB3 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: TUBB3 was set to
Phenotypes for gene: TUBB3 were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 TUBB2B Zornitza Stark gene: TUBB2B was added
gene: TUBB2B was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: TUBB2B was set to
Phenotypes for gene: TUBB2B were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 TUBB2A Zornitza Stark gene: TUBB2A was added
gene: TUBB2A was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: TUBB2A was set to
Phenotypes for gene: TUBB2A were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 TUBB Zornitza Stark gene: TUBB was added
gene: TUBB was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: TUBB was set to
Phenotypes for gene: TUBB were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 TUBA8 Zornitza Stark gene: TUBA8 was added
gene: TUBA8 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: TUBA8 was set to
Phenotypes for gene: TUBA8 were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 TUBA1A Zornitza Stark gene: TUBA1A was added
gene: TUBA1A was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: TUBA1A was set to
Phenotypes for gene: TUBA1A were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 TRAIP Zornitza Stark gene: TRAIP was added
gene: TRAIP was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: TRAIP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRAIP were set to 26595769
Phenotypes for gene: TRAIP were set to Seckel syndrome 9 616777
Cerebral vascular malformations v0.0 TMEM5 Zornitza Stark gene: TMEM5 was added
gene: TMEM5 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: TMEM5 was set to
Phenotypes for gene: TMEM5 were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 TGFBR2 Zornitza Stark gene: TGFBR2 was added
gene: TGFBR2 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: TGFBR2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TGFBR2 were set to Loeys-Dietz syndrome 2 610168
Cerebral vascular malformations v0.0 TGFBR1 Zornitza Stark gene: TGFBR1 was added
gene: TGFBR1 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: TGFBR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TGFBR1 were set to Loeys-Dietz syndrome 1 609192
Cerebral vascular malformations v0.0 TGFB2 Zornitza Stark gene: TGFB2 was added
gene: TGFB2 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: TGFB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TGFB2 were set to Loeys-Dietz syndrome 4 614816
Cerebral vascular malformations v0.0 TEK Zornitza Stark gene: TEK was added
gene: TEK was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: TEK was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: TEK were set to Venous malformations, multiple cutaneous and mucosal, 600195; Multiple Cutaneous and Mucosal Venous Malformations
Cerebral vascular malformations v0.0 STAMBP Zornitza Stark gene: STAMBP was added
gene: STAMBP was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: STAMBP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: STAMBP were set to Microcephaly-capillary malformation syndrome, 614261; Microcephaly-capillary malformation syndrome
Cerebral vascular malformations v0.0 SRPX2 Zornitza Stark gene: SRPX2 was added
gene: SRPX2 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: SRPX2 was set to
Phenotypes for gene: SRPX2 were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 SMARCAL1 Zornitza Stark gene: SMARCAL1 was added
gene: SMARCAL1 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: SMARCAL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SMARCAL1 were set to 9674900
Phenotypes for gene: SMARCAL1 were set to Schimke immunoosseous dysplasia 242900
Cerebral vascular malformations v0.0 SMAD3 Zornitza Stark gene: SMAD3 was added
gene: SMAD3 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: SMAD3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SMAD3 were set to Loeys-Dietz syndrome 3 613795
Cerebral vascular malformations v0.0 RTTN Zornitza Stark gene: RTTN was added
gene: RTTN was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: RTTN was set to
Phenotypes for gene: RTTN were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 RELN Zornitza Stark gene: RELN was added
gene: RELN was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: RELN was set to
Phenotypes for gene: RELN were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 RBBP8 Zornitza Stark gene: RBBP8 was added
gene: RBBP8 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: RBBP8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RBBP8 were set to 21998596
Phenotypes for gene: RBBP8 were set to Seckel syndrome 2 606744
Cerebral vascular malformations v0.0 PTEN Zornitza Stark gene: PTEN was added
gene: PTEN was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: PTEN was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: PTEN were set to Bannayan-Riley-Ruvalcaba Syndrome
Cerebral vascular malformations v0.0 POMT2 Zornitza Stark gene: POMT2 was added
gene: POMT2 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: POMT2 was set to
Phenotypes for gene: POMT2 were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 POMT1 Zornitza Stark gene: POMT1 was added
gene: POMT1 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: POMT1 was set to
Phenotypes for gene: POMT1 were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 POMGNT1 Zornitza Stark gene: POMGNT1 was added
gene: POMGNT1 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: POMGNT1 was set to
Phenotypes for gene: POMGNT1 were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 PIK3R2 Zornitza Stark gene: PIK3R2 was added
gene: PIK3R2 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: PIK3R2 was set to
Phenotypes for gene: PIK3R2 were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 PIK3CA Zornitza Stark gene: PIK3CA was added
gene: PIK3CA was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: PIK3CA was set to
Phenotypes for gene: PIK3CA were set to Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome; Megalencephaly-capillary malformation-polymicrogyria syndrome, somatic; Megalencephaly-capillary malformation-polymicrogyria syndrome, somatic, 602501; Congenital Lipomatous Overgrowth, Vascular Malformations, and Epidermal Nevi; Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 PAFAH1B1 Zornitza Stark gene: PAFAH1B1 was added
gene: PAFAH1B1 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: PAFAH1B1 was set to
Phenotypes for gene: PAFAH1B1 were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 OPHN1 Zornitza Stark gene: OPHN1 was added
gene: OPHN1 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: OPHN1 was set to
Phenotypes for gene: OPHN1 were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 OCLN Zornitza Stark gene: OCLN was added
gene: OCLN was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: OCLN was set to
Phenotypes for gene: OCLN were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 NOTCH3 Zornitza Stark gene: NOTCH3 was added
gene: NOTCH3 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: NOTCH3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NOTCH3 were set to 20301673; 8878478
Phenotypes for gene: NOTCH3 were set to Cerebral Arteriopathy, Autosomal Dominant, With Subcortical Infarcts And Leukoencephalopathy (CADASIL); Moyamoya disease; Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1, 125310; Cerebral Arteriopathy, Autosomal Dominant, With Subcortical Infarcts And Leukoencephalopathy; Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL)
Mode of pathogenicity for gene: NOTCH3 was set to Other - please provide details in the comments
Cerebral vascular malformations v0.0 NIN Zornitza Stark gene: NIN was added
gene: NIN was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: NIN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NIN were set to 22933543
Phenotypes for gene: NIN were set to Seckel syndrome 7 614851
Cerebral vascular malformations v0.0 NDE1 Zornitza Stark gene: NDE1 was added
gene: NDE1 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: NDE1 was set to
Phenotypes for gene: NDE1 were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 MEF2C Zornitza Stark gene: MEF2C was added
gene: MEF2C was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: MEF2C was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: MEF2C were set to Mental retardation, stereotypic movements, epilepsy, and/or cerebral malformations; Intellectual Disability, Stereotypic Movements, Epilepsy, and/or Cerebral Malformations; Mental retardation, stereotypic movements, epilepsy, and/or cerebral malformations, 613443
Cerebral vascular malformations v0.0 LARGE1 Zornitza Stark gene: LARGE1 was added
gene: LARGE1 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: LARGE1 was set to
Phenotypes for gene: LARGE1 were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 LAMC3 Zornitza Stark gene: LAMC3 was added
gene: LAMC3 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: LAMC3 was set to
Phenotypes for gene: LAMC3 were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 LAMB1 Zornitza Stark gene: LAMB1 was added
gene: LAMB1 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: LAMB1 was set to
Phenotypes for gene: LAMB1 were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 KDR Zornitza Stark gene: KDR was added
gene: KDR was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: KDR was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: KDR were set to Hemangioma, capillary infantile, somatic; Hemangioma, capillary infantile, somatic, 602089; {Hemangioma, capillary infantile, susceptibility to}, 602089; {Hemangioma, capillary infantile, susceptibility to}
Cerebral vascular malformations v0.0 JAG1 Zornitza Stark gene: JAG1 was added
gene: JAG1 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: JAG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: JAG1 were set to 22759690
Phenotypes for gene: JAG1 were set to Alagille syndrome 1, 118450; Moyamoya disease
Cerebral vascular malformations v0.0 IL6 Zornitza Stark gene: IL6 was added
gene: IL6 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: IL6 was set to
Phenotypes for gene: IL6 were set to {Intracranial hemorrhage in brain cerebrovascular malformations, susceptibility to}
Cerebral vascular malformations v0.0 HTRA1 Zornitza Stark gene: HTRA1 was added
gene: HTRA1 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: HTRA1 was set to Unknown
Phenotypes for gene: HTRA1 were set to Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 2, 616779; Moyamoya disease
Cerebral vascular malformations v0.0 HLA-DRB1 Zornitza Stark gene: HLA-DRB1 was added
gene: HLA-DRB1 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: HLA-DRB1 was set to Unknown
Publications for gene: HLA-DRB1 were set to PMID: 7886716; 21349441
Phenotypes for gene: HLA-DRB1 were set to Moyamoya disease
Cerebral vascular malformations v0.0 HLA-DQB1 Zornitza Stark gene: HLA-DQB1 was added
gene: HLA-DQB1 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: HLA-DQB1 was set to Unknown
Publications for gene: HLA-DQB1 were set to PMID: 21349441; 9409445
Phenotypes for gene: HLA-DQB1 were set to Moyamoya disease
Cerebral vascular malformations v0.0 HLA-B Zornitza Stark gene: HLA-B was added
gene: HLA-B was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: HLA-B was set to Unknown
Publications for gene: HLA-B were set to 14676447; PMID: 21349441
Phenotypes for gene: HLA-B were set to Moyamoya disease
Cerebral vascular malformations v0.0 GNAQ Zornitza Stark gene: GNAQ was added
gene: GNAQ was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: GNAQ was set to
Phenotypes for gene: GNAQ were set to Cerebral diseases of vascular origin with epilepsy; Capillary malformations, congenital, 1, somatic, mosaic, 163000
Cerebral vascular malformations v0.0 GLMN Zornitza Stark gene: GLMN was added
gene: GLMN was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: GLMN was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: GLMN were set to Glomuvenous Malformation; Glomuvenous malformations
Cerebral vascular malformations v0.0 GLA Zornitza Stark gene: GLA was added
gene: GLA was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: GLA was set to Unknown
Phenotypes for gene: GLA were set to Moyamoya disease
Cerebral vascular malformations v0.0 FOXF1 Zornitza Stark gene: FOXF1 was added
gene: FOXF1 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: FOXF1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: FOXF1 were set to Alveolar capillary dysplasia with misalignment of pulmonary veins, 265380; Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins
Cerebral vascular malformations v0.0 FLT4 Zornitza Stark gene: FLT4 was added
gene: FLT4 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: FLT4 was set to
Phenotypes for gene: FLT4 were set to Hemangioma, capillary infantile, somatic; Hemangioma, capillary infantile, somatic, 602089
Cerebral vascular malformations v0.0 FBN1 Zornitza Stark gene: FBN1 was added
gene: FBN1 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: FBN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: FBN1 were set to Marfan syndrome 154700
Cerebral vascular malformations v0.0 ELN Zornitza Stark gene: ELN was added
gene: ELN was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: ELN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ELN were set to 8460548
Phenotypes for gene: ELN were set to Moyamoya disease; Aneurysm, intracranial berry, 1 105800
Cerebral vascular malformations v0.0 DNA2 Zornitza Stark gene: DNA2 was added
gene: DNA2 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: DNA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNA2 were set to 24389050
Phenotypes for gene: DNA2 were set to Seckel syndrome 8 615807
Cerebral vascular malformations v0.0 DCX Zornitza Stark gene: DCX was added
gene: DCX was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: DCX was set to
Phenotypes for gene: DCX were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 CTSA Zornitza Stark gene: CTSA was added
gene: CTSA was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: CTSA was set to Unknown
Cerebral vascular malformations v0.0 CRB1 Zornitza Stark gene: CRB1 was added
gene: CRB1 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: CRB1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: CRB1 were set to Pigmented Paravenous Chorioretinal Atrophy
Cerebral vascular malformations v0.0 COL4A2 Zornitza Stark gene: COL4A2 was added
gene: COL4A2 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: COL4A2 was set to
Phenotypes for gene: COL4A2 were set to {Hemorrhage, intracerebral, susceptibility to}, 614519; {Hemorrhage, intracerebral, susceptibility to}
Cerebral vascular malformations v0.0 COL4A1 Zornitza Stark gene: COL4A1 was added
gene: COL4A1 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: COL4A1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: COL4A1 were set to {Hemorrhage, intracerebral, susceptibility to}, 614519; Brain small vessel disease with or without ocular anomalies; Brain Small Vessel Disease with Hemorrhage; {Hemorrhage, intracerebral, susceptibility to}
Cerebral vascular malformations v0.0 CEP63 Zornitza Stark gene: CEP63 was added
gene: CEP63 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: CEP63 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP63 were set to 21983783
Phenotypes for gene: CEP63 were set to Seckel syndrome 6 614728
Cerebral vascular malformations v0.0 CENPJ Zornitza Stark gene: CENPJ was added
gene: CENPJ was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: CENPJ was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CENPJ were set to Seckel syndrome 4 613676
Cerebral vascular malformations v0.0 BRCC3 Zornitza Stark gene: BRCC3 was added
gene: BRCC3 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: BRCC3 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: BRCC3 were set to 21596366
Phenotypes for gene: BRCC3 were set to Moyamoya disease
Cerebral vascular malformations v0.0 ATP7A Zornitza Stark gene: ATP7A was added
gene: ATP7A was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: ATP7A was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: ATP7A were set to Moyamoya disease
Cerebral vascular malformations v0.0 ARX Zornitza Stark gene: ARX was added
gene: ARX was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: ARX was set to
Phenotypes for gene: ARX were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 ANTXR1 Zornitza Stark gene: ANTXR1 was added
gene: ANTXR1 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: ANTXR1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: ANTXR1 were set to {Hemangioma, capillary infantile, susceptibility to}, 602089; {Hemangioma, capillary infantile, susceptibility to}
Cerebral vascular malformations v0.0 ADGRG1 Zornitza Stark gene: ADGRG1 was added
gene: ADGRG1 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: ADGRG1 was set to
Phenotypes for gene: ADGRG1 were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 ACE Zornitza Stark gene: ACE was added
gene: ACE was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: ACE was set to
Phenotypes for gene: ACE were set to {Stroke, hemorrhagic}
Cerebral vascular malformations v0.0 ABCC6 Zornitza Stark gene: ABCC6 was added
gene: ABCC6 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: ABCC6 was set to Unknown
Phenotypes for gene: ABCC6 were set to Moyamoya disease
Cerebral vascular malformations v0.0 THSD1 Zornitza Stark gene: THSD1 was added
gene: THSD1 was added to Cerebral vascular malformations. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: THSD1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: THSD1 were set to 27895300
Phenotypes for gene: THSD1 were set to subarachnoid hemorrhage
Cerebral vascular malformations v0.0 SMAD9 Zornitza Stark gene: SMAD9 was added
gene: SMAD9 was added to Cerebral vascular malformations. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: SMAD9 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Cerebral vascular malformations v0.0 PKD2 Zornitza Stark gene: PKD2 was added
gene: PKD2 was added to Cerebral vascular malformations. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: PKD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PKD2 were set to Polycystic kidney disease 2 613095
Cerebral vascular malformations v0.0 PKD1 Zornitza Stark gene: PKD1 was added
gene: PKD1 was added to Cerebral vascular malformations. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: PKD1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: PKD1 were set to Polycystic kidney disease, adult type I 173900
Cerebral vascular malformations v0.0 PCNT Zornitza Stark gene: PCNT was added
gene: PCNT was added to Cerebral vascular malformations. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: PCNT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCNT were set to 15368497
Phenotypes for gene: PCNT were set to Microcephalic osteodysplastic primordial dwarfism, type II 210720; Moyamoya disease
Cerebral vascular malformations v0.0 NF1 Zornitza Stark gene: NF1 was added
gene: NF1 was added to Cerebral vascular malformations. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: NF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NF1 were set to 10754001
Phenotypes for gene: NF1 were set to Moyamoya disease; Neurofibromatosis, type 1 162200
Cerebral vascular malformations v0.0 MYH11 Zornitza Stark gene: MYH11 was added
gene: MYH11 was added to Cerebral vascular malformations. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: MYH11 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MYH11 were set to 16444274; 29263223
Phenotypes for gene: MYH11 were set to Aortic aneurysm, familial thoracic 4, 132900; moyamoya-like angiopath
Cerebral vascular malformations v0.0 MRVI1 Zornitza Stark gene: MRVI1 was added
gene: MRVI1 was added to Cerebral vascular malformations. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: MRVI1 was set to Unknown
Cerebral vascular malformations v0.0 HBB Zornitza Stark gene: HBB was added
gene: HBB was added to Cerebral vascular malformations. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: HBB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HBB were set to 20301551
Phenotypes for gene: HBB were set to Sickle cell anemia 603903
Cerebral vascular malformations v0.0 GDF2 Zornitza Stark gene: GDF2 was added
gene: GDF2 was added to Cerebral vascular malformations. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: GDF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral vascular malformations v0.0 FLVCR2 Zornitza Stark gene: FLVCR2 was added
gene: FLVCR2 was added to Cerebral vascular malformations. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: FLVCR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FLVCR2 were set to 20206334
Phenotypes for gene: FLVCR2 were set to Proliferative Vasculopathy And Hydranencephaly-Hydrocephaly Syndrome
Cerebral vascular malformations v0.0 EPHB4 Zornitza Stark gene: EPHB4 was added
gene: EPHB4 was added to Cerebral vascular malformations. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: EPHB4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: EPHB4 were set to Capillary malformation-arteriovenous malformation 2, 618196
Cerebral vascular malformations v0.0 CEP152 Zornitza Stark gene: CEP152 was added
gene: CEP152 was added to Cerebral vascular malformations. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: CEP152 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP152 were set to 21131973
Phenotypes for gene: CEP152 were set to Seckel syndrome 5 613823
Cerebral vascular malformations v0.0 CBL Zornitza Stark gene: CBL was added
gene: CBL was added to Cerebral vascular malformations. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: CBL was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CBL were set to 25283271; 28343148
Phenotypes for gene: CBL were set to early-onset moyamoya angiopathy; Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia, 613563
Mode of pathogenicity for gene: CBL was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Cerebral vascular malformations v0.0 ATR Zornitza Stark gene: ATR was added
gene: ATR was added to Cerebral vascular malformations. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: ATR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATR were set to 12640452
Phenotypes for gene: ATR were set to Seckel syndrome 1 210600
Cerebral vascular malformations v0.0 ADA2 Zornitza Stark gene: ADA2 was added
gene: ADA2 was added to Cerebral vascular malformations. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: ADA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADA2 were set to 3471198, 25528372
Phenotypes for gene: ADA2 were set to Sneddon syndrome 182410; Polyarteritis nodosa
Cerebral vascular malformations v0.0 YY1AP1 Zornitza Stark gene: YY1AP1 was added
gene: YY1AP1 was added to Cerebral vascular malformations. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: YY1AP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: YY1AP1 were set to Grange syndrome, 602531
Cerebral vascular malformations v0.0 SMAD4 Zornitza Stark gene: SMAD4 was added
gene: SMAD4 was added to Cerebral vascular malformations. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: SMAD4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SMAD4 were set to Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome 175050
Cerebral vascular malformations v0.0 SLC2A10 Zornitza Stark gene: SLC2A10 was added
gene: SLC2A10 was added to Cerebral vascular malformations. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: SLC2A10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC2A10 were set to 16550171
Phenotypes for gene: SLC2A10 were set to 208050; Moyamoya disease; Arterial tortuosity syndrome
Cerebral vascular malformations v0.0 SAMHD1 Zornitza Stark gene: SAMHD1 was added
gene: SAMHD1 was added to Cerebral vascular malformations. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: SAMHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SAMHD1 were set to 20653736; 21402907
Phenotypes for gene: SAMHD1 were set to Moyamoya disease
Cerebral vascular malformations v0.0 RNF213 Zornitza Stark gene: RNF213 was added
gene: RNF213 was added to Cerebral vascular malformations. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: RNF213 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: RNF213 were set to 21048783
Phenotypes for gene: RNF213 were set to {Moyamoya disease 2, susceptibility to}
Cerebral vascular malformations v0.0 RASA1 Zornitza Stark gene: RASA1 was added
gene: RASA1 was added to Cerebral vascular malformations. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: RASA1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RASA1 were set to 14639529
Phenotypes for gene: RASA1 were set to Parkes Weber syndrome; Capillary malformation-arteriovenous malformation, 608354; Parkes Weber Syndrome; Parkes Weber syndrome (PKWS); Parkes Weber syndrome, 608355; Capillary Malformation-Arteriovenous Malformation Syndrome
Cerebral vascular malformations v0.0 PDCD10 Zornitza Stark gene: PDCD10 was added
gene: PDCD10 was added to Cerebral vascular malformations. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: PDCD10 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PDCD10 were set to 15543491; 20301470
Phenotypes for gene: PDCD10 were set to Cerebral Cavernous Malformations; Cerebral cavernous malformations 3; Cerebral cavernous malformations 3, 603285; Cerebral Cavernous Malformation; Familial Cerebral Cavernous Malformation
Mode of pathogenicity for gene: PDCD10 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Cerebral vascular malformations v0.0 KRIT1 Zornitza Stark gene: KRIT1 was added
gene: KRIT1 was added to Cerebral vascular malformations. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: KRIT1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KRIT1 were set to 10508515; 20301470
Phenotypes for gene: KRIT1 were set to Cerebral cavernous malformations 1; Cerebral cavernous malformations-1, 116860; Cerebral Cavernous Malformations; Cerebral Cavernous Malformation; Angiokeratoma Corporis Diffusum with Arteriovenous Fistulas; Familial Cerebral Cavernous Malformation; Hyperkeratotic cutaneous capillary-venous malformations associated with cerebral capillary malformations, 116860
Cerebral vascular malformations v0.0 GUCY1A3 Zornitza Stark gene: GUCY1A3 was added
gene: GUCY1A3 was added to Cerebral vascular malformations. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: GUCY1A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GUCY1A3 were set to 24581742; 26777256
Phenotypes for gene: GUCY1A3 were set to Moyamoya 6 with achalasia; Moyamoya 6 with achalasia, 615750
Cerebral vascular malformations v0.0 ENG Zornitza Stark gene: ENG was added
gene: ENG was added to Cerebral vascular malformations. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: ENG was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ENG were set to 15024723; 20301525
Phenotypes for gene: ENG were set to Telangiectasia, hereditary hemorrhagic, type 1 187300
Cerebral vascular malformations v0.0 COL3A1 Zornitza Stark gene: COL3A1 was added
gene: COL3A1 was added to Cerebral vascular malformations. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: COL3A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: COL3A1 were set to Ehlers-Danlos syndrome, type IV 130050
Cerebral vascular malformations v0.0 CCM2 Zornitza Stark gene: CCM2 was added
gene: CCM2 was added to Cerebral vascular malformations. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: CCM2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CCM2 were set to 14624391; 20301470
Phenotypes for gene: CCM2 were set to Cerebral cavernous malformations 2; Cerebral Cavernous Malformation; Capillary malformation-arteriovenous malformation 608354; Cerebral Cavernous Malformations
Cerebral vascular malformations v0.0 ACVRL1 Zornitza Stark gene: ACVRL1 was added
gene: ACVRL1 was added to Cerebral vascular malformations. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: ACVRL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ACVRL1 were set to Telangiectasia, hereditary hemorrhagic, type 2 600376
Cerebral vascular malformations v0.0 ACTA2 Zornitza Stark gene: ACTA2 was added
gene: ACTA2 was added to Cerebral vascular malformations. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: ACTA2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: ACTA2 were set to Multisystemic smooth muscle dysfunction syndrome,613834; Aortic aneurysm familial thoracic 6,611788; Moyamoya Disease; Moyamoya disease 5; Moyamoya disease 5,614042
Cerebral vascular malformations v0.0 Zornitza Stark Added panel Cerebral vascular malformations
Osteogenesis Imperfecta and Osteoporosis v0.21 P3H1 Zornitza Stark Marked gene: P3H1 as ready
Osteogenesis Imperfecta and Osteoporosis v0.21 P3H1 Zornitza Stark Gene: p3h1 has been classified as Green List (High Evidence).
Osteogenesis Imperfecta and Osteoporosis v0.21 P3H1 Zornitza Stark Phenotypes for gene: P3H1 were changed from to Osteogenesis imperfecta, type VIII, (MIM# 610915)
Osteogenesis Imperfecta and Osteoporosis v0.20 P3H1 Zornitza Stark Publications for gene: P3H1 were set to
Osteogenesis Imperfecta and Osteoporosis v0.19 P3H1 Zornitza Stark Mode of inheritance for gene: P3H1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v0.161 CENPF Zornitza Stark Marked gene: CENPF as ready
Ciliopathies v0.161 CENPF Zornitza Stark Gene: cenpf has been classified as Green List (High Evidence).
Ciliopathies v0.161 CENPF Zornitza Stark Phenotypes for gene: CENPF were changed from to Stromme syndrome (MIM#243605)
Ciliopathies v0.160 CENPF Zornitza Stark Publications for gene: CENPF were set to
Ciliopathies v0.159 CENPF Zornitza Stark Mode of inheritance for gene: CENPF was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Joubert syndrome and other neurological ciliopathies v0.70 DDX59 Zornitza Stark Marked gene: DDX59 as ready
Joubert syndrome and other neurological ciliopathies v0.70 DDX59 Zornitza Stark Gene: ddx59 has been classified as Green List (High Evidence).
Joubert syndrome and other neurological ciliopathies v0.70 DDX59 Zornitza Stark Classified gene: DDX59 as Green List (high evidence)
Joubert syndrome and other neurological ciliopathies v0.70 DDX59 Zornitza Stark Gene: ddx59 has been classified as Green List (High Evidence).
Joubert syndrome and other neurological ciliopathies v0.69 ICK Zornitza Stark Marked gene: ICK as ready
Joubert syndrome and other neurological ciliopathies v0.69 ICK Zornitza Stark Gene: ick has been classified as Amber List (Moderate Evidence).
Joubert syndrome and other neurological ciliopathies v0.69 ICK Zornitza Stark Classified gene: ICK as Amber List (moderate evidence)
Joubert syndrome and other neurological ciliopathies v0.69 ICK Zornitza Stark Gene: ick has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2830 DHCR7 Zornitza Stark Marked gene: DHCR7 as ready
Mendeliome v0.2830 DHCR7 Zornitza Stark Gene: dhcr7 has been classified as Green List (High Evidence).
Mendeliome v0.2830 DHCR7 Zornitza Stark Phenotypes for gene: DHCR7 were changed from to Smith-Lemli-Opitz syndrome (MIM#270400)
Mendeliome v0.2829 DHCR7 Zornitza Stark Publications for gene: DHCR7 were set to
Mendeliome v0.2828 DHCR7 Zornitza Stark Mode of inheritance for gene: DHCR7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Joubert syndrome and other neurological ciliopathies v0.68 DHCR7 Zornitza Stark Marked gene: DHCR7 as ready
Joubert syndrome and other neurological ciliopathies v0.68 DHCR7 Zornitza Stark Gene: dhcr7 has been classified as Amber List (Moderate Evidence).
Joubert syndrome and other neurological ciliopathies v0.68 DHCR7 Zornitza Stark Classified gene: DHCR7 as Amber List (moderate evidence)
Joubert syndrome and other neurological ciliopathies v0.68 DHCR7 Zornitza Stark Gene: dhcr7 has been classified as Amber List (Moderate Evidence).
Ciliopathies v0.158 EVC2 Zornitza Stark Marked gene: EVC2 as ready
Ciliopathies v0.158 EVC2 Zornitza Stark Gene: evc2 has been classified as Green List (High Evidence).
Ciliopathies v0.158 EVC2 Zornitza Stark Phenotypes for gene: EVC2 were changed from to Ellis-van Creveld syndrome (MIM#225500)
Ciliopathies v0.157 EVC2 Zornitza Stark Publications for gene: EVC2 were set to
Ciliopathies v0.156 EVC2 Zornitza Stark Mode of inheritance for gene: EVC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Joubert syndrome and other neurological ciliopathies v0.67 EVC Zornitza Stark Marked gene: EVC as ready
Joubert syndrome and other neurological ciliopathies v0.67 EVC Zornitza Stark Gene: evc has been classified as Amber List (Moderate Evidence).
Joubert syndrome and other neurological ciliopathies v0.67 EVC Zornitza Stark Classified gene: EVC as Amber List (moderate evidence)
Joubert syndrome and other neurological ciliopathies v0.67 EVC Zornitza Stark Gene: evc has been classified as Amber List (Moderate Evidence).
Joubert syndrome and other neurological ciliopathies v0.66 GLI3 Zornitza Stark Marked gene: GLI3 as ready
Joubert syndrome and other neurological ciliopathies v0.66 GLI3 Zornitza Stark Gene: gli3 has been classified as Amber List (Moderate Evidence).
Joubert syndrome and other neurological ciliopathies v0.66 GLI3 Zornitza Stark Mode of inheritance for gene: GLI3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Joubert syndrome and other neurological ciliopathies v0.65 GLI3 Zornitza Stark Classified gene: GLI3 as Amber List (moderate evidence)
Joubert syndrome and other neurological ciliopathies v0.65 GLI3 Zornitza Stark Gene: gli3 has been classified as Amber List (Moderate Evidence).
Ciliopathies v0.155 GLI3 Zornitza Stark Marked gene: GLI3 as ready
Ciliopathies v0.155 GLI3 Zornitza Stark Gene: gli3 has been classified as Green List (High Evidence).
Ciliopathies v0.155 GLI3 Zornitza Stark Phenotypes for gene: GLI3 were changed from to Greig cephalopolysyndactyly syndrome (MIM#175700); Pallister-Hall syndrome (MIM#146510)
Ciliopathies v0.154 GLI3 Zornitza Stark Publications for gene: GLI3 were set to
Ciliopathies v0.153 GLI3 Zornitza Stark Mode of inheritance for gene: GLI3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal Ciliopathies v0.14 TTC21B Zornitza Stark Marked gene: TTC21B as ready
Skeletal Ciliopathies v0.14 TTC21B Zornitza Stark Gene: ttc21b has been classified as Green List (High Evidence).
Skeletal Ciliopathies v0.14 TTC21B Zornitza Stark Phenotypes for gene: TTC21B were changed from to Short-rib thoracic dysplasia 4 with or without polydactyly (MIM#613819)
Skeletal Ciliopathies v0.13 TTC21B Zornitza Stark Publications for gene: TTC21B were set to
Skeletal Ciliopathies v0.12 TTC21B Zornitza Stark Mode of inheritance for gene: TTC21B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Optic Atrophy v0.107 PDXK Zornitza Stark Marked gene: PDXK as ready
Optic Atrophy v0.107 PDXK Zornitza Stark Gene: pdxk has been classified as Amber List (Moderate Evidence).
Optic Atrophy v0.107 PDXK Zornitza Stark Classified gene: PDXK as Amber List (moderate evidence)
Optic Atrophy v0.107 PDXK Zornitza Stark Gene: pdxk has been classified as Amber List (Moderate Evidence).
Optic Atrophy v0.106 PDXK Zornitza Stark gene: PDXK was added
gene: PDXK was added to Optic Atrophy. Sources: Literature
Mode of inheritance for gene: PDXK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDXK were set to 31187503
Phenotypes for gene: PDXK were set to Axonal polyneuropathy; optic atrophy
Review for gene: PDXK was set to AMBER
Added comment: 5 individuals from two unrelated families, cell-based functional assays. Response to pyridoxal 5'-phosphate supplementation.
Sources: Literature
Hereditary Neuropathy v0.60 PDXK Zornitza Stark Marked gene: PDXK as ready
Hereditary Neuropathy v0.60 PDXK Zornitza Stark Gene: pdxk has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy v0.60 PDXK Zornitza Stark Classified gene: PDXK as Amber List (moderate evidence)
Hereditary Neuropathy v0.60 PDXK Zornitza Stark Gene: pdxk has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy v0.59 PDXK Zornitza Stark gene: PDXK was added
gene: PDXK was added to Hereditary Neuropathy - complex. Sources: Literature
Mode of inheritance for gene: PDXK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDXK were set to 31187503
Phenotypes for gene: PDXK were set to Axonal polyneuropathy; optic atrophy
Review for gene: PDXK was set to AMBER
Added comment: 5 individuals from two unrelated families, cell-based functional assays. Response to pyridoxal 5'-phosphate supplementation.
Sources: Literature
Mendeliome v0.2827 PDXK Zornitza Stark Marked gene: PDXK as ready
Mendeliome v0.2827 PDXK Zornitza Stark Gene: pdxk has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2827 PDXK Zornitza Stark Publications for gene: PDXK were set to (PMID: 31187503)
Mendeliome v0.2826 PDXK Zornitza Stark Classified gene: PDXK as Amber List (moderate evidence)
Mendeliome v0.2826 PDXK Zornitza Stark Gene: pdxk has been classified as Amber List (Moderate Evidence).
Osteogenesis Imperfecta and Osteoporosis v0.18 P3H1 Ain Roesley reviewed gene: P3H1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 17277775, 18566967; Phenotypes: Osteogenesis imperfecta, type VIII, (MIM# 610915); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2825 PDXK Zornitza Stark reviewed gene: PDXK: Rating: AMBER; Mode of pathogenicity: None; Publications: 31187503; Phenotypes: Axonal polyneuropathy, optic atrophy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Joubert syndrome and other neurological ciliopathies v0.64 TTC21B Zornitza Stark Marked gene: TTC21B as ready
Joubert syndrome and other neurological ciliopathies v0.64 TTC21B Zornitza Stark Gene: ttc21b has been classified as Red List (Low Evidence).
Joubert syndrome and other neurological ciliopathies v0.64 TTC21B Zornitza Stark Publications for gene: TTC21B were set to
Joubert syndrome and other neurological ciliopathies v0.63 TTC21B Zornitza Stark Classified gene: TTC21B as Red List (low evidence)
Joubert syndrome and other neurological ciliopathies v0.63 TTC21B Zornitza Stark Gene: ttc21b has been classified as Red List (Low Evidence).
Bone Marrow Failure v0.61 MECOM Zornitza Stark Mode of pathogenicity for gene: MECOM was changed from None to Other
Joubert syndrome and other neurological ciliopathies v0.62 CENPF Crystle Lee gene: CENPF was added
gene: CENPF was added to Joubert syndrome and other neurological ciliopathies. Sources: Expert Review
Mode of inheritance for gene: CENPF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CENPF were set to 25564561; 28407396; 26820108
Phenotypes for gene: CENPF were set to Stromme syndrome (MIM#243605)
Review for gene: CENPF was set to AMBER
Added comment: Stromme syndrome is well reported as a ciliopathy phenotype with some overlapping JS features although does not seem to be consistent between patients. Amber for this panel

PMID: 25564561; Waters 2015; 2 families reported. Ciliopathy features such as cerebellar vermis hypoplasia and cleft palate reported in one family. Functional studies performed.
PMID: 28407396; Ozkinay 2017; 1 family reported. Brain MRI showed lissecephaly.
PMID: 26820108; Filges 2016; 2 families reported.
Sources: Expert Review
Ciliopathies v0.152 CENPF Crystle Lee reviewed gene: CENPF: Rating: GREEN; Mode of pathogenicity: None; Publications: 25564561, 28407396, 26820108; Phenotypes: Stromme syndrome (MIM#243605); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Joubert syndrome and other neurological ciliopathies v0.62 DDX59 Crystle Lee gene: DDX59 was added
gene: DDX59 was added to Joubert syndrome and other neurological ciliopathies. Sources: Expert Review
Mode of inheritance for gene: DDX59 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DDX59 were set to 29127725; 23972372; 28711741
Phenotypes for gene: DDX59 were set to Orofaciodigital syndrome V (MIM#174300)
Review for gene: DDX59 was set to GREEN
Added comment: Overlapping JS features including cerebellar vermis hypoplasia, cleft palate and postaxial polydactyly. 4 or 5 families reported to date and functional studies performed.

PMID: 29127725; 1 family with OFD
PMID: 23972372; 2 different hom variants reported in 2 families. Functional studies showed impaired ciliary signaling
PMID: 28711741; Same hom variant reported in 2 apparently unrelated consang families. Cerebellar vermis hypoplasia reported in 1 patient
Sources: Expert Review
Joubert syndrome and other neurological ciliopathies v0.62 ICK Crystle Lee gene: ICK was added
gene: ICK was added to Joubert syndrome and other neurological ciliopathies. Sources: Expert Review
Mode of inheritance for gene: ICK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ICK were set to 19185282; 27069622; 27466187; 24797473; 24853502
Phenotypes for gene: ICK were set to Endocrine-cerebroosteodysplasia (MIM#612651)
Review for gene: ICK was set to AMBER
Added comment: 3 families reported, functional studies and animal models. Primarily a skeletal ciliopathy and rare reports of brain and cerebellar malformations. Amber for this panel.

PMID: 19185282; 6 affected from 2 Amish families with endocrine-cerebro-osteodysplasia (ECO)

PMID: 27069622; A different variant reported in a Turkish fetus presenting with ECO and overlapping features of ciliopathies. Functional studies showed abnormal ciliary localization.

PMID: 27466187; Additional variant identified in a patient with short rib polydactyly syndromes (SRPS). Functional studies showed that the variant caused ciliary defects

PMID: 24797473; Ick deficient mice showed ciliary defects. Authors concluded that ICK is required for normal ciliogenesis

PMID: 24853502; Ick knockout mice recapitulates clinical symptoms of ECO. Defects in ICK caused aberrant ciliogenesis
Sources: Expert Review
Mendeliome v0.2825 DHCR7 Crystle Lee reviewed gene: DHCR7: Rating: GREEN; Mode of pathogenicity: None; Publications: 23059950; Phenotypes: Smith-Lemli-Opitz syndrome (MIM#270400); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Joubert syndrome and other neurological ciliopathies v0.62 DHCR7 Crystle Lee gene: DHCR7 was added
gene: DHCR7 was added to Joubert syndrome and other neurological ciliopathies. Sources: Expert Review
Mode of inheritance for gene: DHCR7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DHCR7 were set to 23059950
Phenotypes for gene: DHCR7 were set to Smith-Lemli-Opitz syndrome (MIM#270400)
Review for gene: DHCR7 was set to AMBER
Added comment: Not a ciliopathy however presents with many overlapping JS features including central nervous system anomalies, cleft palate, postaxial polydactyly

PanelApp UK: Important differential diagnosis of ciliopathy
Sources: Expert Review
Skeletal Ciliopathies v0.11 EVC2 Crystle Lee reviewed gene: EVC2: Rating: AMBER; Mode of pathogenicity: None; Publications: 23220543; Phenotypes: Ellis-van Creveld syndrome (MIM#225500); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v0.152 EVC2 Crystle Lee reviewed gene: EVC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23220543; Phenotypes: Ellis-van Creveld syndrome (MIM#225500); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Joubert syndrome and other neurological ciliopathies v0.62 EVC Crystle Lee gene: EVC was added
gene: EVC was added to Joubert syndrome and other neurological ciliopathies. Sources: Expert Review
Mode of inheritance for gene: EVC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EVC were set to 23220543
Phenotypes for gene: EVC were set to Ellis-van Creveld syndrome (MIM#225500)
Review for gene: EVC was set to AMBER
Added comment: Well established ciliopathy gene, primarily with skeletal manifestations and rare reports of cerebellar malformations (Dandy-Walker malformation)
Sources: Expert Review
Joubert syndrome and other neurological ciliopathies v0.62 GLI3 Crystle Lee gene: GLI3 was added
gene: GLI3 was added to Joubert syndrome and other neurological ciliopathies. Sources: Expert Review
Mode of inheritance for gene: GLI3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: GLI3 were set to Greig cephalopolysyndactyly syndrome (MIM#175700); Pallister-Hall syndrome (MIM#146510)
Review for gene: GLI3 was set to AMBER
Added comment: Ciliopathy with some overlapping features of JS, primarily skeletal manifestation.

PMID: 24736735; In a cohort of 55 families, hypoplastic cerebellum was found in 2 patients but without the characteristic molar tooth sign. There appears to be overlapping JS features including limb and craniofacial abnormalities
Sources: Expert Review
Ciliopathies v0.152 GLI3 Crystle Lee reviewed gene: GLI3: Rating: GREEN; Mode of pathogenicity: None; Publications: 24736735; Phenotypes: Greig cephalopolysyndactyly syndrome (MIM#175700), Pallister-Hall syndrome (MIM#146510); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Skeletal Ciliopathies v0.11 TTC21B Crystle Lee reviewed gene: TTC21B: Rating: GREEN; Mode of pathogenicity: None; Publications: 29068549, 25492405, 21258341; Phenotypes: Short-rib thoracic dysplasia 4 with or without polydactyly (MIM#613819); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2825 PDXK Russell Gear gene: PDXK was added
gene: PDXK was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PDXK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDXK were set to (PMID: 31187503)
Phenotypes for gene: PDXK were set to Axonal polyneuropathy; optic atrophy
Review for gene: PDXK was set to RED
Added comment: Currently two unrelated families with axonal polyneuropathy and optic atrophy described in the same paper, with bi-allelic PDXK pathogenic variants. Functional work in the same paper includes work on patient derived fibroblasts, measurement of an axonal damage biomarker (NFL protein), and response to PLP supplementation treatment.

Need one further unrelated family to upgrade to green?
Sources: Literature
Joubert syndrome and other neurological ciliopathies v0.62 TTC21B Crystle Lee changed review comment from: Weak evidence supporting gene as causative of JS.


PMID: 21258341; Davis 2011; Reported het variants in 3 JBTS patients however one of the missense variants, M1186V, present in gnomAD (10 hets) and multiple MKS patients. T231S in one MKS patient present in gnomAD 280 hets and 2 hom.; to: Weak evidence supporting gene as causative of JS.

PMID: 21258341; Davis 2011; Reported het variants in 3 JBTS patients however one of the missense variants, M1186V, present in gnomAD (10 hets) and multiple MKS patients. T231S in one MKS patient present in gnomAD 280 hets and 2 hom.
Joubert syndrome and other neurological ciliopathies v0.62 TTC21B Crystle Lee reviewed gene: TTC21B: Rating: RED; Mode of pathogenicity: None; Publications: 21258341; Phenotypes: ; Mode of inheritance: None
Joubert syndrome and other neurological ciliopathies v0.62 TTC21B Crystle Lee Deleted their review
Joubert syndrome and other neurological ciliopathies v0.62 TTC21B Crystle Lee reviewed gene: TTC21B: Rating: RED; Mode of pathogenicity: None; Publications: 25492405, 21258341; Phenotypes: Short-rib thoracic dysplasia 4 with or without polydactyly (MIM#613819); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bone Marrow Failure v0.60 MECOM Ain Roesley changed review comment from: PMID: 29146883; 6 unrelated individuals with heamatological defects without RUS. de novo variants cause severe aplastic anemia (AA) occuring within the first months of life that requries hematopoietic stem cel transplatation (HSCT).
Mutational spectrum: 2 missense, 2 frameshifts, 1 nonsense and 1 splice; to: PMID: 29146883; 5 unrelated individuals with heamatological defects without RUS. de novo variants cause severe aplastic anemia (AA) occuring within the first months of life that requries hematopoietic stem cel transplatation (HSCT).
Mutational spectrum: 1 missense, 2 frameshifts, 1 nonsense and 1 splice
Bone Marrow Failure v0.60 MECOM Zornitza Stark Phenotypes for gene: MECOM were changed from Radioulnar synostosis with amegakaryocytic thrombocytopenia 2, MIM#616738 to Radioulnar synostosis with amegakaryocytic thrombocytopenia 2, MIM#616738; Bone marrow failure without radioulnar synostosis (RUS)
Bone Marrow Failure v0.59 MECOM Zornitza Stark Publications for gene: MECOM were set to 26581901; 29519864
Proteinuria v0.109 ANLN Michelle Torres reviewed gene: ANLN: Rating: AMBER; Mode of pathogenicity: None; Publications: 24676636, 30002222; Phenotypes: Focal segmental glomerulosclerosis 8 616032; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Proteinuria v0.109 ANLN Michelle Torres Deleted their review
Proteinuria v0.109 ANLN Michelle Torres reviewed gene: ANLN: Rating: GREEN; Mode of pathogenicity: None; Publications: 24676636, 30002222; Phenotypes: Focal segmental glomerulosclerosis 8 616032; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Bone Marrow Failure v0.58 MECOM Ain Roesley reviewed gene: MECOM: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29146883; Phenotypes: bone marrow failure without radioulnar synostosis (RUS); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ciliopathies v0.152 IQCE Zornitza Stark Marked gene: IQCE as ready
Ciliopathies v0.152 IQCE Zornitza Stark Gene: iqce has been classified as Green List (High Evidence).
Ciliopathies v0.152 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Ciliopathies v0.150 IQCE Bryony Thompson Classified gene: IQCE as Green List (high evidence)
Ciliopathies v0.150 IQCE Bryony Thompson Gene: iqce has been classified as Green List (High Evidence).
Ciliopathies v0.149 IQCE Bryony Thompson gene: IQCE was added
gene: IQCE was added to Ciliopathies. Sources: Literature
Mode of inheritance for gene: IQCE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IQCE were set to 31549751; 28488682
Phenotypes for gene: IQCE were set to Postaxial polydactyly
Joubert syndrome and other neurological ciliopathies v0.61 PDE6D Zornitza Stark Classified gene: PDE6D as Amber List (moderate evidence)
Joubert syndrome and other neurological ciliopathies v0.61 PDE6D Zornitza Stark Gene: pde6d has been classified as Amber List (Moderate Evidence).
Joubert syndrome and other neurological ciliopathies v0.60 PDE6D Zornitza Stark edited their review of gene: PDE6D: Changed rating: AMBER
Joubert syndrome and other neurological ciliopathies v0.60 PDE6D Zornitza Stark commented on gene: PDE6D: Second family reported.
Joubert syndrome and other neurological ciliopathies v0.60 PDE6D Zornitza Stark edited their review of gene: PDE6D: Changed publications: 24166846, 30423442
Ciliopathies v0.147 PDE6D Zornitza Stark edited their review of gene: PDE6D: Changed rating: AMBER; Changed publications: 24166846, 30423442
Joubert syndrome and other neurological ciliopathies v0.60 PDE6D Zornitza Stark Marked gene: PDE6D as ready
Joubert syndrome and other neurological ciliopathies v0.60 PDE6D Zornitza Stark Gene: pde6d has been classified as Red List (Low Evidence).
Joubert syndrome and other neurological ciliopathies v0.60 PDE6D Zornitza Stark Classified gene: PDE6D as Red List (low evidence)
Joubert syndrome and other neurological ciliopathies v0.60 PDE6D Zornitza Stark Gene: pde6d has been classified as Red List (Low Evidence).
Mendeliome v0.2825 NDP Zornitza Stark Marked gene: NDP as ready
Mendeliome v0.2825 NDP Zornitza Stark Gene: ndp has been classified as Green List (High Evidence).
Mendeliome v0.2825 NDP Zornitza Stark Phenotypes for gene: NDP were changed from to Exudative vitreoretinopathy 2, X-linked, MIM 305390; Norrie disease, MIM 310600
Mendeliome v0.2824 NDP Zornitza Stark Publications for gene: NDP were set to
Mendeliome v0.2823 NDP Zornitza Stark Mode of inheritance for gene: NDP was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Joubert syndrome and other neurological ciliopathies v0.59 SCLT1 Zornitza Stark Marked gene: SCLT1 as ready
Joubert syndrome and other neurological ciliopathies v0.59 SCLT1 Zornitza Stark Gene: sclt1 has been classified as Red List (Low Evidence).
Joubert syndrome and other neurological ciliopathies v0.59 SCLT1 Zornitza Stark Phenotypes for gene: SCLT1 were changed from Orofaciodigital syndrome type IX; Senior-Loken syndrome to Orofaciodigital syndrome type IX; Senior-Loken syndrome; Bardet-Biedl syndrome
Joubert syndrome and other neurological ciliopathies v0.58 SCLT1 Zornitza Stark Classified gene: SCLT1 as Red List (low evidence)
Joubert syndrome and other neurological ciliopathies v0.58 SCLT1 Zornitza Stark Gene: sclt1 has been classified as Red List (Low Evidence).
Joubert syndrome and other neurological ciliopathies v0.57 SCLT1 Zornitza Stark reviewed gene: SCLT1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Orofaciodigital syndrome type IX, Senior-Loken syndrome, Bardet-Biedl syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Joubert syndrome and other neurological ciliopathies v0.57 POC1B Zornitza Stark Marked gene: POC1B as ready
Joubert syndrome and other neurological ciliopathies v0.57 POC1B Zornitza Stark Added comment: Comment when marking as ready: Mostly ocular phenotype consistent with ciliopathy, insufficient reports to support association with JS/brain phenotypes.
Joubert syndrome and other neurological ciliopathies v0.57 POC1B Zornitza Stark Gene: poc1b has been classified as Red List (Low Evidence).
Joubert syndrome and other neurological ciliopathies v0.57 POC1B Zornitza Stark Classified gene: POC1B as Red List (low evidence)
Joubert syndrome and other neurological ciliopathies v0.57 POC1B Zornitza Stark Gene: poc1b has been classified as Red List (Low Evidence).
Joubert syndrome and other neurological ciliopathies v0.56 KIAA0753 Zornitza Stark Marked gene: KIAA0753 as ready
Joubert syndrome and other neurological ciliopathies v0.56 KIAA0753 Zornitza Stark Added comment: Comment when marking as ready: Sufficient number of families with neurological features consistent with ciliopathy/JS.
Joubert syndrome and other neurological ciliopathies v0.56 KIAA0753 Zornitza Stark Gene: kiaa0753 has been classified as Green List (High Evidence).
Joubert syndrome and other neurological ciliopathies v0.56 KIAA0753 Zornitza Stark Classified gene: KIAA0753 as Green List (high evidence)
Joubert syndrome and other neurological ciliopathies v0.56 KIAA0753 Zornitza Stark Gene: kiaa0753 has been classified as Green List (High Evidence).
Joubert syndrome and other neurological ciliopathies v0.55 VPS13B Zornitza Stark Marked gene: VPS13B as ready
Joubert syndrome and other neurological ciliopathies v0.55 VPS13B Zornitza Stark Gene: vps13b has been classified as Amber List (Moderate Evidence).
Joubert syndrome and other neurological ciliopathies v0.55 VPS13B Zornitza Stark Classified gene: VPS13B as Amber List (moderate evidence)
Joubert syndrome and other neurological ciliopathies v0.55 VPS13B Zornitza Stark Gene: vps13b has been classified as Amber List (Moderate Evidence).
Joubert syndrome and other neurological ciliopathies v0.54 TMEM107 Zornitza Stark Phenotypes for gene: TMEM107 were changed from Meckel syndrome 13 (MIM#617562); Orofaciodigital syndrome XVI (MIM#617563) to Meckel syndrome 13 (MIM#617562); Orofaciodigital syndrome XVI (MIM#617563); Joubert syndrome 29, MIM# 617562
Mendeliome v0.2822 TMEM107 Zornitza Stark Marked gene: TMEM107 as ready
Mendeliome v0.2822 TMEM107 Zornitza Stark Gene: tmem107 has been classified as Green List (High Evidence).
Mendeliome v0.2822 TMEM107 Zornitza Stark Phenotypes for gene: TMEM107 were changed from to Meckel syndrome 13 (MIM#617562); Orofaciodigital syndrome XVI (MIM#617563); Joubert syndrome 29, MIM# 617562
Mendeliome v0.2821 TMEM107 Zornitza Stark Publications for gene: TMEM107 were set to
Mendeliome v0.2820 TMEM107 Zornitza Stark Mode of inheritance for gene: TMEM107 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2819 TMEM107 Zornitza Stark reviewed gene: TMEM107: Rating: GREEN; Mode of pathogenicity: None; Publications: 26518474, 26595381, 26123494; Phenotypes: Meckel syndrome 13 (MIM#617562), Orofaciodigital syndrome XVI (MIM#617563), Joubert syndrome 29 617562; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v0.146 TMEM107 Zornitza Stark Marked gene: TMEM107 as ready
Ciliopathies v0.146 TMEM107 Zornitza Stark Gene: tmem107 has been classified as Green List (High Evidence).
Ciliopathies v0.146 TMEM107 Zornitza Stark Phenotypes for gene: TMEM107 were changed from to Meckel syndrome 13 (MIM#617562); Orofaciodigital syndrome XVI (MIM#617563); Joubert syndrome 29 617562
Ciliopathies v0.145 TMEM107 Zornitza Stark Publications for gene: TMEM107 were set to
Ciliopathies v0.144 TMEM107 Zornitza Stark Mode of inheritance for gene: TMEM107 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v0.143 TMEM107 Zornitza Stark reviewed gene: TMEM107: Rating: GREEN; Mode of pathogenicity: None; Publications: 26518474, 26595381, 26123494; Phenotypes: Meckel syndrome 13 (MIM#617562), Orofaciodigital syndrome XVI (MIM#617563), Joubert syndrome 29 617562; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.100 Bryony Thompson Panel types changed to Victorian Clinical Genetics Services; KidGen; Royal Melbourne Hospital; Rare Disease
Joubert syndrome and other neurological ciliopathies v0.53 TMEM107 Zornitza Stark Marked gene: TMEM107 as ready
Joubert syndrome and other neurological ciliopathies v0.53 TMEM107 Zornitza Stark Gene: tmem107 has been classified as Amber List (Moderate Evidence).
Joubert syndrome and other neurological ciliopathies v0.53 TMEM107 Zornitza Stark Classified gene: TMEM107 as Amber List (moderate evidence)
Joubert syndrome and other neurological ciliopathies v0.53 TMEM107 Zornitza Stark Gene: tmem107 has been classified as Amber List (Moderate Evidence).
Joubert syndrome and other neurological ciliopathies v0.52 HYLS1 Zornitza Stark Marked gene: HYLS1 as ready
Joubert syndrome and other neurological ciliopathies v0.52 HYLS1 Zornitza Stark Gene: hyls1 has been classified as Amber List (Moderate Evidence).
Joubert syndrome and other neurological ciliopathies v0.52 HYLS1 Zornitza Stark Classified gene: HYLS1 as Amber List (moderate evidence)
Joubert syndrome and other neurological ciliopathies v0.52 HYLS1 Zornitza Stark Gene: hyls1 has been classified as Amber List (Moderate Evidence).
Joubert syndrome and other neurological ciliopathies v0.51 TXNDC15 Zornitza Stark Marked gene: TXNDC15 as ready
Joubert syndrome and other neurological ciliopathies v0.51 TXNDC15 Zornitza Stark Gene: txndc15 has been classified as Green List (High Evidence).
Joubert syndrome and other neurological ciliopathies v0.51 TXNDC15 Zornitza Stark Classified gene: TXNDC15 as Green List (high evidence)
Joubert syndrome and other neurological ciliopathies v0.51 TXNDC15 Zornitza Stark Gene: txndc15 has been classified as Green List (High Evidence).
Skeletal Dysplasia_Fetal v0.21 ALPL Zornitza Stark Marked gene: ALPL as ready
Skeletal Dysplasia_Fetal v0.21 ALPL Zornitza Stark Gene: alpl has been classified as Green List (High Evidence).
Skeletal Dysplasia_Fetal v0.21 ALPL Zornitza Stark Phenotypes for gene: ALPL were changed from to Hypophosphatasia, infantile MIM# 241500
Skeletal Dysplasia_Fetal v0.20 ALPL Zornitza Stark Publications for gene: ALPL were set to
Skeletal Dysplasia_Fetal v0.19 ALPL Zornitza Stark Mode of inheritance for gene: ALPL was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Skeletal Dysplasia_Fetal v0.18 ALPL Zornitza Stark reviewed gene: ALPL: Rating: GREEN; Mode of pathogenicity: None; Publications: 19500388, 23688511; Phenotypes: Hypophosphatasia, infantile MIM# 241500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2819 ALPL Zornitza Stark Marked gene: ALPL as ready
Mendeliome v0.2819 ALPL Zornitza Stark Gene: alpl has been classified as Green List (High Evidence).
Mendeliome v0.2819 ALPL Zornitza Stark Phenotypes for gene: ALPL were changed from to Hypophosphatasia, adult 146300 (AD, AR); Hypophosphatasia, childhood 241510 AR; Hypophosphatasia, infantile 241500 AR; Odontohypophosphatasia 146300 AD, AR
Mendeliome v0.2818 ALPL Zornitza Stark Publications for gene: ALPL were set to
Mendeliome v0.2817 ALPL Zornitza Stark Mode of pathogenicity for gene: ALPL was changed from to Other
Mendeliome v0.2816 ALPL Zornitza Stark Mode of inheritance for gene: ALPL was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Ciliopathies v0.143 MUC1 Zornitza Stark Marked gene: MUC1 as ready
Ciliopathies v0.143 MUC1 Zornitza Stark Added comment: Comment when marking as ready: Agree, some phenotypic overlap but not a ciliopathy and main variant type not currently readily tractable by NGS.
Ciliopathies v0.143 MUC1 Zornitza Stark Gene: muc1 has been classified as Red List (Low Evidence).
Ciliopathies v0.143 MUC1 Zornitza Stark Phenotypes for gene: MUC1 were changed from to Medullary cystic kidney disease 1 (MIM#174000)
Ciliopathies v0.142 MUC1 Zornitza Stark Publications for gene: MUC1 were set to
Ciliopathies v0.141 MUC1 Zornitza Stark Mode of inheritance for gene: MUC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ciliopathies v0.140 MUC1 Zornitza Stark Classified gene: MUC1 as Red List (low evidence)
Ciliopathies v0.140 MUC1 Zornitza Stark Gene: muc1 has been classified as Red List (Low Evidence).
Joubert syndrome and other neurological ciliopathies v0.50 C2CD3 Zornitza Stark Marked gene: C2CD3 as ready
Joubert syndrome and other neurological ciliopathies v0.50 C2CD3 Zornitza Stark Gene: c2cd3 has been classified as Green List (High Evidence).
Joubert syndrome and other neurological ciliopathies v0.50 C2CD3 Zornitza Stark Classified gene: C2CD3 as Green List (high evidence)
Joubert syndrome and other neurological ciliopathies v0.50 C2CD3 Zornitza Stark Gene: c2cd3 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.76 LRRC56 Zornitza Stark Marked gene: LRRC56 as ready
Ciliary Dyskinesia v0.76 LRRC56 Zornitza Stark Gene: lrrc56 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.76 LRRC56 Zornitza Stark Classified gene: LRRC56 as Green List (high evidence)
Ciliary Dyskinesia v0.76 LRRC56 Zornitza Stark Gene: lrrc56 has been classified as Green List (High Evidence).
Mendeliome v0.2815 LRRC56 Zornitza Stark Marked gene: LRRC56 as ready
Mendeliome v0.2815 LRRC56 Zornitza Stark Gene: lrrc56 has been classified as Green List (High Evidence).
Mendeliome v0.2815 LRRC56 Zornitza Stark Classified gene: LRRC56 as Green List (high evidence)
Mendeliome v0.2815 LRRC56 Zornitza Stark Gene: lrrc56 has been classified as Green List (High Evidence).
Mendeliome v0.2814 LRRC56 Zornitza Stark reviewed gene: LRRC56: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 39, MIM# 618254; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2637 IQSEC3 Zornitza Stark Phenotypes for gene: IQSEC3 were changed from Intellectual disability to Intellectual disability; Fetal akinesia
Intellectual disability syndromic and non-syndromic v0.2636 IQSEC3 Zornitza Stark Publications for gene: IQSEC3 were set to 31130284
Joubert syndrome and other neurological ciliopathies v0.49 KIAA0586 Zornitza Stark Marked gene: KIAA0586 as ready
Joubert syndrome and other neurological ciliopathies v0.49 KIAA0586 Zornitza Stark Gene: kiaa0586 has been classified as Green List (High Evidence).
Joubert syndrome and other neurological ciliopathies v0.49 KIAA0586 Zornitza Stark Classified gene: KIAA0586 as Green List (high evidence)
Joubert syndrome and other neurological ciliopathies v0.49 KIAA0586 Zornitza Stark Gene: kiaa0586 has been classified as Green List (High Evidence).
Mendeliome v0.2814 NDP Teresa Zhao reviewed gene: NDP: Rating: GREEN; Mode of pathogenicity: None; Publications: 23444378, 8268931, 17325173, 27217716, 29181528, 31827910; Phenotypes: Exudative vitreoretinopathy 2, X-linked, MIM 305390, Norrie disease, MIM 310600; Mode of inheritance: Other
Joubert syndrome and other neurological ciliopathies v0.48 SCLT1 Elena Savva gene: SCLT1 was added
gene: SCLT1 was added to Joubert syndrome and other neurological ciliopathies. Sources: Expert list
Mode of inheritance for gene: SCLT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCLT1 were set to PMID: 24285566; 32253632; 30425282
Phenotypes for gene: SCLT1 were set to Orofaciodigital syndrome type IX; Senior-Loken syndrome
Review for gene: SCLT1 was set to AMBER
Added comment: PMID: 24285566 - 1 patient with a homozygous splice variant, proven to result in a fs and NMD protein. MRI results show agenesis of corpus callosum and pachygyria - no mention of cerebellar hypoplasia or MTS. Additional features include coloboma and cleft lip/palate

PMID: 32253632 - 2 unrelated patients with Bardet-Biedl syndrome. Both patients were chet for the same variants (missense), one found to have splice consequences. Neither patient had polydactyly, but both had ID and renal dysfunction.

PMID: 30425282 - 1 patient (chet splice/splice) with Senior Løken syndrome. Patient had renal dysfunction, mild ID but no MRI performed. Authors suggest biallelic null LOF variants are more severe.

Summary: no JS patients but a clear relationship to similar ciliopathies. Potentially needs adding to the BBS gene list.
Sources: Expert list
Joubert syndrome and other neurological ciliopathies v0.48 POC1B Elena Savva gene: POC1B was added
gene: POC1B was added to Joubert syndrome and other neurological ciliopathies. Sources: Expert list
Mode of inheritance for gene: POC1B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POC1B were set to PMID: 25044745; 31390656; 25018096
Phenotypes for gene: POC1B were set to Cone-rod dystrophy 20 615973
Review for gene: POC1B was set to RED
Added comment: PMID: 25044745 - 1 homozygous family (missense) with leber congenital amaurosis, JS and polycystic kidney disease. 13 healthy relatives were wildtype or heterozygous carriers only.
MRI shows MTS, cerebellar vermis hypoplasia and malorientated cerebellar peduncles.
Null zebrafish model had cystic kidney and retinal degeneration - no mention of JS features.

PMID: 31390656 - 7 families (8 patients) either chet (PTC/missense) or homozygous (missense) with retinopathies. No mention of JS-related phenotypes eg. polydactyly, brain malformation, intellectual disability

PMID: 25018096 - 1 homozygous family (missense) with cone rod dystrophy. No mention of JS-related phenotypes eg. polydactyly, brain malformation, intellectual disability

Summary: single example of JS, doesnt seem to correlate with a particular genotype
Sources: Expert list
Joubert syndrome and other neurological ciliopathies v0.48 KIAA0753 Elena Savva gene: KIAA0753 was added
gene: KIAA0753 was added to Joubert syndrome and other neurological ciliopathies. Sources: Expert list
Mode of inheritance for gene: KIAA0753 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA0753 were set to PMID: 31816441; 28220259; 29138412; 26643951
Phenotypes for gene: KIAA0753 were set to ?Orofaciodigital syndrome XV 617127; Joubert syndrome
Review for gene: KIAA0753 was set to GREEN
Added comment: PMID: 31816441 - 1 patient with a homozygous PTC. No MTS on MRI at 8 months old, clearly stated by authors. Patient had a skeletal dysplasia. Authors summerize reports, no obvious genotype-phenotype correlation.

PMID: 28220259 - 2 chet (missense/inframe del) siblings with JS. Both siblings showed the MTS on MRI, one also had additional hypoplasia of cerebellar vermis. Functional studies on patient cells demonstrated significantly less cilia.

PMID: 29138412 - All patients had brachydactyly.
Patient 1 and 2 (cousins) - showed MTS on MRI, inferior vermis dysplasia. Patients had a homozygous PTC.
Patient 3 - no MTS, but described as having brain features consistent with JS.
Patient 4 - vermis dysplasia, no mention of MTS. Not regarded as having JS, diagnosed with short-rib thoracic dyplasia. Patient was chet for two PTCs.
Zebrafish null models have skeletal abnormalities, no mention of brain analysis/abnormalities

PMID: 26643951 - 1 chet patient (PTC/splice causing fs) with OFD syndrome. MRI shows MTS and vermis hypoplasia
Sources: Expert list
Joubert syndrome and other neurological ciliopathies v0.48 VPS13B Crystle Lee gene: VPS13B was added
gene: VPS13B was added to Joubert syndrome and other neurological ciliopathies. Sources: Expert Review
Mode of inheritance for gene: VPS13B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VPS13B were set to Cohen syndrome (MIM# 216550)
Review for gene: VPS13B was set to AMBER
Added comment: Well reported to cause Cohen syndrome. Amber for this gene panel due to phenotypic overlap although not strictly a cilipoathy.
Sources: Expert Review
Joubert syndrome and other neurological ciliopathies v0.48 TMEM107 Crystle Lee gene: TMEM107 was added
gene: TMEM107 was added to Joubert syndrome and other neurological ciliopathies. Sources: Expert Review
Mode of inheritance for gene: TMEM107 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM107 were set to 26595381; 26123494
Phenotypes for gene: TMEM107 were set to Meckel syndrome 13 (MIM#617562); Orofaciodigital syndrome XVI (MIM#617563)
Review for gene: TMEM107 was set to AMBER
Added comment: Minimal reports to date. Left as amber for now pending additional reports. Bordeline amber/green

PMID: 26595381; Lambacher 2016: Reported hom (OFDVI female twins) and chet variants (JBTS male) in 2 families. All possesed JBTS-associated molar tooth sign

PMID: 26123494; Shaheen 2015: Same hom splice variant reported in 2 apparently unrelated families (counted as 1). Anaylsis of patient fibroblasts shows ciliogenesis defect.
Sources: Expert Review
Joubert syndrome and other neurological ciliopathies v0.48 HYLS1 Elena Savva gene: HYLS1 was added
gene: HYLS1 was added to Joubert syndrome and other neurological ciliopathies. Sources: Expert list
Mode of inheritance for gene: HYLS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HYLS1 were set to PMID: 26830932
Phenotypes for gene: HYLS1 were set to Hydrolethalus syndrome 236680
Review for gene: HYLS1 was set to AMBER
Added comment: OMIM notes Dandy Walker anomaly as a neurological feature. All patients results in either stillbirths or neonatal death, so limited information available. Almost all patients have the same recurring missense (p.Asp211Gly)

PMID: 18648327 - describes many patients with the recurring missense mutation. Summary table describes brain features of 19 patients, none appear to be consistent with JS

PMID: 26830932 - 2 homozygous living siblings (stop-loss, extension) both diagnosed with JS. Patients had molar tooth signs and dysplasia of cerebellar vermis

Single reported family, but likely due to a unique mutational spectrum separate from the recurring missense
Sources: Expert list
Joubert syndrome and other neurological ciliopathies v0.48 TXNDC15 Crystle Lee gene: TXNDC15 was added
gene: TXNDC15 was added to Joubert syndrome and other neurological ciliopathies. Sources: Expert Review
Mode of inheritance for gene: TXNDC15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TXNDC15 were set to 30851085; 27894351
Phenotypes for gene: TXNDC15 were set to Meckel-Gruber syndrome
Review for gene: TXNDC15 was set to GREEN
Added comment: No OMIM number. Total of 4 families reported with supporting functional studies in ciliogenesis defects. Emerging MKS gene.

PMID: 30851085; Ridnoi 2019: Chet variants identified in a prenatally diagnosed case of Meckel-Gruber syndrome.

