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Mendeliome v1.2204 RUNX1T1 Zornitza Stark Gene: runx1t1 has been classified as Green List (High Evidence).
Mendeliome v1.2204 RUNX1T1 Zornitza Stark Phenotypes for gene: RUNX1T1 were changed from Neurodevelopmental disorder MONDO:0700092 to Neurodevelopmental disorder MONDO:0700092, RUNX1T1-related
Mendeliome v1.2203 RUNX1T1 Zornitza Stark Publications for gene: RUNX1T1 were set to PMID: 39568205, 19172993, 22644616, 31223340
Mitochondrial disease v0.963 PDE12 Zornitza Stark Marked gene: PDE12 as ready
Mitochondrial disease v0.963 PDE12 Zornitza Stark Gene: pde12 has been classified as Green List (High Evidence).
Mitochondrial disease v0.963 PDE12 Zornitza Stark Phenotypes for gene: PDE12 were changed from Mitochondrial disease MONDO:0044970, PDE12-related to Mitochondrial disease MONDO:0044970, PDE12-related
Mitochondrial disease v0.962 PDE12 Zornitza Stark Phenotypes for gene: PDE12 were changed from Mitochondrial disease MONDO:0044970 to Mitochondrial disease MONDO:0044970, PDE12-related
Mitochondrial disease v0.961 PDE12 Zornitza Stark Classified gene: PDE12 as Green List (high evidence)
Mitochondrial disease v0.961 PDE12 Zornitza Stark Gene: pde12 has been classified as Green List (High Evidence).
Mendeliome v1.2202 PDE12 Zornitza Stark Marked gene: PDE12 as ready
Mendeliome v1.2202 PDE12 Zornitza Stark Gene: pde12 has been classified as Green List (High Evidence).
Mendeliome v1.2202 PDE12 Zornitza Stark Phenotypes for gene: PDE12 were changed from Mitochondrial disease MONDO:0044970 to Mitochondrial disease MONDO:0044970, PDE12-related
Dystonia - complex v0.262 NKX6-2 Zornitza Stark Marked gene: NKX6-2 as ready
Dystonia - complex v0.262 NKX6-2 Zornitza Stark Gene: nkx6-2 has been classified as Green List (High Evidence).
Dystonia - complex v0.262 NKX6-2 Zornitza Stark Phenotypes for gene: NKX6-2 were changed from Spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy 617560 to Spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy MIM#617560
Dystonia - complex v0.261 NKX6-2 Zornitza Stark Publications for gene: NKX6-2 were set to
Dystonia - complex v0.260 NPC1 Zornitza Stark Marked gene: NPC1 as ready
Dystonia - complex v0.260 NPC1 Zornitza Stark Gene: npc1 has been classified as Green List (High Evidence).
Dystonia - complex v0.260 NPC1 Zornitza Stark Phenotypes for gene: NPC1 were changed from Niemann-Pick disease type C1 to Niemann-Pick disease, type C1 MONDO:0009757
Dystonia - complex v0.259 NPC1 Zornitza Stark Publications for gene: NPC1 were set to
Dystonia - complex v0.258 NPC2 Zornitza Stark Marked gene: NPC2 as ready
Dystonia - complex v0.258 NPC2 Zornitza Stark Gene: npc2 has been classified as Green List (High Evidence).
Dystonia - complex v0.258 NPC2 Zornitza Stark Phenotypes for gene: NPC2 were changed from Niemann-Pick disease type C2; Dystonia to Niemann-Pick disease, type C2 MONDO:0011873; Dystonia
Dystonia - complex v0.257 NPC2 Zornitza Stark Publications for gene: NPC2 were set to
Dystonia - complex v0.256 PANK2 Zornitza Stark Marked gene: PANK2 as ready
Dystonia - complex v0.256 PANK2 Zornitza Stark Gene: pank2 has been classified as Green List (High Evidence).
Dystonia - complex v0.256 PANK2 Zornitza Stark Phenotypes for gene: PANK2 were changed from pantothenate kinase-associated neurodegeneration; Dystonia to pantothenate kinase-associated neurodegeneration MONDO:0009319; Dystonia
Dystonia - complex v0.255 PANK2 Zornitza Stark Publications for gene: PANK2 were set to
Dystonia - complex v0.254 PANK2 Sangavi Sivagnanasundram changed review comment from: Established gene-disease association with affected individuals presenting with generalised or lower limb dystonia.; to: Established gene-disease association with affected individuals presenting with generalised or lower limb dystonia along with other psychiatric/behavioural problems.
Dystonia - complex v0.254 PANK2 Sangavi Sivagnanasundram reviewed gene: PANK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 15911822; Phenotypes: pantothenate kinase-associated neurodegeneration MONDO:0009319; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia - complex v0.254 NPC2 Sangavi Sivagnanasundram reviewed gene: NPC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34993563, 17470133; Phenotypes: Niemann-Pick disease, type C2 MONDO:0011873; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia - complex v0.254 NPC1 Sangavi Sivagnanasundram reviewed gene: NPC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12555942, 20301473; Phenotypes: Niemann-Pick disease, type C1 MONDO:0009757; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia - complex v0.254 NKX6-2 Sangavi Sivagnanasundram reviewed gene: NKX6-2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30285346, 28575651, 28969374; Phenotypes: spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy MONDO:0033043; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2201 PDE12 Chirag Patel Classified gene: PDE12 as Green List (high evidence)
Mendeliome v1.2201 PDE12 Chirag Patel Gene: pde12 has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.113 CHUK Chirag Patel Classified gene: CHUK as Green List (high evidence)
Combined Immunodeficiency v1.113 CHUK Chirag Patel Gene: chuk has been classified as Green List (High Evidence).
Mendeliome v1.2200 CHUK Chirag Patel Classified gene: CHUK as Green List (high evidence)
Mendeliome v1.2200 CHUK Chirag Patel Gene: chuk has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.112 CHUK Chirag Patel reviewed gene: CHUK: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34533979; Phenotypes: Combined immunodeficiency, MONDO:0015131, CHUK-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2199 CHUK Chirag Patel reviewed gene: CHUK: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34533979; Phenotypes: Combined immunodeficiency, MONDO:0015131, CHUK-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2199 PDE12 Chirag Patel gene: PDE12 was added
gene: PDE12 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PDE12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDE12 were set to PMID: 39567835
Phenotypes for gene: PDE12 were set to Mitochondrial disease MONDO:0044970
Review for gene: PDE12 was set to GREEN
Added comment: 3 families (2 consanguineous) with 5 affected individuals with early onset mitochondrial disease presentation (3 liveborn, 2 intrauterine death).
-Family 1: 1 x infant death @3mths (no clinical information), 1 x 7yr old with neonatal respiratory and lactic acidosis, developmental delay, and mitochondrial respiratory chain deficiencies, and marked cytochrome c oxidase (COX) deficiency in muscle.
-Family 2: 1 x neonatal death @2days with metabolic acidosis and lactic acidosis, respiratory failure, lissencephaly, dysgenesis of the corpus callosum and extensive periventricular and subcortical cysts. Normal pyruvate dehydrogenase complex and electron
transfer chain activities in fibroblasts.
-Family 3: 2 x fetuses (13wks and 22wks) with increase nuchal translucency and reduced fetal movements. One had intra-uterine growth retardation, hydrops and cystic hygroma. The other had permanent flexion contractures of four limbs). Western blotting in fetal skeletal muscle showed absent respiratory chain complexes (I, IV, and V).

WES in all 3 families identified 3 different homozygous missense variants in PDE12 gene (p.Tyr155Cys, p.Gly372Glu, and p.Arg41Pro). All variants segregated with disease, were rare in gnomAD, and in silico pathogenicity prediction tools pointed towards a high likelihood of pathogenicity.

PDE12 gene encodes the poly(A)-specific exoribonuclease, involved in the quality control of mitochondrial non-coding RNAs. Patient-derived primary fibroblasts demonstrate diminished steady-state levels of PDE12 protein, whilst mitochondrial poly(A)-tail RNA sequencing revealed an accumulation of spuriously polyadenylated mitochondrial RNA, consistent with perturbed function of PDE12 protein.
Sources: Literature
Mendeliome v1.2198 RUNX1T1 Chirag Patel Classified gene: RUNX1T1 as Green List (high evidence)
Mendeliome v1.2198 RUNX1T1 Chirag Patel Gene: runx1t1 has been classified as Green List (High Evidence).
Mendeliome v1.2197 RUNX1T1 Chirag Patel gene: RUNX1T1 was added
gene: RUNX1T1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RUNX1T1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RUNX1T1 were set to PMID: 39568205, 19172993, 22644616, 31223340
Phenotypes for gene: RUNX1T1 were set to Neurodevelopmental disorder MONDO:0700092
Review for gene: RUNX1T1 was set to GREEN
Added comment: RUNX1T1 encodes a transcription regulator for hematopoietic genes and is well-known for its involvement in hematologic malignancies. Germline RUNX1T1 variants may also play a role in human congenital neurodevelopmental disorders.

PMID: 39568205
3 unrelated individuals with developmental delay, learning disability, ASD, ADHD, and dysmorphism (1 x heart defects). Trio WES identified de novo variants in RUNX1T1 gene (1 x nonsense variant in 5' region [p.Gln36Ter], 2 x missense variants in C-terminus [p.Gly412Arg and p.His521Tyr]).

PMID: 19172993
1 individual with mild-moderate ID and congenital heart disease, and chromosome t(5;8)(q32;q21.3) translocation. Molecular characterization revealed that one of the break points was within the RUNX1T1 gene. Analysis of RUNX1T1 expression in human embryonic and fetal tissues suggests a role of RUNX1T1 in brain and heart development.

PMID: 22644616
1 individual with mild ID and dysmorphism, and de novo deletion exons 3-7 in RUNX1T1.

PMID: 31223340
1 individual with ID, anaemia, atrial septal defect, dysmorphism, and seizures. Found to have a 2.1 Mb deletion at 8q21.3q22.1 involving entire RUNX1T1 gene (and 2 adjacent genes - SLC26A7 and TRIQK), and a benign familial 4.3 Mb duplication at 1p22.1p21.3 (present in unaffected healthy brother).
Sources: Literature
Dystonia - complex v0.254 HTRA2 Sangavi Sivagnanasundram reviewed gene: HTRA2: Rating: AMBER; Mode of pathogenicity: None; Publications: 27208207, 27696117, 30114719; Phenotypes: 3-methylglutaconic aciduria type 8 MONDO:0044723; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.24 RUNX1T1 Chirag Patel Classified gene: RUNX1T1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.24 RUNX1T1 Chirag Patel Gene: runx1t1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.23 RUNX1T1 Chirag Patel gene: RUNX1T1 was added
gene: RUNX1T1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RUNX1T1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RUNX1T1 were set to PMID: 39568205, 19172993, 22644616, 31223340
Phenotypes for gene: RUNX1T1 were set to Neurodevelopmental disorder MONDO:0700092
Review for gene: RUNX1T1 was set to GREEN
Added comment: RUNX1T1 encodes a transcription regulator for hematopoietic genes and is well-known for its involvement in hematologic malignancies. Germline RUNX1T1 variants may also play a role in human congenital neurodevelopmental disorders.

PMID: 39568205
3 unrelated individuals with developmental delay, learning disability, ASD, ADHD, and dysmorphism (1 x heart defects). Trio WES identified de novo variants in RUNX1T1 gene (1 x nonsense variant in 5' region [p.Gln36Ter], 2 x missense variants in C-terminus [p.Gly412Arg and p.His521Tyr]).

PMID: 19172993
1 individual with mild-moderate ID and congenital heart disease, and chromosome t(5;8)(q32;q21.3) translocation. Molecular characterization revealed that one of the break points was within the RUNX1T1 gene. Analysis of RUNX1T1 expression in human embryonic and fetal tissues suggests a role of RUNX1T1 in brain and heart development.

PMID: 22644616
1 individual with mild ID and dysmorphism, and de novo deletion exons 3-7 in RUNX1T1.

PMID: 31223340
1 individual with ID, anaemia, atrial septal defect, dysmorphism, and seizures. Found to have a 2.1 Mb deletion at 8q21.3q22.1 involving entire RUNX1T1 gene (and 2 adjacent genes - SLC26A7 and TRIQK), and a benign familial 4.3 Mb duplication at 1p22.1p21.3 (present in unaffected healthy brother).
Sources: Literature
Mitochondrial disease v0.959 PDE12 Chirag Patel gene: PDE12 was added
gene: PDE12 was added to Mitochondrial disease. Sources: Literature
Mode of inheritance for gene: PDE12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDE12 were set to PMID: 39567835
Phenotypes for gene: PDE12 were set to Mitochondrial disease MONDO:0044970
Review for gene: PDE12 was set to GREEN
Added comment: 3 families (2 consanguineous) with 5 affected individuals with early onset mitochondrial disease presentation (3 liveborn, 2 intrauterine death).
-Family 1: 1 x infant death @3mths (no clinical information), 1 x 7yr old with neonatal respiratory and lactic acidosis, developmental delay, and mitochondrial respiratory chain deficiencies, and marked cytochrome c oxidase (COX) deficiency in muscle.
-Family 2: 1 x neonatal death @2days with metabolic acidosis and lactic acidosis, respiratory failure, lissencephaly, dysgenesis of the corpus callosum and extensive periventricular and subcortical cysts. Normal pyruvate dehydrogenase complex and electron
transfer chain activities in fibroblasts.
-Family 3: 2 x fetuses (13wks and 22wks) with increase nuchal translucency and reduced fetal movements. One had intra-uterine growth retardation, hydrops and cystic hygroma. The other had permanent flexion contractures of four limbs). Western blotting in fetal skeletal muscle showed absent respiratory chain complexes (I, IV, and V).

WES in all 3 families identified 3 different homozygous missense variants in PDE12 gene (p.Tyr155Cys, p.Gly372Glu, and p.Arg41Pro). All variants segregated with disease, were rare in gnomAD, and in silico pathogenicity prediction tools pointed towards a high likelihood of pathogenicity.

PDE12 gene encodes the poly(A)-specific exoribonuclease, involved in the quality control of mitochondrial non-coding RNAs. Patient-derived primary fibroblasts demonstrate diminished steady-state levels of PDE12 protein, whilst mitochondrial poly(A)-tail RNA sequencing revealed an accumulation of spuriously polyadenylated mitochondrial RNA, consistent with perturbed function of PDE12 protein.
Sources: Literature
Mitochondrial disease v0.959 PDE12 Chirag Patel gene: PDE12 was added
gene: PDE12 was added to Mitochondrial disease. Sources: Literature
Mode of inheritance for gene: PDE12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDE12 were set to PMID: 39567835
Phenotypes for gene: PDE12 were set to Mitochondrial disease MONDO:0044970
Review for gene: PDE12 was set to GREEN
Added comment: 3 families (2 consanguineous) with 5 affected individuals with early onset mitochondrial disease presentation (3 liveborn, 2 intrauterine death).
-Family 1: 1 x infant death @3mths (no clinical information), 1 x 7yr old with neonatal respiratory and lactic acidosis, developmental delay, and mitochondrial respiratory chain deficiencies, and marked cytochrome c oxidase (COX) deficiency in muscle.
-Family 2: 1 x neonatal death @2days with metabolic acidosis and lactic acidosis, respiratory failure, lissencephaly, dysgenesis of the corpus callosum and extensive periventricular and subcortical cysts. Normal pyruvate dehydrogenase complex and electron
transfer chain activities in fibroblasts.
-Family 3: 2 x fetuses (13wks and 22wks) with increase nuchal translucency and reduced fetal movements. One had intra-uterine growth retardation, hydrops and cystic hygroma. The other had permanent flexion contractures of four limbs). Western blotting in fetal skeletal muscle showed absent respiratory chain complexes (I, IV, and V).

WES in all 3 families identified 3 different homozygous missense variants in PDE12 gene (p.Tyr155Cys, p.Gly372Glu, and p.Arg41Pro). All variants segregated with disease, were rare in gnomAD, and in silico pathogenicity prediction tools pointed towards a high likelihood of pathogenicity.

PDE12 gene encodes the poly(A)-specific exoribonuclease, involved in the quality control of mitochondrial non-coding RNAs. Patient-derived primary fibroblasts demonstrate diminished steady-state levels of PDE12 protein, whilst mitochondrial poly(A)-tail RNA sequencing revealed an accumulation of spuriously polyadenylated mitochondrial RNA, consistent with perturbed function of PDE12 protein.
Sources: Literature
Dystonia - complex v0.254 GLB1 Sangavi Sivagnanasundram reviewed gene: GLB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24156116, 35937492, 34514040, 1353343; Phenotypes: GM1 gangliosidosis type 3 MONDO:0009262; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 CENPJ Michelle Torres reviewed gene: CENPJ: Rating: GREEN; Mode of pathogenicity: None; Publications: 36334884; Phenotypes: Microcephaly 6, primary MIM#608393, Seckel syndrome 4 MIM#613676; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 CDH11 Michelle Torres reviewed gene: CDH11: Rating: GREEN; Mode of pathogenicity: None; Publications: 29271567; Phenotypes: Elsahy-Waters syndrome MIM#211380; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia - complex v0.254 GCDH Sangavi Sivagnanasundram reviewed gene: GCDH: Rating: GREEN; Mode of pathogenicity: None; Publications: 32777384, 21912879, 31536184; Phenotypes: glutaryl-CoA dehydrogenase deficiency MONDO:0009281; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 BBS7 Karina Sandoval reviewed gene: BBS7: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 12567324, 21937992, 19797195; Phenotypes: Bardet-Biedl syndrome 7, MIM# 615984, MONDO:0014435; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia - complex v0.254 FTL Sangavi Sivagnanasundram reviewed gene: FTL: Rating: GREEN; Mode of pathogenicity: None; Publications: 11438811, 15099026, 12746423, 18413574; Phenotypes: neuroferritinopathy MONDO:0011638; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dystonia - complex v0.254 FA2H Sangavi Sivagnanasundram reviewed gene: FA2H: Rating: GREEN; Mode of pathogenicity: None; Publications: 19068277, 20104589, 20853438, 31135052; Phenotypes: hereditary spastic paraplegia 35 MONDO:0012866; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia - complex v0.254 DLAT Sangavi Sivagnanasundram reviewed gene: DLAT: Rating: GREEN; Mode of pathogenicity: None; Publications: 39007626, 20022530, 16049940; Phenotypes: pyruvate dehydrogenase E2 deficiency MONDO:0009502; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2196 CAPZA2 Zornitza Stark Publications for gene: CAPZA2 were set to 32338762
Mendeliome v1.2195 CAPZA2 Zornitza Stark Classified gene: CAPZA2 as Green List (high evidence)
Mendeliome v1.2195 CAPZA2 Zornitza Stark Gene: capza2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.22 CAPZA2 Zornitza Stark Phenotypes for gene: CAPZA2 were changed from Intellectual disability to Neurodevelopmental disorder, MONDO:0700092, CAPZA2-related
Intellectual disability syndromic and non-syndromic v1.21 CAPZA2 Zornitza Stark Publications for gene: CAPZA2 were set to 32338762
Intellectual disability syndromic and non-syndromic v1.20 CAPZA2 Zornitza Stark Classified gene: CAPZA2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.20 CAPZA2 Zornitza Stark Gene: capza2 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.56 COL4A1 Zornitza Stark Marked gene: COL4A1 as ready
Spontaneous coronary artery dissection v0.56 COL4A1 Zornitza Stark Gene: col4a1 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.56 COL4A1 Zornitza Stark Phenotypes for gene: COL4A1 were changed from CORONARY ARTERY DISSECTION, SPONTANEOUS MIM#122455 to Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps, MIM#611773
Spontaneous coronary artery dissection v0.55 COL4A1 Zornitza Stark Classified gene: COL4A1 as Green List (high evidence)
Spontaneous coronary artery dissection v0.55 COL4A1 Zornitza Stark Gene: col4a1 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.54 COL4A1 Zornitza Stark reviewed gene: COL4A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps, MIM#611773; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cholestasis v1.0 Zornitza Stark promoted panel to version 1.0
Prepair 1000+ v1.633 SLC24A5 Andrew Coventry reviewed gene: SLC24A5: Rating: GREEN; Mode of pathogenicity: None; Publications: 23364476, 23985994, 26491832; Phenotypes: Albinism, oculocutaneous, type VI MIM#113750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 SLC22A5 Andrew Coventry reviewed gene: SLC22A5: Rating: GREEN; Mode of pathogenicity: None; Publications: 9916797, 10072434, 10051646, 10425211, 10480371, 10679939, 9837751, 23379544, 31399326, 25778941, 17884651, 22420015; Phenotypes: Carnitine deficiency, systemic primary, MIM# 212140, MONDO:0008919; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 SLC16A1 Andrew Coventry reviewed gene: SLC16A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25390740, 20301549, 36082648, 35729663; Phenotypes: Monocarboxylate transporter 1 deficiency MIM#616095; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Prepair 1000+ v1.633 SH2D1A Andrew Coventry reviewed gene: SH2D1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 6306053, 9771704, 11049992, 20301580; Phenotypes: Lymphoproliferative syndrome, X-linked, 1 MIM#308240; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.633 SGSH Andrew Coventry reviewed gene: SGSH: Rating: GREEN; Mode of pathogenicity: None; Publications: 7493035, 9158154, 9401012, 9554748; Phenotypes: Mucopolysaccharidosis type IIIA (Sanfilippo A), MIM# 252900, MONDO:0009655; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 SCO2 Andrew Coventry reviewed gene: SCO2: Rating: GREEN; Mode of pathogenicity: None; Publications: 15210538, 18924171, 22231385, 10545952, 10749987; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 2 MIM#604377; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 RSPH9 Andrew Coventry reviewed gene: RSPH9: Rating: GREEN; Mode of pathogenicity: None; Publications: 25789548, 22384920, 23993197, 19200523, 27626380; Phenotypes: Ciliary dyskinesia, primary, 12 MIM#612650; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 RPL10 Andrew Coventry reviewed gene: RPL10: Rating: GREEN; Mode of pathogenicity: None; Publications: 25316788, 25846674, 26290468, 29066376, 35876338; Phenotypes: Intellectual developmental disorder, X-linked syndromic 35 MIM#300998; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.633 RAB3GAP2 Andrew Coventry reviewed gene: RAB3GAP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 16532399, 20967465, 23420520, 32740904, 32376645, 24891604; Phenotypes: Warburg micro syndrome MONDO:0016649; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 QARS Andrew Coventry reviewed gene: QARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 24656866, 27717089, 31618474, 25471517, 25432320, 24656866, 28620870, 25041233, 32042906; Phenotypes: Microcephaly, progressive, seizures, and cerebral and cerebellar atrophy MIM#615760; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Spontaneous coronary artery dissection v0.54 COL4A1 Stephanie Hesselson gene: COL4A1 was added
gene: COL4A1 was added to Spontaneous coronary artery dissection. Sources: Other
Mode of inheritance for gene: COL4A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COL4A1 were set to PMID: 35583931, 35234813, 37248441
Phenotypes for gene: COL4A1 were set to CORONARY ARTERY DISSECTION, SPONTANEOUS MIM#122455
Penetrance for gene: COL4A1 were set to unknown
Review for gene: COL4A1 was set to GREEN
Added comment: It is possible that rare and common variants in COL4A1 contribute to SCAD risk.

5 individuals with SCAD have been found to carry a LP variant:

PMID: 35234813 reports 3x SCAD participants with a LP variant in COL4A1 p.Gly1484Arg, p.Gly495Arg, and p.Gly160Asp

PMID 35583931 reports 2x SCAD participants with LP variants in COL4A1 p.Gly1198Arg and p.Ala1626Gly

In a meta-GWAS for SCAD, the COL4A1/COL4A2 locus accounted for the second largest proportion of heritability for SCAD in the dataset. It contained two independent GWAS signals at this locus. (PMID 37248441)
Sources: Other
Prepair 1000+ v1.633 PRF1 Andrew Coventry reviewed gene: PRF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19595804, 26199792, 30070073, 19487666, 26184781, 10583959, 19487666; Phenotypes: Hemophagocytic lymphohistiocytosis, familial, 2 MIM#603553; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 POMT1 Andrew Coventry reviewed gene: POMT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15792865, 22549409, 31311558, 20065251, 25088310, 19299310, 19299310; Phenotypes: Myopathy caused by variation in POMT1 MONDO:0700070; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 IMPG2 Andrew Coventry changed review comment from: Retinitis pigmentosa 56 - is an early-onset form of RP with progressive visual-field loss and deterioration of visual acuity. Features include night blindness, progressive visual loss, macular retinal pigment epithelium (RPE) mottling / atrophy, decreased ERG amplitudes (affecting rods more severely than cones), colour vision defect, peripheral visual field loss, central scotoma, retinal blood vessel attenuation, and/or optic disc pallor. These features are largely distinct from the vitelliform macular dystrophy phenotype (MIM#616152).
- biallelic loss-of-function consistently associates with retinitis pigmentosa, while monoallelic loss-of-function consistently associates with vitelliform macular dystrophy.
PMID: 20673862 - 2 families each with 3 affected sibs. Additional 10 index cases identified.
- Those with nonsenses showed early-onset RP, patient with missense variants had a milder maculopathy phenotype.

Further studies and evidence:
Mouse models present exhibiting RP phenotype. (PMID: 38217426 - indicates missense variants had minimal retinal pathology in mice)
Functional study present using patient derived iPS (PMID: 36206764) - confirmed LoF due to lack of expression or lack os post-translational modifications - destabilising outer segments of rods and cones.

ClinGen - curation definitive for AR RP phenotype in association with gene IMPG2, with 10 suspected disease-causing variants scored as part of their curation (five nonsense, one frameshift, one canonical splice site disruption, one in-frame exon deletion, and two missense). Variants curated were in 8 probands (PMID: 24876279, PMID: 20673862, PMID: 31264916, PMID: 34990796).

RP genes already screened for by 1000+, consider above adequate evidence to upgrade to green status for inclusion in v2.; to: Retinitis pigmentosa 56 - is an early-onset form of RP with progressive visual-field loss and deterioration of visual acuity. Features include night blindness, progressive visual loss, macular retinal pigment epithelium (RPE) mottling / atrophy, decreased ERG amplitudes (affecting rods more severely than cones), colour vision defect, peripheral visual field loss, central scotoma, retinal blood vessel attenuation, and/or optic disc pallor. These features are largely distinct from the vitelliform macular dystrophy phenotype (MIM#616152).
- biallelic loss-of-function consistently associates with retinitis pigmentosa, while monoallelic loss-of-function consistently associates with vitelliform macular dystrophy.
PMID: 20673862 - 2 families each with 3 affected sibs. Additional 10 index cases identified.
- Those with nonsenses showed early-onset RP, patient with missense variants had a milder maculopathy phenotype.

Age of onset:
PMID 34990796 - 16yo had night blindness and photophobia. Had 22y.o. sibling that was severely affected. Age of initial onset of visual symptoms said to be ~2-4 years of age.
PMID 31264916 - 8y.o. with photophobia and myopia, 4y.o. with light sensitivity. 17yo with poor vision 'since childhood', 17yo with poor vision since birth and poor night vision, 45yo with poor night vision - starting at 6yo and progressing loss of central vision.
PMID 24876279 - age of onset of patients studied: 1, 5, 6, 1, 2, 3, 2, 3, 1, 4, 1, 2, 1, 2, 6, 1, 1. Symptoms variable, including night blindness, decrease of visual acuity, loss of visual field.

Further studies and evidence:
Mouse models present exhibiting RP phenotype. (PMID: 38217426 - indicates missense variants had minimal retinal pathology in mice)
Functional study present using patient derived iPS (PMID: 36206764) - confirmed LoF due to lack of expression or lack os post-translational modifications - destabilising outer segments of rods and cones.

ClinGen - curation definitive for AR RP phenotype in association with gene IMPG2, with 10 suspected disease-causing variants scored as part of their curation (five nonsense, one frameshift, one canonical splice site disruption, one in-frame exon deletion, and two missense). Variants curated were in 8 probands (PMID: 24876279, PMID: 20673862, PMID: 31264916, PMID: 34990796).

RP genes already screened for by 1000+, consider above adequate evidence to upgrade to green status for inclusion in v2.
Intellectual disability syndromic and non-syndromic v1.19 CAPZA2 Chris Ciotta reviewed gene: CAPZA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32338762, 38374166, 35856264; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, CAPZA2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.2194 CAPZA2 Chris Ciotta reviewed gene: CAPZA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32338762, 38374166, 35856264; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, CAPZA2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic Epilepsy v1.85 USP25 Zornitza Stark Marked gene: USP25 as ready
Genetic Epilepsy v1.85 USP25 Zornitza Stark Gene: usp25 has been classified as Green List (High Evidence).
Motor Neurone Disease v1.27 SQSTM1 Bryony Thompson Marked gene: SQSTM1 as ready
Motor Neurone Disease v1.27 SQSTM1 Bryony Thompson Gene: sqstm1 has been classified as Amber List (Moderate Evidence).
Motor Neurone Disease v1.27 SQSTM1 Bryony Thompson Phenotypes for gene: SQSTM1 were changed from Frontotemporal dementia and/or amyotrophic lateral sclerosis 3 MONDO:0014640 to Frontotemporal dementia and/or amyotrophic lateral sclerosis 3 MONDO:0014640
Motor Neurone Disease v1.26 SQSTM1 Bryony Thompson Phenotypes for gene: SQSTM1 were changed from to Frontotemporal dementia and/or amyotrophic lateral sclerosis 3 MONDO:0014640
Motor Neurone Disease v1.25 SQSTM1 Bryony Thompson Classified gene: SQSTM1 as Amber List (moderate evidence)
Motor Neurone Disease v1.25 SQSTM1 Bryony Thompson Added comment: Comment on list classification: ALS Spectrum Disorders GCEP classify the gene-disease association as Moderate, due to the lack of segregation evidence to support the GDA - https://search.clinicalgenome.org/CCID:006272
Motor Neurone Disease v1.25 SQSTM1 Bryony Thompson Gene: sqstm1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v1.85 CCT6A Ain Roesley Classified gene: CCT6A as Amber List (moderate evidence)
Genetic Epilepsy v1.85 CCT6A Ain Roesley Gene: cct6a has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v1.84 CCT6A Ain Roesley Classified gene: CCT6A as Amber List (moderate evidence)
Genetic Epilepsy v1.84 CCT6A Ain Roesley Gene: cct6a has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v1.83 CCT6A Ain Roesley Marked gene: CCT6A as ready
Genetic Epilepsy v1.83 CCT6A Ain Roesley Gene: cct6a has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v1.19 CCT6A Ain Roesley Classified gene: CCT6A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.19 CCT6A Ain Roesley Gene: cct6a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.18 CCT6A Ain Roesley Marked gene: CCT6A as ready
Intellectual disability syndromic and non-syndromic v1.18 CCT6A Ain Roesley Gene: cct6a has been classified as Red List (Low Evidence).
Mendeliome v1.2194 CCT6A Ain Roesley Marked gene: CCT6A as ready
Mendeliome v1.2194 CCT6A Ain Roesley Gene: cct6a has been classified as Green List (High Evidence).
Mendeliome v1.2194 CCT6A Ain Roesley Classified gene: CCT6A as Green List (high evidence)
Mendeliome v1.2194 CCT6A Ain Roesley Gene: cct6a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.18 CCT6A Ain Roesley gene: CCT6A was added
gene: CCT6A was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CCT6A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CCT6A were set to 39480921
Phenotypes for gene: CCT6A were set to neurodevelopmental disorder MONDO:0700092, CCT6A-related
Penetrance for gene: CCT6A were set to Complete
Review for gene: CCT6A was set to GREEN
gene: CCT6A was marked as current diagnostic
Added comment: previously known as CCT6

5x individuals including 4x de novo
3x PTCS + 1x +5C>G + 1x missense

4/5 DD/ID
2/5 visual impairment
2/5 seizures
Sources: Literature
Genetic Epilepsy v1.83 CCT6A Ain Roesley gene: CCT6A was added
gene: CCT6A was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: CCT6A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CCT6A were set to 39480921
Phenotypes for gene: CCT6A were set to neurodevelopmental disorder MONDO:0700092, CCT6A-related
Penetrance for gene: CCT6A were set to Complete
Review for gene: CCT6A was set to AMBER
gene: CCT6A was marked as current diagnostic
Added comment: previously known as CCT6

5x individuals including 4x de novo
3x PTCS + 1x +5C>G + 1x missense

4/5 DD/ID
2/5 visual impairment
2/5 seizures
Sources: Literature
Mendeliome v1.2193 CCT6A Ain Roesley gene: CCT6A was added
gene: CCT6A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CCT6A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CCT6A were set to 39480921
Phenotypes for gene: CCT6A were set to neurodevelopmental disorder MONDO:0700092, CCT6A-related
Penetrance for gene: CCT6A were set to Complete
Review for gene: CCT6A was set to GREEN
gene: CCT6A was marked as current diagnostic
Added comment: previously known as CCT6

5x individuals including 4x de novo
3x PTCS + 1x +5C>G + 1x missense

4/5 DD/ID
2/5 visual impairment
2/5 seizures
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.17 TCP1 Ain Roesley Marked gene: TCP1 as ready
Intellectual disability syndromic and non-syndromic v1.17 TCP1 Ain Roesley Gene: tcp1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.17 TCP1 Ain Roesley Classified gene: TCP1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.17 TCP1 Ain Roesley Gene: tcp1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.17 TCP1 Ain Roesley Classified gene: TCP1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.17 TCP1 Ain Roesley Gene: tcp1 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.194 TCP1 Ain Roesley Marked gene: TCP1 as ready
Polymicrogyria and Schizencephaly v0.194 TCP1 Ain Roesley Gene: tcp1 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.194 TCP1 Ain Roesley Classified gene: TCP1 as Green List (high evidence)
Polymicrogyria and Schizencephaly v0.194 TCP1 Ain Roesley Gene: tcp1 has been classified as Green List (High Evidence).
Mendeliome v1.2192 TCP1 Ain Roesley Marked gene: TCP1 as ready
Mendeliome v1.2192 TCP1 Ain Roesley Gene: tcp1 has been classified as Green List (High Evidence).
Mendeliome v1.2192 TCP1 Ain Roesley Marked gene: TCP1 as ready
Mendeliome v1.2192 TCP1 Ain Roesley Gene: tcp1 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.82 TCP1 Ain Roesley Marked gene: TCP1 as ready
Genetic Epilepsy v1.82 TCP1 Ain Roesley Gene: tcp1 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.82 TCP1 Ain Roesley Classified gene: TCP1 as Green List (high evidence)
Genetic Epilepsy v1.82 TCP1 Ain Roesley Gene: tcp1 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.193 TCP1 Ain Roesley gene: TCP1 was added
gene: TCP1 was added to Polymicrogyria and Schizencephaly. Sources: Literature
Mode of inheritance for gene: TCP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TCP1 were set to 39480921
Phenotypes for gene: TCP1 were set to neurodevelopmental disorder MONDO:0700092, TCP1-related
Penetrance for gene: TCP1 were set to Complete
Review for gene: TCP1 was set to GREEN
gene: TCP1 was marked as current diagnostic
Added comment: previously known as CCT1

8x individuals including 5x de novo
6x PTCs + 2x missense

6/8 DD/ID
2/8 visual impairment
6/8 seizures
6/8 polymicrogyria + 1x Ventriculomegaly, white matter hyperintensities
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.16 TCP1 Ain Roesley gene: TCP1 was added
gene: TCP1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: TCP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TCP1 were set to 39480921
Phenotypes for gene: TCP1 were set to neurodevelopmental disorder MONDO:0700092, TCP1-related
Penetrance for gene: TCP1 were set to Complete
Review for gene: TCP1 was set to GREEN
gene: TCP1 was marked as current diagnostic
Added comment: previously known as CCT1

8x individuals including 5x de novo
6x PTCs + 2x missense

6/8 DD/ID
2/8 visual impairment
6/8 seizures
6/8 polymicrogyria + 1x Ventriculomegaly, white matter hyperintensities
Sources: Literature
Mendeliome v1.2192 TCP1 Ain Roesley Classified gene: TCP1 as Green List (high evidence)
Mendeliome v1.2192 TCP1 Ain Roesley Gene: tcp1 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.81 TCP1 Ain Roesley gene: TCP1 was added
gene: TCP1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TCP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TCP1 were set to 39480921
Phenotypes for gene: TCP1 were set to neurodevelopmental disorder MONDO:0700092, TCP1-related
Penetrance for gene: TCP1 were set to Complete
Review for gene: TCP1 was set to GREEN
gene: TCP1 was marked as current diagnostic
Added comment: previously known as CCT1

8x individuals including 5x de novo
6x PTCs + 2x missense

6/8 DD/ID
2/8 visual impairment
6/8 seizures
6/8 polymicrogyria + 1x Ventriculomegaly, white matter hyperintensities
Sources: Literature
Mendeliome v1.2191 TCP1 Ain Roesley gene: TCP1 was added
gene: TCP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TCP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TCP1 were set to 39480921
Phenotypes for gene: TCP1 were set to neurodevelopmental disorder MONDO:0700092, TCP1-related
Penetrance for gene: TCP1 were set to Complete
Review for gene: TCP1 was set to GREEN
gene: TCP1 was marked as current diagnostic
Added comment: previously known as CCT1

8x individuals including 5x de novo
6x PTCs + 2x missense

6/8 DD/ID
2/8 visual impairment
6/8 seizures
6/8 polymicrogyria + 1x Ventriculomegaly, white matter hyperintensities
Sources: Literature
Genetic Epilepsy v1.80 CCT3 Ain Roesley Marked gene: CCT3 as ready
Genetic Epilepsy v1.80 CCT3 Ain Roesley Gene: cct3 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.80 CCT3 Ain Roesley Classified gene: CCT3 as Green List (high evidence)
Genetic Epilepsy v1.80 CCT3 Ain Roesley Gene: cct3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.15 CCT3 Ain Roesley Classified gene: CCT3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.15 CCT3 Ain Roesley Gene: cct3 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.79 CCT3 Ain Roesley gene: CCT3 was added
gene: CCT3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: CCT3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CCT3 were set to 39480921
Phenotypes for gene: CCT3 were set to neurodevelopmental disorder MONDO:0700092, CCT3-related
Penetrance for gene: CCT3 were set to Complete
Review for gene: CCT3 was set to GREEN
gene: CCT3 was marked as current diagnostic
Added comment: 4x de novo - 3x PTCs and 1x missense

overlapping phenotypes:
4/4 ID/DD
3/4 visual impairment
2/4 seizures
4/4 Hypomyelination of white matter
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.15 CCT3 Ain Roesley Marked gene: CCT3 as ready
Intellectual disability syndromic and non-syndromic v1.15 CCT3 Ain Roesley Gene: cct3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.15 CCT3 Ain Roesley Classified gene: CCT3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.15 CCT3 Ain Roesley Gene: cct3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.14 CCT3 Ain Roesley gene: CCT3 was added
gene: CCT3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CCT3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CCT3 were set to 39480921
Phenotypes for gene: CCT3 were set to neurodevelopmental disorder MONDO:0700092, CCT3-related
Penetrance for gene: CCT3 were set to Complete
Review for gene: CCT3 was set to GREEN
gene: CCT3 was marked as current diagnostic
Added comment: 4x de novo - 3x PTCs and 1x missense

overlapping phenotypes:
4/4 ID/DD
3/4 visual impairment
2/4 seizures
4/4 Hypomyelination of white matter
Sources: Literature
Mendeliome v1.2190 CCT3 Ain Roesley Marked gene: CCT3 as ready
Mendeliome v1.2190 CCT3 Ain Roesley Gene: cct3 has been classified as Green List (High Evidence).
Mendeliome v1.2190 CCT3 Ain Roesley Marked gene: CCT3 as ready
Mendeliome v1.2190 CCT3 Ain Roesley Gene: cct3 has been classified as Green List (High Evidence).
Mendeliome v1.2190 CCT3 Ain Roesley Phenotypes for gene: CCT3 were changed from to neurodevelopmental disorder MONDO:0700092, CCT3-related
Mendeliome v1.2189 CCT3 Ain Roesley Classified gene: CCT3 as Green List (high evidence)
Mendeliome v1.2189 CCT3 Ain Roesley Gene: cct3 has been classified as Green List (High Evidence).
Mendeliome v1.2188 CCT3 Ain Roesley gene: CCT3 was added
gene: CCT3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CCT3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CCT3 were set to 39480921
Penetrance for gene: CCT3 were set to Complete
Review for gene: CCT3 was set to GREEN
gene: CCT3 was marked as current diagnostic
Added comment: 4x de novo - 3x PTCs and 1x missense

overlapping phenotypes:
4/4 ID/DD
3/4 visual impairment
2/4 seizures
4/4 Hypomyelination of white matter
Sources: Literature
Cholestasis v0.288 UGT1A1 Zornitza Stark Marked gene: UGT1A1 as ready
Cholestasis v0.288 UGT1A1 Zornitza Stark Gene: ugt1a1 has been classified as Green List (High Evidence).
Cholestasis v0.288 UGT1A1 Zornitza Stark Phenotypes for gene: UGT1A1 were changed from to Crigler-Najjar syndrome, type I MIM#218800; Crigler-Najjar syndrome, type II MIM#606785
Cholestasis v0.287 UGT1A1 Zornitza Stark Mode of inheritance for gene: UGT1A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.286 UGT1A1 Zornitza Stark changed review comment from: Well established gene-disease association. Cholestasis is a key feature.; to: Well established gene-disease association. Unconjugated hyperbilirubinaemia is a key feature.
Cholestasis v0.286 UGT1A1 Zornitza Stark reviewed gene: UGT1A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Crigler-Najjar syndrome, type I MIM#218800, Crigler-Najjar syndrome, type II MIM#606785; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.286 TALDO1 Zornitza Stark Marked gene: TALDO1 as ready
Cholestasis v0.286 TALDO1 Zornitza Stark Gene: taldo1 has been classified as Green List (High Evidence).
Cholestasis v0.286 TALDO1 Zornitza Stark Phenotypes for gene: TALDO1 were changed from to Transaldolase deficiency, MIM# 606003
Cholestasis v0.285 TALDO1 Zornitza Stark Mode of inheritance for gene: TALDO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.284 TALDO1 Zornitza Stark reviewed gene: TALDO1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Transaldolase deficiency, MIM# 606003; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.284 SLC25A13 Zornitza Stark Marked gene: SLC25A13 as ready
Cholestasis v0.284 SLC25A13 Zornitza Stark Gene: slc25a13 has been classified as Green List (High Evidence).
Cholestasis v0.284 SLC25A13 Zornitza Stark Phenotypes for gene: SLC25A13 were changed from to Citrullinemia, type II, neonatal-onset, MIM# 605814
Cholestasis v0.283 SLC25A13 Zornitza Stark Mode of inheritance for gene: SLC25A13 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.282 SLC25A13 Zornitza Stark reviewed gene: SLC25A13: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Citrullinemia, type II, neonatal-onset, MIM# 605814; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.282 PEX6 Zornitza Stark Marked gene: PEX6 as ready
Cholestasis v0.282 PEX6 Zornitza Stark Gene: pex6 has been classified as Green List (High Evidence).
Microcephaly v1.292 Ain Roesley removed gene:CLASP1 from the panel
Microcephaly v1.292 CLASP1 Ain Roesley Source: Literature was removed from gene: CLASP1
Cholestasis v0.282 PEX6 Zornitza Stark Phenotypes for gene: PEX6 were changed from to Peroxisome biogenesis disorder 4A (Zellweger) (MIM#614862)
Cholestasis v0.281 PEX6 Zornitza Stark Mode of inheritance for gene: PEX6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.280 PEX6 Zornitza Stark reviewed gene: PEX6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 4A (Zellweger) (MIM#614862); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.13 CLASP1 Ain Roesley Marked gene: CLASP1 as ready
Intellectual disability syndromic and non-syndromic v1.13 CLASP1 Ain Roesley Gene: clasp1 has been classified as Red List (Low Evidence).
Lissencephaly and Band Heterotopia v1.21 CLASP1 Ain Roesley Marked gene: CLASP1 as ready
Lissencephaly and Band Heterotopia v1.21 CLASP1 Ain Roesley Gene: clasp1 has been classified as Red List (Low Evidence).
Cholestasis v0.280 PEX26 Zornitza Stark Marked gene: PEX26 as ready
Cholestasis v0.280 PEX26 Zornitza Stark Gene: pex26 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.78 CLASP1 Ain Roesley Marked gene: CLASP1 as ready
Genetic Epilepsy v1.78 CLASP1 Ain Roesley Gene: clasp1 has been classified as Red List (Low Evidence).
Cholestasis v0.280 PEX26 Zornitza Stark Phenotypes for gene: PEX26 were changed from to Peroxisome biogenesis disorder 7A (Zellweger) MIM#614872
Cholestasis v0.279 PEX26 Zornitza Stark Mode of inheritance for gene: PEX26 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.278 PEX26 Zornitza Stark reviewed gene: PEX26: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 7A (Zellweger) MIM#614872; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.289 CLASP1 Ain Roesley gene: CLASP1 was added
gene: CLASP1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: CLASP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLASP1 were set to 39040917
Phenotypes for gene: CLASP1 were set to neurodevelopmental disorder MONDO:0700092, CLASP1-related
Review for gene: CLASP1 was set to RED
gene: CLASP1 was marked as current diagnostic
Added comment: 3 siblings from a consanguineous family, homozygous for p.(Arg1481His)
at birth, all had low weight and microcephaly (< 3-4SD), profound dev delay, spasticity, seizures and lissencephaly

Arg1481His - 3 hets 0 Homs in v4
codon is highly conserved with a high REVEL score 0.83
Sources: Literature
Microcephaly v1.289 CLASP1 Ain Roesley gene: CLASP1 was added
gene: CLASP1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: CLASP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLASP1 were set to 39040917
Phenotypes for gene: CLASP1 were set to neurodevelopmental disorder MONDO:0700092, CLASP1-related
Review for gene: CLASP1 was set to RED
gene: CLASP1 was marked as current diagnostic
Added comment: 3 siblings from a consanguineous family, homozygous for p.(Arg1481His)
at birth, all had low weight and microcephaly (< 3-4SD), profound dev delay, spasticity, seizures and lissencephaly

Arg1481His - 3 hets 0 Homs in v4
codon is highly conserved with a high REVEL score 0.83
Sources: Literature
Cholestasis v0.278 PEX2 Zornitza Stark Marked gene: PEX2 as ready
Cholestasis v0.278 PEX2 Zornitza Stark Gene: pex2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.13 CLASP1 Ain Roesley gene: CLASP1 was added
gene: CLASP1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CLASP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLASP1 were set to 39040917
Phenotypes for gene: CLASP1 were set to neurodevelopmental disorder MONDO:0700092, CLASP1-related
Review for gene: CLASP1 was set to RED
gene: CLASP1 was marked as current diagnostic
Added comment: 3 siblings from a consanguineous family, homozygous for p.(Arg1481His)
at birth, all had low weight and microcephaly (< 3-4SD), profound dev delay, spasticity, seizures and lissencephaly