PMID: 27894351; Shaheen 2016: Reported 3 diff hom variants in 3 consang families with Meckel-Gruber syndrome.Functional studies performed showing defects in ciliogenesis
Sources: Expert Review
Mendeliome v0.2814 ALPL Melanie Marty reviewed gene: ALPL: Rating: GREEN; Mode of pathogenicity: Other; Publications: 19500388, 23688511; Phenotypes: Hypophosphatasia, adult 146300 (AD, AR), Hypophosphatasia, childhood 241510 AR, Hypophosphatasia, infantile 241500 AR, Odontohypophosphatasia 146300 AD, AR; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Ciliopathies v0.139 MUC1 Crystle Lee reviewed gene: MUC1: Rating: RED; Mode of pathogenicity: None; Publications: 29186029, 29156055, 29520014; Phenotypes: Medullary cystic kidney disease 1 (MIM#174000); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Joubert syndrome and other neurological ciliopathies v0.48 C2CD3 Elena Savva gene: C2CD3 was added
gene: C2CD3 was added to Joubert syndrome and other neurological ciliopathies. Sources: Expert list
Mode of inheritance for gene: C2CD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C2CD3 were set to PMID: 24997988
Phenotypes for gene: C2CD3 were set to Orofaciodigital syndrome XIV 615948
Review for gene: C2CD3 was set to GREEN
Added comment: Molar tooth sign (MTS) a listed phenotype in OMIM

PMID: 24997988 - 1 patient with a homozygous PTC. MRI showed MTS

PMID: 30097616 -
1 chet (two splice) patient with MTS, polydactyly. Sibling also had polydactyly, mild cerebellar hypoplasia and grey matter heterotopia.
1 chet (two missense) patient with MTS, was noted to have a diagnosis of Joubert syndrome
Summary Table 3 reviews previous reports, and notes 6/12 cases also had MTS.
Sources: Expert list
Ciliary Dyskinesia v0.75 LRRC56 Elena Savva gene: LRRC56 was added
gene: LRRC56 was added to Ciliary Dyskinesia. Sources: Expert list
Mode of inheritance for gene: LRRC56 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRRC56 were set to PMID: 30388400
Phenotypes for gene: LRRC56 were set to Ciliary dyskinesia, primary, 39 618254
Review for gene: LRRC56 was set to GREEN
Added comment: PMID: 30388400 - PMID: 30388400 - used protist null model to show abnormal ciliary beatings, replicated the phenotype when the protist was transfected with mutant allele observed in a patient.
3 unrelated families reported with either homozygous splice, missense or chet (nonsense/splice). Patients exhibited phenotypes including chronic respiratory/ear infections, situs inversus
Sources: Expert list
Mendeliome v0.2814 LRRC56 Elena Savva gene: LRRC56 was added
gene: LRRC56 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: LRRC56 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRRC56 were set to PMID: 30388400
Phenotypes for gene: LRRC56 were set to Ciliary dyskinesia, primary, 39 618254
Added comment: PMID: 30388400 - used protist null model to show abnormal ciliary beatings, replicated the phenotype when the protist was transfected with mutant allele observed in a patient.
3 unrelated families reported with either homozygous splice, missense or chet (nonsense/splice). Patients exhibited phenotypes including chronic respiratory/ear infections, situs inversus
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2635 IQSEC3 Elena Savva reviewed gene: IQSEC3: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 32049026, 31130284, 31680123; Phenotypes: Intellectual disability, Fetal akinesia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Joubert syndrome and other neurological ciliopathies v0.48 KIAA0586 Elena Savva gene: KIAA0586 was added
gene: KIAA0586 was added to Joubert syndrome and other neurological ciliopathies. Sources: Literature
Mode of inheritance for gene: KIAA0586 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA0586 were set to PMID: 26096313
Phenotypes for gene: KIAA0586 were set to Joubert syndrome 23 616490; Short-rib thoracic dysplasia 14 with polydactyly 616546
Review for gene: KIAA0586 was set to GREEN
Added comment: PMID: 26096313 - 9 unrelated families with Joubert syndrome. MRI shows the molar tooth sign in 3/3 scanned patients. Patients tended to have biallelic PTCs, though missense also reported. p.Arg143Lysfs*4 appears to be a recurring mutation, seen in patients either as a homozygote or in chet with another unique mutation in 7/9 families. Interestingly these 7 families were of different ethnicity
Sources: Literature
Stroke v0.54 YY1AP1 Bryony Thompson Classified gene: YY1AP1 as Green List (high evidence)
Stroke v0.54 YY1AP1 Bryony Thompson Gene: yy1ap1 has been classified as Green List (High Evidence).
Stroke v0.53 YY1AP1 Bryony Thompson gene: YY1AP1 was added
gene: YY1AP1 was added to Stroke. Sources: Literature
Mode of inheritance for gene: YY1AP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YY1AP1 were set to 31633303; 30356112; 31270375; 22987684; 16691574
Phenotypes for gene: YY1AP1 were set to Grange syndrome MIM#602531
Review for gene: YY1AP1 was set to GREEN
Added comment: At least 3 cases reported with early-onset stroke
Sources: Literature
Osteogenesis Imperfecta and Osteoporosis v0.18 IFITM5 Zornitza Stark Marked gene: IFITM5 as ready
Osteogenesis Imperfecta and Osteoporosis v0.18 IFITM5 Zornitza Stark Gene: ifitm5 has been classified as Green List (High Evidence).
Osteogenesis Imperfecta and Osteoporosis v0.18 IFITM5 Zornitza Stark Phenotypes for gene: IFITM5 were changed from to Osteogenesis imperfecta type V, MIM#610967
Osteogenesis Imperfecta and Osteoporosis v0.17 IFITM5 Zornitza Stark Publications for gene: IFITM5 were set to
Osteogenesis Imperfecta and Osteoporosis v0.16 IFITM5 Zornitza Stark Mode of pathogenicity for gene: IFITM5 was changed from to Other
Osteogenesis Imperfecta and Osteoporosis v0.15 IFITM5 Zornitza Stark Mode of inheritance for gene: IFITM5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Disorders of Glycosylation v0.50 MOGS Zornitza Stark Marked gene: MOGS as ready
Congenital Disorders of Glycosylation v0.50 MOGS Zornitza Stark Gene: mogs has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v0.50 MOGS Zornitza Stark Phenotypes for gene: MOGS were changed from to Congenital disorder of glycosylation, type IIb, MIM# 606056
Congenital Disorders of Glycosylation v0.49 MOGS Zornitza Stark Publications for gene: MOGS were set to
Congenital Disorders of Glycosylation v0.48 MOGS Zornitza Stark Mode of inheritance for gene: MOGS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.47 MOGS Zornitza Stark reviewed gene: MOGS: Rating: GREEN; Mode of pathogenicity: None; Publications: 31925597; Phenotypes: Congenital disorder of glycosylation, type IIb, MIM# 606056; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteogenesis Imperfecta and Osteoporosis v0.14 IFITM5 Chern Lim reviewed gene: IFITM5: Rating: GREEN; Mode of pathogenicity: Other; Publications: 22863190, 22863195, 32383316, 24519609; Phenotypes: Osteogenesis imperfecta type V, MIM#610967; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.2814 MOGS Zornitza Stark Marked gene: MOGS as ready
Mendeliome v0.2814 MOGS Zornitza Stark Gene: mogs has been classified as Green List (High Evidence).
Mendeliome v0.2814 MOGS Zornitza Stark Phenotypes for gene: MOGS were changed from to Congenital disorder of glycosylation, type IIb 606056
Mendeliome v0.2813 MOGS Zornitza Stark Publications for gene: MOGS were set to
Mendeliome v0.2812 MOGS Zornitza Stark Mode of inheritance for gene: MOGS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2811 TCF7L1 Zornitza Stark Marked gene: TCF7L1 as ready
Mendeliome v0.2811 TCF7L1 Zornitza Stark Gene: tcf7l1 has been classified as Red List (Low Evidence).
Mendeliome v0.2811 TCF7L1 Zornitza Stark Phenotypes for gene: TCF7L1 were changed from to Congenital hypopituitarism
Mendeliome v0.2810 TCF7L1 Zornitza Stark Publications for gene: TCF7L1 were set to
Mendeliome v0.2809 TCF7L1 Zornitza Stark Mode of inheritance for gene: TCF7L1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2808 TCF7L1 Zornitza Stark Classified gene: TCF7L1 as Red List (low evidence)
Mendeliome v0.2808 TCF7L1 Zornitza Stark Gene: tcf7l1 has been classified as Red List (Low Evidence).
Stroke v0.52 SMARCAL1 Bryony Thompson Classified gene: SMARCAL1 as Green List (high evidence)
Stroke v0.52 SMARCAL1 Bryony Thompson Gene: smarcal1 has been classified as Green List (High Evidence).
Stroke v0.51 SMARCAL1 Bryony Thompson gene: SMARCAL1 was added
gene: SMARCAL1 was added to Stroke. Sources: Literature
Mode of inheritance for gene: SMARCAL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SMARCAL1 were set to 16840568; 9674900; 30356112; 30026777; 20301550
Phenotypes for gene: SMARCAL1 were set to Schimke immunoosseous dysplasia MIM#242900
Review for gene: SMARCAL1 was set to GREEN
Added comment: Moyamoya type strokes or cerebral ischaemic attacks have been reported as features of the condition.
Sources: Literature
Stroke v0.50 SERPINC1 Bryony Thompson Marked gene: SERPINC1 as ready
Stroke v0.50 SERPINC1 Bryony Thompson Gene: serpinc1 has been classified as Green List (High Evidence).
Stroke v0.50 SERPINC1 Bryony Thompson Classified gene: SERPINC1 as Green List (high evidence)
Stroke v0.50 SERPINC1 Bryony Thompson Gene: serpinc1 has been classified as Green List (High Evidence).
Stroke v0.49 SERPINC1 Bryony Thompson gene: SERPINC1 was added
gene: SERPINC1 was added to Stroke. Sources: Literature
Mode of inheritance for gene: SERPINC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SERPINC1 were set to 31359133; 30356112; 23910795
Phenotypes for gene: SERPINC1 were set to Thrombophilia due to antithrombin III deficiency MIM#613118
Review for gene: SERPINC1 was set to GREEN
Added comment: There is a high incidence of stroke in the condition.
Sources: Literature
Mendeliome v0.2807 TCF7L1 Naomi Baker reviewed gene: TCF7L1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 26764381; Phenotypes: Congenital hypopituitarism; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Stroke v0.48 SCN5A Bryony Thompson Classified gene: SCN5A as Green List (high evidence)
Stroke v0.48 SCN5A Bryony Thompson Gene: scn5a has been classified as Green List (High Evidence).
Stroke v0.47 SCN5A Bryony Thompson gene: SCN5A was added
gene: SCN5A was added to Stroke. Sources: Literature
Mode of inheritance for gene: SCN5A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SCN5A were set to 30356112; 29579189; 28294644; 16684018
Phenotypes for gene: SCN5A were set to Atrial fibrillation, familial, 10 MIM#614022
Review for gene: SCN5A was set to GREEN
Added comment: Early onset stroke has been reported in at least 4 families.
Sources: Literature
Brugada syndrome v0.6 SCN3B Bryony Thompson reviewed gene: SCN3B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Brugada syndrome 7 MIM#613120; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Stroke v0.46 SAMHD1 Bryony Thompson Marked gene: SAMHD1 as ready
Stroke v0.46 SAMHD1 Bryony Thompson Gene: samhd1 has been classified as Green List (High Evidence).
Stroke v0.46 SAMHD1 Bryony Thompson Classified gene: SAMHD1 as Green List (high evidence)
Stroke v0.46 SAMHD1 Bryony Thompson Gene: samhd1 has been classified as Green List (High Evidence).
Stroke v0.45 SAMHD1 Bryony Thompson gene: SAMHD1 was added
gene: SAMHD1 was added to Stroke. Sources: Literature
Mode of inheritance for gene: SAMHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SAMHD1 were set to 20842748; 21402907; 27051737; 25672750; 28289923
Phenotypes for gene: SAMHD1 were set to Aicardi-Goutieres syndrome 5 MIM#612952
Review for gene: SAMHD1 was set to GREEN
Added comment: At least 4 families where early onset stroke has been reported and a zebrafish model.
Sources: Literature
Stroke v0.44 PROS1 Bryony Thompson Marked gene: PROS1 as ready
Stroke v0.44 PROS1 Bryony Thompson Gene: pros1 has been classified as Green List (High Evidence).
Stroke v0.44 PROS1 Bryony Thompson Classified gene: PROS1 as Green List (high evidence)
Stroke v0.44 PROS1 Bryony Thompson Gene: pros1 has been classified as Green List (High Evidence).
Stroke v0.43 PROS1 Bryony Thompson gene: PROS1 was added
gene: PROS1 was added to Stroke. Sources: Literature
Mode of inheritance for gene: PROS1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: PROS1 were set to 20484936; 25997409; 21172841; 19729839
Phenotypes for gene: PROS1 were set to Thrombophilia due to protein S deficiency
Review for gene: PROS1 was set to GREEN
Added comment: At least 3 families reported with stroke and a supporting null mouse model.
Sources: Literature
Stroke v0.42 PROC Bryony Thompson Classified gene: PROC as Green List (high evidence)
Stroke v0.42 PROC Bryony Thompson Gene: proc has been classified as Green List (High Evidence).
Stroke v0.41 PROC Bryony Thompson gene: PROC was added
gene: PROC was added to Stroke. Sources: Literature
Mode of inheritance for gene: PROC was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: PROC were set to 1511989; 20187890; 30356112; 32351850
Phenotypes for gene: PROC were set to Thrombophilia due to protein C deficiency
Review for gene: PROC was set to GREEN
Added comment: PC deficiency is a cause for the development of stroke, particularly in young adults.
Sources: Literature
Stroke v0.40 PDE3A Bryony Thompson Marked gene: PDE3A as ready
Stroke v0.40 PDE3A Bryony Thompson Gene: pde3a has been classified as Green List (High Evidence).
Stroke v0.40 PDE3A Bryony Thompson Classified gene: PDE3A as Green List (high evidence)
Stroke v0.40 PDE3A Bryony Thompson Gene: pde3a has been classified as Green List (High Evidence).
Stroke v0.39 PDE3A Bryony Thompson gene: PDE3A was added
gene: PDE3A was added to Stroke. Sources: Literature
Mode of inheritance for gene: PDE3A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PDE3A were set to 31589936; 25961942; 30356112
Phenotypes for gene: PDE3A were set to Hypertension and brachydactyly syndrome MIM#112410
Review for gene: PDE3A was set to GREEN
Added comment: Stroke is a prominent feature of the condition if left untreated.
Sources: Literature
Stroke v0.38 PDCD10 Bryony Thompson Classified gene: PDCD10 as Green List (high evidence)
Stroke v0.38 PDCD10 Bryony Thompson Gene: pdcd10 has been classified as Green List (High Evidence).
Stroke v0.37 PDCD10 Bryony Thompson gene: PDCD10 was added
gene: PDCD10 was added to Stroke. Sources: Literature
Mode of inheritance for gene: PDCD10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PDCD10 were set to 30356112; 15543491
Phenotypes for gene: PDCD10 were set to Cerebral cavernous malformations 3 MIM#603285
Review for gene: PDCD10 was set to GREEN
Added comment: At least 7 families reported and stroke can be a feature of the condition.
Sources: Literature
Stroke v0.36 PCCB Bryony Thompson Classified gene: PCCB as Green List (high evidence)
Stroke v0.36 PCCB Bryony Thompson Gene: pccb has been classified as Green List (High Evidence).
Stroke v0.35 PCCB Bryony Thompson gene: PCCB was added
gene: PCCB was added to Stroke. Sources: Literature
Mode of inheritance for gene: PCCB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCCB were set to 30356112; 7769171; 6497733; 30037889; 18986243
Review for gene: PCCB was set to GREEN
Added comment: Metabolic stroke can be a feature of the condition.
Sources: Literature
Stroke v0.34 PCCA Bryony Thompson Classified gene: PCCA as Green List (high evidence)
Stroke v0.34 PCCA Bryony Thompson Gene: pcca has been classified as Green List (High Evidence).
Stroke v0.33 PCCA Bryony Thompson gene: PCCA was added
gene: PCCA was added to Stroke. Sources: Literature
Mode of inheritance for gene: PCCA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCCA were set to 21986446; 18986243; 20142522
Review for gene: PCCA was set to GREEN
Added comment: Metabolic stroke can be a feature of the condition.
Sources: Literature
Stroke v0.32 NF1 Bryony Thompson Classified gene: NF1 as Green List (high evidence)
Stroke v0.32 NF1 Bryony Thompson Gene: nf1 has been classified as Green List (High Evidence).
Stroke v0.31 NF1 Bryony Thompson gene: NF1 was added
gene: NF1 was added to Stroke. Sources: Literature
Mode of inheritance for gene: NF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NF1 were set to 31080139; 30356112; 8157015; 31279841
Phenotypes for gene: NF1 were set to Neurofibromatosis, type 1 MIM#162200
Review for gene: NF1 was set to GREEN
Added comment: Stroke can be a feature of the condition, with diolicoectasia, occlusion, and MoyaMoya-like subtypes reported.
Sources: Literature
Polydactyly v0.29 ALX3 Zornitza Stark Classified gene: ALX3 as Red List (low evidence)
Polydactyly v0.29 ALX3 Zornitza Stark Gene: alx3 has been classified as Red List (Low Evidence).
Polydactyly v0.28 ALX3 Zornitza Stark edited their review of gene: ALX3: Added comment: Polydactyly not specifically associated with FND1. One family reported in 8362915, but polydactyly considered to be a separate feature.; Changed rating: RED; Changed publications: 19409524, 8362915
Polydactyly v0.28 ALX3 Zornitza Stark Marked gene: ALX3 as ready
Polydactyly v0.28 ALX3 Zornitza Stark Gene: alx3 has been classified as Green List (High Evidence).
Polydactyly v0.28 ALX3 Zornitza Stark Phenotypes for gene: ALX3 were changed from to Frontonasal dysplasia 1, MIM#136760
Polydactyly v0.27 ALX3 Zornitza Stark Publications for gene: ALX3 were set to
Polydactyly v0.26 ALX3 Zornitza Stark Mode of inheritance for gene: ALX3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.25 B9D2 Zornitza Stark Marked gene: B9D2 as ready
Polydactyly v0.25 B9D2 Zornitza Stark Gene: b9d2 has been classified as Green List (High Evidence).
Polydactyly v0.25 B9D2 Zornitza Stark Phenotypes for gene: B9D2 were changed from to Joubert syndrome 34, MIM#614175; Meckel syndrome 10, MIM#614175
Polydactyly v0.24 B9D2 Zornitza Stark Publications for gene: B9D2 were set to
Polydactyly v0.23 B9D2 Zornitza Stark Mode of inheritance for gene: B9D2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Stroke v0.30 HBB Bryony Thompson Classified gene: HBB as Green List (high evidence)
Stroke v0.30 HBB Bryony Thompson Gene: hbb has been classified as Green List (High Evidence).
Stroke v0.29 HBB Bryony Thompson gene: HBB was added
gene: HBB was added to Stroke. Sources: Literature
Mode of inheritance for gene: HBB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HBB were set to 30356112; 19589461; 7782612; 20301551
Phenotypes for gene: HBB were set to Sickle cell anemia MIM#603903
Review for gene: HBB was set to GREEN
Added comment: Stroke can be a feature of sickle cell anemia, with the following subtypes reported: large artery non-atherosclerosis aneurysms, venous thrombosis, and arterial thrombosis.
Sources: Literature
Stroke v0.28 GUCY1A3 Bryony Thompson Marked gene: GUCY1A3 as ready
Stroke v0.28 GUCY1A3 Bryony Thompson Gene: gucy1a3 has been classified as Green List (High Evidence).
Stroke v0.28 GUCY1A3 Bryony Thompson Classified gene: GUCY1A3 as Green List (high evidence)
Stroke v0.28 GUCY1A3 Bryony Thompson Gene: gucy1a3 has been classified as Green List (High Evidence).
Stroke v0.27 GUCY1A3 Bryony Thompson gene: GUCY1A3 was added
gene: GUCY1A3 was added to Stroke. Sources: Literature
Mode of inheritance for gene: GUCY1A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GUCY1A3 were set to 24581742; 26777256
Phenotypes for gene: GUCY1A3 were set to Moyamoya 6 with achalasia MIM#615750
Review for gene: GUCY1A3 was set to GREEN
Added comment: Ischaemic stroke has been reported in at least one individual from five families.
Sources: Literature
Bleeding and Platelet Disorders v0.21 GFI1B Bryony Thompson Marked gene: GFI1B as ready
Bleeding and Platelet Disorders v0.21 GFI1B Bryony Thompson Gene: gfi1b has been classified as Green List (High Evidence).
Mendeliome v0.2807 GFI1B Bryony Thompson Marked gene: GFI1B as ready
Mendeliome v0.2807 GFI1B Bryony Thompson Gene: gfi1b has been classified as Green List (High Evidence).
Mendeliome v0.2807 GFI1B Bryony Thompson Classified gene: GFI1B as Green List (high evidence)
Mendeliome v0.2807 GFI1B Bryony Thompson Gene: gfi1b has been classified as Green List (High Evidence).
Mendeliome v0.2806 GFI1B Bryony Thompson gene: GFI1B was added
gene: GFI1B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GFI1B was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: GFI1B were set to 24325358; 23927492; 28041820; 11825872
Phenotypes for gene: GFI1B were set to Bleeding disorder, platelet-type, 17 MIM#187900
Review for gene: GFI1B was set to GREEN
Added comment: Three families with a heterozygous variant and one case with a homozygous variant, with supporting in vitro functional assays. A null mouse model contained erythroid and megakaryocytic precursors arrested in their development.
Sources: Literature
Bleeding and Platelet Disorders v0.21 GFI1B Bryony Thompson Classified gene: GFI1B as Green List (high evidence)
Bleeding and Platelet Disorders v0.21 GFI1B Bryony Thompson Gene: gfi1b has been classified as Green List (High Evidence).
Bleeding and Platelet Disorders v0.20 GFI1B Bryony Thompson gene: GFI1B was added
gene: GFI1B was added to Bleeding Disorders. Sources: Literature
Mode of inheritance for gene: GFI1B was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: GFI1B were set to 24325358; 23927492; 28041820; 11825872
Phenotypes for gene: GFI1B were set to Bleeding disorder, platelet-type, 17 MIM#187900
Review for gene: GFI1B was set to GREEN
Added comment: Three families with a heterozygous variant and one case with a homozygous variant, with supporting in vitro functional assays. A null mouse model contained erythroid and megakaryocytic precursors arrested in their development.
Sources: Literature
Mendeliome v0.2805 MOGS Elena Savva reviewed gene: MOGS: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31925597; Phenotypes: Congenital disorder of glycosylation, type IIb 606056; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Spastic Paraplegia v0.87 ATL1 Zornitza Stark Phenotypes for gene: ATL1 were changed from Spastic paraplegia 3A, autosomal dominant MIM#182600 to Hereditary sensory neuropathy type ID, MIM 613708; Spastic paraplegia 3A, MIM 182600; Hereditary spastic paraplegia, AR
Hereditary Spastic Paraplegia v0.86 ATL1 Zornitza Stark Publications for gene: ATL1 were set to
Hereditary Spastic Paraplegia v0.85 ATL1 Zornitza Stark Mode of inheritance for gene: ATL1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary Spastic Paraplegia v0.84 ATL1 Zornitza Stark reviewed gene: ATL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 16401858, 16537571, 17657515, 28396731, 24473461, 26888483; Phenotypes: Hereditary sensory neuropathy type ID, MIM 613708, Spastic paraplegia 3A, MIM 182600, Hereditary spastic paraplegia, AR; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2635 PRKD1 Zornitza Stark Marked gene: PRKD1 as ready
Intellectual disability syndromic and non-syndromic v0.2635 PRKD1 Zornitza Stark Gene: prkd1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2635 PRKD1 Zornitza Stark Phenotypes for gene: PRKD1 were changed from to Congenital heart defects and ectodermal dysplasia, 617364
Intellectual disability syndromic and non-syndromic v0.2634 PRKD1 Zornitza Stark Publications for gene: PRKD1 were set to
Intellectual disability syndromic and non-syndromic v0.2633 PRKD1 Zornitza Stark Mode of inheritance for gene: PRKD1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2632 PRKD1 Zornitza Stark reviewed gene: PRKD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27479907; Phenotypes: Congenital heart defects and ectodermal dysplasia, 617364; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.40 PRKD1 Zornitza Stark Marked gene: PRKD1 as ready
Congenital Heart Defect v0.40 PRKD1 Zornitza Stark Gene: prkd1 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.40 PRKD1 Zornitza Stark Phenotypes for gene: PRKD1 were changed from to Congenital heart defects and ectodermal dysplasia, 617364
Congenital Heart Defect v0.39 PRKD1 Zornitza Stark Publications for gene: PRKD1 were set to
Congenital Heart Defect v0.38 PRKD1 Zornitza Stark Mode of inheritance for gene: PRKD1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.37 PRKD1 Zornitza Stark reviewed gene: PRKD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27479907; Phenotypes: Congenital heart defects and ectodermal dysplasia, 617364; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2805 PRKD1 Zornitza Stark Marked gene: PRKD1 as ready
Mendeliome v0.2805 PRKD1 Zornitza Stark Gene: prkd1 has been classified as Green List (High Evidence).
Mendeliome v0.2805 PRKD1 Zornitza Stark Phenotypes for gene: PRKD1 were changed from to Congenital heart defects and ectodermal dysplasia, 617364
Mendeliome v0.2804 PRKD1 Zornitza Stark Publications for gene: PRKD1 were set to
Mendeliome v0.2803 PRKD1 Zornitza Stark Mode of inheritance for gene: PRKD1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dilated Cardiomyopathy v0.36 JPH2 Zornitza Stark Tag founder tag was added to gene: JPH2.
Holoprosencephaly and septo-optic dysplasia v0.16 NODAL Zornitza Stark Tag disputed tag was added to gene: NODAL.
Ciliopathies v0.139 NODAL Zornitza Stark Tag disputed tag was added to gene: NODAL.
Congenital Heart Defect v0.37 NODAL Zornitza Stark Tag disputed tag was added to gene: NODAL.
Dilated Cardiomyopathy v0.36 JPH2 Zornitza Stark Marked gene: JPH2 as ready
Dilated Cardiomyopathy v0.36 JPH2 Zornitza Stark Added comment: Comment when marking as ready: Likely founder effect.
Dilated Cardiomyopathy v0.36 JPH2 Zornitza Stark Gene: jph2 has been classified as Red List (Low Evidence).
Dilated Cardiomyopathy v0.36 JPH2 Zornitza Stark Classified gene: JPH2 as Red List (low evidence)
Dilated Cardiomyopathy v0.36 JPH2 Zornitza Stark Gene: jph2 has been classified as Red List (Low Evidence).
Mendeliome v0.2802 NODAL Zornitza Stark Marked gene: NODAL as ready
Mendeliome v0.2802 NODAL Zornitza Stark Gene: nodal has been classified as Red List (Low Evidence).
Mendeliome v0.2802 NODAL Zornitza Stark Phenotypes for gene: NODAL were changed from to Heterotaxy, visceral, 5 (MIM#270100)
Mendeliome v0.2801 NODAL Zornitza Stark Publications for gene: NODAL were set to
Mendeliome v0.2800 NODAL Zornitza Stark Mode of inheritance for gene: NODAL was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2799 NODAL Zornitza Stark Classified gene: NODAL as Red List (low evidence)
Mendeliome v0.2799 NODAL Zornitza Stark Gene: nodal has been classified as Red List (Low Evidence).
Mendeliome v0.2798 NODAL Zornitza Stark Tag disputed tag was added to gene: NODAL.
Mendeliome v0.2798 NODAL Zornitza Stark reviewed gene: NODAL: Rating: RED; Mode of pathogenicity: None; Publications: 9354794, 19064609; Phenotypes: Heterotaxy, visceral, 5 (MIM#270100); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.37 NODAL Zornitza Stark Marked gene: NODAL as ready
Congenital Heart Defect v0.37 NODAL Zornitza Stark Gene: nodal has been classified as Red List (Low Evidence).
Congenital Heart Defect v0.37 NODAL Zornitza Stark Phenotypes for gene: NODAL were changed from to Heterotaxy, visceral, 5 (MIM#270100)
Congenital Heart Defect v0.36 NODAL Zornitza Stark Publications for gene: NODAL were set to
Congenital Heart Defect v0.35 NODAL Zornitza Stark Mode of inheritance for gene: NODAL was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.34 NODAL Zornitza Stark Classified gene: NODAL as Red List (low evidence)
Congenital Heart Defect v0.34 NODAL Zornitza Stark Gene: nodal has been classified as Red List (Low Evidence).
Congenital Heart Defect v0.33 NODAL Zornitza Stark reviewed gene: NODAL: Rating: RED; Mode of pathogenicity: None; Publications: 9354794, 19064609; Phenotypes: Heterotaxy, visceral, 5 (MIM#270100); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Holoprosencephaly and septo-optic dysplasia v0.16 NODAL Zornitza Stark Marked gene: NODAL as ready
Holoprosencephaly and septo-optic dysplasia v0.16 NODAL Zornitza Stark Gene: nodal has been classified as Red List (Low Evidence).
Holoprosencephaly and septo-optic dysplasia v0.16 NODAL Zornitza Stark Phenotypes for gene: NODAL were changed from to Heterotaxy, visceral, 5 (MIM#270100)
Holoprosencephaly and septo-optic dysplasia v0.15 NODAL Zornitza Stark Publications for gene: NODAL were set to
Holoprosencephaly and septo-optic dysplasia v0.14 NODAL Zornitza Stark Mode of inheritance for gene: NODAL was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Holoprosencephaly and septo-optic dysplasia v0.13 NODAL Zornitza Stark Classified gene: NODAL as Red List (low evidence)
Holoprosencephaly and septo-optic dysplasia v0.13 NODAL Zornitza Stark Gene: nodal has been classified as Red List (Low Evidence).
Holoprosencephaly and septo-optic dysplasia v0.12 NODAL Zornitza Stark reviewed gene: NODAL: Rating: RED; Mode of pathogenicity: None; Publications: 9354794, 19064609; Phenotypes: Heterotaxy, visceral, 5 (MIM#270100); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ciliopathies v0.139 NODAL Zornitza Stark Mode of inheritance for gene: NODAL was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Heterotaxy v0.40 NODAL Zornitza Stark Marked gene: NODAL as ready
Heterotaxy v0.40 NODAL Zornitza Stark Gene: nodal has been classified as Red List (Low Evidence).
Heterotaxy v0.40 NODAL Zornitza Stark Classified gene: NODAL as Red List (low evidence)
Heterotaxy v0.40 NODAL Zornitza Stark Gene: nodal has been classified as Red List (Low Evidence).
Heterotaxy v0.39 NODAL Zornitza Stark Tag disputed tag was added to gene: NODAL.
Ciliopathies v0.138 NODAL Zornitza Stark Marked gene: NODAL as ready
Ciliopathies v0.138 NODAL Zornitza Stark Gene: nodal has been classified as Red List (Low Evidence).
Ciliopathies v0.138 NODAL Zornitza Stark Phenotypes for gene: NODAL were changed from to Heterotaxy, visceral, 5 (MIM#270100)
Ciliopathies v0.137 NODAL Zornitza Stark Classified gene: NODAL as Red List (low evidence)
Ciliopathies v0.137 NODAL Zornitza Stark Gene: nodal has been classified as Red List (Low Evidence).
Mendeliome v0.2798 PIH1D3 Zornitza Stark Marked gene: PIH1D3 as ready
Mendeliome v0.2798 PIH1D3 Zornitza Stark Gene: pih1d3 has been classified as Green List (High Evidence).
Mendeliome v0.2798 PIH1D3 Zornitza Stark Phenotypes for gene: PIH1D3 were changed from to Ciliary dyskinesia, primary, 36, X-linked (MIM#300991)
Mendeliome v0.2797 PIH1D3 Zornitza Stark Publications for gene: PIH1D3 were set to
Mendeliome v0.2796 PIH1D3 Zornitza Stark Mode of inheritance for gene: PIH1D3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.2795 PIH1D3 Zornitza Stark reviewed gene: PIH1D3: Rating: GREEN; Mode of pathogenicity: None; Publications: 28041644, 24421334, 28176794; Phenotypes: Ciliary dyskinesia, primary, 36, X-linked (MIM#300991); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Heterotaxy v0.39 PIH1D3 Zornitza Stark Marked gene: PIH1D3 as ready
Heterotaxy v0.39 PIH1D3 Zornitza Stark Gene: pih1d3 has been classified as Green List (High Evidence).
Heterotaxy v0.39 PIH1D3 Zornitza Stark Phenotypes for gene: PIH1D3 were changed from to Ciliary dyskinesia, primary, 36, X-linked (MIM#300991)
Heterotaxy v0.38 PIH1D3 Zornitza Stark Publications for gene: PIH1D3 were set to
Heterotaxy v0.37 PIH1D3 Zornitza Stark Mode of inheritance for gene: PIH1D3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Heterotaxy v0.36 PIH1D3 Zornitza Stark reviewed gene: PIH1D3: Rating: GREEN; Mode of pathogenicity: None; Publications: 28041644, 24421334, 28176794; Phenotypes: Ciliary dyskinesia, primary, 36, X-linked (MIM#300991); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Ciliary Dyskinesia v0.75 PIH1D3 Zornitza Stark Marked gene: PIH1D3 as ready
Ciliary Dyskinesia v0.75 PIH1D3 Zornitza Stark Gene: pih1d3 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.75 PIH1D3 Zornitza Stark Phenotypes for gene: PIH1D3 were changed from to Ciliary dyskinesia, primary, 36, X-linked (MIM#300991)
Ciliary Dyskinesia v0.74 PIH1D3 Zornitza Stark Publications for gene: PIH1D3 were set to
Ciliary Dyskinesia v0.73 PIH1D3 Zornitza Stark Mode of inheritance for gene: PIH1D3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.2795 COL10A1 Zornitza Stark Marked gene: COL10A1 as ready
Mendeliome v0.2795 COL10A1 Zornitza Stark Gene: col10a1 has been classified as Green List (High Evidence).
Mendeliome v0.2795 COL10A1 Zornitza Stark Phenotypes for gene: COL10A1 were changed from to Metaphyseal chondrodysplasia, Schmid type, MIM#156500
Mendeliome v0.2794 COL10A1 Zornitza Stark Publications for gene: COL10A1 were set to
Mendeliome v0.2793 COL10A1 Zornitza Stark Mode of inheritance for gene: COL10A1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2792 COL10A1 Zornitza Stark reviewed gene: COL10A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15880705, 31633898; Phenotypes: Metaphyseal chondrodysplasia, Schmid type, MIM#156500; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v0.22 COL10A1 Zornitza Stark Marked gene: COL10A1 as ready
Skeletal dysplasia v0.22 COL10A1 Zornitza Stark Gene: col10a1 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.22 COL10A1 Zornitza Stark Publications for gene: COL10A1 were set to
Skeletal dysplasia v0.21 COL10A1 Zornitza Stark Mode of inheritance for gene: COL10A1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2792 CEP112 Bryony Thompson Classified gene: CEP112 as Amber List (moderate evidence)
Mendeliome v0.2792 CEP112 Bryony Thompson Gene: cep112 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2791 CEP112 Bryony Thompson gene: CEP112 was added
gene: CEP112 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CEP112 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP112 were set to 31654588
Phenotypes for gene: CEP112 were set to Acephalic spermatozoa; infertility
Review for gene: CEP112 was set to AMBER
Added comment: Two unrelated cases reported with acephalic spermatozoa, one case with a homozygous nonsense variant and the other case with biallelic missense variants. CEP112 expression was significantly reduced in one of the cases, suggesting loss of function as a mechanism of disease.
Sources: Literature
Mendeliome v0.2790 PRKD1 Kristin Rigbye changed review comment from: Only 3 pathogenic missense reported to date, although two of these are recurring in unrelated individuals (ClinVar, Decipher, PMID: 27479907). No functional studies performed.; to: Only 3 pathogenic missense reported to date in unrelated individuals (ClinVar, Decipher, PMID: 27479907). No functional studies performed.
Mendeliome v0.2790 PRKD1 Kristin Rigbye reviewed gene: PRKD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27479907; Phenotypes: Congenital heart defects and ectodermal dysplasia, 617364; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Stroke v0.26 FOXC1 Bryony Thompson Marked gene: FOXC1 as ready
Stroke v0.26 FOXC1 Bryony Thompson Gene: foxc1 has been classified as Green List (High Evidence).
Stroke v0.26 FOXC1 Bryony Thompson Classified gene: FOXC1 as Green List (high evidence)
Stroke v0.26 FOXC1 Bryony Thompson Gene: foxc1 has been classified as Green List (High Evidence).
Stroke v0.25 FOXC1 Bryony Thompson gene: FOXC1 was added
gene: FOXC1 was added to Stroke. Sources: Literature
Mode of inheritance for gene: FOXC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOXC1 were set to 29751260; 31719132; 25250569
Phenotypes for gene: FOXC1 were set to Stroke; cerebral small-vessel disease
Review for gene: FOXC1 was set to GREEN
Added comment: >3 cases reported with stroke and a zebrafish model.
Sources: Literature
Dilated Cardiomyopathy v0.35 JPH2 Ain Roesley gene: JPH2 was added
gene: JPH2 was added to Dilated Cardiomyopathy. Sources: Literature
Mode of inheritance for gene: JPH2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: JPH2 were set to PMID: 31227780
Phenotypes for gene: JPH2 were set to dilated cardiomyopathy
Review for gene: JPH2 was set to AMBER
Added comment: 2 consanguineous Iranian families with DCM, harbouring homozygous p.(E641*) with healthy carriers reported.
Sources: Literature
Leukodystrophy v0.126 POLG Zornitza Stark Marked gene: POLG as ready
Leukodystrophy v0.126 POLG Zornitza Stark Gene: polg has been classified as Green List (High Evidence).
Leukodystrophy v0.126 POLG Zornitza Stark Classified gene: POLG as Green List (high evidence)
Leukodystrophy v0.126 POLG Zornitza Stark Gene: polg has been classified as Green List (High Evidence).
Leukodystrophy v0.125 POLG Zornitza Stark gene: POLG was added
gene: POLG was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: POLG was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: POLG were set to Mitochondrial DNA depletion syndrome 4B (MNGIE type), MIM# 613662
Review for gene: POLG was set to GREEN
Added comment: Variable age of onset, including in infancy. White matter changes in some.
Sources: Expert list
Leukodystrophy v0.124 PLP1 Zornitza Stark Marked gene: PLP1 as ready
Leukodystrophy v0.124 PLP1 Zornitza Stark Gene: plp1 has been classified as Green List (High Evidence).
Leukodystrophy v0.124 PLP1 Zornitza Stark Classified gene: PLP1 as Green List (high evidence)
Leukodystrophy v0.124 PLP1 Zornitza Stark Gene: plp1 has been classified as Green List (High Evidence).
Leukodystrophy v0.123 PLP1 Zornitza Stark gene: PLP1 was added
gene: PLP1 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: PLP1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: PLP1 were set to Pelizaeus-Merzbacher disease, MIM# 312080
Review for gene: PLP1 was set to GREEN
Added comment: Hypomyelinative leukodystrophy, typical onset in infancy.
Sources: Expert list
Stroke v0.24 CTSA Bryony Thompson Classified gene: CTSA as Amber List (moderate evidence)
Stroke v0.24 CTSA Bryony Thompson Gene: ctsa has been classified as Amber List (Moderate Evidence).
Stroke v0.23 CTSA Bryony Thompson gene: CTSA was added
gene: CTSA was added to Stroke. Sources: Literature
Mode of inheritance for gene: CTSA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CTSA were set to 27664989; 31177426; 23175731
Phenotypes for gene: CTSA were set to Cathepsin A-related Arteriopathy With Strokes and Leukoencephalopathy (CARASAL)
Review for gene: CTSA was set to AMBER
Added comment: Three families reported with the same variant (c.973C > T), and a study mapping the condition to 20q13, where CTSA is located, but no sequencing conducted.
Sources: Literature
Ciliopathies v0.136 OFD1 Zornitza Stark Marked gene: OFD1 as ready
Ciliopathies v0.136 OFD1 Zornitza Stark Gene: ofd1 has been classified as Green List (High Evidence).
Heterotaxy v0.36 NODAL Crystle Lee gene: NODAL was added
gene: NODAL was added to Heterotaxy. Sources: Expert Review
Mode of inheritance for gene: NODAL was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NODAL were set to 9354794; 19064609
Phenotypes for gene: NODAL were set to Heterotaxy, visceral, 5 (MIM#270100)
Review for gene: NODAL was set to RED
Added comment: Minimal reports and variants in original publications present in gnomAD at a higher than expected frequency, originally concluded to be due to incomplete penetrance.

PMID: 9354794 (1997): R183Q reported in affected daughter and unaffected mother. (26 hets; 1 hom in gnomAD)

PMID: 19064609 (2009): Reported 4 missense, 1 indel and 2 splice site variants. G260R also found in unaffected individual, concluded to have incomplete penetrance (80 hets in gnomAD); R275C (13 hets in gnomAD); E203K (113 hets and 1 hom)
Sources: Expert Review
Ciliopathies v0.136 NODAL Crystle Lee reviewed gene: NODAL: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Heterotaxy, visceral, 5 (MIM#270100); Mode of inheritance: None
Ciliopathies v0.136 OFD1 Zornitza Stark Phenotypes for gene: OFD1 were changed from Retinitis pigmentosa 23, MIM# 300424; Joubert syndrome 10, MIM# 300804; Orofaciodigital syndrome I, MIM# 311200 to Retinitis pigmentosa 23, MIM# 300424; Joubert syndrome 10, MIM# 300804; Orofaciodigital syndrome I, MIM# 311200
Ciliopathies v0.136 OFD1 Zornitza Stark Phenotypes for gene: OFD1 were changed from to Retinitis pigmentosa 23, MIM# 300424; Joubert syndrome 10, MIM# 300804; Orofaciodigital syndrome I, MIM# 311200
Ciliopathies v0.135 OFD1 Zornitza Stark Publications for gene: OFD1 were set to
Ciliopathies v0.134 OFD1 Zornitza Stark Mode of inheritance for gene: OFD1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Ciliopathies v0.133 OFD1 Zornitza Stark reviewed gene: OFD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32276433, 31373179; Phenotypes: Retinitis pigmentosa 23, MIM# 300424, Joubert syndrome 10, MIM# 300804, Orofaciodigital syndrome I, MIM# 311200; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Ciliary Dyskinesia v0.72 OFD1 Zornitza Stark Classified gene: OFD1 as Red List (low evidence)
Ciliary Dyskinesia v0.72 OFD1 Zornitza Stark Gene: ofd1 has been classified as Red List (Low Evidence).
Ciliary Dyskinesia v0.71 OFD1 Zornitza Stark reviewed gene: OFD1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Retinitis pigmentosa 23, MIM# 300424, Joubert syndrome 10, MIM# 300804, Orofaciodigital syndrome I, MIM# 311200; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Ciliary Dyskinesia v0.71 Zornitza Stark removed gene:RAG1 from the panel
Ciliary Dyskinesia v0.70 SCNN1A Zornitza Stark Marked gene: SCNN1A as ready
Ciliary Dyskinesia v0.70 SCNN1A Zornitza Stark Gene: scnn1a has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.70 SCNN1A Zornitza Stark Classified gene: SCNN1A as Green List (high evidence)
Ciliary Dyskinesia v0.70 SCNN1A Zornitza Stark Gene: scnn1a has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.69 SCNN1B Zornitza Stark Marked gene: SCNN1B as ready
Ciliary Dyskinesia v0.69 SCNN1B Zornitza Stark Gene: scnn1b has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.69 SCNN1B Zornitza Stark Classified gene: SCNN1B as Green List (high evidence)
Ciliary Dyskinesia v0.69 SCNN1B Zornitza Stark Gene: scnn1b has been classified as Green List (High Evidence).
Stroke v0.22 COL4A2 Bryony Thompson Marked gene: COL4A2 as ready
Stroke v0.22 COL4A2 Bryony Thompson Gene: col4a2 has been classified as Green List (High Evidence).
Stroke v0.22 COL4A2 Bryony Thompson Classified gene: COL4A2 as Green List (high evidence)
Stroke v0.22 COL4A2 Bryony Thompson Gene: col4a2 has been classified as Green List (High Evidence).
Stroke v0.21 COL4A2 Bryony Thompson gene: COL4A2 was added
gene: COL4A2 was added to Stroke. Sources: Literature
Mode of inheritance for gene: COL4A2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COL4A2 were set to 22209247; 30356112; 27794444
Review for gene: COL4A2 was set to GREEN
Added comment: At least 6 cases reported with intracerebral bleeding/stroke, and a mouse model with stroke.
Sources: Literature
Ciliary Dyskinesia v0.68 PIH1D3 Crystle Lee Deleted their comment
Ciliary Dyskinesia v0.68 PIH1D3 Crystle Lee edited their review of gene: PIH1D3: Added comment: >5 families reported with PCD

PMID: 28176794; 6 families reported

PMID: 28041644; Reported 4 affected males from 2 families. Functional studies showed cilia and flagella immotility. (2016)

PMID: 24421334: Mouse model (2014); Changed publications: 28041644, 24421334, 28176794
Ciliary Dyskinesia v0.68 PIH1D3 Crystle Lee reviewed gene: PIH1D3: Rating: GREEN; Mode of pathogenicity: None; Publications: 28041644, 24421334; Phenotypes: Ciliary dyskinesia, primary, 36, X-linked (MIM#300991); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Skeletal dysplasia v0.20 COL10A1 Kristin Rigbye reviewed gene: COL10A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15880705, 31633898; Phenotypes: Metaphyseal chondrodysplasia, Schmid type, 156500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ciliary Dyskinesia v0.68 RAG1 Crystle Lee Deleted their review
Ciliary Dyskinesia v0.68 RAG1 Crystle Lee gene: RAG1 was added
gene: RAG1 was added to Ciliary Dyskinesia. Sources: Expert Review
Mode of inheritance for gene: RAG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAG1 were set to 26689875; 26186701
Phenotypes for gene: RAG1 were set to Severe combined immunodeficiency, B cell-negative (MIM#601457)
Added comment: Phenotypic over with PCD (recurrent respiratory problems).

PMID: 26689875; Reported 2 patients with classic SCID, 1 atypical SCID and one with Omen syndrome

PMID: 26186701: 1 patient with compound het variants in RAG1

Green in PanelApp UK - Respiratory ciliopathies list
Sources: Expert Review
Ciliary Dyskinesia v0.68 SCNN1A Crystle Lee gene: SCNN1A was added
gene: SCNN1A was added to Ciliary Dyskinesia. Sources: Expert Review
Mode of inheritance for gene: SCNN1A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SCNN1A were set to 22207244; 19017867; 19462466
Phenotypes for gene: SCNN1A were set to Bronchiectasis with or without elevated sweat chloride 2 (MIM#613021)
Review for gene: SCNN1A was set to GREEN
Added comment: Phenotypic overlap with PCD
Encodes for the alpha subunit of the epithelial sodium channel, which is distributed along the motile cilia. (PMID: 22207244)
Sources: Expert Review
Ciliary Dyskinesia v0.68 SCNN1B Crystle Lee gene: SCNN1B was added
gene: SCNN1B was added to Ciliary Dyskinesia. Sources: Expert Review
Mode of inheritance for gene: SCNN1B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SCNN1B were set to 22207244; 16207733; 18507830
Phenotypes for gene: SCNN1B were set to Bronchiectasis with or without elevated sweat chloride 1 (MIM#211400)
Review for gene: SCNN1B was set to GREEN
Added comment: Phenotypic overlap with PCD
Encodes for the beta subunit of the epithelial sodium channel, which is distributed along the motile cilia. (PMID: 22207244)

PMID: 16207733: 2 patients reported
PMID: 18507830: 2 patients with bronchiectasis
Sources: Expert Review
Mendeliome v0.2790 KPNA7 Alison Yeung Marked gene: KPNA7 as ready
Mendeliome v0.2790 KPNA7 Alison Yeung Gene: kpna7 has been classified as Red List (Low Evidence).
Mendeliome v0.2790 KPNA7 Alison Yeung gene: KPNA7 was added
gene: KPNA7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KPNA7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KPNA7 were set to 24045845; 32179771
Phenotypes for gene: KPNA7 were set to Epilepsy; intellectual disability
Review for gene: KPNA7 was set to RED
Added comment: Single family with two siblings
Sources: Literature
Stroke v0.20 COL3A1 Bryony Thompson Marked gene: COL3A1 as ready
Stroke v0.20 COL3A1 Bryony Thompson Gene: col3a1 has been classified as Green List (High Evidence).
Stroke v0.20 COL3A1 Bryony Thompson Classified gene: COL3A1 as Green List (high evidence)
Stroke v0.20 COL3A1 Bryony Thompson Gene: col3a1 has been classified as Green List (High Evidence).
Stroke v0.19 COL3A1 Bryony Thompson gene: COL3A1 was added
gene: COL3A1 was added to Stroke. Sources: Literature
Mode of inheritance for gene: COL3A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COL3A1 were set to 30356112; 12786757; 31903434; 25355833
Phenotypes for gene: COL3A1 were set to Ehlers-Danlos syndrome, vascular type MIM#130050
Review for gene: COL3A1 was set to GREEN
Added comment: At least 4 cervical artery dissection cases with a heterozygous COL3A1 variant, which is a major cause of ischaemic stroke.
Sources: Literature
Stroke v0.18 CD59 Bryony Thompson Marked gene: CD59 as ready
Stroke v0.18 CD59 Bryony Thompson Gene: cd59 has been classified as Green List (High Evidence).
Stroke v0.18 CD59 Bryony Thompson Classified gene: CD59 as Green List (high evidence)
Stroke v0.18 CD59 Bryony Thompson Gene: cd59 has been classified as Green List (High Evidence).
Stroke v0.17 CD59 Bryony Thompson gene: CD59 was added
gene: CD59 was added to Stroke. Sources: Literature
Mode of inheritance for gene: CD59 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CD59 were set to 30356112; 28622911; 1699124; 25716358
Phenotypes for gene: CD59 were set to Hemolytic anemia, CD59-mediated, with or without immune-mediated polyneuropathy MIM#612300
Review for gene: CD59 was set to GREEN
Added comment: Recurrent strokes have been reported in at least 6 cases, with an arterial thrombosis stroke subtype. Condition is paediatric onset.
Sources: Literature
Stroke v0.16 KRIT1 Bryony Thompson Marked gene: KRIT1 as ready
Stroke v0.16 KRIT1 Bryony Thompson Gene: krit1 has been classified as Green List (High Evidence).
Stroke v0.16 KRIT1 Bryony Thompson Classified gene: KRIT1 as Green List (high evidence)
Stroke v0.16 KRIT1 Bryony Thompson Gene: krit1 has been classified as Green List (High Evidence).
Stroke v0.15 KRIT1 Bryony Thompson gene: KRIT1 was added
gene: KRIT1 was added to Stroke. Sources: Literature
Mode of inheritance for gene: KRIT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KRIT1 were set to 30356112; 14755725; 11310633; 9811928
Phenotypes for gene: KRIT1 were set to Cavernous malformations of CNS and retina MIM#116860; Cerebral cavernous malformations-1 MIM#116860; Hyperkeratotic cutaneous capillary-venous malformations associated with cerebral capillary malformations MIM#116860
Review for gene: KRIT1 was set to GREEN
Added comment: Cases reported with intracerebral bleeding and cavernoma stroke subtypes.
Sources: Literature
Mendeliome v0.2789 NR4A2 Zornitza Stark Marked gene: NR4A2 as ready
Mendeliome v0.2789 NR4A2 Zornitza Stark Gene: nr4a2 has been classified as Green List (High Evidence).
Mendeliome v0.2789 NR4A2 Zornitza Stark Classified gene: NR4A2 as Green List (high evidence)
Mendeliome v0.2789 NR4A2 Zornitza Stark Gene: nr4a2 has been classified as Green List (High Evidence).
Mendeliome v0.2788 NR4A2 Zornitza Stark gene: NR4A2 was added
gene: NR4A2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NR4A2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NR4A2 were set to 31428396; 30504930; 29770430; 12756136; 9092472
Phenotypes for gene: NR4A2 were set to Intellectual disability; epilepsy
Review for gene: NR4A2 was set to GREEN
Added comment: Over ten individuals reported with mono-allelic variants in this gene and neurodevelopmental phenotypes. Link with dementia/Parkinson's disease disputed.
Sources: Literature
Incidentalome v0.20 NR4A2 Zornitza Stark Marked gene: NR4A2 as ready
Incidentalome v0.20 NR4A2 Zornitza Stark Gene: nr4a2 has been classified as Red List (Low Evidence).
Incidentalome v0.20 NR4A2 Zornitza Stark Classified gene: NR4A2 as Red List (low evidence)
Incidentalome v0.20 NR4A2 Zornitza Stark Gene: nr4a2 has been classified as Red List (Low Evidence).
Incidentalome v0.19 NR4A2 Zornitza Stark reviewed gene: NR4A2: Rating: RED; Mode of pathogenicity: None; Publications: 12756136, 9092472; Phenotypes: ; Mode of inheritance: None
Genetic Epilepsy v0.703 NR4A2 Zornitza Stark Marked gene: NR4A2 as ready
Genetic Epilepsy v0.703 NR4A2 Zornitza Stark Gene: nr4a2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.703 NR4A2 Zornitza Stark Publications for gene: NR4A2 were set to 31428396
Genetic Epilepsy v0.702 NR4A2 Zornitza Stark reviewed gene: NR4A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32366965; Phenotypes: Intellectual disability, epilepsy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.702 NR4A2 Zornitza Stark Publications for gene: NR4A2 were set to https://doi.org/10.1038/s41436-020-0815-4; 31428396
Genetic Epilepsy v0.701 NR4A2 Zornitza Stark Classified gene: NR4A2 as Green List (high evidence)
Genetic Epilepsy v0.701 NR4A2 Zornitza Stark Gene: nr4a2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2632 NR4A2 Zornitza Stark Marked gene: NR4A2 as ready
Intellectual disability syndromic and non-syndromic v0.2632 NR4A2 Zornitza Stark Added comment: Comment when marking as ready: Upgrade to Green in view of new publication reporting 9 additional individuals.
Intellectual disability syndromic and non-syndromic v0.2632 NR4A2 Zornitza Stark Gene: nr4a2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2632 NR4A2 Zornitza Stark Classified gene: NR4A2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2632 NR4A2 Zornitza Stark Gene: nr4a2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.700 NR4A2 Konstantinos Varvagiannis gene: NR4A2 was added
gene: NR4A2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: NR4A2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NR4A2 were set to https://doi.org/10.1038/s41436-020-0815-4; 31428396
Phenotypes for gene: NR4A2 were set to Generalized hypotonia, Global developmental delay, Intellectual disability, Seizures, Behavioral abnormality, Abnormality of movement, Joint hypermobility
Penetrance for gene: NR4A2 were set to unknown
Review for gene: NR4A2 was set to GREEN
Added comment: Seizures have been reported in at least 6 unrelated individuals with NR4A2 variants (not including cases with contiguous gene deletions spanning also this gene). Please consider inclusion with amber or green rating.
---
Singh et al (2020 - https://doi.org/10.1038/s41436-020-0815-4) provide details on the phenotype of 9 unrelated individuals with NR4A2 pathogenic variants (in almost all cases de novo).

Features included hypotonia (in 6/9), DD (9/9), varying levels of ID (mild to severe in 8/8 for whom this information was available), seizures (6/9 - variable epilepsy phenotypes), behavioral problems (5/9 - with autism reported for one). Less frequent features incl. hypermobility (in 3), ataxia/movement disorder (in 3).

8 total pLoF and missense variants were identified as de novo events following trio exome sequencing with Sanger validation (7/8 variants). For 1(/8) individual with a stopgain variant, a single parental sample was available. A 9th individual was found to harbor a ~3.7 Mb 2q deletion spanning also other genes (which might also contribute to his phenotype of epilepsy).

Only the effect of a variant affecting the splice-acceptor site was studied (c.865-1_865delGCinsAAAAAGGAGT - NM_006186.3) with RT-PCR demonstrating an out-of-frame skipping of exon 4. Another variant (NM_006186.3:c.325dup) found in a subject with DD, ID and epilepsy had also previously been reported in another individual with similar phenotype of epilepsy and ID (Ramos et al - PMID: 31428396 - the variant was de novo with other causes for his phenotype excluded).

As discussed by Singh et al, NR4A2 encodes a steroid-thyroid-retinoid receptor which acts as a nuclear receptor transcription factor. The authors summarize previous reports on NR4A2 haploinsufficiency (NR4A2 has a pLI of 1 and HI score of 1.28% - Z-score is 2.24).

The authors comment on mouse models suggesting a role of NR4A2 for dopaminergic neurons, and provide plausible explanations for the phenotype of ID/seizures.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2631 NR4A2 Konstantinos Varvagiannis reviewed gene: NR4A2: Rating: GREEN; Mode of pathogenicity: None; Publications: https://doi.org/10.1038/s41436-020-0815-4, 31428396, 29770430, 30504930, 28544326, 27569545, 23554088, 28135719, 27479843, 25363768; Phenotypes: Generalized hypotonia, Global developmental delay, Intellectual disability, Seizures, Behavioral abnormality, Abnormality of movement, Joint hypermobility; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Leukodystrophy v0.122 MLC1 Zornitza Stark Marked gene: MLC1 as ready
Leukodystrophy v0.122 MLC1 Zornitza Stark Gene: mlc1 has been classified as Green List (High Evidence).
Leukodystrophy v0.122 MLC1 Zornitza Stark Classified gene: MLC1 as Green List (high evidence)
Leukodystrophy v0.122 MLC1 Zornitza Stark Gene: mlc1 has been classified as Green List (High Evidence).
Leukodystrophy v0.121 MLC1 Zornitza Stark gene: MLC1 was added
gene: MLC1 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: MLC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MLC1 were set to 11254442; 21419380; 21624973
Phenotypes for gene: MLC1 were set to Megalencephalic leukoencephalopathy with subcortical cysts, MIM# 604004
Review for gene: MLC1 was set to GREEN
Added comment: Childhood onset, progressive MRI changes.
Sources: Expert list
Leukodystrophy v0.120 MCOLN1 Zornitza Stark Marked gene: MCOLN1 as ready
Leukodystrophy v0.120 MCOLN1 Zornitza Stark Gene: mcoln1 has been classified as Green List (High Evidence).
Leukodystrophy v0.120 MCOLN1 Zornitza Stark Classified gene: MCOLN1 as Green List (high evidence)
Leukodystrophy v0.120 MCOLN1 Zornitza Stark Gene: mcoln1 has been classified as Green List (High Evidence).
Leukodystrophy v0.119 MCOLN1 Zornitza Stark gene: MCOLN1 was added
gene: MCOLN1 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: MCOLN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCOLN1 were set to 10973263; 11030752
Phenotypes for gene: MCOLN1 were set to Mucolipidosis IV, MIM# 252650
Review for gene: MCOLN1 was set to GREEN
Added comment: Sources: Expert list
Mendeliome v0.2787 TET2 Zornitza Stark edited their review of gene: TET2: Added comment: 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.; Changed publications: 30890702, 31827242, 32330418
Mendeliome v0.2787 TOMM70 Zornitza Stark Marked gene: TOMM70 as ready
Mendeliome v0.2787 TOMM70 Zornitza Stark Gene: tomm70 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2787 TOMM70 Zornitza Stark Classified gene: TOMM70 as Amber List (moderate evidence)
Mendeliome v0.2787 TOMM70 Zornitza Stark Gene: tomm70 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2786 TOMM70 Zornitza Stark gene: TOMM70 was added
gene: TOMM70 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: TOMM70 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TOMM70 were set to 31907385; 32356556
Phenotypes for gene: TOMM70 were set to Severe anaemia, lactic acidosis, developmental delay; White matter abnormalities, developmental delay, regression, movement disorder
Review for gene: TOMM70 was set to AMBER
Added comment: TOM70 is a member of the TOM complex that transports cytosolic proteins into mitochondria.
Bi-allelic disease: one individual reported with compound heterozygous variants in TOMM70 [c.794C>T (p.T265M) and c.1745C>T (p.A582V)]. Clinical features included severe anaemia, lactic acidosis, and developmental delay. Some functional data: in vitro cell model compensatory experiments.
Monoallelic disease: de novo mono allelic variants in the C-terminal region of TOMM70 reported in two individuals. While both individuals exhibited shared symptoms including hypotonia, hyperreflexia, ataxia, dystonia, and significant white matter abnormalities, there were differences between the two individuals, most prominently the age of symptom onset, with one experiencing episodes of regression. Some functional data.
Sources: Expert list
Mitochondrial disease v0.448 TOMM70 Zornitza Stark Publications for gene: TOMM70 were set to
Mitochondrial disease v0.447 TOMM70 Zornitza Stark edited their review of gene: TOMM70: Changed publications: 31907385
Leukodystrophy v0.118 TOMM70 Zornitza Stark Marked gene: TOMM70 as ready
Leukodystrophy v0.118 TOMM70 Zornitza Stark Gene: tomm70 has been classified as Amber List (Moderate Evidence).
Leukodystrophy v0.118 TOMM70 Zornitza Stark Classified gene: TOMM70 as Amber List (moderate evidence)
Leukodystrophy v0.118 TOMM70 Zornitza Stark Gene: tomm70 has been classified as Amber List (Moderate Evidence).
Leukodystrophy v0.117 TOMM70 Zornitza Stark gene: TOMM70 was added
gene: TOMM70 was added to Leukodystrophy - paediatric. Sources: Literature
Mode of inheritance for gene: TOMM70 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TOMM70 were set to 32356556
Phenotypes for gene: TOMM70 were set to White matter abnormalities; Developmental delay; Regression; Movement disorder
Review for gene: TOMM70 was set to AMBER
Added comment: De novo mono allelic variants in the C-terminal region of TOMM70 reported in two individuals. While both individuals exhibited shared symptoms including hypotonia, hyperreflexia, ataxia, dystonia, and significant white matter abnormalities, there were differences between the two individuals, most prominently the age of symptom onset, with one experiencing episodes of regression. Some functional data. Note bi-allelic disease also reported in one individual, with features of a mitochondrial disorder.
Sources: Literature
Mitochondrial disease v0.447 TOMM70 Zornitza Stark Marked gene: TOMM70 as ready
Mitochondrial disease v0.447 TOMM70 Zornitza Stark Gene: tomm70 has been classified as Amber List (Moderate Evidence).
Mitochondrial disease v0.447 TOMM70 Zornitza Stark Classified gene: TOMM70 as Amber List (moderate evidence)
Mitochondrial disease v0.447 TOMM70 Zornitza Stark Gene: tomm70 has been classified as Amber List (Moderate Evidence).
Mitochondrial disease v0.446 TOMM70 Zornitza Stark gene: TOMM70 was added
gene: TOMM70 was added to Mitochondrial disease. Sources: Literature
Mode of inheritance for gene: TOMM70 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TOMM70 were set to Severe anaemia; Lactic acidosis; Developmental delay
Review for gene: TOMM70 was set to AMBER
Added comment: TOM70 is a member of the TOM complex that transports cytosolic proteins into mitochondria. One individual reported with compound heterozygous variants in TOMM70 [c.794C>T (p.T265M) and c.1745C>T (p.A582V)]. Clinical features included severe anaemia, lactic acidosis, and developmental delay. Some functional data: in vitro cell model compensatory experiments.
Sources: Literature
Hypertension and Aldosterone disorders v0.15 CUL3 Zornitza Stark Marked gene: CUL3 as ready
Hypertension and Aldosterone disorders v0.15 CUL3 Zornitza Stark Gene: cul3 has been classified as Green List (High Evidence).
Mendeliome v0.2785 CUL3 Zornitza Stark Publications for gene: CUL3 were set to 22495309; 22914163; 25363760; 27824329; 32341456
Hypertension and Aldosterone disorders v0.15 CUL3 Zornitza Stark Phenotypes for gene: CUL3 were changed from Pseudohypoaldosteronism, type IIE, MIM# 614496 to Pseudohypoaldosteronism, type IIE, MIM# 614496
Mendeliome v0.2784 CUL3 Zornitza Stark edited their review of gene: CUL3: Changed publications: 22495309, 22914163, 25363760, 27824329, 32341456, 22266938
Hypertension and Aldosterone disorders v0.15 CUL3 Zornitza Stark Phenotypes for gene: CUL3 were changed from to Pseudohypoaldosteronism, type IIE, MIM# 614496
Hypertension and Aldosterone disorders v0.14 CUL3 Zornitza Stark Publications for gene: CUL3 were set to
Hypertension and Aldosterone disorders v0.13 CUL3 Zornitza Stark Mode of inheritance for gene: CUL3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertension and Aldosterone disorders v0.12 CUL3 Zornitza Stark reviewed gene: CUL3: Rating: GREEN; Mode of pathogenicity: None; Publications: 22266938; Phenotypes: Pseudohypoaldosteronism, type IIE, MIM# 614496; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2784 CUL3 Zornitza Stark Marked gene: CUL3 as ready
Mendeliome v0.2784 CUL3 Zornitza Stark Gene: cul3 has been classified as Green List (High Evidence).
Mendeliome v0.2784 CUL3 Zornitza Stark Phenotypes for gene: CUL3 were changed from to Pseudohypoaldosteronism, type IIE 614496; Intellectual disability; Autism; Seizures
Mendeliome v0.2783 CUL3 Zornitza Stark Publications for gene: CUL3 were set to
Mendeliome v0.2782 CUL3 Zornitza Stark Mode of inheritance for gene: CUL3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2781 CUL3 Zornitza Stark reviewed gene: CUL3: Rating: GREEN; Mode of pathogenicity: None; Publications: 22495309, 22914163, 25363760, 27824329, 32341456; Phenotypes: Pseudohypoaldosteronism, type IIE 614496, Intellectual disability, Autism, Seizures; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Autism v0.91 CUL3 Zornitza Stark Phenotypes for gene: CUL3 were changed from Autism to Autism; Intellectual disability; Epilepsy
Autism v0.90 CUL3 Zornitza Stark edited their review of gene: CUL3: Added comment: Further publication (PMID 32341456) reporting three unrelated individuals with neurodevelopmental phenotype.; Changed publications: 22495309, 22914163, 25363760, 27824329, 32341456; Changed phenotypes: Autism, Intellectual disability, Epilepsy
Genetic Epilepsy v0.700 CUL3 Zornitza Stark Marked gene: CUL3 as ready
Genetic Epilepsy v0.700 CUL3 Zornitza Stark Gene: cul3 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.700 CUL3 Zornitza Stark Phenotypes for gene: CUL3 were changed from Global developmental delay; Intellectual disability; Seizures; Abnormality of cardiovascular system morphology; Abnormality of the palate; Pseudohypoaldosteronism, type IIE - MIM #614496 to Global developmental delay; Intellectual disability; Seizures; Abnormality of cardiovascular system morphology; Abnormality of the palate
Genetic Epilepsy v0.699 CUL3 Zornitza Stark Classified gene: CUL3 as Amber List (moderate evidence)
Genetic Epilepsy v0.699 CUL3 Zornitza Stark Gene: cul3 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2631 CUL3 Zornitza Stark Marked gene: CUL3 as ready
Intellectual disability syndromic and non-syndromic v0.2631 CUL3 Zornitza Stark Gene: cul3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2631 CUL3 Zornitza Stark Phenotypes for gene: CUL3 were changed from Global developmental delay; Intellectual disability; Seizures; Abnormality of cardiovascular system morphology; Abnormality of the palate; Pseudohypoaldosteronism, type IIE - MIM #614496 to Global developmental delay; Intellectual disability; Seizures; Abnormality of cardiovascular system morphology; Abnormality of the palate
Intellectual disability syndromic and non-syndromic v0.2630 CUL3 Zornitza Stark Classified gene: CUL3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2630 CUL3 Zornitza Stark Gene: cul3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.698 CUL3 Konstantinos Varvagiannis gene: CUL3 was added
gene: CUL3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: CUL3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CUL3 were set to 32341456
Phenotypes for gene: CUL3 were set to Global developmental delay; Intellectual disability; Seizures; Abnormality of cardiovascular system morphology; Abnormality of the palate; Pseudohypoaldosteronism, type IIE - MIM #614496
Penetrance for gene: CUL3 were set to unknown
Review for gene: CUL3 was set to AMBER
Added comment: Nakashima et al (2020 - PMID:32341456) provide clinical details on 3 unrelated individuals with de novo CUL3 variants.

Features included DD, variable degrees of ID (P1: severe, P3: mild, P2: NA although he displayed motor and severe speech and language delay and had severe learning difficulties). Two out of three had intractable seizures (onset 2 - 6 months). One presented with congenital heart defects (ASD, PV stenosis) and another submucosal palatoschisis/bifid uvula. There were no facial dysmorphisms reported.

CUL3 encodes Cullin-3, a core piece of the E3 ubiquitin ligase complex, thus playing a role in the ubiquitin-proteasome system. [ https://ghr.nlm.nih.gov/gene/CUL3 ]. Germline variants in some other Cullin family genes (eg. CUL4B, CUL7) cause disorders with ID as a feature.

The 3 individuals reported by Nakashima had variable previous investigations (karyotype, CMA, metabolic testing) which were non-diagnostic. Singleton or trio exome sequencing identified 2 frameshift and 1 missense variant (NM_003590.4:c.854T>C / p.Val285Ala), further confirmed with Sanger sequencing. De novo occurrence was confirmed by analysis of microsatellite markers in an individual with singleton ES.

While the frameshift variants were presumed to lead to NMD (not studied), studies in HEK293T cells suggested that the Val285Ala reduced binding ability with KEAP1, possibly leading to instability of the Cullin-RING ligase (CRL) complex and impairment of the ubiquitin-proteasome system.

In OMIM, the phenotype associated with heterozygous CUL3 mutations is Pseudohypoaldosteronism type IIE (PHA2E - # 614496). As OMIM and Nakashima et al comment, PHA2E-associated variants are clustered around exon 9, most lead to skipping of exon 9 and produce an in-frame deletion of 57 aa in the cullin homology domain. Few (probably 3) missense variants in exon 9 have also been reported. Individuals with PHA2E do not display DD/ID and conversely individuals with NDD did not display features of PHA2E.

Nakashima et al summarize the phenotypes associated with 12 further de novo CUL3 variants in the literature with most pLOF ones detected in individuals with autism and/or developmental disorders and in few cases with congenital heart disease. Few additional missense variants and a stoploss one have been reported in individuals with NDD and one in SCZ.

Heterozygous Cul3 (/tissue-specific) deletion in mice resulted in autism-like behavior. Cul3 deficient mice also demonstrated NMDAR hypofunction and decreased spine density. [PMIDs cited : 31455858, 31780330]

Overall haploinsufficiency is favored as the underlying mechanism of variants associated with NDD. Nakashima et al comment that the pathogenesis of missense variants remains unknown and/or that a dominant-negative effect on CRL may be possible.

Studies on larger cohorts reporting on individuals with relevant phenotypes due to de novo CUL3 variants (eg. DDD study - PMID: 28135719, Lelieveld et al - PMID: 27479843), are better summarized in denovo-db (after filtering for coding variants):

http://denovo-db.gs.washington.edu/denovo-db/QueryVariantServlet?searchBy=Gene&target=cul3

Overall, this gene can be considered for inclusion in the ID (amber/green), epilepsy (amber) and/or ASD panels.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2629 CUL3 Konstantinos Varvagiannis gene: CUL3 was added
gene: CUL3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CUL3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CUL3 were set to 32341456
Phenotypes for gene: CUL3 were set to Global developmental delay; Intellectual disability; Seizures; Abnormality of cardiovascular system morphology; Abnormality of the palate; Pseudohypoaldosteronism, type IIE - MIM #614496
Penetrance for gene: CUL3 were set to unknown
Review for gene: CUL3 was set to GREEN
Added comment: Please consider inclusion with amber / green rating.
--
Nakashima et al (2020 - PMID:32341456) provide clinical details on 3 unrelated individuals with de novo CUL3 variants.

Features included DD, variable degrees of ID (P1: severe, P3: mild, P2: NA although he displayed motor and severe speech and language delay and had severe learning difficulties). Two out of three had intractable seizures (onset 2 - 6 months). One presented with congenital heart defects (ASD, PV stenosis) and another submucosal palatoschisis/bifid uvula. There were no facial dysmorphisms reported.

CUL3 encodes Cullin-3, a core piece of the E3 ubiquitin ligase complex, thus playing a role in the ubiquitin-proteasome system. [ https://ghr.nlm.nih.gov/gene/CUL3 ]. Germline variants in some other Cullin family genes (eg. CUL4B, CUL7) cause disorders with ID as a feature.

The 3 individuals reported by Nakashima had variable previous investigations (karyotype, CMA, metabolic testing) which were non-diagnostic. Singleton or trio exome sequencing identified 2 frameshift and 1 missense variant (NM_003590.4:c.854T>C / p.Val285Ala), further confirmed with Sanger sequencing. De novo occurrence was confirmed by analysis of microsatellite markers in an individual with singleton ES.

While the frameshift variants were presumed to lead to NMD (not studied), studies in HEK293T cells suggested that the Val285Ala reduced binding ability with KEAP1, possibly leading to instability of the Cullin-RING ligase (CRL) complex and impairment of the ubiquitin-proteasome system.

In OMIM, the phenotype associated with heterozygous CUL3 mutations is Pseudohypoaldosteronism type IIE (PHA2E - # 614496). As OMIM and Nakashima et al comment, PHA2E-associated variants are clustered around exon 9, most lead to skipping of exon 9 and produce an in-frame deletion of 57 aa in the cullin homology domain. Few (probably 3) missense variants in exon 9 have also been reported. Individuals with PHA2E do not display DD/ID and conversely individuals with NDD did not display features of PHA2E.

Nakashima et al summarize the phenotypes associated with 12 further de novo CUL3 variants in the literature with most pLOF ones detected in individuals with autism and/or developmental disorders and in few cases with congenital heart disease. Few additional missense variants and a stoploss one have been reported in individuals with NDD and one in SCZ.

Heterozygous Cul3 (/tissue-specific) deletion in mice resulted in autism-like behavior. Cul3 deficient mice also demonstrated NMDAR hypofunction and decreased spine density. [PMIDs cited : 31455858, 31780330]

Overall haploinsufficiency is favored as the underlying mechanism of variants associated with NDD. Nakashima et al comment that the pathogenesis of missense variants remains unknown and/or that a dominant-negative effect on CRL may be possible.

Studies on larger cohorts reporting on individuals with relevant phenotypes due to de novo CUL3 variants (eg. DDD study - PMID: 28135719, Lelieveld et al - PMID: 27479843), are summarized in denovo-db (after filtering for coding variants):

http://denovo-db.gs.washington.edu/denovo-db/QueryVariantServlet?searchBy=Gene&target=cul3

Overall, this gene can be considered for inclusion in the ID (amber/green), epilepsy (amber) and/or ASD panels.
Sources: Literature
Stroke v0.14 CBS Bryony Thompson Marked gene: CBS as ready
Stroke v0.14 CBS Bryony Thompson Gene: cbs has been classified as Green List (High Evidence).
Stroke v0.14 CBS Bryony Thompson Classified gene: CBS as Green List (high evidence)
Stroke v0.14 CBS Bryony Thompson Gene: cbs has been classified as Green List (High Evidence).
Stroke v0.13 CBS Bryony Thompson gene: CBS was added
gene: CBS was added to Stroke. Sources: Literature
Mode of inheritance for gene: CBS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CBS were set to 30356112; 20142522; 12552044
Phenotypes for gene: CBS were set to Homocystinuria, B6-responsive and nonresponsive types MIM#236200; Thrombosis, hyperhomocysteinemic MIM#236200
Review for gene: CBS was set to GREEN
Added comment: Large artery atherosclerosis/non-atherosclerosis, small-vessel disease, venous thrombosis, and arterial thrombosis stroke subtypes have been reported in the condition.
Sources: Literature
Genetic Epilepsy v0.698 KCNT1 Zornitza Stark Marked gene: KCNT1 as ready
Genetic Epilepsy v0.698 KCNT1 Zornitza Stark Gene: kcnt1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.698 KCNT1 Zornitza Stark Phenotypes for gene: KCNT1 were changed from to Epilepsy, nocturnal frontal lobe, 5, MIM# 615005; Epileptic encephalopathy, early infantile, 14, MIM# 614959
Genetic Epilepsy v0.697 KCNT1 Zornitza Stark Publications for gene: KCNT1 were set to
Genetic Epilepsy v0.696 KCNT1 Zornitza Stark Mode of inheritance for gene: KCNT1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.695 KCNT1 Zornitza Stark reviewed gene: KCNT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23086397, 23086396, 31872048, 31532509; Phenotypes: Epilepsy, nocturnal frontal lobe, 5, MIM# 615005, Epileptic encephalopathy, early infantile, 14, MIM# 614959; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Oligodontia v0.4 WNT10A Zornitza Stark Marked gene: WNT10A as ready
Oligodontia v0.4 WNT10A Zornitza Stark Gene: wnt10a has been classified as Green List (High Evidence).
Oligodontia v0.4 WNT10A Zornitza Stark Phenotypes for gene: WNT10A were changed from to Odontoonychodermal dysplasia 257980 AR; Schopf-Schulz-Passarge syndrome 224750 AR; Tooth agenesis, selective, 4 150400 AR, AD
Oligodontia v0.3 WNT10A Zornitza Stark Publications for gene: WNT10A were set to
Oligodontia v0.2 WNT10A Zornitza Stark Mode of inheritance for gene: WNT10A was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.2781 EGR2 Zornitza Stark Marked gene: EGR2 as ready
Mendeliome v0.2781 EGR2 Zornitza Stark Gene: egr2 has been classified as Green List (High Evidence).
Mendeliome v0.2781 EGR2 Zornitza Stark Phenotypes for gene: EGR2 were changed from to Charcot-Marie-Tooth disease, type 1D 607678 AD; Dejerine-Sottas disease 145900 AD, AR; Hypomyelinating neuropathy, congenital, 1 605253 AD, AR
Mendeliome v0.2780 EGR2 Zornitza Stark Publications for gene: EGR2 were set to
Mendeliome v0.2779 EGR2 Zornitza Stark Mode of pathogenicity for gene: EGR2 was changed from to Other
Mendeliome v0.2778 EGR2 Zornitza Stark Mode of inheritance for gene: EGR2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2777 EGR2 Zornitza Stark reviewed gene: EGR2: Rating: GREEN; Mode of pathogenicity: Other; Publications: 11523566, 31852952; Phenotypes: Charcot-Marie-Tooth disease, type 1D 607678 AD, Dejerine-Sottas disease 145900 AD, AR, Hypomyelinating neuropathy, congenital, 1 605253 AD, AR; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Oligodontia v0.1 WNT10A Michelle Torres reviewed gene: WNT10A: Rating: GREEN; Mode of pathogenicity: None; Publications: 19559398, 30426266; Phenotypes: Odontoonychodermal dysplasia 257980 AR, Schopf-Schulz-Passarge syndrome 224750 AR, Tooth agenesis, selective, 4 150400 AR, AD; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.2777 GAS2L2 Zornitza Stark Marked gene: GAS2L2 as ready
Mendeliome v0.2777 GAS2L2 Zornitza Stark Gene: gas2l2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2777 GAS2L2 Zornitza Stark Phenotypes for gene: GAS2L2 were changed from to Ciliary dyskinesia, primary, 41 (MIM # 618449)
Mendeliome v0.2776 GAS2L2 Zornitza Stark Publications for gene: GAS2L2 were set to
Mendeliome v0.2775 GAS2L2 Zornitza Stark Mode of inheritance for gene: GAS2L2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2774 GAS2L2 Zornitza Stark Classified gene: GAS2L2 as Amber List (moderate evidence)
Mendeliome v0.2774 GAS2L2 Zornitza Stark Gene: gas2l2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2773 GAS2L2 Zornitza Stark reviewed gene: GAS2L2: Rating: AMBER; Mode of pathogenicity: None; Publications: 30665704; Phenotypes: Ciliary dyskinesia, primary, 41 (MIM # 618449); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2629 ADAM22 Zornitza Stark gene: ADAM22 was added
gene: ADAM22 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review
Mode of inheritance for gene: ADAM22 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAM22 were set to 27066583; 30237576
Phenotypes for gene: ADAM22 were set to Epileptic encephalopathy, early infantile, 61, MIM# 617933
Review for gene: ADAM22 was set to AMBER
Added comment: Two families reported; the second one as part of a large consanguineous cohort.
Sources: Expert Review
Differences of Sex Development v0.28 KLB Zornitza Stark Marked gene: KLB as ready
Differences of Sex Development v0.28 KLB Zornitza Stark Gene: klb has been classified as Green List (High Evidence).
Differences of Sex Development v0.28 KLB Zornitza Stark Classified gene: KLB as Green List (high evidence)
Differences of Sex Development v0.28 KLB Zornitza Stark Gene: klb has been classified as Green List (High Evidence).
Differences of Sex Development v0.27 KLB Zornitza Stark gene: KLB was added
gene: KLB was added to Disorders of Sex Differentiation. Sources: Literature
Mode of inheritance for gene: KLB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KLB were set to 28754744
Phenotypes for gene: KLB were set to Hypogonadotropic hypogonadism
Review for gene: KLB was set to GREEN
Added comment: Seven heterozygous loss‐of‐function KLB mutations in 13 individuals reported. In mice, lack of Klb led to delayed puberty, altered estrous cyclicity, and subfertility due to a hypothalamic defect associated with inability of GnRH neurons to release GnRH in response to FGF21. Functional analysis showed decreased activity in response to FGF21 and FGF8. KLB is an obligate coreceptor for FGF21 alongside FGFR1.
Sources: Literature
Mendeliome v0.2773 KLB Zornitza Stark Marked gene: KLB as ready
Mendeliome v0.2773 KLB Zornitza Stark Gene: klb has been classified as Green List (High Evidence).
Mendeliome v0.2773 KLB Zornitza Stark Phenotypes for gene: KLB were changed from to Hypogonadotropic hypogonadism
Mendeliome v0.2772 KLB Zornitza Stark Classified gene: KLB as Green List (high evidence)
Mendeliome v0.2772 KLB Zornitza Stark Gene: klb has been classified as Green List (High Evidence).
Mendeliome v0.2771 KLB Zornitza Stark gene: KLB was added
gene: KLB was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KLB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KLB were set to 28754744
Review for gene: KLB was set to GREEN
Added comment: Seven heterozygous loss‐of‐function KLB mutations in 13 individuals reported. In mice, lack of Klb led to delayed puberty, altered estrous cyclicity, and subfertility due to a hypothalamic defect associated with inability of GnRH neurons to release GnRH in response to FGF21.
Functional analysis showed decreased activity in response to FGF21 and FGF8.
KLB is an obligate coreceptor for FGF21 alongside FGFR1.
Sources: Literature
Differences of Sex Development v0.26 NDNF Zornitza Stark Marked gene: NDNF as ready
Differences of Sex Development v0.26 NDNF Zornitza Stark Gene: ndnf has been classified as Green List (High Evidence).
Differences of Sex Development v0.26 NDNF Zornitza Stark Classified gene: NDNF as Green List (high evidence)
Differences of Sex Development v0.26 NDNF Zornitza Stark Gene: ndnf has been classified as Green List (High Evidence).
Differences of Sex Development v0.25 NDNF Zornitza Stark gene: NDNF was added
gene: NDNF was added to Disorders of Sex Differentiation. Sources: Literature
Mode of inheritance for gene: NDNF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NDNF were set to 31883645
Phenotypes for gene: NDNF were set to Congenital hypogonadotropic hypogonadism (CHH)
Review for gene: NDNF was set to GREEN
Added comment: Three heterozygous protein-truncating variants and one heterozygous missense variant identified in a cohort of 240 unrelated IHH patients. The authors also provided supporting evidence from animal models.
Sources: Literature
Mendeliome v0.2770 NDNF Zornitza Stark Marked gene: NDNF as ready
Mendeliome v0.2770 NDNF Zornitza Stark Gene: ndnf has been classified as Green List (High Evidence).
Mendeliome v0.2770 NDNF Zornitza Stark Classified gene: NDNF as Green List (high evidence)
Mendeliome v0.2770 NDNF Zornitza Stark Gene: ndnf has been classified as Green List (High Evidence).
Mendeliome v0.2769 NDNF Zornitza Stark gene: NDNF was added
gene: NDNF was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NDNF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NDNF were set to 31883645
Phenotypes for gene: NDNF were set to Congenital hypogonadotropic hypogonadism (CHH)
Review for gene: NDNF was set to GREEN
Added comment: Three heterozygous protein-truncating variants and one heterozygous missense variant identified in a cohort of 240 unrelated IHH patients. The authors also provided supporting evidence from animal models.
Sources: Literature
Mendeliome v0.2768 UGDH Zornitza Stark Marked gene: UGDH as ready
Mendeliome v0.2768 UGDH Zornitza Stark Gene: ugdh has been classified as Green List (High Evidence).
Mendeliome v0.2768 UGDH Zornitza Stark Classified gene: UGDH as Green List (high evidence)
Mendeliome v0.2768 UGDH Zornitza Stark Gene: ugdh has been classified as Green List (High Evidence).
Mendeliome v0.2767 UGDH Zornitza Stark gene: UGDH was added
gene: UGDH was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: UGDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UGDH were set to 32001716
Phenotypes for gene: UGDH were set to Epileptic encephalopathy, early infantile, 84 - MIM #618792
Review for gene: UGDH was set to GREEN
Added comment: 36 individuals with biallelic UGDH pathogenic variants reported. The phenotype corresponded overall to a developmental epileptic encephalopathy with hypotonia, feeding difficulties, severe global DD, moderate or commonly severe ID in all. Hypotonia and motor disorder (incl. spasticity, dystonia, ataxia, chorea, etc) often occurred prior to the onset of seizures. A single individual did not present seizures and 2 sibs had only seizures in the setting of fever. There were no individuals with biallelic pLoF variants identified. Parental/sib studies were all compatible with AR inheritance mode.

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

Attempts to model the disorder using an already developped zebrafish model (for a hypomorphic LoF allele) were unsuccessful as fish did not exhibit seizures spontaneously or upon induction with PTZ. Modelling of the disorder in vitro using patient-derived cerebral organoids demonstrated smaller organoids due to reduced number of proliferating neural progenitors
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2628 UGDH Zornitza Stark Marked gene: UGDH as ready
Intellectual disability syndromic and non-syndromic v0.2628 UGDH Zornitza Stark Gene: ugdh has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2628 UGDH Zornitza Stark Classified gene: UGDH as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2628 UGDH Zornitza Stark Gene: ugdh has been classified as Green List (High Evidence).
Genetic Epilepsy v0.695 UGDH Zornitza Stark Marked gene: UGDH as ready
Genetic Epilepsy v0.695 UGDH Zornitza Stark Gene: ugdh has been classified as Green List (High Evidence).
Genetic Epilepsy v0.695 UGDH Zornitza Stark Classified gene: UGDH as Green List (high evidence)
Genetic Epilepsy v0.695 UGDH Zornitza Stark Gene: ugdh has been classified as Green List (High Evidence).
Mendeliome v0.2766 TRIM33 Zornitza Stark Marked gene: TRIM33 as ready
Mendeliome v0.2766 TRIM33 Zornitza Stark Gene: trim33 has been classified as Red List (Low Evidence).
Mendeliome v0.2766 TRIM33 Zornitza Stark Classified gene: TRIM33 as Red List (low evidence)
Mendeliome v0.2766 TRIM33 Zornitza Stark Gene: trim33 has been classified as Red List (Low Evidence).
Mendeliome v0.2765 TRIM33 Zornitza Stark reviewed gene: TRIM33: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Ciliopathies v0.133 ADAMTS9 Zornitza Stark Marked gene: ADAMTS9 as ready
Ciliopathies v0.133 ADAMTS9 Zornitza Stark Gene: adamts9 has been classified as Green List (High Evidence).
Ciliopathies v0.133 ADAMTS9 Zornitza Stark Classified gene: ADAMTS9 as Green List (high evidence)
Ciliopathies v0.133 ADAMTS9 Zornitza Stark Gene: adamts9 has been classified as Green List (High Evidence).
Ciliopathies v0.132 ADAMTS9 Zornitza Stark gene: ADAMTS9 was added
gene: ADAMTS9 was added to Ciliopathies. Sources: Expert list
Mode of inheritance for gene: ADAMTS9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAMTS9 were set to 30609407
Phenotypes for gene: ADAMTS9 were set to Nephronophthisis-Related Ciliopathy
Review for gene: ADAMTS9 was set to GREEN
Added comment: Two families reported with functional evidence.
Sources: Expert list
Genetic Epilepsy v0.694 UGDH Konstantinos Varvagiannis gene: UGDH was added
gene: UGDH was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: UGDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UGDH were set to 32001716
Phenotypes for gene: UGDH were set to Epileptic encephalopathy, early infantile, 84 - MIM #618792
Penetrance for gene: UGDH were set to Complete
Review for gene: UGDH was set to GREEN
Added comment: Hengel et al (2020 - PMID: 32001716) report on 36 individuals with biallelic UGDH pathogenic variants.

The phenotype corresponded overall to a developmental epileptic encephalopathy with hypotonia, feeding difficulties, severe global DD, moderate or commonly severe ID in all. Hypotonia and motor disorder (incl. spasticity, dystonia, ataxia, chorea, etc) often occurred prior to the onset of seizures. A single individual did not present seizures and 2 sibs had only seizures in the setting of fever.

Affected subjects were tested by exome sequencing and UGDH variants were the only/best candidates for the phenotype following also segregation studies. Many were compound heterozygous or homozygous (~6 families were consanguineous) for missense variants and few were compound heterozygous for missense and pLoF variants. There were no individuals with biallelic pLoF variants identified. Parental/sib studies were all compatible with AR inheritance mode.

UGDH encodes the enzyme UDP-glucose dehydrogenase which converts UDP-glucose to UDP-glucuronate, the latter being a critical component of the glycosaminoglycans, hyaluronan, chondroitin sulfate, and heparan sulfate [OMIM].

Patient fibroblast and biochemical assays suggested a LoF effect of variants leading to impairment of UGDH stability, oligomerization or enzymatic activity (decreased UGDH-catalyzed reduction of NAD+ to NADH / hyaluronic acid production which requires UDP-glucuronate).

Attempts to model the disorder using an already developped zebrafish model (for a hypomorphic LoF allele) were unsuccessful as fish did not exhibit seizures spontaneously or upon induction with PTZ.

Modelling of the disorder in vitro using patient-derived cerebral organoids demonstrated smaller organoids due to reduced number of proliferating neural progenitors.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2627 UGDH Konstantinos Varvagiannis gene: UGDH was added
gene: UGDH was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: UGDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UGDH were set to 32001716
Phenotypes for gene: UGDH were set to Epileptic encephalopathy, early infantile, 84 - MIM #618792
Penetrance for gene: UGDH were set to Complete
Review for gene: UGDH was set to GREEN
Added comment: Hengel et al (2020 - PMID: 32001716) report on 36 individuals with biallelic UGDH pathogenic variants.

The phenotype corresponded overall to a developmental epileptic encephalopathy with hypotonia, feeding difficulties, severe global DD, moderate or commonly severe ID in all. Hypotonia and motor disorder (incl. spasticity, dystonia, ataxia, chorea, etc) often occurred prior to the onset of seizures. A single individual did not present seizures and 2 sibs had only seizures in the setting of fever.

Affected subjects were tested by exome sequencing and UGDH variants were the only/best candidates for the phenotype following also segregation studies. Many were compound heterozygous or homozygous (~6 families were consanguineous) for missense variants and few were compound heterozygous for missense and pLoF variants. There were no individuals with biallelic pLoF variants identified. Parental/sib studies were all compatible with AR inheritance mode.

UGDH encodes the enzyme UDP-glucose dehydrogenase which converts UDP-glucose to UDP-glucuronate, the latter being a critical component of the glycosaminoglycans, hyaluronan, chondroitin sulfate, and heparan sulfate [OMIM].

Patient fibroblast and biochemical assays suggested a LoF effect of variants leading to impairment of UGDH stability, oligomerization or enzymatic activity (decreased UGDH-catalyzed reduction of NAD+ to NADH / hyaluronic acid production which requires UDP-glucuronate).

Attempts to model the disorder using an already developped zebrafish model (for a hypomorphic LoF allele) were unsuccessful as fish did not exhibit seizures spontaneously or upon induction with PTZ.

Modelling of the disorder in vitro using patient-derived cerebral organoids demonstrated smaller organoids due to reduced number of proliferating neural progenitors.
Sources: Literature
Leukodystrophy v0.116 L2HGDH Zornitza Stark Marked gene: L2HGDH as ready
Leukodystrophy v0.116 L2HGDH Zornitza Stark Gene: l2hgdh has been classified as Green List (High Evidence).
Leukodystrophy v0.116 L2HGDH Zornitza Stark Classified gene: L2HGDH as Green List (high evidence)
Leukodystrophy v0.116 L2HGDH Zornitza Stark Gene: l2hgdh has been classified as Green List (High Evidence).
Leukodystrophy v0.115 L2HGDH Zornitza Stark gene: L2HGDH was added
gene: L2HGDH was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: L2HGDH was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: L2HGDH were set to L-2-hydroxyglutaric aciduria, MIM# 236792
Review for gene: L2HGDH was set to GREEN
Added comment: Age of onset is variable, but typically in infancy/childhood.
Sources: Expert list
Genetic Epilepsy v0.694 SPTBN4 Zornitza Stark Marked gene: SPTBN4 as ready
Genetic Epilepsy v0.694 SPTBN4 Zornitza Stark Gene: sptbn4 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.694 SPTBN4 Zornitza Stark Classified gene: SPTBN4 as Green List (high evidence)
Genetic Epilepsy v0.694 SPTBN4 Zornitza Stark Gene: sptbn4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2627 SPTBN4 Zornitza Stark Marked gene: SPTBN4 as ready
Intellectual disability syndromic and non-syndromic v0.2627 SPTBN4 Zornitza Stark Gene: sptbn4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2627 SPTBN4 Zornitza Stark Classified gene: SPTBN4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2627 SPTBN4 Zornitza Stark Gene: sptbn4 has been classified as Green List (High Evidence).
Mendeliome v0.2765 YIF1B Zornitza Stark Marked gene: YIF1B as ready
Mendeliome v0.2765 YIF1B Zornitza Stark Gene: yif1b has been classified as Green List (High Evidence).
Mendeliome v0.2765 YIF1B Zornitza Stark Classified gene: YIF1B as Green List (high evidence)
Mendeliome v0.2765 YIF1B Zornitza Stark Gene: yif1b has been classified as Green List (High Evidence).
Mendeliome v0.2764 YIF1B Zornitza Stark gene: YIF1B was added
gene: YIF1B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: YIF1B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YIF1B were set to 32006098; 26077767
Phenotypes for gene: YIF1B were set to Central hypotonia; Failure to thrive; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Spasticity; Abnormality of movement
Review for gene: YIF1B was set to GREEN
Added comment: 6 individuals (from 5 families) with biallelic YIF1B truncating variants reported. Presenting features: hypotonia, failure to thrive, microcephaly (5/6), severe global DD and ID as well as features suggestive of a motor disorder (dystonia/spasticity/dyskinesia). Seizures were reported in 2 unrelated individuals (2/6). MRI abnormalities were observed in some with thin CC being a feature in 3. Affected individuals were found to be homozygous for truncating variants (4/5 families being consanguineous). The following 3 variants were identified (NM_001039672.2) : c.186dupT or p.Ala64fs / c.360_361insACAT or p.Gly121fs / c.598G>T or p.Glu200*. Yif1B KO mice demonstrate a disorganized Golgi architecture in pyramidal hippocampal neurons (Alterio et al 2015 - PMID: 26077767). Functional/network analysis of genes co-regulated with YIF1B based on available RNAseq data, suggest enrichement in in genes important for nervous system development and function.
Sources: Literature
Microcephaly v0.123 YIF1B Zornitza Stark Marked gene: YIF1B as ready
Microcephaly v0.123 YIF1B Zornitza Stark Gene: yif1b has been classified as Green List (High Evidence).
Microcephaly v0.123 YIF1B Zornitza Stark Classified gene: YIF1B as Green List (high evidence)
Microcephaly v0.123 YIF1B Zornitza Stark Gene: yif1b has been classified as Green List (High Evidence).
Microcephaly v0.122 YIF1B Zornitza Stark gene: YIF1B was added
gene: YIF1B was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: YIF1B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YIF1B were set to 32006098; 26077767
Phenotypes for gene: YIF1B were set to Central hypotonia; Failure to thrive; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Spasticity; Abnormality of movement
Review for gene: YIF1B was set to GREEN
Added comment: 6 individuals (from 5 families) with biallelic YIF1B truncating variants reported. Presenting features: hypotonia, failure to thrive, microcephaly (5/6), severe global DD and ID as well as features suggestive of a motor disorder (dystonia/spasticity/dyskinesia). Seizures were reported in 2 unrelated individuals (2/6). MRI abnormalities were observed in some with thin CC being a feature in 3. Affected individuals were found to be homozygous for truncating variants (4/5 families being consanguineous). The following 3 variants were identified (NM_001039672.2) : c.186dupT or p.Ala64fs / c.360_361insACAT or p.Gly121fs / c.598G>T or p.Glu200*. Yif1B KO mice demonstrate a disorganized Golgi architecture in pyramidal hippocampal neurons (Alterio et al 2015 - PMID: 26077767). Functional/network analysis of genes co-regulated with YIF1B based on available RNAseq data, suggest enrichement in in genes important for nervous system development and function.
Sources: Literature
Genetic Epilepsy v0.693 YIF1B Zornitza Stark Marked gene: YIF1B as ready
Genetic Epilepsy v0.693 YIF1B Zornitza Stark Gene: yif1b has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.693 YIF1B Zornitza Stark Classified gene: YIF1B as Amber List (moderate evidence)
Genetic Epilepsy v0.693 YIF1B Zornitza Stark Gene: yif1b has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2626 YIF1B Zornitza Stark Marked gene: YIF1B as ready
Intellectual disability syndromic and non-syndromic v0.2626 YIF1B Zornitza Stark Gene: yif1b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2626 YIF1B Zornitza Stark Classified gene: YIF1B as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2626 YIF1B Zornitza Stark Gene: yif1b has been classified as Green List (High Evidence).
Leukodystrophy v0.114 HEXA Zornitza Stark Marked gene: HEXA as ready
Leukodystrophy v0.114 HEXA Zornitza Stark Gene: hexa has been classified as Green List (High Evidence).
Leukodystrophy v0.114 HEXA Zornitza Stark Classified gene: HEXA as Green List (high evidence)
Leukodystrophy v0.114 HEXA Zornitza Stark Gene: hexa has been classified as Green List (High Evidence).
Leukodystrophy v0.113 HEXA Zornitza Stark gene: HEXA was added
gene: HEXA was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: HEXA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: HEXA were set to Tay-Sachs disease, MIM# 272800
Review for gene: HEXA was set to GREEN
Added comment: Sources: Expert list
Genetic Epilepsy v0.692 YIF1B Konstantinos Varvagiannis changed review comment from: Abnormality of movement
AlMuhaizea et al (2020 - PMID: 32006098) report on the phenotype of 6 individuals (from 5 families) with biallelic YIF1B truncating variants.

Affected subjects presented hypotonia, failure to thrive, microcephaly (5/6), severe global DD and ID (as evident from best motor/language milestones achieved - Table S1) as well as features suggestive of a motor disorder (dystonia/spasticity/dyskinesia). Seizures were reported in 2 unrelated individuals (2/6). MRI abnormalities were observed in some with thin CC being a feature in 3.

Variable initial investigations were performed including SNP CMA, MECP2, microcephaly / neurotransmitter disorders gene panel testing did not reveal P/LP variants.

YIF1B variants were identified in 3 families within ROH. Following exome sequencing, affected individuals were found to be homozygous for truncating variants (4/5 families being consanguineous). The following 3 variants were identified (NM_001039672.2) : c.186dupT or p.Ala64fs / c.360_361insACAT or p.Gly121fs / c.598G>T or p.Glu200*.

YIF1B encodes an intracellular transmembrane protein.

It has been previously demonstrated that - similarly to other proteins of the Yip family being implicated in intracellular traffic between the Golgi - Yif1B is involved in the anterograde traffic pathway. Yif1B KO mice demonstrate a disorganized Golgi architecture in pyramidal hippocampal neurons (Alterio et al 2015 - PMID: 26077767). The rat ortholog interacts with serotonin receptor 1 (5-HT1AR) with colocalization of Yif1BB and 5-HT1AR in intermediate compartment vesicles and involvement of the former in intracellular trafficing/modulation of 5-HT1AR transport to dendrites (PMID cited: 18685031).

Available mRNA and protein expression data (Protein Atlas) suggest that the gene is widely expressed in all tissues incl. neuronal cells. Immunochemistry data from the Human Brain Atlas also suggest that YIF1B is found in vesicles and localized to the Golgi apparatus. Immunohistochemistry in normal human brain tissue (cerebral cortex) demonstrated labeling of neuronal cells (Human Protein Atlas).

Functional/network analysis of genes co-regulated with YIF1B based on available RNAseq data, suggest enrichement in in genes important for nervous system development and function.

Please consider inclusion in other panels that may be relevant (e.g. microcephaly, etc).
Sources: Literature; to: AlMuhaizea et al (2020 - PMID: 32006098) report on the phenotype of 6 individuals (from 5 families) with biallelic YIF1B truncating variants.

Affected subjects presented hypotonia, failure to thrive, microcephaly (5/6), severe global DD and ID (as evident from best motor/language milestones achieved - Table S1) as well as features suggestive of a motor disorder (dystonia/spasticity/dyskinesia). Seizures were reported in 2 unrelated individuals (2/6). MRI abnormalities were observed in some with thin CC being a feature in 3.

Variable initial investigations were performed including SNP CMA, MECP2, microcephaly / neurotransmitter disorders gene panel testing did not reveal P/LP variants.

YIF1B variants were identified in 3 families within ROH. Following exome sequencing, affected individuals were found to be homozygous for truncating variants (4/5 families being consanguineous). The following 3 variants were identified (NM_001039672.2) : c.186dupT or p.Ala64fs / c.360_361insACAT or p.Gly121fs / c.598G>T or p.Glu200*.

YIF1B encodes an intracellular transmembrane protein.

It has been previously demonstrated that - similarly to other proteins of the Yip family being implicated in intracellular traffic between the Golgi - Yif1B is involved in the anterograde traffic pathway. Yif1B KO mice demonstrate a disorganized Golgi architecture in pyramidal hippocampal neurons (Alterio et al 2015 - PMID: 26077767). The rat ortholog interacts with serotonin receptor 1 (5-HT1AR) with colocalization of Yif1BB and 5-HT1AR in intermediate compartment vesicles and involvement of the former in intracellular trafficing/modulation of 5-HT1AR transport to dendrites (PMID cited: 18685031).

Available mRNA and protein expression data (Protein Atlas) suggest that the gene is widely expressed in all tissues incl. neuronal cells. Immunochemistry data from the Human Brain Atlas also suggest that YIF1B is found in vesicles and localized to the Golgi apparatus. Immunohistochemistry in normal human brain tissue (cerebral cortex) demonstrated labeling of neuronal cells (Human Protein Atlas).

Functional/network analysis of genes co-regulated with YIF1B based on available RNAseq data, suggest enrichement in in genes important for nervous system development and function.

Please consider inclusion in other panels that may be relevant (e.g. microcephaly, etc).
Sources: Literature
Genetic Epilepsy v0.692 YIF1B Konstantinos Varvagiannis gene: YIF1B was added
gene: YIF1B was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: YIF1B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YIF1B were set to 32006098
Phenotypes for gene: YIF1B were set to Central hypotonia; Failure to thrive; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Spasticity; Abnormality of movement
Penetrance for gene: YIF1B were set to Complete
Review for gene: YIF1B was set to AMBER
Added comment: Abnormality of movement
AlMuhaizea et al (2020 - PMID: 32006098) report on the phenotype of 6 individuals (from 5 families) with biallelic YIF1B truncating variants.

Affected subjects presented hypotonia, failure to thrive, microcephaly (5/6), severe global DD and ID (as evident from best motor/language milestones achieved - Table S1) as well as features suggestive of a motor disorder (dystonia/spasticity/dyskinesia). Seizures were reported in 2 unrelated individuals (2/6). MRI abnormalities were observed in some with thin CC being a feature in 3.

Variable initial investigations were performed including SNP CMA, MECP2, microcephaly / neurotransmitter disorders gene panel testing did not reveal P/LP variants.

YIF1B variants were identified in 3 families within ROH. Following exome sequencing, affected individuals were found to be homozygous for truncating variants (4/5 families being consanguineous). The following 3 variants were identified (NM_001039672.2) : c.186dupT or p.Ala64fs / c.360_361insACAT or p.Gly121fs / c.598G>T or p.Glu200*.

YIF1B encodes an intracellular transmembrane protein.

It has been previously demonstrated that - similarly to other proteins of the Yip family being implicated in intracellular traffic between the Golgi - Yif1B is involved in the anterograde traffic pathway. Yif1B KO mice demonstrate a disorganized Golgi architecture in pyramidal hippocampal neurons (Alterio et al 2015 - PMID: 26077767). The rat ortholog interacts with serotonin receptor 1 (5-HT1AR) with colocalization of Yif1BB and 5-HT1AR in intermediate compartment vesicles and involvement of the former in intracellular trafficing/modulation of 5-HT1AR transport to dendrites (PMID cited: 18685031).

Available mRNA and protein expression data (Protein Atlas) suggest that the gene is widely expressed in all tissues incl. neuronal cells. Immunochemistry data from the Human Brain Atlas also suggest that YIF1B is found in vesicles and localized to the Golgi apparatus. Immunohistochemistry in normal human brain tissue (cerebral cortex) demonstrated labeling of neuronal cells (Human Protein Atlas).

Functional/network analysis of genes co-regulated with YIF1B based on available RNAseq data, suggest enrichement in in genes important for nervous system development and function.

Please consider inclusion in other panels that may be relevant (e.g. microcephaly, etc).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2625 YIF1B Konstantinos Varvagiannis gene: YIF1B was added
gene: YIF1B was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: YIF1B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YIF1B were set to 32006098
Phenotypes for gene: YIF1B were set to Central hypotonia; Failure to thrive; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Spasticity; Abnormality of movement
Penetrance for gene: YIF1B were set to Complete
Review for gene: YIF1B was set to GREEN
Added comment: AlMuhaizea et al (2020 - PMID: 32006098) report on the phenotype of 6 individuals (from 5 families) with biallelic YIF1B truncating variants.

Affected subjects presented hypotonia, failure to thrive, microcephaly (5/6), severe global DD and ID (as evident from best motor/language milestones achieved - Table S1) as well as features suggestive of a motor disorder (dystonia/spasticity/dyskinesia). Seizures were reported in 2 unrelated individuals (2/6). MRI abnormalities were observed in some with thin CC being a feature in 3.

Variable initial investigations were performed including SNP CMA, MECP2, microcephaly / neurotransmitter disorders gene panel testing did not reveal P/LP variants.

YIF1B variants were identified in 3 families within ROH. Following exome sequencing, affected individuals were found to be homozygous for truncating variants (4/5 families being consanguineous). The following 3 variants were identified (NM_001039672.2) : c.186dupT or p.Ala64fs / c.360_361insACAT or p.Gly121fs / c.598G>T or p.Glu200*.

YIF1B encodes an intracellular transmembrane protein.

It has been previously demonstrated that - similarly to other proteins of the Yip family being implicated in intracellular traffic between the Golgi - Yif1B is involved in the anterograde traffic pathway. Yif1B KO mice demonstrate a disorganized Golgi architecture in pyramidal hippocampal neurons (Alterio et al 2015 - PMID: 26077767). The rat ortholog interacts with serotonin receptor 1 (5-HT1AR) with colocalization of Yif1BB and 5-HT1AR in intermediate compartment vesicles and involvement of the former in intracellular trafficing/modulation of 5-HT1AR transport to dendrites (PMID cited: 18685031).

Available mRNA and protein expression data (Protein Atlas) suggest that the gene is widely expressed in all tissues incl. neuronal cells. Immunochemistry data from the Human Brain Atlas also suggest that YIF1B is found in vesicles and localized to the Golgi apparatus. Immunohistochemistry in normal human brain tissue (cerebral cortex) demonstrated labeling of neuronal cells (Human Protein Atlas).

Functional/network analysis of genes co-regulated with YIF1B based on available RNAseq data, suggest enrichement in in genes important for nervous system development and function.

Please consider inclusion in other panels that may be relevant (e.g. microcephaly, etc).
Sources: Literature
Genetic Epilepsy v0.692 SPTBN4 Konstantinos Varvagiannis gene: SPTBN4 was added
gene: SPTBN4 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SPTBN4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPTBN4 were set to 28540413; 28940097; 29861105; 31230720; 31857255
Phenotypes for gene: SPTBN4 were set to Neurodevelopmental disorder with hypotonia, neuropathy, and deafness MIM#617519
Penetrance for gene: SPTBN4 were set to Complete
Review for gene: SPTBN4 was set to GREEN
Added comment: Biallelic pathogenic SPTBN4 variants cause Neurodevelopmental disorder with hypotonia, neuropathy, and deafness (MIM #617519).

There are several reports on the phenotype of relevant affected individuals with severe/profound DD/ID in at least 9 individuals :

- Knierim et al (2017 - PMID: 28540413) [1 affected individual]
- Anazi et al (2017 - PMID: 28940097) [1]
- Wang et al (2018 - PMID: 29861105) [6]
- Pehlivan et al (2019 - PMID: 31230720) [1]

A recent article by Häusler et al (2019 - PMID: 31857255) describes the phenotype of 2 sibs, both presenting with motor and speech delay, although the older one had reportedly 'normal' cognitive performance allowing attendance of regular school at the age of 6 years.

Features include congenital hypotonia, severe DD and ID (in most as outlined above, ID was the primary indication for testing on several occasions), poor or absent reflexes and weakness secondary to axonal motor neuropathy, feeding and respiratory difficulties, hearing and visual impairment. Seizures have been reported in at least 4 unrelated individuals (3 by Wang et al / 1 by Pehlivan et al).

Variants in most cases were nonsense/frameshift although biallelic missense variants have also been reported. Sibs in the report by Häusler et al harbored a homozygous splicing variant.

SPTBN4 encodes a member of the beta-spectrin protein family that is expressed in the brain, peripheral nervous system, pancreas, and skeletal muscle.

βIV spectrin links ankyrinG and clustered ion channels (at axon initial segments and nodes of Ranvier) to the axonal cytoskeleton. Pathogenic variants are proposed to disrupt the cytoskeletal machinery controlling proper localization of ion channels and function of axonal domains where ion channels are normally clustered in high density. Among the evidence provided : nerve biopsies from an affected individual displayed reduced nodal Na+ channels and no nodal KCNQ2 K+ channels / Loss of AnkyrinG and βIV spectrin in animal model resulted in loss of KCNQ2- and KCNQ3- subunit containing K+ channels.

Apart from the ID / epilepsy panels please consider inclusion in other relevant ones.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2625 SPTBN4 Konstantinos Varvagiannis reviewed gene: SPTBN4: Rating: GREEN; Mode of pathogenicity: None; Publications: 28540413, 28940097, 29861105, 31230720, 31857255; Phenotypes: Neurodevelopmental disorder with hypotonia, neuropathy, and deafness MIM#617519; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2763 TNRC6B Zornitza Stark Phenotypes for gene: TNRC6B were changed from to Global developmental delay; Intellectual disability; Autistic behavior
Mendeliome v0.2762 TNRC6B Zornitza Stark Publications for gene: TNRC6B were set to
Mendeliome v0.2761 TNRC6B Zornitza Stark Mode of inheritance for gene: TNRC6B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2760 TNRC6B Zornitza Stark Classified gene: TNRC6B as Green List (high evidence)
Mendeliome v0.2760 TNRC6B Zornitza Stark Gene: tnrc6b has been classified as Green List (High Evidence).
Mendeliome v0.2759 TNRC6B Zornitza Stark edited their review of gene: TNRC6B: Added comment: 17 unrelated individuals with heterozygous TNRC6B variants reported. Features included hypotonia (10/17), DD/ID (17/17 - ID was not universal: average IQ of 12 individuals was 73 (range : 50-113) with 4 having below 70), ADHD (11/17), ASD or autistic traits (8/17 and 5/17). Some/few presented with abnormal OFC (micro- / macrocephaly in 3/17 and 2/17), abnormal vision or hearing, variable other congenital anomalies, echocardiographic, GI or renal abnormalities, etc. Epilepsy was reported in 1/17. There was no recognisable gestalt.Detected variants included 14 pLoF, 1 missense SNV and 2 intragenic deletions. Variants had occurred as de novo events in 10/13 subjects for whom testing of both parents was possible. 3/13 subjects had inherited the variant from a parent with milder phenotype. Based on the type of variants identified, the pLI score of 1 in gnomAD and the HI index of 5.61%, the authors suggest haploinsufficiency as the most likely mechanism. Individuals with de novo TNRC6B variants have also been reported in larger cohorts (e.g. DDD study - PMID: 28135719, Iossifov et al - PMID: 25363768, Lelieveld et al - PMID: 27479843, Jónsson et al - PMID: 28959963). A previous study provided details on 2 sibs harboring a translocation which disrupted both TNRC6B and TCF20 (also associated with ID)(Babbs et al - PMID: 25228304).; Changed rating: GREEN; Changed publications: 32152250, 28135719, 25363768, 27479843, 28959963, 25228304; Changed phenotypes: Global developmental delay, Intellectual disability, Autistic behavior; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Autism v0.90 TNRC6B Zornitza Stark Phenotypes for gene: TNRC6B were changed from to Global developmental delay; Intellectual disability; Autistic behavior
Autism v0.89 TNRC6B Zornitza Stark Publications for gene: TNRC6B were set to
Autism v0.88 TNRC6B Zornitza Stark Mode of inheritance for gene: TNRC6B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Autism v0.87 TNRC6B Zornitza Stark Classified gene: TNRC6B as Green List (high evidence)
Autism v0.87 TNRC6B Zornitza Stark Gene: tnrc6b has been classified as Green List (High Evidence).
Autism v0.86 TNRC6B Zornitza Stark edited their review of gene: TNRC6B: Added comment: 17 unrelated individuals with heterozygous TNRC6B variants reported. Features included hypotonia (10/17), DD/ID (17/17 - ID was not universal: average IQ of 12 individuals was 73 (range : 50-113) with 4 having below 70), ADHD (11/17), ASD or autistic traits (8/17 and 5/17). Some/few presented with abnormal OFC (micro- / macrocephaly in 3/17 and 2/17), abnormal vision or hearing, variable other congenital anomalies, echocardiographic, GI or renal abnormalities, etc. Epilepsy was reported in 1/17. There was no recognisable gestalt.Detected variants included 14 pLoF, 1 missense SNV and 2 intragenic deletions. Variants had occurred as de novo events in 10/13 subjects for whom testing of both parents was possible. 3/13 subjects had inherited the variant from a parent with milder phenotype. Based on the type of variants identified, the pLI score of 1 in gnomAD and the HI index of 5.61%, the authors suggest haploinsufficiency as the most likely mechanism. Individuals with de novo TNRC6B variants have also been reported in larger cohorts (e.g. DDD study - PMID: 28135719, Iossifov et al - PMID: 25363768, Lelieveld et al - PMID: 27479843, Jónsson et al - PMID: 28959963). A previous study provided details on 2 sibs harboring a translocation which disrupted both TNRC6B and TCF20 (also associated with ID)(Babbs et al - PMID: 25228304).; Changed rating: GREEN; Changed publications: 32152250, 28135719, 25363768, 27479843, 28959963, 25228304; Changed phenotypes: Global developmental delay, Intellectual disability, Autistic behavior; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2625 TNRC6B Zornitza Stark Phenotypes for gene: TNRC6B were changed from to Global developmental delay; Intellectual disability; Autistic behavior
Intellectual disability syndromic and non-syndromic v0.2624 TNRC6B Zornitza Stark Publications for gene: TNRC6B were set to
Intellectual disability syndromic and non-syndromic v0.2623 TNRC6B Zornitza Stark Mode of inheritance for gene: TNRC6B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2622 TNRC6B Zornitza Stark Classified gene: TNRC6B as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2622 TNRC6B Zornitza Stark Gene: tnrc6b has been classified as Green List (High Evidence).
Mendeliome v0.2759 CDC42BPB Zornitza Stark Marked gene: CDC42BPB as ready
Mendeliome v0.2759 CDC42BPB Zornitza Stark Gene: cdc42bpb has been classified as Green List (High Evidence).
Mendeliome v0.2759 CDC42BPB Zornitza Stark Classified gene: CDC42BPB as Green List (high evidence)
Mendeliome v0.2759 CDC42BPB Zornitza Stark Gene: cdc42bpb has been classified as Green List (High Evidence).
Mendeliome v0.2758 CDC42BPB Zornitza Stark gene: CDC42BPB was added
gene: CDC42BPB was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CDC42BPB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDC42BPB were set to 32031333
Phenotypes for gene: CDC42BPB were set to Central hypotonia; Global developmental delay; Intellectual disability; Seizures; Autistic behavior; Behavioral abnormality
Review for gene: CDC42BPB was set to GREEN
Added comment: 14 individuals with missense and loss-of-function CDC42BPB variants reported. Features included hypotonia (8/11), DD (12/13 - the 14th was a fetus), ID (7/13), ASD (8/12), clinical seizures (in 3 - a 4th had abnormal EEG without seizures), behavioral abnormalities. Variable non-specific dysmorphic features were reported in some (sparse hair being the most frequent - 4/8). Additional features were observed in few (=<4) incl. cryptorchidism, ophthalmological issues, constipation, kidney abnormalities, micropenis, etc. Most variants occurred as de novo events (11/14) while inheritance was not available for few (3/14).
Sources: Literature
Genetic Epilepsy v0.692 CDC42BPB Zornitza Stark Marked gene: CDC42BPB as ready
Genetic Epilepsy v0.692 CDC42BPB Zornitza Stark Added comment: Comment when marking as ready: Primarily an ID gene, remains to be seen whether seizures are a prominent part of the phenotype.
Genetic Epilepsy v0.692 CDC42BPB Zornitza Stark Gene: cdc42bpb has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.692 CDC42BPB Zornitza Stark Mode of inheritance for gene: CDC42BPB was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.691 CDC42BPB Zornitza Stark Classified gene: CDC42BPB as Amber List (moderate evidence)
Genetic Epilepsy v0.691 CDC42BPB Zornitza Stark Gene: cdc42bpb has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.691 CDC42BPB Zornitza Stark Classified gene: CDC42BPB as Green List (high evidence)
Genetic Epilepsy v0.691 CDC42BPB Zornitza Stark Gene: cdc42bpb has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2621 CDC42BPB Zornitza Stark Marked gene: CDC42BPB as ready
Intellectual disability syndromic and non-syndromic v0.2621 CDC42BPB Zornitza Stark Gene: cdc42bpb has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2621 CDC42BPB Zornitza Stark Mode of inheritance for gene: CDC42BPB was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2620 CDC42BPB Zornitza Stark Classified gene: CDC42BPB as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2620 CDC42BPB Zornitza Stark Gene: cdc42bpb has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2619 TNRC6B Konstantinos Varvagiannis reviewed gene: TNRC6B: Rating: GREEN; Mode of pathogenicity: None; Publications: 32152250, 28135719, 25363768, 27479843, 28959963, 25228304; Phenotypes: Global developmental delay, Intellectual disability, Autistic behavior; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic Epilepsy v0.690 CDC42BPB Konstantinos Varvagiannis gene: CDC42BPB was added
gene: CDC42BPB was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: CDC42BPB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CDC42BPB were set to 32031333
Phenotypes for gene: CDC42BPB were set to Central hypotonia; Global developmental delay; Intellectual disability; Seizures; Autistic behavior; Behavioral abnormality
Penetrance for gene: CDC42BPB were set to unknown
Review for gene: CDC42BPB was set to AMBER
Added comment: Chilton et al (2020 - PMID: 32031333) report on 14 individuals with missense and loss-of-function CDC42BPB variants.

Features included hypotonia (8/11), DD (12/13 - the 14th was a fetus), ID (7/13), ASD (8/12), clinical seizures (in 3 - a 4th had abnormal EEG without seizures), behavioral abnormalities. Variable non-specific dysmorphic features were reported in some (sparse hair being the most frequent - 4/8). Additional features were observed in few (=<4) incl. cryptorchidism, ophthalmological issues, constipation, kidney abnormalities, micropenis, etc.

All individuals had non-diagnostic prior genetic testing (incl. CMA, FMR1, MECP2, Angelman/Prader-Willi methylation studies, autism gene panel - suggesting relevance to the current panel) or metabolic testing.

Variants were identified following clinical exome sequencing with Sanger confirmation. Most occurred as de novo events (11/14) while inheritance was not available for few (3/14). Missense variants did not display (particular) clustering.

Almost all variants were absent from gnomAD and were predicted to be deleterious in silico (among others almost all had CADD scores >25).

As the authors comment, CDC42BPB encodes myotonic dystrophy-related Cdc42-binding kinase β (MRCKβ) a serine/threonine protein kinase playing a role in regulation of cytoskeletal reorganization and cell migration in nonmuscle cells (through phosporylation of MLC2).

Previous studies have demonstrated that it is ubiquitously expressed with prenatal brain expression.

The gene appears to be intolerant to pLoF (pLI of 1) as well as to missense variants (Z-score of 3.66).

CDC42BPB is a downstream effector of CDC42. Mutations of the latter cause Takenouchi-Kosaki syndrome with DD/ID and some further overlapping features (with CDC42BPB-associated phenotypes).

Homozygous Cdc42bpb KO in mouse appears to be nonviable (MGI:2136459). Loss of gek in the eyes of Drosophila results in disrupted growth cone targeting to the lamina (gek is the fly CDC42BPB ortholog).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2619 CDC42BPB Konstantinos Varvagiannis gene: CDC42BPB was added
gene: CDC42BPB was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CDC42BPB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CDC42BPB were set to 32031333
Phenotypes for gene: CDC42BPB were set to Central hypotonia; Global developmental delay; Intellectual disability; Seizures; Autistic behavior; Behavioral abnormality
Penetrance for gene: CDC42BPB were set to unknown
Review for gene: CDC42BPB was set to GREEN
Added comment: Chilton et al (2020 - PMID: 32031333) report on 14 individuals with missense and loss-of-function CDC42BPB variants.

Features included hypotonia (8/11), DD (12/13 - the 14th was a fetus), ID (7/13), ASD (8/12), clinical seizures (in 3 - a 4th had abnormal EEG without seizures), behavioral abnormalities. Variable non-specific dysmorphic features were reported in some (sparse hair being the most frequent - 4/8). Additional features were observed in few (=<4) incl. cryptorchidism, ophthalmological issues, constipation, kidney abnormalities, micropenis, etc.

All individuals had non-diagnostic prior genetic testing (incl. CMA, FMR1, MECP2, Angelman/Prader-Willi methylation studies, autism gene panel - suggesting relevance to the current panel) or metabolic testing.

Variants were identified following clinical exome sequencing with Sanger confirmation. Most occurred as de novo events (11/14) while inheritance was not available for few (3/14). Missense variants did not display (particular) clustering.

Almost all variants were absent from gnomAD and were predicted to be deleterious in silico (among others almost all had CADD scores >25).

As the authors comment, CDC42BPB encodes myotonic dystrophy-related Cdc42-binding kinase β (MRCKβ) a serine/threonine protein kinase playing a role in regulation of cytoskeletal reorganization and cell migration in nonmuscle cells (through phosporylation of MLC2).

Previous studies have demonstrated that it is ubiquitously expressed with prenatal brain expression.

The gene appears to be intolerant to pLoF (pLI of 1) as well as to missense variants (Z-score of 3.66).

CDC42BPB is a downstream effector of CDC42. Mutations of the latter cause Takenouchi-Kosaki syndrome with DD/ID and some further overlapping features (with CDC42BPB-associated phenotypes).

Homozygous Cdc42bpb KO in mouse appears to be nonviable (MGI:2136459). Loss of gek in the eyes of Drosophila results in disrupted growth cone targeting to the lamina (gek is the fly CDC42BPB ortholog).

Please consider inclusion with amber / green rating in the ID panel (>=4 relevant individuals / variants) and other panels (e.g. for epilepsy, ASD).
Sources: Literature
Ciliopathies v0.131 ACVR2B Zornitza Stark Marked gene: ACVR2B as ready
Ciliopathies v0.131 ACVR2B Zornitza Stark Gene: acvr2b has been classified as Red List (Low Evidence).
Ciliary Dyskinesia v0.68 ARMC4 Zornitza Stark Marked gene: ARMC4 as ready
Ciliary Dyskinesia v0.68 ARMC4 Zornitza Stark Gene: armc4 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.68 RSPH3 Zornitza Stark Marked gene: RSPH3 as ready
Ciliary Dyskinesia v0.68 RSPH3 Zornitza Stark Gene: rsph3 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.68 RSPH3 Zornitza Stark Phenotypes for gene: RSPH3 were changed from Ciliary dyskinesia, primary, 32 (MIM#616481) to Ciliary dyskinesia, primary, 32 (MIM#616481)
Heterotaxy v0.36 GDF1 Zornitza Stark Marked gene: GDF1 as ready
Heterotaxy v0.36 GDF1 Zornitza Stark Gene: gdf1 has been classified as Green List (High Evidence).
Heterotaxy v0.36 GDF1 Zornitza Stark Classified gene: GDF1 as Green List (high evidence)
Heterotaxy v0.36 GDF1 Zornitza Stark Gene: gdf1 has been classified as Green List (High Evidence).
Heterotaxy v0.35 GDF1 Zornitza Stark gene: GDF1 was added
gene: GDF1 was added to Heterotaxy. Sources: Expert list
Mode of inheritance for gene: GDF1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: GDF1 were set to 32144877
Phenotypes for gene: GDF1 were set to Congenital heart defects, multiple types, 6 613854; Right atrial isomerism (Ivemark) 208530
Review for gene: GDF1 was set to GREEN
Added comment: PMID: 32144877 - founder PTC in Arab population causing congenital heart detects AND right isomerism in 3 (unrelated?) families. Reviews other publications and reports additional chet (two PTC) or homozygous (missense) families with situs inversus and/or heart defects. No apparent genotype-phenotype correlation btw dominant and recessive disease.
Sources: Expert list
Ciliopathies v0.131 GDF1 Zornitza Stark Marked gene: GDF1 as ready
Ciliopathies v0.131 GDF1 Zornitza Stark Added comment: Comment when marking as ready: Agree, this gene belongs on the Heterotaxy panel.
Ciliopathies v0.131 GDF1 Zornitza Stark Gene: gdf1 has been classified as Red List (Low Evidence).
Ciliopathies v0.131 GDF1 Zornitza Stark Phenotypes for gene: GDF1 were changed from Congenital heart defects, multiple types, 6 613854; Right atrial isomerism (Ivemark) 208530 to Congenital heart defects, multiple types, 6 613854; Right atrial isomerism (Ivemark) 208530
Ciliopathies v0.131 GDF1 Zornitza Stark Phenotypes for gene: GDF1 were changed from to Congenital heart defects, multiple types, 6 613854; Right atrial isomerism (Ivemark) 208530
Ciliary Dyskinesia v0.67 RSPH3 Zornitza Stark Phenotypes for gene: RSPH3 were changed from to Ciliary dyskinesia, primary, 32 (MIM#616481)
Ciliary Dyskinesia v0.66 RSPH3 Zornitza Stark Publications for gene: RSPH3 were set to
Ciliopathies v0.130 GDF1 Zornitza Stark Publications for gene: GDF1 were set to
Ciliopathies v0.129 GDF1 Zornitza Stark Mode of inheritance for gene: GDF1 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Ciliary Dyskinesia v0.65 RSPH3 Zornitza Stark Mode of inheritance for gene: RSPH3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v0.128 GDF1 Zornitza Stark Classified gene: GDF1 as Red List (low evidence)
Ciliopathies v0.128 GDF1 Zornitza Stark Gene: gdf1 has been classified as Red List (Low Evidence).
Ciliary Dyskinesia v0.64 RSPH4A Zornitza Stark Marked gene: RSPH4A as ready
Ciliary Dyskinesia v0.64 RSPH4A Zornitza Stark Gene: rsph4a has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.64 RSPH4A Zornitza Stark Phenotypes for gene: RSPH4A were changed from to Ciliary dyskinesia, primary, 11 (MIM#612649)
Ciliary Dyskinesia v0.63 RSPH4A Zornitza Stark Publications for gene: RSPH4A were set to 25789548; 22448264
Ciliary Dyskinesia v0.63 RSPH4A Zornitza Stark Publications for gene: RSPH4A were set to
Ciliary Dyskinesia v0.62 RSPH4A Zornitza Stark Mode of inheritance for gene: RSPH4A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2757 DNAJB13 Zornitza Stark Marked gene: DNAJB13 as ready
Mendeliome v0.2757 DNAJB13 Zornitza Stark Gene: dnajb13 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2757 DNAJB13 Zornitza Stark Phenotypes for gene: DNAJB13 were changed from to Ciliary dyskinesia, primary, 34, MIM# 617091
Mendeliome v0.2756 DNAJB13 Zornitza Stark Publications for gene: DNAJB13 were set to
Mendeliome v0.2755 DNAJB13 Zornitza Stark Mode of inheritance for gene: DNAJB13 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2754 DNAJB13 Zornitza Stark Classified gene: DNAJB13 as Amber List (moderate evidence)
Mendeliome v0.2754 DNAJB13 Zornitza Stark Gene: dnajb13 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2753 DNAJB13 Zornitza Stark reviewed gene: DNAJB13: Rating: AMBER; Mode of pathogenicity: None; Publications: 27486783; Phenotypes: Ciliary dyskinesia, primary, 34, MIM# 617091; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.34 DNAJB13 Zornitza Stark Marked gene: DNAJB13 as ready
Heterotaxy v0.34 DNAJB13 Zornitza Stark Gene: dnajb13 has been classified as Red List (Low Evidence).
Heterotaxy v0.34 DNAJB13 Zornitza Stark Phenotypes for gene: DNAJB13 were changed from to Ciliary dyskinesia, primary, 34, MIM# 617091
Heterotaxy v0.33 DNAJB13 Zornitza Stark Publications for gene: DNAJB13 were set to
Heterotaxy v0.32 DNAJB13 Zornitza Stark Mode of inheritance for gene: DNAJB13 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.31 DNAJB13 Zornitza Stark Classified gene: DNAJB13 as Red List (low evidence)
Heterotaxy v0.31 DNAJB13 Zornitza Stark Gene: dnajb13 has been classified as Red List (Low Evidence).
Heterotaxy v0.30 DNAJB13 Zornitza Stark reviewed gene: DNAJB13: Rating: RED; Mode of pathogenicity: None; Publications: 27486783; Phenotypes: Ciliary dyskinesia, primary, 34 617091; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.61 DNAJB13 Zornitza Stark Marked gene: DNAJB13 as ready
Ciliary Dyskinesia v0.61 DNAJB13 Zornitza Stark Gene: dnajb13 has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v0.61 DNAJB13 Zornitza Stark Classified gene: DNAJB13 as Amber List (moderate evidence)
Ciliary Dyskinesia v0.61 DNAJB13 Zornitza Stark Gene: dnajb13 has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v0.60 DNAH1 Zornitza Stark Marked gene: DNAH1 as ready
Ciliary Dyskinesia v0.60 DNAH1 Zornitza Stark Gene: dnah1 has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v0.60 DNAH1 Zornitza Stark Phenotypes for gene: DNAH1 were changed from to ?Ciliary dyskinesia, primary, 37 617577; Spermatogenic failure 18 617576
Ciliary Dyskinesia v0.59 DNAH1 Zornitza Stark Publications for gene: DNAH1 were set to
Ciliary Dyskinesia v0.58 DNAH1 Zornitza Stark Mode of inheritance for gene: DNAH1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.57 DNAH1 Zornitza Stark Classified gene: DNAH1 as Amber List (moderate evidence)
Ciliary Dyskinesia v0.57 DNAH1 Zornitza Stark Gene: dnah1 has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v0.56 RSPH9 Zornitza Stark Marked gene: RSPH9 as ready
Ciliary Dyskinesia v0.56 RSPH9 Zornitza Stark Gene: rsph9 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.56 RSPH9 Zornitza Stark Phenotypes for gene: RSPH9 were changed from to Ciliary dyskinesia, primary, 12 (MIM#612650)
Ciliary Dyskinesia v0.55 RSPH9 Zornitza Stark Publications for gene: RSPH9 were set to
Ciliary Dyskinesia v0.54 RSPH9 Zornitza Stark Mode of inheritance for gene: RSPH9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.30 ZIC3 Zornitza Stark Marked gene: ZIC3 as ready
Heterotaxy v0.30 ZIC3 Zornitza Stark Gene: zic3 has been classified as Green List (High Evidence).
Heterotaxy v0.30 ZIC3 Zornitza Stark Classified gene: ZIC3 as Green List (high evidence)
Heterotaxy v0.30 ZIC3 Zornitza Stark Gene: zic3 has been classified as Green List (High Evidence).
Ciliopathies v0.127 ZIC3 Zornitza Stark Marked gene: ZIC3 as ready
Ciliopathies v0.127 ZIC3 Zornitza Stark Gene: zic3 has been classified as Red List (Low Evidence).
Ciliopathies v0.127 ZIC3 Zornitza Stark Phenotypes for gene: ZIC3 were changed from to Heterotaxy, visceral, 1, X-linked (MIM#306955)
Ciliopathies v0.126 ZIC3 Zornitza Stark Publications for gene: ZIC3 were set to
Ciliopathies v0.125 ZIC3 Zornitza Stark Mode of inheritance for gene: ZIC3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Ciliopathies v0.124 ZIC3 Zornitza Stark Classified gene: ZIC3 as Red List (low evidence)
Ciliopathies v0.124 ZIC3 Zornitza Stark Gene: zic3 has been classified as Red List (Low Evidence).
Ciliopathies v0.123 ZIC3 Zornitza Stark reviewed gene: ZIC3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital heart defects, nonsyndromic, 1, X-linked (MIM#306955), Heterotaxy, visceral, 1, X-linked (MIM#306955); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Heterotaxy v0.29 CRELD1 Zornitza Stark Marked gene: CRELD1 as ready
Heterotaxy v0.29 CRELD1 Zornitza Stark Gene: creld1 has been classified as Green List (High Evidence).
Heterotaxy v0.29 CRELD1 Zornitza Stark Classified gene: CRELD1 as Green List (high evidence)
Heterotaxy v0.29 CRELD1 Zornitza Stark Gene: creld1 has been classified as Green List (High Evidence).
Heterotaxy v0.28 CRELD1 Zornitza Stark gene: CRELD1 was added
gene: CRELD1 was added to Heterotaxy. Sources: Expert list
Mode of inheritance for gene: CRELD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CRELD1 were set to 22740159
Phenotypes for gene: CRELD1 were set to Atrioventricular septal defect, partial, with heterotaxy syndrome 606217
Review for gene: CRELD1 was set to GREEN
Added comment: Three families reported with heterozygous missense variants and heterotaxy phenotype.
Sources: Expert list
Ciliopathies v0.123 CRELD1 Zornitza Stark Marked gene: CRELD1 as ready
Ciliopathies v0.123 CRELD1 Zornitza Stark Gene: creld1 has been classified as Red List (Low Evidence).
Ciliopathies v0.123 CRELD1 Zornitza Stark Phenotypes for gene: CRELD1 were changed from to Atrioventricular septal defect, partial, with heterotaxy syndrome 606217
Ciliopathies v0.122 CRELD1 Zornitza Stark Publications for gene: CRELD1 were set to
Ciliopathies v0.121 CRELD1 Zornitza Stark Mode of inheritance for gene: CRELD1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ciliopathies v0.120 CRELD1 Zornitza Stark Classified gene: CRELD1 as Red List (low evidence)
Ciliopathies v0.120 CRELD1 Zornitza Stark Gene: creld1 has been classified as Red List (Low Evidence).
Mendeliome v0.2753 CFC1 Zornitza Stark Marked gene: CFC1 as ready
Mendeliome v0.2753 CFC1 Zornitza Stark Gene: cfc1 has been classified as Green List (High Evidence).
Mendeliome v0.2753 CFC1 Zornitza Stark Phenotypes for gene: CFC1 were changed from to Heterotaxy, visceral, 2, autosomal 605376
Mendeliome v0.2752 CFC1 Zornitza Stark Publications for gene: CFC1 were set to
Mendeliome v0.2751 CFC1 Zornitza Stark Mode of inheritance for gene: CFC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Heterotaxy v0.27 CFC1 Zornitza Stark Marked gene: CFC1 as ready
Heterotaxy v0.27 CFC1 Zornitza Stark Gene: cfc1 has been classified as Green List (High Evidence).
Mendeliome v0.2750 CFC1 Zornitza Stark reviewed gene: CFC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31633655, 18162845, 25423076, 11062482; Phenotypes: Heterotaxy, visceral, 2, autosomal 605376; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Heterotaxy v0.27 CFC1 Zornitza Stark Classified gene: CFC1 as Green List (high evidence)
Heterotaxy v0.27 CFC1 Zornitza Stark Gene: cfc1 has been classified as Green List (High Evidence).
Heterotaxy v0.26 CFC1 Zornitza Stark gene: CFC1 was added
gene: CFC1 was added to Heterotaxy. Sources: Expert list
Mode of inheritance for gene: CFC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CFC1 were set to 31633655; 18162845; 25423076; 11062482
Phenotypes for gene: CFC1 were set to Heterotaxy, visceral, 2, autosomal 605376
Review for gene: CFC1 was set to GREEN
Added comment: PMID: 31633655 - 1 patient with a heterozygous missense, paternally inherited. The proband has situs inversus with biliary atresia, while the father did not have biliary atresia but DID have situs inversus PMID: 18162845 - recurring missense (p.Ala145Thr) reported in 5 patients with biliary atresia splenic malformation syndrome. Authors conclude the variant may not be completely causative but create a predisposition to the syndrome. This variant has 145 hets in the population (gnomAD) but with strong strand bias - may not be real. PMID: 25423076 - 8 patients reported with heterotaxy and CNVs resulting in the deletion of CFC1. Clear breakpoints not mentioned, but CNVs are suggestive to be multigenic. PMID: 11062482 - 9 heterozygous patients with mostly missense but also one PTC. Null zebrafish model recapitulate the mutant phenotype, could not be rescued by 2 mutant mRNA.
Sources: Expert list
Ciliopathies v0.119 CFC1 Zornitza Stark Marked gene: CFC1 as ready
Ciliopathies v0.119 CFC1 Zornitza Stark Gene: cfc1 has been classified as Red List (Low Evidence).
Ciliopathies v0.119 CFC1 Zornitza Stark Phenotypes for gene: CFC1 were changed from to Heterotaxy, visceral, 2, autosomal 605376
Ciliopathies v0.118 CFC1 Zornitza Stark Publications for gene: CFC1 were set to
Ciliopathies v0.117 CFC1 Zornitza Stark Mode of inheritance for gene: CFC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ciliopathies v0.116 CFC1 Zornitza Stark Classified gene: CFC1 as Red List (low evidence)
Ciliopathies v0.116 CFC1 Zornitza Stark Gene: cfc1 has been classified as Red List (Low Evidence).
Ciliary Dyskinesia v0.53 SCNN1G Zornitza Stark Marked gene: SCNN1G as ready
Ciliary Dyskinesia v0.53 SCNN1G Zornitza Stark Gene: scnn1g has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.53 SCNN1G Zornitza Stark Classified gene: SCNN1G as Green List (high evidence)
Ciliary Dyskinesia v0.53 SCNN1G Zornitza Stark Gene: scnn1g has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.52 SCNN1G Zornitza Stark gene: SCNN1G was added
gene: SCNN1G was added to Ciliary Dyskinesia. Sources: Expert list
Mode of inheritance for gene: SCNN1G was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SCNN1G were set to Bronchiectasis with or without elevated sweat chloride 3, MIM# 613071
Review for gene: SCNN1G was set to GREEN
Added comment: Phenotypic overlap with PCD.
Sources: Expert list
Ciliopathies v0.115 SCNN1G Zornitza Stark Marked gene: SCNN1G as ready
Ciliopathies v0.115 SCNN1G Zornitza Stark Gene: scnn1g has been classified as Red List (Low Evidence).
Ciliopathies v0.115 SCNN1G Zornitza Stark edited their review of gene: SCNN1G: Changed phenotypes: Bronchiectasis with or without elevated sweat chloride 3 (MIM#613071)
Ciliopathies v0.115 SCNN1G Zornitza Stark reviewed gene: SCNN1G: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Ciliopathies v0.115 SCNN1G Zornitza Stark Classified gene: SCNN1G as Red List (low evidence)
Ciliopathies v0.115 SCNN1G Zornitza Stark Gene: scnn1g has been classified as Red List (Low Evidence).
Ciliopathies v0.114 SCNN1G Zornitza Stark Classified gene: SCNN1G as Amber List (moderate evidence)
Ciliopathies v0.114 SCNN1G Zornitza Stark Gene: scnn1g has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v0.51 SPAG1 Zornitza Stark Marked gene: SPAG1 as ready
Ciliary Dyskinesia v0.51 SPAG1 Zornitza Stark Gene: spag1 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.51 SPAG1 Zornitza Stark Phenotypes for gene: SPAG1 were changed from to Ciliary dyskinesia, primary, 28 (MIM#615505)
Ciliary Dyskinesia v0.50 SPAG1 Zornitza Stark Publications for gene: SPAG1 were set to
Ciliary Dyskinesia v0.49 SPAG1 Zornitza Stark Mode of inheritance for gene: SPAG1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v0.113 PMM2 Zornitza Stark Marked gene: PMM2 as ready
Ciliopathies v0.113 PMM2 Zornitza Stark Gene: pmm2 has been classified as Red List (Low Evidence).
Ciliopathies v0.113 PMM2 Zornitza Stark Classified gene: PMM2 as Red List (low evidence)
Ciliopathies v0.113 PMM2 Zornitza Stark Gene: pmm2 has been classified as Red List (Low Evidence).
Ciliopathies v0.112 PMM2 Zornitza Stark reviewed gene: PMM2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type Ia (MIM#212065); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v0.112 PRKCSH Zornitza Stark Marked gene: PRKCSH as ready
Ciliopathies v0.112 PRKCSH Zornitza Stark Added comment: Comment when marking as ready: Potential phenotypic overlap with ciliopathies.
Ciliopathies v0.112 PRKCSH Zornitza Stark Gene: prkcsh has been classified as Amber List (Moderate Evidence).
Ciliopathies v0.112 PRKCSH Zornitza Stark Phenotypes for gene: PRKCSH were changed from to Polycystic liver disease 1 (MIM#174050)
Ciliopathies v0.111 PRKCSH Zornitza Stark Publications for gene: PRKCSH were set to 19876928
Ciliopathies v0.111 PRKCSH Zornitza Stark Publications for gene: PRKCSH were set to 19876928
Ciliopathies v0.111 PRKCSH Zornitza Stark Publications for gene: PRKCSH were set to
Ciliopathies v0.110 PRKCSH Zornitza Stark Mode of pathogenicity for gene: PRKCSH was changed from to Other
Ciliopathies v0.109 PRKCSH Zornitza Stark Mode of inheritance for gene: PRKCSH was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ciliopathies v0.108 PRKCSH Zornitza Stark Classified gene: PRKCSH as Amber List (moderate evidence)
Ciliopathies v0.108 PRKCSH Zornitza Stark Gene: prkcsh has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2750 CFAP53 Zornitza Stark Marked gene: CFAP53 as ready
Mendeliome v0.2750 CFAP53 Zornitza Stark Gene: cfap53 has been classified as Green List (High Evidence).
Mendeliome v0.2750 CFAP53 Zornitza Stark Phenotypes for gene: CFAP53 were changed from to Heterotaxy, visceral, 6, autosomal recessive 614779
Mendeliome v0.2749 CFAP53 Zornitza Stark Publications for gene: CFAP53 were set to
Mendeliome v0.2748 CFAP53 Zornitza Stark Mode of inheritance for gene: CFAP53 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2747 CFAP53 Zornitza Stark reviewed gene: CFAP53: Rating: GREEN; Mode of pathogenicity: None; Publications: 28621423, 22577226, 26531781; Phenotypes: Heterotaxy, visceral, 6, autosomal recessive 614779; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.48 CFAP53 Zornitza Stark Marked gene: CFAP53 as ready
Ciliary Dyskinesia v0.48 CFAP53 Zornitza Stark Gene: cfap53 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.48 CFAP53 Zornitza Stark Classified gene: CFAP53 as Green List (high evidence)
Ciliary Dyskinesia v0.48 CFAP53 Zornitza Stark Gene: cfap53 has been classified as Green List (High Evidence).
Ciliopathies v0.107 CFAP53 Zornitza Stark Marked gene: CFAP53 as ready
Ciliopathies v0.107 CFAP53 Zornitza Stark Gene: cfap53 has been classified as Red List (Low Evidence).
Ciliopathies v0.107 CFAP53 Zornitza Stark Phenotypes for gene: CFAP53 were changed from to Heterotaxy, visceral, 6, autosomal recessive 614779
Ciliopathies v0.106 CFAP53 Zornitza Stark Publications for gene: CFAP53 were set to
Ciliopathies v0.105 CFAP53 Zornitza Stark Mode of inheritance for gene: CFAP53 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v0.104 CFAP53 Zornitza Stark Classified gene: CFAP53 as Red List (low evidence)
Ciliopathies v0.104 CFAP53 Zornitza Stark Gene: cfap53 has been classified as Red List (Low Evidence).
Mendeliome v0.2747 TTC25 Zornitza Stark Marked gene: TTC25 as ready
Mendeliome v0.2747 TTC25 Zornitza Stark Gene: ttc25 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2747 TTC25 Zornitza Stark Phenotypes for gene: TTC25 were changed from to Ciliary dyskinesia, primary, 35 (MIM#617092)
Mendeliome v0.2746 TTC25 Zornitza Stark Publications for gene: TTC25 were set to
Mendeliome v0.2745 TTC25 Zornitza Stark Mode of inheritance for gene: TTC25 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2744 TTC25 Zornitza Stark Classified gene: TTC25 as Amber List (moderate evidence)
Mendeliome v0.2744 TTC25 Zornitza Stark Gene: ttc25 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2743 TTC25 Zornitza Stark reviewed gene: TTC25: Rating: AMBER; Mode of pathogenicity: None; Publications: 27486780; Phenotypes: Ciliary dyskinesia, primary, 35 (MIM#617092); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.25 TTC25 Zornitza Stark Marked gene: TTC25 as ready
Heterotaxy v0.25 TTC25 Zornitza Stark Gene: ttc25 has been classified as Amber List (Moderate Evidence).
Heterotaxy v0.25 TTC25 Zornitza Stark Phenotypes for gene: TTC25 were changed from to Ciliary dyskinesia, primary, 35 (MIM#617092)
Heterotaxy v0.24 TTC25 Zornitza Stark Publications for gene: TTC25 were set to
Heterotaxy v0.23 TTC25 Zornitza Stark Mode of inheritance for gene: TTC25 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.22 TTC25 Zornitza Stark Classified gene: TTC25 as Amber List (moderate evidence)
Heterotaxy v0.22 TTC25 Zornitza Stark Gene: ttc25 has been classified as Amber List (Moderate Evidence).
Heterotaxy v0.21 TTC25 Zornitza Stark reviewed gene: TTC25: Rating: AMBER; Mode of pathogenicity: None; Publications: 27486780; Phenotypes: Ciliary dyskinesia, primary, 35 (MIM#617092); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.47 TTC25 Zornitza Stark Marked gene: TTC25 as ready
Ciliary Dyskinesia v0.47 TTC25 Zornitza Stark Gene: ttc25 has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v0.47 TTC25 Zornitza Stark Classified gene: TTC25 as Amber List (moderate evidence)
Ciliary Dyskinesia v0.47 TTC25 Zornitza Stark Gene: ttc25 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2743 CFAP43 Zornitza Stark Marked gene: CFAP43 as ready
Mendeliome v0.2743 CFAP43 Zornitza Stark Added comment: Comment when marking as ready: Good evidence for bi-allelic disease, much less so for mono-allelic.
Mendeliome v0.2743 CFAP43 Zornitza Stark Gene: cfap43 has been classified as Green List (High Evidence).
Mendeliome v0.2743 CFAP43 Zornitza Stark Classified gene: CFAP43 as Green List (high evidence)
Mendeliome v0.2743 CFAP43 Zornitza Stark Gene: cfap43 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.46 CFAP43 Zornitza Stark Marked gene: CFAP43 as ready
Ciliary Dyskinesia v0.46 CFAP43 Zornitza Stark Added comment: Comment when marking as ready: Good evidence for bi-allelic disease, much less so for mono allelic.
Ciliary Dyskinesia v0.46 CFAP43 Zornitza Stark Gene: cfap43 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.46 CFAP43 Zornitza Stark Classified gene: CFAP43 as Green List (high evidence)
Ciliary Dyskinesia v0.46 CFAP43 Zornitza Stark Gene: cfap43 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.45 RSPH3 Crystle Lee reviewed gene: RSPH3: Rating: GREEN; Mode of pathogenicity: None; Publications: 26073779; Phenotypes: Ciliary dyskinesia, primary, 32 (MIM#616481); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v0.103 GDF1 Elena Savva reviewed gene: GDF1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 32144877; Phenotypes: Congenital heart defects, multiple types, 6 613854, Right atrial isomerism (Ivemark) 208530; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Ciliary Dyskinesia v0.45 RSPH4A Crystle Lee reviewed gene: RSPH4A: Rating: GREEN; Mode of pathogenicity: None; Publications: 25789548, 22448264; Phenotypes: Ciliary dyskinesia, primary, 11 (MIM#612649); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.45 DNAJB13 Elena Savva gene: DNAJB13 was added
gene: DNAJB13 was added to Ciliary Dyskinesia. Sources: Literature
Mode of inheritance for gene: DNAJB13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAJB13 were set to PMID:27486783
Phenotypes for gene: DNAJB13 were set to Ciliary dyskinesia, primary, 34 617091
Review for gene: DNAJB13 was set to AMBER
Added comment: PMID: 27486783 - 2 unrelated families (missense, splice). One family hadsinopulmonary syndrome and TEM of nasal cells shows a reduction in cilia. Of remaining cilia, there was a reduction in motility. Functional studies of missense shows increased protein instability and degradation -> protein is absent from patient cilia.