Arg1481His - 3 hets 0 Homs in v4
codon is highly conserved with a high REVEL score 0.83
Sources: Literature
Cholestasis v0.278 PEX2 Zornitza Stark Phenotypes for gene: PEX2 were changed from Peroxisome biogenesis disorder 5A (Zellweger) MIM#614866 to Peroxisome biogenesis disorder 5A (Zellweger) MIM#614866
Lissencephaly and Band Heterotopia v1.21 CLASP1 Ain Roesley gene: CLASP1 was added
gene: CLASP1 was added to Lissencephaly and Band Heterotopia. Sources: Literature
Mode of inheritance for gene: CLASP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLASP1 were set to 39040917
Phenotypes for gene: CLASP1 were set to neurodevelopmental disorder MONDO:0700092, CLASP1-related
Review for gene: CLASP1 was set to RED
gene: CLASP1 was marked as current diagnostic
Added comment: 3 siblings from a consanguineous family, homozygous for p.(Arg1481His)
at birth, all had low weight and microcephaly (< 3-4SD), profound dev delay, spasticity, seizures and lissencephaly

Arg1481His - 3 hets 0 Homs in v4
codon is highly conserved with a high REVEL score 0.83
Sources: Literature
Cholestasis v0.278 PEX2 Zornitza Stark Phenotypes for gene: PEX2 were changed from to Peroxisome biogenesis disorder 5A (Zellweger) MIM#614866
Genetic Epilepsy v1.78 CLASP1 Ain Roesley gene: CLASP1 was added
gene: CLASP1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: CLASP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLASP1 were set to 39040917
Phenotypes for gene: CLASP1 were set to neurodevelopmental disorder MONDO:0700092, CLASP1-related
Review for gene: CLASP1 was set to RED
gene: CLASP1 was marked as current diagnostic
Added comment: 3 siblings from a consanguineous family, homozygous for p.(Arg1481His)
at birth, all had low weight and microcephaly (< 3-4SD), profound dev delay, spasticity, seizures and lissencephaly

Arg1481His - 3 hets 0 Homs in v4
codon is highly conserved with a high REVEL score 0.83
Sources: Literature
Mendeliome v1.2187 CLASP1 Ain Roesley Marked gene: CLASP1 as ready
Mendeliome v1.2187 CLASP1 Ain Roesley Gene: clasp1 has been classified as Red List (Low Evidence).
Mendeliome v1.2187 CLASP1 Ain Roesley gene: CLASP1 was added
gene: CLASP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CLASP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLASP1 were set to 39040917
Phenotypes for gene: CLASP1 were set to neurodevelopmental disorder MONDO:0700092, CLASP1-related
Review for gene: CLASP1 was set to RED
gene: CLASP1 was marked as current diagnostic
Added comment: 3 siblings from a consanguineous family, homozygous for p.(Arg1481His)
at birth, all had low weight and microcephaly (< 3-4SD), profound dev delay, spasticity, seizures and lissencephaly