Summary: 2 unrelated families. Functional studies prove LOF but no animal models to make it green in this list
Sources: Literature
Ciliary Dyskinesia v0.45 DNAH1 Elena Savva reviewed gene: DNAH1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 31507630, 31765523, 25927852, 24360805; Phenotypes: ?Ciliary dyskinesia, primary, 37 617577, Spermatogenic failure 18 617576; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.45 RSPH9 Crystle Lee reviewed gene: RSPH9: Rating: GREEN; Mode of pathogenicity: None; Publications: 25789548, 31285900; Phenotypes: Ciliary dyskinesia, primary, 12 (MIM#612650); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.45 RSPH9 Crystle Lee Deleted their review
Ciliary Dyskinesia v0.45 RSPH9 Crystle Lee reviewed gene: RSPH9: Rating: GREEN; Mode of pathogenicity: None; Publications: 23993197; Phenotypes: Ciliary dyskinesia, primary, 12 (MIM#612650); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.21 ZIC3 Crystle Lee gene: ZIC3 was added
gene: ZIC3 was added to Heterotaxy. Sources: Expert Review
Mode of inheritance for gene: ZIC3 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: ZIC3 were set to 27406248; 30120289
Phenotypes for gene: ZIC3 were set to Heterotaxy, visceral, 1, X-linked (MIM#306955)
Review for gene: ZIC3 was set to GREEN
Added comment: Pathogenic loss of function variants reported in >5 patients with heterotaxy

PMID: 27406248; Paulussen 2016: Reported 6 pathogenic variants in a cohort of patients with congenital heart disease including heterotaxy and reviewed previously published cases. Functional studies performed confirming LoF mechanism. Classified inframe dups within polyA region as VUS.

PMID: 30120289; Li 2018: 1 additional hemi missense reported in a male patients inherited from carrier mother.
Sources: Expert Review
Ciliopathies v0.103 ZIC3 Crystle Lee reviewed gene: ZIC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 27406248, 20452998; Phenotypes: Congenital heart defects, nonsyndromic, 1, X-linked (MIM#306955), Heterotaxy, visceral, 1, X-linked (MIM#306955); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Ciliopathies v0.103 CRELD1 Elena Savva reviewed gene: CRELD1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 22740159; Phenotypes: {Atrioventricular septal defect, susceptibility to, 2} 606217, Atrioventricular septal defect, partial, with heterotaxy syndrome 606217; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Ciliopathies v0.103 CFC1 Elena Savva reviewed gene: CFC1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 31633655, 18162845, 25423076, 11062482; Phenotypes: Heterotaxy, visceral, 2, autosomal 605376; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Ciliopathies v0.103 SCNN1G Crystle Lee gene: SCNN1G was added
gene: SCNN1G was added to Ciliopathies. Sources: Expert Review
Mode of inheritance for gene: SCNN1G was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SCNN1G were set to 22207244; 31655555; 30801930; 28484659
Phenotypes for gene: SCNN1G were set to Bronchiectasis with or without elevated sweat chloride 3 (MIM#613071); Liddle syndrome 2 (MIM#618114); Pseudohypoaldosteronism, type I (MIM#264350)
Review for gene: SCNN1G was set to AMBER
Added comment: Encodes for the gamma subunit of the epithelial sodium channel, which is distributed along the motile cilia. (PMID: 22207244). Respiratory problems is a feature of pseudohypoaldosteronism Type I. Minimal reports to date.

Kozina 2019; PMID: 31655555: Reported one family and reviewed 6 other families with het truncating variants in SCNN1G causing Liddle syndrome. Unsure if features resemble ciliopathies

Bush 2019; PMID: 30801930; ENaC mutations, especially in-trans with a CFTR mutation, are thought to be risk factors for bronchiectasis, rather than actually causative

Nur 2017; PMID: 28484659; Review of PHA1. 2 patients reported with biallelic LoF type variants in SCNN1G.
Sources: Expert Review
Ciliary Dyskinesia v0.45 SPAG1 Crystle Lee reviewed gene: SPAG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24055112; Phenotypes: Ciliary dyskinesia, primary, 28 (MIM#615505); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v0.103 PMM2 Crystle Lee gene: PMM2 was added
gene: PMM2 was added to Ciliopathies. Sources: Expert Review
Mode of inheritance for gene: PMM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PMM2 were set to 28108845
Phenotypes for gene: PMM2 were set to Congenital disorder of glycosylation, type Ia (MIM#212065)
Review for gene: PMM2 was set to AMBER
Added comment: Encodes for phosphomannomutase 2 required for glycosylation. Not a ciliopathy gene however CDG has many overlapping features with ciliopathy. Left as Amber.

PMID: 28108845: Review article. Well reported gene causing CDG. >700 patients reported

PMID: 25497157; Many patients reported. Similar features as ciliopathies
Sources: Expert Review
Ciliopathies v0.103 PRKCSH Crystle Lee reviewed gene: PRKCSH: Rating: AMBER; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 19876928; Phenotypes: Polycystic liver disease 1 (MIM#174050); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Ciliary Dyskinesia v0.45 CFAP53 Elena Savva gene: CFAP53 was added
gene: CFAP53 was added to Ciliary Dyskinesia. Sources: Literature
Mode of inheritance for gene: CFAP53 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFAP53 were set to PMID:28621423; 22577226; 26531781
Phenotypes for gene: CFAP53 were set to Heterotaxy, visceral, 6, autosomal recessive 614779
Review for gene: CFAP53 was set to GREEN
Added comment: aka CCDC11

PMID: 22577226 - 2 siblings with a homozygous splice variant. One sibling had situs invertus syndrome and the other heterotaxy. One sibling far less severely affected. Patients had normal beating cilia, no respiratory issues

PMID: 28621423 - no new patients, performs functional studies on patient cells from ^, and frog animal models. Assays demonstrate mislocalized protein, increased cilia length in patient samples, while animal models showed CFAP53/CCDC11 is important for left-right patterning.

PMID: 26531781 - 1 patient with a homozygous PTC with situs inversus. Respiratory function was described as normal. Zebrafish model recapitulates the human phenotype.

Summary: 2 patients described with primary cilia dyskinesia conditions + animal models
Sources: Literature
Ciliopathies v0.103 CFAP53 Elena Savva reviewed gene: CFAP53: Rating: RED; Mode of pathogenicity: None; Publications: PMID:28621423, 22577226, 26531781; Phenotypes: Heterotaxy, visceral, 6, autosomal recessive 614779; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.45 TTC25 Crystle Lee gene: TTC25 was added
gene: TTC25 was added to Ciliary Dyskinesia. Sources: Expert Review
Mode of inheritance for gene: TTC25 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTC25 were set to 27486780
Phenotypes for gene: TTC25 were set to Ciliary dyskinesia, primary, 35 (MIM#617092)
Review for gene: TTC25 was set to AMBER
Added comment: 2 families reported with PCD. Mouse model showed immotile nodal cilia. Left as amber for now.

Gene ncodes a component of the outer dynein arm required to develop the main mechanical force to generate ciliary beats
(Gene is non coding in gnomad v2 and coding in v3)
Sources: Expert Review
Mendeliome v0.2742 CFAP43 Elena Savva gene: CFAP43 was added
gene: CFAP43 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CFAP43 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: CFAP43 were set to PMID: 31884020; 28552195; 31004071; 29449551
Phenotypes for gene: CFAP43 were set to Hydrocephalus, normal pressure, 1 236690; Spermatogenic failure 19 617592
Added comment: aka WDR96

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

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

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

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

Summary: single report of AD hydrocephaly
Sources: Literature
Ciliary Dyskinesia v0.45 CFAP43 Elena Savva gene: CFAP43 was added
gene: CFAP43 was added to Ciliary Dyskinesia. Sources: Expert Review
Mode of inheritance for gene: CFAP43 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: CFAP43 were set to PMID: 31884020; 28552195; 31004071; 29449551
Phenotypes for gene: CFAP43 were set to Hydrocephalus, normal pressure, 1 236690; Spermatogenic failure 19 617592
Review for gene: CFAP43 was set to GREEN
Added comment: aka WDR96

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

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

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

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

Summary: single report of AD hydrocephaly
Sources: Expert Review
Leukodystrophy v0.112 HEPACAM Zornitza Stark Marked gene: HEPACAM as ready
Leukodystrophy v0.112 HEPACAM Zornitza Stark Gene: hepacam has been classified as Green List (High Evidence).
Leukodystrophy v0.112 HEPACAM Zornitza Stark Classified gene: HEPACAM as Green List (high evidence)
Leukodystrophy v0.112 HEPACAM Zornitza Stark Gene: hepacam has been classified as Green List (High Evidence).
Leukodystrophy v0.111 HEPACAM Zornitza Stark gene: HEPACAM was added
gene: HEPACAM was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: HEPACAM was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: HEPACAM were set to 21419380; 21419380
Phenotypes for gene: HEPACAM were set to Megalencephalic leukoencephalopathy with subcortical cysts 2A, MIM# 613925; Megalencephalic leukoencephalopathy with subcortical cysts 2B, remitting, with or without mental retardation, MIM# 613926
Review for gene: HEPACAM was set to GREEN
Added comment: Multiple families reported with both mono-allelic and bi-allelic disease; bi-allelic disease is generally more severe. Onset is typically in infancy.
Sources: Expert list
Differences of Sex Development v0.24 MYRF Zornitza Stark Marked gene: MYRF as ready
Differences of Sex Development v0.24 MYRF Zornitza Stark Gene: myrf has been classified as Green List (High Evidence).
Differences of Sex Development v0.24 MYRF Zornitza Stark Classified gene: MYRF as Green List (high evidence)
Differences of Sex Development v0.24 MYRF Zornitza Stark Gene: myrf has been classified as Green List (High Evidence).
Mendeliome v0.2742 MYLK2 Zornitza Stark Marked gene: MYLK2 as ready
Mendeliome v0.2742 MYLK2 Zornitza Stark Gene: mylk2 has been classified as Red List (Low Evidence).
Mendeliome v0.2742 MYLK2 Zornitza Stark Phenotypes for gene: MYLK2 were changed from to Cardiomyopathy, hypertrophic, 1, digenic, 192600
Mendeliome v0.2741 MYLK2 Zornitza Stark Publications for gene: MYLK2 were set to
Mendeliome v0.2740 MYLK2 Zornitza Stark Mode of inheritance for gene: MYLK2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2739 MYLK2 Zornitza Stark Classified gene: MYLK2 as Red List (low evidence)
Mendeliome v0.2739 MYLK2 Zornitza Stark Gene: mylk2 has been classified as Red List (Low Evidence).
Mendeliome v0.2738 MYLK2 Zornitza Stark reviewed gene: MYLK2: Rating: RED; Mode of pathogenicity: None; Publications: 11733062, 24082139, 25825456, 20301725; Phenotypes: Cardiomyopathy, hypertrophic, 1, digenic, 192600; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy v0.28 MYLK2 Zornitza Stark Marked gene: MYLK2 as ready
Hypertrophic cardiomyopathy v0.28 MYLK2 Zornitza Stark Gene: mylk2 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy v0.28 MYLK2 Zornitza Stark Phenotypes for gene: MYLK2 were changed from to Cardiomyopathy, hypertrophic, 1, digenic, 192600
Hypertrophic cardiomyopathy v0.27 MYLK2 Zornitza Stark Publications for gene: MYLK2 were set to
Hypertrophic cardiomyopathy v0.26 MYLK2 Zornitza Stark Mode of pathogenicity for gene: MYLK2 was changed from to Other
Hypertrophic cardiomyopathy v0.25 MYLK2 Zornitza Stark Mode of inheritance for gene: MYLK2 was changed from Unknown to Other
Hypertrophic cardiomyopathy v0.24 MYLK2 Zornitza Stark Classified gene: MYLK2 as Red List (low evidence)
Hypertrophic cardiomyopathy v0.24 MYLK2 Zornitza Stark Gene: mylk2 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy v0.23 MYLK2 Kristin Rigbye reviewed gene: MYLK2: Rating: RED; Mode of pathogenicity: Other; Publications: 11733062, 24082139, 25825456, 20301725; Phenotypes: Cardiomyopathy, hypertrophic, 1, digenic, 192600; Mode of inheritance: Other
Mendeliome v0.2738 CDX2 Zornitza Stark Marked gene: CDX2 as ready
Mendeliome v0.2738 CDX2 Zornitza Stark Gene: cdx2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2738 CDX2 Zornitza Stark Phenotypes for gene: CDX2 were changed from to Persistent cloaca
Mendeliome v0.2737 CDX2 Zornitza Stark Publications for gene: CDX2 were set to
Mendeliome v0.2736 CDX2 Zornitza Stark Mode of inheritance for gene: CDX2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2735 CDX2 Zornitza Stark Classified gene: CDX2 as Amber List (moderate evidence)
Mendeliome v0.2735 CDX2 Zornitza Stark Gene: cdx2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2734 CDX2 Zornitza Stark reviewed gene: CDX2: Rating: AMBER; Mode of pathogenicity: None; Publications: 29177441; Phenotypes: Persistent cloaca; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Leukodystrophy v0.110 GLB1 Zornitza Stark Marked gene: GLB1 as ready
Leukodystrophy v0.110 GLB1 Zornitza Stark Gene: glb1 has been classified as Green List (High Evidence).
Leukodystrophy v0.110 GLB1 Zornitza Stark Classified gene: GLB1 as Green List (high evidence)
Leukodystrophy v0.110 GLB1 Zornitza Stark Gene: glb1 has been classified as Green List (High Evidence).
Leukodystrophy v0.109 GLB1 Zornitza Stark gene: GLB1 was added
gene: GLB1 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: GLB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GLB1 were set to 25691190
Phenotypes for gene: GLB1 were set to GM1-gangliosidosis, type I, MIM# 230500; GM1-gangliosidosis, type II, MIM# 230600
Review for gene: GLB1 was set to GREEN
Added comment: Sources: Expert list
Leukodystrophy v0.108 GJC2 Zornitza Stark Marked gene: GJC2 as ready
Leukodystrophy v0.108 GJC2 Zornitza Stark Gene: gjc2 has been classified as Green List (High Evidence).
Leukodystrophy v0.108 GJC2 Zornitza Stark Classified gene: GJC2 as Green List (high evidence)
Leukodystrophy v0.108 GJC2 Zornitza Stark Gene: gjc2 has been classified as Green List (High Evidence).
Leukodystrophy v0.107 GJC2 Zornitza Stark gene: GJC2 was added
gene: GJC2 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: GJC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GJC2 were set to 22669416; 24374284; 15192806
Phenotypes for gene: GJC2 were set to Leukodystrophy, hypomyelinating, 2, MIM# 608804
Review for gene: GJC2 was set to GREEN
Added comment: Multiple affected families reported, onset is typically in infancy.
Sources: Expert list
Leukodystrophy v0.106 GFAP Zornitza Stark Marked gene: GFAP as ready
Leukodystrophy v0.106 GFAP Zornitza Stark Gene: gfap has been classified as Green List (High Evidence).
Leukodystrophy v0.106 GFAP Zornitza Stark Classified gene: GFAP as Green List (high evidence)
Leukodystrophy v0.106 GFAP Zornitza Stark Gene: gfap has been classified as Green List (High Evidence).
Leukodystrophy v0.105 GFAP Zornitza Stark gene: GFAP was added
gene: GFAP was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: GFAP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: GFAP were set to Alexander disease, MIM# 203450
Review for gene: GFAP was set to GREEN
Added comment: 3 forms of Alexander disease are recognised, based on age of onset: infantile, juvenile, and adult. Younger patients typically present with seizures, megalencephaly, developmental delay, and spasticity. In older patients, bulbar or pseudobulbar symptoms predominate, frequently accompanied by spasticity.
Sources: Expert list
Leukodystrophy v0.104 GALC Zornitza Stark Marked gene: GALC as ready
Leukodystrophy v0.104 GALC Zornitza Stark Gene: galc has been classified as Green List (High Evidence).
Leukodystrophy v0.104 GALC Zornitza Stark Classified gene: GALC as Green List (high evidence)
Leukodystrophy v0.104 GALC Zornitza Stark Gene: galc has been classified as Green List (High Evidence).
Leukodystrophy v0.103 GALC Zornitza Stark gene: GALC was added
gene: GALC was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: GALC was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GALC were set to Krabbe disease, MIM# 245200
Review for gene: GALC was set to GREEN
Added comment: Typically presents in infancy, though later onset in childhood, adolescence and adulthood described.
Sources: Expert list
Leukodystrophy v0.102 EPRS Zornitza Stark Marked gene: EPRS as ready
Leukodystrophy v0.102 EPRS Zornitza Stark Gene: eprs has been classified as Green List (High Evidence).
Leukodystrophy v0.102 EPRS Zornitza Stark Classified gene: EPRS as Green List (high evidence)
Leukodystrophy v0.102 EPRS Zornitza Stark Gene: eprs has been classified as Green List (High Evidence).
Leukodystrophy v0.101 EPRS Zornitza Stark gene: EPRS was added
gene: EPRS was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: EPRS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EPRS were set to 29576217
Phenotypes for gene: EPRS were set to Leukodystrophy, hypomyelinating, 15, MIM# 617951
Review for gene: EPRS was set to GREEN
Added comment: Four unrelated families reported with this neurodegenerative disorder. Onset of motor and cognitive impairment in the first or second decade of life. Features include dystonia, ataxia, spasticity, dysphagia, severe optic atrophy, and some have hearing loss. Brain imaging shows hypomyelinating leukodystrophy with thin corpus callosum.
Sources: Expert list
Leukodystrophy v0.100 EIF2B5 Zornitza Stark Marked gene: EIF2B5 as ready
Leukodystrophy v0.100 EIF2B5 Zornitza Stark Gene: eif2b5 has been classified as Green List (High Evidence).
Leukodystrophy v0.100 EIF2B5 Zornitza Stark Classified gene: EIF2B5 as Green List (high evidence)
Leukodystrophy v0.100 EIF2B5 Zornitza Stark Gene: eif2b5 has been classified as Green List (High Evidence).
Leukodystrophy v0.99 EIF2B5 Zornitza Stark gene: EIF2B5 was added
gene: EIF2B5 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: EIF2B5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: EIF2B5 were set to Leukoencephalopathy with vanishing white matter, MIM# 603896
Review for gene: EIF2B5 was set to GREEN
Added comment: Age of onset can vary from infancy to adulthood.
Sources: Expert list
Leukodystrophy v0.98 EIF2B4 Zornitza Stark Marked gene: EIF2B4 as ready
Leukodystrophy v0.98 EIF2B4 Zornitza Stark Gene: eif2b4 has been classified as Green List (High Evidence).
Leukodystrophy v0.98 EIF2B4 Zornitza Stark Classified gene: EIF2B4 as Green List (high evidence)
Leukodystrophy v0.98 EIF2B4 Zornitza Stark Gene: eif2b4 has been classified as Green List (High Evidence).
Leukodystrophy v0.97 EIF2B4 Zornitza Stark gene: EIF2B4 was added
gene: EIF2B4 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: EIF2B4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: EIF2B4 were set to Leukoencephalopathy with vanishing white matter, MIM# 603896
Review for gene: EIF2B4 was set to GREEN
Added comment: Onset can vary from infancy to adulthood.
Sources: Expert list
Leukodystrophy v0.96 EIF2B3 Zornitza Stark Marked gene: EIF2B3 as ready
Leukodystrophy v0.96 EIF2B3 Zornitza Stark Gene: eif2b3 has been classified as Green List (High Evidence).
Leukodystrophy v0.96 EIF2B3 Zornitza Stark Classified gene: EIF2B3 as Green List (high evidence)
Leukodystrophy v0.96 EIF2B3 Zornitza Stark Gene: eif2b3 has been classified as Green List (High Evidence).
Leukodystrophy v0.95 EIF2B3 Zornitza Stark gene: EIF2B3 was added
gene: EIF2B3 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: EIF2B3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: EIF2B3 were set to Leukoencephalopathy with vanishing white matter, MIM# 603896
Review for gene: EIF2B3 was set to GREEN
Added comment: Age of onset can vary from infancy to adulthood.
Sources: Expert list
Leukodystrophy v0.94 EIF2B2 Zornitza Stark Marked gene: EIF2B2 as ready
Leukodystrophy v0.94 EIF2B2 Zornitza Stark Gene: eif2b2 has been classified as Green List (High Evidence).
Leukodystrophy v0.94 EIF2B2 Zornitza Stark Classified gene: EIF2B2 as Green List (high evidence)
Leukodystrophy v0.94 EIF2B2 Zornitza Stark Gene: eif2b2 has been classified as Green List (High Evidence).
Leukodystrophy v0.93 EIF2B2 Zornitza Stark gene: EIF2B2 was added
gene: EIF2B2 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: EIF2B2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: EIF2B2 were set to Leukoencephalopathy with vanishing white matter, MIM# 603896
Review for gene: EIF2B2 was set to GREEN
Added comment: Age of onset can vary from infancy to adulthood.
Sources: Expert list
Leukodystrophy v0.92 EIF2B1 Zornitza Stark Marked gene: EIF2B1 as ready
Leukodystrophy v0.92 EIF2B1 Zornitza Stark Gene: eif2b1 has been classified as Green List (High Evidence).
Leukodystrophy v0.92 EIF2B1 Zornitza Stark Classified gene: EIF2B1 as Green List (high evidence)
Leukodystrophy v0.92 EIF2B1 Zornitza Stark Gene: eif2b1 has been classified as Green List (High Evidence).
Leukodystrophy v0.91 EIF2B1 Zornitza Stark gene: EIF2B1 was added
gene: EIF2B1 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: EIF2B1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: EIF2B1 were set to Leukoencephalopathy with vanishing white matter, MIM# 603896
Review for gene: EIF2B1 was set to GREEN
Added comment: Age of onset can vary from infancy to adulthood.
Sources: Expert list
Leukodystrophy v0.90 EARS2 Zornitza Stark Marked gene: EARS2 as ready
Leukodystrophy v0.90 EARS2 Zornitza Stark Gene: ears2 has been classified as Green List (High Evidence).
Leukodystrophy v0.90 EARS2 Zornitza Stark Classified gene: EARS2 as Green List (high evidence)
Leukodystrophy v0.90 EARS2 Zornitza Stark Gene: ears2 has been classified as Green List (High Evidence).
Leukodystrophy v0.89 EARS2 Zornitza Stark gene: EARS2 was added
gene: EARS2 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: EARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EARS2 were set to 22492562; 23008233; 25854774; 26619324; 26893310
Phenotypes for gene: EARS2 were set to Combined oxidative phosphorylation deficiency 12, MIM# 614924; Leukoencephalopathy with thalamus and brainstem involvement and high lactate
Review for gene: EARS2 was set to GREEN
Added comment: Multiple families reported, onset typically in infancy/childhood.
Sources: Expert list
Ciliopathies v0.103 SEC63 Zornitza Stark Marked gene: SEC63 as ready
Ciliopathies v0.103 SEC63 Zornitza Stark Added comment: Comment when marking as ready: Agree, not a ciliopathy. Retain as Amber due to phenotypic overlap.
Ciliopathies v0.103 SEC63 Zornitza Stark Gene: sec63 has been classified as Amber List (Moderate Evidence).
Ciliopathies v0.103 SEC63 Zornitza Stark Phenotypes for gene: SEC63 were changed from to Polycystic liver disease 2 (MIM#617004)
Ciliopathies v0.102 SEC63 Zornitza Stark Publications for gene: SEC63 were set to
Ciliopathies v0.101 SEC63 Zornitza Stark Mode of inheritance for gene: SEC63 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ciliopathies v0.100 SEC63 Zornitza Stark Classified gene: SEC63 as Amber List (moderate evidence)
Ciliopathies v0.100 SEC63 Zornitza Stark Gene: sec63 has been classified as Amber List (Moderate Evidence).
Ciliopathies v0.99 CEP55 Zornitza Stark Marked gene: CEP55 as ready
Ciliopathies v0.99 CEP55 Zornitza Stark Gene: cep55 has been classified as Amber List (Moderate Evidence).
Ciliopathies v0.99 CEP55 Zornitza Stark Phenotypes for gene: CEP55 were changed from to Multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly, MIM# 236500
Ciliopathies v0.98 CEP55 Zornitza Stark Publications for gene: CEP55 were set to
Ciliopathies v0.97 CEP55 Zornitza Stark Mode of inheritance for gene: CEP55 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v0.96 CEP55 Zornitza Stark Classified gene: CEP55 as Amber List (moderate evidence)
Ciliopathies v0.96 CEP55 Zornitza Stark Gene: cep55 has been classified as Amber List (Moderate Evidence).
Osteogenesis Imperfecta and Osteoporosis v0.14 TAPT1 Zornitza Stark Marked gene: TAPT1 as ready
Osteogenesis Imperfecta and Osteoporosis v0.14 TAPT1 Zornitza Stark Gene: tapt1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v0.20 TAPT1 Zornitza Stark Marked gene: TAPT1 as ready
Skeletal dysplasia v0.20 TAPT1 Zornitza Stark Gene: tapt1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v0.20 TAPT1 Zornitza Stark Classified gene: TAPT1 as Amber List (moderate evidence)
Skeletal dysplasia v0.20 TAPT1 Zornitza Stark Gene: tapt1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v0.19 TAPT1 Zornitza Stark reviewed gene: TAPT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 26365339; Phenotypes: Osteochondrodysplasia, complex lethal, Symoens-Barnes-Gistelinck type (MIM#616897); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteogenesis Imperfecta and Osteoporosis v0.14 TAPT1 Zornitza Stark Phenotypes for gene: TAPT1 were changed from to Osteochondrodysplasia, complex lethal, Symoens-Barnes-Gistelinck type (MIM#616897)
Osteogenesis Imperfecta and Osteoporosis v0.13 TAPT1 Zornitza Stark Publications for gene: TAPT1 were set to
Osteogenesis Imperfecta and Osteoporosis v0.12 TAPT1 Zornitza Stark Mode of inheritance for gene: TAPT1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Osteogenesis Imperfecta and Osteoporosis v0.12 TAPT1 Zornitza Stark Mode of inheritance for gene: TAPT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Osteogenesis Imperfecta and Osteoporosis v0.11 TAPT1 Zornitza Stark Classified gene: TAPT1 as Amber List (moderate evidence)
Osteogenesis Imperfecta and Osteoporosis v0.11 TAPT1 Zornitza Stark Gene: tapt1 has been classified as Amber List (Moderate Evidence).
Osteogenesis Imperfecta and Osteoporosis v0.10 TAPT1 Zornitza Stark reviewed gene: TAPT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 26365339; Phenotypes: Osteochondrodysplasia, complex lethal, Symoens-Barnes-Gistelinck type (MIM#616897); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2734 TAPT1 Zornitza Stark Marked gene: TAPT1 as ready
Mendeliome v0.2734 TAPT1 Zornitza Stark Gene: tapt1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2734 TAPT1 Zornitza Stark Phenotypes for gene: TAPT1 were changed from to Osteochondrodysplasia, complex lethal, Symoens-Barnes-Gistelinck type (MIM#616897)
Mendeliome v0.2733 TAPT1 Zornitza Stark Publications for gene: TAPT1 were set to
Mendeliome v0.2732 TAPT1 Zornitza Stark Mode of inheritance for gene: TAPT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2731 TAPT1 Zornitza Stark Classified gene: TAPT1 as Amber List (moderate evidence)
Mendeliome v0.2731 TAPT1 Zornitza Stark Gene: tapt1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2730 TAPT1 Zornitza Stark reviewed gene: TAPT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 26365339; Phenotypes: Osteochondrodysplasia, complex lethal, Symoens-Barnes-Gistelinck type (MIM#616897); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v0.95 TAPT1 Zornitza Stark Phenotypes for gene: TAPT1 were changed from Osteochondrodysplasia, complex lethal, Symoens-Barnes-Gistelinck type (MIM#616897) to Osteochondrodysplasia, complex lethal, Symoens-Barnes-Gistelinck type (MIM#616897)
Ciliopathies v0.95 TAPT1 Zornitza Stark Marked gene: TAPT1 as ready
Ciliopathies v0.95 TAPT1 Zornitza Stark Gene: tapt1 has been classified as Amber List (Moderate Evidence).
Ciliopathies v0.95 TAPT1 Zornitza Stark Phenotypes for gene: TAPT1 were changed from to Osteochondrodysplasia, complex lethal, Symoens-Barnes-Gistelinck type (MIM#616897)
Ciliopathies v0.94 TAPT1 Zornitza Stark Publications for gene: TAPT1 were set to
Ciliopathies v0.93 TAPT1 Zornitza Stark Mode of inheritance for gene: TAPT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v0.92 TAPT1 Zornitza Stark Classified gene: TAPT1 as Amber List (moderate evidence)
Ciliopathies v0.92 TAPT1 Zornitza Stark Gene: tapt1 has been classified as Amber List (Moderate Evidence).
Joubert syndrome and other neurological ciliopathies v0.48 CCDC28B Zornitza Stark Marked gene: CCDC28B as ready
Joubert syndrome and other neurological ciliopathies v0.48 CCDC28B Zornitza Stark Gene: ccdc28b has been classified as Amber List (Moderate Evidence).
Joubert syndrome and other neurological ciliopathies v0.48 CCDC28B Zornitza Stark Classified gene: CCDC28B as Amber List (moderate evidence)
Joubert syndrome and other neurological ciliopathies v0.48 CCDC28B Zornitza Stark Gene: ccdc28b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2730 CCDC28B Zornitza Stark Classified gene: CCDC28B as Amber List (moderate evidence)
Mendeliome v0.2730 CCDC28B Zornitza Stark Gene: ccdc28b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2729 CCDC28B Zornitza Stark edited their review of gene: CCDC28B: Added comment: PMID: 32139166 - Single family with Joubert syndrome. Patient was homozygous for a missense, with polydactyly, severe ID, and the molar tooth sign observed in MRI. Sibling fetus MRI showed vermis hypoplasia, and was also homozygous for the variant. Parents confirmed unaffected carriers. Knockdown of CCDC28B in human TERT retinal pigment epithelial cells reduced both the number and length of cilia 430C-T variant is postulated to be a modifier of BBS.; Changed rating: AMBER; Changed publications: 32139166; Changed phenotypes: {Bardet-Biedl syndrome 1, modifier of}, MIM#209900, Joubert syndrome
Joubert syndrome and other neurological ciliopathies v0.47 CCDC28B Zornitza Stark gene: CCDC28B was added
gene: CCDC28B was added to Joubert syndrome and other neurological ciliopathies. Sources: Expert list
Mode of inheritance for gene: CCDC28B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC28B were set to 32139166
Phenotypes for gene: CCDC28B were set to Joubert syndrome
Review for gene: CCDC28B was set to AMBER
Added comment: PMID: 32139166 - Single family with Joubert syndrome. Patient was homozygous for a missense, with polydactyly, severe ID, and the molar tooth sign observed in MRI. Sibling fetus MRI showed vermis hypoplasia, and was also homozygous for the variant. Parents confirmed unaffected carriers. Knockdown of CCDC28B in human TERT retinal pigment epithelial cells reduced both the number and length of cilia 430C-T variant is postulated to be a modifier of BBS.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2619 ARMC9 Zornitza Stark Marked gene: ARMC9 as ready
Intellectual disability syndromic and non-syndromic v0.2619 ARMC9 Zornitza Stark Gene: armc9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2619 ARMC9 Zornitza Stark Phenotypes for gene: ARMC9 were changed from Joubert syndrome 30, MIM# 617622 to Joubert syndrome 30, MIM# 617622
Ciliopathies v0.91 CCDC28B Zornitza Stark Phenotypes for gene: CCDC28B were changed from {Bardet-Biedl syndrome 1, modifier of}, MIM#209900 to {Bardet-Biedl syndrome 1, modifier of}, MIM#209900; Joubert syndrome
Ciliopathies v0.90 CCDC28B Zornitza Stark Publications for gene: CCDC28B were set to 32139166
Ciliopathies v0.90 CCDC28B Zornitza Stark Publications for gene: CCDC28B were set to
Ciliopathies v0.89 CCDC28B Zornitza Stark Classified gene: CCDC28B as Amber List (moderate evidence)
Ciliopathies v0.89 CCDC28B Zornitza Stark Gene: ccdc28b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2729 C21orf59 Zornitza Stark Marked gene: C21orf59 as ready
Mendeliome v0.2729 C21orf59 Zornitza Stark Added comment: Comment when marking as ready: p.Tyr245* recurrent in the Ashkenazi Jewish population
Mendeliome v0.2729 C21orf59 Zornitza Stark Gene: c21orf59 has been classified as Green List (High Evidence).
Mendeliome v0.2729 C21orf59 Zornitza Stark Tag founder tag was added to gene: C21orf59.
Heterotaxy v0.21 C21orf59 Zornitza Stark Marked gene: C21orf59 as ready
Heterotaxy v0.21 C21orf59 Zornitza Stark Added comment: Comment when marking as ready: p.Tyr245* recurring in the Ashkenazi Jewish population
Heterotaxy v0.21 C21orf59 Zornitza Stark Gene: c21orf59 has been classified as Green List (High Evidence).
Heterotaxy v0.21 C21orf59 Zornitza Stark Tag founder tag was added to gene: C21orf59.
Ciliary Dyskinesia v0.45 C21orf59 Zornitza Stark Tag founder tag was added to gene: C21orf59.
Ciliary Dyskinesia v0.45 C21orf59 Zornitza Stark Publications for gene: C21orf59 were set to 24094744
Ciliopathies v0.88 VPS13B Zornitza Stark Marked gene: VPS13B as ready
Ciliopathies v0.88 VPS13B Zornitza Stark Added comment: Comment when marking as ready: Agree retinopathy, obesity and ID overlap significantly with typical phenotypic features of ciliopathies, therefore reasonable to include in this panel even though not strictly a ciliopathy.
Ciliopathies v0.88 VPS13B Zornitza Stark Gene: vps13b has been classified as Amber List (Moderate Evidence).
Ciliopathies v0.88 VPS13B Zornitza Stark Classified gene: VPS13B as Amber List (moderate evidence)
Ciliopathies v0.88 VPS13B Zornitza Stark Gene: vps13b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2729 C11orf70 Zornitza Stark Marked gene: C11orf70 as ready
Mendeliome v0.2729 C11orf70 Zornitza Stark Gene: c11orf70 has been classified as Green List (High Evidence).
Mendeliome v0.2729 C11orf70 Zornitza Stark Tag new gene name tag was added to gene: C11orf70.
Mendeliome v0.2729 C11orf70 Zornitza Stark Phenotypes for gene: C11orf70 were changed from to Ciliary dyskinesia, primary, 38, MIM# 618063
Mendeliome v0.2728 C11orf70 Zornitza Stark Publications for gene: C11orf70 were set to
Mendeliome v0.2727 C11orf70 Zornitza Stark Mode of inheritance for gene: C11orf70 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2726 C11orf70 Zornitza Stark reviewed gene: C11orf70: Rating: GREEN; Mode of pathogenicity: None; Publications: 29727693, 29727692; Phenotypes: Ciliary dyskinesia, primary, 38, MIM# 618063; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.44 C11orf70 Zornitza Stark Tag new gene name tag was added to gene: C11orf70.
Heterotaxy v0.21 C11orf70 Zornitza Stark Marked gene: C11orf70 as ready
Heterotaxy v0.21 C11orf70 Zornitza Stark Gene: c11orf70 has been classified as Green List (High Evidence).
Heterotaxy v0.21 C11orf70 Zornitza Stark Phenotypes for gene: C11orf70 were changed from to Ciliary dyskinesia, primary, 38, MIM# 618063
Heterotaxy v0.20 C11orf70 Zornitza Stark Publications for gene: C11orf70 were set to
Heterotaxy v0.19 C11orf70 Zornitza Stark Mode of inheritance for gene: C11orf70 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.18 C11orf70 Zornitza Stark reviewed gene: C11orf70: Rating: GREEN; Mode of pathogenicity: None; Publications: 29727693, 29727692; Phenotypes: Ciliary dyskinesia, primary, 38, MIM# 618063; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.18 C11orf70 Zornitza Stark Tag new gene name tag was added to gene: C11orf70.
Ciliary Dyskinesia v0.44 C11orf70 Zornitza Stark Marked gene: C11orf70 as ready
Ciliary Dyskinesia v0.44 C11orf70 Zornitza Stark Gene: c11orf70 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.44 C11orf70 Zornitza Stark Classified gene: C11orf70 as Green List (high evidence)
Ciliary Dyskinesia v0.44 C11orf70 Zornitza Stark Gene: c11orf70 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2618 ARMC9 Zornitza Stark Phenotypes for gene: ARMC9 were changed from to Joubert syndrome 30, MIM# 617622
Intellectual disability syndromic and non-syndromic v0.2617 ARMC9 Zornitza Stark Publications for gene: ARMC9 were set to
Intellectual disability syndromic and non-syndromic v0.2616 ARMC9 Zornitza Stark Mode of inheritance for gene: ARMC9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2615 ARMC9 Zornitza Stark reviewed gene: ARMC9: Rating: GREEN; Mode of pathogenicity: None; Publications: 28625504; Phenotypes: Joubert syndrome 30, MIM# 617622; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Joubert syndrome and other neurological ciliopathies v0.46 ARMC9 Zornitza Stark Marked gene: ARMC9 as ready
Joubert syndrome and other neurological ciliopathies v0.46 ARMC9 Zornitza Stark Gene: armc9 has been classified as Green List (High Evidence).
Joubert syndrome and other neurological ciliopathies v0.46 ARMC9 Zornitza Stark Classified gene: ARMC9 as Green List (high evidence)
Joubert syndrome and other neurological ciliopathies v0.46 ARMC9 Zornitza Stark Gene: armc9 has been classified as Green List (High Evidence).
Mendeliome v0.2726 ARMC9 Zornitza Stark Marked gene: ARMC9 as ready
Mendeliome v0.2726 ARMC9 Zornitza Stark Gene: armc9 has been classified as Green List (High Evidence).
Mendeliome v0.2726 ARMC9 Zornitza Stark Phenotypes for gene: ARMC9 were changed from to Joubert syndrome 30, MIM#617622
Mendeliome v0.2725 ARMC9 Zornitza Stark Publications for gene: ARMC9 were set to
Mendeliome v0.2724 ARMC9 Zornitza Stark Mode of inheritance for gene: ARMC9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2723 ARMC9 Zornitza Stark Deleted their comment
Mendeliome v0.2723 ARMC9 Zornitza Stark edited their review of gene: ARMC9: Added comment: ARMC9 localizes to the ciliary basal body and daughter centriole and is predicted to function in ciliogenesis PMID: 28625504 - 8 families with Joubert syndrome, all variant types detected. Functional studies show protein localizes at the basal body and upregulates during ciliogenesis. Zebrafish with frameshift mutation recapitulated the human phenotype including a curved body, coloboma, retinal dystrophy and less cilia.; Changed rating: GREEN; Changed publications: 28625504
Joubert syndrome and other neurological ciliopathies v0.45 ARMC9 Zornitza Stark gene: ARMC9 was added
gene: ARMC9 was added to Joubert syndrome and other neurological ciliopathies. Sources: Expert list
Mode of inheritance for gene: ARMC9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARMC9 were set to 28625504
Phenotypes for gene: ARMC9 were set to Joubert syndrome 30, MIM# 617622
Review for gene: ARMC9 was set to GREEN
Added comment: ARMC9 localizes to the ciliary basal body and daughter centriole and is predicted to function in ciliogenesis PMID: 28625504 - 8 families with Joubert syndrome, all variant types detected. Functional studies show protein localizes at the basal body and upregulates during ciliogenesis. Zebrafish with frameshift mutation recapitulated the human phenotype including a curved body, coloboma, retinal dystrophy and less cilia.
Sources: Expert list
Ciliopathies v0.87 ARMC9 Zornitza Stark Marked gene: ARMC9 as ready
Ciliopathies v0.87 ARMC9 Zornitza Stark Gene: armc9 has been classified as Green List (High Evidence).
Ciliopathies v0.87 ARMC9 Zornitza Stark Classified gene: ARMC9 as Green List (high evidence)
Ciliopathies v0.87 ARMC9 Zornitza Stark Gene: armc9 has been classified as Green List (High Evidence).
Polydactyly v0.22 ARMC8 Zornitza Stark Marked gene: ARMC8 as ready
Polydactyly v0.22 ARMC8 Zornitza Stark Gene: armc8 has been classified as Red List (Low Evidence).
Polydactyly v0.22 ARMC8 Zornitza Stark Classified gene: ARMC8 as Red List (low evidence)
Polydactyly v0.22 ARMC8 Zornitza Stark Gene: armc8 has been classified as Red List (Low Evidence).
Polydactyly v0.21 ARMC8 Zornitza Stark reviewed gene: ARMC8: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.2723 ARMC8 Zornitza Stark Marked gene: ARMC8 as ready
Mendeliome v0.2723 ARMC8 Zornitza Stark Gene: armc8 has been classified as Red List (Low Evidence).
Mendeliome v0.2723 ARMC8 Zornitza Stark Classified gene: ARMC8 as Red List (low evidence)
Mendeliome v0.2723 ARMC8 Zornitza Stark Gene: armc8 has been classified as Red List (Low Evidence).
Mendeliome v0.2722 ARMC8 Zornitza Stark reviewed gene: ARMC8: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Joubert syndrome and other neurological ciliopathies v0.44 ARMC8 Zornitza Stark Marked gene: ARMC8 as ready
Joubert syndrome and other neurological ciliopathies v0.44 ARMC8 Zornitza Stark Gene: armc8 has been classified as Red List (Low Evidence).
Joubert syndrome and other neurological ciliopathies v0.44 ARMC8 Zornitza Stark Classified gene: ARMC8 as Red List (low evidence)
Joubert syndrome and other neurological ciliopathies v0.44 ARMC8 Zornitza Stark Gene: armc8 has been classified as Red List (Low Evidence).
Joubert syndrome and other neurological ciliopathies v0.43 ARMC8 Zornitza Stark reviewed gene: ARMC8: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.2722 ARMC4 Zornitza Stark Marked gene: ARMC4 as ready
Mendeliome v0.2722 ARMC4 Zornitza Stark Gene: armc4 has been classified as Green List (High Evidence).
Ciliopathies v0.86 ARMC8 Zornitza Stark Marked gene: ARMC8 as ready
Ciliopathies v0.86 ARMC8 Zornitza Stark Gene: armc8 has been classified as Red List (Low Evidence).
Ciliopathies v0.86 ARMC8 Zornitza Stark Classified gene: ARMC8 as Red List (low evidence)
Ciliopathies v0.86 ARMC8 Zornitza Stark Gene: armc8 has been classified as Red List (Low Evidence).
Mendeliome v0.2722 ARMC4 Zornitza Stark Phenotypes for gene: ARMC4 were changed from to Ciliary dyskinesia, primary, 23, MIM# 615451
Heterotaxy v0.18 ARMC4 Zornitza Stark Marked gene: ARMC4 as ready
Heterotaxy v0.18 ARMC4 Zornitza Stark Gene: armc4 has been classified as Green List (High Evidence).
Mendeliome v0.2721 ARMC4 Zornitza Stark Publications for gene: ARMC4 were set to
Mendeliome v0.2720 ARMC4 Zornitza Stark Mode of inheritance for gene: ARMC4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2719 ARMC4 Zornitza Stark reviewed gene: ARMC4: Rating: GREEN; Mode of pathogenicity: None; Publications: 31765523, 23849778; Phenotypes: Ciliary dyskinesia, primary, 23, MIM# 615451; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.18 ARMC4 Zornitza Stark Phenotypes for gene: ARMC4 were changed from to Ciliary dyskinesia, primary, 23, MIM# 615451
Heterotaxy v0.17 ARMC4 Zornitza Stark Publications for gene: ARMC4 were set to
Heterotaxy v0.16 ARMC4 Zornitza Stark Mode of inheritance for gene: ARMC4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.15 ARMC4 Zornitza Stark edited their review of gene: ARMC4: Changed publications: 31765523, 23849778
Heterotaxy v0.15 ARMC4 Zornitza Stark reviewed gene: ARMC4: Rating: GREEN; Mode of pathogenicity: None; Publications: 31765523; Phenotypes: Ciliary dyskinesia, primary, 23, MIM# 615451; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.43 ARMC4 Zornitza Stark Phenotypes for gene: ARMC4 were changed from to Ciliary dyskinesia, primary, 23, MIM# 615451
Ciliary Dyskinesia v0.42 ARMC4 Zornitza Stark Publications for gene: ARMC4 were set to
Ciliary Dyskinesia v0.41 ARMC4 Zornitza Stark Mode of inheritance for gene: ARMC4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v0.85 ZSWIM6 Zornitza Stark Phenotypes for gene: ZSWIM6 were changed from Acromelic frontonasal dysostosis (MIM#603671) to Acromelic frontonasal dysostosis (MIM#603671); Neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features, MIM# 617865
Ciliopathies v0.84 ZSWIM6 Zornitza Stark Marked gene: ZSWIM6 as ready
Ciliopathies v0.84 ZSWIM6 Zornitza Stark Added comment: Comment when marking as ready: Agree, link to cilia not well established.
Ciliopathies v0.84 ZSWIM6 Zornitza Stark Gene: zswim6 has been classified as Amber List (Moderate Evidence).
Ciliopathies v0.84 ZSWIM6 Zornitza Stark Classified gene: ZSWIM6 as Amber List (moderate evidence)
Ciliopathies v0.84 ZSWIM6 Zornitza Stark Gene: zswim6 has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v0.33 ACVR2B Zornitza Stark Phenotypes for gene: ACVR2B were changed from to Heterotaxy, visceral, 4, autosomal 613751
Mendeliome v0.2719 ACVR2B Zornitza Stark Marked gene: ACVR2B as ready
Mendeliome v0.2719 ACVR2B Zornitza Stark Gene: acvr2b has been classified as Red List (Low Evidence).
Mendeliome v0.2719 ACVR2B Zornitza Stark Phenotypes for gene: ACVR2B were changed from to Heterotaxy, visceral, 4, autosomal 613751
Congenital Heart Defect v0.32 ACVR2B Zornitza Stark Publications for gene: ACVR2B were set to
Mendeliome v0.2718 ACVR2B Zornitza Stark Publications for gene: ACVR2B were set to
Mendeliome v0.2717 ACVR2B Zornitza Stark Mode of inheritance for gene: ACVR2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2716 ACVR2B Zornitza Stark Classified gene: ACVR2B as Red List (low evidence)
Mendeliome v0.2716 ACVR2B Zornitza Stark Gene: acvr2b has been classified as Red List (Low Evidence).
Mendeliome v0.2715 ACVR2B Zornitza Stark reviewed gene: ACVR2B: Rating: RED; Mode of pathogenicity: None; Publications: 9916847, 30622330, 21864452; Phenotypes: Heterotaxy, visceral, 4, autosomal 613751; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.31 ACVR2B Zornitza Stark Mode of inheritance for gene: ACVR2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.30 ACVR2B Zornitza Stark Classified gene: ACVR2B as Red List (low evidence)
Congenital Heart Defect v0.30 ACVR2B Zornitza Stark Gene: acvr2b has been classified as Red List (Low Evidence).
Congenital Heart Defect v0.29 ACVR2B Zornitza Stark reviewed gene: ACVR2B: Rating: RED; Mode of pathogenicity: None; Publications: 9916847, 30622330, 21864452; Phenotypes: Heterotaxy, visceral, 4, autosomal 613751; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ciliopathies v0.83 ACVR2B Zornitza Stark Phenotypes for gene: ACVR2B were changed from to Heterotaxy, visceral, 4, autosomal 613751
Ciliopathies v0.82 ACVR2B Zornitza Stark Publications for gene: ACVR2B were set to 9916847; 30622330; 21864452
Ciliopathies v0.82 ACVR2B Zornitza Stark Tag disputed tag was added to gene: ACVR2B.
Ciliopathies v0.82 ACVR2B Zornitza Stark Publications for gene: ACVR2B were set to
Ciliopathies v0.81 ACVR2B Zornitza Stark Mode of inheritance for gene: ACVR2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ciliopathies v0.80 ACVR2B Zornitza Stark Classified gene: ACVR2B as Red List (low evidence)
Ciliopathies v0.80 ACVR2B Zornitza Stark Gene: acvr2b has been classified as Red List (Low Evidence).
Ciliopathies v0.79 WDR81 Zornitza Stark Marked gene: WDR81 as ready
Ciliopathies v0.79 WDR81 Zornitza Stark Gene: wdr81 has been classified as Red List (Low Evidence).
Ciliopathies v0.79 WDR81 Zornitza Stark Classified gene: WDR81 as Red List (low evidence)
Ciliopathies v0.79 WDR81 Zornitza Stark Gene: wdr81 has been classified as Red List (Low Evidence).
Joubert syndrome and other neurological ciliopathies v0.43 WDR81 Zornitza Stark Marked gene: WDR81 as ready
Joubert syndrome and other neurological ciliopathies v0.43 WDR81 Zornitza Stark Gene: wdr81 has been classified as Red List (Low Evidence).
Joubert syndrome and other neurological ciliopathies v0.43 WDR81 Zornitza Stark Phenotypes for gene: WDR81 were changed from to Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 2 610185; Hydrocephalus, congenital, 3, with brain anomalies 617967
Joubert syndrome and other neurological ciliopathies v0.42 WDR81 Zornitza Stark Publications for gene: WDR81 were set to
Joubert syndrome and other neurological ciliopathies v0.41 WDR81 Zornitza Stark Mode of inheritance for gene: WDR81 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Joubert syndrome and other neurological ciliopathies v0.40 WDR81 Zornitza Stark Classified gene: WDR81 as Red List (low evidence)
Joubert syndrome and other neurological ciliopathies v0.40 WDR81 Zornitza Stark Gene: wdr81 has been classified as Red List (Low Evidence).
Joubert syndrome and other neurological ciliopathies v0.39 WDR81 Zornitza Stark reviewed gene: WDR81: Rating: RED; Mode of pathogenicity: None; Publications: 28556411, 21885617; Phenotypes: Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 2 610185, Hydrocephalus, congenital, 3, with brain anomalies 617967; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v0.78 SEC63 Crystle Lee reviewed gene: SEC63: Rating: AMBER; Mode of pathogenicity: None; Publications: 15133510, 19876928; Phenotypes: Polycystic liver disease 2 (MIM#617004); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Ciliopathies v0.78 CEP55 Elena Savva reviewed gene: CEP55: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 28264986, 28295209, 32100459; Phenotypes: Multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly 236500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v0.78 CEP55 Elena Savva Deleted their review
Ciliopathies v0.78 CEP55 Elena Savva reviewed gene: CEP55: Rating: ; Mode of pathogenicity: None; Publications: PMID: 28264986; Phenotypes: Multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly 236500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v0.78 TAPT1 Crystle Lee changed review comment from: 2 families reported with function studies showing absent or abnormal primary cillia formation.

PMID: 26365339; Reported 2 consang fam (1 splice and 1 missense) with Complex Lethal Osteochondrodysplasia. Functional studies showed abnormal ciliogenesis. Tapt1b deficient zebrafish showed decreased cilial length; to: 2 families reported with function studies showing absent or abnormal primary cillia formation. Amber/Green pending additional reports

PMID: 26365339; Reported 2 consang fam (1 splice and 1 missense) with Complex Lethal Osteochondrodysplasia. Functional studies showed abnormal ciliogenesis. Tapt1b deficient zebrafish showed decreased cilial length
Ciliopathies v0.78 TAPT1 Crystle Lee reviewed gene: TAPT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 26365339; Phenotypes: Osteochondrodysplasia, complex lethal, Symoens-Barnes-Gistelinck type (MIM#616897); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v0.78 CCDC28B Elena Savva reviewed gene: CCDC28B: Rating: AMBER; Mode of pathogenicity: Other; Publications: PMID: 32139166; Phenotypes: {Bardet-Biedl syndrome 1, modifier of} 209900, Joubert syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.40 C21orf59 Elena Savva reviewed gene: C21orf59: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 24094744, 26904945; Phenotypes: Ciliary dyskinesia, primary, 26 615500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v0.78 VPS13B Crystle Lee gene: VPS13B was added
gene: VPS13B was added to Ciliopathies. Sources: Expert Review
Mode of inheritance for gene: VPS13B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VPS13B were set to Cohen syndrome (MIM# 216550)
Review for gene: VPS13B was set to AMBER
Added comment: Well reported to cause Cohen syndrome, however, protein forms part of the golgi apparatus and plays an important role in glycosylation. Unsure if ciliopathy?

PanelApp UK: Was confirmed with the Clinical Team that this gene should be green on this panel.
Sources: Expert Review
Ciliary Dyskinesia v0.40 C11orf70 Elena Savva gene: C11orf70 was added
gene: C11orf70 was added to Ciliary Dyskinesia. Sources: Expert list
Mode of inheritance for gene: C11orf70 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C11orf70 were set to PMID: 29727693; 29727692
Phenotypes for gene: C11orf70 were set to Ciliary dyskinesia, primary, 38 618063
Review for gene: C11orf70 was set to GREEN
Added comment: aka CFAP300

OMIM: CFAP300 is an evolutionarily conserved protein essential for assembly of dynein arms.

PMID: 29727692 - 2 unrelated families, one with a homozygous missense, the other chet for two PTCs. Patients have immotile respiratory cilia. Paramecium knockouts have lost cilia and swimming velocity,

PMID: 29727693 - 5 families with biallelic PTCs. Patients had increased respiratory infections and 1 situs invertus
Sources: Expert list
Ciliopathies v0.78 ARMC9 Elena Savva gene: ARMC9 was added
gene: ARMC9 was added to Ciliopathies. Sources: Expert list
Mode of inheritance for gene: ARMC9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARMC9 were set to PMID: 28625504
Phenotypes for gene: ARMC9 were set to Joubert syndrome 30 617622 AR
Review for gene: ARMC9 was set to GREEN
Added comment: OMIM: ARMC9 localizes to the ciliary basal body and daughter centriole and is predicted to function in ciliogenesis

PMID: 28625504 - 8 families with Joubert syndrome, all variant types detected. Functional studies show protein localizes at the basal body and upregulates during ciliogenesis. Zebrafish with frameshift mutation recapitulated the human phenotype including a curved body, coloboma, retinal dystrophy and less cilia.
Sources: Expert list
Polydactyly v0.21 ARMC8 Elena Savva reviewed gene: ARMC8: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.2715 ARMC8 Elena Savva reviewed gene: ARMC8: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Joubert syndrome and other neurological ciliopathies v0.39 ARMC8 Elena Savva reviewed gene: ARMC8: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Ciliopathies v0.78 ARMC8 Elena Savva reviewed gene: ARMC8: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Ciliary Dyskinesia v0.40 ARMC4 Elena Savva reviewed gene: ARMC4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31765523; Phenotypes: Ciliary dyskinesia, primary, 23 615451; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v0.78 ZSWIM6 Crystle Lee gene: ZSWIM6 was added
gene: ZSWIM6 was added to Ciliopathies. Sources: Expert Review
Mode of inheritance for gene: ZSWIM6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ZSWIM6 were set to 25105228; 28213462; 29198722
Phenotypes for gene: ZSWIM6 were set to Acromelic frontonasal dysostosis (MIM#603671)
Mode of pathogenicity for gene: ZSWIM6 was set to Other
Review for gene: ZSWIM6 was set to AMBER
Added comment: Minimal reports to date. Acromelic frontonasal dysostosis considered as likely ciliopathy in one paper.

PMID: 25105228: 4 pts with AFND (Arg1163Trp)

PMID: 28213462; AFND caused by this gene was classified as "Likely ciliopathy"

PMID: 29198722; Reported 7 unrelated individuals with a recurrent truncating variant. This patients were "Neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features". No functional studies performed but postulated to be dominant-negative.

Rated green in PanelApp UK - Rare multisystem ciliopathy disorders list
Sources: Expert Review
Mendeliome v0.2715 ACVR2B Elena Savva reviewed gene: ACVR2B: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 9916847, 30622330, 21864452; Phenotypes: Heterotaxy, visceral, 4, autosomal 613751; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Ciliopathies v0.78 ACVR2B Elena Savva reviewed gene: ACVR2B: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 9916847, 30622330, 21864452; Phenotypes: Heterotaxy, visceral, 4, autosomal 613751; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Ciliopathies v0.78 WDR81 Elena Savva gene: WDR81 was added
gene: WDR81 was added to Ciliopathies. Sources: Expert list
Mode of inheritance for gene: WDR81 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR81 were set to PMID: 28556411; 21885617
Phenotypes for gene: WDR81 were set to Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 2 610185; Hydrocephalus, congenital, 3, with brain anomalies 617967
Review for gene: WDR81 was set to RED
Added comment: No mention of ciliary involvement in OMIM

PMID: 28556411 - 2 families with congenital hydrocephalus, families were homozygous for a PTC and missense

PMID: 21885617 - 1 super giant family with a homozygous missense. Authors describe the protein as transmembrane protein where the WD repeats support of beta propeller component. Mouse model also described, no mention of a Joubert-type phenotype
Sources: Expert list
Ciliopathies v0.78 SCAPER Zornitza Stark Classified gene: SCAPER as Green List (high evidence)
Ciliopathies v0.78 SCAPER Zornitza Stark Gene: scaper has been classified as Green List (High Evidence).
Ciliopathies v0.78 SCAPER Zornitza Stark Marked gene: SCAPER as ready
Ciliopathies v0.78 SCAPER Zornitza Stark Gene: scaper has been classified as Green List (High Evidence).
Ciliopathies v0.78 SCAPER Zornitza Stark Classified gene: SCAPER as Green List (high evidence)
Ciliopathies v0.78 SCAPER Zornitza Stark Gene: scaper has been classified as Green List (High Evidence).
Ciliopathies v0.77 SCAPER Zornitza Stark Classified gene: SCAPER as Green List (high evidence)
Ciliopathies v0.77 SCAPER Zornitza Stark Gene: scaper has been classified as Green List (High Evidence).
Ciliopathies v0.77 Zornitza Stark removed gene:NID1 from the panel
Ciliopathies v0.76 Zornitza Stark removed gene:VLDLR from the panel
Ciliopathies v0.76 Zornitza Stark removed gene:WNT1 from the panel
Ciliopathies v0.76 Zornitza Stark removed gene:ZIC1 from the panel
Mendeliome v0.2715 NID1 Zornitza Stark Marked gene: NID1 as ready
Mendeliome v0.2715 NID1 Zornitza Stark Gene: nid1 has been classified as Green List (High Evidence).
Mendeliome v0.2715 NID1 Zornitza Stark Phenotypes for gene: NID1 were changed from to Dandy-Walker malformation and occipital cephalocele; Hydrocephalus with or without seizures
Mendeliome v0.2714 NID1 Zornitza Stark Publications for gene: NID1 were set to
Mendeliome v0.2713 NID1 Zornitza Stark Mode of inheritance for gene: NID1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Regression v0.116 ZIC4 Crystle Lee reviewed gene: ZIC4: Rating: RED; Mode of pathogenicity: None; Publications: 21204220, 15338008; Phenotypes: ; Mode of inheritance: Unknown
Mendeliome v0.2712 NID1 Zornitza Stark reviewed gene: NID1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23674478, 25558065, 12480912, 30773799; Phenotypes: Dandy-Walker malformation and occipital cephalocele, Hydrocephalus with or without seizures; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2712 ZIC4 Crystle Lee reviewed gene: ZIC4: Rating: RED; Mode of pathogenicity: None; Publications: 21204220, 15338008; Phenotypes: ; Mode of inheritance: Unknown
Joubert syndrome and other neurological ciliopathies v0.39 WNT1 Zornitza Stark Marked gene: WNT1 as ready
Joubert syndrome and other neurological ciliopathies v0.39 WNT1 Zornitza Stark Gene: wnt1 has been classified as Red List (Low Evidence).
Joubert syndrome and other neurological ciliopathies v0.39 WNT1 Zornitza Stark Phenotypes for gene: WNT1 were changed from to Osteogenesis imperfecta, type XV (MIM#615220)
Joubert syndrome and other neurological ciliopathies v0.38 WNT1 Zornitza Stark Publications for gene: WNT1 were set to
Joubert syndrome and other neurological ciliopathies v0.37 WNT1 Zornitza Stark Mode of inheritance for gene: WNT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.445 NDUFS7 Ain Roesley reviewed gene: NDUFS7: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 22644603; Phenotypes: Mitochondrial complex I deficiency, nuclear type 3 (MIM# 618224); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Joubert syndrome and other neurological ciliopathies v0.36 NID1 Zornitza Stark Marked gene: NID1 as ready
Joubert syndrome and other neurological ciliopathies v0.36 NID1 Zornitza Stark Gene: nid1 has been classified as Amber List (Moderate Evidence).
Joubert syndrome and other neurological ciliopathies v0.36 NID1 Zornitza Stark Phenotypes for gene: NID1 were changed from to Dandy-Walker malformation and occipital cephalocele; Hydrocephalus with or without seizures
Joubert syndrome and other neurological ciliopathies v0.35 NID1 Zornitza Stark Publications for gene: NID1 were set to
Joubert syndrome and other neurological ciliopathies v0.34 NID1 Zornitza Stark Mode of inheritance for gene: NID1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ciliopathies v0.75 ICK Zornitza Stark Marked gene: ICK as ready
Ciliopathies v0.75 ICK Zornitza Stark Gene: ick has been classified as Green List (High Evidence).
Ciliopathies v0.75 ICK Zornitza Stark Classified gene: ICK as Green List (high evidence)
Ciliopathies v0.75 ICK Zornitza Stark Gene: ick has been classified as Green List (High Evidence).
Joubert syndrome and other neurological ciliopathies v0.33 ZIC4 Zornitza Stark Marked gene: ZIC4 as ready
Joubert syndrome and other neurological ciliopathies v0.33 ZIC4 Zornitza Stark Gene: zic4 has been classified as Red List (Low Evidence).
Joubert syndrome and other neurological ciliopathies v0.33 ZIC4 Zornitza Stark Publications for gene: ZIC4 were set to
Joubert syndrome and other neurological ciliopathies v0.32 ZIC4 Zornitza Stark Classified gene: ZIC4 as Red List (low evidence)
Joubert syndrome and other neurological ciliopathies v0.32 ZIC4 Zornitza Stark Gene: zic4 has been classified as Red List (Low Evidence).
Joubert syndrome and other neurological ciliopathies v0.31 NID1 Zornitza Stark Classified gene: NID1 as Amber List (moderate evidence)
Joubert syndrome and other neurological ciliopathies v0.31 NID1 Zornitza Stark Gene: nid1 has been classified as Amber List (Moderate Evidence).
Joubert syndrome and other neurological ciliopathies v0.30 NID1 Zornitza Stark reviewed gene: NID1: Rating: AMBER; Mode of pathogenicity: None; Publications: 23674478, 25558065, 12480912, 30773799; Phenotypes: Dandy-Walker malformation and occipital cephalocele, Hydrocephalus with or without seizures; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Joubert syndrome and other neurological ciliopathies v0.30 Zornitza Stark Panel name changed from Joubert syndrome and other cerebellar malformations to Joubert syndrome and other neurological ciliopathies
Panel types changed to Victorian Clinical Genetics Services; Rare Disease
Joubert syndrome and other neurological ciliopathies v0.29 ZIC1 Zornitza Stark Marked gene: ZIC1 as ready
Joubert syndrome and other neurological ciliopathies v0.29 ZIC1 Zornitza Stark Gene: zic1 has been classified as Red List (Low Evidence).
Joubert syndrome and other neurological ciliopathies v0.29 ZIC1 Zornitza Stark Phenotypes for gene: ZIC1 were changed from to Structural brain anomalies with impaired intellectual development and craniosynostosis (MIM#618736)
Ciliopathies v0.74 PIBF1 Zornitza Stark Marked gene: PIBF1 as ready
Ciliopathies v0.74 PIBF1 Zornitza Stark Gene: pibf1 has been classified as Green List (High Evidence).
Ciliopathies v0.74 PIBF1 Zornitza Stark Classified gene: PIBF1 as Green List (high evidence)
Ciliopathies v0.74 PIBF1 Zornitza Stark Gene: pibf1 has been classified as Green List (High Evidence).
Joubert syndrome and other neurological ciliopathies v0.28 ZIC1 Zornitza Stark Mode of pathogenicity for gene: ZIC1 was changed from Other to Other
Joubert syndrome and other neurological ciliopathies v0.27 ZIC1 Zornitza Stark Mode of pathogenicity for gene: ZIC1 was changed from to Other
Joubert syndrome and other neurological ciliopathies v0.27 ZIC1 Zornitza Stark Publications for gene: ZIC1 were set to
Joubert syndrome and other neurological ciliopathies v0.26 ZIC1 Zornitza Stark Mode of inheritance for gene: ZIC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Joubert syndrome and other neurological ciliopathies v0.25 ZIC1 Zornitza Stark Classified gene: ZIC1 as Red List (low evidence)
Joubert syndrome and other neurological ciliopathies v0.25 ZIC1 Zornitza Stark Gene: zic1 has been classified as Red List (Low Evidence).
Joubert syndrome and other neurological ciliopathies v0.24 ZIC1 Zornitza Stark reviewed gene: ZIC1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Structural brain anomalies with impaired intellectual development and craniosynostosis (MIM#618736); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebellar and Pontocerebellar Hypoplasia v0.139 VLDLR Zornitza Stark edited their review of gene: VLDLR: Added comment: VLDLR guides neuroblast migration in the cerebral cortex and cerebellum (PMID: 16080122).

PMID: 16080122 - Whole gene homozygous deletion affecting 8 patients in 3 related Hutterite families. The deletion extended in neighbouring LOC401491 (no known function)
Patients displayed symptoms including delayed ambulation, truncal ataxia, strabismus and pes planus in the majority of patients, seizures in 40% of patients, and short stature in 15% of patients. Magnetic resonance imaging (MRI) demonstrates inferior cerebellar hypoplasia and mild cortical gyral simplification.

PMID: 18326629 - Two families with homozygous PTCs. Patients had impaired cerebrocerebellar function including cerebrocerebellar hypoplasia, vermial hypoplasia, and gait.

PMID: 10380922 - Mouse models are neurologically normal. Knockout mice show malformation of neuronal layers, Purkinje cell assemble incorrectly, there are inverted cortical layers

Summary: 3 independant families + animal studies; Changed publications: 16080122, 18326629, 10380922
Joubert syndrome and other neurological ciliopathies v0.24 VLDLR Zornitza Stark Marked gene: VLDLR as ready
Joubert syndrome and other neurological ciliopathies v0.24 VLDLR Zornitza Stark Gene: vldlr has been classified as Red List (Low Evidence).
Joubert syndrome and other neurological ciliopathies v0.24 VLDLR Zornitza Stark Phenotypes for gene: VLDLR were changed from to Cerebellar hypoplasia and mental retardation with or without quadrupedal locomotion 1, MIM# 224050
Joubert syndrome and other neurological ciliopathies v0.23 VLDLR Zornitza Stark Mode of inheritance for gene: VLDLR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Joubert syndrome and other neurological ciliopathies v0.22 VLDLR Zornitza Stark Classified gene: VLDLR as Red List (low evidence)
Joubert syndrome and other neurological ciliopathies v0.22 VLDLR Zornitza Stark Gene: vldlr has been classified as Red List (Low Evidence).
Joubert syndrome and other neurological ciliopathies v0.21 VLDLR Zornitza Stark reviewed gene: VLDLR: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebellar hypoplasia and mental retardation with or without quadrupedal locomotion 1, MIM# 224050; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Joubert syndrome and other neurological ciliopathies v0.21 WNT1 Zornitza Stark Classified gene: WNT1 as Red List (low evidence)
Joubert syndrome and other neurological ciliopathies v0.21 WNT1 Zornitza Stark Gene: wnt1 has been classified as Red List (Low Evidence).
Joubert syndrome and other neurological ciliopathies v0.20 WNT1 Zornitza Stark reviewed gene: WNT1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Osteogenesis imperfecta, type XV (MIM#615220); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v0.73 WNT1 Crystle Lee gene: WNT1 was added
gene: WNT1 was added to Ciliopathies. Sources: Expert Review
Mode of inheritance for gene: WNT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WNT1 were set to 26671912; 23499309; 23434763
Phenotypes for gene: WNT1 were set to Osteogenesis imperfecta, type XV (MIM#615220)
Added comment: WNT1 causes AR OI, brain (cerebellar) malformations not a consistent feature.

PMID: 26671912; Reviewed clinical and brain imaging of 6 patients from 4 families (2 unrelated Hmong fams with same variant, likely founder). Cerebellar hypoplasia in 5 of 6 patients with varied severity. Cerebellar abnormalities inconsistent between the 3 Hmong patients with same variant.

PMID: 23499309; Reported hom variants in 5 consang fams with autosomal-recessive OI. Ataxia, other signs of
cerebellar dysfunction not a key feature, only one patient showed brain malformations.

PMID: 23434763; Reported 3 families with OI, no brain malformations described.
Sources: Expert Review
Joubert syndrome and other neurological ciliopathies v0.20 WNT1 Crystle Lee reviewed gene: WNT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 26671912, 23499309, 23434763; Phenotypes: Osteogenesis imperfecta, type XV (MIM#615220); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v0.73 VLDLR Elena Savva gene: VLDLR was added
gene: VLDLR was added to Ciliopathies. Sources: Expert list
Mode of inheritance for gene: VLDLR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VLDLR were set to PMID: 16080122; 18326629; 10380922
Phenotypes for gene: VLDLR were set to Cerebellar hypoplasia and mental retardation with or without quadrupedal locomotion 1 224050
Review for gene: VLDLR was set to GREEN
Added comment: VLDLR guides neuroblast migration in the cerebral cortex and cerebellum (PMID: 16080122).

PMID: 16080122 - Whole gene homozygous deletion affecting 8 patients in 3 related Hutterite families. The deletion extended in neighbouring LOC401491 (no known function)
Patients displayed symptoms including delayed ambulation, truncal ataxia, strabismus and pes planus in the majority of patients, seizures in 40% of patients, and short stature in 15% of patients. Magnetic resonance imaging (MRI) demonstrates inferior cerebellar hypoplasia and mild cortical gyral simplification.

PMID: 18326629 - Two families with homozygous PTCs. Patients had impaired cerebrocerebellar function including cerebrocerebellar hypoplasia, vermial hypoplasia, and gait.

PMID: 10380922 - Mouse models are neurologically normal. Knockout mice show malformation of neuronal layers, Purkinje cell assemble incorrectly, there are inverted cortical layers

Summary: 3 independant families + animal studies
Sources: Expert list
Ciliopathies v0.73 ZIC1 Crystle Lee gene: ZIC1 was added
gene: ZIC1 was added to Ciliopathies. Sources: Expert Review
Mode of inheritance for gene: ZIC1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ZIC1 were set to 26340333; 9412507; 14981711
Phenotypes for gene: ZIC1 were set to Structural brain anomalies with impaired intellectual development and craniosynostosis (MIM#618736)
Mode of pathogenicity for gene: ZIC1 was set to Other
Review for gene: ZIC1 was set to AMBER
Added comment: Single paper from 2015 with reports of variants in ZIC1 - unsure if JS phenotype? Amber/Red

PMID: 26340333; Reported 5 families with coronal craniosynotosis and learning disabilities with inconsistent brain abnormalities (1 pt with abnormalities of the cerebellum and pons). 4 nonsense and 1 missense reported to cause disease through GoF mechanism

PMID: 9412507; Zic1 deficient mice presented with ataxia and cerebellar hypoplasia (1998)

PMID: 14981711; This 2004 paper acknowledges that null mice shows JS phenotype, but excluded ZIC1 as causative gene because no pathogenic variants found in cohort of 47 JS patients
Sources: Expert Review
Joubert syndrome and other neurological ciliopathies v0.20 ZIC1 Crystle Lee changed review comment from: PMID: 26340333; Reported 5 families with coronal craniosynotosis and learning disabilities with inconsistent brain abnormalities (1 pt with abnormalities of the cerebellum and pons). 4 nonsense and 1 missense reported to cause disease through GoF mechanism

PMID: 9412507; Zic1 deficient mice presented with ataxia and cerebellar hypoplasia (1998)

PMID: 14981711; This 2004 paper acknowledges that null mice shows JS phenotype, but excluded ZIC1 as causative gene because no pathogenic variants found in cohort of 47 JS patients; to: Single paper from 2015 with reports of variants in ZIC1 - unsure if JS phenotype? Amber/Red

PMID: 26340333; Reported 5 families with coronal craniosynotosis and learning disabilities with inconsistent brain abnormalities (1 pt with abnormalities of the cerebellum and pons). 4 nonsense and 1 missense reported to cause disease through GoF mechanism

PMID: 9412507; Zic1 deficient mice presented with ataxia and cerebellar hypoplasia (1998)

PMID: 14981711; This 2004 paper acknowledges that null mice shows JS phenotype, but excluded ZIC1 as causative gene because no pathogenic variants found in cohort of 47 JS patients
Joubert syndrome and other neurological ciliopathies v0.20 ZIC1 Crystle Lee Deleted their comment
Joubert syndrome and other neurological ciliopathies v0.20 ZIC1 Crystle Lee changed review comment from: PMID: 26340333; Reported 5 families with coronal craniosynotosis and learning disabilities with inconsistent brain abnormalities (1 pt with abnormalities of the cerebellum and pons). 4 nonsense and 1 missense reported to cause disease through GoF mechanism

PMID: 9412507; Zic1 deficient mice presented with ataxia and cerebellar hypoplasia

PMID: 14981711; This 2004 paper acknowledges that null mice shows JS phenotype, but excluded ZIC1 as causative gene because no pathogenic variants found in cohort of 47 JS patients; to: PMID: 26340333; Reported 5 families with coronal craniosynotosis and learning disabilities with inconsistent brain abnormalities (1 pt with abnormalities of the cerebellum and pons). 4 nonsense and 1 missense reported to cause disease through GoF mechanism

PMID: 9412507; Zic1 deficient mice presented with ataxia and cerebellar hypoplasia (1998)

PMID: 14981711; This 2004 paper acknowledges that null mice shows JS phenotype, but excluded ZIC1 as causative gene because no pathogenic variants found in cohort of 47 JS patients
Joubert syndrome and other neurological ciliopathies v0.20 ZIC1 Crystle Lee changed review comment from: PMID: 26340333; Reported 5 families with coronal craniosynotosis and learning disabilities with inconsistent brain abnormalities (1 pt with abnormalities of the cerebellum and pons). 4 nonsense and 1 missense reported to cause disease through GoF mechanism

PMID: 9412507; Zic1 deficient mice presented with ataxia and cerebellar hypoplasia; to: PMID: 26340333; Reported 5 families with coronal craniosynotosis and learning disabilities with inconsistent brain abnormalities (1 pt with abnormalities of the cerebellum and pons). 4 nonsense and 1 missense reported to cause disease through GoF mechanism

PMID: 9412507; Zic1 deficient mice presented with ataxia and cerebellar hypoplasia (1998)
Joubert syndrome and other neurological ciliopathies v0.20 ZIC1 Crystle Lee commented on gene: ZIC1: PMID: 26340333; Reported 5 families with coronal craniosynotosis and learning disabilities with inconsistent brain abnormalities (1 pt with abnormalities of the cerebellum and pons). 4 nonsense and 1 missense reported to cause disease through GoF mechanism

PMID: 9412507; Zic1 deficient mice presented with ataxia and cerebellar hypoplasia

PMID: 14981711; This 2004 paper acknowledges that null mice shows JS phenotype, but excluded ZIC1 as causative gene because no pathogenic variants found in cohort of 47 JS patients
Joubert syndrome and other neurological ciliopathies v0.20 ZIC1 Crystle Lee edited their review of gene: ZIC1: Changed publications: 26340333, 9412507, 14981711
Joubert syndrome and other neurological ciliopathies v0.20 ZIC1 Crystle Lee reviewed gene: ZIC1: Rating: AMBER; Mode of pathogenicity: Other; Publications: 26340333, 9412507; Phenotypes: Structural brain anomalies with impaired intellectual development and craniosynostosis (MIM#618736); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Ciliopathies v0.73 PIBF1 Elena Savva gene: PIBF1 was added
gene: PIBF1 was added to Ciliopathies. Sources: Expert Review
Mode of inheritance for gene: PIBF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIBF1 were set to PMID:26167768; 30858804; 29695797
Phenotypes for gene: PIBF1 were set to Joubert syndrome 33, OMIM #617767
Review for gene: PIBF1 was set to GREEN
Added comment: 7 families altogether: 3 of these are Hutterite and share the same founder variant.
Sources: Expert list
Sources: Expert Review
Ciliopathies v0.73 NID1 Elena Savva gene: NID1 was added
gene: NID1 was added to Ciliopathies. Sources: Expert Review
Mode of inheritance for gene: NID1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NID1 were set to PMID: 23674478; 25558065; 12480912; 30773799
Phenotypes for gene: NID1 were set to Dandy-Walker malformation and occipital cephalocele; Hydrocephalus with or without seizures
Added comment: no OMIM disease association

PMID: 23674478 - single Vietnamese family (14 affecteds) with Dandy-Walker variant/cerebellar vermal hypoplasia ± cephalocele had a heterozygous nonsense. Normal eye examination.

PMID: 25558065 - reports 2 sibs with hydrocephalus with a heterozygous splice variant resulting in an inframe insertion (confirmed by RT-PCR). Brother shows additional phenotypes of seizures and focal epilepsy.

PMID: 12480912 - mouse model with neurological deficits including seizure-like symptoms, altered basement membrane morphology in brain capillaries and the lens capsule.

PMID: 30773799 - 1 family Dandy-Walker malformation and occipital cephalocele with the nonsense from PMID: 23674478. Familial variation, affecteds lack cerebellar involvement

Summary: 3 families & animal model - hard to tell if the phenotype is related
Sources: Expert Review
Leukodystrophy v0.88 DARS2 Zornitza Stark Marked gene: DARS2 as ready
Leukodystrophy v0.88 DARS2 Zornitza Stark Gene: dars2 has been classified as Green List (High Evidence).
Leukodystrophy v0.88 DARS2 Zornitza Stark Classified gene: DARS2 as Green List (high evidence)
Leukodystrophy v0.88 DARS2 Zornitza Stark Gene: dars2 has been classified as Green List (High Evidence).
Leukodystrophy v0.87 DARS2 Zornitza Stark gene: DARS2 was added
gene: DARS2 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: DARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DARS2 were set to 17384640; 15002045; 16788019
Phenotypes for gene: DARS2 were set to Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, MIM# 611105
Review for gene: DARS2 was set to GREEN
Added comment: Slowly progressive disorder with variable age of onset, but onset of symptoms reported in childhood in many.
Sources: Expert list
Hereditary Spastic Paraplegia v0.84 DARS Zornitza Stark Marked gene: DARS as ready
Hereditary Spastic Paraplegia v0.84 DARS Zornitza Stark Gene: dars has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v0.84 DARS Zornitza Stark Classified gene: DARS as Green List (high evidence)
Hereditary Spastic Paraplegia v0.84 DARS Zornitza Stark Gene: dars has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v0.83 DARS Zornitza Stark Tag new gene name tag was added to gene: DARS.
Hereditary Spastic Paraplegia v0.83 DARS Zornitza Stark gene: DARS was added
gene: DARS was added to Hereditary Spastic Paraplegia - paediatric. Sources: Expert list
Mode of inheritance for gene: DARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DARS were set to 25527264; 23643384
Phenotypes for gene: DARS were set to Hypomyelination with brainstem and spinal cord involvement and leg spasticity, MIM# 615281
Review for gene: DARS was set to GREEN
Added comment: Onset typically in infancy with lower limb spasticity. Brain MRI shows extensive white matter abnormalities involving the supratentorial white matter, brainstem, cerebellar peduncles, and dorsal columns and lateral corticospinal tracts of the spinal cord. However, two individuals with adolescent onset described in 25527264, mimicking steroid-responsive neuroinflammatory disorder. HGNC approved name DARS1.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2615 DARS Zornitza Stark Marked gene: DARS as ready
Intellectual disability syndromic and non-syndromic v0.2615 DARS Zornitza Stark Gene: dars has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2615 DARS Zornitza Stark Phenotypes for gene: DARS were changed from to Hypomyelination with brainstem and spinal cord involvement and leg spasticity, MIM# 615281
Intellectual disability syndromic and non-syndromic v0.2614 DARS Zornitza Stark Publications for gene: DARS were set to
Intellectual disability syndromic and non-syndromic v0.2613 DARS Zornitza Stark Mode of inheritance for gene: DARS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2612 DARS Zornitza Stark Tag new gene name tag was added to gene: DARS.
Intellectual disability syndromic and non-syndromic v0.2612 DARS Zornitza Stark reviewed gene: DARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 25527264, 23643384; Phenotypes: Hypomyelination with brainstem and spinal cord involvement and leg spasticity, MIM# 615281; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2712 DARS Zornitza Stark Marked gene: DARS as ready
Mendeliome v0.2712 DARS Zornitza Stark Gene: dars has been classified as Green List (High Evidence).
Mendeliome v0.2712 DARS Zornitza Stark Phenotypes for gene: DARS were changed from to Hypomyelination with brainstem and spinal cord involvement and leg spasticity, MIM# 615281
Mendeliome v0.2711 DARS Zornitza Stark Publications for gene: DARS were set to
Mendeliome v0.2710 DARS Zornitza Stark Mode of inheritance for gene: DARS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2709 DARS Zornitza Stark Tag new gene name tag was added to gene: DARS.
Mendeliome v0.2709 DARS Zornitza Stark reviewed gene: DARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 25527264, 23643384; Phenotypes: Hypomyelination with brainstem and spinal cord involvement and leg spasticity, MIM# 615281; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mackenzie's Mission_Reproductive Carrier Screening v0.6 DARS Zornitza Stark Marked gene: DARS as ready
Mackenzie's Mission_Reproductive Carrier Screening v0.6 DARS Zornitza Stark Gene: dars has been classified as Green List (High Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.6 DARS Zornitza Stark Tag new gene name tag was added to gene: DARS.
Mackenzie's Mission_Reproductive Carrier Screening v0.6 DARS Zornitza Stark reviewed gene: DARS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypomyelination with brainstem and spinal cord involvement and leg spasticity, MIM# 615281; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Joubert syndrome and other neurological ciliopathies v0.20 ZIC4 Crystle Lee reviewed gene: ZIC4: Rating: RED; Mode of pathogenicity: None; Publications: 21204220, 15338008; Phenotypes: ; Mode of inheritance: Unknown
Leukodystrophy v0.86 DARS Zornitza Stark Marked gene: DARS as ready
Leukodystrophy v0.86 DARS Zornitza Stark Gene: dars has been classified as Green List (High Evidence).
Leukodystrophy v0.86 DARS Zornitza Stark Tag new gene name tag was added to gene: DARS.
Leukodystrophy v0.86 DARS Zornitza Stark Classified gene: DARS as Green List (high evidence)
Leukodystrophy v0.86 DARS Zornitza Stark Gene: dars has been classified as Green List (High Evidence).
Leukodystrophy v0.85 DARS Zornitza Stark gene: DARS was added
gene: DARS was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: DARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DARS were set to 23643384
Phenotypes for gene: DARS were set to Hypomyelination with brainstem and spinal cord involvement and leg spasticity, MIM# 615281
Review for gene: DARS was set to GREEN
Added comment: Onset typically in infancy with lower limb spasticity. Brain MRI shows extensive white matter abnormalities involving the supratentorial white matter, brainstem, cerebellar peduncles, and dorsal columns and lateral corticospinal tracts of the spinal cord. HGNC approved name DARS1.
Sources: Expert list
Leukodystrophy v0.84 CLCN2 Zornitza Stark Marked gene: CLCN2 as ready
Leukodystrophy v0.84 CLCN2 Zornitza Stark Gene: clcn2 has been classified as Green List (High Evidence).
Leukodystrophy v0.84 CLCN2 Zornitza Stark Classified gene: CLCN2 as Green List (high evidence)
Leukodystrophy v0.84 CLCN2 Zornitza Stark Gene: clcn2 has been classified as Green List (High Evidence).
Leukodystrophy v0.83 CLCN2 Zornitza Stark gene: CLCN2 was added
gene: CLCN2 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: CLCN2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLCN2 were set to 23707145
Phenotypes for gene: CLCN2 were set to Leukoencephalopathy with ataxia, MIM# 615651
Review for gene: CLCN2 was set to GREEN
Added comment: At least six families reported, three with adult onset and three with childhood onset.
Sources: Expert list
Ciliopathies v0.73 ICK Crystle Lee gene: ICK was added
gene: ICK was added to Ciliopathies. Sources: Expert Review
Mode of inheritance for gene: ICK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ICK were set to 19185282; 27069622; 27466187; 24797473; 24853502
Phenotypes for gene: ICK were set to Endocrine-cerebroosteodysplasia (MIM#612651)
Review for gene: ICK was set to GREEN
Added comment: 3 families reported, functional studies and animal models.

PMID: 19185282; 6 affected from 2 Amish families with endocrine-cerebro-osteodysplasia (ECO)

PMID: 27069622; A different variant reported in a Turkish fetus presenting with ECO and overlapping features of ciliopathies. Functional studies showed abnormal ciliary localization.

PMID: 27466187; Additional variant identified in a patient with short rib polydactyly syndromes (SRPS). Functional studies showed that the variant caused ciliary defects

PMID: 24797473; Ick deficient mice showed ciliary defects. Authors concluded that ICK is required for normal ciliogenesis

PMID: 24853502; Ick knockout mice recapitulates clinical symptoms of ECO. Defects in ICK caused aberrant ciliogenesis
Sources: Expert Review
Skeletal Ciliopathies v0.11 ICK Crystle Lee edited their review of gene: ICK: Changed publications: 19185282, 27069622, 27466187, 24797473, 24853502
Leukodystrophy v0.82 ASPA Zornitza Stark Marked gene: ASPA as ready
Leukodystrophy v0.82 ASPA Zornitza Stark Gene: aspa has been classified as Green List (High Evidence).
Leukodystrophy v0.82 ASPA Zornitza Stark Classified gene: ASPA as Green List (high evidence)
Leukodystrophy v0.82 ASPA Zornitza Stark Gene: aspa has been classified as Green List (High Evidence).
Leukodystrophy v0.81 ASPA Zornitza Stark gene: ASPA was added
gene: ASPA was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: ASPA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ASPA were set to Canavan disease, MIM# 271900
Review for gene: ASPA was set to GREEN
Added comment: Congenital, infantile, and late-onset forms of Canavan disease reported.
Sources: Expert list
Skeletal Ciliopathies v0.11 ICK Crystle Lee changed review comment from: 3 families reported, functional studies and animal models.

PMID: 19185282; 6 affected from 2 Amish families with endocrine-cerebro-osteodysplasia (ECO)

PMID: 27069622; A different variant reported in a Turkish fetus presenting with ECO and overlapping features of ciliopathies. Functional studies showed abnormal ciliary localization.

PMID: 27466187; Additional variant identified in a patient with short rib polydactyly syndromes (SRPS). Functional studies showed that the variant caused ciliary defects

PMID: 24797473; Ick deficient mice showed ciliary defects. Authors concluded that ICK is required for normal ciliogenesis

PMID: 24853502; Ick knockout mice recapitulates clinical symptoms of ECO. Defects in ICK caused aberrant ciliogenesis; to: 3 families reported, functional studies and animal models.

PMID: 19185282; 6 affected from 2 Amish families with endocrine-cerebro-osteodysplasia (ECO)

PMID: 27069622; A different variant reported in a Turkish fetus presenting with ECO and overlapping features of ciliopathies. Functional studies showed abnormal ciliary localization.

PMID: 27466187; Additional variant identified in a patient with short rib polydactyly syndromes (SRPS). Functional studies showed that the variant caused ciliary defects

PMID: 24797473; Ick deficient mice showed ciliary defects. Authors concluded that ICK is required for normal ciliogenesis

PMID: 24853502; Ick knockout mice recapitulates clinical symptoms of ECO. Defects in ICK caused aberrant ciliogenesis
Skeletal Ciliopathies v0.11 ICK Crystle Lee changed review comment from: 3 families reported, functional studies and animal models.

PMID: 19185282; 6 affected from 2 Amish families with endocrine-cerebro-osteodysplasia (ECO)

PMID: 27069622; A different variant reported in a Turkish fetus presenting with ECO and overlapping features of ciliopathies. Functional studies showed abnormal ciliary localization.

PMID:27069622; Additional variant identified in a patient with short rib polydactyly syndromes (SRPS) . Functional studies showed that the variant caused ciliary defects

PMID: 24797473; Ick deficient mice showed ciliary defects. Authors concluded that ICK is required for normal ciliogenesis

PMID: 24853502; Ick knockout mice recapitulates clinical symptoms of ECO. Defects in ICK caused aberrant ciliogenesis; to: 3 families reported, functional studies and animal models.

PMID: 19185282; 6 affected from 2 Amish families with endocrine-cerebro-osteodysplasia (ECO)

PMID: 27069622; A different variant reported in a Turkish fetus presenting with ECO and overlapping features of ciliopathies. Functional studies showed abnormal ciliary localization.

PMID: 27466187; Additional variant identified in a patient with short rib polydactyly syndromes (SRPS). Functional studies showed that the variant caused ciliary defects

PMID: 24797473; Ick deficient mice showed ciliary defects. Authors concluded that ICK is required for normal ciliogenesis

PMID: 24853502; Ick knockout mice recapitulates clinical symptoms of ECO. Defects in ICK caused aberrant ciliogenesis
Leukodystrophy v0.80 ARSA Zornitza Stark Marked gene: ARSA as ready
Leukodystrophy v0.80 ARSA Zornitza Stark Gene: arsa has been classified as Green List (High Evidence).
Leukodystrophy v0.80 ARSA Zornitza Stark Classified gene: ARSA as Green List (high evidence)
Leukodystrophy v0.80 ARSA Zornitza Stark Gene: arsa has been classified as Green List (High Evidence).
Leukodystrophy v0.79 ARSA Zornitza Stark gene: ARSA was added
gene: ARSA was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: ARSA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ARSA were set to Metachromatic leukodystrophy, MIM# 250100
Review for gene: ARSA was set to GREEN
Added comment: More severe forms present in infancy/childhood.
Sources: Expert list
Skeletal Ciliopathies v0.11 ICK Crystle Lee reviewed gene: ICK: Rating: GREEN; Mode of pathogenicity: None; Publications: 19185282, 27069622, 27069622, 24797473, 24853502; Phenotypes: Endocrine-cerebroosteodysplasia (MIM#612651); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy v0.78 ALDH3A2 Zornitza Stark Marked gene: ALDH3A2 as ready
Leukodystrophy v0.78 ALDH3A2 Zornitza Stark Gene: aldh3a2 has been classified as Green List (High Evidence).
Leukodystrophy v0.78 ALDH3A2 Zornitza Stark Classified gene: ALDH3A2 as Green List (high evidence)
Leukodystrophy v0.78 ALDH3A2 Zornitza Stark Gene: aldh3a2 has been classified as Green List (High Evidence).
Leukodystrophy v0.77 ALDH3A2 Zornitza Stark gene: ALDH3A2 was added
gene: ALDH3A2 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: ALDH3A2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ALDH3A2 were set to Sjogren-Larsson syndrome, MIM# 270200
Review for gene: ALDH3A2 was set to GREEN
Added comment: Onset of signs and symptoms is typically in infancy, though white matter changes become more pronounced with age.
Sources: Expert list
Mendeliome v0.2709 CCDC65 Zornitza Stark Tag founder tag was added to gene: CCDC65.
Mendeliome v0.2709 CCDC65 Zornitza Stark Marked gene: CCDC65 as ready
Mendeliome v0.2709 CCDC65 Zornitza Stark Gene: ccdc65 has been classified as Green List (High Evidence).
Mendeliome v0.2709 CCDC65 Zornitza Stark Phenotypes for gene: CCDC65 were changed from to Ciliary dyskinesia, primary, 27, MIM# 615504
Mendeliome v0.2708 CCDC65 Zornitza Stark Publications for gene: CCDC65 were set to
Mendeliome v0.2707 CCDC65 Zornitza Stark Mode of inheritance for gene: CCDC65 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2706 CCDC65 Zornitza Stark reviewed gene: CCDC65: Rating: GREEN; Mode of pathogenicity: None; Publications: 23991085, 24094744; Phenotypes: Ciliary dyskinesia, primary, 27, MIM# 615504; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.15 CCDC65 Zornitza Stark Marked gene: CCDC65 as ready
Heterotaxy v0.15 CCDC65 Zornitza Stark Gene: ccdc65 has been classified as Green List (High Evidence).
Heterotaxy v0.15 CCDC65 Zornitza Stark Tag founder tag was added to gene: CCDC65.
Heterotaxy v0.15 CCDC65 Zornitza Stark Phenotypes for gene: CCDC65 were changed from to Ciliary dyskinesia, primary, 27, MIM# 615504
Heterotaxy v0.14 CCDC65 Zornitza Stark Publications for gene: CCDC65 were set to
Heterotaxy v0.13 CCDC65 Zornitza Stark Mode of inheritance for gene: CCDC65 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.12 CCDC65 Zornitza Stark reviewed gene: CCDC65: Rating: GREEN; Mode of pathogenicity: None; Publications: 23991085, 24094744; Phenotypes: Ciliary dyskinesia, primary, 27, MIM# 615504; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.40 CCDC65 Zornitza Stark Classified gene: CCDC65 as Green List (high evidence)
Ciliary Dyskinesia v0.40 CCDC65 Zornitza Stark Gene: ccdc65 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.39 CCDC65 Zornitza Stark reviewed gene: CCDC65: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 27, MIM# 615504; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.39 CCDC65 Zornitza Stark Deleted their review
Ciliary Dyskinesia v0.39 CCDC65 Zornitza Stark Deleted their comment
Ciliopathies v0.73 SCAPER Elena Savva gene: SCAPER was added
gene: SCAPER was added to Ciliopathies. Sources: Expert Review
Mode of inheritance for gene: SCAPER was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCAPER were set to PMID:30723319; 28794130; 31069901; 31192531; 30723319
Phenotypes for gene: SCAPER were set to Intellectual developmental disorder and retinitis pigmentosa, OMIM #618195; Bardet-Biedl syndrome
Review for gene: SCAPER was set to GREEN
Added comment: Two distantly related consanguineous families reported plus note some of the individuals in the preceding papers had a BBS phenotype. Functional data to associate SCAPER with ciliary dynamics and disassembly.
Sources: Literature
Sources: Expert Review
Ciliary Dyskinesia v0.39 CCDC65 Zornitza Stark Marked gene: CCDC65 as ready
Ciliary Dyskinesia v0.39 CCDC65 Zornitza Stark Added comment: Comment when marking as ready: Agree, single founder variant reported, functional data.
Ciliary Dyskinesia v0.39 CCDC65 Zornitza Stark Gene: ccdc65 has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v0.39 CCDC65 Zornitza Stark Phenotypes for gene: CCDC65 were changed from to Ciliary dyskinesia, primary, 27, MIM# 615504
Ciliary Dyskinesia v0.38 CCDC65 Zornitza Stark Publications for gene: CCDC65 were set to
Ciliary Dyskinesia v0.37 CCDC65 Zornitza Stark Mode of inheritance for gene: CCDC65 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.36 CCDC65 Zornitza Stark Classified gene: CCDC65 as Amber List (moderate evidence)
Ciliary Dyskinesia v0.36 CCDC65 Zornitza Stark Gene: ccdc65 has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v0.35 CCDC65 Zornitza Stark Tag founder tag was added to gene: CCDC65.
Ciliary Dyskinesia v0.35 CCDC65 Elena Savva reviewed gene: CCDC65: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 23991085, 24094744; Phenotypes: Ciliary dyskinesia, primary, 27 615504; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy v0.76 ADAR Zornitza Stark Marked gene: ADAR as ready
Leukodystrophy v0.76 ADAR Zornitza Stark Gene: adar has been classified as Green List (High Evidence).
Leukodystrophy v0.76 ADAR Zornitza Stark Classified gene: ADAR as Green List (high evidence)
Leukodystrophy v0.76 ADAR Zornitza Stark Gene: adar has been classified as Green List (High Evidence).
Leukodystrophy v0.75 ADAR Zornitza Stark gene: ADAR was added
gene: ADAR was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: ADAR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ADAR were set to Aicardi-Goutieres syndrome 6, MIM# 615010
Review for gene: ADAR was set to GREEN
Added comment: White matter changes reported in some.
Sources: Expert list
Leukodystrophy v0.74 CYP7B1 Zornitza Stark Marked gene: CYP7B1 as ready
Leukodystrophy v0.74 CYP7B1 Zornitza Stark Gene: cyp7b1 has been classified as Green List (High Evidence).
Leukodystrophy v0.74 CYP7B1 Zornitza Stark Classified gene: CYP7B1 as Green List (high evidence)
Leukodystrophy v0.74 CYP7B1 Zornitza Stark Gene: cyp7b1 has been classified as Green List (High Evidence).
Leukodystrophy v0.73 CYP7B1 Zornitza Stark gene: CYP7B1 was added
gene: CYP7B1 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: CYP7B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYP7B1 were set to 24117163; 19439420; 19187859
Phenotypes for gene: CYP7B1 were set to Spastic paraplegia 5A, autosomal recessive, MIM# 270800
Review for gene: CYP7B1 was set to GREEN
Added comment: White matter lesions have been reported as a feature of the condition in >3 cases. Age of onset highly variable, generally in adolescence but onset in early childhood reported.
Sources: Expert list
Leukodystrophy v0.72 NPC1 Zornitza Stark Marked gene: NPC1 as ready
Leukodystrophy v0.72 NPC1 Zornitza Stark Gene: npc1 has been classified as Green List (High Evidence).
Leukodystrophy v0.72 NPC1 Zornitza Stark Classified gene: NPC1 as Green List (high evidence)
Leukodystrophy v0.72 NPC1 Zornitza Stark Gene: npc1 has been classified as Green List (High Evidence).
Leukodystrophy v0.71 NPC1 Zornitza Stark gene: NPC1 was added
gene: NPC1 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: NPC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NPC1 were set to 26910362; 29406968
Phenotypes for gene: NPC1 were set to Niemann-Pick disease, type C1/D, MIM# 257220
Review for gene: NPC1 was set to GREEN
Added comment: Age of onset/severity highly variable.
Sources: Expert list
Leukodystrophy v0.70 RPIA Zornitza Stark Marked gene: RPIA as ready
Leukodystrophy v0.70 RPIA Zornitza Stark Gene: rpia has been classified as Green List (High Evidence).
Leukodystrophy v0.70 RPIA Zornitza Stark Classified gene: RPIA as Green List (high evidence)
Leukodystrophy v0.70 RPIA Zornitza Stark Gene: rpia has been classified as Green List (High Evidence).
Leukodystrophy v0.69 RPIA Zornitza Stark gene: RPIA was added
gene: RPIA was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: RPIA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RPIA were set to 31247379; 14988808; 31056085
Phenotypes for gene: RPIA were set to Ribose 5-phosphate isomerase deficiency, MIM# 608611
Review for gene: RPIA was set to GREEN
Added comment: Four unrelated individuals described to date, variable onset of leukodystrophy in childhood/adolescence, though other symptoms generally precede.
Sources: Expert list
Leukodystrophy v0.68 SNORD118 Zornitza Stark Marked gene: SNORD118 as ready
Leukodystrophy v0.68 SNORD118 Zornitza Stark Gene: snord118 has been classified as Green List (High Evidence).
Leukodystrophy v0.68 SNORD118 Zornitza Stark Classified gene: SNORD118 as Green List (high evidence)
Leukodystrophy v0.68 SNORD118 Zornitza Stark Gene: snord118 has been classified as Green List (High Evidence).
Leukodystrophy v0.67 SNORD118 Zornitza Stark edited their review of gene: SNORD118: Changed rating: GREEN; Changed phenotypes: Leukoencephalopathy, brain calcifications, and cysts 614561
Leukodystrophy v0.67 SNORD118 Zornitza Stark gene: SNORD118 was added
gene: SNORD118 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: SNORD118 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNORD118 were set to 27571260
Phenotypes for gene: SNORD118 were set to Leukoencephalopathy, brain calcifications, and cysts 614561
Added comment: Over 30 families reported, age at presentation ranged between infancy and 54 years.
Sources: Expert list
Leukodystrophy v0.66 DCAF17 Zornitza Stark Marked gene: DCAF17 as ready
Leukodystrophy v0.66 DCAF17 Zornitza Stark Gene: dcaf17 has been classified as Green List (High Evidence).
Leukodystrophy v0.66 DCAF17 Zornitza Stark Classified gene: DCAF17 as Green List (high evidence)
Leukodystrophy v0.66 DCAF17 Zornitza Stark Gene: dcaf17 has been classified as Green List (High Evidence).
Leukodystrophy v0.65 DCAF17 Zornitza Stark gene: DCAF17 was added
gene: DCAF17 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: DCAF17 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DCAF17 were set to 19026396; 20507343
Phenotypes for gene: DCAF17 were set to Woodhouse-Sakati syndrome, MIM# 241080
Review for gene: DCAF17 was set to GREEN
Added comment: White matter changes are part of the phenotype.
Sources: Expert list
Leukodystrophy v0.64 PTEN Zornitza Stark Marked gene: PTEN as ready
Leukodystrophy v0.64 PTEN Zornitza Stark Gene: pten has been classified as Green List (High Evidence).
Leukodystrophy v0.64 PTEN Zornitza Stark Classified gene: PTEN as Green List (high evidence)
Leukodystrophy v0.64 PTEN Zornitza Stark Gene: pten has been classified as Green List (High Evidence).
Leukodystrophy v0.63 PTEN Zornitza Stark gene: PTEN was added
gene: PTEN was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: PTEN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTEN were set to 29720545; 29152901; 30664625
Phenotypes for gene: PTEN were set to Cowden syndrome 1, MIM# 158350
Review for gene: PTEN was set to GREEN
Added comment: White matter changes described in many individuals.
Sources: Expert list
Mendeliome v0.2706 C21orf59 Zornitza Stark Marked gene: C21orf59 as ready
Mendeliome v0.2706 C21orf59 Zornitza Stark Gene: c21orf59 has been classified as Green List (High Evidence).
Mendeliome v0.2706 C21orf59 Zornitza Stark Phenotypes for gene: C21orf59 were changed from to Ciliary dyskinesia, primary, 26, MIM# 615500
Mendeliome v0.2705 C21orf59 Zornitza Stark Publications for gene: C21orf59 were set to
Mendeliome v0.2704 C21orf59 Zornitza Stark Mode of inheritance for gene: C21orf59 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2703 C21orf59 Zornitza Stark Tag new gene name tag was added to gene: C21orf59.
Mendeliome v0.2703 C21orf59 Zornitza Stark reviewed gene: C21orf59: Rating: GREEN; Mode of pathogenicity: None; Publications: 24094744; Phenotypes: Ciliary dyskinesia, primary, 26, MIM# 615500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.12 C21orf59 Zornitza Stark Marked gene: C21orf59 as ready
Heterotaxy v0.12 C21orf59 Zornitza Stark Gene: c21orf59 has been classified as Green List (High Evidence).
Heterotaxy v0.12 C21orf59 Zornitza Stark Phenotypes for gene: C21orf59 were changed from to Ciliary dyskinesia, primary, 26, MIM# 615500
Heterotaxy v0.11 C21orf59 Zornitza Stark Publications for gene: C21orf59 were set to
Heterotaxy v0.10 C21orf59 Zornitza Stark Mode of inheritance for gene: C21orf59 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.9 C21orf59 Zornitza Stark Tag new gene name tag was added to gene: C21orf59.
Heterotaxy v0.9 C21orf59 Zornitza Stark reviewed gene: C21orf59: Rating: GREEN; Mode of pathogenicity: None; Publications: 24094744; Phenotypes: Ciliary dyskinesia, primary, 26, MIM# 615500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.35 C21orf59 Zornitza Stark changed review comment from: At least three unrelated families reported.; to: At least three unrelated families reported. HGNC approved name CFAP298.
Ciliary Dyskinesia v0.35 C21orf59 Zornitza Stark Marked gene: C21orf59 as ready
Ciliary Dyskinesia v0.35 C21orf59 Zornitza Stark Gene: c21orf59 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.35 C21orf59 Zornitza Stark Phenotypes for gene: C21orf59 were changed from to Ciliary dyskinesia, primary, 26, MIM# 615500
Ciliary Dyskinesia v0.34 C21orf59 Zornitza Stark Publications for gene: C21orf59 were set to
Ciliary Dyskinesia v0.33 C21orf59 Zornitza Stark Mode of inheritance for gene: C21orf59 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.32 C21orf59 Zornitza Stark reviewed gene: C21orf59: Rating: GREEN; Mode of pathogenicity: None; Publications: 24094744; Phenotypes: Ciliary dyskinesia, primary, 26, MIM# 615500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.32 C21orf59 Zornitza Stark Tag new gene name tag was added to gene: C21orf59.
Mendeliome v0.2703 WISP3 Zornitza Stark Marked gene: WISP3 as ready
Mendeliome v0.2703 WISP3 Zornitza Stark Gene: wisp3 has been classified as Green List (High Evidence).
Mendeliome v0.2703 WISP3 Zornitza Stark Phenotypes for gene: WISP3 were changed from to Arthropathy, progressive pseudorheumatoid, of childhood, MIM# 208230; Spondyloepiphyseal dysplasia tarda with progressive arthropathy, MIM# 208230
Mendeliome v0.2702 WISP3 Zornitza Stark Publications for gene: WISP3 were set to
Mendeliome v0.2701 WISP3 Zornitza Stark Mode of inheritance for gene: WISP3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2700 WISP3 Zornitza Stark Tag new gene name tag was added to gene: WISP3.
Mendeliome v0.2700 WISP3 Zornitza Stark reviewed gene: WISP3: Rating: GREEN; Mode of pathogenicity: None; Publications: 10471507; Phenotypes: Arthropathy, progressive pseudorheumatoid, of childhood, MIM# 208230, Spondyloepiphyseal dysplasia tarda with progressive arthropathy, MIM# 208230; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mackenzie's Mission_Reproductive Carrier Screening v0.6 WISP3 Zornitza Stark Marked gene: WISP3 as ready
Mackenzie's Mission_Reproductive Carrier Screening v0.6 WISP3 Zornitza Stark Added comment: Comment when marking as ready: HGNC approved name CCN6
Mackenzie's Mission_Reproductive Carrier Screening v0.6 WISP3 Zornitza Stark Gene: wisp3 has been classified as Green List (High Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.6 WISP3 Zornitza Stark Tag new gene name tag was added to gene: WISP3.
Skeletal dysplasia v0.19 WISP3 Zornitza Stark Marked gene: WISP3 as ready
Skeletal dysplasia v0.19 WISP3 Zornitza Stark Added comment: Comment when marking as ready: HGNC approved name CCN6
Skeletal dysplasia v0.19 WISP3 Zornitza Stark Gene: wisp3 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.19 WISP3 Zornitza Stark Tag new gene name tag was added to gene: WISP3.
Mitochondrial disease v0.445 ATP5E Zornitza Stark Marked gene: ATP5E as ready
Mitochondrial disease v0.445 ATP5E Zornitza Stark Added comment: Comment when marking as ready: HGNC approved name ATP5F1E.
Mitochondrial disease v0.445 ATP5E Zornitza Stark Gene: atp5e has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2700 ATP5E Zornitza Stark Marked gene: ATP5E as ready
Mendeliome v0.2700 ATP5E Zornitza Stark Gene: atp5e has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2700 ATP5E Zornitza Stark Phenotypes for gene: ATP5E were changed from to Mitochondrial complex V (ATP synthase) deficiency, nuclear type 3 MIM#614053
Mendeliome v0.2699 ATP5E Zornitza Stark Publications for gene: ATP5E were set to
Mendeliome v0.2698 ATP5E Zornitza Stark Mode of inheritance for gene: ATP5E was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2697 ATP5E Zornitza Stark Classified gene: ATP5E as Amber List (moderate evidence)
Mendeliome v0.2697 ATP5E Zornitza Stark Gene: atp5e has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2696 ATP5E Zornitza Stark Tag new gene name tag was added to gene: ATP5E.
Mendeliome v0.2696 ATP5E Zornitza Stark reviewed gene: ATP5E: Rating: AMBER; Mode of pathogenicity: None; Publications: 20566710, 27626380, 20026007; Phenotypes: Mitochondrial complex V (ATP synthase) deficiency, nuclear type 3 MIM#614053; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.445 ATP5E Zornitza Stark Tag new gene name tag was added to gene: ATP5E.
Mendeliome v0.2696 ATP5D Zornitza Stark Marked gene: ATP5D as ready
Mendeliome v0.2696 ATP5D Zornitza Stark Gene: atp5d has been classified as Green List (High Evidence).
Mendeliome v0.2696 ATP5D Zornitza Stark Phenotypes for gene: ATP5D were changed from to Mitochondrial complex V (ATP synthase) deficiency, MIM# 618120
Mendeliome v0.2695 ATP5D Zornitza Stark Publications for gene: ATP5D were set to
Mendeliome v0.2694 ATP5D Zornitza Stark Mode of inheritance for gene: ATP5D was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2693 ATP5D Zornitza Stark Tag new gene name tag was added to gene: ATP5D.
Mendeliome v0.2693 ATP5D Zornitza Stark reviewed gene: ATP5D: Rating: GREEN; Mode of pathogenicity: None; Publications: 29478781; Phenotypes: Mitochondrial complex V (ATP synthase) deficiency, MIM# 618120; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.445 ATP5D Zornitza Stark Marked gene: ATP5D as ready
Mitochondrial disease v0.445 ATP5D Zornitza Stark Gene: atp5d has been classified as Green List (High Evidence).
Mitochondrial disease v0.445 ATP5D Zornitza Stark Phenotypes for gene: ATP5D were changed from to Mitochondrial complex V (ATP synthase) deficiency, MIM# 618120
Mitochondrial disease v0.444 ATP5D Zornitza Stark Publications for gene: ATP5D were set to
Mitochondrial disease v0.443 ATP5D Zornitza Stark Mode of inheritance for gene: ATP5D was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.443 ATP5D Zornitza Stark Mode of inheritance for gene: ATP5D was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.442 ATP5D Zornitza Stark Tag new gene name tag was added to gene: ATP5D.
Mitochondrial disease v0.442 ATP5D Zornitza Stark reviewed gene: ATP5D: Rating: GREEN; Mode of pathogenicity: None; Publications: 29478781; Phenotypes: Mitochondrial complex V (ATP synthase) deficiency, MIM# 618120; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.442 ATP5A1 Zornitza Stark Marked gene: ATP5A1 as ready
Mitochondrial disease v0.442 ATP5A1 Zornitza Stark Added comment: Comment when marking as ready: HGNC approved name: ATP5F1A
Mitochondrial disease v0.442 ATP5A1 Zornitza Stark Gene: atp5a1 has been classified as Amber List (Moderate Evidence).
Mitochondrial disease v0.442 ATP5A1 Zornitza Stark Tag new gene name tag was added to gene: ATP5A1.
Mendeliome v0.2693 ATP5A1 Zornitza Stark Marked gene: ATP5A1 as ready
Mendeliome v0.2693 ATP5A1 Zornitza Stark Added comment: Comment when marking as ready: HGNC approved name: ATP5F1A
Mendeliome v0.2693 ATP5A1 Zornitza Stark Gene: atp5a1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.690 ATP5A1 Zornitza Stark Marked gene: ATP5A1 as ready
Genetic Epilepsy v0.690 ATP5A1 Zornitza Stark Added comment: Comment when marking as ready: HGNC approved name: ATP5F1A
Genetic Epilepsy v0.690 ATP5A1 Zornitza Stark Gene: atp5a1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.690 ATP5A1 Zornitza Stark Tag new gene name tag was added to gene: ATP5A1.
Mendeliome v0.2693 ATP5A1 Zornitza Stark Phenotypes for gene: ATP5A1 were changed from to Combined oxidative phosphorylation deficiency 22 616045; Mitochondrial complex V (ATP synthase) deficiency nuclear type 4, 615228
Mendeliome v0.2692 ATP5A1 Zornitza Stark Tag new gene name tag was added to gene: ATP5A1.
Mendeliome v0.2692 ATP5A1 Zornitza Stark Publications for gene: ATP5A1 were set to
Mendeliome v0.2691 ATP5A1 Zornitza Stark Mode of inheritance for gene: ATP5A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2690 ATP5A1 Zornitza Stark Classified gene: ATP5A1 as Amber List (moderate evidence)
Mendeliome v0.2690 ATP5A1 Zornitza Stark Gene: atp5a1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2689 ATP5A1 Zornitza Stark reviewed gene: ATP5A1: Rating: AMBER; Mode of pathogenicity: None; Publications: 23599390; Phenotypes: Combined oxidative phosphorylation deficiency 22 616045, Mitochondrial complex V (ATP synthase) deficiency nuclear type 4, 615228; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Blepharophimosis v0.14 COLEC10 Zornitza Stark Marked gene: COLEC10 as ready
Blepharophimosis v0.14 COLEC10 Zornitza Stark Gene: colec10 has been classified as Green List (High Evidence).
Blepharophimosis v0.14 COLEC10 Zornitza Stark Classified gene: COLEC10 as Green List (high evidence)
Blepharophimosis v0.14 COLEC10 Zornitza Stark Gene: colec10 has been classified as Green List (High Evidence).
Blepharophimosis v0.13 COLEC10 Zornitza Stark gene: COLEC10 was added
gene: COLEC10 was added to Blepharophimosis. Sources: Expert Review
Mode of inheritance for gene: COLEC10 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: COLEC10 were set to 3MC syndrome 3, MIM# 248340
Review for gene: COLEC10 was set to GREEN
Added comment: Sources: Expert Review
Blepharophimosis v0.12 COLEC11 Zornitza Stark Marked gene: COLEC11 as ready
Blepharophimosis v0.12 COLEC11 Zornitza Stark Gene: colec11 has been classified as Green List (High Evidence).
Blepharophimosis v0.12 COLEC11 Zornitza Stark Classified gene: COLEC11 as Green List (high evidence)
Blepharophimosis v0.12 COLEC11 Zornitza Stark Gene: colec11 has been classified as Green List (High Evidence).
Blepharophimosis v0.11 COLEC11 Zornitza Stark gene: COLEC11 was added
gene: COLEC11 was added to Blepharophimosis. Sources: Expert Review
Mode of inheritance for gene: COLEC11 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: COLEC11 were set to 3MC syndrome 2, MIM# 265050
Review for gene: COLEC11 was set to GREEN
Added comment: Sources: Expert Review
Blepharophimosis v0.10 ERCC1 Zornitza Stark Marked gene: ERCC1 as ready
Blepharophimosis v0.10 ERCC1 Zornitza Stark Gene: ercc1 has been classified as Green List (High Evidence).
Blepharophimosis v0.10 ERCC1 Zornitza Stark Classified gene: ERCC1 as Green List (high evidence)
Blepharophimosis v0.10 ERCC1 Zornitza Stark Gene: ercc1 has been classified as Green List (High Evidence).
Blepharophimosis v0.9 ERCC1 Zornitza Stark gene: ERCC1 was added
gene: ERCC1 was added to Blepharophimosis. Sources: Expert Review
Mode of inheritance for gene: ERCC1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ERCC1 were set to Cerebrooculofacioskeletal syndrome 4, MIM# 610758
Review for gene: ERCC1 was set to GREEN
Added comment: Sources: Expert Review
Blepharophimosis v0.8 ERCC5 Zornitza Stark Marked gene: ERCC5 as ready
Blepharophimosis v0.8 ERCC5 Zornitza Stark Gene: ercc5 has been classified as Green List (High Evidence).
Blepharophimosis v0.8 ERCC5 Zornitza Stark Classified gene: ERCC5 as Green List (high evidence)
Blepharophimosis v0.8 ERCC5 Zornitza Stark Gene: ercc5 has been classified as Green List (High Evidence).
Blepharophimosis v0.7 ERCC5 Zornitza Stark gene: ERCC5 was added
gene: ERCC5 was added to Blepharophimosis. Sources: Expert Review
Mode of inheritance for gene: ERCC5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ERCC5 were set to Cerebrooculofacioskeletal syndrome 3,MIM# 616570
Review for gene: ERCC5 was set to GREEN
Added comment: Sources: Expert Review
Blepharophimosis v0.6 ERCC2 Zornitza Stark Marked gene: ERCC2 as ready
Blepharophimosis v0.6 ERCC2 Zornitza Stark Gene: ercc2 has been classified as Red List (Low Evidence).
Blepharophimosis v0.6 ERCC2 Zornitza Stark gene: ERCC2 was added
gene: ERCC2 was added to Blepharophimosis. Sources: Expert list
Mode of inheritance for gene: ERCC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERCC2 were set to 11443545
Phenotypes for gene: ERCC2 were set to Cerebrooculofacioskeletal syndrome 2, MIM# 610756
Review for gene: ERCC2 was set to RED
Added comment: ERCC2 is associated with trichothiodystrophy and xeroderma pigmentosum. Only one family reported with COFS phenotype in 2001.
Sources: Expert list
Blepharophimosis v0.4 ERCC6 Zornitza Stark Marked gene: ERCC6 as ready
Blepharophimosis v0.4 ERCC6 Zornitza Stark Gene: ercc6 has been classified as Green List (High Evidence).
Blepharophimosis v0.4 ERCC6 Zornitza Stark Classified gene: ERCC6 as Green List (high evidence)
Blepharophimosis v0.4 ERCC6 Zornitza Stark Gene: ercc6 has been classified as Green List (High Evidence).
Blepharophimosis v0.3 ERCC6 Zornitza Stark gene: ERCC6 was added
gene: ERCC6 was added to Blepharophimosis. Sources: Expert Review
Mode of inheritance for gene: ERCC6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ERCC6 were set to Cerebrooculofacioskeletal syndrome 1, MIM# 214150
Review for gene: ERCC6 was set to GREEN
Added comment: Sources: Expert Review
Mendeliome v0.2689 GLDC Zornitza Stark Marked gene: GLDC as ready
Mendeliome v0.2689 GLDC Zornitza Stark Gene: gldc has been classified as Green List (High Evidence).
Mendeliome v0.2689 GLDC Zornitza Stark Phenotypes for gene: GLDC were changed from to Glycine encephalopathy (MIM#605899)
Mendeliome v0.2688 GLDC Zornitza Stark Publications for gene: GLDC were set to
Mendeliome v0.2687 GLDC Zornitza Stark Mode of inheritance for gene: GLDC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2686 GLDC Crystle Lee reviewed gene: GLDC: Rating: GREEN; Mode of pathogenicity: None; Publications: 27362913; Phenotypes: Glycine encephalopathy (MIM#605899); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.18 PPM1F Zornitza Stark edited their review of gene: PPM1F: Changed phenotypes: sclerosing cholangitis, short stature, hypothyroidism, abnormal tongue pigmentation
Haematuria_Alport v0.35 COL4A4 Zornitza Stark Marked gene: COL4A4 as ready
Haematuria_Alport v0.35 COL4A4 Zornitza Stark Gene: col4a4 has been classified as Green List (High Evidence).
Haematuria_Alport v0.35 COL4A4 Zornitza Stark Phenotypes for gene: COL4A4 were changed from to Alport syndrome 2, autosomal recessive, 203780; Thin basement membrane nephropathy (TBMN), AD; Focal segmental glomerulosclerosis (FSGS), AD
Haematuria_Alport v0.34 COL4A4 Zornitza Stark Publications for gene: COL4A4 were set to
Haematuria_Alport v0.33 COL4A4 Zornitza Stark Mode of inheritance for gene: COL4A4 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2612 ARID1B Zornitza Stark Marked gene: ARID1B as ready
Intellectual disability syndromic and non-syndromic v0.2612 ARID1B Zornitza Stark Gene: arid1b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2612 ARID1B Zornitza Stark Phenotypes for gene: ARID1B were changed from to Coffin-Siris syndrome 1, MIM 135900
Intellectual disability syndromic and non-syndromic v0.2611 ARID1B Zornitza Stark Publications for gene: ARID1B were set to
Intellectual disability syndromic and non-syndromic v0.2610 ARID1B Zornitza Stark Mode of inheritance for gene: ARID1B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2609 ARID1B Teresa Zhao reviewed gene: ARID1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 25674384, 30349098, 26506440; Phenotypes: Coffin-Siris syndrome 1, MIM 135900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.2686 CD4 Zornitza Stark reviewed gene: CD4: Rating: AMBER; Mode of pathogenicity: None; Publications: 31781092; Phenotypes: Absence of CD4+ T cells, exuberant, relapsing, treatment-refractory warts; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Susceptibility to Viral Infections v0.54 CD4 Zornitza Stark Marked gene: CD4 as ready
Susceptibility to Viral Infections v0.54 CD4 Zornitza Stark Gene: cd4 has been classified as Amber List (Moderate Evidence).
Susceptibility to Viral Infections v0.54 CD4 Zornitza Stark Classified gene: CD4 as Amber List (moderate evidence)
Susceptibility to Viral Infections v0.54 CD4 Zornitza Stark Gene: cd4 has been classified as Amber List (Moderate Evidence).
Susceptibility to Viral Infections v0.53 CD4 Zornitza Stark gene: CD4 was added
gene: CD4 was added to Susceptibility to Viral Infections. Sources: Literature
Mode of inheritance for gene: CD4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CD4 were set to 31781092
Phenotypes for gene: CD4 were set to Absence of CD4+ T cells; exuberant, relapsing, treatment-refractory warts
Review for gene: CD4 was set to AMBER
Added comment: Single individual reported, functional data, emerging gene.
Sources: Literature
Haematuria_Alport v0.32 COL4A4 Ee Ming Wong reviewed gene: COL4A4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMIDs: 17942953, 24052634, 12631110, 26346198, 30450445; Phenotypes: Alport syndrome 2, autosomal recessive, 203780, Thin basement membrane nephropathy (TBMN), AD, Focal segmental glomerulosclerosis (FSGS), AD; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.2686 TNK2 Zornitza Stark Mode of inheritance for gene: TNK2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.690 TNK2 Zornitza Stark Classified gene: TNK2 as Amber List (moderate evidence)
Genetic Epilepsy v0.690 TNK2 Zornitza Stark Gene: tnk2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.689 TNK2 Zornitza Stark changed review comment from: Three unrelated families reported.; to: Three unrelated families reported, however report in Hitomi (2013) is questionable due to this variant being present in 6 homozygotes in gnomAD,
Genetic Epilepsy v0.689 TNK2 Zornitza Stark edited their review of gene: TNK2: Changed rating: AMBER
Mendeliome v0.2685 TNK2 Zornitza Stark Marked gene: TNK2 as ready
Mendeliome v0.2685 TNK2 Zornitza Stark Gene: tnk2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2685 TNK2 Zornitza Stark Phenotypes for gene: TNK2 were changed from to late onset infantile epilepsy; Mayer-Rokitansky-Küster-Hauser syndrome
Mendeliome v0.2684 TNK2 Zornitza Stark Publications for gene: TNK2 were set to
Mendeliome v0.2683 TNK2 Zornitza Stark Mode of inheritance for gene: TNK2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2682 TNK2 Zornitza Stark Classified gene: TNK2 as Amber List (moderate evidence)
Mendeliome v0.2682 TNK2 Zornitza Stark Gene: tnk2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2681 MAN2B2 Zornitza Stark Marked gene: MAN2B2 as ready
Mendeliome v0.2681 MAN2B2 Zornitza Stark Gene: man2b2 has been classified as Red List (Low Evidence).
Mendeliome v0.2681 MAN2B2 Zornitza Stark gene: MAN2B2 was added
gene: MAN2B2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MAN2B2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAN2B2 were set to 31775018
Phenotypes for gene: MAN2B2 were set to Congenital disorder of glycosylation; immunodeficiency
Review for gene: MAN2B2 was set to RED
Added comment: Single individual reported.
Sources: Literature
Congenital Disorders of Glycosylation v0.47 MAN2B2 Zornitza Stark Marked gene: MAN2B2 as ready
Congenital Disorders of Glycosylation v0.47 MAN2B2 Zornitza Stark Gene: man2b2 has been classified as Red List (Low Evidence).
Mendeliome v0.2680 TNK2 Elena Savva reviewed gene: TNK2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID 27977884, 23686771, 31517310; Phenotypes: late onset infantile epilepsy, Mayer-Rokitansky-Küster-Hauser syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.47 MAN2B2 Zornitza Stark gene: MAN2B2 was added
gene: MAN2B2 was added to Congenital Disorders of Glycosylation. Sources: Literature
Mode of inheritance for gene: MAN2B2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAN2B2 were set to 31775018
Phenotypes for gene: MAN2B2 were set to Congenital disorder of glycosylation; immunodeficiency
Review for gene: MAN2B2 was set to RED
Added comment: Single individual reported.
Sources: Literature
Mendeliome v0.2680 RIPK1 Zornitza Stark Marked gene: RIPK1 as ready
Mendeliome v0.2680 RIPK1 Zornitza Stark Gene: ripk1 has been classified as Green List (High Evidence).
Mendeliome v0.2680 RIPK1 Zornitza Stark Phenotypes for gene: RIPK1 were changed from to Immunodeficiency 57, MIM#618108
Mendeliome v0.2679 RIPK1 Zornitza Stark Publications for gene: RIPK1 were set to
Mendeliome v0.2678 RIPK1 Zornitza Stark Mode of inheritance for gene: RIPK1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2677 RIPK1 Zornitza Stark reviewed gene: RIPK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30026316, 30591564, 31213653, 31827280; Phenotypes: Immunodeficiency 57, MIM#618108; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Disorders of immune dysregulation v0.58 RIPK1 Zornitza Stark changed review comment from: Two families reported with mono-allelic variants and an auto inflammatory syndrome, PMID 31827280; to: Two families reported with mono-allelic variants and an auto inflammatory syndrome, PMID 31827280
Disorders of immune dysregulation v0.58 RIPK1 Zornitza Stark Publications for gene: RIPK1 were set to 30026316
Disorders of immune dysregulation v0.57 RIPK1 Zornitza Stark Mode of inheritance for gene: RIPK1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Disorders of immune dysregulation v0.56 RIPK1 Zornitza Stark edited their review of gene: RIPK1: Added comment: Two families reported with mono-allelic variants and an auto inflammatory syndrome, PMID 31827280; Changed publications: 30026316, 30591564, 31213653, 31827280; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Inflammatory bowel disease v0.26 RIPK1 Zornitza Stark Marked gene: RIPK1 as ready
Inflammatory bowel disease v0.26 RIPK1 Zornitza Stark Gene: ripk1 has been classified as Green List (High Evidence).
Inflammatory bowel disease v0.26 RIPK1 Zornitza Stark Classified gene: RIPK1 as Green List (high evidence)
Inflammatory bowel disease v0.26 RIPK1 Zornitza Stark Gene: ripk1 has been classified as Green List (High Evidence).
Inflammatory bowel disease v0.25 RIPK1 Zornitza Stark gene: RIPK1 was added
gene: RIPK1 was added to Inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: RIPK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RIPK1 were set to 30026316; 30591564; 31213653
Phenotypes for gene: RIPK1 were set to Immunodeficiency 57, MIM#618108
Review for gene: RIPK1 was set to GREEN
Added comment: Ten families reported, inflammatory bowel disease/enteropathy is a common feature of this immune dysregulation syndrome.
Sources: Literature
Disorders of immune dysregulation v0.56 RIPK1 Zornitza Stark edited their review of gene: RIPK1: Added comment: Seven further families reported, inflammatory bowel disease/enteropathy common features.; Changed publications: 30026316, 30591564, 31213653
Mendeliome v0.2677 PIK3CG Zornitza Stark Marked gene: PIK3CG as ready
Mendeliome v0.2677 PIK3CG Zornitza Stark Gene: pik3cg has been classified as Green List (High Evidence).
Mendeliome v0.2677 PIK3CG Zornitza Stark Classified gene: PIK3CG as Green List (high evidence)
Mendeliome v0.2677 PIK3CG Zornitza Stark Gene: pik3cg has been classified as Green List (High Evidence).
Mendeliome v0.2676 PIK3CG Zornitza Stark gene: PIK3CG was added
gene: PIK3CG was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PIK3CG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIK3CG were set to 32001535; 31554793
Phenotypes for gene: PIK3CG were set to Immune dysregulation; HLH-like; childhood-onset antibody defects; cytopenias; T lymphocytic pneumonitis and colitis
Review for gene: PIK3CG was set to GREEN
Added comment: Two individuals with complex immunological phenotypes reported and a mouse model.
Sources: Literature
Mendeliome v0.2675 RC3H1 Zornitza Stark Marked gene: RC3H1 as ready
Mendeliome v0.2675 RC3H1 Zornitza Stark Gene: rc3h1 has been classified as Amber List (Moderate Evidence).
Autoinflammatory Disorders v0.80 PIK3CG Zornitza Stark Marked gene: PIK3CG as ready
Autoinflammatory Disorders v0.80 PIK3CG Zornitza Stark Gene: pik3cg has been classified as Green List (High Evidence).
Autoinflammatory Disorders v0.80 PIK3CG Zornitza Stark Classified gene: PIK3CG as Green List (high evidence)
Autoinflammatory Disorders v0.80 PIK3CG Zornitza Stark Gene: pik3cg has been classified as Green List (High Evidence).
Autoinflammatory Disorders v0.79 PIK3CG Zornitza Stark gene: PIK3CG was added
gene: PIK3CG was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Literature
Mode of inheritance for gene: PIK3CG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIK3CG were set to 32001535; 31554793
Phenotypes for gene: PIK3CG were set to Immune dysregulation; HLH-like; childhood-onset antibody defects; cytopenias; T lymphocytic pneumonitis and colitis
Review for gene: PIK3CG was set to GREEN
Added comment: Two individuals with complex immunological phenotypes reported and a mouse model.
Sources: Literature
Mendeliome v0.2675 RC3H1 Zornitza Stark Classified gene: RC3H1 as Amber List (moderate evidence)
Mendeliome v0.2675 RC3H1 Zornitza Stark Gene: rc3h1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2675 RC3H1 Zornitza Stark Classified gene: RC3H1 as Amber List (moderate evidence)
Mendeliome v0.2675 RC3H1 Zornitza Stark Gene: rc3h1 has been classified as Amber List (Moderate Evidence).
Autoinflammatory Disorders v0.78 RC3H1 Zornitza Stark Classified gene: RC3H1 as Amber List (moderate evidence)
Autoinflammatory Disorders v0.78 RC3H1 Zornitza Stark Gene: rc3h1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2674 RC3H1 Zornitza Stark changed review comment from: Single individual with bi-allelic LoF variant and relapsing HLH reported, some functional data.
Sources: Literature; to: Single individual with bi-allelic LoF variant and relapsing HLH reported, some functional data including mouse model.
Sources: Literature
Mendeliome v0.2674 RC3H1 Zornitza Stark edited their review of gene: RC3H1: Changed rating: AMBER; Changed publications: 31636267, 15917799
Autoinflammatory Disorders v0.77 RC3H1 Zornitza Stark changed review comment from: Single individual with bi-allelic LoF variant and relapsing HLH reported, some functional data.
Sources: Literature; to: Single individual with bi-allelic LoF variant and relapsing HLH reported, some functional data including mouse model.
Sources: Literature
Autoinflammatory Disorders v0.77 RC3H1 Zornitza Stark edited their review of gene: RC3H1: Changed rating: AMBER; Changed publications: 31636267, 15917799
Mendeliome v0.2674 RC3H1 Zornitza Stark gene: RC3H1 was added
gene: RC3H1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RC3H1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RC3H1 were set to 31636267
Phenotypes for gene: RC3H1 were set to Relapsing HLH
Review for gene: RC3H1 was set to RED
Added comment: Single individual with bi-allelic LoF variant and relapsing HLH reported, some functional data.
Sources: Literature
Autoinflammatory Disorders v0.77 RC3H1 Zornitza Stark Marked gene: RC3H1 as ready
Autoinflammatory Disorders v0.77 RC3H1 Zornitza Stark Gene: rc3h1 has been classified as Red List (Low Evidence).
Autoinflammatory Disorders v0.77 RC3H1 Zornitza Stark gene: RC3H1 was added
gene: RC3H1 was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Literature
Mode of inheritance for gene: RC3H1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RC3H1 were set to 31636267
Phenotypes for gene: RC3H1 were set to Relapsing HLH
Review for gene: RC3H1 was set to RED
Added comment: Single individual with bi-allelic LoF variant and relapsing HLH reported, some functional data.
Sources: Literature
Stroke v0.12 CCM2 Bryony Thompson Marked gene: CCM2 as ready
Stroke v0.12 CCM2 Bryony Thompson Gene: ccm2 has been classified as Green List (High Evidence).
Stroke v0.12 CCM2 Bryony Thompson Classified gene: CCM2 as Green List (high evidence)
Stroke v0.12 CCM2 Bryony Thompson Gene: ccm2 has been classified as Green List (High Evidence).
Stroke v0.11 CCM2 Bryony Thompson gene: CCM2 was added
gene: CCM2 was added to Stroke. Sources: Literature
Mode of inheritance for gene: CCM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CCM2 were set to 14624391; 18779516; 30356112
Phenotypes for gene: CCM2 were set to Cerebral cavernous malformations-2 MIM#603284
Review for gene: CCM2 was set to GREEN
Added comment: Cases reported with intracerebral bleeding and cavernoma stroke subtypes.
Sources: Literature
Stroke v0.10 ADAMTS13 Bryony Thompson Marked gene: ADAMTS13 as ready
Stroke v0.10 ADAMTS13 Bryony Thompson Gene: adamts13 has been classified as Green List (High Evidence).
Stroke v0.10 ADAMTS13 Bryony Thompson Classified gene: ADAMTS13 as Green List (high evidence)
Stroke v0.10 ADAMTS13 Bryony Thompson Gene: adamts13 has been classified as Green List (High Evidence).
Stroke v0.9 ADAMTS13 Bryony Thompson gene: ADAMTS13 was added
gene: ADAMTS13 was added to Stroke. Sources: Literature
Mode of inheritance for gene: ADAMTS13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAMTS13 were set to 32103696; 31585956; 30930238; 28591212
Phenotypes for gene: ADAMTS13 were set to Thrombotic thrombocytopenic purpura, hereditary MIM#274150
Review for gene: ADAMTS13 was set to GREEN
Added comment: Strokes reported in at least 7 cases with the condition.
Sources: Literature
Stroke v0.8 ACTA2 Bryony Thompson Classified gene: ACTA2 as Green List (high evidence)
Stroke v0.8 ACTA2 Bryony Thompson Gene: acta2 has been classified as Green List (High Evidence).
Stroke v0.7 ACTA2 Bryony Thompson gene: ACTA2 was added
gene: ACTA2 was added to Stroke. Sources: Literature
Mode of inheritance for gene: ACTA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ACTA2 were set to 20734336; 19409525; 30356112
Phenotypes for gene: ACTA2 were set to Multisystemic smooth muscle dysfunction syndrome MIM#613834
Review for gene: ACTA2 was set to GREEN
Added comment: Condition reported with large artery atherosclerosis/non-atherosclerosis, small vessel disease, and cardio embolism due to morphologic defect stroke subtypes.
Sources: Literature
Stroke v0.6 ABCA1 Bryony Thompson Classified gene: ABCA1 as Green List (high evidence)
Stroke v0.6 ABCA1 Bryony Thompson Gene: abca1 has been classified as Green List (High Evidence).
Stroke v0.5 ABCA1 Bryony Thompson gene: ABCA1 was added
gene: ABCA1 was added to Stroke. Sources: Literature
Mode of inheritance for gene: ABCA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABCA1 were set to 30356112; 22913675; 30278532; 31487778
Phenotypes for gene: ABCA1 were set to Tangier disease MIM#205400
Review for gene: ABCA1 was set to GREEN
Added comment: Cases have been reported with large artery atherosclerosis, cardio embolism due to cardiomyopathy, intracerebral bleeding, and bleeding tendency stroke subtypes. Also a hamster model with ischemic stroke.
Sources: Literature
Mendeliome v0.2673 IFNG Zornitza Stark Marked gene: IFNG as ready
Mendeliome v0.2673 IFNG Zornitza Stark Gene: ifng has been classified as Red List (Low Evidence).
Mendeliome v0.2673 IFNG Zornitza Stark Phenotypes for gene: IFNG were changed from to Mendelian susceptibility to mycobacterial disease
Mendeliome v0.2672 IFNG Zornitza Stark Publications for gene: IFNG were set to
Mendeliome v0.2671 IFNG Zornitza Stark Mode of inheritance for gene: IFNG was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2670 IFNG Zornitza Stark Classified gene: IFNG as Red List (low evidence)
Mendeliome v0.2670 IFNG Zornitza Stark Gene: ifng has been classified as Red List (Low Evidence).
Mendeliome v0.2669 IFNG Zornitza Stark reviewed gene: IFNG: Rating: RED; Mode of pathogenicity: None; Publications: 32163377; Phenotypes: Mendelian susceptibility to mycobacterial disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2669 ITPKB Zornitza Stark gene: ITPKB was added
gene: ITPKB was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ITPKB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ITPKB were set to 31987846
Phenotypes for gene: ITPKB were set to Severe combined immunodeficiency, absent T cells, present B cells and NK cells
Review for gene: ITPKB was set to RED
Added comment: Single individual with homozygous bi-allelic LoF variant reported.
Sources: Literature
Severe Combined Immunodeficiency v0.19 ITPKB Zornitza Stark Marked gene: ITPKB as ready
Severe Combined Immunodeficiency v0.19 ITPKB Zornitza Stark Gene: itpkb has been classified as Red List (Low Evidence).
Severe Combined Immunodeficiency v0.19 ITPKB Zornitza Stark Publications for gene: ITPKB were set to
Severe Combined Immunodeficiency v0.18 ITPKB Zornitza Stark edited their review of gene: ITPKB: Changed publications: 31987846
Severe Combined Immunodeficiency v0.18 ITPKB Zornitza Stark gene: ITPKB was added
gene: ITPKB was added to Severe Combined Immunodeficiency (absent T present B cells). Sources: Literature
Mode of inheritance for gene: ITPKB was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ITPKB were set to Severe combined immunodeficiency, absent T cells, present B cells and NK cells
Review for gene: ITPKB was set to RED
Added comment: Single individual with homozygous bi-allelic LoF variant reported.
Sources: Literature
Mendeliome v0.2668 PSMB10 Zornitza Stark Marked gene: PSMB10 as ready
Mendeliome v0.2668 PSMB10 Zornitza Stark Gene: psmb10 has been classified as Red List (Low Evidence).
Mendeliome v0.2668 PSMB10 Zornitza Stark gene: PSMB10 was added
gene: PSMB10 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PSMB10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMB10 were set to 31783057
Phenotypes for gene: PSMB10 were set to Autoinflammatory syndrome
Review for gene: PSMB10 was set to RED
Added comment: PSMB10 is part of the immunoproteasome, and other components cause auto inflammatory disorders. Single individual with homozygous missense variant reported.
Sources: Literature
Autoinflammatory Disorders v0.76 PSMB10 Zornitza Stark Marked gene: PSMB10 as ready
Autoinflammatory Disorders v0.76 PSMB10 Zornitza Stark Gene: psmb10 has been classified as Red List (Low Evidence).
Autoinflammatory Disorders v0.76 PSMB10 Zornitza Stark gene: PSMB10 was added
gene: PSMB10 was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Literature
Mode of inheritance for gene: PSMB10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMB10 were set to 31783057
Phenotypes for gene: PSMB10 were set to Autoinflammatory syndrome
Review for gene: PSMB10 was set to RED
Added comment: PSMB10 is part of the immunoproteasome, and other components cause auto inflammatory disorders. Single individual with homozygous missense variant reported.
Sources: Literature
Autoinflammatory Disorders v0.75 CDC42 Zornitza Stark Publications for gene: CDC42 were set to 31601675; 32303876
Autoinflammatory Disorders v0.74 CDC42 Zornitza Stark edited their review of gene: CDC42: Changed publications: 31601675, 32303876, 32231661
Autoinflammatory Disorders v0.74 CDC42 Zornitza Stark changed review comment from: PMID 31601675: four unrelated individuals with superimposable features, including neonatal-onset cytopenia with dyshematopoiesis, autoinflammation, rash, and HLH. All shared the same de novo CDC42 mutation (Chr1:22417990C>T, p.R186C). Another pair of sibs reported in PMID 32303876 with infantile myelofibrosis and myeloproliferation and same variant (parental mosaicism). Note other missense variants in this gene cause Takenouchi-Kosaki syndrome, MIM# 616737
Sources: Literature; to: PMID 31601675: four unrelated individuals with superimposable features, including neonatal-onset cytopenia with dyshematopoiesis, autoinflammation, rash, and HLH. All shared the same de novo CDC42 mutation (Chr1:22417990C>T, p.R186C). Another pair of sibs reported in PMID 32303876 with infantile myelofibrosis and myeloproliferation and same variant (parental mosaicism). Yet another individual in PMID 32231661 with different de novo variant, p.Cys81Tyr who in addition developed haematological malignancy and also had syndromic features, including ID. Note other missense variants in this gene cause Takenouchi-Kosaki syndrome, MIM# 616737
Sources: Literature
Autoinflammatory Disorders v0.74 CDC42 Zornitza Stark Marked gene: CDC42 as ready
Autoinflammatory Disorders v0.74 CDC42 Zornitza Stark Gene: cdc42 has been classified as Green List (High Evidence).
Autoinflammatory Disorders v0.74 CDC42 Zornitza Stark Classified gene: CDC42 as Green List (high evidence)
Autoinflammatory Disorders v0.74 CDC42 Zornitza Stark Gene: cdc42 has been classified as Green List (High Evidence).
Autoinflammatory Disorders v0.73 CDC42 Zornitza Stark gene: CDC42 was added
gene: CDC42 was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Literature
Mode of inheritance for gene: CDC42 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDC42 were set to 31601675; 32303876
Phenotypes for gene: CDC42 were set to Neonatal-onset cytopaenia with dyshaematopoiesis; autoinflammation; rash; HLH
Review for gene: CDC42 was set to GREEN
Added comment: PMID 31601675: four unrelated individuals with superimposable features, including neonatal-onset cytopenia with dyshematopoiesis, autoinflammation, rash, and HLH. All shared the same de novo CDC42 mutation (Chr1:22417990C>T, p.R186C). Another pair of sibs reported in PMID 32303876 with infantile myelofibrosis and myeloproliferation and same variant (parental mosaicism). Note other missense variants in this gene cause Takenouchi-Kosaki syndrome, MIM# 616737
Sources: Literature
Autoinflammatory Disorders v0.72 STAT2 Zornitza Stark Marked gene: STAT2 as ready
Autoinflammatory Disorders v0.72 STAT2 Zornitza Stark Gene: stat2 has been classified as Green List (High Evidence).
Autoinflammatory Disorders v0.72 STAT2 Zornitza Stark Phenotypes for gene: STAT2 were changed from to Autoinflammatory disorder
Autoinflammatory Disorders v0.71 STAT2 Zornitza Stark Classified gene: STAT2 as Green List (high evidence)
Autoinflammatory Disorders v0.71 STAT2 Zornitza Stark Gene: stat2 has been classified as Green List (High Evidence).
Autoinflammatory Disorders v0.70 STAT2 Zornitza Stark gene: STAT2 was added
gene: STAT2 was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Literature
Mode of inheritance for gene: STAT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STAT2 were set to 31836668; 32092142
Review for gene: STAT2 was set to GREEN
Added comment: Three individuals from two unrelated families reported with bi-allelic GoF variants and severe auto inflammatory disease. Functional data. Note gene is already associated with other immune phenotypes.
Sources: Literature
Mendeliome v0.2667 ABHD12 Zornitza Stark Marked gene: ABHD12 as ready
Mendeliome v0.2667 ABHD12 Zornitza Stark Gene: abhd12 has been classified as Green List (High Evidence).
Mendeliome v0.2667 ABHD12 Zornitza Stark Phenotypes for gene: ABHD12 were changed from to Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract MIM#612674
Mendeliome v0.2666 ABHD12 Zornitza Stark Mode of inheritance for gene: ABHD12 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2665 ABCC6 Zornitza Stark Marked gene: ABCC6 as ready
Mendeliome v0.2665 ABCC6 Zornitza Stark Gene: abcc6 has been classified as Green List (High Evidence).
Mendeliome v0.2665 AAAS Zornitza Stark Marked gene: AAAS as ready
Mendeliome v0.2665 AAAS Zornitza Stark Gene: aaas has been classified as Green List (High Evidence).
Mendeliome v0.2665 AAAS Zornitza Stark Phenotypes for gene: AAAS were changed from to Achalasia-addisonianism-alacrimia syndrome, MIM#231550
Mendeliome v0.2664 AAAS Zornitza Stark Mode of inheritance for gene: AAAS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.442 DNM2 Kristin Rigbye commented on gene: DNM2
Susceptibility to Viral Infections v0.52 POLR3C Zornitza Stark Marked gene: POLR3C as ready
Susceptibility to Viral Infections v0.52 POLR3C Zornitza Stark Gene: polr3c has been classified as Amber List (Moderate Evidence).
Susceptibility to Viral Infections v0.52 IL18BP Zornitza Stark Marked gene: IL18BP as ready
Susceptibility to Viral Infections v0.52 IL18BP Zornitza Stark Gene: il18bp has been classified as Red List (Low Evidence).
Mendeliome v0.2663 NOS2 Zornitza Stark Marked gene: NOS2 as ready
Mendeliome v0.2663 NOS2 Zornitza Stark Gene: nos2 has been classified as Red List (Low Evidence).
Mendeliome v0.2663 NOS2 Zornitza Stark Phenotypes for gene: NOS2 were changed from to {Malaria, resistance to} 611162; Disseminated CMV disease
Stroke v0.4 NOS3 Bryony Thompson Classified gene: NOS3 as Red List (low evidence)
Stroke v0.4 NOS3 Bryony Thompson Gene: nos3 has been classified as Red List (Low Evidence).
Stroke v0.3 NOS3 Bryony Thompson reviewed gene: NOS3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Ischemic stroke, susceptibility to} MIM#601367; Mode of inheritance: Unknown
Mendeliome v0.2662 NOS2 Zornitza Stark Publications for gene: NOS2 were set to
Mendeliome v0.2661 NOS2 Zornitza Stark Classified gene: NOS2 as Red List (low evidence)
Mendeliome v0.2661 NOS2 Zornitza Stark Gene: nos2 has been classified as Red List (Low Evidence).
Stroke v0.3 MMACHC Bryony Thompson Classified gene: MMACHC as Green List (high evidence)
Stroke v0.3 MMACHC Bryony Thompson Gene: mmachc has been classified as Green List (High Evidence).
Mendeliome v0.2660 NOS2 Zornitza Stark edited their review of gene: NOS2: Changed rating: RED
Stroke v0.2 MMACHC Bryony Thompson gene: MMACHC was added
gene: MMACHC was added to Stroke. Sources: Literature
Mode of inheritance for gene: MMACHC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MMACHC were set to 12552044; 11742888; 30356112
Phenotypes for gene: MMACHC were set to Methylmalonic aciduria and homocystinuria, cblC type MIM#277400
Review for gene: MMACHC was set to GREEN
Added comment: Large artery atherosclerosis, large artery non-atherosclerosis with dissections, coagulation pathology venous thrombosis, and coagulation pathology arterial thrombosis are stroke subtypes reported in this condition.
Sources: Literature
Mendeliome v0.2660 NOS2 Zornitza Stark reviewed gene: NOS2: Rating: AMBER; Mode of pathogenicity: None; Publications: 12433515, 31995689; Phenotypes: {Malaria, resistance to} 611162, Disseminated CMV disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Susceptibility to Viral Infections v0.52 NOS2 Zornitza Stark Marked gene: NOS2 as ready
Susceptibility to Viral Infections v0.52 NOS2 Zornitza Stark Gene: nos2 has been classified as Red List (Low Evidence).
Susceptibility to Viral Infections v0.52 NOS2 Zornitza Stark gene: NOS2 was added
gene: NOS2 was added to Susceptibility to Viral Infections. Sources: Expert list
Mode of inheritance for gene: NOS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NOS2 were set to 31995689
Phenotypes for gene: NOS2 were set to Disseminated CMV disease
Review for gene: NOS2 was set to RED
Added comment: Single individual reported with progressive, fatal CMV disease and homozygous LoF variant in NOS2.
Sources: Expert list
Susceptibility to Viral Infections v0.51 CD70 Zornitza Stark Marked gene: CD70 as ready
Susceptibility to Viral Infections v0.51 CD70 Zornitza Stark Gene: cd70 has been classified as Green List (High Evidence).
Susceptibility to Viral Infections v0.51 CD70 Zornitza Stark Classified gene: CD70 as Green List (high evidence)
Susceptibility to Viral Infections v0.51 CD70 Zornitza Stark Gene: cd70 has been classified as Green List (High Evidence).
Susceptibility to Viral Infections v0.50 CD70 Zornitza Stark gene: CD70 was added
gene: CD70 was added to Susceptibility to Viral Infections. Sources: Expert list
Mode of inheritance for gene: CD70 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CD70 were set to 28011864; 28011863,
Phenotypes for gene: CD70 were set to Lymphoproliferative syndrome 3, MIM# 618261; Host response to EBV
Review for gene: CD70 was set to GREEN
Added comment: Three unrelated families reported.
Sources: Expert list
Susceptibility to Viral Infections v0.49 CD27 Zornitza Stark Marked gene: CD27 as ready
Susceptibility to Viral Infections v0.49 CD27 Zornitza Stark Gene: cd27 has been classified as Green List (High Evidence).
Susceptibility to Viral Infections v0.49 CD27 Zornitza Stark Classified gene: CD27 as Green List (high evidence)
Susceptibility to Viral Infections v0.49 CD27 Zornitza Stark Gene: cd27 has been classified as Green List (High Evidence).
Susceptibility to Viral Infections v0.48 CD27 Zornitza Stark gene: CD27 was added
gene: CD27 was added to Susceptibility to Viral Infections. Sources: Expert list
Mode of inheritance for gene: CD27 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CD27 were set to 22801960; 22197273
Phenotypes for gene: CD27 were set to Lymphoproliferative syndrome 2, MIM# 615122; Host response to EBV
Review for gene: CD27 was set to GREEN
Added comment: At least four families reported.
Sources: Expert list
Susceptibility to Viral Infections v0.47 ITK Zornitza Stark Marked gene: ITK as ready
Susceptibility to Viral Infections v0.47 ITK Zornitza Stark Gene: itk has been classified as Green List (High Evidence).
Susceptibility to Viral Infections v0.47 ITK Zornitza Stark Classified gene: ITK as Green List (high evidence)
Susceptibility to Viral Infections v0.47 ITK Zornitza Stark Gene: itk has been classified as Green List (High Evidence).
Susceptibility to Viral Infections v0.46 ITK Zornitza Stark gene: ITK was added
gene: ITK was added to Susceptibility to Viral Infections. Sources: Expert list
Mode of inheritance for gene: ITK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ITK were set to 19425169; 22289921; 21109689
Phenotypes for gene: ITK were set to Lymphoproliferative syndrome 1, MIM# 613011; EBV- associated B cell lymphoproliferation, lymphoma
Review for gene: ITK was set to GREEN
Added comment: At least three families reported, abnormal host response to EBV.
Sources: Expert list
Susceptibility to Viral Infections v0.45 XIAP Zornitza Stark Marked gene: XIAP as ready
Susceptibility to Viral Infections v0.45 XIAP Zornitza Stark Gene: xiap has been classified as Green List (High Evidence).
Susceptibility to Viral Infections v0.45 XIAP Zornitza Stark Classified gene: XIAP as Green List (high evidence)
Susceptibility to Viral Infections v0.45 XIAP Zornitza Stark Gene: xiap has been classified as Green List (High Evidence).
Susceptibility to Viral Infections v0.44 XIAP Zornitza Stark gene: XIAP was added
gene: XIAP was added to Susceptibility to Viral Infections. Sources: Expert list
Mode of inheritance for gene: XIAP was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: XIAP were set to 17080092
Phenotypes for gene: XIAP were set to Lymphoproliferative syndrome, X-linked, 2 300635; Host response to EBV
Review for gene: XIAP was set to GREEN
Added comment: Sources: Expert list
Susceptibility to Viral Infections v0.43 SH2D1A Zornitza Stark Marked gene: SH2D1A as ready
Susceptibility to Viral Infections v0.43 SH2D1A Zornitza Stark Gene: sh2d1a has been classified as Green List (High Evidence).
Susceptibility to Viral Infections v0.43 SH2D1A Zornitza Stark Classified gene: SH2D1A as Green List (high evidence)
Susceptibility to Viral Infections v0.43 SH2D1A Zornitza Stark Gene: sh2d1a has been classified as Green List (High Evidence).
Susceptibility to Viral Infections v0.42 SH2D1A Zornitza Stark gene: SH2D1A was added
gene: SH2D1A was added to Susceptibility to Viral Infections. Sources: Expert list
Mode of inheritance for gene: SH2D1A was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SH2D1A were set to 9771704
Phenotypes for gene: SH2D1A were set to Host response to EBV infection; Lymphoproliferative syndrome, X-linked, 1 308240
Review for gene: SH2D1A was set to GREEN
Added comment: Sources: Expert list
Susceptibility to Viral Infections v0.41 NLRP1 Zornitza Stark Marked gene: NLRP1 as ready
Susceptibility to Viral Infections v0.41 NLRP1 Zornitza Stark Gene: nlrp1 has been classified as Red List (Low Evidence).
Susceptibility to Viral Infections v0.41 NLRP1 Zornitza Stark gene: NLRP1 was added
gene: NLRP1 was added to Susceptibility to Viral Infections. Sources: Expert list
Mode of inheritance for gene: NLRP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NLRP1 were set to 31484767
Phenotypes for gene: NLRP1 were set to Recurrent respiratory papillomatosis
Review for gene: NLRP1 was set to RED
Added comment: Single family reported with homozygous GoF variants in siblings with recurrent respiratory papillomatosis. Note gene is associated with multiple, mono- and bi-allelic immunological phenotypes.
Sources: Expert list
Susceptibility to Viral Infections v0.40 CIB1 Zornitza Stark Marked gene: CIB1 as ready
Susceptibility to Viral Infections v0.40 CIB1 Zornitza Stark Gene: cib1 has been classified as Green List (High Evidence).
Susceptibility to Viral Infections v0.40 CIB1 Zornitza Stark Classified gene: CIB1 as Green List (high evidence)
Susceptibility to Viral Infections v0.40 CIB1 Zornitza Stark Gene: cib1 has been classified as Green List (High Evidence).
Susceptibility to Viral Infections v0.39 CIB1 Zornitza Stark gene: CIB1 was added
gene: CIB1 was added to Susceptibility to Viral Infections. Sources: Expert list
Mode of inheritance for gene: CIB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CIB1 were set to 30068544
Phenotypes for gene: CIB1 were set to Epidermodysplasia verruciformis 3, MIM# 618267; HPV infections and cancer of the skin
Review for gene: CIB1 was set to GREEN
Added comment: 24 individuals from six families reported.
Sources: Expert list
Mendeliome v0.2660 SNORA31 Zornitza Stark Marked gene: SNORA31 as ready
Mendeliome v0.2660 SNORA31 Zornitza Stark Gene: snora31 has been classified as Green List (High Evidence).
Mendeliome v0.2660 SNORA31 Zornitza Stark Classified gene: SNORA31 as Green List (high evidence)
Mendeliome v0.2660 SNORA31 Zornitza Stark Gene: snora31 has been classified as Green List (High Evidence).
Mendeliome v0.2659 SNORA31 Zornitza Stark gene: SNORA31 was added
gene: SNORA31 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SNORA31 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SNORA31 were set to 31806906
Phenotypes for gene: SNORA31 were set to Susceptibility to HSV1 encephalitis
Review for gene: SNORA31 was set to GREEN
Added comment: Five unrelated individuals reported with rare missense variants in this gene, functional data to support susceptibility to herpes simplex encephalitis.
Sources: Expert list
Susceptibility to Viral Infections v0.38 SNORA31 Zornitza Stark Marked gene: SNORA31 as ready
Susceptibility to Viral Infections v0.38 SNORA31 Zornitza Stark Gene: snora31 has been classified as Green List (High Evidence).
Susceptibility to Viral Infections v0.38 SNORA31 Zornitza Stark Phenotypes for gene: SNORA31 were changed from Susceptibility to herpes simplex encephalitis to Susceptibility to HSV1 encephalitis
Susceptibility to Viral Infections v0.37 SNORA31 Zornitza Stark Classified gene: SNORA31 as Green List (high evidence)
Susceptibility to Viral Infections v0.37 SNORA31 Zornitza Stark Gene: snora31 has been classified as Green List (High Evidence).
Susceptibility to Viral Infections v0.36 SNORA31 Zornitza Stark gene: SNORA31 was added
gene: SNORA31 was added to Susceptibility to Viral Infections. Sources: Expert list
Mode of inheritance for gene: SNORA31 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SNORA31 were set to 31806906
Phenotypes for gene: SNORA31 were set to Susceptibility to herpes simplex encephalitis
Review for gene: SNORA31 was set to GREEN
Added comment: Five unrelated individuals reported with rare missense variants in this gene, functional data to support susceptibility to herpes simplex encephalitis.
Sources: Expert list
Macular Dystrophy/Stargardt Disease v0.10 PRDM13 Bryony Thompson Classified gene: PRDM13 as Green List (high evidence)
Macular Dystrophy/Stargardt Disease v0.10 PRDM13 Bryony Thompson Added comment: Comment on list classification: Cause of condition cannot be detected by WES
Macular Dystrophy/Stargardt Disease v0.10 PRDM13 Bryony Thompson Gene: prdm13 has been classified as Green List (High Evidence).
Macular Dystrophy/Stargardt Disease v0.9 PRDM13 Bryony Thompson edited their review of gene: PRDM13: Changed rating: GREEN
Macular Dystrophy/Stargardt Disease v0.9 PRDM13 Bryony Thompson Deleted their comment
Cerebellar and Pontocerebellar Hypoplasia v0.139 Bryony Thompson Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Cerebellar and Pontocerebellar Hypoplasia v0.137 FKRP Zornitza Stark Marked gene: FKRP as ready
Cerebellar and Pontocerebellar Hypoplasia v0.137 FKRP Zornitza Stark Gene: fkrp has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.137 FKRP Zornitza Stark Classified gene: FKRP as Green List (high evidence)
Cerebellar and Pontocerebellar Hypoplasia v0.137 FKRP Zornitza Stark Gene: fkrp has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.136 POMT2 Zornitza Stark Marked gene: POMT2 as ready
Cerebellar and Pontocerebellar Hypoplasia v0.136 POMT2 Zornitza Stark Gene: pomt2 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.136 POMT2 Zornitza Stark Classified gene: POMT2 as Green List (high evidence)
Cerebellar and Pontocerebellar Hypoplasia v0.136 POMT2 Zornitza Stark Gene: pomt2 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.135 ROBO3 Zornitza Stark Marked gene: ROBO3 as ready
Cerebellar and Pontocerebellar Hypoplasia v0.135 ROBO3 Zornitza Stark Gene: robo3 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.135 ROBO3 Zornitza Stark Classified gene: ROBO3 as Green List (high evidence)
Cerebellar and Pontocerebellar Hypoplasia v0.135 ROBO3 Zornitza Stark Gene: robo3 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.134 FKTN Zornitza Stark Marked gene: FKTN as ready
Cerebellar and Pontocerebellar Hypoplasia v0.134 FKTN Zornitza Stark Added comment: Comment when marking as ready: Agree, structural brain abnormalities are a feature of more severe FKTN-associated disease, though PCH/cerebellar hypoplasia not prominent (more unusual abnormalities like cerebellar polymicrogyria described).
Cerebellar and Pontocerebellar Hypoplasia v0.134 FKTN Zornitza Stark Gene: fktn has been classified as Amber List (Moderate Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.134 FKTN Zornitza Stark Phenotypes for gene: FKTN were changed from Cardiomyopathy, dilated, 1X 611615; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 253800; Muscular dystrophy-dystroglycanopathy (congenital without mental retardation), type B, 4 613152; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 4 611588; Walker-Warburg syndrome to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 253800; Muscular dystrophy-dystroglycanopathy (congenital without mental retardation), type B, 4 613152; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 4 611588; Walker-Warburg syndrome
Cerebellar and Pontocerebellar Hypoplasia v0.133 FKTN Zornitza Stark Classified gene: FKTN as Amber List (moderate evidence)
Cerebellar and Pontocerebellar Hypoplasia v0.133 FKTN Zornitza Stark Gene: fktn has been classified as Amber List (Moderate Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.132 GMPPB Zornitza Stark Marked gene: GMPPB as ready
Cerebellar and Pontocerebellar Hypoplasia v0.132 GMPPB Zornitza Stark Gene: gmppb has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.132 GMPPB Zornitza Stark Classified gene: GMPPB as Green List (high evidence)
Cerebellar and Pontocerebellar Hypoplasia v0.132 GMPPB Zornitza Stark Gene: gmppb has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.131 POMT1 Zornitza Stark Marked gene: POMT1 as ready
Cerebellar and Pontocerebellar Hypoplasia v0.131 POMT1 Zornitza Stark Gene: pomt1 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.131 POMT1 Zornitza Stark Classified gene: POMT1 as Green List (high evidence)
Cerebellar and Pontocerebellar Hypoplasia v0.131 POMT1 Zornitza Stark Gene: pomt1 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.130 ISPD Zornitza Stark Marked gene: ISPD as ready
Cerebellar and Pontocerebellar Hypoplasia v0.130 ISPD Zornitza Stark Gene: ispd has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.130 ISPD Zornitza Stark Classified gene: ISPD as Green List (high evidence)
Cerebellar and Pontocerebellar Hypoplasia v0.130 ISPD Zornitza Stark Gene: ispd has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.129 KIAA1109 Zornitza Stark Marked gene: KIAA1109 as ready
Cerebellar and Pontocerebellar Hypoplasia v0.129 KIAA1109 Zornitza Stark Gene: kiaa1109 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.129 KIAA1109 Zornitza Stark Phenotypes for gene: KIAA1109 were changed from to Alkuraya-Kucinskas syndrome, MIM# 617822
Cerebellar and Pontocerebellar Hypoplasia v0.128 KIAA1109 Zornitza Stark Publications for gene: KIAA1109 were set to
Cerebellar and Pontocerebellar Hypoplasia v0.127 KIAA1109 Zornitza Stark Mode of inheritance for gene: KIAA1109 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cerebellar and Pontocerebellar Hypoplasia v0.126 POMGNT2 Zornitza Stark Marked gene: POMGNT2 as ready
Cerebellar and Pontocerebellar Hypoplasia v0.126 POMGNT2 Zornitza Stark Gene: pomgnt2 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.126 POMGNT2 Zornitza Stark Classified gene: POMGNT2 as Green List (high evidence)
Cerebellar and Pontocerebellar Hypoplasia v0.126 POMGNT2 Zornitza Stark Gene: pomgnt2 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.125 POMGNT1 Zornitza Stark Marked gene: POMGNT1 as ready
Cerebellar and Pontocerebellar Hypoplasia v0.125 POMGNT1 Zornitza Stark Gene: pomgnt1 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.125 POMGNT1 Zornitza Stark Classified gene: POMGNT1 as Green List (high evidence)
Cerebellar and Pontocerebellar Hypoplasia v0.125 POMGNT1 Zornitza Stark Gene: pomgnt1 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.124 LARGE1 Zornitza Stark Marked gene: LARGE1 as ready
Cerebellar and Pontocerebellar Hypoplasia v0.124 LARGE1 Zornitza Stark Gene: large1 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.124 LARGE1 Zornitza Stark Publications for gene: LARGE1 were set to PMID: 17878207; 19067344; PMID: 24709677
Cerebellar and Pontocerebellar Hypoplasia v0.123 LARGE1 Zornitza Stark Classified gene: LARGE1 as Green List (high evidence)
Cerebellar and Pontocerebellar Hypoplasia v0.123 LARGE1 Zornitza Stark Gene: large1 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.122 LARGE1 Zornitza Stark Tag SV/CNV tag was added to gene: LARGE1.
Cerebellar and Pontocerebellar Hypoplasia v0.122 MACF1 Zornitza Stark Marked gene: MACF1 as ready
Cerebellar and Pontocerebellar Hypoplasia v0.122 MACF1 Zornitza Stark Gene: macf1 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.122 MACF1 Zornitza Stark Classified gene: MACF1 as Green List (high evidence)
Cerebellar and Pontocerebellar Hypoplasia v0.122 MACF1 Zornitza Stark Gene: macf1 has been classified as Green List (High Evidence).
Pierre Robin Sequence v0.6 TCOF1 Zornitza Stark Marked gene: TCOF1 as ready
Pierre Robin Sequence v0.6 TCOF1 Zornitza Stark Gene: tcof1 has been classified as Green List (High Evidence).
Pierre Robin Sequence v0.6 TCOF1 Zornitza Stark Phenotypes for gene: TCOF1 were changed from to Treacher Collins syndrome 1, MIM# 154500
Pierre Robin Sequence v0.5 TCOF1 Zornitza Stark Publications for gene: TCOF1 were set to
Pierre Robin Sequence v0.4 TCOF1 Zornitza Stark Mode of inheritance for gene: TCOF1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pierre Robin Sequence v0.3 TCOF1 Zornitza Stark reviewed gene: TCOF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12444270, 15150774, 21951868; Phenotypes: Treacher Collins syndrome 1, MIM# 154500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2658 TCOF1 Zornitza Stark Marked gene: TCOF1 as ready
Mendeliome v0.2658 TCOF1 Zornitza Stark Gene: tcof1 has been classified as Green List (High Evidence).
Mendeliome v0.2658 TCOF1 Zornitza Stark Phenotypes for gene: TCOF1 were changed from to Treacher Collins syndrome 1, MIM# 154500
Mendeliome v0.2657 TCOF1 Zornitza Stark Publications for gene: TCOF1 were set to
Mendeliome v0.2656 TCOF1 Zornitza Stark Mode of inheritance for gene: TCOF1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2655 TCOF1 Zornitza Stark reviewed gene: TCOF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12444270, 15150774, 21951868; Phenotypes: Treacher Collins syndrome 1, MIM# 154500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mandibulofacial Acrofacial dysostosis v0.6 TCOF1 Zornitza Stark Marked gene: TCOF1 as ready
Mandibulofacial Acrofacial dysostosis v0.6 TCOF1 Zornitza Stark Gene: tcof1 has been classified as Green List (High Evidence).
Mandibulofacial Acrofacial dysostosis v0.6 TCOF1 Zornitza Stark Phenotypes for gene: TCOF1 were changed from to Treacher Collins syndrome 1, MIM# 154500
Mandibulofacial Acrofacial dysostosis v0.5 TCOF1 Zornitza Stark Publications for gene: TCOF1 were set to
Mandibulofacial Acrofacial dysostosis v0.4 TCOF1 Zornitza Stark Mode of inheritance for gene: TCOF1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2609 EMX2 Zornitza Stark Tag disputed tag was added to gene: EMX2.
Intellectual disability syndromic and non-syndromic v0.2609 EMX2 Zornitza Stark Marked gene: EMX2 as ready
Intellectual disability syndromic and non-syndromic v0.2609 EMX2 Zornitza Stark Gene: emx2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2609 EMX2 Zornitza Stark Phenotypes for gene: EMX2 were changed from to Schizencephaly, MIM# 269160
Intellectual disability syndromic and non-syndromic v0.2608 EMX2 Zornitza Stark Publications for gene: EMX2 were set to
Intellectual disability syndromic and non-syndromic v0.2607 EMX2 Zornitza Stark Mode of inheritance for gene: EMX2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2606 EMX2 Zornitza Stark Classified gene: EMX2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2606 EMX2 Zornitza Stark Gene: emx2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2605 EMX2 Zornitza Stark reviewed gene: EMX2: Rating: AMBER; Mode of pathogenicity: None; Publications: 8528262, 9359037, 9153481, 9153481, 18409201; Phenotypes: Schizencephaly, MIM# 269160; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Callosome v0.142 EMX2 Zornitza Stark Marked gene: EMX2 as ready
Callosome v0.142 EMX2 Zornitza Stark Gene: emx2 has been classified as Red List (Low Evidence).
Callosome v0.142 EMX2 Zornitza Stark Phenotypes for gene: EMX2 were changed from to Schizencephaly, MIM# 269160
Callosome v0.141 EMX2 Zornitza Stark Publications for gene: EMX2 were set to 8528262; 9359037; 9153481; 9153481; 18409201
Callosome v0.140 EMX2 Zornitza Stark Publications for gene: EMX2 were set to
Callosome v0.139 EMX2 Zornitza Stark Classified gene: EMX2 as Red List (low evidence)
Callosome v0.139 EMX2 Zornitza Stark Gene: emx2 has been classified as Red List (Low Evidence).
Callosome v0.139 EMX2 Zornitza Stark Classified gene: EMX2 as Red List (low evidence)
Callosome v0.139 EMX2 Zornitza Stark Gene: emx2 has been classified as Red List (Low Evidence).
Callosome v0.138 EMX2 Zornitza Stark reviewed gene: EMX2: Rating: RED; Mode of pathogenicity: None; Publications: 8528262, 9359037, 9153481, 9153481, 18409201; Phenotypes: Schizencephaly, MIM# 269160; Mode of inheritance: None
Genetic Epilepsy v0.689 EMX2 Zornitza Stark Marked gene: EMX2 as ready
Genetic Epilepsy v0.689 EMX2 Zornitza Stark Gene: emx2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.689 EMX2 Zornitza Stark Phenotypes for gene: EMX2 were changed from to Schizencephaly, MIM# 269160
Genetic Epilepsy v0.688 EMX2 Zornitza Stark Tag disputed tag was added to gene: EMX2.
Genetic Epilepsy v0.688 EMX2 Zornitza Stark Publications for gene: EMX2 were set to
Genetic Epilepsy v0.687 EMX2 Zornitza Stark Mode of inheritance for gene: EMX2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.686 EMX2 Zornitza Stark Classified gene: EMX2 as Amber List (moderate evidence)
Genetic Epilepsy v0.686 EMX2 Zornitza Stark Gene: emx2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2655 EMX2 Zornitza Stark Tag disputed tag was added to gene: EMX2.
Genetic Epilepsy v0.685 EMX2 Zornitza Stark reviewed gene: EMX2: Rating: AMBER; Mode of pathogenicity: None; Publications: 8528262, 9359037, 9153481, 9153481, 18409201; Phenotypes: Schizencephaly, MIM# 269160; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebellar and Pontocerebellar Hypoplasia v0.121 GPAA1 Zornitza Stark Marked gene: GPAA1 as ready
Cerebellar and Pontocerebellar Hypoplasia v0.121 GPAA1 Zornitza Stark Gene: gpaa1 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.121 GPAA1 Zornitza Stark Phenotypes for gene: GPAA1 were changed from to Glycosylphosphatidylinositol biosynthesis defect 15, MIM# 617810
Cerebellar and Pontocerebellar Hypoplasia v0.120 GPAA1 Zornitza Stark Publications for gene: GPAA1 were set to
Cerebellar and Pontocerebellar Hypoplasia v0.119 GPAA1 Zornitza Stark Mode of inheritance for gene: GPAA1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cerebellar and Pontocerebellar Hypoplasia v0.118 PPP1CB Zornitza Stark Marked gene: PPP1CB as ready
Cerebellar and Pontocerebellar Hypoplasia v0.118 PPP1CB Zornitza Stark Gene: ppp1cb has been classified as Red List (Low Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.118 PPP1CB Zornitza Stark Phenotypes for gene: PPP1CB were changed from to Noonan syndrome-like disorder with loose anagen hair 2 (MIM#617506)
Cerebellar and Pontocerebellar Hypoplasia v0.117 PPP1CB Zornitza Stark Publications for gene: PPP1CB were set to
Cerebellar and Pontocerebellar Hypoplasia v0.116 PPP1CB Zornitza Stark Mode of inheritance for gene: PPP1CB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebellar and Pontocerebellar Hypoplasia v0.115 PPP1CB Zornitza Stark Classified gene: PPP1CB as Red List (low evidence)
Cerebellar and Pontocerebellar Hypoplasia v0.115 PPP1CB Zornitza Stark Gene: ppp1cb has been classified as Red List (Low Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.114 PPP1CB Zornitza Stark reviewed gene: PPP1CB: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Noonan syndrome-like disorder with loose anagen hair 2 (MIM#617506); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebellar and Pontocerebellar Hypoplasia v0.114 FOXP1 Zornitza Stark Marked gene: FOXP1 as ready
Cerebellar and Pontocerebellar Hypoplasia v0.114 FOXP1 Zornitza Stark Added comment: Comment when marking as ready: Agree, appears a rare manifestation of this syndrome.
Cerebellar and Pontocerebellar Hypoplasia v0.114 FOXP1 Zornitza Stark Gene: foxp1 has been classified as Red List (Low Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.114 FOXP1 Zornitza Stark Classified gene: FOXP1 as Red List (low evidence)
Cerebellar and Pontocerebellar Hypoplasia v0.114 FOXP1 Zornitza Stark Gene: foxp1 has been classified as Red List (Low Evidence).
Skeletal Ciliopathies v0.11 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Rare Disease
Mandibulofacial Acrofacial dysostosis v0.3 TCOF1 Melanie Marty changed review comment from: The majority of the variants reported are PTCs that lead to truncation or NMD (PMID: 21951868). More than 60% cases arise from de novo variants (PMID: 15150774, 21951868). Penetrance of the genetic variants causing TCS is thought to be very high. However, extreme inter- and intra- familial phenotypic variation has been reported (PMID: 15150774).; to: The majority of the variants reported are PTCs that lead to truncation or NMD, only a few missense have been reported (ClinVar; PMID: 21951868). More than 60% cases arise from de novo variants (PMID: 15150774, 21951868). Penetrance of the genetic variants causing TCS is thought to be very high. However, extreme inter- and intra- familial phenotypic variation has been reported (PMID: 15150774).
Mandibulofacial Acrofacial dysostosis v0.3 TCOF1 Melanie Marty changed review comment from: The majority of the variants reported are PTCs that lead to truncation or NMD (PMID: 21951868). More than 60% cases arise from de novo variants (PMID: 15150774, 21951868). Penetrance of the genetic variants causing TCS is thought to be very high. However, extreme inter- and intra- familial phenotypic variation has been reported (PMID: 15150774).; to: The majority of the variants reported are PTCs that lead to truncation or NMD (PMID: 21951868). More than 60% cases arise from de novo variants (PMID: 15150774, 21951868). Penetrance of the genetic variants causing TCS is thought to be very high. However, extreme inter- and intra- familial phenotypic variation has been reported (PMID: 15150774).
Mandibulofacial Acrofacial dysostosis v0.3 TCOF1 Melanie Marty reviewed gene: TCOF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12444270, 15150774, 21951868; Phenotypes: Treacher Collins syndrome 1 154500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebellar and Pontocerebellar Hypoplasia v0.113 MACF1 Crystle Lee gene: MACF1 was added
gene: MACF1 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Expert Review
Mode of inheritance for gene: MACF1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MACF1 were set to 30471716
Phenotypes for gene: MACF1 were set to Lissencephaly 9 with complex brainstem malformation (MIM#618325)
Mode of pathogenicity for gene: MACF1 was set to Other
Review for gene: MACF1 was set to GREEN
Added comment: Pontine/Vermis hypoplasia reported in multiple patients with de novo missense variants within the GAR domain