Arg1481His - 3 hets 0 Homs in v4
codon is highly conserved with a high REVEL score 0.83
Sources: Literature
Cholestasis v0.277 PEX2 Zornitza Stark Mode of inheritance for gene: PEX2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.276 PEX2 Zornitza Stark reviewed gene: PEX2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 5A (Zellweger) MIM#614866; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.276 PEX12 Zornitza Stark Marked gene: PEX12 as ready
Cholestasis v0.276 PEX12 Zornitza Stark Gene: pex12 has been classified as Green List (High Evidence).
Cholestasis v0.276 PEX12 Zornitza Stark Phenotypes for gene: PEX12 were changed from to Peroxisome biogenesis disorder 3A (Zellweger) (MIM#614859)
Cholestasis v0.275 PEX12 Zornitza Stark Mode of inheritance for gene: PEX12 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.274 PEX12 Zornitza Stark reviewed gene: PEX12: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 3A (Zellweger) (MIM#614859); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.274 PEX1 Zornitza Stark Marked gene: PEX1 as ready
Cholestasis v0.274 PEX1 Zornitza Stark Gene: pex1 has been classified as Green List (High Evidence).
Cholestasis v0.274 PEX1 Zornitza Stark Phenotypes for gene: PEX1 were changed from to Peroxisome biogenesis disorder 1A (Zellweger), MIM# 214100
Cholestasis v0.273 PEX1 Zornitza Stark Mode of inheritance for gene: PEX1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.272 PEX1 Zornitza Stark reviewed gene: PEX1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 1A (Zellweger), MIM# 214100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.272 NPC2 Zornitza Stark Marked gene: NPC2 as ready
Cholestasis v0.272 NPC2 Zornitza Stark Gene: npc2 has been classified as Green List (High Evidence).
Cholestasis v0.272 NPC2 Zornitza Stark Phenotypes for gene: NPC2 were changed from to Niemann-pick disease, type C2 MIM#607625
Cholestasis v0.271 NPC2 Zornitza Stark Mode of inheritance for gene: NPC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.270 NPC2 Zornitza Stark reviewed gene: NPC2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Niemann-pick disease, type C2 MIM#607625; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.270 NPC1 Zornitza Stark Marked gene: NPC1 as ready
Cholestasis v0.270 NPC1 Zornitza Stark Gene: npc1 has been classified as Green List (High Evidence).
Cholestasis v0.270 NPC1 Zornitza Stark Phenotypes for gene: NPC1 were changed from to Niemann-Pick disease, MIM# 257220
Cholestasis v0.269 NPC1 Zornitza Stark Mode of inheritance for gene: NPC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.268 NPC1 Zornitza Stark reviewed gene: NPC1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Niemann-Pick disease, MIM# 257220; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.268 JAG1 Zornitza Stark Marked gene: JAG1 as ready
Cholestasis v0.268 JAG1 Zornitza Stark Gene: jag1 has been classified as Green List (High Evidence).
Cholestasis v0.268 JAG1 Zornitza Stark Phenotypes for gene: JAG1 were changed from to Alagille syndrome, MIM#118450
Cholestasis v0.267 JAG1 Zornitza Stark Mode of inheritance for gene: JAG1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cholestasis v0.266 JAG1 Zornitza Stark reviewed gene: JAG1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Alagille syndrome, MIM# 1, 118450; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cholestasis v0.266 FAH Zornitza Stark Marked gene: FAH as ready
Cholestasis v0.266 FAH Zornitza Stark Gene: fah has been classified as Green List (High Evidence).
Cholestasis v0.266 FAH Zornitza Stark Phenotypes for gene: FAH were changed from Tyrosinemia, type I, MIM# 276700 to Tyrosinaemia, type I, MIM# 276700
Cholestasis v0.265 FAH Zornitza Stark Phenotypes for gene: FAH were changed from to Tyrosinemia, type I, MIM# 276700
Cholestasis v0.264 FAH Zornitza Stark Mode of inheritance for gene: FAH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.263 FAH Zornitza Stark reviewed gene: FAH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Tyrosinemia, type I, MIM# 276700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.263 DCDC2 Zornitza Stark Marked gene: DCDC2 as ready
Cholestasis v0.263 DCDC2 Zornitza Stark Gene: dcdc2 has been classified as Green List (High Evidence).
Cholestasis v0.263 DCDC2 Zornitza Stark Phenotypes for gene: DCDC2 were changed from to Sclerosing cholangitis, neonatal, MIM# 617394
Cholestasis v0.262 DCDC2 Zornitza Stark Publications for gene: DCDC2 were set to
Cholestasis v0.261 DCDC2 Zornitza Stark Mode of inheritance for gene: DCDC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.260 DCDC2 Zornitza Stark edited their review of gene: DCDC2: Added comment: At least 8 families reported. Affected infants have jaundice, cholestasis, acholic stools, and progressive liver dysfunction resulting in fibrosis and cirrhosis; most require liver transplantation in the first few decades of life.; Changed publications: 27319779, 27469900
Cholestasis v0.260 DCDC2 Zornitza Stark reviewed gene: DCDC2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Sclerosing cholangitis, neonatal, MIM# 617394; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.260 CYP27A1 Zornitza Stark Marked gene: CYP27A1 as ready
Cholestasis v0.260 CYP27A1 Zornitza Stark Gene: cyp27a1 has been classified as Green List (High Evidence).
Cholestasis v0.260 CYP27A1 Zornitza Stark Phenotypes for gene: CYP27A1 were changed from to Cerebrotendinous xanthomatosis, MIM# 213700
Cholestasis v0.259 CYP27A1 Zornitza Stark Mode of inheritance for gene: CYP27A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.258 CYP27A1 Zornitza Stark reviewed gene: CYP27A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebrotendinous xanthomatosis, MIM# 213700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.258 CLDN1 Zornitza Stark Marked gene: CLDN1 as ready
Cholestasis v0.258 CLDN1 Zornitza Stark Gene: cldn1 has been classified as Green List (High Evidence).
Cholestasis v0.258 CLDN1 Zornitza Stark Phenotypes for gene: CLDN1 were changed from to Ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis MIM#607626
Cholestasis v0.257 CLDN1 Zornitza Stark Publications for gene: CLDN1 were set to
Cholestasis v0.256 CLDN1 Zornitza Stark Mode of inheritance for gene: CLDN1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.255 CLDN1 Zornitza Stark reviewed gene: CLDN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12164927, 11889141, 29146216; Phenotypes: Ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis MIM#607626; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.255 CC2D2A Zornitza Stark Marked gene: CC2D2A as ready
Cholestasis v0.255 CC2D2A Zornitza Stark Gene: cc2d2a has been classified as Green List (High Evidence).
Cholestasis v0.255 CC2D2A Zornitza Stark Phenotypes for gene: CC2D2A were changed from to COACH syndrome 2, MIM# 619111; Meckel syndrome 6, MIM#612284
Cholestasis v0.254 CC2D2A Zornitza Stark Mode of inheritance for gene: CC2D2A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.253 CC2D2A Zornitza Stark edited their review of gene: CC2D2A: Changed phenotypes: COACH syndrome 2, MIM# 619111, Meckel syndrome 6, MIM#612284
Cholestasis v0.253 CC2D2A Zornitza Stark reviewed gene: CC2D2A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: COACH syndrome 2, MIM# 619111; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.253 AMACR Zornitza Stark Marked gene: AMACR as ready
Cholestasis v0.253 AMACR Zornitza Stark Gene: amacr has been classified as Green List (High Evidence).
Cholestasis v0.253 AMACR Zornitza Stark Phenotypes for gene: AMACR were changed from to Bile acid synthesis defect, congenital, 4, MIM# 214950
Cholestasis v0.252 AMACR Zornitza Stark Publications for gene: AMACR were set to
Cholestasis v0.251 AMACR Zornitza Stark Mode of inheritance for gene: AMACR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.250 AMACR Zornitza Stark reviewed gene: AMACR: Rating: GREEN; Mode of pathogenicity: None; Publications: 31951345, 24735479, 12512044, 10655068, 34267495, 33047465; Phenotypes: Bile acid synthesis defect, congenital, 4, MIM# 214950; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteogenesis Imperfecta and Osteoporosis v1.0 Zornitza Stark promoted panel to version 1.0
Osteogenesis Imperfecta and Osteoporosis v0.133 SERPINH1 Zornitza Stark Mode of inheritance for gene: SERPINH1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Osteogenesis Imperfecta and Osteoporosis v0.133 SERPINH1 Zornitza Stark Mode of inheritance for gene: SERPINH1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Osteogenesis Imperfecta and Osteoporosis v0.132 SERPINH1 Zornitza Stark Publications for gene: SERPINH1 were set to 33524049
Osteogenesis Imperfecta and Osteoporosis v0.132 SERPINH1 Zornitza Stark Publications for gene: SERPINH1 were set to
Osteogenesis Imperfecta and Osteoporosis v0.131 SERPINH1 Zornitza Stark Phenotypes for gene: SERPINH1 were changed from Osteogenesis imperfecta, type X, MIM# 613848 to Osteogenesis imperfecta, type X, MIM# 613848
Osteogenesis Imperfecta and Osteoporosis v0.131 SERPINH1 Zornitza Stark Phenotypes for gene: SERPINH1 were changed from to Osteogenesis imperfecta, type X, MIM# 613848
Osteogenesis Imperfecta and Osteoporosis v0.130 ANO5 Zornitza Stark Marked gene: ANO5 as ready
Osteogenesis Imperfecta and Osteoporosis v0.130 ANO5 Zornitza Stark Gene: ano5 has been classified as Green List (High Evidence).
Osteogenesis Imperfecta and Osteoporosis v0.130 COL1A1 Zornitza Stark Marked gene: COL1A1 as ready
Osteogenesis Imperfecta and Osteoporosis v0.130 COL1A1 Zornitza Stark Gene: col1a1 has been classified as Green List (High Evidence).
Osteogenesis Imperfecta and Osteoporosis v0.130 COL1A1 Zornitza Stark Phenotypes for gene: COL1A1 were changed from to combined osteogenesis imperfecta and Ehlers-Danlos syndrome 1 MONDO:0030854; Osteogenesis imperfecta type 1 MONDO:0008146; Osteogenesis imperfecta type 2 MONDO:0008147; Osteogenesis imperfecta type 3 MONDO:0009804; Osteogenesis imperfecta type 4; MONDO:0008148
Osteogenesis Imperfecta and Osteoporosis v0.129 COL1A1 Zornitza Stark Publications for gene: COL1A1 were set to
Osteogenesis Imperfecta and Osteoporosis v0.128 COL1A1 Zornitza Stark Mode of inheritance for gene: COL1A1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Osteogenesis Imperfecta and Osteoporosis v0.127 COL1A2 Zornitza Stark Marked gene: COL1A2 as ready
Osteogenesis Imperfecta and Osteoporosis v0.127 COL1A2 Zornitza Stark Gene: col1a2 has been classified as Green List (High Evidence).
Osteogenesis Imperfecta and Osteoporosis v0.127 COL1A2 Zornitza Stark Phenotypes for gene: COL1A2 were changed from to Osteogenesis imperfecta type 1 MONDO:0008146; Osteogenesis imperfecta type 2 MONDO:0008147; Osteogenesis imperfecta type 3 MONDO:0009804; Osteogenesis imperfecta type 4 MONDO:0008148
Osteogenesis Imperfecta and Osteoporosis v0.126 COL1A2 Zornitza Stark Publications for gene: COL1A2 were set to
Osteogenesis Imperfecta and Osteoporosis v0.125 COL1A2 Zornitza Stark Mode of inheritance for gene: COL1A2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Osteogenesis Imperfecta and Osteoporosis v0.124 FKBP10 Zornitza Stark Marked gene: FKBP10 as ready
Osteogenesis Imperfecta and Osteoporosis v0.124 FKBP10 Zornitza Stark Gene: fkbp10 has been classified as Green List (High Evidence).
Osteogenesis Imperfecta and Osteoporosis v0.124 FKBP10 Zornitza Stark Phenotypes for gene: FKBP10 were changed from to osteogenesis imperfecta type 11 MONDO:0012592; Bruck syndrome MONDO:0017195
Osteogenesis Imperfecta and Osteoporosis v0.123 FKBP10 Zornitza Stark Publications for gene: FKBP10 were set to
Osteogenesis Imperfecta and Osteoporosis v0.122 FKBP10 Zornitza Stark Mode of inheritance for gene: FKBP10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Osteogenesis Imperfecta and Osteoporosis v0.121 LRP5 Zornitza Stark Marked gene: LRP5 as ready
Osteogenesis Imperfecta and Osteoporosis v0.121 LRP5 Zornitza Stark Gene: lrp5 has been classified as Green List (High Evidence).
Osteogenesis Imperfecta and Osteoporosis v0.121 LRP5 Zornitza Stark Phenotypes for gene: LRP5 were changed from to osteoporosis-pseudoglioma syndrome MONDO:0009820
Osteogenesis Imperfecta and Osteoporosis v0.120 LRP5 Zornitza Stark Publications for gene: LRP5 were set to
Osteogenesis Imperfecta and Osteoporosis v0.119 LRP5 Zornitza Stark Mode of inheritance for gene: LRP5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Osteogenesis Imperfecta and Osteoporosis v0.118 PLS3 Zornitza Stark Marked gene: PLS3 as ready
Osteogenesis Imperfecta and Osteoporosis v0.118 PLS3 Zornitza Stark Gene: pls3 has been classified as Green List (High Evidence).
Osteogenesis Imperfecta and Osteoporosis v0.118 PLS3 Zornitza Stark Phenotypes for gene: PLS3 were changed from to X-linked osteoporosis with fractures MONDO:0018315
Osteogenesis Imperfecta and Osteoporosis v0.117 PLS3 Zornitza Stark Publications for gene: PLS3 were set to
Osteogenesis Imperfecta and Osteoporosis v0.116 PLS3 Zornitza Stark Mode of inheritance for gene: PLS3 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Dystonia - complex v0.254 APTX Zornitza Stark Marked gene: APTX as ready
Dystonia - complex v0.254 APTX Zornitza Stark Gene: aptx has been classified as Green List (High Evidence).
Dystonia - complex v0.254 APTX Zornitza Stark Publications for gene: APTX were set to
Spontaneous coronary artery dissection v0.54 COL3A1 Zornitza Stark Publications for gene: COL3A1 were set to 30071989
Dystonia - complex v0.253 ATP13A2 Zornitza Stark Marked gene: ATP13A2 as ready
Dystonia - complex v0.253 ATP13A2 Zornitza Stark Gene: atp13a2 has been classified as Green List (High Evidence).
Dystonia - complex v0.253 ATP13A2 Zornitza Stark Phenotypes for gene: ATP13A2 were changed from Parkinson disease; Kufor-Rakeb syndrome 606693; Dystonia to Kufor-Rakeb syndrome MIM#606693
Dystonia - complex v0.252 ATP13A2 Zornitza Stark Publications for gene: ATP13A2 were set to
Dystonia - complex v0.251 BCAP31 Zornitza Stark Marked gene: BCAP31 as ready
Dystonia - complex v0.251 BCAP31 Zornitza Stark Gene: bcap31 has been classified as Green List (High Evidence).
Dystonia - complex v0.251 BCAP31 Zornitza Stark Phenotypes for gene: BCAP31 were changed from Deafness, dystonia and cerebellar hypomyelination, 300475 to Deafness, dystonia and cerebellar hypomyelination, MIM#300475
Dystonia - complex v0.250 BCAP31 Zornitza Stark Publications for gene: BCAP31 were set to
Dystonia - complex v0.249 C19orf12 Zornitza Stark Marked gene: C19orf12 as ready
Dystonia - complex v0.249 C19orf12 Zornitza Stark Gene: c19orf12 has been classified as Green List (High Evidence).
Dystonia - complex v0.249 C19orf12 Zornitza Stark Phenotypes for gene: C19orf12 were changed from mitochondrial membrane protein-associated neurodegeneration; neurodegeneration with brain iron accumulation-4; Dystonia to neurodegeneration with brain iron accumulation 4 MONDO:0013674
Dystonia - complex v0.248 C19orf12 Zornitza Stark Publications for gene: C19orf12 were set to
Differences of Sex Development v1.0 Zornitza Stark promoted panel to version 1.0
Differences of Sex Development v0.380 TWNK Zornitza Stark Marked gene: TWNK as ready
Differences of Sex Development v0.380 TWNK Zornitza Stark Gene: twnk has been classified as Green List (High Evidence).
Differences of Sex Development v0.380 TWNK Zornitza Stark Phenotypes for gene: TWNK were changed from Perrault syndrome 5; MIM# 616138 to Perrault syndrome 5, MIM# 616138
Differences of Sex Development v0.379 TWNK Zornitza Stark Publications for gene: TWNK were set to PMID: 25355836, 31852434, 31455392
Differences of Sex Development v0.378 POLR1C Zornitza Stark Marked gene: POLR1C as ready
Differences of Sex Development v0.378 POLR1C Zornitza Stark Gene: polr1c has been classified as Red List (Low Evidence).
Differences of Sex Development v0.378 POLR1C Zornitza Stark Publications for gene: POLR1C were set to PMID: 26151409, 32042905, 33005949, ............22855961
Differences of Sex Development v0.375 AXL Zornitza Stark Marked gene: AXL as ready
Differences of Sex Development v0.375 AXL Zornitza Stark Gene: axl has been classified as Red List (Low Evidence).
Differences of Sex Development v0.375 SOX2 Zornitza Stark Marked gene: SOX2 as ready
Differences of Sex Development v0.375 SOX2 Zornitza Stark Gene: sox2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.375 POLR3B Zornitza Stark Marked gene: POLR3B as ready
Differences of Sex Development v0.375 POLR3B Zornitza Stark Gene: polr3b has been classified as Green List (High Evidence).
Differences of Sex Development v0.375 POLR3B Zornitza Stark Publications for gene: POLR3B were set to PubMed: 27512013, 23355746, 22036171, 22036172, 25339210, 33005949, 22855961
Differences of Sex Development v0.374 POLR3A Zornitza Stark Marked gene: POLR3A as ready
Differences of Sex Development v0.374 POLR3A Zornitza Stark Gene: polr3a has been classified as Green List (High Evidence).
Differences of Sex Development v0.374 POLR3A Zornitza Stark Publications for gene: POLR3A were set to PubMed: 21855841, 25339210, 33005949, 22855961
Differences of Sex Development v0.373 MARS2 Zornitza Stark Marked gene: MARS2 as ready
Differences of Sex Development v0.373 MARS2 Zornitza Stark Gene: mars2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.373 MARS2 Zornitza Stark Publications for gene: MARS2 were set to PMID: 27650058, 21464306, 27087618
Differences of Sex Development v0.372 LARS2 Zornitza Stark Marked gene: LARS2 as ready
Differences of Sex Development v0.372 LARS2 Zornitza Stark Gene: lars2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.372 LARS2 Zornitza Stark Phenotypes for gene: LARS2 were changed from Perrault syndrome 4; MIM# 615300 to Perrault syndrome 4, MIM# 615300
Differences of Sex Development v0.371 LARS2 Zornitza Stark Publications for gene: LARS2 were set to PMID: 32423379, 29205794, 23541342, 30737337, 26657938,
Differences of Sex Development v0.370 IRF6 Zornitza Stark Marked gene: IRF6 as ready
Differences of Sex Development v0.370 IRF6 Zornitza Stark Gene: irf6 has been classified as Green List (High Evidence).
Differences of Sex Development v0.370 HHAT Zornitza Stark Marked gene: HHAT as ready
Differences of Sex Development v0.370 HHAT Zornitza Stark Gene: hhat has been classified as Green List (High Evidence).
Differences of Sex Development v0.370 HHAT Zornitza Stark Publications for gene: HHAT were set to PMID: 24784881, 33749989, 35045414
Differences of Sex Development v0.369 HARS2 Zornitza Stark Marked gene: HARS2 as ready
Differences of Sex Development v0.369 HARS2 Zornitza Stark Gene: hars2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.369 HARS2 Zornitza Stark Publications for gene: HARS2 were set to PMID: 27650058, 21464306, 27087618
Differences of Sex Development v0.368 FREM2 Zornitza Stark Marked gene: FREM2 as ready
Differences of Sex Development v0.368 FREM2 Zornitza Stark Gene: frem2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.368 FREM2 Zornitza Stark Publications for gene: FREM2 were set to PMID: 15838507, 29688405, 18203166, 18671281, 18000968
Differences of Sex Development v0.367 WT1 Zornitza Stark Marked gene: WT1 as ready
Differences of Sex Development v0.367 WT1 Zornitza Stark Gene: wt1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.367 WT1 Zornitza Stark Phenotypes for gene: WT1 were changed from to Wilms tumor, MONDO:0006058; Wilms tumor 1, MONDO:0008679; Wilms tumor, type 1, MIM#194070; Denys-Drash syndrome, MIM#194080; Frasier syndrome, MIM#136680
Differences of Sex Development v0.366 WT1 Zornitza Stark Mode of inheritance for gene: WT1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.365 SRY Zornitza Stark Marked gene: SRY as ready
Differences of Sex Development v0.365 SRY Zornitza Stark Gene: sry has been classified as Green List (High Evidence).
Differences of Sex Development v0.365 SRY Zornitza Stark Phenotypes for gene: SRY were changed from to 46XX sex reversal 1, MIM# 400045; 46XY sex reversal 1 , MIM#400044
Differences of Sex Development v0.364 SRY Zornitza Stark Publications for gene: SRY were set to
Differences of Sex Development v0.363 SRY Zornitza Stark Mode of inheritance for gene: SRY was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Differences of Sex Development v0.362 SOX9 Zornitza Stark Marked gene: SOX9 as ready
Differences of Sex Development v0.362 SOX9 Zornitza Stark Gene: sox9 has been classified as Green List (High Evidence).
Differences of Sex Development v0.362 SOX9 Zornitza Stark Phenotypes for gene: SOX9 were changed from to Campomelic dysplasia, MIM# 114290; Campomelic dysplasia, MONDO:0007251; Acampomelic campomelic dysplasia, MIM # 114290, 46XX sex reversal 2, MIM# 278850; 46XY sex reversal 10, MIM # 616425
Differences of Sex Development v0.361 SOX9 Zornitza Stark Mode of inheritance for gene: SOX9 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.360 FGFR1 Zornitza Stark Marked gene: FGFR1 as ready
Differences of Sex Development v0.360 FGFR1 Zornitza Stark Gene: fgfr1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.360 FGFR1 Zornitza Stark Phenotypes for gene: FGFR1 were changed from to Encephalocraniocutaneous lipomatosis, somatic mosaic 613001; Hartsfield syndrome 615465; Hypogonadotropic hypogonadism 2 with or without anosmia 147950; Osteoglophonic dysplasia 166250
Differences of Sex Development v0.359 FGFR1 Zornitza Stark Publications for gene: FGFR1 were set to
Differences of Sex Development v0.358 FGFR1 Zornitza Stark Mode of inheritance for gene: FGFR1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences of Sex Development v0.357 FGFR2 Zornitza Stark Marked gene: FGFR2 as ready
Differences of Sex Development v0.357 FGFR2 Zornitza Stark Gene: fgfr2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.357 FGFR2 Zornitza Stark Phenotypes for gene: FGFR2 were changed from to Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis,MIM# 207410, Apert syndrome, MIM# 101200, Beare-Stevenson cutis gyrata syndrome, MIM# 123790, Bent bone dysplasia syndrome, MIM# 614592
Differences of Sex Development v0.356 FGFR2 Zornitza Stark Publications for gene: FGFR2 were set to
Differences of Sex Development v0.355 FGFR2 Zornitza Stark Mode of inheritance for gene: FGFR2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.354 FSHB Zornitza Stark Marked gene: FSHB as ready
Differences of Sex Development v0.354 FSHB Zornitza Stark Gene: fshb has been classified as Green List (High Evidence).
Differences of Sex Development v0.354 FSHB Zornitza Stark Phenotypes for gene: FSHB were changed from to Hypogonadotropic hypogonadism 24 without anosmia, MIM#229070
Differences of Sex Development v0.353 FSHB Zornitza Stark Publications for gene: FSHB were set to
Differences of Sex Development v0.352 FSHB Zornitza Stark Mode of inheritance for gene: FSHB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.351 FSHR Zornitza Stark Phenotypes for gene: FSHR were changed from to Ovarian dysgenesis 1 MONDO:0024463; Ovarian hyperstimulation syndrome MONDO:0011972
Differences of Sex Development v0.350 FSHR Zornitza Stark Marked gene: FSHR as ready
Differences of Sex Development v0.350 FSHR Zornitza Stark Gene: fshr has been classified as Green List (High Evidence).
Differences of Sex Development v0.350 FSHR Zornitza Stark Publications for gene: FSHR were set to
Differences of Sex Development v0.349 FSHR Zornitza Stark Mode of inheritance for gene: FSHR was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Dystonia - complex v0.247 COASY Zornitza Stark Marked gene: COASY as ready
Dystonia - complex v0.247 COASY Zornitza Stark Gene: coasy has been classified as Green List (High Evidence).
Dystonia - complex v0.247 COASY Zornitza Stark Phenotypes for gene: COASY were changed from COASY protein-associated neurodegeneration; Neurodegeneration with brain iron accumulation 6 615643 to neurodegeneration with brain iron accumulation 6, MONDO:0014290; Neurodegeneration with brain iron accumulation 6 615643
Dystonia - complex v0.246 COASY Zornitza Stark Publications for gene: COASY were set to
Dystonia - complex v0.245 DCAF17 Zornitza Stark Marked gene: DCAF17 as ready
Dystonia - complex v0.245 DCAF17 Zornitza Stark Gene: dcaf17 has been classified as Green List (High Evidence).
Dystonia - complex v0.245 DCAF17 Zornitza Stark Phenotypes for gene: DCAF17 were changed from Woodhouse-Sakati syndrome; Dystonia to Woodhouse-Sakati syndrome MONDO:0009419; Dystonia
Dystonia - complex v0.244 DCAF17 Zornitza Stark Publications for gene: DCAF17 were set to
Syndromic Retinopathy v0.219 GPATCH11 Zornitza Stark Publications for gene: GPATCH11 were set to
Syndromic Retinopathy v0.218 GPATCH11 Zornitza Stark reviewed gene: GPATCH11: Rating: GREEN; Mode of pathogenicity: None; Publications: 39572588; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.12 GPATCH11 Zornitza Stark Publications for gene: GPATCH11 were set to
Intellectual disability syndromic and non-syndromic v1.11 GPATCH11 Zornitza Stark reviewed gene: GPATCH11: Rating: GREEN; Mode of pathogenicity: None; Publications: 39572588; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2186 GPATCH11 Zornitza Stark Publications for gene: GPATCH11 were set to
Dystonia - complex v0.243 DDC Zornitza Stark Marked gene: DDC as ready
Dystonia - complex v0.243 DDC Zornitza Stark Gene: ddc has been classified as Green List (High Evidence).
Dystonia - complex v0.243 DDC Zornitza Stark Publications for gene: DDC were set to
Paroxysmal Dyskinesia v0.141 ALDH5A1 Zornitza Stark Marked gene: ALDH5A1 as ready
Paroxysmal Dyskinesia v0.141 ALDH5A1 Zornitza Stark Gene: aldh5a1 has been classified as Green List (High Evidence).
Paroxysmal Dyskinesia v0.141 ALDH5A1 Zornitza Stark Phenotypes for gene: ALDH5A1 were changed from epilepsy; paroxysmal exercise induced dyskinesia; globus pallidus hyperintensities on MRI to Succinic semialdehyde dehydrogenase deficiency, MIM# 271980
Paroxysmal Dyskinesia v0.140 ALDH5A1 Zornitza Stark Classified gene: ALDH5A1 as Green List (high evidence)
Paroxysmal Dyskinesia v0.140 ALDH5A1 Zornitza Stark Gene: aldh5a1 has been classified as Green List (High Evidence).
Paroxysmal Dyskinesia v0.139 ALDH5A1 Zornitza Stark reviewed gene: ALDH5A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Succinic semialdehyde dehydrogenase deficiency, MIM# 271980; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paroxysmal Dyskinesia v0.139 SPR Zornitza Stark Marked gene: SPR as ready
Paroxysmal Dyskinesia v0.139 SPR Zornitza Stark Gene: spr has been classified as Amber List (Moderate Evidence).
Paroxysmal Dyskinesia v0.139 SPR Zornitza Stark Phenotypes for gene: SPR were changed from to Dopa-responsive dystonia due to sepiapterin reductase deficiency MONDO:0012994
Paroxysmal Dyskinesia v0.138 SPR Zornitza Stark Publications for gene: SPR were set to
Paroxysmal Dyskinesia v0.137 SPR Zornitza Stark Mode of inheritance for gene: SPR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Paroxysmal Dyskinesia v0.136 SPR Zornitza Stark Classified gene: SPR as Amber List (moderate evidence)
Paroxysmal Dyskinesia v0.136 SPR Zornitza Stark Gene: spr has been classified as Amber List (Moderate Evidence).
Paroxysmal Dyskinesia v0.135 SPR Zornitza Stark reviewed gene: SPR: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Dopa-responsive dystonia due to sepiapterin reductase deficiency MONDO:0012994; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paroxysmal Dyskinesia v0.135 KCNJ10 Zornitza Stark Publications for gene: KCNJ10 were set to 38979912
Paroxysmal Dyskinesia v0.134 KCNJ10 Zornitza Stark Mode of inheritance for gene: KCNJ10 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.2185 HMGCS1 Zornitza Stark Marked gene: HMGCS1 as ready
Mendeliome v1.2185 HMGCS1 Zornitza Stark Gene: hmgcs1 has been classified as Green List (High Evidence).
Mendeliome v1.2185 HMGCS1 Zornitza Stark Classified gene: HMGCS1 as Green List (high evidence)
Mendeliome v1.2185 HMGCS1 Zornitza Stark Gene: hmgcs1 has been classified as Green List (High Evidence).
Mendeliome v1.2184 HMGCS1 Zornitza Stark gene: HMGCS1 was added
gene: HMGCS1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HMGCS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HMGCS1 were set to 39531736
Phenotypes for gene: HMGCS1 were set to Rigid spine syndrome, MONDO:0019951, HMGCS1-related
Review for gene: HMGCS1 was set to GREEN
Added comment: Five individuals from four families reported. All individuals presented with spinal rigidity primarily affecting the cervical and dorsolumbar regions, scoliosis, and respiratory insufficiency. Creatine kinase levels were variably elevated. The clinical course worsened with intercurrent disease or certain drugs in some; one individual died from respiratory failure following infection. Muscle biopsies revealed irregularities in oxidative enzyme staining with occasional internal nuclei and rimmed vacuoles.
HMGCS1 encodes a critical enzyme of the mevalonate pathway. Notably, biallelic hypomorphic variants in downstream enzymes including HMGCR and GGPS1 are associated with muscular dystrophy. Hmgcs1 mutant zebrafish displayed severe early defects, including immobility at 2 days and death by day 3 post-fertilisation and were rescued by HMGCS1 mRNA. Four variants tested (S447P, Q29L M70T, and C268S) have reduced function compared to wildtype HMGCS1 in zebrafish rescue assays
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.81 HMGCS1 Zornitza Stark Marked gene: HMGCS1 as ready
Muscular dystrophy and myopathy_Paediatric v1.81 HMGCS1 Zornitza Stark Gene: hmgcs1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.81 HMGCS1 Zornitza Stark Classified gene: HMGCS1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.81 HMGCS1 Zornitza Stark Gene: hmgcs1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.80 HMGCS1 Zornitza Stark gene: HMGCS1 was added
gene: HMGCS1 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: HMGCS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HMGCS1 were set to 39531736
Phenotypes for gene: HMGCS1 were set to Rigid spine syndrome, MONDO:0019951, HMGCS1-related
Review for gene: HMGCS1 was set to GREEN
Added comment: Five individuals from four families reported. All individuals presented with spinal rigidity primarily affecting the cervical and dorsolumbar regions, scoliosis, and respiratory insufficiency. Creatine kinase levels were variably elevated. The clinical course worsened with intercurrent disease or certain drugs in some; one individual died from respiratory failure following infection. Muscle biopsies revealed irregularities in oxidative enzyme staining with occasional internal nuclei and rimmed vacuoles.
HMGCS1 encodes a critical enzyme of the mevalonate pathway. Notably, biallelic hypomorphic variants in downstream enzymes including HMGCR and GGPS1 are associated with muscular dystrophy. Hmgcs1 mutant zebrafish displayed severe early defects, including immobility at 2 days and death by day 3 post-fertilisation and were rescued by HMGCS1 mRNA. Four variants tested (S447P, Q29L M70T, and C268S) have reduced function compared to wildtype HMGCS1 in zebrafish rescue assays
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.11 MGA Zornitza Stark Marked gene: MGA as ready
Intellectual disability syndromic and non-syndromic v1.11 MGA Zornitza Stark Gene: mga has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.11 MGA Zornitza Stark Classified gene: MGA as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.11 MGA Zornitza Stark Gene: mga has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.10 MGA Zornitza Stark gene: MGA was added
gene: MGA was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: MGA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MGA were set to 39600096; 20044811
Phenotypes for gene: MGA were set to Syndromic disease, MONDO:0002254, MGA-related
Review for gene: MGA was set to GREEN
Added comment: Three individuals with de novo LoF variants reported in individuals with ID and congenital anomalies. Zebrafish model supports role of this transcription factor in organogenesis. Note there are previous, less clear reports of association with NDD/CHD. Gene is constrained for LoF variants in gnomad v4; however, note there are ~30 individuals with LoF variants present. Borderline Green/Amber.
Sources: Literature
Mendeliome v1.2183 CMPK2 Zornitza Stark Marked gene: CMPK2 as ready
Mendeliome v1.2183 CMPK2 Zornitza Stark Gene: cmpk2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2183 CMPK2 Zornitza Stark Classified gene: CMPK2 as Amber List (moderate evidence)
Mendeliome v1.2183 CMPK2 Zornitza Stark Gene: cmpk2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2182 CMPK2 Zornitza Stark gene: CMPK2 was added
gene: CMPK2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CMPK2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CMPK2 were set to 36443312
Phenotypes for gene: CMPK2 were set to bilateral striopallidodentate calcinosis, MONDO:0008947, CMPK2-related
Review for gene: CMPK2 was set to AMBER
Added comment: Three individuals from two unrelated families reported. One family (two sibs) with homozygous start loss variant, and the other family with compound het variants. Adult-onset neurodegenerative disorder. Extensive functional data including mouse model. Evidence of underlying mitochondrial dysfunction.
Sources: Literature
Brain Calcification v1.99 CMPK2 Zornitza Stark Marked gene: CMPK2 as ready
Brain Calcification v1.99 CMPK2 Zornitza Stark Gene: cmpk2 has been classified as Amber List (Moderate Evidence).
Brain Calcification v1.99 CMPK2 Zornitza Stark Classified gene: CMPK2 as Amber List (moderate evidence)
Brain Calcification v1.99 CMPK2 Zornitza Stark Gene: cmpk2 has been classified as Amber List (Moderate Evidence).
Brain Calcification v1.98 CMPK2 Zornitza Stark gene: CMPK2 was added
gene: CMPK2 was added to Brain Calcification. Sources: Literature
Mode of inheritance for gene: CMPK2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CMPK2 were set to 36443312
Phenotypes for gene: CMPK2 were set to bilateral striopallidodentate calcinosis, MONDO:0008947, CMPK2-related
Review for gene: CMPK2 was set to AMBER
Added comment: Three individuals from two unrelated families reported. One family (two sibs) with homozygous start loss variant, and the other family with compound het variants. Adult-onset neurodegenerative disorder. Extensive functional data including mouse model. Evidence of underlying mitochondrial dysfunction.
Sources: Literature
Mitochondrial disease v0.958 CMPK2 Zornitza Stark Classified gene: CMPK2 as Amber List (moderate evidence)
Mitochondrial disease v0.958 CMPK2 Zornitza Stark Gene: cmpk2 has been classified as Amber List (Moderate Evidence).
Mitochondrial disease v0.958 CMPK2 Zornitza Stark Marked gene: CMPK2 as ready
Mitochondrial disease v0.958 CMPK2 Zornitza Stark Gene: cmpk2 has been classified as Amber List (Moderate Evidence).
Mitochondrial disease v0.958 CMPK2 Zornitza Stark Classified gene: CMPK2 as Amber List (moderate evidence)
Mitochondrial disease v0.958 CMPK2 Zornitza Stark Gene: cmpk2 has been classified as Amber List (Moderate Evidence).
Mitochondrial disease v0.957 CMPK2 Zornitza Stark gene: CMPK2 was added
gene: CMPK2 was added to Mitochondrial disease. Sources: Literature
Mode of inheritance for gene: CMPK2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CMPK2 were set to 36443312
Phenotypes for gene: CMPK2 were set to bilateral striopallidodentate calcinosis, MONDO:0008947, CMPK2-related
Review for gene: CMPK2 was set to AMBER
Added comment: Three individuals from two unrelated families reported. One family (two sibs) with homozygous start loss variant, and the other family with compound het variants. Adult-onset neurodegenerative disorder. Extensive functional data including mouse model. Evidence of underlying mitochondrial dysfunction.
Sources: Literature
Vascular Malformations_Somatic v1.14 MAP3K3 Zornitza Stark Phenotypes for gene: MAP3K3 were changed from Verrucous venous malformation; Cerebral malformation, MONDO:0016054, MAP3K3-related to Verrucous venous malformation; Cerebral cavernous malformations 5, MIM# 621032
Vascular Malformations_Somatic v1.13 MAP3K3 Zornitza Stark reviewed gene: MAP3K3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebral cavernous malformations 5, MIM# 621032; Mode of inheritance: None
Mendeliome v1.2181 MAP3K3 Zornitza Stark Phenotypes for gene: MAP3K3 were changed from Cerebral malformation, MONDO:0016054, MAP3K3-related to Cerebral cavernous malformations 5, MIM# 621032
Mendeliome v1.2180 MAP3K3 Zornitza Stark edited their review of gene: MAP3K3: Changed phenotypes: Cerebral cavernous malformations 5, MIM# 621032
Pulmonary Fibrosis_Interstitial Lung Disease v0.84 POLA2 Bryony Thompson Marked gene: POLA2 as ready
Pulmonary Fibrosis_Interstitial Lung Disease v0.84 POLA2 Bryony Thompson Gene: pola2 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.84 POLA2 Bryony Thompson Classified gene: POLA2 as Green List (high evidence)
Pulmonary Fibrosis_Interstitial Lung Disease v0.84 POLA2 Bryony Thompson Gene: pola2 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.83 POLA2 Bryony Thompson gene: POLA2 was added
gene: POLA2 was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Literature
Mode of inheritance for gene: POLA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLA2 were set to 39616267
Phenotypes for gene: POLA2 were set to Telomere biology syndrome MONDO:0100137
Review for gene: POLA2 was set to GREEN
Added comment: Pulmonary fibrosis is a feature of the phenotype in 4 cases from 2 unrelated families with biallelic variants with functional evidence supporting an effect on telomere length. Pulmonary fibrosis is a common feature of telomere biology disorders.
Sources: Literature
Syndromic Retinopathy v0.218 POLA2 Bryony Thompson Marked gene: POLA2 as ready
Syndromic Retinopathy v0.218 POLA2 Bryony Thompson Gene: pola2 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.218 POLA2 Bryony Thompson Classified gene: POLA2 as Green List (high evidence)
Syndromic Retinopathy v0.218 POLA2 Bryony Thompson Gene: pola2 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.217 POLA2 Bryony Thompson gene: POLA2 was added
gene: POLA2 was added to Syndromic Retinopathy. Sources: Literature
Mode of inheritance for gene: POLA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLA2 were set to 39616267
Phenotypes for gene: POLA2 were set to Telomere biology syndrome MONDO:0100137
Review for gene: POLA2 was set to GREEN
Added comment: Retinal telangiectasias/exudates (Coats disease) is a feature of the phenotype. 5 cases from 2 unrelated families with biallelic variants with functional evidence supporting an effect on telomere length.
Sources: Literature
Mendeliome v1.2180 POLA2 Bryony Thompson Phenotypes for gene: POLA2 were changed from Telomere biology disorders; Coats plus syndrome MONDO:0012815 to Telomere biology syndrome MONDO:0100137
Bone Marrow Failure v1.108 POLA2 Bryony Thompson Phenotypes for gene: POLA2 were changed from Telomere biology disorders; Coats plus syndrome MONDO:0012815 to Telomere biology syndrome MONDO:0100137
Bone Marrow Failure v1.107 POLA2 Bryony Thompson Marked gene: POLA2 as ready
Bone Marrow Failure v1.107 POLA2 Bryony Thompson Gene: pola2 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.107 POLA2 Bryony Thompson Classified gene: POLA2 as Green List (high evidence)
Bone Marrow Failure v1.107 POLA2 Bryony Thompson Gene: pola2 has been classified as Green List (High Evidence).
Mendeliome v1.2179 POLA2 Bryony Thompson Marked gene: POLA2 as ready
Mendeliome v1.2179 POLA2 Bryony Thompson Gene: pola2 has been classified as Green List (High Evidence).
Mendeliome v1.2179 POLA2 Bryony Thompson Classified gene: POLA2 as Green List (high evidence)
Mendeliome v1.2179 POLA2 Bryony Thompson Gene: pola2 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.296 CTGF Bryony Thompson Marked gene: CTGF as ready
Skeletal dysplasia v0.296 CTGF Bryony Thompson Gene: ctgf has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v0.296 CTGF Bryony Thompson Phenotypes for gene: CTGF were changed from Kyphomelic dysplasia to Kyphomelic dysplasia MONDO:0008881; Spondyloepimetaphyseal dysplasia MONDO:0100510
Skeletal dysplasia v0.295 CTGF Bryony Thompson Classified gene: CTGF as Amber List (moderate evidence)
Skeletal dysplasia v0.295 CTGF Bryony Thompson Gene: ctgf has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v0.294 CTGF Bryony Thompson reviewed gene: CTGF: Rating: RED; Mode of pathogenicity: None; Publications: 39414788, 20534727; Phenotypes: Spondyloepimetaphyseal dysplasia MONDO:0100510; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.2178 CTGF Bryony Thompson Marked gene: CTGF as ready
Mendeliome v1.2178 CTGF Bryony Thompson Gene: ctgf has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2178 CTGF Bryony Thompson Phenotypes for gene: CTGF were changed from Kyphomelic dysplasia to Kyphomelic dysplasia MONDO:0008881; Spondyloepimetaphyseal dysplasia MONDO:0100510
Mendeliome v1.2177 CTGF Bryony Thompson Publications for gene: CTGF were set to 39506047
Mendeliome v1.2176 CTGF Bryony Thompson Classified gene: CTGF as Amber List (moderate evidence)
Mendeliome v1.2176 CTGF Bryony Thompson Gene: ctgf has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2175 CTGF Bryony Thompson edited their review of gene: CTGF: Changed publications: 39414788, 20534727
Mendeliome v1.2175 CTGF Bryony Thompson edited their review of gene: CTGF: Changed publications: 39414788, 39414788
Mendeliome v1.2175 CTGF Bryony Thompson reviewed gene: CTGF: Rating: RED; Mode of pathogenicity: None; Publications: 39414788; Phenotypes: Spondyloepimetaphyseal dysplasia MONDO:0100510; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal Dysplasia_Fetal v0.225 CTGF Bryony Thompson Marked gene: CTGF as ready
Skeletal Dysplasia_Fetal v0.225 CTGF Bryony Thompson Gene: ctgf has been classified as Amber List (Moderate Evidence).
Skeletal Dysplasia_Fetal v0.225 CTGF Bryony Thompson Phenotypes for gene: CTGF were changed from Kyphomelic dysplasia to Kyphomelic dysplasia MONDO:0008881
Skeletal Dysplasia_Fetal v0.224 CTGF Bryony Thompson Classified gene: CTGF as Amber List (moderate evidence)
Skeletal Dysplasia_Fetal v0.224 CTGF Bryony Thompson Gene: ctgf has been classified as Amber List (Moderate Evidence).
Combined Immunodeficiency v1.112 GUK1 Bryony Thompson Marked gene: GUK1 as ready
Combined Immunodeficiency v1.112 GUK1 Bryony Thompson Gene: guk1 has been classified as Amber List (Moderate Evidence).
Combined Immunodeficiency v1.112 GUK1 Bryony Thompson Classified gene: GUK1 as Amber List (moderate evidence)
Combined Immunodeficiency v1.112 GUK1 Bryony Thompson Gene: guk1 has been classified as Amber List (Moderate Evidence).
Combined Immunodeficiency v1.111 GUK1 Bryony Thompson gene: GUK1 was added
gene: GUK1 was added to Combined Immunodeficiency. Sources: Literature
Mode of inheritance for gene: GUK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GUK1 were set to 39230499
Phenotypes for gene: GUK1 were set to Mitochondrial DNA depletion syndrome MONDO:0018158, GUK1-related
Review for gene: GUK1 was set to AMBER
Added comment: Three cases from 2 unrelated families with biallelic variants leading to GUK1 deficiency had altered T-lymphocyte profiles, along with ptosis, ophthalmoparesis, myopathic proximal limb weakness, and variable hepatopathy. One additional case in this study had a normal lymphocyte profile.
Sources: Literature
Mitochondrial disease v0.956 GUK1 Bryony Thompson Marked gene: GUK1 as ready
Mitochondrial disease v0.956 GUK1 Bryony Thompson Gene: guk1 has been classified as Green List (High Evidence).
Mitochondrial disease v0.956 GUK1 Bryony Thompson Classified gene: GUK1 as Green List (high evidence)
Mitochondrial disease v0.956 GUK1 Bryony Thompson Gene: guk1 has been classified as Green List (High Evidence).
Mitochondrial disease v0.956 GUK1 Bryony Thompson Classified gene: GUK1 as Green List (high evidence)
Mitochondrial disease v0.956 GUK1 Bryony Thompson Gene: guk1 has been classified as Green List (High Evidence).
Mitochondrial disease v0.955 GUK1 Bryony Thompson gene: GUK1 was added
gene: GUK1 was added to Mitochondrial disease. Sources: Literature
Mode of inheritance for gene: GUK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GUK1 were set to 39230499
Phenotypes for gene: GUK1 were set to Mitochondrial DNA depletion syndrome MONDO:0018158, GUK1-related
Review for gene: GUK1 was set to GREEN
Added comment: 4 adult cases from 3 unrelated families with biallelic variants leading to GUK1 deficiency. Cases presented with ptosis, ophthalmoparesis, myopathic proximal limb weakness, variable hepatopathy, and altered T-lymphocyte profiles. Initial manifestations in childhood or adolescence and developed ptosis and skeletal myopathy. mtDNA depletion/deletions are present in muscle biopsies of reduced activities of mitochondrial respiratory chain enzymes in all 4 cases.
Sources: Literature
Rhabdomyolysis and Metabolic Myopathy v1.19 GUK1 Bryony Thompson Marked gene: GUK1 as ready
Rhabdomyolysis and Metabolic Myopathy v1.19 GUK1 Bryony Thompson Gene: guk1 has been classified as Green List (High Evidence).
Nucleotide metabolism disorders v0.4 GUK1 Bryony Thompson Marked gene: GUK1 as ready
Nucleotide metabolism disorders v0.4 GUK1 Bryony Thompson Gene: guk1 has been classified as Green List (High Evidence).
Nucleotide metabolism disorders v0.4 GUK1 Bryony Thompson Classified gene: GUK1 as Green List (high evidence)
Nucleotide metabolism disorders v0.4 GUK1 Bryony Thompson Gene: guk1 has been classified as Green List (High Evidence).
Nucleotide metabolism disorders v0.3 GUK1 Bryony Thompson gene: GUK1 was added
gene: GUK1 was added to Nucleotide metabolism disorders. Sources: Literature
Mode of inheritance for gene: GUK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GUK1 were set to 39230499
Phenotypes for gene: GUK1 were set to Mitochondrial DNA depletion syndrome MONDO:0018158, GUK1-related
Review for gene: GUK1 was set to GREEN
Added comment: Guanylate kinase, encoded by GUK1, is a nucleotide monophosphate kinase. 4 adult cases from 3 unrelated families with biallelic variants leading to GUK1 deficiency. Cases presented with ptosis, ophthalmoparesis, myopathic proximal limb weakness, variable hepatopathy, and altered T-lymphocyte profiles. Initial manifestations in childhood or adolescence and developed ptosis and skeletal myopathy. mtDNA depletion/deletions are present in muscle biopsies of reduced activities of mitochondrial respiratory chain enzymes in all 4 cases.
Sources: Literature
Mendeliome v1.2175 GUK1 Bryony Thompson Phenotypes for gene: GUK1 were changed from Mitochondrial DNA depletion syndrome MONDO:0018158 to Mitochondrial DNA depletion syndrome MONDO:0018158, GUK1-related
Rhabdomyolysis and Metabolic Myopathy v1.19 GUK1 Bryony Thompson Classified gene: GUK1 as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v1.19 GUK1 Bryony Thompson Gene: guk1 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v1.18 GUK1 Bryony Thompson gene: GUK1 was added
gene: GUK1 was added to Rhabdomyolysis and Metabolic Myopathy. Sources: Literature
Mode of inheritance for gene: GUK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GUK1 were set to 39230499
Phenotypes for gene: GUK1 were set to Mitochondrial DNA depletion syndrome MONDO:0018158, GUK1-related
Review for gene: GUK1 was set to GREEN
Added comment: 4 adult cases from 3 unrelated families with biallelic variants leading to GUK1 deficiency. Cases presented with ptosis, ophthalmoparesis, myopathic proximal limb weakness, variable hepatopathy, and altered T-lymphocyte profiles. Initial manifestations in childhood or adolescence and developed ptosis and skeletal myopathy. mtDNA depletion/deletions are present in muscle biopsies of reduced activities of mitochondrial respiratory chain enzymes in all 4 cases. The condition presents with a mitochondrial myopathy.
Sources: Literature
Mendeliome v1.2174 GUK1 Bryony Thompson Marked gene: GUK1 as ready
Mendeliome v1.2174 GUK1 Bryony Thompson Gene: guk1 has been classified as Green List (High Evidence).
Mendeliome v1.2174 GUK1 Bryony Thompson Classified gene: GUK1 as Green List (high evidence)
Mendeliome v1.2174 GUK1 Bryony Thompson Gene: guk1 has been classified as Green List (High Evidence).
Mendeliome v1.2173 GUK1 Bryony Thompson gene: GUK1 was added
gene: GUK1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GUK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GUK1 were set to 39230499
Phenotypes for gene: GUK1 were set to Mitochondrial DNA depletion syndrome MONDO:0018158
Review for gene: GUK1 was set to GREEN
Added comment: 4 adult cases from 3 unrelated families with biallelic variants leading to GUK1 deficiency. Cases presented with ptosis, ophthalmoparesis, myopathic proximal limb weakness, variable hepatopathy, and altered T-lymphocyte profiles. Initial manifestations in childhood or adolescence and developed ptosis and skeletal myopathy. mtDNA depletion/deletions are present in muscle biopsies of reduced activities of mitochondrial respiratory chain enzymes in all 4 cases.
Sources: Literature
Mendeliome v1.2172 PPP2R2B Bryony Thompson Phenotypes for gene: PPP2R2B were changed from to Neurodevelopmental disorder MONDO:0700092, PPP2R2B-related
Intellectual disability syndromic and non-syndromic v1.9 PPP2R2B Bryony Thompson Marked gene: PPP2R2B as ready
Intellectual disability syndromic and non-syndromic v1.9 PPP2R2B Bryony Thompson Gene: ppp2r2b has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2171 PPP2R2B Bryony Thompson Publications for gene: PPP2R2B were set to
Intellectual disability syndromic and non-syndromic v1.9 PPP2R2B Bryony Thompson Classified gene: PPP2R2B as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v1.9 PPP2R2B Bryony Thompson Gene: ppp2r2b has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2170 PPP2R2B Bryony Thompson Mode of inheritance for gene: PPP2R2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v1.8 PPP2R2B Bryony Thompson Classified gene: PPP2R2B as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v1.8 PPP2R2B Bryony Thompson Gene: ppp2r2b has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2169 PPP2R2B Bryony Thompson Classified gene: PPP2R2B as Amber List (moderate evidence)
Mendeliome v1.2169 PPP2R2B Bryony Thompson Gene: ppp2r2b has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2168 PPP2R2B Bryony Thompson reviewed gene: PPP2R2B: Rating: AMBER; Mode of pathogenicity: None; Publications: 25356899, 39565297; Phenotypes: Neurodevelopmental disorder MONDO:0700092, PPP2R2B-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v1.7 PPP2R2B Bryony Thompson gene: PPP2R2B was added
gene: PPP2R2B was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PPP2R2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPP2R2B were set to 25356899; 39565297
Phenotypes for gene: PPP2R2B were set to Neurodevelopmental disorder MONDO:0700092, PPP2R2B-related
Review for gene: PPP2R2B was set to AMBER
Added comment: 5 cases with NDD and heterozygous missense (4/5 confirmed de novo): p.Thr246Lys (unknown inheritance), p.Asn310Lys (confirmed de novo), p.Glu37Lys (confirmed de novo, also had RNU4-2 path de novo Path variant), p.Ile427Thr (confirmed de novo, also had TAOK1 inherited Path variant), p.Arg149Pro (confirmed de novo). 5/5 with intellectual disability and developmental delay, 4/5 with seizures, 2/5 with hearing loss/auditory neuropathy. Study includes in vitro functional assays supporting a possible loss of function mechanism of disease. The 2 missense with additional diagnoses (E37K & I427T) demonstrated a partial reduction in PP2A holoenzyme assembly. Only 3 cases with a possible diagnosis that could be attributed to the PPP2R2B only, and only 2 were confirmed de novo.
Sources: Literature
Mendeliome v1.2168 PPP2R2B Bryony Thompson Deleted their review
Genetic Epilepsy v1.77 PPP2R2B Bryony Thompson Marked gene: PPP2R2B as ready
Genetic Epilepsy v1.77 PPP2R2B Bryony Thompson Gene: ppp2r2b has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v1.77 PPP2R2B Bryony Thompson Classified gene: PPP2R2B as Amber List (moderate evidence)
Genetic Epilepsy v1.77 PPP2R2B Bryony Thompson Gene: ppp2r2b has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v1.76 PPP2R2B Bryony Thompson gene: PPP2R2B was added
gene: PPP2R2B was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PPP2R2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPP2R2B were set to 25356899; 39565297
Phenotypes for gene: PPP2R2B were set to Neurodevelopmental disorder MONDO:0700092, PPP2R2B-related
Review for gene: PPP2R2B was set to AMBER
Added comment: 5 cases with NDD and heterozygous missense (4/5 confirmed de novo): p.Thr246Lys (unknown inheritance), p.Asn310Lys (confirmed de novo), p.Glu37Lys (confirmed de novo, also had RNU4-2 path de novo Path variant), p.Ile427Thr (confirmed de novo, also had TAOK1 inherited Path variant), p.Arg149Pro (confirmed de novo). 5/5 with intellectual disability and developmental delay, 4/5 with seizures, 2/5 with hearing loss/auditory neuropathy. Study includes in vitro functional assays supporting a possible loss of function mechanism of disease. The 2 missense with additional diagnoses (E37K & I427T) demonstrated a partial reduction in PP2A holoenzyme assembly. Only 3 cases with a possible diagnosis that could be attributed to the PPP2R2B only, and only 2 were confirmed de novo.
Sources: Literature
Mendeliome v1.2168 PPP2R2B Bryony Thompson Deleted their comment
Mendeliome v1.2168 PPP2R2B Bryony Thompson edited their review of gene: PPP2R2B: Added comment: 5 cases with NDD and heterozygous missense (4/5 confirmed de novo): p.Thr246Lys (unknown inheritance), p.Asn310Lys (confirmed de novo), p.Glu37Lys (confirmed de novo, also had RNU4-2 path de novo Path variant), p.Ile427Thr (confirmed de novo, also had TAOK1 inherited Path variant), p.Arg149Pro (confirmed de novo). 5/5 with intellectual disability and developmental delay, 4/5 with seizures, 2/5 with hearing loss/auditory neuropathy. Study includes in vitro functional assays supporting a possible loss of function mechanism of disease. The 2 missense with additional diagnoses (E37K & I427T) demonstrated a partial reduction in PP2A holoenzyme assembly. Only 3 cases with a possible diagnosis that could be attributed to the PPP2R2B only, and only 2 were confirmed de novo.; Changed rating: AMBER; Changed publications: 25356899, 39565297; Changed phenotypes: Neurodevelopmental disorder MONDO:0700092
Mendeliome v1.2168 PPP2R2B Bryony Thompson Deleted their comment
Early-onset Dementia v1.27 KIF5A Bryony Thompson Marked gene: KIF5A as ready
Early-onset Dementia v1.27 KIF5A Bryony Thompson Gene: kif5a has been classified as Amber List (Moderate Evidence).
Early-onset Dementia v1.27 KIF5A Bryony Thompson Classified gene: KIF5A as Amber List (moderate evidence)
Early-onset Dementia v1.27 KIF5A Bryony Thompson Gene: kif5a has been classified as Amber List (Moderate Evidence).
Early-onset Dementia v1.26 KIF5A Bryony Thompson gene: KIF5A was added
gene: KIF5A was added to Early-onset Dementia. Sources: Other
Mode of inheritance for gene: KIF5A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF5A were set to 33077544; 36604770
Phenotypes for gene: KIF5A were set to Amyotrophic lateral sclerosis, susceptibility to, 25 MONDO:0060670
Mode of pathogenicity for gene: KIF5A was set to Other
Review for gene: KIF5A was set to AMBER
Added comment: ALS-FTD phenotype has been reported in two families with KIF5A variants. The mechanism of disease is likely gain of function.
Sources: Other
Paroxysmal Dyskinesia v0.133 KCNJ10 Shekeeb Mohammad reviewed gene: KCNJ10: Rating: GREEN; Mode of pathogenicity: None; Publications: 38436103, 38436103; Phenotypes: paroxysmal kinesigenic dyskinesia; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Paroxysmal Dyskinesia v0.133 SPR Shekeeb Mohammad reviewed gene: SPR: Rating: AMBER; Mode of pathogenicity: None; Publications: 32591469; Phenotypes: dopamine responsive dystonia, oculogyric crises; Mode of inheritance: None
Paroxysmal Dyskinesia v0.133 PDHA1 Shekeeb Mohammad reviewed gene: PDHA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: paroyxsmal exercise induced dyskinesia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Paroxysmal Dyskinesia v0.133 ALDH5A1 Shekeeb Mohammad gene: ALDH5A1 was added
gene: ALDH5A1 was added to Paroxysmal Dyskinesia. Sources: Literature
Mode of inheritance for gene: ALDH5A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALDH5A1 were set to 17438226; 38499966
Phenotypes for gene: ALDH5A1 were set to epilepsy; paroxysmal exercise induced dyskinesia; globus pallidus hyperintensities on MRI
Review for gene: ALDH5A1 was set to GREEN
gene: ALDH5A1 was marked as current diagnostic
Added comment: Reported cases with paroyxsmal dyskinesia; exercise induced
current patient under my care with isolated paroxysmal dyskinesia without epilepsy with confirmed pathogenic variants in ALDH5A1 and supportive MRI changes.
This is an important differential for Paroxysmal dyskinesia with globus pallidus changes (in addition to ECHS1 and pyruvate dehydrogenase deficiency)
Sources: Literature
Dystonia - complex v0.242 DDC Sangavi Sivagnanasundram reviewed gene: DDC: Rating: GREEN; Mode of pathogenicity: None; Publications: 20505134; Phenotypes: aromatic L-amino acid decarboxylase deficiency MONDO:0012084; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2168 GPATCH11 Sangavi Sivagnanasundram edited their review of gene: GPATCH11: Changed phenotypes: early-onset retinal dystrophy with neurological impairment MONDO:0019118
Mendeliome v1.2168 CTGF Sangavi Sivagnanasundram edited their review of gene: CTGF: Changed phenotypes: Kyphomelic dysplasia, skeletal dysplasia MONDO:0018230
Skeletal dysplasia v0.294 CTGF Sangavi Sivagnanasundram edited their review of gene: CTGF: Changed phenotypes: Kyphomelic dysplasia, skeletal dysplasia MONDO:0018230
Dystonia - complex v0.242 DCAF17 Sangavi Sivagnanasundram reviewed gene: DCAF17: Rating: GREEN; Mode of pathogenicity: None; Publications: 18175354, 36185913, 17167799; Phenotypes: Woodhouse-Sakati syndrome MONDO:0009419; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia - complex v0.242 COASY Sangavi Sivagnanasundram reviewed gene: COASY: Rating: GREEN; Mode of pathogenicity: None; Publications: 23447832, 24360804, 27021474; Phenotypes: neurodegeneration with brain iron accumulation 6 MONDO:0014290; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Callosome v0.540 WDR47 Bryony Thompson Marked gene: WDR47 as ready
Callosome v0.540 WDR47 Bryony Thompson Gene: wdr47 has been classified as Green List (High Evidence).
Callosome v0.540 WDR47 Bryony Thompson Classified gene: WDR47 as Green List (high evidence)
Callosome v0.540 WDR47 Bryony Thompson Gene: wdr47 has been classified as Green List (High Evidence).
Mendeliome v1.2168 WDR47 Bryony Thompson Marked gene: WDR47 as ready
Mendeliome v1.2168 WDR47 Bryony Thompson Gene: wdr47 has been classified as Green List (High Evidence).
Mendeliome v1.2168 WDR47 Bryony Thompson Classified gene: WDR47 as Green List (high evidence)
Mendeliome v1.2168 WDR47 Bryony Thompson Gene: wdr47 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.75 WDR47 Bryony Thompson Marked gene: WDR47 as ready
Genetic Epilepsy v1.75 WDR47 Bryony Thompson Gene: wdr47 has been classified as Green List (High Evidence).
Microcephaly v1.288 WDR47 Bryony Thompson Marked gene: WDR47 as ready
Microcephaly v1.288 WDR47 Bryony Thompson Gene: wdr47 has been classified as Green List (High Evidence).
Mendeliome v1.2167 WDR47 Bryony Thompson gene: WDR47 was added
gene: WDR47 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: WDR47 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR47 were set to 39609633; 35474353
Phenotypes for gene: WDR47 were set to Complex neurodevelopmental disorder MONDO:0100038, WDR47-related; Congenital heart disease MONDO:0005453
Review for gene: WDR47 was set to GREEN
Added comment: PMID: 39609633 - 7 cases from 5 unrelated families with biallelic variants and a complex neurodevelopmental syndrome. The most frequent phenotypes were corpus callosum dysgenesis (7/7), microcephaly (7/7), mild to severe intellectual disability (7/7), epilepsy (7/7). Additionally, mouse models recapitulate the human phenotype. Loss of function is the mechanism of disease. Heterozygous parents had no phenotype.

Limited evidence for mono allelic association with congenital heart defects
PMID: 35474353 - rare assumed de novo heterozygous variant (NM_014969.5:c.2056G>A p.(Val686Ile) - 10 hets in gnomAD v4.1) detected in a case with heterotaxy including AVCD, vena azygos continuation, artery lusoria, truncus bicaroticus and polysplenia. Screening of exams for 2,019 individuals with situs inversus totalis, heterotaxy, or isolated CHD detected 2 additional individuals with monoallelic rare missense variants. No functional assays or other supporting evidence. All variants are VUS
Sources: Literature
Genetic Epilepsy v1.75 WDR47 Bryony Thompson Classified gene: WDR47 as Green List (high evidence)
Genetic Epilepsy v1.75 WDR47 Bryony Thompson Gene: wdr47 has been classified as Green List (High Evidence).
Microcephaly v1.288 WDR47 Bryony Thompson Classified gene: WDR47 as Green List (high evidence)
Microcephaly v1.288 WDR47 Bryony Thompson Gene: wdr47 has been classified as Green List (High Evidence).
Callosome v0.539 WDR47 Bryony Thompson gene: WDR47 was added
gene: WDR47 was added to Callosome. Sources: Literature
Mode of inheritance for gene: WDR47 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR47 were set to 39609633
Phenotypes for gene: WDR47 were set to Complex neurodevelopmental disorder MONDO:0100038, WDR47-related
Review for gene: WDR47 was set to GREEN
Added comment: 7 cases from 5 unrelated families with biallelic variants and a complex neurodevelopmental syndrome. The most frequent phenotypes were corpus callosum dysgenesis (7/7), microcephaly (7/7), mild to severe intellectual disability (7/7), epilepsy (7/7). Additionally, mouse models recapitulate the human phenotype. Loss of function is the mechanism of disease. Heterozygous parents had no phenotype.
Sources: Literature
Genetic Epilepsy v1.74 WDR47 Bryony Thompson gene: WDR47 was added
gene: WDR47 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: WDR47 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR47 were set to 39609633
Phenotypes for gene: WDR47 were set to Complex neurodevelopmental disorder MONDO:0100038, WDR47-related
Review for gene: WDR47 was set to GREEN
Added comment: 7 cases from 5 unrelated families with biallelic variants and a complex neurodevelopmental syndrome. The most frequent phenotypes were corpus callosum dysgenesis (7/7), microcephaly (7/7), mild to severe intellectual disability (7/7), epilepsy (7/7). Additionally, mouse models recapitulate the human phenotype. Loss of function is the mechanism of disease. Heterozygous parents had no phenotype.
Sources: Literature
Microcephaly v1.287 WDR47 Bryony Thompson gene: WDR47 was added
gene: WDR47 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: WDR47 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR47 were set to 39609633
Phenotypes for gene: WDR47 were set to Complex neurodevelopmental disorder MONDO:0100038, WDR47-related
Review for gene: WDR47 was set to GREEN
Added comment: 7 cases from 5 unrelated families with biallelic variants and a complex neurodevelopmental syndrome. The most frequent phenotypes were corpus callosum dysgenesis (7/7), microcephaly (7/7), mild to severe intellectual disability (7/7), epilepsy (7/7). Additionally, mouse models recapitulate the human phenotype. Loss of function is the mechanism of disease. Heterozygous parents had no phenotype.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.6 WDR47 Bryony Thompson Marked gene: WDR47 as ready
Intellectual disability syndromic and non-syndromic v1.6 WDR47 Bryony Thompson Gene: wdr47 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.6 WDR47 Bryony Thompson Classified gene: WDR47 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.6 WDR47 Bryony Thompson Gene: wdr47 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.5 WDR47 Bryony Thompson gene: WDR47 was added
gene: WDR47 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: WDR47 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR47 were set to 39609633
Phenotypes for gene: WDR47 were set to Complex neurodevelopmental disorder MONDO:0100038, WDR47-related
Review for gene: WDR47 was set to GREEN
Added comment: 7 cases from 5 unrelated families with biallelic variants and a complex neurodevelopmental syndrome. The most frequent phenotypes were corpus callosum dysgenesis (7/7), microcephaly (7/7), mild to severe intellectual disability (7/7), epilepsy (7/7). Additionally, mouse models recapitulate the human phenotype. Loss of function is the mechanism of disease. Heterozygous parents had no phenotype.
Sources: Literature
Congenital Heart Defect v0.424 WDR47 Bryony Thompson Marked gene: WDR47 as ready
Congenital Heart Defect v0.424 WDR47 Bryony Thompson Gene: wdr47 has been classified as Red List (Low Evidence).
Congenital Heart Defect v0.424 WDR47 Bryony Thompson gene: WDR47 was added
gene: WDR47 was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: WDR47 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WDR47 were set to 35474353; 39609633
Phenotypes for gene: WDR47 were set to Congenital heart disease MONDO:0005453
Review for gene: WDR47 was set to RED
Added comment: A rare assumed de novo heterozygous variant (NM_014969.5:c.2056G>A p.(Val686Ile) - 10 hets in gnomAD v4.1) detected in a case with heterotaxy including AVCD, vena azygos continuation, artery lusoria, truncus bicaroticus and polysplenia. Screening of exams for 2,019 individuals with situs inversus totalis, heterotaxy, or isolated CHD detected 2 additional individuals with monoallelic rare missense variants. No functional assays or other supporting evidence. All variants are VUS. In a recent publication of biallelic variants associated with a complex neurodevelopmental syndrome, heterozygous carriers had no phenotype.
Sources: Literature
Differences of Sex Development v0.348 FSHR Chirag Patel reviewed gene: FSHR: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 16630814, 7553856, 9020851, 9769327, 20087398, 9854118, 12930928, 12930927, 17721928, 26911863; Phenotypes: Ovarian dysgenesis 1 MONDO:0024463, Ovarian hyperstimulation syndrome MONDO:0011972; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences of Sex Development v0.348 FSHB Chirag Patel reviewed gene: FSHB: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 8220432, 9280841, 9624193, 9806482, 9271483, 16630814; Phenotypes: Hypogonadotropic hypogonadism 24 without anosmia, MIM#229070; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.348 FGFR2 Chirag Patel reviewed gene: FGFR2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29848297, 32879300; Phenotypes: Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis,MIM# 207410, Apert syndrome, MIM# 101200, Beare-Stevenson cutis gyrata syndrome, MIM# 123790, Bent bone dysplasia syndrome, MIM# 614592; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.348 FGFR1 Chirag Patel reviewed gene: FGFR1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 18034870, 23812909, 26942290; Phenotypes: Encephalocraniocutaneous lipomatosis, somatic mosaic 613001, Hartsfield syndrome 615465, Hypogonadotropic hypogonadism 2 with or without anosmia 147950, Osteoglophonic dysplasia 166250; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences of Sex Development v0.348 SOX9 Chirag Patel reviewed gene: SOX9: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Campomelic dysplasia, MIM# 114290, Campomelic dysplasia, MONDO:0007251, Acampomelic campomelic dysplasia, MIM # 114290, 46XX sex reversal 2, MIM# 278850, 46XY sex reversal 10, MIM # 616425; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.348 SRY Chirag Patel reviewed gene: SRY: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 9143916 15863672; Phenotypes: 46XX sex reversal 1, MIM# 400045, 46XY sex reversal 1 , MIM#400044; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Differences of Sex Development v0.348 WT1 Chirag Patel reviewed gene: WT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Wilms tumor, MONDO:0006058, Wilms tumor 1, MONDO:0008679, Wilms tumor, type 1, MIM#194070, Denys-Drash syndrome, MIM#194080, Frasier syndrome, MIM#136680; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v0.294 CTGF Sangavi Sivagnanasundram gene: CTGF was added
gene: CTGF was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: CTGF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTGF were set to 39506047
Phenotypes for gene: CTGF were set to Kyphomelic dysplasia
Review for gene: CTGF was set to AMBER
Added comment: CCN2 is the new HGNC approved name.