PMID: 30471716; Dobyns 2018: Reported 3 different missense in 7 patients. All reported with brainsteam/cerebellum hypoplasia (Pontine hypoplasia/ Vermis hypoplasia). Postulated to exert Gain of function or dominant negative mechanism

Green in PanelApp UK list
Sources: Expert Review
Cerebellar and Pontocerebellar Hypoplasia v0.113 LARGE1 Elena Savva gene: LARGE1 was added
gene: LARGE1 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Expert list
Mode of inheritance for gene: LARGE1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LARGE1 were set to PMID: 17878207; 19067344; PMID: 24709677
Phenotypes for gene: LARGE1 were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 6 613154; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 6 608840; Walker Warburg syndrome
Added comment: Gross deletions and rearrangements are commonly reported for this gene (PMID: 24709677)

PMID: 17878207 - single reported patient with WWS had cerebellar hypoplasia, died in infancy. Patient had a heterozygous PTC.

PMID: 19067344 - 2 chet patients (missense/PTC) had congenital muscular dystrophy. Patients were both reported with hypoplastic pontine abnormality, one also had a dysplastic vermis. A third patient is reported but this is the same as ^.

PMID: 24709677 - 4 patients.
1/4 mild pontine hyoplasia and inferior vermis hypoplasia, 1/4 very small pons, hypoplastic brainstem and cerebellar cysts, 1/4 small pons, 1/4 hypoplastic pons.
3/4 were diagnosed with WWS, 1/4 with Fukuyama Congenital Muscular Dystrophy
Sources: Expert list
Cerebellar and Pontocerebellar Hypoplasia v0.113 POMGNT1 Crystle Lee gene: POMGNT1 was added
gene: POMGNT1 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Expert Review
Mode of inheritance for gene: POMGNT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POMGNT1 were set to 19067344
Phenotypes for gene: POMGNT1 were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 3 (MIM#253280)
Review for gene: POMGNT1 was set to GREEN
Added comment: Cerebellar hypoplasia is a feature of Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A3 (OMIM)

PMID: 19067344; Clement 2008: Reported 7 patients, all showed either cerebellar or pontine hypoplasia and cerebellar cysts
Sources: Expert Review
Cerebellar and Pontocerebellar Hypoplasia v0.113 POMGNT2 Crystle Lee gene: POMGNT2 was added
gene: POMGNT2 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Expert Review
Mode of inheritance for gene: POMGNT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POMGNT2 were set to 22958903; 27066570
Phenotypes for gene: POMGNT2 were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 8 (MIM#614830)
Review for gene: POMGNT2 was set to GREEN
Added comment: POMGNT2 (also known as GTDC2). Associated phenotype also referred to as Walker-Warburg syndrome.

PMID: 22958903; Manzini 2012: 3 different hom variants in 3 consang. families, all reported with cerebellar hypoplasia. (2 nonsense and 1 missense). "knockdown in zebrafish showed all WWS features (hydrocephalus, ocular defects, and muscular dystrophy)"

PMID: 27066570; Endo 2015: reported 3 hom/chet missense with no cerebellar hypoplasia. Missense variants showed to reduced activity, which likely explains the milder phenotype.

Green in PanelApp UK list.
Sources: Expert Review
Cerebellar and Pontocerebellar Hypoplasia v0.113 KIAA1109 Elena Savva reviewed gene: KIAA1109: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29290337, 30906834; Phenotypes: Alkuraya-Kucinskas syndrome 617822; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebellar and Pontocerebellar Hypoplasia v0.113 ISPD Elena Savva gene: ISPD was added
gene: ISPD was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Expert list
Mode of inheritance for gene: ISPD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ISPD were set to PMID: 22522421; 22522420
Phenotypes for gene: ISPD were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7 614643; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 7 616052; Walker–Warburg syndrome
Review for gene: ISPD was set to GREEN
Added comment: PMID: 22522421 - 11 patients with severe WWS, only two survived beyond 2 years of age. "Routine cerebral MRI
showed typical features of cobblestone lissencephaly together with hydrocephalus, cerebellar hypoplasia and a kinked brainstem".
10/11 patients either had chet mutations (missense, PTC) or homozygous PTCs/exon deletions, and diagnosed with either WSS or MEB. A single patient was homozygous for a missense. 10/11 reported specifically with "cerebellar abnormalities", no specific numbers for cerebellar hypoplasia.

PMID: 22522420 - single patient with WWS, chet for exon deletions/PTC. MRI taken at 5 months of age shows hypoplastic brainstem and cerebellar vermis.
Sources: Expert list
Cerebellar and Pontocerebellar Hypoplasia v0.113 GPAA1 Elena Savva reviewed gene: GPAA1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29100095, 31353022; Phenotypes: Glycosylphosphatidylinositol biosynthesis defect 15 617810; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebellar and Pontocerebellar Hypoplasia v0.113 POMT1 Crystle Lee gene: POMT1 was added
gene: POMT1 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Expert Review
Mode of inheritance for gene: POMT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POMT1 were set to 24491487; 31311558
Phenotypes for gene: POMT1 were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1 (MIM#236670); Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 1 (MIM#613155)
Review for gene: POMT1 was set to GREEN
Added comment: Cerebellar hypoplasia is a feature of Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 (previously Walker-Warburg syndrome) and type B1 (OMIM)

PMID: 24491487; Wallace 2015: Reports 3 patients and reviews variability of clinical outcomes associated with a single frameshift variant (ie h chet missense/fs associated with less severe phenotype).

PMID: 31311558; Geis 2019: Multiple WWS families reported. Cerebellar hypoplasia is a consistent feature.
Sources: Expert Review
Cerebellar and Pontocerebellar Hypoplasia v0.113 GMPPB Elena Savva reviewed gene: GMPPB: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30257713, 30684953, 23768512; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 615350, Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 14 615351, Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 615352; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebellar and Pontocerebellar Hypoplasia v0.113 GMPPB Elena Savva Deleted their review
Cerebellar and Pontocerebellar Hypoplasia v0.113 GMPPB Elena Savva gene: GMPPB was added
gene: GMPPB was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Expert list
Mode of inheritance for gene: GMPPB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GMPPB were set to PMID: 30257713; 30684953; 23768512
Phenotypes for gene: GMPPB were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 615350; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 14 615351; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 615352
Added comment: Decipher: Patient: 363842 is described with abnormality of the cerebellar vermis

PMID: 30257713 - 3/6 patients with MRIs has mild cerebellar hypoplasia. Patients were all chet with mostly two missense in trans, or a missense/PTC. All patients with hypoplasia were diagnosed with congenital muscular dystrophy with cerebellar involvement (CRB). Age at examination unknown, patients range from 20 months - 74 years old).

PMID: 30684953 - patient with Limb-girdle muscular dystrophy, MRI was normal. Patient had chet missense.

PMID: 23768512 - 3/7 patients had cerebellar/pontine hypoplasia. Patients were diagnosed with MEB, muscle-eye-brain disease or CRB.
Sources: Expert list
Cerebellar and Pontocerebellar Hypoplasia v0.113 POMT2 Crystle Lee gene: POMT2 was added
gene: POMT2 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Expert Review
Mode of inheritance for gene: POMT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POMT2 were set to 15894594; 17634419
Phenotypes for gene: POMT2 were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 2 (MIM#613150); Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 2 (MIM#613156)
Review for gene: POMT2 was set to GREEN
Added comment: Cerebellar hypoplasia is a feature of Muscular dystrophy-dystroglycanopathy type A2 (previously Walker-Warburg syndrome) and B2 (OMIM). Severity of phenotype likely correlates with amount of residual activity.

PMID: 15894594; van Reeuwijk 2005: Reported LoF type variants in 3 families. Cerebellar hypoplasia reported in 2 patients.

PMID: 17634419; Yanagisawa 2007: Cerebellar vermis hypoplasis was a feature all 4 patients reported. (Hom missense and chet missense/nonsense)
Sources: Expert Review
Cerebellar and Pontocerebellar Hypoplasia v0.113 FOXP1 Elena Savva reviewed gene: FOXP1: Rating: AMBER; Mode of pathogenicity: Other; Publications: PMID: 29090079, 28735298; Phenotypes: Mental retardation with language impairment and with or without autistic features 613670; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Cerebellar and Pontocerebellar Hypoplasia v0.113 PPP1CB Crystle Lee reviewed gene: PPP1CB: Rating: AMBER; Mode of pathogenicity: None; Publications: 27264673, 28211982, 30236064; Phenotypes: Noonan syndrome-like disorder with loose anagen hair 2 (MIM#617506); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Cerebellar and Pontocerebellar Hypoplasia v0.113 FKTN Elena Savva gene: FKTN was added
gene: FKTN was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Expert Review
Mode of inheritance for gene: FKTN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FKTN were set to PMID: 17878207; 25821721; 19342235; 18177472; 12601708
Phenotypes for gene: FKTN were set to Cardiomyopathy, dilated, 1X 611615; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 253800; Muscular dystrophy-dystroglycanopathy (congenital without mental retardation), type B, 4 613152; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 4 611588; Walker-Warburg syndrome
Review for gene: FKTN was set to AMBER
Added comment: PMID: 17878207 - 1/6 unrelated families had cerebellar hypoplasia, patient was homozygous for a PTC, had Walker-Warburg syndrome (WWS)

PMID: 25821721 - 1 patient with muscular dystrophy, had a normal MRI and two chet missense.

PMID: 19342235 - 2 siblings chet for two missense, do not report any cognitive issues. No MRI, were diagnosed with Limb-Girdle Muscular Dystrophy Without Mental Retardation

PMID: 18177472 - Two patients with WWS, one died soon after birth and was chet for a missense and 3' UTR deletion. This patient only had an MRI showing severe brain malformation but no mention of cerebellar hypoplasia. The second patient was homozygous for a PTC.

PMID: 12601708 - 1 patient with WWS and a homozygous PTC. Patient was an infant and tomography showed cortical atrophy

Summary: Cerebellar hypoplasia may be a feature exclusive to severe WWS, which requires two null/near-null alleles. Need more reports to make it GREEN
Sources: Expert Review
Mendeliome v0.2655 EMX2 Zornitza Stark Marked gene: EMX2 as ready
Mendeliome v0.2655 EMX2 Zornitza Stark Gene: emx2 has been classified as Amber List (Moderate Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.113 ROBO3 Crystle Lee gene: ROBO3 was added
gene: ROBO3 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Expert Review
Mode of inheritance for gene: ROBO3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ROBO3 were set to 15105459
Phenotypes for gene: ROBO3 were set to Gaze palsy, familial horizontal, with progressive scoliosis, 1 (MIM#607313)
Review for gene: ROBO3 was set to GREEN
Added comment: Pontine hypoplasia is a feature of the associated phenotype.

PMID: 15105459; Jen 2004: Reported hom variants in 10 patients.
Sources: Expert Review
Mendeliome v0.2655 EMX2 Zornitza Stark Phenotypes for gene: EMX2 were changed from to Schizencephaly, MIM# 269160
Mendeliome v0.2654 EMX2 Zornitza Stark Publications for gene: EMX2 were set to
Mendeliome v0.2653 EMX2 Zornitza Stark Mode of inheritance for gene: EMX2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2652 EMX2 Zornitza Stark Classified gene: EMX2 as Amber List (moderate evidence)
Mendeliome v0.2652 EMX2 Zornitza Stark Gene: emx2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2651 EMX2 Zornitza Stark reviewed gene: EMX2: Rating: AMBER; Mode of pathogenicity: None; Publications: 8528262, 9359037, 9153481, 9153481, 18409201; Phenotypes: Schizencephaly, MIM# 269160; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebellar and Pontocerebellar Hypoplasia v0.113 FKRP Elena Savva gene: FKRP was added
gene: FKRP was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Expert Review
Mode of inheritance for gene: FKRP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FKRP were set to PMID: 16476814; 21293871; 20236121
Phenotypes for gene: FKRP were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 5 613153; Muscular dystrophy-dystroglycanopathy (congenital with or without mental retardation), type B, 5 606612; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 5 607155; Walker–Warburg syndrome
Review for gene: FKRP was set to GREEN
Added comment: PMID: 16476814 - Pons/cerebellar hypoplasia reported in 3/13 patients with MRI results (aged 22 months - 11 years), additional 4/13 had cerebellar cysts. One patient had MED, the other WWS (Walker-Warburg syndrome)
Describes other papers where patients had vermis hypoplasia.

PMID: 21293871 - 2/9 patients with MRI scan had cerebellar atrophy (aged 65, 69 years old), patients had limb-girdle muscular dystrophy 2I

PMID: 20236121 - 2 homozygous siblings with Walker–Warburg syndrome. Postnatal MRI of one sibling shows cerbellar vermis and cortex hypoplasia

Summary: Uncommon feature but reported in >3 patients, more commonly with Walker-Warburg syndrome patients
Sources: Expert Review
Polymicrogyria and Schizencephaly v0.57 FIG4 Zornitza Stark Marked gene: FIG4 as ready
Polymicrogyria and Schizencephaly v0.57 FIG4 Zornitza Stark Gene: fig4 has been classified as Amber List (Moderate Evidence).
Polymicrogyria and Schizencephaly v0.57 FIG4 Zornitza Stark Phenotypes for gene: FIG4 were changed from to Polymicrogyria with epilepsy MIM# 612691
Polymicrogyria and Schizencephaly v0.56 FIG4 Zornitza Stark Publications for gene: FIG4 were set to
Polymicrogyria and Schizencephaly v0.55 FIG4 Zornitza Stark Mode of inheritance for gene: FIG4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polymicrogyria and Schizencephaly v0.54 FIG4 Zornitza Stark Classified gene: FIG4 as Amber List (moderate evidence)
Polymicrogyria and Schizencephaly v0.54 FIG4 Zornitza Stark Gene: fig4 has been classified as Amber List (Moderate Evidence).
Polymicrogyria and Schizencephaly v0.53 FIG4 Lauren Akesson reviewed gene: FIG4: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 18758830, 24598713; Phenotypes: ? Polymicrogyria with epilepsy MIM# 612691; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polymicrogyria and Schizencephaly v0.53 EMX2 Zornitza Stark Marked gene: EMX2 as ready
Polymicrogyria and Schizencephaly v0.53 EMX2 Zornitza Stark Gene: emx2 has been classified as Amber List (Moderate Evidence).
Polymicrogyria and Schizencephaly v0.53 EMX2 Zornitza Stark Phenotypes for gene: EMX2 were changed from to Schizencephaly MIM# 269160
Polymicrogyria and Schizencephaly v0.52 EMX2 Zornitza Stark Publications for gene: EMX2 were set to 8528262; 9359037; 9153481
Polymicrogyria and Schizencephaly v0.51 EMX2 Zornitza Stark Publications for gene: EMX2 were set to
Polymicrogyria and Schizencephaly v0.50 EMX2 Zornitza Stark Mode of inheritance for gene: EMX2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polymicrogyria and Schizencephaly v0.49 EMX2 Zornitza Stark Classified gene: EMX2 as Amber List (moderate evidence)
Polymicrogyria and Schizencephaly v0.49 EMX2 Zornitza Stark Gene: emx2 has been classified as Amber List (Moderate Evidence).
Polymicrogyria and Schizencephaly v0.48 EMX2 Zornitza Stark Tag disputed tag was added to gene: EMX2.
Cobblestone Malformations v0.5 COL3A1 Zornitza Stark Marked gene: COL3A1 as ready
Cobblestone Malformations v0.5 COL3A1 Zornitza Stark Gene: col3a1 has been classified as Green List (High Evidence).
Cobblestone Malformations v0.5 COL3A1 Zornitza Stark Phenotypes for gene: COL3A1 were changed from to Polymicrogyria with or without vascular-type Ehlers-Danlos syndrome, MIM # 618343
Cobblestone Malformations v0.4 COL3A1 Zornitza Stark Publications for gene: COL3A1 were set to
Cobblestone Malformations v0.3 COL3A1 Zornitza Stark Mode of inheritance for gene: COL3A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polymicrogyria and Schizencephaly v0.48 COL18A1 Zornitza Stark Marked gene: COL18A1 as ready
Polymicrogyria and Schizencephaly v0.48 COL18A1 Zornitza Stark Gene: col18a1 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.48 COL18A1 Zornitza Stark Phenotypes for gene: COL18A1 were changed from to Knobloch syndrome, type 1 MIM# 267750
Polymicrogyria and Schizencephaly v0.47 COL18A1 Zornitza Stark Publications for gene: COL18A1 were set to
Polymicrogyria and Schizencephaly v0.46 COL18A1 Zornitza Stark Mode of inheritance for gene: COL18A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2605 ATAD3A Zornitza Stark Phenotypes for gene: ATAD3A were changed from Harel-Yoon syndrome, MIM# 617183 to Harel-Yoon syndrome, MIM# 617183; Pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal (PHRINL SYNDROME) 618810
Intellectual disability syndromic and non-syndromic v0.2604 ATAD3A Zornitza Stark Publications for gene: ATAD3A were set to 27640307; 32004445
Intellectual disability syndromic and non-syndromic v0.2603 ATAD3A Zornitza Stark Mode of pathogenicity for gene: ATAD3A was changed from to Other
Intellectual disability syndromic and non-syndromic v0.2602 ATAD3A Zornitza Stark edited their review of gene: ATAD3A: Added comment: Note mode of pathogenicity includes:
i) bi-allelic missense and nonsense variants and bi-allelic deletions that create an ATAD3B/ATAD3A fusion gene under the lowly expressed ATAD3B promoter
ii) monoallelic dominant-negative missense variants (either de novo or inherited) and de novo monoallelic duplications creating a dominant negative ATAD3A/ATAD3C fusion gene; Changed publications: 27640307, 32004445, 28549128; Changed phenotypes: Harel-Yoon syndrome, MIM# 617183, Pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal (PHRINL SYNDROME) 618810
Cerebellar and Pontocerebellar Hypoplasia v0.113 ATAD3A Zornitza Stark Marked gene: ATAD3A as ready
Cerebellar and Pontocerebellar Hypoplasia v0.113 ATAD3A Zornitza Stark Gene: atad3a has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.113 ATAD3A Zornitza Stark Classified gene: ATAD3A as Green List (high evidence)
Cerebellar and Pontocerebellar Hypoplasia v0.113 ATAD3A Zornitza Stark Gene: atad3a has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.112 ATAD3A Zornitza Stark gene: ATAD3A was added
gene: ATAD3A was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Expert Review
SV/CNV tags were added to gene: ATAD3A.
Mode of inheritance for gene: ATAD3A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATAD3A were set to 28549128
Phenotypes for gene: ATAD3A were set to Pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal (PHRINL SYNDROME), MIM# 618810
Review for gene: ATAD3A was set to GREEN
Added comment: Four unrelated families reported with deletions that generate chimeric ATAD3B/ATAD3A fusion genes and fatal congenital pontocerebellar hypoplasia. One family with genomic rearrangements affecting the ATAD3C/ATAD3B genes on one allele and ATAD3B/ATAD3A genes on the other displayed later-onset encephalopathy with cerebellar atrophy, ataxia and dystonia.
Sources: Expert Review
Mendeliome v0.2651 ATAD3A Zornitza Stark Phenotypes for gene: ATAD3A were changed from Harel-Yoon syndrome, MIM# 617183 to Harel-Yoon syndrome, MIM# 617183; Pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal (PHRINL SYNDROME) 618810
Mendeliome v0.2650 ATAD3A Zornitza Stark Publications for gene: ATAD3A were set to 27640307; 32004445
Mendeliome v0.2649 ATAD3A Zornitza Stark edited their review of gene: ATAD3A: Added comment: Mode of pathogenicity includes:
i) bi-allelic missense and nonsense variants and bi-allelic deletions that create an ATAD3B/ATAD3A fusion gene under the lowly expressed ATAD3B promoter
ii) monoallelic dominant-negative missense variants (either de novo or inherited) and de novo monoallelic duplications creating a dominant negative ATAD3A/ATAD3C fusion gene; Changed publications: 27640307, 32004445, 28549128; Changed phenotypes: Harel-Yoon syndrome, MIM# 617183, Pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal (PHRINL SYNDROME) 618810
Mitochondrial disease v0.442 ATAD3A Zornitza Stark Phenotypes for gene: ATAD3A were changed from Harel-Yoon syndrome, MIM# 617183 to Harel-Yoon syndrome, MIM# 617183; Pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal (PHRINL SYNDROME), MIM# 618810
Mitochondrial disease v0.441 ATAD3A Zornitza Stark Publications for gene: ATAD3A were set to 27640307; 32004445
Mitochondrial disease v0.440 ATAD3A Zornitza Stark Mode of pathogenicity for gene: ATAD3A was changed from to Other
Mitochondrial disease v0.439 GDAP1 Kristin Rigbye reviewed gene: GDAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mitochondrial disease v0.439 ATAD3A David Thorburn reviewed gene: ATAD3A: Rating: GREEN; Mode of pathogenicity: Other; Publications: 28549128; Phenotypes: Pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal (PHRINL SYNDROME) 618810; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2649 CTSA Zornitza Stark Marked gene: CTSA as ready
Mendeliome v0.2649 CTSA Zornitza Stark Gene: ctsa has been classified as Green List (High Evidence).
Mendeliome v0.2649 CTSA Zornitza Stark Phenotypes for gene: CTSA were changed from to Galactosialidosis, MIM# 256540; Cathepsin A-related arteriopathy with strokes and leukoencephalopathy
Mendeliome v0.2648 CTSA Zornitza Stark Publications for gene: CTSA were set to
Mendeliome v0.2647 CTSA Zornitza Stark Mode of inheritance for gene: CTSA was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2646 CTSA Zornitza Stark Deleted their comment
Mendeliome v0.2646 CTSA Zornitza Stark commented on gene: CTSA: Mono-allelic variants cause arteriopathy with strokes and leukodystrophy.
Polymicrogyria and Schizencephaly v0.45 EMX2 Lauren Akesson reviewed gene: EMX2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 8528262, 9359037, 9153481; Phenotypes: Schizencephaly MIM# 269160; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cobblestone Malformations v0.2 COL3A1 Lauren Akesson reviewed gene: COL3A1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28742248, 19455184, 25205403; Phenotypes: Polymicrogyria with or without vascular-type ehlers-danlos syndrome, MIM # 618343; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polymicrogyria and Schizencephaly v0.45 COL18A1 Lauren Akesson reviewed gene: COL18A1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25456301, 19160445, 17546652; Phenotypes: Knobloch syndrome, type 1 MIM# 267750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebellar and Pontocerebellar Hypoplasia v0.111 AMPD2 Zornitza Stark Marked gene: AMPD2 as ready
Cerebellar and Pontocerebellar Hypoplasia v0.111 AMPD2 Zornitza Stark Gene: ampd2 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.111 AMPD2 Zornitza Stark Phenotypes for gene: AMPD2 were changed from to Pontocerebellar hypoplasia, type 9, MIM# 615809
Cerebellar and Pontocerebellar Hypoplasia v0.110 AMPD2 Zornitza Stark Publications for gene: AMPD2 were set to
Cerebellar and Pontocerebellar Hypoplasia v0.109 AMPD2 Zornitza Stark Mode of inheritance for gene: AMPD2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cerebellar and Pontocerebellar Hypoplasia v0.108 AMPD2 Zornitza Stark commented on gene: AMPD2: At least six families reported.
Cerebellar and Pontocerebellar Hypoplasia v0.108 AMPD2 Zornitza Stark reviewed gene: AMPD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23911318, 27066553; Phenotypes: Pontocerebellar hypoplasia, type 9, MIM# 615809; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2646 MN1 Zornitza Stark Phenotypes for gene: MN1 were changed from Intellectual disability; dysmophic features; rhombencephalosynapsis to CEBALID syndrome, MIM#618774; Intellectual disability; dysmophic features; rhombencephalosynapsis
Mendeliome v0.2645 MN1 Zornitza Stark edited their review of gene: MN1: Changed phenotypes: CEBALID syndrome, MIM#618774, Intellectual disability, dysmophic features, rhombencephalosynapsis
Intellectual disability syndromic and non-syndromic v0.2602 MN1 Zornitza Stark Phenotypes for gene: MN1 were changed from Intellectual disability; dysmophic features; rhombencephalosynapsis to CEBALID syndrome, MIM#618774; Intellectual disability; dysmophic features; rhombencephalosynapsis
Intellectual disability syndromic and non-syndromic v0.2601 MN1 Zornitza Stark Mode of inheritance for gene: MN1 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2600 MN1 Zornitza Stark edited their review of gene: MN1: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebellar and Pontocerebellar Hypoplasia v0.108 PTF1A Zornitza Stark Marked gene: PTF1A as ready
Cerebellar and Pontocerebellar Hypoplasia v0.108 PTF1A Zornitza Stark Gene: ptf1a has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.108 PTF1A Zornitza Stark Classified gene: PTF1A as Green List (high evidence)
Cerebellar and Pontocerebellar Hypoplasia v0.108 PTF1A Zornitza Stark Gene: ptf1a has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.107 PTF1A Zornitza Stark gene: PTF1A was added
gene: PTF1A was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Expert list
Mode of inheritance for gene: PTF1A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTF1A were set to 21749365; 10507728; 15543146; 19650412
Phenotypes for gene: PTF1A were set to Pancreatic and cerebellar agenesis, MIM# 609069
Review for gene: PTF1A was set to GREEN
Added comment: At least three unrelated families reported.
Sources: Expert list
Cerebellar and Pontocerebellar Hypoplasia v0.106 MAST1 Zornitza Stark Marked gene: MAST1 as ready
Cerebellar and Pontocerebellar Hypoplasia v0.106 MAST1 Zornitza Stark Gene: mast1 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.106 MAST1 Zornitza Stark Classified gene: MAST1 as Green List (high evidence)
Cerebellar and Pontocerebellar Hypoplasia v0.106 MAST1 Zornitza Stark Gene: mast1 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.105 MAST1 Zornitza Stark gene: MAST1 was added
gene: MAST1 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Expert list
Mode of inheritance for gene: MAST1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAST1 were set to 30449657
Phenotypes for gene: MAST1 were set to Mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations, MIM# 618273
Review for gene: MAST1 was set to GREEN
Added comment: Six unrelated individuals with de novo variants in this gene and a mouse model.
Sources: Expert list
Mendeliome v0.2645 PI4KA Zornitza Stark Marked gene: PI4KA as ready
Mendeliome v0.2645 PI4KA Zornitza Stark Gene: pi4ka has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2645 PI4KA Zornitza Stark Phenotypes for gene: PI4KA were changed from to Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis, MIM# 616531
Mendeliome v0.2644 PI4KA Zornitza Stark Publications for gene: PI4KA were set to
Mendeliome v0.2643 PI4KA Zornitza Stark Mode of inheritance for gene: PI4KA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2642 PI4KA Zornitza Stark Classified gene: PI4KA as Amber List (moderate evidence)
Mendeliome v0.2642 PI4KA Zornitza Stark Gene: pi4ka has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2641 PI4KA Zornitza Stark reviewed gene: PI4KA: Rating: AMBER; Mode of pathogenicity: None; Publications: 25855803; Phenotypes: Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis, MIM# 616531; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polymicrogyria and Schizencephaly v0.45 PI4KA Zornitza Stark Marked gene: PI4KA as ready
Polymicrogyria and Schizencephaly v0.45 PI4KA Zornitza Stark Gene: pi4ka has been classified as Amber List (Moderate Evidence).
Polymicrogyria and Schizencephaly v0.45 PI4KA Zornitza Stark Phenotypes for gene: PI4KA were changed from to Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis, MIM# 616531
Polymicrogyria and Schizencephaly v0.44 PI4KA Zornitza Stark Publications for gene: PI4KA were set to
Polymicrogyria and Schizencephaly v0.43 PI4KA Zornitza Stark Mode of inheritance for gene: PI4KA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polymicrogyria and Schizencephaly v0.42 PI4KA Zornitza Stark Classified gene: PI4KA as Amber List (moderate evidence)
Polymicrogyria and Schizencephaly v0.42 PI4KA Zornitza Stark Gene: pi4ka has been classified as Amber List (Moderate Evidence).
Polymicrogyria and Schizencephaly v0.41 PI4KA Zornitza Stark reviewed gene: PI4KA: Rating: AMBER; Mode of pathogenicity: None; Publications: 25855803; Phenotypes: Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis, MIM# 616531; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebellar and Pontocerebellar Hypoplasia v0.104 PI4KA Zornitza Stark Marked gene: PI4KA as ready
Cerebellar and Pontocerebellar Hypoplasia v0.104 PI4KA Zornitza Stark Gene: pi4ka has been classified as Amber List (Moderate Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.104 PI4KA Zornitza Stark Classified gene: PI4KA as Amber List (moderate evidence)
Cerebellar and Pontocerebellar Hypoplasia v0.104 PI4KA Zornitza Stark Gene: pi4ka has been classified as Amber List (Moderate Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.103 PI4KA Zornitza Stark gene: PI4KA was added
gene: PI4KA was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Expert list
Mode of inheritance for gene: PI4KA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PI4KA were set to 25855803
Phenotypes for gene: PI4KA were set to Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis, MIM# 616531
Review for gene: PI4KA was set to AMBER
Added comment: Single family reported, aware of at least one other yet to be published family identified internally.
Sources: Expert list
Mendeliome v0.2641 CDK5 Zornitza Stark changed review comment from: Single consanguineous family with multiple affected individuals reported.; to: Single consanguineous family with multiple affected individuals reported.
Cerebellar and Pontocerebellar Hypoplasia v0.102 CDK5 Zornitza Stark changed review comment from: Single consanguineous family with multiple affected individuals reported, lishencephaly prominent.
Sources: Expert list; to: Single consanguineous family with multiple affected individuals reported, lissencephaly prominent.
Sources: Expert list
Lissencephaly and Band Heterotopia v0.35 CDK5 Zornitza Stark Marked gene: CDK5 as ready
Lissencephaly and Band Heterotopia v0.35 CDK5 Zornitza Stark Gene: cdk5 has been classified as Red List (Low Evidence).
Lissencephaly and Band Heterotopia v0.35 CDK5 Zornitza Stark gene: CDK5 was added
gene: CDK5 was added to Lissencephaly and Band Heterotopia. Sources: Expert list
Mode of inheritance for gene: CDK5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDK5 were set to 25560765
Phenotypes for gene: CDK5 were set to Lissencephaly 7 with cerebellar hypoplasia, MIM# 616342
Review for gene: CDK5 was set to RED
Added comment: Single consanguineous family with multiple affected individuals reported, lissencephaly prominent.
Sources: Expert list
Callosome v0.138 CDK5 Zornitza Stark Marked gene: CDK5 as ready
Callosome v0.138 CDK5 Zornitza Stark Gene: cdk5 has been classified as Red List (Low Evidence).
Callosome v0.138 CDK5 Zornitza Stark Phenotypes for gene: CDK5 were changed from to Lissencephaly 7 with cerebellar hypoplasia, MIM# 616342
Callosome v0.137 CDK5 Zornitza Stark Publications for gene: CDK5 were set to
Callosome v0.136 CDK5 Zornitza Stark Mode of inheritance for gene: CDK5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Callosome v0.135 CDK5 Zornitza Stark Classified gene: CDK5 as Red List (low evidence)
Callosome v0.135 CDK5 Zornitza Stark Gene: cdk5 has been classified as Red List (Low Evidence).
Callosome v0.134 CDK5 Zornitza Stark reviewed gene: CDK5: Rating: RED; Mode of pathogenicity: None; Publications: 25560765; Phenotypes: Lissencephaly 7 with cerebellar hypoplasia, MIM# 616342; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2641 CDK5 Zornitza Stark Marked gene: CDK5 as ready
Mendeliome v0.2641 CDK5 Zornitza Stark Gene: cdk5 has been classified as Red List (Low Evidence).
Mendeliome v0.2641 CDK5 Zornitza Stark Phenotypes for gene: CDK5 were changed from to Lissencephaly 7 with cerebellar hypoplasia, MIM# 616342
Mendeliome v0.2640 CDK5 Zornitza Stark Publications for gene: CDK5 were set to
Mendeliome v0.2639 CDK5 Zornitza Stark Mode of inheritance for gene: CDK5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2638 CDK5 Zornitza Stark Classified gene: CDK5 as Red List (low evidence)
Mendeliome v0.2638 CDK5 Zornitza Stark Gene: cdk5 has been classified as Red List (Low Evidence).
Mendeliome v0.2637 CDK5 Zornitza Stark reviewed gene: CDK5: Rating: RED; Mode of pathogenicity: None; Publications: 25560765; Phenotypes: Lissencephaly 7 with cerebellar hypoplasia, MIM# 616342; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebellar and Pontocerebellar Hypoplasia v0.102 CDK5 Zornitza Stark Marked gene: CDK5 as ready
Cerebellar and Pontocerebellar Hypoplasia v0.102 CDK5 Zornitza Stark Gene: cdk5 has been classified as Red List (Low Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.102 CDK5 Zornitza Stark gene: CDK5 was added
gene: CDK5 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Expert list
Mode of inheritance for gene: CDK5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDK5 were set to 25560765
Phenotypes for gene: CDK5 were set to Lissencephaly 7 with cerebellar hypoplasia, MIM# 616342
Review for gene: CDK5 was set to RED
Added comment: Single consanguineous family with multiple affected individuals reported, lishencephaly prominent.
Sources: Expert list
Cerebellar and Pontocerebellar Hypoplasia v0.101 OXR1 Zornitza Stark Marked gene: OXR1 as ready
Cerebellar and Pontocerebellar Hypoplasia v0.101 OXR1 Zornitza Stark Gene: oxr1 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.101 OXR1 Zornitza Stark Classified gene: OXR1 as Green List (high evidence)
Cerebellar and Pontocerebellar Hypoplasia v0.101 OXR1 Zornitza Stark Gene: oxr1 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.100 OXR1 Zornitza Stark gene: OXR1 was added
gene: OXR1 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Expert list
Mode of inheritance for gene: OXR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OXR1 were set to 31785787
Phenotypes for gene: OXR1 were set to Cerebellar hypoplasia/atrophy, epilepsy, and global developmental delay, MIM# 213000
Review for gene: OXR1 was set to GREEN
Added comment: 5 individuals from 3 unrelated families reported with bi-allelic variants in this gene. Presentation was in early childhood with hypotonia, global developmental delay, delayed walking at about age 3 years, and severely impaired intellectual development with profound speech delay or even absent language. All also developed epilepsy between 7 and 10 years of age, but the seizures were controlled by medication in most. Subtle nonspecific dysmorphic features included poor overall growth, large forehead, tall face, mild hypertelorism, joint hyperlaxity, and long fingers and toes. Brain imaging in all 5 individuals showed cerebellar atrophy and dysplasia. Additional cerebellar features, such as tremor, ataxia, and nystagmus, were not noted in these individuals.
Sources: Expert list
Cerebellar and Pontocerebellar Hypoplasia v0.99 OPHN1 Zornitza Stark Marked gene: OPHN1 as ready
Cerebellar and Pontocerebellar Hypoplasia v0.99 OPHN1 Zornitza Stark Gene: ophn1 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.99 OPHN1 Zornitza Stark Phenotypes for gene: OPHN1 were changed from to Mental retardation, X-linked, with cerebellar hypoplasia and distinctive facial appearance, MIM# 300486
Cerebellar and Pontocerebellar Hypoplasia v0.98 OPHN1 Zornitza Stark Publications for gene: OPHN1 were set to
Cerebellar and Pontocerebellar Hypoplasia v0.97 OPHN1 Zornitza Stark Mode of inheritance for gene: OPHN1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cerebellar and Pontocerebellar Hypoplasia v0.96 OPHN1 Zornitza Stark reviewed gene: OPHN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20528889, 9582072, 12807966, 16221952; Phenotypes: Mental retardation, X-linked, with cerebellar hypoplasia and distinctive facial appearance, MIM# 300486; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Microcephaly v0.121 VPS51 Zornitza Stark changed review comment from: Two families reported with bi-allelic variants in this gene and global developmental delay, impaired intellectual development with absent speech, microcephaly, and progressive atrophy of the cerebellar vermis and brainstem. Additional features, including seizures and visual impairment, are variable.
Sources: Expert list; to: Two families reported with bi-allelic variants in this gene and global developmental delay, impaired intellectual development with absent speech, microcephaly, and progressive atrophy of the cerebellar vermis and brainstem. Additional features, including seizures and visual impairment, are variable. Microcephaly -3/-4SD.
Sources: Expert list
Microcephaly v0.121 VPS51 Zornitza Stark gene: VPS51 was added
gene: VPS51 was added to Microcephaly. Sources: Expert list
Mode of inheritance for gene: VPS51 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS51 were set to 30624672; 31207318
Phenotypes for gene: VPS51 were set to Pontocerebellar hypoplasia, type 13, MIM# 618606
Review for gene: VPS51 was set to AMBER
Added comment: Two families reported with bi-allelic variants in this gene and global developmental delay, impaired intellectual development with absent speech, microcephaly, and progressive atrophy of the cerebellar vermis and brainstem. Additional features, including seizures and visual impairment, are variable.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2600 VPS51 Zornitza Stark Marked gene: VPS51 as ready
Intellectual disability syndromic and non-syndromic v0.2600 VPS51 Zornitza Stark Gene: vps51 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2600 VPS51 Zornitza Stark Classified gene: VPS51 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2600 VPS51 Zornitza Stark Gene: vps51 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2599 VPS51 Zornitza Stark gene: VPS51 was added
gene: VPS51 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: VPS51 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS51 were set to 30624672; 31207318
Phenotypes for gene: VPS51 were set to Pontocerebellar hypoplasia, type 13, MIM# 618606
Review for gene: VPS51 was set to AMBER
Added comment: Two families reported with bi-allelic variants in this gene and global developmental delay, impaired intellectual development with absent speech, microcephaly, and progressive atrophy of the cerebellar vermis and brainstem. Additional features, including seizures and visual impairment, are variable.
Sources: Expert list
Mendeliome v0.2637 VPS51 Zornitza Stark Marked gene: VPS51 as ready
Mendeliome v0.2637 VPS51 Zornitza Stark Gene: vps51 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2637 VPS51 Zornitza Stark Classified gene: VPS51 as Amber List (moderate evidence)
Mendeliome v0.2637 VPS51 Zornitza Stark Gene: vps51 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2636 VPS51 Zornitza Stark gene: VPS51 was added
gene: VPS51 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: VPS51 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS51 were set to 30624672; 31207318
Phenotypes for gene: VPS51 were set to Pontocerebellar hypoplasia, type 13, MIM# 618606
Review for gene: VPS51 was set to AMBER
Added comment: Two families reported with bi-allelic variants in this gene and global developmental delay, impaired intellectual development with absent speech, microcephaly, and progressive atrophy of the cerebellar vermis and brainstem. Additional features, including seizures and visual impairment, are variable.
Sources: Expert list
Cerebellar and Pontocerebellar Hypoplasia v0.96 VPS51 Zornitza Stark Marked gene: VPS51 as ready
Cerebellar and Pontocerebellar Hypoplasia v0.96 VPS51 Zornitza Stark Gene: vps51 has been classified as Amber List (Moderate Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.96 VPS51 Zornitza Stark Classified gene: VPS51 as Amber List (moderate evidence)
Cerebellar and Pontocerebellar Hypoplasia v0.96 VPS51 Zornitza Stark Gene: vps51 has been classified as Amber List (Moderate Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.95 VPS51 Zornitza Stark gene: VPS51 was added
gene: VPS51 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Expert list
Mode of inheritance for gene: VPS51 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS51 were set to 30624672; 31207318
Phenotypes for gene: VPS51 were set to Pontocerebellar hypoplasia, type 13, MIM# 618606
Review for gene: VPS51 was set to AMBER
Added comment: Two families reported with bi-allelic variants in this gene and global developmental delay, impaired intellectual development with absent speech, microcephaly, and progressive atrophy of the cerebellar vermis and brainstem. Additional features, including seizures and visual impairment, are variable.
Sources: Expert list
Cerebellar and Pontocerebellar Hypoplasia v0.94 VLDLR Zornitza Stark Marked gene: VLDLR as ready
Cerebellar and Pontocerebellar Hypoplasia v0.94 VLDLR Zornitza Stark Gene: vldlr has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.94 VLDLR Zornitza Stark Phenotypes for gene: VLDLR were changed from to Cerebellar hypoplasia and mental retardation with or without quadrupedal locomotion 1, MIM# 224050
Cerebellar and Pontocerebellar Hypoplasia v0.93 VLDLR Zornitza Stark Publications for gene: VLDLR were set to
Cerebellar and Pontocerebellar Hypoplasia v0.92 VLDLR Zornitza Stark Mode of inheritance for gene: VLDLR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cerebellar and Pontocerebellar Hypoplasia v0.91 VLDLR Zornitza Stark reviewed gene: VLDLR: Rating: GREEN; Mode of pathogenicity: None; Publications: 16080122, 18326629; Phenotypes: Cerebellar hypoplasia and mental retardation with or without quadrupedal locomotion 1, MIM# 224050; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebellar and Pontocerebellar Hypoplasia v0.91 UFM1 Zornitza Stark Marked gene: UFM1 as ready
Cerebellar and Pontocerebellar Hypoplasia v0.91 UFM1 Zornitza Stark Gene: ufm1 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.91 UFM1 Zornitza Stark Phenotypes for gene: UFM1 were changed from to Leukodystrophy, hypomyelinating, 14, MIM# 617899
Cerebellar and Pontocerebellar Hypoplasia v0.90 UFM1 Zornitza Stark Publications for gene: UFM1 were set to
Cerebellar and Pontocerebellar Hypoplasia v0.89 UFM1 Zornitza Stark Mode of inheritance for gene: UFM1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cerebellar and Pontocerebellar Hypoplasia v0.88 TERT Zornitza Stark Marked gene: TERT as ready
Cerebellar and Pontocerebellar Hypoplasia v0.88 TERT Zornitza Stark Gene: tert has been classified as Amber List (Moderate Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.88 TERT Zornitza Stark Classified gene: TERT as Amber List (moderate evidence)
Cerebellar and Pontocerebellar Hypoplasia v0.88 TERT Zornitza Stark Gene: tert has been classified as Amber List (Moderate Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.87 EXOSC9 Zornitza Stark Marked gene: EXOSC9 as ready
Cerebellar and Pontocerebellar Hypoplasia v0.87 EXOSC9 Zornitza Stark Gene: exosc9 has been classified as Amber List (Moderate Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.87 EXOSC9 Zornitza Stark Phenotypes for gene: EXOSC9 were changed from to Pontocerebellar hypoplasia, type 1D 618065
Cerebellar and Pontocerebellar Hypoplasia v0.86 EXOSC9 Zornitza Stark Publications for gene: EXOSC9 were set to
Cerebellar and Pontocerebellar Hypoplasia v0.85 EXOSC9 Zornitza Stark Mode of inheritance for gene: EXOSC9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cerebellar and Pontocerebellar Hypoplasia v0.84 EXOSC9 Zornitza Stark Classified gene: EXOSC9 as Amber List (moderate evidence)
Cerebellar and Pontocerebellar Hypoplasia v0.84 EXOSC9 Zornitza Stark Gene: exosc9 has been classified as Amber List (Moderate Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.83 SLC25A46 Zornitza Stark Marked gene: SLC25A46 as ready
Cerebellar and Pontocerebellar Hypoplasia v0.83 SLC25A46 Zornitza Stark Gene: slc25a46 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.83 SLC25A46 Zornitza Stark Phenotypes for gene: SLC25A46 were changed from to Neuropathy, hereditary motor and sensory, type VIB (MIM#616505)
Cerebellar and Pontocerebellar Hypoplasia v0.82 SLC25A46 Zornitza Stark Publications for gene: SLC25A46 were set to
Cerebellar and Pontocerebellar Hypoplasia v0.81 SLC25A46 Zornitza Stark Mode of inheritance for gene: SLC25A46 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cerebellar and Pontocerebellar Hypoplasia v0.80 SETD2 Zornitza Stark Marked gene: SETD2 as ready
Cerebellar and Pontocerebellar Hypoplasia v0.80 SETD2 Zornitza Stark Gene: setd2 has been classified as Amber List (Moderate Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.80 SETD2 Zornitza Stark Phenotypes for gene: SETD2 were changed from to Luscan-Lumish syndrome (MIM#616831)
Cerebellar and Pontocerebellar Hypoplasia v0.79 SETD2 Zornitza Stark Publications for gene: SETD2 were set to
Cerebellar and Pontocerebellar Hypoplasia v0.78 SETD2 Zornitza Stark Mode of inheritance for gene: SETD2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebellar and Pontocerebellar Hypoplasia v0.77 SETD2 Zornitza Stark Classified gene: SETD2 as Amber List (moderate evidence)
Cerebellar and Pontocerebellar Hypoplasia v0.77 SETD2 Zornitza Stark Gene: setd2 has been classified as Amber List (Moderate Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.76 RAB11B Zornitza Stark Marked gene: RAB11B as ready
Cerebellar and Pontocerebellar Hypoplasia v0.76 RAB11B Zornitza Stark Gene: rab11b has been classified as Amber List (Moderate Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.76 RAB11B Zornitza Stark Phenotypes for gene: RAB11B were changed from to Neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter (MIM#617807)
Cerebellar and Pontocerebellar Hypoplasia v0.75 RAB11B Zornitza Stark Publications for gene: RAB11B were set to
Cerebellar and Pontocerebellar Hypoplasia v0.74 RAB11B Zornitza Stark Mode of inheritance for gene: RAB11B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebellar and Pontocerebellar Hypoplasia v0.73 RAB11B Zornitza Stark Classified gene: RAB11B as Amber List (moderate evidence)
Cerebellar and Pontocerebellar Hypoplasia v0.73 RAB11B Zornitza Stark Gene: rab11b has been classified as Amber List (Moderate Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.72 PUS3 Zornitza Stark Marked gene: PUS3 as ready
Cerebellar and Pontocerebellar Hypoplasia v0.72 PUS3 Zornitza Stark Gene: pus3 has been classified as Red List (Low Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.72 PUS3 Zornitza Stark Phenotypes for gene: PUS3 were changed from to Mental retardation, autosomal recessive 55 (MIM#617051)
Cerebellar and Pontocerebellar Hypoplasia v0.71 PUS3 Zornitza Stark Publications for gene: PUS3 were set to
Cerebellar and Pontocerebellar Hypoplasia v0.70 PUS3 Zornitza Stark Mode of inheritance for gene: PUS3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cerebellar and Pontocerebellar Hypoplasia v0.69 PUS3 Zornitza Stark Classified gene: PUS3 as Red List (low evidence)
Cerebellar and Pontocerebellar Hypoplasia v0.69 PUS3 Zornitza Stark Gene: pus3 has been classified as Red List (Low Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.6 LAT Zornitza Stark Marked gene: LAT as ready
Mackenzie's Mission_Reproductive Carrier Screening v0.6 LAT Zornitza Stark Gene: lat has been classified as Green List (High Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.6 LAT Zornitza Stark Classified gene: LAT as Green List (high evidence)
Mackenzie's Mission_Reproductive Carrier Screening v0.6 LAT Zornitza Stark Gene: lat has been classified as Green List (High Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.5 LAT Zornitza Stark gene: LAT was added
gene: LAT was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Expert Review
Mode of inheritance for gene: LAT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LAT were set to 27242165; 27522155
Phenotypes for gene: LAT were set to Immunodeficiency 52, MIM# 617514
Review for gene: LAT was set to GREEN
Added comment: Sources: Expert Review
Mackenzie's Mission_Reproductive Carrier Screening v0.4 Zornitza Stark removed gene:SPNS1 from the panel
Cerebellar and Pontocerebellar Hypoplasia v0.68 PUS3 Crystle Lee reviewed gene: PUS3: Rating: RED; Mode of pathogenicity: None; Publications: 27055666, 30308082, 30697592, 31444731; Phenotypes: Mental retardation, autosomal recessive 55 (MIM#617051); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebellar and Pontocerebellar Hypoplasia v0.68 RAB11B Crystle Lee reviewed gene: RAB11B: Rating: AMBER; Mode of pathogenicity: None; Publications: 29106825; Phenotypes: Neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter (MIM#617807); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.2635 CTSA Zornitza Stark changed review comment from: Bi-allelic variants cause galactosialidosis, and mono-allelic variants cause CARASAL.; to: Bi-allelic variants associated with galactosialidosis, and mono-allelic variants associated with CARASAL.
Mendeliome v0.2635 CTSA Zornitza Stark reviewed gene: CTSA: Rating: GREEN; Mode of pathogenicity: None; Publications: 31177426; Phenotypes: Galactosialidosis, MIM# 256540, Cathepsin A-related arteriopathy with strokes and leukoencephalopathy; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Leukodystrophy v0.62 CTC1 Zornitza Stark Marked gene: CTC1 as ready
Leukodystrophy v0.62 CTC1 Zornitza Stark Gene: ctc1 has been classified as Green List (High Evidence).
Leukodystrophy v0.62 CTC1 Zornitza Stark Classified gene: CTC1 as Green List (high evidence)
Leukodystrophy v0.62 CTC1 Zornitza Stark Gene: ctc1 has been classified as Green List (High Evidence).
Leukodystrophy v0.61 CTC1 Zornitza Stark gene: CTC1 was added
gene: CTC1 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: CTC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTC1 were set to 22267198; 22387016
Phenotypes for gene: CTC1 were set to Cerebroretinal microangiopathy with calcifications and cysts, MIM# 612199
Review for gene: CTC1 was set to GREEN
Added comment: Onset typically in infancy/childhood with intracranial calcifications, leukoencephalopathy, and early-onset retinal changes, associated with extra-neurologic manifestations including early-onset bone fractures, gastrointestinal ectasia, and variable hair, nail, and skin changes, and/or anemia.
Sources: Expert list
Cerebellar and Pontocerebellar Hypoplasia v0.68 SETD2 Crystle Lee reviewed gene: SETD2: Rating: AMBER; Mode of pathogenicity: None; Publications: 31643139, 31474318, 26084711; Phenotypes: Luscan-Lumish syndrome (MIM#616831); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Cerebellar and Pontocerebellar Hypoplasia v0.68 SLC25A46 Crystle Lee reviewed gene: SLC25A46: Rating: GREEN; Mode of pathogenicity: None; Publications: 27543974, 28637197, 28376086, 26168012; Phenotypes: Neuropathy, hereditary motor and sensory, type VIB (MIM#616505); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebellar and Pontocerebellar Hypoplasia v0.68 EXOSC9 Elena Savva reviewed gene: EXOSC9: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 29727687, 30690203; Phenotypes: Pontocerebellar hypoplasia, type 1D 618065; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2598 MN1 Chern Lim reviewed gene: MN1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: CEBALID syndrome, MIM#618774; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Leukodystrophy v0.60 AUH Zornitza Stark Marked gene: AUH as ready
Leukodystrophy v0.60 AUH Zornitza Stark Gene: auh has been classified as Green List (High Evidence).
Leukodystrophy v0.60 AUH Zornitza Stark Classified gene: AUH as Green List (high evidence)
Leukodystrophy v0.60 AUH Zornitza Stark Gene: auh has been classified as Green List (High Evidence).
Leukodystrophy v0.59 AUH Zornitza Stark gene: AUH was added
gene: AUH was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: AUH was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: AUH were set to 3-methylglutaconic aciduria, type I, MIM# 250950
Review for gene: AUH was set to GREEN
Added comment: Onset is typically in childhood, though presentation is variable so worth keeping on both paediatric and adult panels.
Sources: Expert list
Leukodystrophy v0.58 APOPT1 Zornitza Stark Marked gene: APOPT1 as ready
Leukodystrophy v0.58 APOPT1 Zornitza Stark Gene: apopt1 has been classified as Green List (High Evidence).
Leukodystrophy v0.58 APOPT1 Zornitza Stark Classified gene: APOPT1 as Green List (high evidence)
Leukodystrophy v0.58 APOPT1 Zornitza Stark Gene: apopt1 has been classified as Green List (High Evidence).
Leukodystrophy v0.57 APOPT1 Zornitza Stark gene: APOPT1 was added
gene: APOPT1 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: APOPT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: APOPT1 were set to 25175347
Phenotypes for gene: APOPT1 were set to Mitochondrial complex IV deficiency, MIM# 220110
Review for gene: APOPT1 was set to GREEN
Added comment: Cavitating leukodystrophy reported as part of this mitochondrial disorder, onset described as late infancy/early childhood.
Sources: Expert list
Cerebellar and Pontocerebellar Hypoplasia v0.68 EXOSC5 Zornitza Stark Marked gene: EXOSC5 as ready
Cerebellar and Pontocerebellar Hypoplasia v0.68 EXOSC5 Zornitza Stark Added comment: Comment when marking as ready: Pre-print
Cerebellar and Pontocerebellar Hypoplasia v0.68 EXOSC5 Zornitza Stark Gene: exosc5 has been classified as Amber List (Moderate Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.68 EXOSC5 Zornitza Stark Phenotypes for gene: EXOSC5 were changed from to Developmental delays, short stature, cerebellar hypoplasia and motor weakness
Cerebellar and Pontocerebellar Hypoplasia v0.67 EXOSC5 Zornitza Stark Publications for gene: EXOSC5 were set to
Cerebellar and Pontocerebellar Hypoplasia v0.66 EXOSC5 Zornitza Stark Mode of inheritance for gene: EXOSC5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cerebellar and Pontocerebellar Hypoplasia v0.65 EXOSC5 Zornitza Stark Classified gene: EXOSC5 as Amber List (moderate evidence)
Cerebellar and Pontocerebellar Hypoplasia v0.65 EXOSC5 Zornitza Stark Gene: exosc5 has been classified as Amber List (Moderate Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.64 SMPD4 Zornitza Stark Marked gene: SMPD4 as ready
Cerebellar and Pontocerebellar Hypoplasia v0.64 SMPD4 Zornitza Stark Gene: smpd4 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.64 SMPD4 Zornitza Stark Classified gene: SMPD4 as Green List (high evidence)
Cerebellar and Pontocerebellar Hypoplasia v0.64 SMPD4 Zornitza Stark Gene: smpd4 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.63 DDX3X Zornitza Stark Marked gene: DDX3X as ready
Cerebellar and Pontocerebellar Hypoplasia v0.63 DDX3X Zornitza Stark Gene: ddx3x has been classified as Amber List (Moderate Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.63 DDX3X Zornitza Stark Phenotypes for gene: DDX3X were changed from to Mental retardation, X-linked 102, MIM# 300958
Cerebellar and Pontocerebellar Hypoplasia v0.62 DDX3X Zornitza Stark Publications for gene: DDX3X were set to
Cerebellar and Pontocerebellar Hypoplasia v0.61 EXOSC5 Elena Savva changed review comment from: No phenotype association in OMIM, emerging gene with a single paper