PMID: 39506047
Three individuals from two unrelated consanguineous families presented with short stature, facial dysmorphism and kyphomelic skeletal dysplasia.

A rare missense variant in family 1 (Cys148Tyr) and novel frameshift variant (Pro260LeufsTer7) in family 2 was identified in homozygous state.
Zebrafish model was also conducted that showed altered body curvature and impaired cartilage formation in craniofacial region resulting in either bent or missing tails.

A missense variant c.443G>A; p.(Cys148Tyr) in exon 3 and a frameshift variant, c.779_786del; p.(Pro260LeufsTer7) in exon 5.
Sources: Literature
Mendeliome v1.2166 CTGF Sangavi Sivagnanasundram changed review comment from: CCN2 is the new HGNC approved name.

PMID: 39506047
Three individuals from two unrelated consanguineous families presented with short stature, facial dysmorphism and kyphomelic skeletal dysplasia.

A rare missense variant in family 1 (Cys148Tyr) and novel frameshift variant (Pro260LeufsTer7) in family 2 was identified in homozygous state.
Zebrafish model was also conducted that showed altered body curvature and impaired cartilage formation in craniofacial region resulting in either bent of missing tails.

A missense variant c.443G>A; p.(Cys148Tyr) in exon 3 and a frameshift variant, c.779_786del; p.(Pro260LeufsTer7) in exon 5.
Sources: Literature; to: CCN2 is the new HGNC approved name.

PMID: 39506047
Three individuals from two unrelated consanguineous families presented with short stature, facial dysmorphism and kyphomelic skeletal dysplasia.

A rare missense variant in family 1 (Cys148Tyr) and novel frameshift variant (Pro260LeufsTer7) in family 2 was identified in homozygous state.
Zebrafish model was also conducted that showed altered body curvature and impaired cartilage formation in craniofacial region resulting in either bent or missing tails.

A missense variant c.443G>A; p.(Cys148Tyr) in exon 3 and a frameshift variant, c.779_786del; p.(Pro260LeufsTer7) in exon 5.
Sources: Literature
Skeletal Dysplasia_Fetal v0.223 CTGF Sangavi Sivagnanasundram gene: CTGF was added
gene: CTGF was added to Skeletal Dysplasia_Fetal. Sources: Literature
Mode of inheritance for gene: CTGF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTGF were set to 39506047
Phenotypes for gene: CTGF were set to Kyphomelic dysplasia
Review for gene: CTGF was set to AMBER
Added comment: CCN2 is the new HGNC approved name.

PMID: 39506047
Three individuals from two unrelated consanguineous families presented with short stature, facial dysmorphism and kyphomelic skeletal dysplasia.

A rare missense variant in family 1 (Cys148Tyr) and novel frameshift variant (Pro260LeufsTer7) in family 2 was identified in homozygous state.
Zebrafish model was also conducted that showed altered body curvature and impaired cartilage formation in craniofacial region resulting in either bent or missing tails.

A missense variant c.443G>A; p.(Cys148Tyr) in exon 3 and a frameshift variant, c.779_786del; p.(Pro260LeufsTer7) in exon 5.
Sources: Literature
Mendeliome v1.2166 CTGF Sangavi Sivagnanasundram gene: CTGF was added
gene: CTGF was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CTGF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTGF were set to 39506047
Phenotypes for gene: CTGF were set to Kyphomelic dysplasia
Review for gene: CTGF was set to AMBER
Added comment: CCN2 is the new HGNC approved name.

PMID: 39506047
Three individuals from two unrelated consanguineous families presented with short stature, facial dysmorphism and kyphomelic skeletal dysplasia.

A rare missense variant in family 1 (Cys148Tyr) and novel frameshift variant (Pro260LeufsTer7) in family 2 was identified in homozygous state.
Zebrafish model was also conducted that showed altered body curvature and impaired cartilage formation in craniofacial region resulting in either bent of missing tails.

A missense variant c.443G>A; p.(Cys148Tyr) in exon 3 and a frameshift variant, c.779_786del; p.(Pro260LeufsTer7) in exon 5.
Sources: Literature
Mendeliome v1.2166 GPATCH11 Sangavi Sivagnanasundram reviewed gene: GPATCH11: Rating: GREEN; Mode of pathogenicity: None; Publications: 39572588; Phenotypes: early-onset retinal dystrophy with neurological impairment; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bone Marrow Failure v1.106 POLA2 Sangavi Sivagnanasundram edited their review of gene: POLA2: Changed rating: GREEN
Bone Marrow Failure v1.106 POLA2 Sangavi Sivagnanasundram gene: POLA2 was added
gene: POLA2 was added to Bone Marrow Failure. Sources: Literature
Mode of inheritance for gene: POLA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLA2 were set to 39616267
Phenotypes for gene: POLA2 were set to Telomere biology disorders; Coats plus syndrome MONDO:0012815
Added comment: New gene-disease association.

PMID: 39616267 - Five individuals from two unrelated swedish families presenting with clinical phenotype suggestive of a TBD disorder with Coats plus features including retinal and gastrointestinal telangiectasias. Affected individuals also presented with shortened telomeres.

Compound heterozygous variants were identified in both families.
Family A (Ile96Thr;Pro424Leu) - Both variants are present in gnomAD v4.1 but FAF is rare enough for AR condition [c.287 T > C, p.(Ile96Thr) - FAF 0.002%; c.1271 C > T, p.(Pro424Leu) - FAF 0.0002 %]
Family B (Ile96Thr; intragenic SNV resulting in the deletion of the 5’ terminal and exon 1) - same missense as the other family along with an SNV.

In vitro assay using CRISPR/Cas9 genome engineering into HEK293T to assess whether the p.(Ile96Thr) would affect telomere length. The subclones carrying the missense variant showed telomeric shortening of ~4kb compared to the WT subclones.
Sources: Literature
Mendeliome v1.2166 POLA2 Sangavi Sivagnanasundram gene: POLA2 was added
gene: POLA2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: POLA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLA2 were set to 39616267
Phenotypes for gene: POLA2 were set to Telomere biology disorders; Coats plus syndrome MONDO:0012815
Review for gene: POLA2 was set to GREEN
Added comment: New gene-disease association.

PMID: 39616267 - Five individuals from two unrelated swedish families presenting with clinical phenotype suggestive of a TBD disorder with Coats plus features including retinal and gastrointestinal telangiectasias. Affected individuals also presented with shortened telomeres.

Compound heterozygous variants were identified in both families.
Family A (Ile96Thr;Pro424Leu) - Both variants are present in gnomAD v4.1 but FAF is rare enough for AR condition [c.287 T > C, p.(Ile96Thr) - FAF 0.002%; c.1271 C > T, p.(Pro424Leu) - FAF 0.0002 %]
Family B (Ile96Thr; intragenic SNV resulting in the deletion of the 5’ terminal and exon 1) - same missense as the other family along with an SNV.

In vitro assay using CRISPR/Cas9 genome engineering into HEK293T to assess whether the p.(Ile96Thr) would affect telomere length. The subclones carrying the missense variant showed telomeric shortening of ~4kb compared to the WT subclones.
Sources: Literature
Differences of Sex Development v0.348 FRAS1 Zornitza Stark Marked gene: FRAS1 as ready
Differences of Sex Development v0.348 FRAS1 Zornitza Stark Gene: fras1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.348 FRAS1 Zornitza Stark Publications for gene: FRAS1 were set to PMID: 12766769, 18671281, 18000968
Mendeliome v1.2166 FGF8 Zornitza Stark edited their review of gene: FGF8: Added comment: Association with CHD: Two individuals reported but extensive functional data. MODERATE by ClinGen.; Changed publications: 32664970, 7768185, 32664970, 10603341, 19509466, 9462741, 10603341, 12223415; Changed phenotypes: Hypogonadotropic hypogonadism 6 with or without anosmia, MIM# 612702, Hypoplastic femurs and pelvis, MIM#619545, Congenital heart disease MONDO:0005453, FGF8-related
Congenital Heart Defect v0.423 FGF8 Zornitza Stark Marked gene: FGF8 as ready
Congenital Heart Defect v0.423 FGF8 Zornitza Stark Gene: fgf8 has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v0.423 FGF8 Zornitza Stark Classified gene: FGF8 as Amber List (moderate evidence)
Congenital Heart Defect v0.423 FGF8 Zornitza Stark Gene: fgf8 has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v0.422 FGF8 Zornitza Stark gene: FGF8 was added
gene: FGF8 was added to Congenital Heart Defect. Sources: Expert list
Mode of inheritance for gene: FGF8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FGF8 were set to 32664970; 7768185; 32664970; 10603341; 19509466; 9462741; 10603341; 12223415
Phenotypes for gene: FGF8 were set to Congenital heart disease MONDO:0005453, FGF8-related
Review for gene: FGF8 was set to AMBER
Added comment: Two individuals reported but extensive functional data. MODERATE by ClinGen.
Sources: Expert list
Differences of Sex Development v0.347 FGF8 Zornitza Stark Marked gene: FGF8 as ready
Differences of Sex Development v0.347 FGF8 Zornitza Stark Gene: fgf8 has been classified as Green List (High Evidence).
Differences of Sex Development v0.347 FGF8 Zornitza Stark Phenotypes for gene: FGF8 were changed from to Hypogonadotropic hypogonadism 6 with or without anosmia, MIM# 612702
Differences of Sex Development v0.346 FGF8 Zornitza Stark Publications for gene: FGF8 were set to
Differences of Sex Development v0.345 FGF8 Zornitza Stark Mode of inheritance for gene: FGF8 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.344 FGF8 Zornitza Stark reviewed gene: FGF8: Rating: GREEN; Mode of pathogenicity: None; Publications: 20463092, 18596921, 24280688, 31748124; Phenotypes: Hypogonadotropic hypogonadism 6 with or without anosmia, MIM# 612702; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.344 DHCR7 Zornitza Stark Marked gene: DHCR7 as ready
Differences of Sex Development v0.344 DHCR7 Zornitza Stark Gene: dhcr7 has been classified as Green List (High Evidence).
Differences of Sex Development v0.344 DHCR7 Zornitza Stark Phenotypes for gene: DHCR7 were changed from to Smith-Lemli-Opitz syndrome, MIM#270400
Differences of Sex Development v0.343 DHCR7 Zornitza Stark Mode of inheritance for gene: DHCR7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.342 DHCR7 Zornitza Stark reviewed gene: DHCR7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Smith-Lemli-Opitz syndrome, MIM#270400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.342 CTU2 Zornitza Stark Marked gene: CTU2 as ready
Differences of Sex Development v0.342 CTU2 Zornitza Stark Gene: ctu2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.342 CTU2 Zornitza Stark Publications for gene: CTU2 were set to PMID: 27480277, 26633546, 31301155, 38348206
Differences of Sex Development v0.341 CHD7 Zornitza Stark Marked gene: CHD7 as ready
Differences of Sex Development v0.341 CHD7 Zornitza Stark Gene: chd7 has been classified as Green List (High Evidence).
Differences of Sex Development v0.341 CHD7 Zornitza Stark Phenotypes for gene: CHD7 were changed from to Hypogonadotropic hypogonadism 5 with or without anosmia MIM#612370; CHARGE syndrome MIM#214800
Differences of Sex Development v0.340 CHD7 Zornitza Stark Publications for gene: CHD7 were set to
Differences of Sex Development v0.339 CHD7 Zornitza Stark Mode of inheritance for gene: CHD7 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.338 CHD7 Zornitza Stark reviewed gene: CHD7: Rating: GREEN; Mode of pathogenicity: None; Publications: 26411921; Phenotypes: Hypogonadotropic hypogonadism 5 with or without anosmia MIM#612370, CHARGE syndrome MIM#214800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.338 CHD4 Zornitza Stark Marked gene: CHD4 as ready
Differences of Sex Development v0.338 CHD4 Zornitza Stark Gene: chd4 has been classified as Green List (High Evidence).
Differences of Sex Development v0.338 CHD4 Zornitza Stark Publications for gene: CHD4 were set to PMID: 31388190, 32881470
Differences of Sex Development v0.337 ATRX Zornitza Stark Marked gene: ATRX as ready
Differences of Sex Development v0.337 ATRX Zornitza Stark Gene: atrx has been classified as Green List (High Evidence).
Differences of Sex Development v0.337 ATRX Zornitza Stark Phenotypes for gene: ATRX were changed from to ATR-X-related syndrome MONDO:0016980
Differences of Sex Development v0.336 ATRX Zornitza Stark Mode of inheritance for gene: ATRX was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Differences of Sex Development v0.335 ATRX Zornitza Stark reviewed gene: ATRX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ATR-X-related syndrome MONDO:0016980; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Differences of Sex Development v0.335 ARX Zornitza Stark Marked gene: ARX as ready
Differences of Sex Development v0.335 ARX Zornitza Stark Gene: arx has been classified as Green List (High Evidence).
Differences of Sex Development v0.335 ARX Zornitza Stark Phenotypes for gene: ARX were changed from to X-linked lissencephaly with abnormal genitalia, MONDO:0010268
Differences of Sex Development v0.334 ARX Zornitza Stark Publications for gene: ARX were set to
Differences of Sex Development v0.333 ARX Zornitza Stark Mode of inheritance for gene: ARX was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Differences of Sex Development v0.332 ARX Zornitza Stark reviewed gene: ARX: Rating: GREEN; Mode of pathogenicity: None; Publications: 14722918; Phenotypes: X-linked lissencephaly with abnormal genitalia, MONDO:0010268; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Differences of Sex Development v0.332 AR Zornitza Stark Marked gene: AR as ready
Differences of Sex Development v0.332 AR Zornitza Stark Gene: ar has been classified as Green List (High Evidence).
Differences of Sex Development v0.332 AR Zornitza Stark Phenotypes for gene: AR were changed from to Hypospadias 1, X-linked MIM#30063; Androgen insensitivity MIM#300068; Androgen insensitivity, partial, with or without breast cancer MIM#312300
Differences of Sex Development v0.331 AR Zornitza Stark Publications for gene: AR were set to
Differences of Sex Development v0.330 AR Zornitza Stark Mode of inheritance for gene: AR was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Differences of Sex Development v0.329 AR Zornitza Stark reviewed gene: AR: Rating: GREEN; Mode of pathogenicity: None; Publications: 22334387; Phenotypes: Hypospadias 1, X-linked MIM#30063, Androgen insensitivity MIM#300068, Androgen insensitivity, partial, with or without breast cancer MIM#312300; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Differences of Sex Development v0.329 AMHR2 Zornitza Stark Marked gene: AMHR2 as ready
Differences of Sex Development v0.329 AMHR2 Zornitza Stark Gene: amhr2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.329 AMHR2 Zornitza Stark Phenotypes for gene: AMHR2 were changed from to Persistent Mullerian duct syndrome, type II MIM#261550
Differences of Sex Development v0.328 AMHR2 Zornitza Stark Publications for gene: AMHR2 were set to
Differences of Sex Development v0.327 AMHR2 Zornitza Stark Mode of inheritance for gene: AMHR2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.326 AMHR2 Zornitza Stark reviewed gene: AMHR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34810374; Phenotypes: Persistent Mullerian duct syndrome, type II MIM#261550; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Spontaneous coronary artery dissection v0.53 PKD1 Stephanie Hesselson reviewed gene: PKD1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29650765,33125268,26971055,24303518,19557720,9719186,18992981,26069747,20634758,33969096,28915698; Phenotypes: CORONARY ARTERY DISSECTION SPONTANEOUS MIM#122455, POLYCYSTIC KIDNEY DISEASE 1 WITH OR WITHOUT POLYCYSTIC LIVER DISEASE, PKD1 MIM#173900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dystonia - complex v0.242 C19orf12 Sangavi Sivagnanasundram reviewed gene: C19orf12: Rating: GREEN; Mode of pathogenicity: None; Publications: 21981780, 22508347; Phenotypes: neurodegeneration with brain iron accumulation 4 MONDO:0013674; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia - complex v0.242 BCAP31 Sangavi Sivagnanasundram reviewed gene: BCAP31: Rating: GREEN; Mode of pathogenicity: None; Publications: 24011989, 28332767, 30713915, 31330203, 32652807; Phenotypes: severe motor and intellectual disabilities-sensorineural deafness-dystonia syndrome MONDO:0010334; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Dystonia - complex v0.242 ATP13A2 Sangavi Sivagnanasundram reviewed gene: ATP13A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 21094623, 20853184, 20310007; Phenotypes: Kufor-Rakeb syndrome MONDO:0011706; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.325 Chirag Patel Panel types changed to Victorian Clinical Genetics Services; Genetic Health Queensland; Royal Melbourne Hospital; Rare Disease
Differences of Sex Development v0.324 FREM2 Chirag Patel Classified gene: FREM2 as Green List (high evidence)
Differences of Sex Development v0.324 FREM2 Chirag Patel Gene: frem2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.324 FREM2 Chirag Patel Classified gene: FREM2 as Green List (high evidence)
Differences of Sex Development v0.324 FREM2 Chirag Patel Gene: frem2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.323 FREM2 Chirag Patel Classified gene: FREM2 as Green List (high evidence)
Differences of Sex Development v0.323 FREM2 Chirag Patel Gene: frem2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.323 FRAS1 Chirag Patel Classified gene: FRAS1 as Green List (high evidence)
Differences of Sex Development v0.323 FRAS1 Chirag Patel Gene: fras1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.322 FRAS1 Chirag Patel gene: FRAS1 was added
gene: FRAS1 was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: FRAS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FRAS1 were set to PMID: 12766769, 18671281, 18000968
Phenotypes for gene: FRAS1 were set to Fraser syndrome 1, MIM#219000
Review for gene: FRAS1 was set to GREEN
Added comment: Fraser syndrome is an autosomal recessive malformation disorder. Major criteria include syndactyly, cryptophthalmos spectrum, urinary tract abnormalities, ambiguous genitalia, laryngeal and tracheal anomalies, and positive family history. Minor criteria include anorectal defects, dysplastic ears, skull ossification defects, umbilical abnormalities, and nasal anomalies.
Established gene-disease association.
Sources: Literature
Differences of Sex Development v0.321 FREM2 Chirag Patel gene: FREM2 was added
gene: FREM2 was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: FREM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FREM2 were set to PMID: 15838507, 29688405, 18203166, 18671281, 18000968
Phenotypes for gene: FREM2 were set to Fraser syndrome 2, MIM#617666
Review for gene: FREM2 was set to GREEN
Added comment: Fraser syndrome is an autosomal recessive malformation disorder. Major criteria include syndactyly, cryptophthalmos spectrum, urinary tract abnormalities, ambiguous genitalia, laryngeal and tracheal anomalies, and positive family history. Minor criteria include anorectal defects, dysplastic ears, skull ossification defects, umbilical abnormalities, and nasal anomalies.
Established gene-disease association.
Sources: Literature
Differences of Sex Development v0.320 SOX2 Chirag Patel Classified gene: SOX2 as Green List (high evidence)
Differences of Sex Development v0.320 SOX2 Chirag Patel Gene: sox2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.319 SOX2 Chirag Patel gene: SOX2 was added
gene: SOX2 was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: SOX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOX2 were set to PMID: 20301477
Phenotypes for gene: SOX2 were set to Anophthalmia/microphthalmia-esophageal atresia syndrome MONDO:0008799; Microphthalmia, syndromic 3, MIM# 206900; Optic nerve hypoplasia and abnormalities of the central nervous system, MIM# 206900
Review for gene: SOX2 was set to GREEN
Added comment: SOX2 disorder includes anophthalmia and/or microphthalmia, brain malformations, developmental delay / intellectual disability, oesophageal atresia, pituitary hypoplasia, postnatal growth delay, hypotonia, seizures, and spastic or dystonic movements, and hypogonadotropic hypogonadism (manifest as cryptorchidism and micropenis in males, gonadal dysgenesis infrequently in females, and delayed puberty in both sexes). Established gene-disease association.
Sources: Literature
Differences of Sex Development v0.318 IRF6 Chirag Patel Classified gene: IRF6 as Green List (high evidence)
Differences of Sex Development v0.318 IRF6 Chirag Patel Gene: irf6 has been classified as Green List (High Evidence).
Dystonia - complex v0.242 ATM Sangavi Sivagnanasundram reviewed gene: ATM: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301790, 29436738, 30504431, 22345219; Phenotypes: ataxia telangiectasia MONDO:0008840; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.317 IRF6 Chirag Patel gene: IRF6 was added
gene: IRF6 was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: IRF6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IRF6 were set to PMID: 20301581
Phenotypes for gene: IRF6 were set to Popliteal pterygium syndrome 1, OMIM #119500
Review for gene: IRF6 was set to GREEN
Added comment: IRF6-related disorders span a spectrum from isolated cleft lip and palate and Van der Woude syndrome (VWS) at the mild end to popliteal pterygium syndrome (PPS) at the more severe end.
Established gene-disease association.