3 patients reported: one patient with cerebellar hypoplasia, another with reduced cerebellar vermis; to: No phenotype association in OMIM, emerging gene with a single paper

3 patients reported: one patient with cerebellar hypoplasia, another with reduced cerebellar vermis

Summary: 2/3 patients have cerebellar/vermis hypoplasia
Cerebellar and Pontocerebellar Hypoplasia v0.61 EXOSC5 Elena Savva reviewed gene: EXOSC5: Rating: AMBER; Mode of pathogenicity: None; Publications: doi: https://doi.org/10.1101/2020.04.01.839274; Phenotypes: Developmental delays, short stature, cerebellar hypoplasia and motor weakness; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebellar and Pontocerebellar Hypoplasia v0.61 DDX3X Zornitza Stark Mode of inheritance for gene: DDX3X was changed from Unknown to Other
Cerebellar and Pontocerebellar Hypoplasia v0.60 DDX3X Zornitza Stark Classified gene: DDX3X as Amber List (moderate evidence)
Cerebellar and Pontocerebellar Hypoplasia v0.60 DDX3X Zornitza Stark Gene: ddx3x has been classified as Amber List (Moderate Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.59 DDX3X Zornitza Stark reviewed gene: DDX3X: Rating: AMBER; Mode of pathogenicity: None; Publications: 30936465; Phenotypes: Mental retardation, X-linked 102, MIM# 300958; Mode of inheritance: Other
Cerebellar and Pontocerebellar Hypoplasia v0.59 SNX14 Zornitza Stark reviewed gene: SNX14: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinocerebellar ataxia, autosomal recessive 20 (MIM#616354); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebellar and Pontocerebellar Hypoplasia v0.59 SNX14 Zornitza Stark Marked gene: SNX14 as ready
Cerebellar and Pontocerebellar Hypoplasia v0.59 SNX14 Zornitza Stark Gene: snx14 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.59 SNX14 Zornitza Stark Classified gene: SNX14 as Green List (high evidence)
Cerebellar and Pontocerebellar Hypoplasia v0.59 SNX14 Zornitza Stark Gene: snx14 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.58 TBCK Zornitza Stark Marked gene: TBCK as ready
Cerebellar and Pontocerebellar Hypoplasia v0.58 TBCK Zornitza Stark Added comment: Comment when marking as ready: Agree, uncertain about whether reported findings truly reflect cerebellar/pontocerebellar hypoplasia.
Cerebellar and Pontocerebellar Hypoplasia v0.58 TBCK Zornitza Stark Gene: tbck has been classified as Amber List (Moderate Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.58 TBCK Zornitza Stark Marked gene: TBCK as ready
Cerebellar and Pontocerebellar Hypoplasia v0.58 TBCK Zornitza Stark Gene: tbck has been classified as Amber List (Moderate Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.58 TBCK Zornitza Stark Phenotypes for gene: TBCK were changed from to Hypotonia, infantile, with psychomotor retardation and characteristic facies 3 (MIM#616900)
Cerebellar and Pontocerebellar Hypoplasia v0.57 TBCK Zornitza Stark Publications for gene: TBCK were set to
Cerebellar and Pontocerebellar Hypoplasia v0.56 TBCK Zornitza Stark Mode of inheritance for gene: TBCK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cerebellar and Pontocerebellar Hypoplasia v0.55 TBCK Zornitza Stark Classified gene: TBCK as Amber List (moderate evidence)
Cerebellar and Pontocerebellar Hypoplasia v0.55 TBCK Zornitza Stark Gene: tbck has been classified as Amber List (Moderate Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.54 DKC1 Zornitza Stark Marked gene: DKC1 as ready
Cerebellar and Pontocerebellar Hypoplasia v0.54 DKC1 Zornitza Stark Gene: dkc1 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.54 DKC1 Zornitza Stark Classified gene: DKC1 as Green List (high evidence)
Cerebellar and Pontocerebellar Hypoplasia v0.54 DKC1 Zornitza Stark Gene: dkc1 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.53 DKC1 Elena Savva gene: DKC1 was added
gene: DKC1 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Expert Review
Mode of inheritance for gene: DKC1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: DKC1 were set to PMID: 31269755; 26951492; 29081935
Phenotypes for gene: DKC1 were set to Dyskeratosis congenita, X-linked 305000; Hoyeraal-Hreidarsson Syndrome
Review for gene: DKC1 was set to GREEN
Added comment: OMIM - Cerebellar ataxia (seen in HHS variant), Cerebellar hypoplasia (seen in HHS variant)
Hoyeraal-Hreidarsson Syndrome is the severe form of Dyskeratosis congenita

PMID: 31269755 - 1 child with cerebellar hypoplasia, a hemizygous missense and Hoyeraal–Hreidarsson Syndrome*

PMID: 26951492 - 1 child with pontocerebellar hypoplasia, a hemizygous missense and Hoyeraal–Hreidarsson Syndrome*

PMID: 29081935 - 1 family (2 first cousins) with the same variant. One has DC, the other HHS and cerebellar hypoplasia*

PMID: 24914498 - 1 baby (3 months old) with a missense in exon 3 and Hoyeraal-Hreidarsson syndrome and cerebellar atrophy.

*All missense found close together in exon 11

Summary: is a common feature of severe Hoyeraal-Hreidarsson syndrome
Sources: Expert Review
Cerebellar and Pontocerebellar Hypoplasia v0.53 SMPD4 Crystle Lee gene: SMPD4 was added
gene: SMPD4 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Expert Review
Mode of inheritance for gene: SMPD4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SMPD4 were set to 31495489
Phenotypes for gene: SMPD4 were set to Neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies (MIM#618622)
Review for gene: SMPD4 was set to GREEN
Added comment: Cerebellar hypoplasia is a feature of the associated OMIM phenotype.

Magini 2019: Reported 23 patients from 12 unrelated families. Cerebellar hypoplasia was one of the main features.
Sources: Expert Review
Cerebellar and Pontocerebellar Hypoplasia v0.53 DDX3X Elena Savva reviewed gene: DDX3X: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 26235985, 30936465; Phenotypes: Mental retardation, X-linked 102 300958; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cerebellar and Pontocerebellar Hypoplasia v0.53 SNX14 Crystle Lee gene: SNX14 was added
gene: SNX14 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Expert Review
Mode of inheritance for gene: SNX14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNX14 were set to 25439728; 24501761; 25848753
Phenotypes for gene: SNX14 were set to Spinocerebellar ataxia, autosomal recessive 20 (MIM#616354)
Review for gene: SNX14 was set to AMBER
Added comment: Not sure if cerebellar hypoplasia or atrophy. Appears to be mostly atrophy but early onset.

Green in PanelApp UK: "Unclear if predominantly cerebellar atrophy/hypoplasia. Childhood presentation reported" 2016

Thomas 2014: 7 affected individuals from 3 unrelated consanguineous families. Appears to be predominantly cerebellar atrophy, 4 of which were progressive.

Sousa 2014: Reported cerebellar hypotrophy in 2 sisters (>15 years old). Noted as cerebellar hypoplasia in OMIM.

Akizu 2015: 12 families with cerebellar atrophy. Childhood-onset recessive cerebellar atrophy with ataxia (supp data indicates all <5 years old)
Sources: Expert Review
Cerebellar and Pontocerebellar Hypoplasia v0.53 TBCK Crystle Lee edited their review of gene: TBCK: Changed publications: 27040692, 30103036, 27040691
Cerebellar and Pontocerebellar Hypoplasia v0.53 TBCK Crystle Lee reviewed gene: TBCK: Rating: AMBER; Mode of pathogenicity: None; Publications: 27040692; Phenotypes: Hypotonia, infantile, with psychomotor retardation and characteristic facies 3 (MIM#616900); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebellar and Pontocerebellar Hypoplasia v0.53 TERT Crystle Lee gene: TERT was added
gene: TERT was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Expert Review
Mode of inheritance for gene: TERT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TERT were set to 17785587
Phenotypes for gene: TERT were set to Autosomal Recessive Dyskeratosis Congenita 4 (MIM#613989)
Review for gene: TERT was set to AMBER
Added comment: 1 patient reported with cerebellar hypoplasia.

Marrone (2007): Reported hom missense (not in gnomAD) in 1 patient from consang fam with Hoyeraal-Hreidarsson syndrome, which is a severe variant of DKC
Sources: Expert Review
Mackenzie's Mission_Reproductive Carrier Screening v0.3 GALT Zornitza Stark Marked gene: GALT as ready
Mackenzie's Mission_Reproductive Carrier Screening v0.3 GALT Zornitza Stark Added comment: Comment when marking as ready: Only screened in Victoria as galactosaemia is not part of newborn screening.
Mackenzie's Mission_Reproductive Carrier Screening v0.3 GALT Zornitza Stark Gene: galt has been classified as Amber List (Moderate Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.3 GALT Zornitza Stark Classified gene: GALT as Amber List (moderate evidence)
Mackenzie's Mission_Reproductive Carrier Screening v0.3 GALT Zornitza Stark Gene: galt has been classified as Amber List (Moderate Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.2 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Rare Disease; New South Wales Health Pathology; PathWest
Genetic Epilepsy v0.685 CDK19 Zornitza Stark Marked gene: CDK19 as ready
Genetic Epilepsy v0.685 CDK19 Zornitza Stark Gene: cdk19 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.685 CDK19 Zornitza Stark Classified gene: CDK19 as Green List (high evidence)
Genetic Epilepsy v0.685 CDK19 Zornitza Stark Gene: cdk19 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.684 CDK19 Zornitza Stark gene: CDK19 was added
gene: CDK19 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: CDK19 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDK19 were set to 32330417
Phenotypes for gene: CDK19 were set to Intellectual disability; epileptic encephalopathy
Review for gene: CDK19 was set to GREEN
Added comment: Three unrelated individuals with de novo missense variants reported, and intellectual disability/epileptic encephalopathy. Supportive functional data.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2598 CDK19 Zornitza Stark Marked gene: CDK19 as ready
Intellectual disability syndromic and non-syndromic v0.2598 CDK19 Zornitza Stark Gene: cdk19 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2598 CDK19 Zornitza Stark Classified gene: CDK19 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2598 CDK19 Zornitza Stark Gene: cdk19 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2597 CDK19 Zornitza Stark gene: CDK19 was added
gene: CDK19 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CDK19 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDK19 were set to 32330417
Phenotypes for gene: CDK19 were set to Intellectual disability; epileptic encephalopathy
Review for gene: CDK19 was set to GREEN
Added comment: Three unrelated individuals with de novo missense variants reported, and intellectual disability/epileptic encephalopathy. Supportive functional data.
Sources: Literature
Mendeliome v0.2635 CDK19 Zornitza Stark Marked gene: CDK19 as ready
Mendeliome v0.2635 CDK19 Zornitza Stark Gene: cdk19 has been classified as Green List (High Evidence).
Mendeliome v0.2635 CDK19 Zornitza Stark Classified gene: CDK19 as Green List (high evidence)
Mendeliome v0.2635 CDK19 Zornitza Stark Gene: cdk19 has been classified as Green List (High Evidence).
Mendeliome v0.2634 CDK19 Zornitza Stark gene: CDK19 was added
gene: CDK19 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CDK19 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDK19 were set to 32330417
Phenotypes for gene: CDK19 were set to Intellectual disability; epileptic encephalopathy
Review for gene: CDK19 was set to GREEN
Added comment: Three unrelated individuals with de novo missense variants reported, and intellectual disability/epileptic encephalopathy. Supportive functional data.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2596 PTPN23 Zornitza Stark Marked gene: PTPN23 as ready
Intellectual disability syndromic and non-syndromic v0.2596 PTPN23 Zornitza Stark Gene: ptpn23 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2596 PTPN23 Zornitza Stark Mode of inheritance for gene: PTPN23 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2595 PTPN23 Zornitza Stark Publications for gene: PTPN23 were set to
Intellectual disability syndromic and non-syndromic v0.2594 PTPN23 Zornitza Stark Phenotypes for gene: PTPN23 were changed from to Intellectual disability; brain abnormalities; seizures; optic atrophy; microcephaly
Intellectual disability syndromic and non-syndromic v0.2593 PTPN23 Zornitza Stark reviewed gene: PTPN23: Rating: GREEN; Mode of pathogenicity: None; Publications: 31395947; Phenotypes: Intellectual disability, brain abnormalities, seizures, optic atrophy, microcephaly; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2633 MNS1 Zornitza Stark Marked gene: MNS1 as ready
Mendeliome v0.2633 MNS1 Zornitza Stark Gene: mns1 has been classified as Green List (High Evidence).
Mendeliome v0.2633 MNS1 Zornitza Stark Classified gene: MNS1 as Green List (high evidence)
Mendeliome v0.2633 MNS1 Zornitza Stark Gene: mns1 has been classified as Green List (High Evidence).
Mendeliome v0.2632 MNS1 Zornitza Stark gene: MNS1 was added
gene: MNS1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MNS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MNS1 were set to 31534215; 30148830
Phenotypes for gene: MNS1 were set to Heterotaxy; male infertility
Review for gene: MNS1 was set to GREEN
Added comment: Eight families reported altogether, three LoF variants. Four Amish families share same homozygous founder variant, and some of the other reported families are consanguineous and share another founder variant. A reported female with a third variant, also had a homozygous variant in DNAH5 with a blended phenotype postulated.
Sources: Literature
Heterotaxy v0.9 MNS1 Zornitza Stark Marked gene: MNS1 as ready
Heterotaxy v0.9 MNS1 Zornitza Stark Added comment: Comment when marking as ready: A reported female with a third variant, also had a homozygous variant in DNAH5 with a blended phenotype postulated.
Heterotaxy v0.9 MNS1 Zornitza Stark Gene: mns1 has been classified as Green List (High Evidence).
Heterotaxy v0.9 MNS1 Zornitza Stark Classified gene: MNS1 as Green List (high evidence)
Heterotaxy v0.9 MNS1 Zornitza Stark Gene: mns1 has been classified as Green List (High Evidence).
Heterotaxy v0.8 MNS1 Zornitza Stark gene: MNS1 was added
gene: MNS1 was added to Heterotaxy. Sources: Literature
Mode of inheritance for gene: MNS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MNS1 were set to 31534215; 30148830
Phenotypes for gene: MNS1 were set to Heterotaxy; male infertility
Review for gene: MNS1 was set to GREEN
Added comment: Eight families reported altogether. However, four are Amish and share same homozygous founder variant, and some of the other reported families are consanguineous and share another founder variant.
Sources: Literature
Ataxia v0.213 SCYL1 Zornitza Stark Phenotypes for gene: SCYL1 were changed from Spinocerebellar ataxia, autosomal recessive 21, 616719 to Spinocerebellar ataxia, autosomal recessive 21, 616719; Early-onset ataxia (<1 year) with recurrent episodes of liver failure, sensory-motor axonal neuropathy, cerebellar atrophy
Ataxia v0.212 SCYL1 Zornitza Stark edited their review of gene: SCYL1: Changed phenotypes: Spinocerebellar ataxia, autosomal recessive 21, MIM# 616719, Early-onset ataxia (<1 year) with recurrent episodes of liver failure, sensory-motor axonal neuropathy, cerebellar atrophy
Mendeliome v0.2631 DHX37 Zornitza Stark Marked gene: DHX37 as ready
Mendeliome v0.2631 DHX37 Zornitza Stark Gene: dhx37 has been classified as Green List (High Evidence).
Mendeliome v0.2631 DHX37 Zornitza Stark Classified gene: DHX37 as Green List (high evidence)
Mendeliome v0.2631 DHX37 Zornitza Stark Gene: dhx37 has been classified as Green List (High Evidence).
Mendeliome v0.2630 DHX37 Zornitza Stark gene: DHX37 was added
gene: DHX37 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DHX37 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DHX37 were set to 31337883; 31745530
Phenotypes for gene: DHX37 were set to 46,XY gonadal dysgenesis; testicular regression syndrome (TRS)
Review for gene: DHX37 was set to GREEN
Added comment: Seventeen individuals with 46,XY gonadal dysgenesis reported in two studies.
Sources: Literature
Mendeliome v0.2629 ALPK1 Zornitza Stark Phenotypes for gene: ALPK1 were changed from Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome to Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome; ROSAH syndrome; retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache
Mendeliome v0.2628 ALPK1 Zornitza Stark Classified gene: ALPK1 as Green List (high evidence)
Mendeliome v0.2628 ALPK1 Zornitza Stark Gene: alpk1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.23 DHX37 Zornitza Stark Marked gene: DHX37 as ready
Differences of Sex Development v0.23 DHX37 Zornitza Stark Gene: dhx37 has been classified as Green List (High Evidence).
Differences of Sex Development v0.23 DHX37 Zornitza Stark Classified gene: DHX37 as Green List (high evidence)
Differences of Sex Development v0.23 DHX37 Zornitza Stark Gene: dhx37 has been classified as Green List (High Evidence).
Differences of Sex Development v0.22 DHX37 Zornitza Stark gene: DHX37 was added
gene: DHX37 was added to Disorders of Sex Differentiation. Sources: Literature
Mode of inheritance for gene: DHX37 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DHX37 were set to 31337883; 31745530
Phenotypes for gene: DHX37 were set to 46,XY gonadal dysgenesis; testicular regression syndrome (TRS)
Review for gene: DHX37 was set to GREEN
Added comment: Seventeen individuals reported in two studies.
Sources: Literature
Vitreoretinopathy v0.7 JAG1 Zornitza Stark Marked gene: JAG1 as ready
Vitreoretinopathy v0.7 JAG1 Zornitza Stark Gene: jag1 has been classified as Amber List (Moderate Evidence).
Vitreoretinopathy v0.7 JAG1 Zornitza Stark Classified gene: JAG1 as Amber List (moderate evidence)
Vitreoretinopathy v0.7 JAG1 Zornitza Stark Gene: jag1 has been classified as Amber List (Moderate Evidence).
Vitreoretinopathy v0.6 JAG1 Zornitza Stark gene: JAG1 was added
gene: JAG1 was added to Vitreoretinopathy. Sources: Literature
Mode of inheritance for gene: JAG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: JAG1 were set to 31273345
Phenotypes for gene: JAG1 were set to Familial exudative vitreoretinopathy
Review for gene: JAG1 was set to AMBER
Added comment: Three families reported with rare variants in JAG1: c.413C>T p. (A138V), c.1415G>A p. (R472H), and c.2884A>G p. (T962A. Some functional data.
Sources: Literature
Mendeliome v0.2627 RAMP2 Zornitza Stark Marked gene: RAMP2 as ready
Mendeliome v0.2627 RAMP2 Zornitza Stark Gene: ramp2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2627 RAMP2 Zornitza Stark Classified gene: RAMP2 as Amber List (moderate evidence)
Mendeliome v0.2627 RAMP2 Zornitza Stark Gene: ramp2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2626 RAMP2 Zornitza Stark gene: RAMP2 was added
gene: RAMP2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RAMP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAMP2 were set to 31000793
Phenotypes for gene: RAMP2 were set to Primary open angle glaucoma
Review for gene: RAMP2 was set to AMBER
Added comment: Six variants identified in 16 of 4763 POAG patients from large cohorts; none identified in 10,953 control individuals. Some functional data.
Sources: Literature
Mendeliome v0.2625 ALPK1 Zornitza Stark changed review comment from: Three unrelated families reported. One of the variants segregated in four affected individuals in one family and another was found to be de novo. The third variant however was not segregated, and is also present in 18 individuals in gnomad. Hence the evidence for variant pathogenicity in this third case is not compelling.
Sources: Literature; to: Three unrelated families reported with PFAPA phenotype. One of the variants segregated in four affected individuals in one family and another was found to be de novo. The third variant however was not segregated, and is also present in 18 individuals in gnomad. Hence the evidence for variant pathogenicity in this third case is not compelling.
Sources: Literature
Mendeliome v0.2625 ALPK1 Zornitza Stark edited their review of gene: ALPK1: Added comment: Six unrelated families reported with same recurrent missense variant c.710C>T, (p.Thr237Met) and ROSAH syndrome phenotype. Pancytopaenia and recurrent infections present in some.; Changed rating: GREEN; Changed publications: 31053777, 30967659, 31939038; Changed phenotypes: Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome, ROSAH syndrome, retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache
Mendeliome v0.2625 MEPE Zornitza Stark Classified gene: MEPE as Amber List (moderate evidence)
Mendeliome v0.2625 MEPE Zornitza Stark Gene: mepe has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2624 MEPE Zornitza Stark gene: MEPE was added
gene: MEPE was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MEPE was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MEPE were set to 30287925
Phenotypes for gene: MEPE were set to hereditary congenital facial paresis; otosclerosis
Review for gene: MEPE was set to AMBER
Added comment: Single four-generation family reported with variant in this gene segregating nonprogressive HCFP and mixed hearing loss (HL). Damaging variants (truncating/frameshift) found to be enriched in otosclerosis cohort (p = 0.0006–0.0060).
Sources: Literature
Mendeliome v0.2623 PAICS Zornitza Stark Marked gene: PAICS as ready
Mendeliome v0.2623 PAICS Zornitza Stark Gene: paics has been classified as Red List (Low Evidence).
Mendeliome v0.2623 PAICS Zornitza Stark gene: PAICS was added
gene: PAICS was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PAICS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PAICS were set to 31600779
Phenotypes for gene: PAICS were set to Polyhydramnios; multiple congenital abnormalities
Review for gene: PAICS was set to RED
Added comment: Two sibs from single family reported with homozygous missense variant. Functional data to demonstrate effect on protein function.
Sources: Literature
Cholestasis v0.18 GALM Zornitza Stark Marked gene: GALM as ready
Cholestasis v0.18 GALM Zornitza Stark Gene: galm has been classified as Green List (High Evidence).
Cholestasis v0.18 GALM Zornitza Stark Classified gene: GALM as Green List (high evidence)
Cholestasis v0.18 GALM Zornitza Stark Gene: galm has been classified as Green List (High Evidence).
Cholestasis v0.17 GALM Zornitza Stark gene: GALM was added
gene: GALM was added to Cholestasis. Sources: Literature
Mode of inheritance for gene: GALM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GALM were set to 30451973; 30910422
Phenotypes for gene: GALM were set to type IV galactosaemia
Review for gene: GALM was set to GREEN
Added comment: Homozygous and compound heterozygous variants (missense, nonsense and frameshift) found in 8 Japanese patients from unrelated families with unexplained galactosaemia. (No variants in GALT, GALK1, and GALE). This is therefore type IV galactosaemia. In vitro expression analysis and enzyme activity assay of the patients’ peripheral blood mononuclear cells showed total lack of or compromised expression of GALM protein. Loss-of-function mechanism. One homozygote for one of these variants p.(Gly142Arg) in gnomAD (African population). (Wada, Y. et al 2019; PMID: 30451973) In vitro expression assay and an enzyme activity assay of 67 GALM variants, taken from ExAc database (missense, nonsense, frameshift and splice). 30 variants concluded to be pathogenic due to no protein expression or faint expression. 5 variants with mildly lower levels were determined as likely pathogenic. All concluded to be loss-of-function mechanism. Incidence of galactosaemia by GALM deficiency is comparable to that of other galactosaemias. Carrier frequency and incidence was estimated for different populations. (Iwasawa, S. et al. (2019); PMID: 30910422)

Note only two individuals were reported as having transient cholestasis.
Sources: Literature
Cataract v0.138 GALM Zornitza Stark Marked gene: GALM as ready
Cataract v0.138 GALM Zornitza Stark Gene: galm has been classified as Green List (High Evidence).
Cataract v0.138 GALM Zornitza Stark Classified gene: GALM as Green List (high evidence)
Cataract v0.138 GALM Zornitza Stark Gene: galm has been classified as Green List (High Evidence).
Cataract v0.137 GALM Zornitza Stark gene: GALM was added
gene: GALM was added to Cataract. Sources: Literature
Mode of inheritance for gene: GALM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GALM were set to 30451973; 30910422
Phenotypes for gene: GALM were set to galactosaemia; type IV galactosaemia
Review for gene: GALM was set to GREEN
Added comment: Homozygous and compound heterozygous variants (missense, nonsense and frameshift) found in 8 Japanese patients from unrelated families with unexplained galactosaemia. (No variants in GALT, GALK1, and GALE). This is therefore type IV galactosaemia. In vitro expression analysis and enzyme activity assay of the patients’ peripheral blood mononuclear cells showed total lack of or compromised expression of GALM protein. Loss-of-function mechanism. One homozygote for one of these variants p.(Gly142Arg) in gnomAD (African population). (Wada, Y. et al 2019; PMID: 30451973) In vitro expression assay and an enzyme activity assay of 67 GALM variants, taken from ExAc database (missense, nonsense, frameshift and splice). 30 variants concluded to be pathogenic due to no protein expression or faint expression. 5 variants with mildly lower levels were determined as likely pathogenic. All concluded to be loss-of-function mechanism. Incidence of galactosaemia by GALM deficiency is comparable to that of other galactosaemias. Carrier frequency and incidence was estimated for different populations. (Iwasawa, S. et al. (2019); PMID: 30910422)

Note only two of the reported individuals had cataracts.
Sources: Literature
Mendeliome v0.2622 GALM Zornitza Stark Marked gene: GALM as ready
Mendeliome v0.2622 GALM Zornitza Stark Gene: galm has been classified as Green List (High Evidence).
Mendeliome v0.2622 GALM Zornitza Stark Classified gene: GALM as Green List (high evidence)
Mendeliome v0.2622 GALM Zornitza Stark Gene: galm has been classified as Green List (High Evidence).
Mendeliome v0.2621 POLR3GL Zornitza Stark Marked gene: POLR3GL as ready
Mendeliome v0.2621 POLR3GL Zornitza Stark Added comment: Comment when marking as ready: Three cases altogether but the phenotypes are very different -- may still represent a spectrum with the more severe phenotypes resulting from truncating variants but further cases needed.
Mendeliome v0.2621 POLR3GL Zornitza Stark Gene: polr3gl has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2621 POLR3GL Zornitza Stark Classified gene: POLR3GL as Amber List (moderate evidence)
Mendeliome v0.2621 POLR3GL Zornitza Stark Gene: polr3gl has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2620 GALM Hazel Phillimore gene: GALM was added
gene: GALM was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GALM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GALM were set to PMID: 30451973; 30910422
Phenotypes for gene: GALM were set to galactosaemia; type IV galactosaemia
Review for gene: GALM was set to GREEN
Added comment: Homozygous and compound heterozygous variants (missense, nonsense and frameshift) found in 8 Japanese patients from unrelated families with unexplained galactosaemia. (No variants in GALT, GALK1, and GALE). This is therefore type IV galactosaemia.
In vitro expression analysis and enzyme activity assay of the patients’ peripheral blood mononuclear cells showed total lack of or compromised expression of GALM protein. Loss-of-function mechanism. One homozygote for one of these variants p.(Gly142Arg) in gnomAD (African population). (Wada, Y. et al 2019; PMID: 30451973)
In vitro expression assay and an enzyme activity assay of 67 GALM variants, taken from ExAc database (missense, nonsense, frameshift and splice). 30 variants concluded to be pathogenic due to no protein expression or faint expression. 5 variants with mildly lower levels were determined as likely pathogenic. All concluded to be loss-of-function mechanism. Incidence of galactosaemia by GALM deficiency is comparable to that of other galactosaemias. Carrier frequency and incidence was estimated for different populations. (Iwasawa, S. et al. (2019); PMID: 30910422)
Sources: Literature
Mendeliome v0.2620 POLR3GL Paul De Fazio gene: POLR3GL was added
gene: POLR3GL was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: POLR3GL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR3GL were set to 31089205; 31695177
Phenotypes for gene: POLR3GL were set to endosteal hyperostosis; oligodontia; growth retardation; facial dysmorphisms; lipodystrophy
Review for gene: POLR3GL was set to AMBER
gene: POLR3GL was marked as current diagnostic
Added comment: Biallelic canonical splice variants were identified in monozygotic twins and another individual with similar phenotypes from 2 unrelated families. Variants were inherited from carrier parents. RNA studies confirmed exon skipping occurs in all affected individuals.

A separate study identified a homozygous nonsense variant in an individual with features of Neonatal progeroid syndrome/Wiedemann–Rautenstrauch syndrome. Quantitative PCR showed reduction in mRNA suggestive of NMD.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2593 PHF21A Zornitza Stark Phenotypes for gene: PHF21A were changed from no OMIM number yet. to Intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures, MIM# 618725
Intellectual disability syndromic and non-syndromic v0.2592 PHF21A Zornitza Stark edited their review of gene: PHF21A: Changed rating: GREEN
Intellectual disability syndromic and non-syndromic v0.2592 PHF21A Zornitza Stark reviewed gene: PHF21A: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures 618725; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.2592 CYFIP2 Zornitza Stark Phenotypes for gene: CYFIP2 were changed from Epileptic encephalopathy, early infantile, 65, MIM#618008 to Epileptic encephalopathy, early infantile, 65, MIM#618008; Intellectual disability
Intellectual disability syndromic and non-syndromic v0.2591 CYFIP2 Zornitza Stark Publications for gene: CYFIP2 were set to 29534297
Intellectual disability syndromic and non-syndromic v0.2590 CYFIP2 Zornitza Stark edited their review of gene: CYFIP2: Added comment: Further 12 independent patients with a variety of de novo variants in CYFIP2 reported with eight distinct de novo variants and a shared phenotype of intellectual disability, seizures, and muscular hypotonia. Seven different missense variants detected, of which two occurred recurrently (p.(Arg87Cys) and p.(Ile664Met)). Preliminary genotype–phenotype correlation indicates a profound phenotype in p.Arg87 substitutions and a more variable phenotype in other alterations.; Changed publications: 29534297, 30664714; Changed phenotypes: Epileptic encephalopathy, early infantile, 65, MIM#618008, Intellectual disability
Deafness_IsolatedAndComplex v0.344 TSPEAR Zornitza Stark Tag disputed tag was added to gene: TSPEAR.
Mendeliome v0.2620 TSPEAR Zornitza Stark Marked gene: TSPEAR as ready
Mendeliome v0.2620 TSPEAR Zornitza Stark Added comment: Comment when marking as ready: Association with isolated deafness is DISPUTED.
Mendeliome v0.2620 TSPEAR Zornitza Stark Gene: tspear has been classified as Green List (High Evidence).
Mendeliome v0.2620 TSPEAR Zornitza Stark Phenotypes for gene: TSPEAR were changed from to Ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis, MIM#618180
Mendeliome v0.2619 TSPEAR Zornitza Stark Publications for gene: TSPEAR were set to
Mendeliome v0.2618 TSPEAR Zornitza Stark Mode of inheritance for gene: TSPEAR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2617 PDGFRB Zornitza Stark Marked gene: PDGFRB as ready
Mendeliome v0.2617 PDGFRB Zornitza Stark Gene: pdgfrb has been classified as Green List (High Evidence).
Mendeliome v0.2617 PDGFRB Zornitza Stark Phenotypes for gene: PDGFRB were changed from to Premature aging syndrome, Penttinen type, 601812
Mendeliome v0.2616 PDGFRB Zornitza Stark Mode of pathogenicity for gene: PDGFRB was changed from to Other
Mendeliome v0.2615 PDGFRB Zornitza Stark Publications for gene: PDGFRB were set to
Mendeliome v0.2614 PDGFRB Zornitza Stark Mode of inheritance for gene: PDGFRB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v0.344 TBL1Y Zornitza Stark Marked gene: TBL1Y as ready
Deafness_IsolatedAndComplex v0.344 TBL1Y Zornitza Stark Gene: tbl1y has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v0.344 TBL1Y Zornitza Stark gene: TBL1Y was added
gene: TBL1Y was added to Deafness. Sources: Literature
Mode of inheritance for gene: TBL1Y was set to Other
Publications for gene: TBL1Y were set to 30341416
Phenotypes for gene: TBL1Y were set to Hearing loss
Review for gene: TBL1Y was set to RED
Added comment: Y-linked inheritance pattern. Complete segregation of a missense variant demonstrated in 9 affected males in a 5-generation pedigree. Functional studies show the missense variant causes reduced protein stability. The gene has restricted expression in the cochlea and prostate.
Sources: Literature
Mendeliome v0.2613 TBL1Y Zornitza Stark Marked gene: TBL1Y as ready
Mendeliome v0.2613 TBL1Y Zornitza Stark Added comment: Comment when marking as ready: Single family, some functional data.
Mendeliome v0.2613 TBL1Y Zornitza Stark Gene: tbl1y has been classified as Red List (Low Evidence).
Mendeliome v0.2613 TBL1Y Zornitza Stark Classified gene: TBL1Y as Red List (low evidence)
Mendeliome v0.2613 TBL1Y Zornitza Stark Gene: tbl1y has been classified as Red List (Low Evidence).
Mendeliome v0.2612 DGCR8 Zornitza Stark Marked gene: DGCR8 as ready
Mendeliome v0.2612 DGCR8 Zornitza Stark Gene: dgcr8 has been classified as Red List (Low Evidence).
Mendeliome v0.2612 DGCR8 Zornitza Stark Classified gene: DGCR8 as Red List (low evidence)
Mendeliome v0.2612 DGCR8 Zornitza Stark Gene: dgcr8 has been classified as Red List (Low Evidence).
Mendeliome v0.2611 TSPEAR Chern Lim changed review comment from: Still a rare disease gene for ectodermal dysplasia but has been reported in at least 3 unrelated families. Functional study supported LoF. (PMIDs: 27736875, 30046887); to: Still a rare disease gene for ectodermal dysplasia but has been reported in at least 3 unrelated families in 2 papers. Functional study supported LoF. (PMIDs: 27736875, 30046887)
Mendeliome v0.2611 TSPEAR Chern Lim reviewed gene: TSPEAR: Rating: GREEN; Mode of pathogenicity: None; Publications: 27736875, 30046887; Phenotypes: Ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis, MIM#618180; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.2611 PDGFRB Ee Ming Wong changed review comment from: - > 3 unrelated families
- Functional studies on patient fibroblasts, HeLa and HEK293 cells harbouring mutant constructs demonstrate constitutive tyrosine kinase activation (gain of function) compared with WT constructs; to: - > 3 unrelated individuals diagnosed with Penttinen syndrome
- Functional studies on patient fibroblasts, HeLa and HEK293 cells harbouring mutant constructs demonstrate constitutive tyrosine kinase activation (gain of function) compared with WT constructs
Mendeliome v0.2611 PDGFRB Ee Ming Wong reviewed gene: PDGFRB: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 30573803, 26279204; Phenotypes: Premature aging syndrome, Penttinen type, 601812; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2611 TBL1Y Paul De Fazio changed review comment from: 9 affected males in a single 5-generation pedigree described with Y-linked inheritance pattern. Functional studies show the missense variant causes reduced protein stability. The gene has restricted expression in the cochlea and prostate.
Sources: Literature; to: Y-linked inheritance pattern. Complete segregation of a missense variant demonstrated in 9 affected males in a 5-generation pedigree. Functional studies show the missense variant causes reduced protein stability. The gene has restricted expression in the cochlea and prostate.
Sources: Literature
Mendeliome v0.2611 TBL1Y Paul De Fazio changed review comment from: 9 affected males in a single pedigree described with Y-linked inheritance pattern. Functional studies show the missense variant causes reduced protein stability. The gene has restricted expression in the cochlea and prostate.
Sources: Literature; to: 9 affected males in a single 5-generation pedigree described with Y-linked inheritance pattern. Functional studies show the missense variant causes reduced protein stability. The gene has restricted expression in the cochlea and prostate.
Sources: Literature
Mendeliome v0.2611 TBL1Y Paul De Fazio gene: TBL1Y was added
gene: TBL1Y was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TBL1Y was set to Other
Publications for gene: TBL1Y were set to 30341416
Phenotypes for gene: TBL1Y were set to Hearing loss
Review for gene: TBL1Y was set to RED
gene: TBL1Y was marked as current diagnostic
Added comment: 9 affected males in a single pedigree described with Y-linked inheritance pattern. Functional studies show the missense variant causes reduced protein stability. The gene has restricted expression in the cochlea and prostate.
Sources: Literature
Deafness_IsolatedAndComplex v0.343 FOXF2 Zornitza Stark Marked gene: FOXF2 as ready
Deafness_IsolatedAndComplex v0.343 FOXF2 Zornitza Stark Gene: foxf2 has been classified as Amber List (Moderate Evidence).
Deafness_IsolatedAndComplex v0.343 FOXF2 Zornitza Stark Classified gene: FOXF2 as Amber List (moderate evidence)
Deafness_IsolatedAndComplex v0.343 FOXF2 Zornitza Stark Gene: foxf2 has been classified as Amber List (Moderate Evidence).
Deafness_IsolatedAndComplex v0.342 FOXF2 Zornitza Stark gene: FOXF2 was added
gene: FOXF2 was added to Deafness. Sources: Literature
Mode of inheritance for gene: FOXF2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FOXF2 were set to 30561639; 22022403
Phenotypes for gene: FOXF2 were set to profound sensorineural hearing loss (SNHL); cochlea malformations; incomplete partition type I anomaly of the cochlea
Review for gene: FOXF2 was set to AMBER
Added comment: Single family: variant has functional data to demonstrate effect on protein, plus mouse model supports gene-disease association.
Sources: Literature
Cataract v0.136 TDRD7 Zornitza Stark Marked gene: TDRD7 as ready
Cataract v0.136 TDRD7 Zornitza Stark Gene: tdrd7 has been classified as Green List (High Evidence).
Mendeliome v0.2611 FOXF2 Zornitza Stark Marked gene: FOXF2 as ready
Mendeliome v0.2611 FOXF2 Zornitza Stark Added comment: Comment when marking as ready: Single family: variant has functional data to demonstrate effect on protein, plus mouse model supports gene-disease association.
Mendeliome v0.2611 FOXF2 Zornitza Stark Gene: foxf2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2611 FOXF2 Zornitza Stark Classified gene: FOXF2 as Amber List (moderate evidence)
Mendeliome v0.2611 FOXF2 Zornitza Stark Gene: foxf2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2610 DGCR8 Chern Lim gene: DGCR8 was added
gene: DGCR8 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DGCR8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DGCR8 were set to 31805011
Phenotypes for gene: DGCR8 were set to Early-onset multinodular goiter and schwannomatosis
Review for gene: DGCR8 was set to RED
Added comment: A germline missense variant segregates in one family with autosomal dominant mendelian tumor susceptibility syndrome: familial multinodular goiter (MNG) with schwannomatosis. The missense is also a recurrent somatic missense variant in Wilms tumour. (PMID:31805011)
Sources: Literature
Cataract v0.136 TDRD7 Zornitza Stark Phenotypes for gene: TDRD7 were changed from to Cataract 36 613887; glaucoma; nonobstructive azoospermia; arrested spermatogenesis
Cataract v0.135 TDRD7 Zornitza Stark Publications for gene: TDRD7 were set to
Cataract v0.134 TDRD7 Zornitza Stark Mode of inheritance for gene: TDRD7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cataract v0.133 TDRD7 Zornitza Stark reviewed gene: TDRD7: Rating: GREEN; Mode of pathogenicity: None; Publications: 28837160, 21436445; Phenotypes: Cataract 36 613887, glaucoma, nonobstructive azoospermia, arrested spermatogenesis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2610 TDRD7 Zornitza Stark Phenotypes for gene: TDRD7 were changed from to Cataract 36 613887; glaucoma; nonobstructive azoospermia; arrested spermatogenesis
Mendeliome v0.2609 TDRD7 Zornitza Stark Publications for gene: TDRD7 were set to
Mendeliome v0.2608 TDRD7 Zornitza Stark Mode of inheritance for gene: TDRD7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2607 TDRD7 Ee Ming Wong reviewed gene: TDRD7: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28837160, 21436445; Phenotypes: cataract, glaucoma, nonobstructive azoospermia, arrested spermatogenesis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2607 FOXF2 Hazel Phillimore changed review comment from: Homozygous missense, NM_001452.1: c.325A>T (p.I109F), in a 10 year old girl (consanguineous, parents were first cousins) with profound sensorineural hearing loss (SNHL) associated with incomplete partition type I anomaly of the cochlea. This variant is absent in the gnomAD v2.1.1. In vitro studies indicated instability, shorter half-life of the protein compared to wildtype. Embryonic knockout mouse showed shortened and malformed cochleae, in addition to altered shape of hair cells with innervation and planar cell polarity defects. Homozygous knockout mice do not survive. (Bademci, G. et al. (2019); PMID: 30561639).
This gene has also been reported in association with other anomalies including cleft lip, cleft palate, brain anomalies, intestine anomalies, and eye anomalies. Eye anomalies include anterior segment dysgenesis, as shown in mice with variant, W174R, affecting the Fox domain. Homozygote mice do not survive. (McKeone, R. et al. (2011); PMID: 22022403).
Sources: Literature; to: Homozygous missense, NM_001452.1: c.325A>T (p.I109F), in a 10 year old girl (consanguineous, parents were first cousins) with profound sensorineural hearing loss (SNHL) associated with incomplete partition type I anomaly of the cochlea. This variant is absent in the gnomAD v2.1.1. In vitro studies indicated instability, shorter half-life of the protein compared to wildtype. Embryonic knockout mouse showed shortened and malformed cochleae, in addition to altered shape of hair cells with innervation and planar cell polarity defects. Homozygous knockout mice do not survive. (Bademci, G. et al. (2019); PMID: 30561639).
This gene has also been reported in association with other anomalies including cleft lip, cleft palate, brain anomalies, intestine anomalies, and eye anomalies. Eye anomalies include anterior segment dysgenesis, as shown in mice with variant, W174R, affecting the Fox domain. Homozygote mice do not survive. (McKeone, R. et al. (2011); PMID: 22022403).
Previous names for FOXF2 include FKHL6 and FREAC2.
Sources: Literature
Mendeliome v0.2607 FOXF2 Hazel Phillimore gene: FOXF2 was added
gene: FOXF2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FOXF2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FOXF2 were set to PMID: 30561639; 22022403
Phenotypes for gene: FOXF2 were set to profound sensorineural hearing loss (SNHL); cochlea malformations; incomplete partition type I anomaly of the cochlea
Review for gene: FOXF2 was set to AMBER
Added comment: Homozygous missense, NM_001452.1: c.325A>T (p.I109F), in a 10 year old girl (consanguineous, parents were first cousins) with profound sensorineural hearing loss (SNHL) associated with incomplete partition type I anomaly of the cochlea. This variant is absent in the gnomAD v2.1.1. In vitro studies indicated instability, shorter half-life of the protein compared to wildtype. Embryonic knockout mouse showed shortened and malformed cochleae, in addition to altered shape of hair cells with innervation and planar cell polarity defects. Homozygous knockout mice do not survive. (Bademci, G. et al. (2019); PMID: 30561639).
This gene has also been reported in association with other anomalies including cleft lip, cleft palate, brain anomalies, intestine anomalies, and eye anomalies. Eye anomalies include anterior segment dysgenesis, as shown in mice with variant, W174R, affecting the Fox domain. Homozygote mice do not survive. (McKeone, R. et al. (2011); PMID: 22022403).
Sources: Literature
Congenital Myasthenia v0.21 COL13A1 Zornitza Stark Marked gene: COL13A1 as ready
Congenital Myasthenia v0.21 COL13A1 Zornitza Stark Gene: col13a1 has been classified as Green List (High Evidence).
Congenital Myasthenia v0.21 COL13A1 Zornitza Stark Publications for gene: COL13A1 were set to
Congenital Myasthenia v0.20 COL13A1 Zornitza Stark reviewed gene: COL13A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31081514, 28369367, 20844119; Phenotypes: Myasthenic syndrome, congenital, 19 (OMIM #616720); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2607 COL13A1 Zornitza Stark Marked gene: COL13A1 as ready
Mendeliome v0.2607 COL13A1 Zornitza Stark Gene: col13a1 has been classified as Green List (High Evidence).
Mendeliome v0.2607 COL13A1 Zornitza Stark Phenotypes for gene: COL13A1 were changed from to Myasthenic syndrome, congenital, 19 (OMIM #616720)
Mendeliome v0.2606 COL13A1 Zornitza Stark Publications for gene: COL13A1 were set to
Mendeliome v0.2605 COL13A1 Zornitza Stark Mode of inheritance for gene: COL13A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2604 KIAA1161 Zornitza Stark Phenotypes for gene: KIAA1161 were changed from Basal ganglia calcification, idiopathic, 7, autosomal recessive; OMIM #618317 to Basal ganglia calcification, idiopathic, 7, autosomal recessive; OMIM #618317; primary familial brain calcifications (PFBC); ataxia; dysarthria; cerebellar atrophy; akinetic-hypertonic syndrome
Mendeliome v0.2603 KIAA1161 Zornitza Stark Publications for gene: KIAA1161 were set to 30656188; 30649222; 30460687; 29910000
Mendeliome v0.2602 COL13A1 Hazel Phillimore reviewed gene: COL13A1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31081514, 28369367, 20844119; Phenotypes: Myasthenic syndrome, congenital, 19 (OMIM #616720); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2602 KIAA1161 Hazel Phillimore reviewed gene: KIAA1161: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29910000, 31009047; Phenotypes: Basal ganglia calcification, idiopathic, 7, autosomal recessive (OMIM #618317), primary familial brain calcifications (PFBC), ataxia, dysarthria, cerebellar atrophy, akinetic-hypertonic syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia v0.212 CACNA1A Bryony Thompson Classified gene: CACNA1A as Green List (high evidence)
Ataxia v0.212 CACNA1A Bryony Thompson Added comment: Comment on list classification: Ataxia can be caused by a triplet repeat expansion in this gene, which is not detectable with current WES/WGS technologies. However, SNVs have also been reported as disease-causing.
Ataxia v0.212 CACNA1A Bryony Thompson Gene: cacna1a has been classified as Green List (High Evidence).
Ataxia v0.211 CACNA1A Bryony Thompson Tag STR tag was added to gene: CACNA1A.
Ciliary Dyskinesia v0.32 SPEF2 Zornitza Stark edited their review of gene: SPEF2: Changed phenotypes: Spermatogenic failure 43, MIM#618751, Primary ciliary dyskinesia-like phenotype
Mitochondrial disease v0.438 GMPR Zornitza Stark Marked gene: GMPR as ready
Mitochondrial disease v0.438 GMPR Zornitza Stark Gene: gmpr has been classified as Red List (Low Evidence).
Mendeliome v0.2602 CACNB4 Zornitza Stark changed review comment from: One multigenerational family and supportive animal model data.; to: One multigenerational family with ataxia and supportive animal model data.
Mendeliome v0.2602 CACNB4 Zornitza Stark edited their review of gene: CACNB4: Added comment: PMID 32176688: A homozygous missense variant (Leu126Pro) reported in two siblings with intellectual disability, psychomotor retardation, blindness, epilepsy, movement disorder and cerebellar atrophy. Some functional data.; Changed publications: 10762541, 9628818, 27003325, 32176688; Changed phenotypes: Episodic ataxia, type 5, MIM#613855, Intellectual disability, Epilepsy, Movement disorder
Intellectual disability syndromic and non-syndromic v0.2590 CEP55 Zornitza Stark Marked gene: CEP55 as ready
Intellectual disability syndromic and non-syndromic v0.2590 CEP55 Zornitza Stark Gene: cep55 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2590 CEP55 Zornitza Stark Classified gene: CEP55 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2590 CEP55 Zornitza Stark Gene: cep55 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2589 CEP55 Zornitza Stark gene: CEP55 was added
gene: CEP55 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CEP55 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP55 were set to 32100459
Phenotypes for gene: CEP55 were set to Multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly, MIM# 236500; Microcephaly; Intellectual disability
Review for gene: CEP55 was set to GREEN
Added comment: Homozygous nonsense variants in CEP55 are associated with a lethal condition characterized by multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly (MARCH syndrome) also known as Meckel-like syndrome. New report of seven living individuals from five families with biallelic CEP55 variants. Four unrelated individuals with microcephaly, speech delays, and bilateral toe syndactyly all had a common CEP55 variant c.70G>A p.(Glu24Lys) in trans with nonsense variants. Three siblings were homozygous for a consensus splice site variant near the end of the gene. These affected girls all had severely delayed development, microcephaly, and varying degrees of lissencephaly/pachygyria. This series suggests that individuals with compound heterozygosity for nonsense and missense variants in CEP55 have a different viable phenotype.
Sources: Literature
Microcephaly v0.120 CEP55 Zornitza Stark Marked gene: CEP55 as ready
Microcephaly v0.120 CEP55 Zornitza Stark Gene: cep55 has been classified as Green List (High Evidence).
Microcephaly v0.120 CEP55 Zornitza Stark Classified gene: CEP55 as Green List (high evidence)
Microcephaly v0.120 CEP55 Zornitza Stark Gene: cep55 has been classified as Green List (High Evidence).
Microcephaly v0.119 CEP55 Zornitza Stark gene: CEP55 was added
gene: CEP55 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: CEP55 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP55 were set to 32100459
Phenotypes for gene: CEP55 were set to Multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly, MIM# 236500; Microcephaly; Intellectual disability
Review for gene: CEP55 was set to GREEN
Added comment: Homozygous nonsense variants in CEP55 are associated with a lethal condition characterized by multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly (MARCH syndrome) also known as Meckel-like syndrome. New report of seven living individuals from five families with biallelic CEP55 variants. Four unrelated individuals with microcephaly, speech delays, and bilateral toe syndactyly all had a common CEP55 variant c.70G>A p.(Glu24Lys) in trans with nonsense variants. Three siblings were homozygous for a consensus splice site variant near the end of the gene. These affected girls all had severely delayed development, microcephaly, and varying degrees of lissencephaly/pachygyria. This series suggests that individuals with compound heterozygosity for nonsense and missense variants in CEP55 have a different viable phenotype.
Sources: Literature
Cholestasis v0.16 WDR83OS Zornitza Stark Marked gene: WDR83OS as ready
Cholestasis v0.16 WDR83OS Zornitza Stark Gene: wdr83os has been classified as Red List (Low Evidence).
Cholestasis v0.16 WDR83OS Zornitza Stark gene: WDR83OS was added
gene: WDR83OS was added to Cholestasis. Sources: Literature
Mode of inheritance for gene: WDR83OS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR83OS were set to 30250217
Phenotypes for gene: WDR83OS were set to Cholestasis
Review for gene: WDR83OS was set to RED
Added comment: - 1 consanguineous family with 3 affected individuals found to carry a homozygous splice site variant in WDR83OS - The variant results in an aberrant truncated RNA transcript as demonstrated by RT-PCR
Sources: Literature
Mendeliome v0.2602 WDR83OS Zornitza Stark Marked gene: WDR83OS as ready
Mendeliome v0.2602 WDR83OS Zornitza Stark Gene: wdr83os has been classified as Red List (Low Evidence).
Mendeliome v0.2602 WDR83OS Zornitza Stark Publications for gene: WDR83OS were set to PMID: 30250217
Mendeliome v0.2601 WDR83OS Zornitza Stark Classified gene: WDR83OS as Red List (low evidence)
Mendeliome v0.2601 WDR83OS Zornitza Stark Gene: wdr83os has been classified as Red List (Low Evidence).
Fatty Acid Oxidation Defects v0.8 Bryony Thompson Panel name changed from Fatty Oxidation Defects to Fatty Acid Oxidation Defects
Fatty Acid Oxidation Defects v0.7 ACADSB Bryony Thompson gene: ACADSB was added
gene: ACADSB was added to Fatty Oxidation Defects. Sources: Expert list
Mode of inheritance for gene: ACADSB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACADSB were set to 11013134; 17945527; 30730842
Phenotypes for gene: ACADSB were set to 2-methylbutyrylglycinuria MIM#610006
Review for gene: ACADSB was set to GREEN
Added comment: The enzyme catalyses the dehydrogenation of acyl-CoA derivatives in the metabolism of fatty acids or branch chained amino acids. SBCAD deficiency is symptomatic in about 10% of reported patients.
Sources: Expert list
Fatty Acid Oxidation Defects v0.6 OXCT1 Bryony Thompson Classified gene: OXCT1 as Green List (high evidence)
Fatty Acid Oxidation Defects v0.6 OXCT1 Bryony Thompson Gene: oxct1 has been classified as Green List (High Evidence).
Fatty Acid Oxidation Defects v0.5 OXCT1 Bryony Thompson gene: OXCT1 was added
gene: OXCT1 was added to Fatty Oxidation Defects. Sources: Expert list
Mode of inheritance for gene: OXCT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OXCT1 were set to 8751852; 10964512; 28178565
Phenotypes for gene: OXCT1 were set to Succinyl CoA:3-oxoacid CoA transferase deficiency MIM#245050
Review for gene: OXCT1 was set to GREEN
Added comment: The enzyme catalyses the first step of ketone body utilization, ketone bodies are produced predominantly in the liver from fatty acid oxidation-derived acetyl-coenzyme A (CoA), and they are transported to extrahepatic tissues for terminal oxidation. At least 4 cases reported with the condition.
Sources: Expert list
Fatty Acid Oxidation Defects v0.4 ACAT1 Bryony Thompson Classified gene: ACAT1 as Green List (high evidence)
Fatty Acid Oxidation Defects v0.4 ACAT1 Bryony Thompson Gene: acat1 has been classified as Green List (High Evidence).
Fatty Acid Oxidation Defects v0.3 ACAT1 Bryony Thompson gene: ACAT1 was added
gene: ACAT1 was added to Fatty Oxidation Defects. Sources: Expert list
Mode of inheritance for gene: ACAT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACAT1 were set to 17236799; 1715688
Phenotypes for gene: ACAT1 were set to Alpha-methylacetoacetic aciduria MIM#203750; Deficiency of acetyl-CoA acetyltransferase
Review for gene: ACAT1 was set to GREEN
Added comment: Is one of the enzymes that catalyzes the last step of the mitochondrial beta-oxidation pathway, an aerobic process breaking down fatty acids into acetyl-CoA. Biallelic variants have been identified in at least 7 families.
Sources: Expert list
Cholestasis v0.15 LSR Zornitza Stark Marked gene: LSR as ready
Cholestasis v0.15 LSR Zornitza Stark Gene: lsr has been classified as Amber List (Moderate Evidence).
Cholestasis v0.15 LSR Zornitza Stark Classified gene: LSR as Amber List (moderate evidence)
Cholestasis v0.15 LSR Zornitza Stark Gene: lsr has been classified as Amber List (Moderate Evidence).
Cholestasis v0.14 LSR Zornitza Stark gene: LSR was added
gene: LSR was added to Cholestasis. Sources: Literature
Mode of inheritance for gene: LSR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LSR were set to 32303357; 30250217
Phenotypes for gene: LSR were set to transient neonatal cholestasis; intellectual disability; short stature
Review for gene: LSR was set to AMBER
Added comment: Two families reported.
Sources: Literature
Mendeliome v0.2600 LSR Zornitza Stark Marked gene: LSR as ready
Mendeliome v0.2600 LSR Zornitza Stark Gene: lsr has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2600 LSR Zornitza Stark Publications for gene: LSR were set to PMID: 30250217
Mendeliome v0.2599 LSR Zornitza Stark Classified gene: LSR as Amber List (moderate evidence)
Mendeliome v0.2599 LSR Zornitza Stark Gene: lsr has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2598 WDR83OS Ee Ming Wong gene: WDR83OS was added
gene: WDR83OS was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: WDR83OS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR83OS were set to PMID: 30250217
Phenotypes for gene: WDR83OS were set to Cholestasis
Review for gene: WDR83OS was set to RED
Added comment: - 1 consanguineous family with 3 affected individuals found to carry a homozygous splice site variant in WDR83OS
- The variant results in an aberrant truncated RNA transcript as demonstrated by RT-PCR
Sources: Literature
Mendeliome v0.2598 LSR Zornitza Stark reviewed gene: LSR: Rating: AMBER; Mode of pathogenicity: None; Publications: 32303357, 30250217; Phenotypes: Cholestasis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2598 LSR Zornitza Stark Deleted their review
Mendeliome v0.2598 LSR Zornitza Stark Classified gene: LSR as Green List (high evidence)
Mendeliome v0.2598 LSR Zornitza Stark Gene: lsr has been classified as Green List (High Evidence).
Mendeliome v0.2597 LSR Zornitza Stark reviewed gene: LSR: Rating: GREEN; Mode of pathogenicity: None; Publications: 32303357; Phenotypes: Cholestasis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2597 LSR Zornitza Stark Classified gene: LSR as Amber List (moderate evidence)
Mendeliome v0.2597 LSR Zornitza Stark Gene: lsr has been classified as Amber List (Moderate Evidence).
Cholestasis v0.13 USP53 Zornitza Stark Marked gene: USP53 as ready
Cholestasis v0.13 USP53 Zornitza Stark Gene: usp53 has been classified as Green List (High Evidence).
Cholestasis v0.13 USP53 Zornitza Stark Classified gene: USP53 as Green List (high evidence)
Cholestasis v0.13 USP53 Zornitza Stark Gene: usp53 has been classified as Green List (High Evidence).
Cholestasis v0.12 USP53 Zornitza Stark gene: USP53 was added
gene: USP53 was added to Cholestasis. Sources: Literature
Mode of inheritance for gene: USP53 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: USP53 were set to 30250217; 32124521
Phenotypes for gene: USP53 were set to Cholestasis; deafness
Review for gene: USP53 was set to GREEN
Added comment: 8 unrelated families with cholestasis reported. Jaundice began at age <7 months. Cholestasis was transient in 7 families, with documented resolution of hyperbilirubinaemia in all (oldest patient aged 5 years). In another family, one individual required liver transplantation. Three individuals from two families had deafness.
Sources: Literature
Mendeliome v0.2596 USP53 Zornitza Stark Publications for gene: USP53 were set to PMID: 30250217
Mendeliome v0.2595 LSR Ee Ming Wong reviewed gene: LSR: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 32303357, 30250217; Phenotypes: Intrahepatic cholestasis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2595 USP53 Zornitza Stark Marked gene: USP53 as ready
Mendeliome v0.2595 USP53 Zornitza Stark Gene: usp53 has been classified as Green List (High Evidence).
Mendeliome v0.2595 USP53 Zornitza Stark Phenotypes for gene: USP53 were changed from Deafness to Cholestasis; deafness
Mendeliome v0.2594 USP53 Zornitza Stark Classified gene: USP53 as Green List (high evidence)
Mendeliome v0.2594 USP53 Zornitza Stark Gene: usp53 has been classified as Green List (High Evidence).
Mendeliome v0.2593 USP53 Zornitza Stark reviewed gene: USP53: Rating: GREEN; Mode of pathogenicity: None; Publications: 32124521; Phenotypes: Cholestasis, deafness; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2593 LSR Ee Ming Wong Deleted their review
Mendeliome v0.2593 USP53 Zornitza Stark Classified gene: USP53 as Red List (low evidence)
Mendeliome v0.2593 USP53 Zornitza Stark Gene: usp53 has been classified as Red List (Low Evidence).
Mendeliome v0.2592 LSR Ee Ming Wong gene: LSR was added
gene: LSR was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LSR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LSR were set to PMID: 30250217
Phenotypes for gene: LSR were set to transient neonatal cholestasis; intellectual disability; short stature
Review for gene: LSR was set to RED
Added comment: 1 individual from 1 consanguineous family carrying a homozygous missense variant in LSR
Sources: Literature
Cholestasis v0.11 PPM1F Zornitza Stark Marked gene: PPM1F as ready
Cholestasis v0.11 PPM1F Zornitza Stark Gene: ppm1f has been classified as Red List (Low Evidence).
Cholestasis v0.11 PPM1F Zornitza Stark gene: PPM1F was added
gene: PPM1F was added to Cholestasis. Sources: Literature
Mode of inheritance for gene: PPM1F was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPM1F were set to 30250217
Phenotypes for gene: PPM1F were set to sclerosing cholangitis; short stature; hypothyroidism; abnormal tongue pigmentatio
Review for gene: PPM1F was set to RED
Added comment: One consanguineous family reported.
Sources: Literature
Mendeliome v0.2592 PPM1F Zornitza Stark Marked gene: PPM1F as ready
Mendeliome v0.2592 PPM1F Zornitza Stark Gene: ppm1f has been classified as Red List (Low Evidence).
Mendeliome v0.2592 PPM1F Zornitza Stark Classified gene: PPM1F as Red List (low evidence)
Mendeliome v0.2592 PPM1F Zornitza Stark Gene: ppm1f has been classified as Red List (Low Evidence).
Mendeliome v0.2591 USP53 Ee Ming Wong gene: USP53 was added
gene: USP53 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: USP53 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: USP53 were set to PMID: 30250217
Phenotypes for gene: USP53 were set to Deafness
Review for gene: USP53 was set to RED
Added comment: 1 consanguineous family carrying a homozygous truncating variant in USP53
Sources: Literature
Mendeliome v0.2591 PPM1F Ee Ming Wong gene: PPM1F was added
gene: PPM1F was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PPM1F was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPM1F were set to PMID: 30250217
Phenotypes for gene: PPM1F were set to sclerosing cholangitis; short stature; hypothyroidism; abnormal tongue pigmentation
Review for gene: PPM1F was set to RED
Added comment: 1 consanguineous family found to carry a homozygous missense variant in PPM1F
Sources: Literature
Fatty Acid Oxidation Defects v0.2 Bryony Thompson Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Aortopathy_Connective Tissue Disorders v0.24 Bryony Thompson Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Glycogen Storage Diseases v0.4 RBCK1 Bryony Thompson Classified gene: RBCK1 as Green List (high evidence)
Glycogen Storage Diseases v0.4 RBCK1 Bryony Thompson Gene: rbck1 has been classified as Green List (High Evidence).
Glycogen Storage Diseases v0.3 RBCK1 Bryony Thompson gene: RBCK1 was added
gene: RBCK1 was added to Glycogen Storage Diseases. Sources: Expert list
Mode of inheritance for gene: RBCK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RBCK1 were set to 23798481; 23104095
Phenotypes for gene: RBCK1 were set to Polyglucosan body myopathy 1 with or without immunodeficiency MIM#615895
Review for gene: RBCK1 was set to GREEN
Added comment: Biallelic variants cause polyglucosan storage myopathy associated with progressive muscle weakness and cardiomyopathy, which is characterised as a glycogen storage disorder. At least 9 families reported.
Sources: Expert list
Glycogen Storage Diseases v0.2 Bryony Thompson Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Stroke v0.1 Bryony Thompson Panel status changed from internal to public
Panel types changed to Royal Melbourne Hospital; Rare Disease
Stroke v0.0 NOS3 Bryony Thompson gene: NOS3 was added
gene: NOS3 was added to Stroke. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: NOS3 was set to Unknown
Stroke v0.0 MYH11 Bryony Thompson gene: MYH11 was added
gene: MYH11 was added to Stroke. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: MYH11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: MYH11 were set to Aortic aneurysm, familial thoracic 4
Stroke v0.0 MUT Bryony Thompson gene: MUT was added
gene: MUT was added to Stroke. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: MUT was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MUT were set to Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency
Stroke v0.0 GLA Bryony Thompson gene: GLA was added
gene: GLA was added to Stroke. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: GLA was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: GLA were set to Fabry disease
Stroke v0.0 FLNA Bryony Thompson gene: FLNA was added
gene: FLNA was added to Stroke. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: FLNA was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: FLNA were set to Periventricular nodular heterotopia 1
Stroke v0.0 WFS1 Bryony Thompson gene: WFS1 was added
gene: WFS1 was added to Stroke. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: WFS1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WFS1 were set to Diabetes mellitus AND insipidus with optic atrophy AND deafness
Stroke v0.0 TTR Bryony Thompson gene: TTR was added
gene: TTR was added to Stroke. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: TTR was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TTR were set to Amyloidogenic transthyretin amyloidosis
Stroke v0.0 TREX1 Bryony Thompson gene: TREX1 was added
gene: TREX1 was added to Stroke. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: TREX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TREX1 were set to Vasculopathy, retinal, with cerebral leukodystrophy
Stroke v0.0 STIM1 Bryony Thompson gene: STIM1 was added
gene: STIM1 was added to Stroke. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: STIM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: STIM1 were set to Stormorken syndrome
Stroke v0.0 SMAD4 Bryony Thompson gene: SMAD4 was added
gene: SMAD4 was added to Stroke. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: SMAD4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SMAD4 were set to Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome 175050
Stroke v0.0 SLC2A10 Bryony Thompson gene: SLC2A10 was added
gene: SLC2A10 was added to Stroke. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: SLC2A10 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC2A10 were set to 208050; Moyamoya disease; Arterial tortuosity syndrome
Stroke v0.0 POLG Bryony Thompson gene: POLG was added
gene: POLG was added to Stroke. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: POLG was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Stroke v0.0 OTC Bryony Thompson gene: OTC was added
gene: OTC was added to Stroke. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: OTC was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: OTC were set to Ornithine carbamoyltransferase deficiency
Stroke v0.0 NOTCH3 Bryony Thompson gene: NOTCH3 was added
gene: NOTCH3 was added to Stroke. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: NOTCH3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: NOTCH3 were set to Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL)
Stroke v0.0 HTRA1 Bryony Thompson gene: HTRA1 was added
gene: HTRA1 was added to Stroke. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: HTRA1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: HTRA1 were set to Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy; Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 2, 616779
Stroke v0.0 ENG Bryony Thompson gene: ENG was added
gene: ENG was added to Stroke. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: ENG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ENG were set to Telangiectasia, hereditary hemorrhagic, type 1 187300
Stroke v0.0 CST3 Bryony Thompson gene: CST3 was added
gene: CST3 was added to Stroke. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: CST3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CST3 were set to Hereditary cerebral amyloid angiopathy, Icelandic type
Stroke v0.0 COL4A1 Bryony Thompson gene: COL4A1 was added
gene: COL4A1 was added to Stroke. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: COL4A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: COL4A1 were set to Brain small vessel disease with or without ocular anomalies; Brain Small Vessel Disease with Hemorrhage
Stroke v0.0 ASS1 Bryony Thompson gene: ASS1 was added
gene: ASS1 was added to Stroke. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: ASS1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ASS1 were set to Citrullinemia type
Stroke v0.0 APP Bryony Thompson gene: APP was added
gene: APP was added to Stroke. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: APP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: APP were set to Cerebral amyloid angiopathy, APP-related
Stroke v0.0 ADA2 Bryony Thompson gene: ADA2 was added
gene: ADA2 was added to Stroke. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: ADA2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ADA2 were set to Polyarteritis nodosa; Sneddon syndrome 182410
Stroke v0.0 ACVRL1 Bryony Thompson gene: ACVRL1 was added
gene: ACVRL1 was added to Stroke. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: ACVRL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ACVRL1 were set to Telangiectasia, hereditary hemorrhagic, type 2 600376
Stroke v0.0 ACAD9 Bryony Thompson gene: ACAD9 was added
gene: ACAD9 was added to Stroke. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: ACAD9 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ACAD9 were set to Acyl-CoA dehydrogenase family, member 9, deficiency of
Stroke v0.0 ABCC6 Bryony Thompson gene: ABCC6 was added
gene: ABCC6 was added to Stroke. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: ABCC6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ABCC6 were set to Pseudoxanthoma elasticum, forme fruste
Stroke v0.0 Bryony Thompson Added panel Stroke
Ciliary Dyskinesia v0.32 SPEF2 Zornitza Stark Marked gene: SPEF2 as ready
Ciliary Dyskinesia v0.32 SPEF2 Zornitza Stark Gene: spef2 has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v0.32 SPEF2 Zornitza Stark Phenotypes for gene: SPEF2 were changed from Spermatogenic failure 43, MIM#618751; Spermatogenic failure 43, MIM#618751; Primary ciliary dyskinesia-like phenotype to Spermatogenic failure 43, MIM#618751; Primary ciliary dyskinesia-like phenotype
Ciliary Dyskinesia v0.31 SPEF2 Zornitza Stark Classified gene: SPEF2 as Amber List (moderate evidence)
Ciliary Dyskinesia v0.31 SPEF2 Zornitza Stark Gene: spef2 has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v0.30 SPEF2 Zornitza Stark gene: SPEF2 was added
gene: SPEF2 was added to Ciliary Dyskinesia. Sources: Literature
Mode of inheritance for gene: SPEF2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPEF2 were set to 31151990; 31278745; 31048344; 31942643
Phenotypes for gene: SPEF2 were set to Spermatogenic failure 43, MIM#618751; Spermatogenic failure 43, MIM#618751; Primary ciliary dyskinesia-like phenotype
Review for gene: SPEF2 was set to AMBER
Added comment: 4 families reported with bi-allelic variants and sperm morphological abnormalities plus recurrent sinopulmonary infections and bronchiectasis, consistent with a PCD-like phenotype. Morphological abnormalities of the respiratory cilia were not observed. Mouse model recapitulated the infertility phenotype but also had hydrocephalus and sinusitis, again arguing for broader impact on ciliary function. Note other reports of individuals with bi-allelic variants and no respiratory phenotype reported. Given respiratory phenotype is milder and currently it is unclear in what proportion of individuals it is present, Amber rating on this panel for now.
Sources: Literature
Mendeliome v0.2591 SPEF2 Zornitza Stark Phenotypes for gene: SPEF2 were changed from Spermatogenic failure 43, MIM#618751 to Spermatogenic failure 43, MIM#618751; Spermatogenic failure 43, MIM#618751; Primary ciliary dyskinesia-like phenotype
Mendeliome v0.2590 SPEF2 Zornitza Stark Publications for gene: SPEF2 were set to 31151990; 31278745; 31048344
Mendeliome v0.2589 SPEF2 Zornitza Stark reviewed gene: SPEF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31942643; Phenotypes: Spermatogenic failure 43, MIM#618751, Primary ciliary dyskinesia-like phenotype; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy v0.58 KLC2 Zornitza Stark Marked gene: KLC2 as ready
Hereditary Neuropathy v0.58 KLC2 Zornitza Stark Gene: klc2 has been classified as Green List (High Evidence).
Hereditary Neuropathy v0.58 KLC2 Zornitza Stark Classified gene: KLC2 as Green List (high evidence)
Hereditary Neuropathy v0.58 KLC2 Zornitza Stark Gene: klc2 has been classified as Green List (High Evidence).
Hereditary Neuropathy v0.57 KLC2 Zornitza Stark reviewed gene: KLC2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia, optic atrophy, and neuropathy MIM#609541; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Spastic Paraplegia v0.82 KLC2 Zornitza Stark Classified gene: KLC2 as Green List (high evidence)
Hereditary Spastic Paraplegia v0.82 KLC2 Zornitza Stark Gene: klc2 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v0.81 KLC2 Zornitza Stark reviewed gene: KLC2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2589 KLC2 Zornitza Stark Marked gene: KLC2 as ready
Mendeliome v0.2589 KLC2 Zornitza Stark Gene: klc2 has been classified as Green List (High Evidence).
Mendeliome v0.2589 KLC2 Zornitza Stark Tag SV/CNV tag was added to gene: KLC2.
Mendeliome v0.2589 KLC2 Zornitza Stark Classified gene: KLC2 as Green List (high evidence)
Mendeliome v0.2589 KLC2 Zornitza Stark Gene: klc2 has been classified as Green List (High Evidence).
Mendeliome v0.2588 KLC2 Zornitza Stark gene: KLC2 was added
gene: KLC2 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: KLC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KLC2 were set to 26385635
Phenotypes for gene: KLC2 were set to Spastic paraplegia, optic atrophy, and neuropathy MIM#609541
Review for gene: KLC2 was set to GREEN
Added comment: In 73 Brazilian patients and 2 sibs of Egyptian descent with SPOAN, a homozygous 216-bp deletion in the noncoding upstream region of the KLC2 gene was identified. Only reported cause of condition is the upstream large deletion, which is not detected by whole-exome sequencing.
Sources: Expert Review
Cholestasis v0.10 KIF12 Zornitza Stark Marked gene: KIF12 as ready
Cholestasis v0.10 KIF12 Zornitza Stark Gene: kif12 has been classified as Green List (High Evidence).
Cholestasis v0.10 KIF12 Zornitza Stark Classified gene: KIF12 as Green List (high evidence)
Cholestasis v0.10 KIF12 Zornitza Stark Gene: kif12 has been classified as Green List (High Evidence).
Cholestasis v0.9 KIF12 Zornitza Stark gene: KIF12 was added
gene: KIF12 was added to Cholestasis. Sources: Expert list
Mode of inheritance for gene: KIF12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF12 were set to 30250217; 30976738
Phenotypes for gene: KIF12 were set to Cholestasis; High Gamma-Glutamyltransferase (GGT)
Review for gene: KIF12 was set to GREEN
Added comment: Five unrelated consanguineous families, with four different homozygous variants identified, some truncating, others missense.
Sources: Expert list
Mendeliome v0.2587 KIF12 Zornitza Stark Phenotypes for gene: KIF12 were changed from Prenatal cholestasis; High Gamma-Glutamyltransferase (GGT) to Cholestasis; High Gamma-Glutamyltransferase (GGT)
Mendeliome v0.2586 KIF12 Zornitza Stark Marked gene: KIF12 as ready
Mendeliome v0.2586 KIF12 Zornitza Stark Gene: kif12 has been classified as Green List (High Evidence).
Mendeliome v0.2586 KIF12 Zornitza Stark Publications for gene: KIF12 were set to PMID: 30250217; 30976738
Mendeliome v0.2585 KIF12 Zornitza Stark Classified gene: KIF12 as Green List (high evidence)
Mendeliome v0.2585 KIF12 Zornitza Stark Gene: kif12 has been classified as Green List (High Evidence).
Mendeliome v0.2584 KIF12 Zornitza Stark reviewed gene: KIF12: Rating: GREEN; Mode of pathogenicity: None; Publications: 30250217, 30976738; Phenotypes: Cholestasis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paroxysmal Dyskinesia v0.27 GCH1 Zornitza Stark reviewed gene: GCH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Dopa-responsive dystonia, exercise-induced dystonia, Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, MIM# 128230; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Paroxysmal Dyskinesia v0.27 PNKD Zornitza Stark Marked gene: PNKD as ready
Paroxysmal Dyskinesia v0.27 PNKD Zornitza Stark Gene: pnkd has been classified as Green List (High Evidence).
Paroxysmal Dyskinesia v0.27 PNKD Zornitza Stark Phenotypes for gene: PNKD were changed from to Paroxysmal nonkinesigenic dyskinesia 1, MIM# 118800
Paroxysmal Dyskinesia v0.26 PNKD Zornitza Stark Mode of inheritance for gene: PNKD was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Paroxysmal Dyskinesia v0.25 PNKD Zornitza Stark reviewed gene: PNKD: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Paroxysmal nonkinesigenic dyskinesia 1, MIM# 118800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Paroxysmal Dyskinesia v0.25 ECHS1 Zornitza Stark Marked gene: ECHS1 as ready
Paroxysmal Dyskinesia v0.25 ECHS1 Zornitza Stark Gene: echs1 has been classified as Green List (High Evidence).
Paroxysmal Dyskinesia v0.25 ECHS1 Zornitza Stark Phenotypes for gene: ECHS1 were changed from early onset Leigh syndrome; later onset Leigh-like syndrome; paroxysmal dyskinesia (isolated or with other features of a mitochondrial disease) to Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency, MIM# 616277; paroxysmal dyskinesia (isolated or with other features of a mitochondrial disease)
Paroxysmal Dyskinesia v0.24 ECHS1 Zornitza Stark Publications for gene: ECHS1 were set to Olgiati S, Skorvanek M, Quadri M, et al. Paroxysmal exercise-induced dystonia within the phenotypic spectrum of ECHS1 deficiency. Mov Disord 2016; 31:1041–8 (PMID: 2709; 0768); Mahajan A, Constantinou J, Sidiropoulos C. ECHS1 deficiency-associated paroxysmal exercise-induced dyskinesias: case presentation and initial benefit of intervention. J Neurol 2017; 264:185–7. (PMID: 2803; 9521)
Paroxysmal Dyskinesia v0.23 ECHS1 Zornitza Stark reviewed gene: ECHS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27090768, 28039521; Phenotypes: Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency, MIM# 616277, paroxysmal dyskinesia (isolated or with other features of a mitochondrial disease); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paroxysmal Dyskinesia v0.23 ECHS1 Zornitza Stark Classified gene: ECHS1 as Green List (high evidence)
Paroxysmal Dyskinesia v0.23 ECHS1 Zornitza Stark Gene: echs1 has been classified as Green List (High Evidence).
Paroxysmal Dyskinesia v0.22 PDHA1 Zornitza Stark Marked gene: PDHA1 as ready
Paroxysmal Dyskinesia v0.22 PDHA1 Zornitza Stark Gene: pdha1 has been classified as Green List (High Evidence).
Paroxysmal Dyskinesia v0.22 PDHA1 Zornitza Stark Phenotypes for gene: PDHA1 were changed from Paroxysmal dyskinesia (exercise induced or without clear trigger; isolated or with additional features); mitochondrial disorder (Leigh syndrome, ataxia); neurodevelopmental disability; epilepsy. to Pyruvate dehydrogenase E1-alpha deficiency, MIM# 312170; Paroxysmal dyskinesia (exercise induced or without clear trigger
Paroxysmal Dyskinesia v0.21 PDHA1 Zornitza Stark Publications for gene: PDHA1 were set to Barnerias C et al. 2010 Dev Med Child Neurol. 52:e1-e9 (PMID: 2000; 2125); Patel et al. 2012 Mol Genet Metab 105(1):34-43 (PMID: 2207; 9328)
Paroxysmal Dyskinesia v0.20 PDHA1 Zornitza Stark reviewed gene: PDHA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20002125, 22079328; Phenotypes: Pyruvate dehydrogenase E1-alpha deficiency, MIM# 312170, Paroxysmal dyskinesia (exercise induced or without clear trigger; Mode of inheritance: Other
Paroxysmal Dyskinesia v0.20 PDHA1 Zornitza Stark Classified gene: PDHA1 as Green List (high evidence)
Paroxysmal Dyskinesia v0.20 PDHA1 Zornitza Stark Gene: pdha1 has been classified as Green List (High Evidence).
Paroxysmal Dyskinesia v0.19 PDHX Zornitza Stark Marked gene: PDHX as ready
Paroxysmal Dyskinesia v0.19 PDHX Zornitza Stark Gene: pdhx has been classified as Green List (High Evidence).
Paroxysmal Dyskinesia v0.19 PDHX Zornitza Stark Phenotypes for gene: PDHX were changed from to Lactic acidemia due to PDX1 deficiency, MIM# 245349; episodic dystonia; Paroxysmal dyskinesia (exercise induced or without clear trigger; isolated or with additional features)
Paroxysmal Dyskinesia v0.18 PDHX Zornitza Stark Publications for gene: PDHX were set to
Paroxysmal Dyskinesia v0.17 PDHX Zornitza Stark Mode of inheritance for gene: PDHX was changed from Other to BIALLELIC, autosomal or pseudoautosomal
Paroxysmal Dyskinesia v0.16 PDHX Zornitza Stark Classified gene: PDHX as Green List (high evidence)
Paroxysmal Dyskinesia v0.16 PDHX Zornitza Stark Gene: pdhx has been classified as Green List (High Evidence).
Paroxysmal Dyskinesia v0.15 PDHX Zornitza Stark commented on gene: PDHX: Paroxysmal dystonia secondary to basal ganglia lesions
Paroxysmal Dyskinesia v0.15 PDHX Zornitza Stark edited their review of gene: PDHX: Changed publications: 16566017, 20002125
Paroxysmal Dyskinesia v0.15 PDHX Zornitza Stark reviewed gene: PDHX: Rating: GREEN; Mode of pathogenicity: None; Publications: 16566017; Phenotypes: Lactic acidemia due to PDX1 deficiency, MIM# 245349, episodic dystonia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paroxysmal Dyskinesia v0.15 DLAT Zornitza Stark Marked gene: DLAT as ready
Paroxysmal Dyskinesia v0.15 DLAT Zornitza Stark Gene: dlat has been classified as Green List (High Evidence).
Paroxysmal Dyskinesia v0.15 DLAT Zornitza Stark Phenotypes for gene: DLAT were changed from to Pyruvate dehydrogenase E2 deficiency, MIM# 245348; Episodic dystonia (Exercise induced or without clear trigger)
Paroxysmal Dyskinesia v0.14 DLAT Zornitza Stark Publications for gene: DLAT were set to
Paroxysmal Dyskinesia v0.13 DLAT Zornitza Stark Classified gene: DLAT as Green List (high evidence)
Paroxysmal Dyskinesia v0.13 DLAT Zornitza Stark Gene: dlat has been classified as Green List (High Evidence).
Paroxysmal Dyskinesia v0.12 DLAT Zornitza Stark reviewed gene: DLAT: Rating: GREEN; Mode of pathogenicity: None; Publications: 20022530, 29093066; Phenotypes: Pyruvate dehydrogenase E2 deficiency, MIM# 245348, Episodic dystonia (Exercise induced or without clear trigger); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paroxysmal Dyskinesia v0.12 GCH1 Zornitza Stark Marked gene: GCH1 as ready
Paroxysmal Dyskinesia v0.12 GCH1 Zornitza Stark Gene: gch1 has been classified as Green List (High Evidence).
Paroxysmal Dyskinesia v0.12 GCH1 Zornitza Stark Phenotypes for gene: GCH1 were changed from Dopa-responsive dystonia; exercise-induced dystonia to Dopa-responsive dystonia; exercise-induced dystonia; Dystonia, DOPA-responsive, with or without hyperphenylalaninemia 128230
Paroxysmal Dyskinesia v0.11 GCH1 Zornitza Stark Classified gene: GCH1 as Green List (high evidence)
Paroxysmal Dyskinesia v0.11 GCH1 Zornitza Stark Gene: gch1 has been classified as Green List (High Evidence).
Autoinflammatory Disorders v0.69 ALPK1 Zornitza Stark Marked gene: ALPK1 as ready
Autoinflammatory Disorders v0.69 ALPK1 Zornitza Stark Gene: alpk1 has been classified as Amber List (Moderate Evidence).
Autoinflammatory Disorders v0.69 ALPK1 Zornitza Stark Classified gene: ALPK1 as Amber List (moderate evidence)
Autoinflammatory Disorders v0.69 ALPK1 Zornitza Stark Gene: alpk1 has been classified as Amber List (Moderate Evidence).
Autoinflammatory Disorders v0.68 ALPK1 Zornitza Stark gene: ALPK1 was added
gene: ALPK1 was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Literature
Mode of inheritance for gene: ALPK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ALPK1 were set to 31053777
Phenotypes for gene: ALPK1 were set to Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome
Review for gene: ALPK1 was set to AMBER
Added comment: Three unrelated families reported. One of the variants segregated in four affected individuals in one family and another was found to be de novo. The third variant however was not segregated, and is also present in 18 individuals in gnomad. Hence the evidence for variant pathogenicity in this third case is not compelling.
Sources: Literature
Congenital Disorders of Glycosylation v0.46 CSGALNACT1 Zornitza Stark Marked gene: CSGALNACT1 as ready
Congenital Disorders of Glycosylation v0.46 CSGALNACT1 Zornitza Stark Gene: csgalnact1 has been classified as Green List (High Evidence).
Mendeliome v0.2584 ALPK1 Zornitza Stark Marked gene: ALPK1 as ready
Mendeliome v0.2584 ALPK1 Zornitza Stark Gene: alpk1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2584 ALPK1 Zornitza Stark Classified gene: ALPK1 as Amber List (moderate evidence)
Mendeliome v0.2584 ALPK1 Zornitza Stark Gene: alpk1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2583 ALPK1 Zornitza Stark gene: ALPK1 was added
gene: ALPK1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ALPK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ALPK1 were set to 31053777
Phenotypes for gene: ALPK1 were set to Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome
Review for gene: ALPK1 was set to AMBER
Added comment: Three unrelated families reported. One of the variants segregated in four affected individuals in one family and another was found to be de novo. The third variant however was not segregated, and is also present in 18 individuals in gnomad. Hence the evidence for variant pathogenicity in this third case is not compelling.
Sources: Literature
Paroxysmal Dyskinesia v0.10 GCH1 Eunice Chan edited their review of gene: GCH1: Changed phenotypes: Dopa-responsive dystonia, exercise-induced dystonia; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2588 LRRC32 Zornitza Stark Marked gene: LRRC32 as ready
Intellectual disability syndromic and non-syndromic v0.2588 LRRC32 Zornitza Stark Gene: lrrc32 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2588 LRRC32 Zornitza Stark Classified gene: LRRC32 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2588 LRRC32 Zornitza Stark Gene: lrrc32 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2587 LRRC32 Zornitza Stark gene: LRRC32 was added
gene: LRRC32 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: LRRC32 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRRC32 were set to 30976112
Phenotypes for gene: LRRC32 were set to Intellectual disability; cleft palate; proliferative retinopathy
Review for gene: LRRC32 was set to AMBER
Added comment: Three individuals from two consanguineous families segregated the same homozygous bi-allelic variant, c.1630C>T; p.(Arg544Ter), shared haplotype indicative of founder effect. Mouse model has cleft palate and neonatal death.
Sources: Literature
Mendeliome v0.2582 LRRC32 Zornitza Stark Marked gene: LRRC32 as ready
Mendeliome v0.2582 LRRC32 Zornitza Stark Gene: lrrc32 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2582 LRRC32 Zornitza Stark Classified gene: LRRC32 as Amber List (moderate evidence)
Mendeliome v0.2582 LRRC32 Zornitza Stark Gene: lrrc32 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2581 LRRC32 Zornitza Stark gene: LRRC32 was added
gene: LRRC32 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LRRC32 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRRC32 were set to 30976112
Phenotypes for gene: LRRC32 were set to Intellectual disability; cleft palate; proliferative retinopathy
Review for gene: LRRC32 was set to AMBER
Added comment: Three individuals from two consanguineous families segregated the same homozygous bi-allelic variant, c.1630C>T; p.(Arg544Ter), shared haplotype indicative of founder effect. Mouse model has cleft palate and neonatal death.
Sources: Literature
Mendeliome v0.2580 KIF12 Ee Ming Wong gene: KIF12 was added
gene: KIF12 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KIF12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF12 were set to PMID: 30250217; 30976738
Phenotypes for gene: KIF12 were set to Prenatal cholestasis; High Gamma-Glutamyltransferase (GGT)
Review for gene: KIF12 was set to AMBER
gene: KIF12 was marked as current diagnostic
Added comment: > 3 unrelated families,but they are all consanguineous families
Sources: Literature
Paroxysmal Dyskinesia v0.10 GCH1 Eunice Chan commented on gene: GCH1
Paroxysmal Dyskinesia v0.10 GCH1 Eunice Chan gene: GCH1 was added
gene: GCH1 was added to Paroxysmal Dyskinesia. Sources: Literature
Mode of inheritance for gene: GCH1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: GCH1 were set to Dopa-responsive dystonia; exercise-induced dystonia
Aortopathy_Connective Tissue Disorders v0.23 SMAD4 Zornitza Stark Marked gene: SMAD4 as ready
Aortopathy_Connective Tissue Disorders v0.23 SMAD4 Zornitza Stark Gene: smad4 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.23 SMAD4 Zornitza Stark Classified gene: SMAD4 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.23 SMAD4 Zornitza Stark Gene: smad4 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.22 SMAD4 Zornitza Stark gene: SMAD4 was added
gene: SMAD4 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: SMAD4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMAD4 were set to 30809044
Phenotypes for gene: SMAD4 were set to Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, MIM# 175050; Thoracic aortic aneurysm
Review for gene: SMAD4 was set to GREEN
Added comment: SMAD4 pathogenic variants cause juvenile polyposis (JPS) and hereditary hemorrhagic telangiectasia (HHT), and 40% of affected individuals also have thoracic aortic disease. Three individuals recently reported with rare/novel missense and isolated thoracic aortic aneurysm.
Sources: Literature
Paroxysmal Dyskinesia v0.10 DLAT Eunice Chan edited their review of gene: DLAT: Changed publications: McWilliam et al. 2010. Eur J Paediatr Neurol 14(4):349-53 (PMID: 2002, 2530), Friedman J et al. 2017. Neurology 89: 2297-2298 (PMID:; Changed phenotypes: Episodic dystonia (Exercise induced or without clear trigger)
Paroxysmal Dyskinesia v0.10 PDHX Eunice Chan commented on gene: PDHX: PDX1 deficiency
Paroxysmal Dyskinesia v0.10 DLAT Eunice Chan gene: DLAT was added
gene: DLAT was added to Paroxysmal Dyskinesia. Sources: Literature
Mode of inheritance for gene: DLAT was set to BIALLELIC, autosomal or pseudoautosomal
Added comment: Also known as pyruvate dehydrogenase E2 deficiency
Sources: Literature
Bardet Biedl syndrome v0.26 SCAPER Zornitza Stark Marked gene: SCAPER as ready
Bardet Biedl syndrome v0.26 SCAPER Zornitza Stark Gene: scaper has been classified as Green List (High Evidence).
Bardet Biedl syndrome v0.26 SCAPER Zornitza Stark Classified gene: SCAPER as Green List (high evidence)
Bardet Biedl syndrome v0.26 SCAPER Zornitza Stark Gene: scaper has been classified as Green List (High Evidence).
Paroxysmal Dyskinesia v0.10 PDHX Eunice Chan reviewed gene: PDHX: Rating: ; Mode of pathogenicity: None; Publications: Schiff et al 2006 Ann Neurol 59(4):709-14 (PMID: 1656, 6017); Phenotypes: Paroxysmal dyskinesia (exercise induced or without clear trigger, isolated or with additional features), mitochondrial disorder (Leigh syndrome, ataxia), neurodevelopmental disability, epilepsy.; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bardet Biedl syndrome v0.25 SCAPER Zornitza Stark gene: SCAPER was added
gene: SCAPER was added to Bardet Biedl syndrome. Sources: Literature
Mode of inheritance for gene: SCAPER was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCAPER were set to 30723319; 28794130; 31069901; 31192531; 30723319
Phenotypes for gene: SCAPER were set to Intellectual developmental disorder and retinitis pigmentosa, OMIM #618195; Bardet-Biedl syndrome
Review for gene: SCAPER was set to GREEN
Added comment: Two distantly related consanguineous families reported plus note some of the individuals in the preceding papers had a BBS phenotype. Functional data to associate SCAPER with ciliary dynamics and disassembly.
Sources: Literature
Paroxysmal Dyskinesia v0.10 PDHX Eunice Chan gene: PDHX was added
gene: PDHX was added to Paroxysmal Dyskinesia. Sources: Literature
Mode of inheritance for gene: PDHX was set to Other
Paroxysmal Dyskinesia v0.10 PDHA1 Eunice Chan gene: PDHA1 was added
gene: PDHA1 was added to Paroxysmal Dyskinesia. Sources: Expert Review
Mode of inheritance for gene: PDHA1 was set to Other
Publications for gene: PDHA1 were set to Barnerias C et al. 2010 Dev Med Child Neurol. 52:e1-e9 (PMID: 2000; 2125); Patel et al. 2012 Mol Genet Metab 105(1):34-43 (PMID: 2207; 9328)
Phenotypes for gene: PDHA1 were set to Paroxysmal dyskinesia (exercise induced or without clear trigger; isolated or with additional features); mitochondrial disorder (Leigh syndrome, ataxia); neurodevelopmental disability; epilepsy.
Added comment: Phenotype can be quite broad
XLR inheritance - phenotype in females dependent on X-chromosome inactivation patterns

May respond to thiamine supplementation
Sources: Expert Review
Mendeliome v0.2580 CSGALNACT1 Zornitza Stark Publications for gene: CSGALNACT1 were set to
Mendeliome v0.2579 CSGALNACT1 Zornitza Stark reviewed gene: CSGALNACT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31705726, 31325655; Phenotypes: Congenital disorder of glycosylation, skeletal dysplasia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.46 CSGALNACT1 Zornitza Stark Classified gene: CSGALNACT1 as Green List (high evidence)
Congenital Disorders of Glycosylation v0.46 CSGALNACT1 Zornitza Stark Gene: csgalnact1 has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v0.45 CSGALNACT1 Zornitza Stark gene: CSGALNACT1 was added
gene: CSGALNACT1 was added to Congenital Disorders of Glycosylation. Sources: Literature
Mode of inheritance for gene: CSGALNACT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CSGALNACT1 were set to 31705726; 31325655
Phenotypes for gene: CSGALNACT1 were set to Congenital disorder of glycosylation; skeletal dysplasia
Review for gene: CSGALNACT1 was set to GREEN
Added comment: Four unrelated families reported.
Sources: Literature
Mendeliome v0.2579 UBAP1 Zornitza Stark Phenotypes for gene: UBAP1 were changed from Spastic paraplegia 80, autosomal dominant 618418 to Childhood-onset hereditary spastic paraplegia; Spastic paraplegia 80, autosomal dominant 618418
Mendeliome v0.2578 UBAP1 Zornitza Stark Publications for gene: UBAP1 were set to 31203368
Mendeliome v0.2577 UBAP1 Zornitza Stark reviewed gene: UBAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31696996; Phenotypes: Childhood-onset hereditary spastic paraplegia, Spastic paraplegia 80, autosomal dominant 618418; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Paroxysmal Dyskinesia v0.10 ECHS1 Eunice Chan gene: ECHS1 was added
gene: ECHS1 was added to Paroxysmal Dyskinesia. Sources: Literature
Mode of inheritance for gene: ECHS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ECHS1 were set to Olgiati S, Skorvanek M, Quadri M, et al. Paroxysmal exercise-induced dystonia within the phenotypic spectrum of ECHS1 deficiency. Mov Disord 2016; 31:1041–8 (PMID: 2709; 0768); Mahajan A, Constantinou J, Sidiropoulos C. ECHS1 deficiency-associated paroxysmal exercise-induced dyskinesias: case presentation and initial benefit of intervention. J Neurol 2017; 264:185–7. (PMID: 2803; 9521)
Phenotypes for gene: ECHS1 were set to early onset Leigh syndrome; later onset Leigh-like syndrome; paroxysmal dyskinesia (isolated or with other features of a mitochondrial disease)
Added comment: PxD phenotype
- intermittent episodes of long-duration dystonia or episodes of dystonia induced by sustained exercise
Sources: Literature
Hereditary Spastic Paraplegia v0.81 UBAP1 Zornitza Stark Marked gene: UBAP1 as ready
Hereditary Spastic Paraplegia v0.81 UBAP1 Zornitza Stark Gene: ubap1 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v0.81 UBAP1 Zornitza Stark Classified gene: UBAP1 as Green List (high evidence)
Hereditary Spastic Paraplegia v0.81 UBAP1 Zornitza Stark Gene: ubap1 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v0.80 UBAP1 Zornitza Stark gene: UBAP1 was added
gene: UBAP1 was added to Hereditary Spastic Paraplegia - paediatric. Sources: Literature
Mode of inheritance for gene: UBAP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: UBAP1 were set to 31696996
Phenotypes for gene: UBAP1 were set to Childhood-onset hereditary spastic paraplegia; Spastic paraplegia 80, autosomal dominant 618418
Mode of pathogenicity for gene: UBAP1 was set to Other
Review for gene: UBAP1 was set to GREEN
Added comment: Five unrelated families reported with childhood-onset HSP. A recurrent two‐base pair deletion (c.426_427delGA, p.K143Sfs*15) in the UBAP1 gene was found in four families, and a similar variant (c.475_476delTT, p.F159*) was detected in a fifth family. The variant was confirmed to be de novo in two families and inherited from an affected parent in two other families. RNA studies performed in lymphocytes from one patient with the de novo c.426_427delGA variant demonstrated escape of nonsense‐mediated decay of the UBAP1 mutant transcript, suggesting the generation of a truncated protein. Both variants identified are predicted to result in truncated proteins losing the capacity of binding to ubiquitinated proteins, hence appearing to exhibit a dominant‐negative effect on the normal function of the endosome‐specific endosomal sorting complexes required for the transport‐I complex.
Sources: Literature
Paroxysmal Dyskinesia v0.10 PNKD Eunice Chan commented on gene: PNKD
Mendeliome v0.2577 RHOA Zornitza Stark Phenotypes for gene: RHOA were changed from normal cognition; leukoencephalopathy; micro-ophthalmia; strabismus; linear hypopigmentation; malar hypoplasia; downslanting palpebral fissures; microstomia to normal cognition; leukoencephalopathy; micro-ophthalmia; strabismus; linear hypopigmentation; malar hypoplasia; downslanting palpebral fissures; microstomia; dental anomalies; body asymmetry; limb length discrepancy
Mendeliome v0.2576 RHOA Zornitza Stark Publications for gene: RHOA were set to 31570889
Mendeliome v0.2575 RHOA Zornitza Stark reviewed gene: RHOA: Rating: GREEN; Mode of pathogenicity: None; Publications: 31821646; Phenotypes: hypopigmented areas of the skin, dental anomalies, body asymmetry, limb length discrepancy, MRI abnormalities; Mode of inheritance: Other
Intellectual disability syndromic and non-syndromic v0.2586 NTNG2 Zornitza Stark edited their review of gene: NTNG2: Changed phenotypes: Intellectual disability, autism, dysmorphic features, Neurodevelopmental disorder with behavioral abnormalities, absent speech, and hypotonia, MIM# 618718
Intellectual disability syndromic and non-syndromic v0.2586 NTNG2 Zornitza Stark Publications for gene: NTNG2 were set to 31668703
Intellectual disability syndromic and non-syndromic v0.2585 NTNG2 Zornitza Stark edited their review of gene: NTNG2: Added comment: Two more families reported, phenotype described as Rett-like. Both families had same homozygous frameshift mutation (chr9:135073515, c.376dupT, p.(Ser126PhefsTer241).; Changed publications: 31668703, 31692205
Intellectual disability syndromic and non-syndromic v0.2585 TAF1 Zornitza Stark Marked gene: TAF1 as ready
Intellectual disability syndromic and non-syndromic v0.2585 TAF1 Zornitza Stark Gene: taf1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2585 TAF1 Zornitza Stark Phenotypes for gene: TAF1 were changed from to Mental retardation, X-linked, syndromic 33, MIM# 300966
Intellectual disability syndromic and non-syndromic v0.2584 TAF1 Zornitza Stark Publications for gene: TAF1 were set to
Intellectual disability syndromic and non-syndromic v0.2583 TAF1 Zornitza Stark Mode of inheritance for gene: TAF1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2582 TAF1 Zornitza Stark reviewed gene: TAF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31646703; Phenotypes: Mental retardation, X-linked, syndromic 33, MIM# 300966; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Genetic Epilepsy v0.683 SCN1A Zornitza Stark Marked gene: SCN1A as ready
Genetic Epilepsy v0.683 SCN1A Zornitza Stark Gene: scn1a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.683 SCN1A Zornitza Stark Phenotypes for gene: SCN1A were changed from to Epilepsy, generalized, with febrile seizures plus, type 2 604403; Epileptic encephalopathy, early infantile, 6 (Dravet syndrome) 607208; Febrile seizures, familial, 3A 604403
Genetic Epilepsy v0.682 SCN1A Zornitza Stark Mode of inheritance for gene: SCN1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.681 SCN1A Zornitza Stark reviewed gene: SCN1A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Epilepsy, generalized, with febrile seizures plus, type 2 604403, Epileptic encephalopathy, early infantile, 6 (Dravet syndrome) 607208, Febrile seizures, familial, 3A 604403; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2575 IQCE Zornitza Stark Marked gene: IQCE as ready
Mendeliome v0.2575 IQCE Zornitza Stark Gene: iqce has been classified as Green List (High Evidence).
Mendeliome v0.2575 IQCE Zornitza Stark Classified gene: IQCE as Green List (high evidence)
Mendeliome v0.2575 IQCE Zornitza Stark Gene: iqce has been classified as Green List (High Evidence).
Mendeliome v0.2574 IQCE Zornitza Stark gene: IQCE was added
gene: IQCE was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: IQCE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IQCE were set to 31549751; 28488682
Phenotypes for gene: IQCE were set to Postaxial polydactyly
Review for gene: IQCE was set to GREEN
Added comment: Four families reported with bi-allelic variants in this gene. The c.895_904del (p.Val301Serfs*8) was found in three of the families without sharing a common haplotype, suggesting a recurrent mechanism. RNA expression analysis on patients’ fibroblasts showed that the dysfunction of IQCE leads to the dysregulation of genes associated with the hedgehog‐signaling pathway, and zebrafish experiments demonstrated a full spectrum of phenotypes linked to defective cilia: Body curvature, kidney cysts, left–right asymmetry, misdirected cilia in the pronephric duct, and retinal defects.
Sources: Literature
Polydactyly v0.21 IQCE Zornitza Stark Marked gene: IQCE as ready
Polydactyly v0.21 IQCE Zornitza Stark Gene: iqce has been classified as Green List (High Evidence).
Polydactyly v0.21 IQCE Zornitza Stark Classified gene: IQCE as Green List (high evidence)
Polydactyly v0.21 IQCE Zornitza Stark Gene: iqce has been classified as Green List (High Evidence).
Polydactyly v0.20 IQCE Zornitza Stark gene: IQCE was added
gene: IQCE was added to Polydactyly. Sources: Literature
Mode of inheritance for gene: IQCE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IQCE were set to 31549751; 28488682
Phenotypes for gene: IQCE were set to Postaxial polydactyly
Review for gene: IQCE was set to GREEN
Added comment: Four families reported with bi-allelic variants in this gene. The c.895_904del (p.Val301Serfs*8) was found in three of the families without sharing a common haplotype, suggesting a recurrent mechanism. RNA expression analysis on patients’ fibroblasts showed that the dysfunction of IQCE leads to the dysregulation of genes associated with the hedgehog‐signaling pathway, and zebrafish experiments demonstrated a full spectrum of phenotypes linked to defective cilia: Body curvature, kidney cysts, left–right asymmetry, misdirected cilia in the pronephric duct, and retinal defects.
Sources: Literature
Mendeliome v0.2573 NKX2-3 Zornitza Stark Marked gene: NKX2-3 as ready
Mendeliome v0.2573 NKX2-3 Zornitza Stark Gene: nkx2-3 has been classified as Red List (Low Evidence).
Mendeliome v0.2573 NKX2-3 Zornitza Stark gene: NKX2-3 was added
gene: NKX2-3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NKX2-3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NKX2-3 were set to 31498527
Phenotypes for gene: NKX2-3 were set to Intestinal varicosities
Review for gene: NKX2-3 was set to RED
Added comment: Single multiplex family where truncating variant in this gene segregated with intestinal varicosities with a LOD score of 3.3. NKX2‐3 is a component of a molecular pathway underlying spleen and gut vasculature development in mice.
Sources: Literature
Mendeliome v0.2572 RPSA Zornitza Stark changed review comment from: Four families reported with mono allelic variants and idiopathic intestinal varies.; to: Four families reported with mono allelic variants and idiopathic intestinal varies, often in combination with asplenia.
Mendeliome v0.2572 RPSA Zornitza Stark Marked gene: RPSA as ready
Mendeliome v0.2572 RPSA Zornitza Stark Gene: rpsa has been classified as Green List (High Evidence).
Mendeliome v0.2572 RPSA Zornitza Stark Phenotypes for gene: RPSA were changed from to Asplenia, isolated congenital 271400; Idiopathic intestinal varices
Mendeliome v0.2571 RPSA Zornitza Stark Publications for gene: RPSA were set to
Mendeliome v0.2570 RPSA Zornitza Stark Mode of inheritance for gene: RPSA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2569 RPSA Zornitza Stark reviewed gene: RPSA: Rating: GREEN; Mode of pathogenicity: None; Publications: 23579497, 31498527; Phenotypes: Asplenia, isolated congenital 271400, Idiopathic intestinal varices; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2569 TBX6 Zornitza Stark Phenotypes for gene: TBX6 were changed from to Skeletal dysplasia; spondylocostal dysostosis; congenital scoliosis
Mendeliome v0.2568 TBX6 Zornitza Stark Publications for gene: TBX6 were set to
Mitochondrial disease v0.438 CRAT Zornitza Stark Marked gene: CRAT as ready
Mitochondrial disease v0.438 CRAT Zornitza Stark Gene: crat has been classified as Amber List (Moderate Evidence).
Mitochondrial disease v0.438 CRAT Zornitza Stark Classified gene: CRAT as Amber List (moderate evidence)
Mitochondrial disease v0.438 CRAT Zornitza Stark Gene: crat has been classified as Amber List (Moderate Evidence).
Mitochondrial disease v0.437 CRAT Zornitza Stark gene: CRAT was added
gene: CRAT was added to Mitochondrial disease. Sources: Literature
Mode of inheritance for gene: CRAT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CRAT were set to 29395073; 31448845
Phenotypes for gene: CRAT were set to Neurodegeneration with brain iron accumulation 8, MIM# 617917; Leigh syndrome
Review for gene: CRAT was set to AMBER
Added comment: Two unrelated families reported with bi-allelic variants, one with NBIA and one with Leigh syndrome phenotype.
Sources: Literature
Regression v0.116 CRAT Zornitza Stark Marked gene: CRAT as ready
Regression v0.116 CRAT Zornitza Stark Gene: crat has been classified as Amber List (Moderate Evidence).
Regression v0.116 CRAT Zornitza Stark Classified gene: CRAT as Amber List (moderate evidence)
Regression v0.116 CRAT Zornitza Stark Gene: crat has been classified as Amber List (Moderate Evidence).
Regression v0.115 CRAT Zornitza Stark gene: CRAT was added
gene: CRAT was added to Regression. Sources: Literature
Mode of inheritance for gene: CRAT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CRAT were set to 29395073; 31448845
Phenotypes for gene: CRAT were set to Neurodegeneration with brain iron accumulation 8, MIM# 617917; Leigh syndrome
Review for gene: CRAT was set to AMBER
Added comment: Two unrelated families reported with bi-allelic variants, one with NBIA and one with Leigh syndrome phenotype.
Sources: Literature
Mendeliome v0.2567 CRAT Zornitza Stark Marked gene: CRAT as ready
Mendeliome v0.2567 CRAT Zornitza Stark Gene: crat has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2567 CRAT Zornitza Stark Classified gene: CRAT as Amber List (moderate evidence)
Mendeliome v0.2567 CRAT Zornitza Stark Gene: crat has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2566 CRAT Zornitza Stark gene: CRAT was added
gene: CRAT was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CRAT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CRAT were set to 29395073; 31448845
Phenotypes for gene: CRAT were set to Neurodegeneration with brain iron accumulation 8, MIM# 617917; Leigh syndrome
Review for gene: CRAT was set to AMBER
Added comment: Two unrelated families reported with bi-allelic variants, one with NBIA and one with Leigh syndrome phenotype.
Sources: Literature
Genetic Epilepsy v0.681 KCNB1 Zornitza Stark Marked gene: KCNB1 as ready
Genetic Epilepsy v0.681 KCNB1 Zornitza Stark Gene: kcnb1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.681 KCNB1 Zornitza Stark Phenotypes for gene: KCNB1 were changed from to Epileptic encephalopathy, early infantile, 26, MIM# 616056
Genetic Epilepsy v0.680 KCNB1 Zornitza Stark Publications for gene: KCNB1 were set to
Genetic Epilepsy v0.679 KCNB1 Zornitza Stark Mode of inheritance for gene: KCNB1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.678 KCNB1 Zornitza Stark reviewed gene: KCNB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31600826, 31513310; Phenotypes: Epileptic encephalopathy, early infantile, 26, MIM# 616056; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2582 KCNB1 Zornitza Stark Marked gene: KCNB1 as ready
Intellectual disability syndromic and non-syndromic v0.2582 KCNB1 Zornitza Stark Gene: kcnb1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2582 KCNB1 Zornitza Stark Phenotypes for gene: KCNB1 were changed from to Epileptic encephalopathy, early infantile, 26, MIM# 616056
Intellectual disability syndromic and non-syndromic v0.2581 KCNB1 Zornitza Stark Publications for gene: KCNB1 were set to
Intellectual disability syndromic and non-syndromic v0.2580 KCNB1 Zornitza Stark Mode of inheritance for gene: KCNB1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2579 KCNB1 Zornitza Stark reviewed gene: KCNB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31600826, 31513310; Phenotypes: Epileptic encephalopathy, early infantile, 26, MIM# 616056; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Optic Atrophy v0.105 Bryony Thompson Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Optic Atrophy v0.104 KLC2 Bryony Thompson Marked gene: KLC2 as ready
Optic Atrophy v0.104 KLC2 Bryony Thompson Gene: klc2 has been classified as Green List (High Evidence).
Optic Atrophy v0.104 KLC2 Bryony Thompson Classified gene: KLC2 as Green List (high evidence)
Optic Atrophy v0.104 KLC2 Bryony Thompson Added comment: Comment on list classification: Only reported cause of condition is the upstream large deletion, which is not detected by whole-exome sequencing.
Optic Atrophy v0.104 KLC2 Bryony Thompson Gene: klc2 has been classified as Green List (High Evidence).
Optic Atrophy v0.103 KLC2 Bryony Thompson gene: KLC2 was added
gene: KLC2 was added to Optic Atrophy. Sources: Literature
SV/CNV tags were added to gene: KLC2.
Mode of inheritance for gene: KLC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KLC2 were set to 26385635
Phenotypes for gene: KLC2 were set to Spastic paraplegia, optic atrophy, and neuropathy MIM#609541
Review for gene: KLC2 was set to GREEN
Added comment: In 73 Brazilian patients and 2 sibs of Egyptian descent with SPOAN, a homozygous 216-bp deletion in the noncoding upstream region of the KLC2 gene was identified. Optic atrophy is a feature of the condition.
Sources: Literature
Cerebellar and Pontocerebellar Hypoplasia v0.53 BCL11A Zornitza Stark Marked gene: BCL11A as ready
Cerebellar and Pontocerebellar Hypoplasia v0.53 BCL11A Zornitza Stark Gene: bcl11a has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.53 BCL11A Zornitza Stark Phenotypes for gene: BCL11A were changed from to Dias-Logan syndrome, MIM# 617101
Cerebellar and Pontocerebellar Hypoplasia v0.52 BCL11A Zornitza Stark Publications for gene: BCL11A were set to
Cerebellar and Pontocerebellar Hypoplasia v0.51 BCL11A Zornitza Stark Mode of inheritance for gene: BCL11A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebellar and Pontocerebellar Hypoplasia v0.50 TUBB Zornitza Stark Marked gene: TUBB as ready
Cerebellar and Pontocerebellar Hypoplasia v0.50 TUBB Zornitza Stark Gene: tubb has been classified as Amber List (Moderate Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.50 TUBB Zornitza Stark Classified gene: TUBB as Amber List (moderate evidence)
Cerebellar and Pontocerebellar Hypoplasia v0.50 TUBB Zornitza Stark Gene: tubb has been classified as Amber List (Moderate Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.49 CACNA1G Zornitza Stark Marked gene: CACNA1G as ready
Cerebellar and Pontocerebellar Hypoplasia v0.49 CACNA1G Zornitza Stark Gene: cacna1g has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.49 CACNA1G Zornitza Stark Classified gene: CACNA1G as Green List (high evidence)
Cerebellar and Pontocerebellar Hypoplasia v0.49 CACNA1G Zornitza Stark Gene: cacna1g has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.48 TRAPPC6B Zornitza Stark Marked gene: TRAPPC6B as ready
Cerebellar and Pontocerebellar Hypoplasia v0.48 TRAPPC6B Zornitza Stark Gene: trappc6b has been classified as Red List (Low Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.48 TRAPPC6B Zornitza Stark Phenotypes for gene: TRAPPC6B were changed from to Neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy (MIM#617862)
Cerebellar and Pontocerebellar Hypoplasia v0.47 TRAPPC6B Zornitza Stark Publications for gene: TRAPPC6B were set to
Cerebellar and Pontocerebellar Hypoplasia v0.46 TRAPPC6B Zornitza Stark Mode of inheritance for gene: TRAPPC6B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cerebellar and Pontocerebellar Hypoplasia v0.45 TRAPPC6B Zornitza Stark Classified gene: TRAPPC6B as Red List (low evidence)
Cerebellar and Pontocerebellar Hypoplasia v0.45 TRAPPC6B Zornitza Stark Gene: trappc6b has been classified as Red List (Low Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.44 CEP55 Zornitza Stark Marked gene: CEP55 as ready
Cerebellar and Pontocerebellar Hypoplasia v0.44 CEP55 Zornitza Stark Gene: cep55 has been classified as Amber List (Moderate Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.44 CEP55 Zornitza Stark Phenotypes for gene: CEP55 were changed from to Multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly 236500
Cerebellar and Pontocerebellar Hypoplasia v0.43 CEP55 Zornitza Stark Publications for gene: CEP55 were set to
Cerebellar and Pontocerebellar Hypoplasia v0.42 CEP55 Zornitza Stark Mode of inheritance for gene: CEP55 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cerebellar and Pontocerebellar Hypoplasia v0.41 CEP55 Zornitza Stark Classified gene: CEP55 as Amber List (moderate evidence)
Cerebellar and Pontocerebellar Hypoplasia v0.41 CEP55 Zornitza Stark Gene: cep55 has been classified as Amber List (Moderate Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.40 TMEM5 Zornitza Stark Marked gene: TMEM5 as ready
Cerebellar and Pontocerebellar Hypoplasia v0.40 TMEM5 Zornitza Stark Gene: tmem5 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.40 TMEM5 Zornitza Stark Classified gene: TMEM5 as Green List (high evidence)
Cerebellar and Pontocerebellar Hypoplasia v0.40 TMEM5 Zornitza Stark Gene: tmem5 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.39 TINF2 Zornitza Stark Marked gene: TINF2 as ready
Cerebellar and Pontocerebellar Hypoplasia v0.39 TINF2 Zornitza Stark Gene: tinf2 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.39 TINF2 Zornitza Stark Classified gene: TINF2 as Green List (high evidence)
Cerebellar and Pontocerebellar Hypoplasia v0.39 TINF2 Zornitza Stark Gene: tinf2 has been classified as Green List (High Evidence).
Mendeliome v0.2565 CWF19L1 Zornitza Stark Marked gene: CWF19L1 as ready
Mendeliome v0.2565 CWF19L1 Zornitza Stark Gene: cwf19l1 has been classified as Green List (High Evidence).
Mendeliome v0.2565 CWF19L1 Zornitza Stark Phenotypes for gene: CWF19L1 were changed from to Spinocerebellar ataxia, autosomal recessive 17, MIM#616127; intellectual disability, developmental delay
Mendeliome v0.2564 CWF19L1 Zornitza Stark Publications for gene: CWF19L1 were set to
Mendeliome v0.2563 CWF19L1 Zornitza Stark Mode of inheritance for gene: CWF19L1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2562 CWF19L1 Zornitza Stark reviewed gene: CWF19L1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25361784, 15981765, 26197978, 27016154, 30167849; Phenotypes: Spinocerebellar ataxia, autosomal recessive 17, MIM#616127, intellectual disability, developmental delay; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebellar and Pontocerebellar Hypoplasia v0.38 CWF19L1 Zornitza Stark Marked gene: CWF19L1 as ready
Cerebellar and Pontocerebellar Hypoplasia v0.38 CWF19L1 Zornitza Stark Gene: cwf19l1 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.38 CWF19L1 Zornitza Stark Classified gene: CWF19L1 as Green List (high evidence)
Cerebellar and Pontocerebellar Hypoplasia v0.38 CWF19L1 Zornitza Stark Gene: cwf19l1 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.41 AHI1 Zornitza Stark Marked gene: AHI1 as ready
Polymicrogyria and Schizencephaly v0.41 AHI1 Zornitza Stark Gene: ahi1 has been classified as Amber List (Moderate Evidence).
Polymicrogyria and Schizencephaly v0.41 AHI1 Zornitza Stark Phenotypes for gene: AHI1 were changed from to Joubert syndrome 3, MIM# 608629
Polymicrogyria and Schizencephaly v0.40 AHI1 Zornitza Stark Publications for gene: AHI1 were set to
Polymicrogyria and Schizencephaly v0.39 AHI1 Zornitza Stark Mode of inheritance for gene: AHI1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polymicrogyria and Schizencephaly v0.38 AHI1 Zornitza Stark Classified gene: AHI1 as Amber List (moderate evidence)
Polymicrogyria and Schizencephaly v0.38 AHI1 Zornitza Stark Gene: ahi1 has been classified as Amber List (Moderate Evidence).
Polymicrogyria and Schizencephaly v0.37 ASTN1 Zornitza Stark Marked gene: ASTN1 as ready
Polymicrogyria and Schizencephaly v0.37 ASTN1 Zornitza Stark Gene: astn1 has been classified as Amber List (Moderate Evidence).
Polymicrogyria and Schizencephaly v0.37 ASTN1 Zornitza Stark Phenotypes for gene: ASTN1 were changed from to Polymicrogyria; hypoplastic corpus callosum
Polymicrogyria and Schizencephaly v0.36 ASTN1 Zornitza Stark Publications for gene: ASTN1 were set to
Polymicrogyria and Schizencephaly v0.35 ASTN1 Zornitza Stark Mode of inheritance for gene: ASTN1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polymicrogyria and Schizencephaly v0.34 ASTN1 Zornitza Stark Classified gene: ASTN1 as Amber List (moderate evidence)
Polymicrogyria and Schizencephaly v0.34 ASTN1 Zornitza Stark Gene: astn1 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v0.11 B4GAT1 Zornitza Stark Classified gene: B4GAT1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.11 B4GAT1 Zornitza Stark Gene: b4gat1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.10 B4GAT1 Zornitza Stark changed review comment from: Two families reported.; to: Two families reported and two animal models.
Muscular dystrophy and myopathy_Paediatric v0.10 B4GAT1 Zornitza Stark edited their review of gene: B4GAT1: Changed rating: GREEN; Changed publications: 23359570, 23877401, 23359570, 23217742
Mendeliome v0.2562 B4GAT1 Zornitza Stark Classified gene: B4GAT1 as Green List (high evidence)
Mendeliome v0.2562 B4GAT1 Zornitza Stark Gene: b4gat1 has been classified as Green List (High Evidence).
Mendeliome v0.2561 B4GAT1 Zornitza Stark changed review comment from: Two families reported.; to: Two families reported and two animal models.
Mendeliome v0.2561 B4GAT1 Zornitza Stark edited their review of gene: B4GAT1: Changed rating: GREEN; Changed publications: 23359570, 23877401, 23359570, 23217742
Callosome v0.134 B4GAT1 Zornitza Stark edited their review of gene: B4GAT1: Changed rating: GREEN
Callosome v0.134 B4GAT1 Zornitza Stark changed review comment from: Two families reported.; to: Two families reported and two animal models.
Callosome v0.134 B4GAT1 Zornitza Stark Publications for gene: B4GAT1 were set to 23359570; 23877401; 23359570; 23217742
Arthrogryposis v0.46 B4GAT1 Zornitza Stark Publications for gene: B4GAT1 were set to 23359570; 23877401
Arthrogryposis v0.45 B4GAT1 Zornitza Stark Classified gene: B4GAT1 as Green List (high evidence)
Arthrogryposis v0.45 B4GAT1 Zornitza Stark Gene: b4gat1 has been classified as Green List (High Evidence).
Arthrogryposis v0.44 B4GAT1 Zornitza Stark changed review comment from: Two families reported.; to: Two families and two animal models.
Callosome v0.133 B4GAT1 Zornitza Stark Publications for gene: B4GAT1 were set to 23359570; 23877401; 23359570; 23217742
Arthrogryposis v0.44 B4GAT1 Zornitza Stark edited their review of gene: B4GAT1: Changed rating: GREEN; Changed publications: 23359570, 23877401, 23359570, 23217742
Callosome v0.132 B4GAT1 Zornitza Stark Classified gene: B4GAT1 as Green List (high evidence)
Callosome v0.132 B4GAT1 Zornitza Stark Gene: b4gat1 has been classified as Green List (High Evidence).
Lissencephaly and Band Heterotopia v0.34 B4GAT1 Zornitza Stark Marked gene: B4GAT1 as ready
Lissencephaly and Band Heterotopia v0.34 B4GAT1 Zornitza Stark Gene: b4gat1 has been classified as Green List (High Evidence).
Callosome v0.132 B4GAT1 Zornitza Stark Publications for gene: B4GAT1 were set to 23359570; 23877401
Lissencephaly and Band Heterotopia v0.34 B4GAT1 Zornitza Stark Publications for gene: B4GAT1 were set to 23359570; 23877401
Lissencephaly and Band Heterotopia v0.34 B4GAT1 Zornitza Stark Classified gene: B4GAT1 as Green List (high evidence)
Lissencephaly and Band Heterotopia v0.34 B4GAT1 Zornitza Stark Gene: b4gat1 has been classified as Green List (High Evidence).
Lissencephaly and Band Heterotopia v0.33 B4GAT1 Zornitza Stark reviewed gene: B4GAT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23359570, 23877401, 23359570, 23217742; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 13 MIM# 615287; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Callosome v0.131 B4GAT1 Zornitza Stark Marked gene: B4GAT1 as ready
Callosome v0.131 B4GAT1 Zornitza Stark Gene: b4gat1 has been classified as Amber List (Moderate Evidence).
Callosome v0.131 B4GAT1 Zornitza Stark Phenotypes for gene: B4GAT1 were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 13 MIM# 615287
Callosome v0.130 B4GAT1 Zornitza Stark Publications for gene: B4GAT1 were set to
Callosome v0.129 B4GAT1 Zornitza Stark Mode of inheritance for gene: B4GAT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Callosome v0.128 B4GAT1 Zornitza Stark Classified gene: B4GAT1 as Amber List (moderate evidence)
Callosome v0.128 B4GAT1 Zornitza Stark Gene: b4gat1 has been classified as Amber List (Moderate Evidence).
Callosome v0.127 B4GAT1 Zornitza Stark reviewed gene: B4GAT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 23359570, 23877401; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 13 MIM# 615287; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.10 B4GAT1 Zornitza Stark Marked gene: B4GAT1 as ready
Muscular dystrophy and myopathy_Paediatric v0.10 B4GAT1 Zornitza Stark Gene: b4gat1 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v0.10 B4GAT1 Zornitza Stark Phenotypes for gene: B4GAT1 were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 13 MIM# 615287
Arthrogryposis v0.44 B4GAT1 Zornitza Stark Marked gene: B4GAT1 as ready
Arthrogryposis v0.44 B4GAT1 Zornitza Stark Gene: b4gat1 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v0.9 B4GAT1 Zornitza Stark Publications for gene: B4GAT1 were set to
Muscular dystrophy and myopathy_Paediatric v0.8 B4GAT1 Zornitza Stark Mode of inheritance for gene: B4GAT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.7 B4GAT1 Zornitza Stark Classified gene: B4GAT1 as Amber List (moderate evidence)
Muscular dystrophy and myopathy_Paediatric v0.7 B4GAT1 Zornitza Stark Gene: b4gat1 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.44 B4GAT1 Zornitza Stark Phenotypes for gene: B4GAT1 were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 13 MIM# 615287
Muscular dystrophy and myopathy_Paediatric v0.6 B4GAT1 Zornitza Stark reviewed gene: B4GAT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 23359570, 23877401; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 13 MIM# 615287; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2561 B4GAT1 Zornitza Stark Marked gene: B4GAT1 as ready
Mendeliome v0.2561 B4GAT1 Zornitza Stark Gene: b4gat1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2561 B4GAT1 Zornitza Stark Phenotypes for gene: B4GAT1 were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 13 MIM# 615287
Mendeliome v0.2560 B4GAT1 Zornitza Stark Publications for gene: B4GAT1 were set to
Mendeliome v0.2559 B4GAT1 Zornitza Stark Mode of inheritance for gene: B4GAT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2558 B4GAT1 Zornitza Stark Classified gene: B4GAT1 as Amber List (moderate evidence)
Mendeliome v0.2558 B4GAT1 Zornitza Stark Gene: b4gat1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2557 B4GAT1 Zornitza Stark reviewed gene: B4GAT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 23359570, 23877401; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 13 MIM# 615287; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.43 B4GAT1 Zornitza Stark Publications for gene: B4GAT1 were set to
Arthrogryposis v0.42 B4GAT1 Zornitza Stark Mode of inheritance for gene: B4GAT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.41 B4GAT1 Zornitza Stark Classified gene: B4GAT1 as Amber List (moderate evidence)
Arthrogryposis v0.41 B4GAT1 Zornitza Stark Gene: b4gat1 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.40 B4GAT1 Zornitza Stark reviewed gene: B4GAT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 23359570, 23877401; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 13 MIM# 615287; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Lissencephaly and Band Heterotopia v0.33 B4GAT1 Zornitza Stark Phenotypes for gene: B4GAT1 were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 13 MIM# 615287
Lissencephaly and Band Heterotopia v0.32 B4GAT1 Zornitza Stark Publications for gene: B4GAT1 were set to
Lissencephaly and Band Heterotopia v0.31 B4GAT1 Zornitza Stark Mode of inheritance for gene: B4GAT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Lissencephaly and Band Heterotopia v0.30 B4GAT1 Zornitza Stark Classified gene: B4GAT1 as Amber List (moderate evidence)
Lissencephaly and Band Heterotopia v0.30 B4GAT1 Zornitza Stark Gene: b4gat1 has been classified as Amber List (Moderate Evidence).
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v0.7 BRAF Zornitza Stark Marked gene: BRAF as ready
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v0.7 BRAF Zornitza Stark Gene: braf has been classified as Amber List (Moderate Evidence).
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v0.7 BRAF Zornitza Stark Phenotypes for gene: BRAF were changed from to RASopathies; Focal cortical dysplasia
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v0.6 BRAF Zornitza Stark Publications for gene: BRAF were set to
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v0.5 BRAF Zornitza Stark Mode of inheritance for gene: BRAF was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v0.4 BRAF Zornitza Stark Classified gene: BRAF as Amber List (moderate evidence)
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v0.4 BRAF Zornitza Stark Gene: braf has been classified as Amber List (Moderate Evidence).
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v0.3 BRAF Zornitza Stark Tag somatic tag was added to gene: BRAF.
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v0.3 BRAF Zornitza Stark reviewed gene: BRAF: Rating: AMBER; Mode of pathogenicity: None; Publications: 25356392; Phenotypes: Focal cortical dysplasia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2557 RSRC1 Zornitza Stark Classified gene: RSRC1 as Green List (high evidence)
Mendeliome v0.2557 RSRC1 Zornitza Stark Gene: rsrc1 has been classified as Green List (High Evidence).
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v0.3 BRAF Lauren Akesson reviewed gene: BRAF: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 18039946, 18039235; Phenotypes: RASopathies; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2556 THG1L Zornitza Stark changed review comment from: Five individuals from two Ashkenazi Jewish families with same homozygous missense variant, and another family ascertained through a large microcephaly cohort, also with SCA.
Sources: Literature; to: Four Ashkenazi Jewish families with same homozygous missense variant, and another family ascertained through a large microcephaly cohort, also with SCA. A carrier rate of 0.8%, but no THG1L V55A homozygotes, was found in a cohort of 3,232 unrelated Ashkenazi Jewish individuals, and no homozygotes found in Exac or gnomAD.
Sources: Literature
Mendeliome v0.2556 THG1L Zornitza Stark edited their review of gene: THG1L: Changed rating: GREEN; Changed phenotypes: Spinocerebellar ataxia, autosomal recessive 28, MIM# 618800
Mendeliome v0.2556 THG1L Zornitza Stark Marked gene: THG1L as ready
Mendeliome v0.2556 THG1L Zornitza Stark Gene: thg1l has been classified as Green List (High Evidence).
Mendeliome v0.2556 THG1L Zornitza Stark Classified gene: THG1L as Green List (high evidence)
Mendeliome v0.2556 THG1L Zornitza Stark Gene: thg1l has been classified as Green List (High Evidence).
Mendeliome v0.2555 THG1L Zornitza Stark Classified gene: THG1L as Amber List (moderate evidence)
Mendeliome v0.2555 THG1L Zornitza Stark Gene: thg1l has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2554 THG1L Zornitza Stark gene: THG1L was added
gene: THG1L was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: THG1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: THG1L were set to 27307223; 31168944; 30214071
Phenotypes for gene: THG1L were set to Spinocerebellar ataxia, autosomal recessive 28, MIM# 618800
Review for gene: THG1L was set to AMBER
Added comment: Five individuals from two Ashkenazi Jewish families with same homozygous missense variant, and another family ascertained through a large microcephaly cohort, also with SCA.
Sources: Literature
Mendeliome v0.2553 TRPV1 Zornitza Stark Marked gene: TRPV1 as ready
Mendeliome v0.2553 TRPV1 Zornitza Stark Gene: trpv1 has been classified as Red List (Low Evidence).
Mendeliome v0.2553 TRPV1 Zornitza Stark gene: TRPV1 was added
gene: TRPV1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TRPV1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRPV1 were set to 29930394
Phenotypes for gene: TRPV1 were set to Susceptibility to malignant hyperthermia
Review for gene: TRPV1 was set to RED
Added comment: Two individuals reported with rare/novel missense variants in this gene, some functional data.
Sources: Literature
Mendeliome v0.2552 ZP2 Zornitza Stark Marked gene: ZP2 as ready
Mendeliome v0.2552 ZP2 Zornitza Stark Gene: zp2 has been classified as Green List (High Evidence).