Popliteal pterygium syndrome (PPS) features including orofacial anomalies such as lower lip pits, cleft lip and/or palate, and syngnathia, and skin and genital abnormalities including webbing of the lower limbs, syndactyly, hypoplasia of the labia majora/vagina/uterus, cryptorchidism, and bifid or hypoplastic scrotum.
Sources: Literature
Differences of Sex Development v0.316 CHD4 Chirag Patel Classified gene: CHD4 as Green List (high evidence)
Differences of Sex Development v0.316 CHD4 Chirag Patel Gene: chd4 has been classified as Green List (High Evidence).
Differences of Sex Development v0.315 CHD4 Chirag Patel gene: CHD4 was added
gene: CHD4 was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: CHD4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHD4 were set to PMID: 31388190, 32881470
Phenotypes for gene: CHD4 were set to Sifrim-Hitz-Weiss syndrome, MIM #617159
Review for gene: CHD4 was set to GREEN
Added comment: Sifrim-Hitz-Weiss syndrome is an autosomal dominant intellectual developmental disorder with variable congenital defects affecting other systems, including cardiac, skeletal, and urogenital. Some patients may have short stature, enlarged head circumference, hearing loss, and nonspecific dysmorphic facial features. Established gene-disease association.

Hypogonadism is common in males (cryptorchidism and/or microphallus), with hormonal profile consistent with hypogonadotropic hypogonadism.
Sources: Literature
Differences of Sex Development v0.314 POLR1C Chirag Patel gene: POLR1C was added
gene: POLR1C was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: POLR1C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR1C were set to PMID: 26151409, 32042905, 33005949
Phenotypes for gene: POLR1C were set to Leukodystrophy, hypomyelinating, 11, OMIM#616494
Review for gene: POLR1C was set to RED
Added comment: Hypomyelinating leukodystrophy-11 (HLD11) is an autosomal recessive neurologic disorder characterized by delayed psychomotor development and other neurologic features associated with hypomyelination on brain imaging. Some patients may have additional nonneurologic features, particularly dental abnormalities and possibly hypogonadotropic hypogonadism.

Thiffault et al. (2015) reported 8 unrelated patients with hypomyelinating leukodystrophy and 13 homozygous or compound heterozygous mutations in the POLR1C gene. All had neurologic abnormalities, including delayed psychomotor development, loss or lack of independent ambulation, abnormal cognition, tremor, ataxia, spasticity, and cerebellar findings. Three had myopia and 3 had dental abnormalities. Six patients were too young to be assessed for hypogonadotropic hypogonadism, and 2 did not have hypogonadism.

Gauquelin et al. (2019) reported 23 patients with hypomyelinating leukodystrophy and 29 different variants (homozygous or compound heterozygous) in the POLR1C gene. Patients too young to comment on hypogonadotropic hypogonadism.
Sources: Literature
Differences of Sex Development v0.314 POLR1C Chirag Patel gene: POLR1C was added
gene: POLR1C was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: POLR1C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR1C were set to PMID: 26151409, 32042905, 33005949
Phenotypes for gene: POLR1C were set to Leukodystrophy, hypomyelinating, 11, OMIM#616494
Review for gene: POLR1C was set to RED
Added comment: Hypomyelinating leukodystrophy-11 (HLD11) is an autosomal recessive neurologic disorder characterized by delayed psychomotor development and other neurologic features associated with hypomyelination on brain imaging. Some patients may have additional nonneurologic features, particularly dental abnormalities and possibly hypogonadotropic hypogonadism.

Thiffault et al. (2015) reported 8 unrelated patients with hypomyelinating leukodystrophy and 13 homozygous or compound heterozygous mutations in the POLR1C gene. All had neurologic abnormalities, including delayed psychomotor development, loss or lack of independent ambulation, abnormal cognition, tremor, ataxia, spasticity, and cerebellar findings. Three had myopia and 3 had dental abnormalities. Six patients were too young to be assessed for hypogonadotropic hypogonadism, and 2 did not have hypogonadism.

Gauquelin et al. (2019) reported 23 patients with hypomyelinating leukodystrophy and 29 different variants (homozygous or compound heterozygous) in the POLR1C gene. Patients too young to comment on hypogonadotropic hypogonadism.
Sources: Literature
Differences of Sex Development v0.314 POLR1C Chirag Patel gene: POLR1C was added
gene: POLR1C was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: POLR1C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR1C were set to PMID: 26151409, 32042905, 33005949, ............22855961
Phenotypes for gene: POLR1C were set to Leukodystrophy, hypomyelinating, 11, OMIM#616494
Review for gene: POLR1C was set to RED
Added comment: Hypomyelinating leukodystrophy-11 (HLD11) is an autosomal recessive neurologic disorder characterized by delayed psychomotor development and other neurologic features associated with hypomyelination on brain imaging. Some patients may have additional nonneurologic features, particularly dental abnormalities and possibly hypogonadotropic hypogonadism.

Thiffault et al. (2015) reported 8 unrelated patients with hypomyelinating leukodystrophy and 13 homozygous or compound heterozygous mutations in the POLR1C gene. All had neurologic abnormalities, including delayed psychomotor development, loss or lack of independent ambulation, abnormal cognition, tremor, ataxia, spasticity, and cerebellar findings. Three had myopia and 3 had dental abnormalities. Six patients were too young to be assessed for hypogonadotropic hypogonadism, and 2 did not have hypogonadism.

Gauquelin et al. (2019) reported 23 patients with hypomyelinating leukodystrophy and 29 different variants (homozygous or compound heterozygous) in the POLR1C gene. Patients too young to comment on hypogonadotropic hypogonadism.
Sources: Literature
Differences of Sex Development v0.313 POLR3B Chirag Patel Classified gene: POLR3B as Green List (high evidence)
Differences of Sex Development v0.313 POLR3B Chirag Patel Gene: polr3b has been classified as Green List (High Evidence).
Differences of Sex Development v0.312 POLR3A Chirag Patel Classified gene: POLR3A as Green List (high evidence)
Differences of Sex Development v0.312 POLR3A Chirag Patel Gene: polr3a has been classified as Green List (High Evidence).
Differences of Sex Development v0.312 POLR3B Chirag Patel gene: POLR3B was added
gene: POLR3B was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: POLR3B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR3B were set to PubMed: 27512013, 23355746, 22036171, 22036172, 25339210, 33005949, 22855961
Phenotypes for gene: POLR3B were set to Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism; OMIM #614381
Review for gene: POLR3B was set to GREEN
Added comment: Hypomyelinating leukodystrophy-8 (HLD8) is an autosomal recessive neurologic disorder characterized by early childhood onset of cerebellar ataxia and mild intellectual disabilities associated with diffuse hypomyelination apparent on brain MRI. Variable features include oligodontia and/or hypogonadotropic hypogonadism. There is considerable inter- and intrafamilial variability.

Multiples families reported with compound heterozygous mutations in POL3RB gene.

Wolf et al. (2014) performed a cross-sectional observational study of 105 patients with 4H syndrome, including 43 with mutations in the POLR3A gene and 62 with mutations in the POLR3B gene. Delayed puberty/HH, in those old enough to assess, occurred in 81% of patients with POLR3A mutations and in 69% of those with POLR3B mutations.
Sources: Literature
Differences of Sex Development v0.311 POLR3A Chirag Patel gene: POLR3A was added
gene: POLR3A was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: POLR3A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR3A were set to PubMed: 21855841, 25339210, 33005949, 22855961
Phenotypes for gene: POLR3A were set to Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism, OMIM#607694
Review for gene: POLR3A was set to GREEN
Added comment: Hypomyelinating leukodystrophy-7 (HLD7) is an autosomal recessive neurodegenerative disorder characterized by childhood onset of progressive motor decline manifest as spasticity, ataxia, tremor, and cerebellar signs, as well as mild cognitive regression. Other common features may include hypodontia or oligodontia and hypogonadotropic hypogonadism. There is considerable inter- and intrafamilial variability.

Bernard et al. (2011) identified 14 different mutations in the POLR3A gene (homozygous or compound heterozygous state), in 19 patients from 12 families. The mutations were spread throughout the gene, and there were no obvious genotype/phenotype correlations. Immunoblot analysis showed decreased levels of POLR3A protein in fibroblasts from 4 affected individuals, and decreased levels in the cortex and cerebral white matter of another patient, suggesting that loss of function is responsible for the disorder.

Wolf et al. (2014) performed a cross-sectional observational study of 105 patients with 4H syndrome, including 43 with mutations in the POLR3A gene and 62 with mutations in the POLR3B gene. Delayed puberty/HH, in those old enough to assess, occurred in 81% of patients with POLR3A mutations and in 69% of those with POLR3B mutations.
Sources: Literature
Differences of Sex Development v0.310 HARS2 Chirag Patel Classified gene: HARS2 as Green List (high evidence)
Differences of Sex Development v0.310 HARS2 Chirag Patel Gene: hars2 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.53 COL3A1 Stephanie Hesselson reviewed gene: COL3A1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 39130004; Phenotypes: CORONARY ARTERY DISSECTION, SPONTANEOUS MIM#122455; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dystonia - complex v0.242 KCNQ2 Bryony Thompson Publications for gene: KCNQ2 were set to 12742592
Dystonia - complex v0.241 KCNQ2 Bryony Thompson Classified gene: KCNQ2 as Amber List (moderate evidence)
Dystonia - complex v0.241 KCNQ2 Bryony Thompson Gene: kcnq2 has been classified as Amber List (Moderate Evidence).
Dystonia - complex v0.240 KCNQ2 Bryony Thompson edited their review of gene: KCNQ2: Added comment: Now 2 cases have been reported with dystonic features as part of a complex neurological phenotype.; Changed rating: AMBER; Changed publications: 12742592, 32585800
Differences of Sex Development v0.309 HHAT Chirag Patel Classified gene: HHAT as Green List (high evidence)
Differences of Sex Development v0.309 HHAT Chirag Patel Gene: hhat has been classified as Green List (High Evidence).
Differences of Sex Development v0.308 HHAT Chirag Patel gene: HHAT was added
gene: HHAT was added to Differences of Sex Development. Sources: Expert list
Mode of inheritance for gene: HHAT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HHAT were set to PMID: 24784881, 33749989, 35045414
Phenotypes for gene: HHAT were set to Nivelon-Nivelon-Mabille syndrome, OMIM:600092
Review for gene: HHAT was set to GREEN
Added comment: 3 individuals from 3 families with 46, XY karyotype and sex reversal, with supportive mouse model reported in 24784881.

PMID:24784881 - Callier et al 2014 - report a family with 2 siblings with Disorder of Sex Development (DSD) and chondrodysplasia (Nivelon-Nivelon-Mabille syndrome). The first sibling (46,XY karyotype) displayed severe dwarfism with generalized chondrodysplasia, a narrow, bell-shaped thorax, micromelia, brachydactyly, severe microcephaly (-7.5 SD at age 16 (PMID:15578577) with cerebellar vermis hypoplasia, facial anomalies, hypoplastic irides, and coloboma of both optic discs. Complete gonadal dysgenesis ( including normal external female genitalia, lack of pubertal development, primary amenorrhea, and hypergonadotrophic hypogonadism) and intellectual disability is also noted. The second sibling (46,XX karyotype) had histologically normal ovaries and similar phenotypic abnormalities including severe dwarfism and generalized chondrodysplasia. Using WES a homozygous missense variant was found NM_001122834:c.860G>T:p.(Gly287Val) in HHAT in the first sibling which is in the conserved MBOAT domain. The parents were heterozygous. They also found that mice lacking functional Hhat show a similar phenotype as the syndromic 46,XY DSD patient including testicular dysgenesis and skeletal defects.

PMID: 33749989 - Pande et al 2021 - report multiple malformations in three pregnancies with a novel biallelic in-frame deletion, c.365_367del; (p.Thr122del), in exon 5 of HHAT in the living proband. She shows severe microphthalmia, microcephaly (−8 SD head circumference at age 7), skeletal dysplasia (narrow bell-shaped thorax, short and angel-shaped epiphyses of hands and feet) and midface retrusion, short columella with a groove at the base, prominent ears, long philtrum, depressed nasal bridge, everted lower lip, and a single central incisor. She also has complete sex reversal (karyotype of 46, XY, normal internal organs including uterus and ovaries.)

PMID: 35045414 - Mazen et al 2022 - report an Egyptian patient with 46,XY DSD (ambiguous genitalia and microcephaly) and a homozygous missense variant in HHAT, which segregated with the phenotype in the family.
Sources: Expert list
Dystonia - complex v0.240 APTX Sangavi Sivagnanasundram reviewed gene: APTX: Rating: GREEN; Mode of pathogenicity: None; Publications: 15876520; Phenotypes: ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia MONDO:0008842; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.307 CTU2 Chirag Patel changed review comment from: DREAM-PL syndrome presents with dysmorphic facies, renal agenesis, ambiguous genitalia, microcephaly, polydactyly, and lissencephaly. Other anomalies include corpus callosum agenesis or dysgenesis, septal defects, PDA, hypoplastic right ventricle and joint contractures.

PMID:26633546. Affected members of all 3 families have microcephaly, facial dysmorphia and unilateral renal agenesis. 2/3 families have ambiguous genitalia; however, only 1 family had karyotyping done, which showed normal male karyotype (46 XY). 2/3 had congenital heart disease.

PMID: 27480277. Same variant as PMID:26633546. Affected individuals in this extended family have similar phenotype as PMID:26633546. Patient 1: in addition to microcephaly also has renal anomalies (small kidneys) and possible ambiguous genitalia with normal XY karyotype. Patient 2: cousin of patient 1. In addition to microcephaly did not have renal anomalies and nor ambiguous genitalia. Both patients have congenital heart disease.

PMID: 31301155. 5 new cases, all with microcephaly. 4/5 with renal anomalies, 2/5 with ambiguous genitalia, 4/5 congenital heart disease.

Functional characterization using patient-derived cells for each of these alleles, as well as the original founder allele; revealed a specific impairment of wobble uridine thiolation in all known thiol-containing tRNAs.
Sources: Literature; to: DREAM-PL syndrome presents with dysmorphic facies, renal agenesis, ambiguous genitalia, microcephaly, polydactyly, and lissencephaly.

PMID:26633546. Affected members of all 3 families have microcephaly, facial dysmorphia and unilateral renal agenesis. 2/3 families have ambiguous genitalia; however, only 1 family had karyotyping done, which showed normal male karyotype (46 XY). 2/3 had congenital heart disease.

PMID: 27480277. Same variant as PMID:26633546. Affected individuals in this extended family have similar phenotype as PMID:26633546. Patient 1: in addition to microcephaly also has renal anomalies (small kidneys) and possible ambiguous genitalia with normal XY karyotype. Patient 2: cousin of patient 1. In addition to microcephaly did not have renal anomalies and nor ambiguous genitalia. Both patients have congenital heart disease.

PMID: 31301155. 5 new cases, all with microcephaly. 4/5 with renal anomalies, 2/5 with ambiguous genitalia, 4/5 congenital heart disease.

Functional characterization using patient-derived cells for each of these alleles, as well as the original founder allele; revealed a specific impairment of wobble uridine thiolation in all known thiol-containing tRNAs.
Sources: Literature
Differences of Sex Development v0.307 CTU2 Chirag Patel changed review comment from: DREAM-PL syndrome presents with dysmorphic facies, renal agenesis, ambiguous genitalia, microcephaly, polydactyly, and lissencephaly. Other anomalies include corpus callosum agenesis or dysgenesis, septal defects, PDA, hypoplastic right ventricle and joint contractures.

More than 6 families reported, four had the same founder variant. Functional characterization using patient-derived cells for each of these alleles, as well as the original founder allele; revealed a specific impairment of wobble uridine thiolation in all known thiol-containing tRNAs
Sources: Literature; to: DREAM-PL syndrome presents with dysmorphic facies, renal agenesis, ambiguous genitalia, microcephaly, polydactyly, and lissencephaly. Other anomalies include corpus callosum agenesis or dysgenesis, septal defects, PDA, hypoplastic right ventricle and joint contractures.

PMID:26633546. Affected members of all 3 families have microcephaly, facial dysmorphia and unilateral renal agenesis. 2/3 families have ambiguous genitalia; however, only 1 family had karyotyping done, which showed normal male karyotype (46 XY). 2/3 had congenital heart disease.

PMID: 27480277. Same variant as PMID:26633546. Affected individuals in this extended family have similar phenotype as PMID:26633546. Patient 1: in addition to microcephaly also has renal anomalies (small kidneys) and possible ambiguous genitalia with normal XY karyotype. Patient 2: cousin of patient 1. In addition to microcephaly did not have renal anomalies and nor ambiguous genitalia. Both patients have congenital heart disease.

PMID: 31301155. 5 new cases, all with microcephaly. 4/5 with renal anomalies, 2/5 with ambiguous genitalia, 4/5 congenital heart disease.

Functional characterization using patient-derived cells for each of these alleles, as well as the original founder allele; revealed a specific impairment of wobble uridine thiolation in all known thiol-containing tRNAs.
Sources: Literature
Differences of Sex Development v0.307 CTU2 Chirag Patel Classified gene: CTU2 as Green List (high evidence)
Differences of Sex Development v0.307 CTU2 Chirag Patel Gene: ctu2 has been classified as Green List (High Evidence).
Dystonia - complex v0.240 ADAR Sangavi Sivagnanasundram reviewed gene: ADAR: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301648, 24262145; Phenotypes: Aicardi-Goutieres syndrome MONDO:0018866; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.306 CTU2 Chirag Patel gene: CTU2 was added
gene: CTU2 was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: CTU2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTU2 were set to PMID: 27480277, 26633546, 31301155, 38348206
Phenotypes for gene: CTU2 were set to DREAM-PL syndrome (Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome), MIM#618142
Review for gene: CTU2 was set to GREEN
Added comment: DREAM-PL syndrome presents with dysmorphic facies, renal agenesis, ambiguous genitalia, microcephaly, polydactyly, and lissencephaly. Other anomalies include corpus callosum agenesis or dysgenesis, septal defects, PDA, hypoplastic right ventricle and joint contractures.

More than 6 families reported, four had the same founder variant. Functional characterization using patient-derived cells for each of these alleles, as well as the original founder allele; revealed a specific impairment of wobble uridine thiolation in all known thiol-containing tRNAs
Sources: Literature
Differences of Sex Development v0.305 TWNK Chirag Patel Classified gene: TWNK as Green List (high evidence)
Differences of Sex Development v0.305 TWNK Chirag Patel Gene: twnk has been classified as Green List (High Evidence).
Differences of Sex Development v0.305 TWNK Chirag Patel Classified gene: TWNK as Green List (high evidence)
Differences of Sex Development v0.305 TWNK Chirag Patel Gene: twnk has been classified as Green List (High Evidence).
Differences of Sex Development v0.304 TWNK Chirag Patel gene: TWNK was added
gene: TWNK was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: TWNK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TWNK were set to PMID: 25355836, 31852434, 31455392
Phenotypes for gene: TWNK were set to Perrault syndrome 5; MIM# 616138
Review for gene: TWNK was set to GREEN
Added comment: Perrault syndrome-5 (PRLTS5) is an autosomal recessive disorder characterized by progressive ataxia, axonal neuropathy, hyporeflexia, and abnormal eye movements, accompanied by progressive hearing loss and ovarian dysgenesis.

PMID: 25355836: 4 women from 2 unrelated families with Perrault syndrome-5.
2 sisters in each family presented with primary amenorrhea, lack of secondary sexual characteristics, and gonadal dysgenesis; 2 sisters in 1 family showed streak ovaries. Three of the 4 girls had onset of sensorineural hearing loss at 7 to 8 years of age; the fourth had onset of hearing loss at age 13. All 4 patients developed neurologic involvement in the second or third decades, with features including ataxia, nystagmus, hyporeflexia, and sensory axonal neuropathy with distal sensory impairment. WES identified compound heterozygous variants in each family, but functional studies of the variants were not performed.

PMID: 31852434: female with severe bilateral hypoacusis, severe ataxia, polyneuropathy, lower limb spastic paraparesis with pyramidal signs, and gonadal dysgenesis, and compound heterozygous variants in TWNK gene (but functional studies of the variants were not performed).

PMID: 31455392: 3 siblings from one family with childhood-onset bilateral sensorineural hearing impairment, neurological signs (spinocerebellar ataxia, polyneuropathy), and gonadal dysfunction with early cessation of menses in the 2 females. WES identified compound heterozygous pathogenic mutations in the TWNK gene, which segregated with disease.
,
Sources: Literature
Differences of Sex Development v0.303 MARS2 Chirag Patel Classified gene: MARS2 as Green List (high evidence)
Differences of Sex Development v0.303 MARS2 Chirag Patel Gene: mars2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.302 MARS2 Chirag Patel gene: MARS2 was added
gene: MARS2 was added to Differences of Sex Development. Sources: Expert Review
Mode of inheritance for gene: MARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MARS2 were set to PMID: 27650058, 21464306, 27087618
Phenotypes for gene: MARS2 were set to Perrault syndrome 2, MIM# 614926
Review for gene: MARS2 was set to GREEN
Added comment: Perrault syndrome-2 (PRLTS2) is an autosomal recessive disorder characterized by sensorineural deafness in both males and females. Affected females have primary amenorrhea, streak gonads (ovarian dysgenesis), and infertility, whereas affected males show normal pubertal development and are fertile. No neurological abnormalities reported.

PMID: 21464306: five affected siblings from one family with three females with ovarian dysgenesis with primary amenorrhea and streak gonads along with sensorineural hearing loss (two males had normal fertility) had two variants in HARS2 with confirmed biparental inheritance. Functional studies showed that the mutations resulted in decreased enzyme activity, and knockdown of the HARS2 homolog in C. elegans caused severe gonadal defects and infertility.

PMID: 27650058: two unrelated probands with Perrault syndrome with profound deafness and secondary amenorrhoea with gonadal dysgenesis were found to have a homozygous variant in HARS2. These probands were not related but were from the same region in Morocco.

PMID: 27087618: 2 siblings in Turkish family with Perrault syndrome (female sibling had with secondary amenorrhea and gonadal dysgenesis) were found to have a homozygous variant in HARS2. No functional work.
Sources: Expert Review
Differences of Sex Development v0.301 HARS2 Chirag Patel gene: HARS2 was added
gene: HARS2 was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: HARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HARS2 were set to PMID: 27650058, 21464306, 27087618
Phenotypes for gene: HARS2 were set to Perrault syndrome 2, MIM# 614926
Review for gene: HARS2 was set to GREEN
Added comment: Perrault syndrome-2 (PRLTS2) is an autosomal recessive disorder characterized by sensorineural deafness in both males and females. Affected females have primary amenorrhea, streak gonads (ovarian dysgenesis), and infertility, whereas affected males show normal pubertal development and are fertile. No neurological abnormalities reported.

PMID: 21464306: five affected siblings from one family with three females with ovarian dysgenesis with primary amenorrhea and streak gonads along with sensorineural hearing loss (two males had normal fertility) had two variants in HARS2 with confirmed biparental inheritance. Functional studies showed that the mutations resulted in decreased enzyme activity, and knockdown of the HARS2 homolog in C. elegans caused severe gonadal defects and infertility.

PMID: 27650058: two unrelated probands with Perrault syndrome with profound deafness and secondary amenorrhoea with gonadal dysgenesis were found to have a homozygous variant in HARS2. These probands were not related but were from the same region in Morocco.

PMID: 27087618: 2 siblings in Turkish family with Perrault syndrome (female sibling had with secondary amenorrhea and gonadal dysgenesis) were found to have a homozygous variant in HARS2. No functional work.
Sources: Literature
Differences of Sex Development v0.300 LARS2 Chirag Patel Classified gene: LARS2 as Green List (high evidence)
Differences of Sex Development v0.300 LARS2 Chirag Patel Gene: lars2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.299 LARS2 Chirag Patel gene: LARS2 was added
gene: LARS2 was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: LARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LARS2 were set to PMID: 32423379, 29205794, 23541342, 30737337, 26657938,
Phenotypes for gene: LARS2 were set to Perrault syndrome 4; MIM# 615300
Review for gene: LARS2 was set to GREEN
Added comment: Perrault syndrome-4 (PRLTS4) is an autosomal recessive disorder primarily characterized by early-onset sensorineural hearing loss in both males and females, and premature ovarian failure (POF) due to ovarian dysgenesis in females. Affected individuals may also develop neurologic involvement, including developmental delay or learning difficulties in childhood or onset of progressive movement abnormalities, such as spasticity, in adulthood. Brain imaging may show progressive leukodystrophy. At least 6 families with affected females reported with biallelic variants in LARS2 (mostly missense), which segregated in family. Patient-derived mitochondria showed decreased LARS2 aminoacylation activity (about 50% of controls) in one study.
Sources: Literature
Differences of Sex Development v0.298 ERAL1 Chirag Patel Classified gene: ERAL1 as Amber List (moderate evidence)
Differences of Sex Development v0.298 ERAL1 Chirag Patel Gene: eral1 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.297 ERAL1 Chirag Patel reviewed gene: ERAL1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 28449065; Phenotypes: Perrault syndrome 6, MIM# 617565; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 MMAA Ee Ming Wong reviewed gene: MMAA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Methylmalonic aciduria, vitamin B12-responsive, cblA type (MIM#251100); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.633 MERTK Ee Ming Wong reviewed gene: MERTK: Rating: GREEN; Mode of pathogenicity: None; Publications: 11062461, 17301963, 20300561, 22180149; Phenotypes: Retinitis pigmentosa 38 (MIM#613862); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.633 MARS Ee Ming Wong reviewed gene: MARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 24103465, 25913036; Phenotypes: Interstitial lung and liver disease, MIM#615486; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.633 KCNJ1 Cassandra Muller reviewed gene: KCNJ1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Bartter syndrome, type 2, 241200 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 IKBKB Cassandra Muller reviewed gene: IKBKB: Rating: GREEN; Mode of pathogenicity: None; Publications: 24369075, 25216719, 24679846, 32117824, 2513935; Phenotypes: Immunodeficiency 15, 615592 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 HPS1 Cassandra Muller reviewed gene: HPS1: Rating: ; Mode of pathogenicity: None; Publications: 8896559, 9497254, 9705234, 27593200, 31898847; Phenotypes: Hermansky-Pudlak syndrome 1, 203300 (3); Mode of inheritance: None
Prepair 1000+ v1.633 HPD Cassandra Muller reviewed gene: HPD: Rating: AMBER; Mode of pathogenicity: None; Publications: 10942115, 23036342, 37817461, 28649543; Phenotypes: Tyrosinemia, type III, 276710 (3); Mode of inheritance: None
Osteogenesis Imperfecta and Osteoporosis v0.115 PLS3 Sangavi Sivagnanasundram reviewed gene: PLS3: Rating: GREEN; Mode of pathogenicity: None; Publications: 24088043; Phenotypes: X-linked osteoporosis with fractures MONDO:0018315; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Osteogenesis Imperfecta and Osteoporosis v0.115 LRP5 Sangavi Sivagnanasundram reviewed gene: LRP5: Rating: GREEN; Mode of pathogenicity: None; Publications: 20034086; Phenotypes: osteoporosis-pseudoglioma syndrome MONDO:0009820; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 HFE2 Cassandra Muller reviewed gene: HFE2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hemochromatosis, type 2A, 602390 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteogenesis Imperfecta and Osteoporosis v0.115 FKBP10 Sangavi Sivagnanasundram reviewed gene: FKBP10: Rating: GREEN; Mode of pathogenicity: None; Publications: 20362275, 20839288; Phenotypes: osteogenesis imperfecta type 11 MONDO:0012592, Bruck syndrome MONDO:0017195; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteogenesis Imperfecta and Osteoporosis v0.115 COL1A2 Sangavi Sivagnanasundram reviewed gene: COL1A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301472, 2897363, 8257992, 8401517; Phenotypes: Osteogenesis imperfecta type 1 MONDO:0008146, Osteogenesis imperfecta type 2 MONDO:0008147, Osteogenesis imperfecta type 3 MONDO:0009804, Osteogenesis imperfecta type 4 MONDO:0008148; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Osteogenesis Imperfecta and Osteoporosis v0.115 COL1A1 Sangavi Sivagnanasundram edited their review of gene: COL1A1: Changed publications: 20301472, 15728585, 17078022, 23692737
Prepair 1000+ v1.633 GLYCTK Cassandra Muller reviewed gene: GLYCTK: Rating: GREEN; Mode of pathogenicity: None; Publications: 20949620, 31837836, 39619776; Phenotypes: D-glyceric aciduria, 220120 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteogenesis Imperfecta and Osteoporosis v0.115 COL1A1 Sangavi Sivagnanasundram reviewed gene: COL1A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15728585, 17078022, 23692737; Phenotypes: combined osteogenesis imperfecta and Ehlers-Danlos syndrome 1 MONDO:0030854, Osteogenesis imperfecta type 1 MONDO:0008146, Osteogenesis imperfecta type 2 MONDO:0008147, Osteogenesis imperfecta type 3 MONDO:0009804, Osteogenesis imperfecta type 4, MONDO:0008148; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Neurodegeneration with brain iron accumulation v0.35 WDR45 Sangavi Sivagnanasundram reviewed gene: WDR45: Rating: GREEN; Mode of pathogenicity: None; Publications: 23447832, 23176820; Phenotypes: X-linked complex neurodevelopmental disorder MONDO:0100148; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Neurodegeneration with brain iron accumulation v0.35 PLA2G6 Sangavi Sivagnanasundram reviewed gene: PLA2G6: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301718, 24745848, 27516098; Phenotypes: PLA2G6-associated neurodegeneration MONDO:0017998; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Neurodegeneration with brain iron accumulation v0.35 PANK2 Sangavi Sivagnanasundram reviewed gene: PANK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 15911822, 22127788; Phenotypes: Neurodegeneration with brain iron accumulation 1 MIM#234200, pantothenate kinase-associated neurodegeneration MONDO:0009319; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Familial hypercholesterolaemia v1.0 Bryony Thompson promoted panel to version 1.0
Congenital Heart Defect v0.421 ROCK2 Bryony Thompson Marked gene: ROCK2 as ready
Congenital Heart Defect v0.421 ROCK2 Bryony Thompson Gene: rock2 has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v0.421 ROCK2 Bryony Thompson Classified gene: ROCK2 as Amber List (moderate evidence)
Congenital Heart Defect v0.421 ROCK2 Bryony Thompson Gene: rock2 has been classified as Amber List (Moderate Evidence).
Neurodegeneration with brain iron accumulation v0.35 FTL Sangavi Sivagnanasundram reviewed gene: FTL: Rating: GREEN; Mode of pathogenicity: None; Publications: 11438811, 12746423, 15099026; Phenotypes: Neurodegeneration with brain iron accumulation 3 MIIM#606159; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.2166 ROCK2 Bryony Thompson Marked gene: ROCK2 as ready
Mendeliome v1.2166 ROCK2 Bryony Thompson Gene: rock2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2166 ROCK2 Bryony Thompson Classified gene: ROCK2 as Amber List (moderate evidence)
Mendeliome v1.2166 ROCK2 Bryony Thompson Gene: rock2 has been classified as Amber List (Moderate Evidence).
Familial hypercholesterolaemia v0.46 PCSK9 Bryony Thompson Marked gene: PCSK9 as ready
Familial hypercholesterolaemia v0.46 PCSK9 Bryony Thompson Gene: pcsk9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.4 PPP5C Bryony Thompson Marked gene: PPP5C as ready
Intellectual disability syndromic and non-syndromic v1.4 PPP5C Bryony Thompson Gene: ppp5c has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.4 PPP5C Bryony Thompson Classified gene: PPP5C as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v1.4 PPP5C Bryony Thompson Gene: ppp5c has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2165 PPP5C Bryony Thompson Marked gene: PPP5C as ready
Mendeliome v1.2165 PPP5C Bryony Thompson Gene: ppp5c has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2165 PPP5C Bryony Thompson Classified gene: PPP5C as Amber List (moderate evidence)
Mendeliome v1.2165 PPP5C Bryony Thompson Gene: ppp5c has been classified as Amber List (Moderate Evidence).
Familial hypercholesterolaemia v0.46 PCSK9 Bryony Thompson Phenotypes for gene: PCSK9 were changed from to hypercholesterolemia, autosomal dominant, 3 MONDO:0011369
Familial hypercholesterolaemia v0.45 PCSK9 Bryony Thompson Publications for gene: PCSK9 were set to
Familial hypercholesterolaemia v0.44 PCSK9 Bryony Thompson Mode of pathogenicity for gene: PCSK9 was changed from to Other
Familial hypercholesterolaemia v0.43 PCSK9 Bryony Thompson Mode of inheritance for gene: PCSK9 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Familial hypercholesterolaemia v0.42 LIPA Bryony Thompson Marked gene: LIPA as ready
Familial hypercholesterolaemia v0.42 LIPA Bryony Thompson Gene: lipa has been classified as Green List (High Evidence).
Familial hypercholesterolaemia v0.42 LIPA Bryony Thompson Phenotypes for gene: LIPA were changed from to Cholesteryl ester storage disease, MIM# 278000; Wolman disease, MIM# 278000; Lysosomal acid lipase deficiency, MONDO:0010204
Familial hypercholesterolaemia v0.41 LIPA Bryony Thompson Publications for gene: LIPA were set to 11487567
Familial hypercholesterolaemia v0.40 LIPA Bryony Thompson Publications for gene: LIPA were set to
Familial hypercholesterolaemia v0.39 LIPA Bryony Thompson Mode of inheritance for gene: LIPA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Familial hypercholesterolaemia v0.38 CYP27A1 Bryony Thompson Marked gene: CYP27A1 as ready
Familial hypercholesterolaemia v0.38 CYP27A1 Bryony Thompson Gene: cyp27a1 has been classified as Green List (High Evidence).
Familial hypercholesterolaemia v0.38 CYP27A1 Bryony Thompson Phenotypes for gene: CYP27A1 were changed from to Cerebrotendinous xanthomatosis MONDO:0008948
Familial hypercholesterolaemia v0.37 CYP27A1 Bryony Thompson Classified gene: CYP27A1 as Green List (high evidence)
Familial hypercholesterolaemia v0.37 CYP27A1 Bryony Thompson Added comment: Comment on list classification: Included on this panel as a differential diagnosis for FH, particularly with the presence of xanthomas.
Familial hypercholesterolaemia v0.37 CYP27A1 Bryony Thompson Gene: cyp27a1 has been classified as Green List (High Evidence).
Neurodegeneration with brain iron accumulation v0.35 FA2H Sangavi Sivagnanasundram reviewed gene: FA2H: Rating: GREEN; Mode of pathogenicity: None; Publications: 20853438, 19068277; Phenotypes: hereditary spastic paraplegia 35 MONDO:0012866; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Familial hypercholesterolaemia v0.36 CYP27A1 Bryony Thompson Mode of inheritance for gene: CYP27A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Familial hypercholesterolaemia v0.35 APOB Sangavi Sivagnanasundram changed review comment from: Classified as Definitive by ClinGen General Gene Curation GCEP on 14/11/2018 -
https://search.clinicalgenome.org/CCID:004156

Mechanism of disease is LoF that typically impair LDL-C binding to the LDLR.; to: Classified as Definitive by ClinGen General Gene Curation GCEP on 14/11/2018 -
https://search.clinicalgenome.org/CCID:004156
Familial hypercholesterolaemia v0.35 APOB Bryony Thompson Added comment: Comment on mode of pathogenicity: The mechanism for disease involves defective apo B100 on LDL particles that fail to bind to LDLR.
Familial hypercholesterolaemia v0.35 APOB Bryony Thompson Mode of pathogenicity for gene: APOB was changed from to Other
Familial hypercholesterolaemia v0.34 APOB Bryony Thompson Phenotypes for gene: APOB were changed from to hypercholesterolemia, autosomal dominant, type B MONDO:0007751
Familial hypercholesterolaemia v0.33 APOB Bryony Thompson Publications for gene: APOB were set to
Familial hypercholesterolaemia v0.32 APOB Bryony Thompson Mode of inheritance for gene: APOB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Familial hypercholesterolaemia v0.31 ABCG8 Bryony Thompson Mode of inheritance for gene: ABCG8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Familial hypercholesterolaemia v0.30 ABCG8 Bryony Thompson Publications for gene: ABCG8 were set to
Familial hypercholesterolaemia v0.29 ABCG8 Bryony Thompson Phenotypes for gene: ABCG8 were changed from to Sitosterolemia MONDO:0008863
Mendeliome v1.2164 RAB35 Bryony Thompson changed review comment from: PMID: 38432637 - a single case with a neurodevelopmental disorder and a homozygous missense variant (c.80G>A; p.R27H) and supporting in vitro functional assays.
PMID: 36928819 - Posterior probability association (PPA) 0.955 for familial hypercholesterolaemia under a dominant MOI in the 100,000 Genomes project “Rareservoir” using a Bayesian statistical method - BeviMed. 469 FH cases and 55,033 controls used in BeviMed analysis. A nonsense variant and frameshift enriched in the FH cohort (n=6).
Sources: Literature; to: PMID: 38432637 - a single case with a neurodevelopmental disorder and a homozygous missense variant (c.80G>A; p.R27H) and supporting in vitro functional assays.
PMID: 36928819 - Posterior probability association (PPA) 0.955 for familial hypercholesterolaemia under a dominant MOI in the 100,000 Genomes project “Rareservoir” using a Bayesian statistical method - BeviMed. 469 FH cases and 55,033 controls used in BeviMed analysis. A nonsense variant and frameshift enriched in the FH cohort (n=6). Cosegergation in 1 affected relative also reported.
Sources: Literature
Mendeliome v1.2164 RAB35 Bryony Thompson Marked gene: RAB35 as ready
Mendeliome v1.2164 RAB35 Bryony Thompson Gene: rab35 has been classified as Red List (Low Evidence).
Mendeliome v1.2164 RAB35 Bryony Thompson gene: RAB35 was added
gene: RAB35 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RAB35 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: RAB35 were set to 38432637; 36928819
Phenotypes for gene: RAB35 were set to familial hypercholesterolemia MONDO:0005439; neurodevelopmental disorder MONDO:0700092
Review for gene: RAB35 was set to RED
Added comment: PMID: 38432637 - a single case with a neurodevelopmental disorder and a homozygous missense variant (c.80G>A; p.R27H) and supporting in vitro functional assays.
PMID: 36928819 - Posterior probability association (PPA) 0.955 for familial hypercholesterolaemia under a dominant MOI in the 100,000 Genomes project “Rareservoir” using a Bayesian statistical method - BeviMed. 469 FH cases and 55,033 controls used in BeviMed analysis. A nonsense variant and frameshift enriched in the FH cohort (n=6).
Sources: Literature
Hereditary Neuropathy_CMT - isolated v1.51 ARPC3 Bryony Thompson Marked gene: ARPC3 as ready
Hereditary Neuropathy_CMT - isolated v1.51 ARPC3 Bryony Thompson Gene: arpc3 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy_CMT - isolated v1.51 ARPC3 Bryony Thompson Classified gene: ARPC3 as Amber List (moderate evidence)
Hereditary Neuropathy_CMT - isolated v1.51 ARPC3 Bryony Thompson Gene: arpc3 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy_CMT - isolated v1.50 ARPC3 Bryony Thompson gene: ARPC3 was added
gene: ARPC3 was added to Hereditary Neuropathy_CMT - isolated. Sources: Literature
Mode of inheritance for gene: ARPC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARPC3 were set to 36928819; 26166300
Phenotypes for gene: ARPC3 were set to Charcot-Marie-Tooth disease MONDO:0015626
Review for gene: ARPC3 was set to AMBER
Added comment: Posterior probability association (PPA) 0.995 for Charcot-Marie Tooth disease under a dominant MOI in the 100,000 Genomes project “Rareservoir” using a Bayesian statistical method - BeviMed. 549 CMT cases and 54,856 controls used in BeviMed analysis. 5 rare variants (missense, splice region, a splice acceptor site) enriched in the CMT cohort (n=14). Additionally, ArpC3 conditional knockout mice fail to ensheath axons causing axon dysfunction.
Sources: Literature
Mendeliome v1.2163 ARPC3 Bryony Thompson Marked gene: ARPC3 as ready
Mendeliome v1.2163 ARPC3 Bryony Thompson Gene: arpc3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2163 ARPC3 Bryony Thompson Classified gene: ARPC3 as Amber List (moderate evidence)
Mendeliome v1.2163 ARPC3 Bryony Thompson Gene: arpc3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2162 ARPC3 Bryony Thompson gene: ARPC3 was added
gene: ARPC3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ARPC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARPC3 were set to 36928819; 26166300
Phenotypes for gene: ARPC3 were set to Charcot-Marie-Tooth disease MONDO:0015626
Review for gene: ARPC3 was set to AMBER
Added comment: Posterior probability association (PPA) 0.995 for Charcot-Marie Tooth disease under a dominant MOI in the 100,000 Genomes project “Rareservoir” using a Bayesian statistical method - BeviMed. 549 CMT cases and 54,856 controls used in BeviMed analysis. 5 rare variants (missense, splice region, a splice acceptor site) enriched in the CMT cohort (n=14).
Additionally, ArpC3 conditional knockout mice fail to ensheath axons causing axon dysfunction.
Sources: Literature
Hypertension and Aldosterone disorders v1.15 USP33 Bryony Thompson changed review comment from: Posterior probability association (PPA) 0.977 for extreme early-onset hypertension under a dominant MOI in the 100,000 Genomes project “Rareservoir” using a Bayesian statistical method - BeviMed. 2 splice site variants enriched in a renal and urinary tract disorders cohort (n=6).
Sources: Literature; to: Posterior probability association (PPA) 0.977 for extreme early-onset hypertension under a dominant MOI in the 100,000 Genomes project “Rareservoir” using a Bayesian statistical method - BeviMed. 182 early-onset hypertension cases and 55,305 controls used in BeviMed analysis. 2 splice site variants enriched in a renal and urinary tract disorders cohort (n=6).
Sources: Literature
Mendeliome v1.2161 USP33 Bryony Thompson changed review comment from: Posterior probability association (PPA) 0.977 for extreme early-onset hypertension under a dominant MOI in the 100,000 Genomes project “Rareservoir” using a Bayesian statistical method - BeviMed. 2 splice site variants enriched in a renal and urinary tract disorders cohort (n=6).
Sources: Literature; to: Posterior probability association (PPA) 0.977 for extreme early-onset hypertension under a dominant MOI in the 100,000 Genomes project “Rareservoir” using a Bayesian statistical method - BeviMed. 182 early-onset hypertension cases and 55,305 controls used in BeviMed analysis. 2 splice site variants enriched in a renal and urinary tract disorders cohort (n=6).
Sources: Literature
Deafness_IsolatedAndComplex v1.208 FMN1 Bryony Thompson changed review comment from: PMID: 36928819 - Posterior probability association (PPA) between 0.95-0.96 for congenital hearing impairment under a recessive MOI in the 100,000 Genomes project “Rareservoir” using a Bayesian statistical method - BeviMed. A splice variant (n=3) & frameshift variant (n=1), possibly in 2 cases and possibly in trans (cosegregation in 2 unaffected relatives mentioned)

PMID: 20610440; 19383632; 15202026 - A 263 Kb homozygous deletion of FMN1 has been identified in a single case with oligosyndactyly, radioulnar synostosis, hearing loss and renal defects. Also, a supporting null mouse model with oligosyndactyly. Also, a large duplication including GREM1 reported in association with Cenani–Lenz syndrome.
Sources: Literature; to: PMID: 36928819 - Posterior probability association (PPA) between 0.95-0.96 for congenital hearing impairment under a recessive MOI in the 100,000 Genomes project “Rareservoir” using a Bayesian statistical method - BeviMed. 510 CHI cases assessed and 54,738 controls in BeviMed analysis. A splice variant (n=3) & frameshift variant (n=1), possibly in 2 cases and possibly in trans (cosegregation in 2 unaffected relatives mentioned)

PMID: 20610440; 19383632; 15202026 - A 263 Kb homozygous deletion of FMN1 has been identified in a single case with oligosyndactyly, radioulnar synostosis, hearing loss and renal defects. Also, a supporting null mouse model with oligosyndactyly. Also, a large duplication including GREM1 reported in association with Cenani–Lenz syndrome.
Sources: Literature
Mendeliome v1.2161 FMN1 Bryony Thompson changed review comment from: PMID: 36928819 - Posterior probability association (PPA) between 0.95-0.96 for congenital hearing impairment under a recessive MOI in the 100,000 Genomes project “Rareservoir” using a Bayesian statistical method - BeviMed. A splice variant (n=3) & frameshift variant (n=1), possibly in 2 cases and possibly in trans (cosegregation in 2 unaffected relatives mentioned); to: PMID: 36928819 - Posterior probability association (PPA) between 0.95-0.96 for congenital hearing impairment under a recessive MOI in the 100,000 Genomes project “Rareservoir” using a Bayesian statistical method - BeviMed. 510 CHI cases assessed and 54,738 controls in BeviMed analysis. A splice variant (n=3) & frameshift variant (n=1), possibly in 2 cases and possibly in trans (cosegregation in 2 unaffected relatives mentioned)
Hypertension and Aldosterone disorders v1.15 USP33 Bryony Thompson Marked gene: USP33 as ready
Hypertension and Aldosterone disorders v1.15 USP33 Bryony Thompson Gene: usp33 has been classified as Red List (Low Evidence).
Mendeliome v1.2161 USP33 Bryony Thompson Classified gene: USP33 as Red List (low evidence)
Mendeliome v1.2161 USP33 Bryony Thompson Gene: usp33 has been classified as Red List (Low Evidence).
Hypertension and Aldosterone disorders v1.15 USP33 Bryony Thompson gene: USP33 was added
gene: USP33 was added to Hypertension and Aldosterone disorders. Sources: Literature
Mode of inheritance for gene: USP33 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: USP33 were set to 36928819
Phenotypes for gene: USP33 were set to Renal hypertension MONDO:0001105
Review for gene: USP33 was set to AMBER
Added comment: Posterior probability association (PPA) 0.977 for extreme early-onset hypertension under a dominant MOI in the 100,000 Genomes project “Rareservoir” using a Bayesian statistical method - BeviMed. 2 splice site variants enriched in a renal and urinary tract disorders cohort (n=6).
Sources: Literature
Mendeliome v1.2160 USP33 Bryony Thompson Marked gene: USP33 as ready
Mendeliome v1.2160 USP33 Bryony Thompson Gene: usp33 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2160 USP33 Bryony Thompson Classified gene: USP33 as Amber List (moderate evidence)
Mendeliome v1.2160 USP33 Bryony Thompson Gene: usp33 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2159 USP33 Bryony Thompson gene: USP33 was added
gene: USP33 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: USP33 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: USP33 were set to 36928819
Phenotypes for gene: USP33 were set to Renal hypertension MONDO:0001105
Review for gene: USP33 was set to AMBER
Added comment: Posterior probability association (PPA) 0.977 for extreme early-onset hypertension under a dominant MOI in the 100,000 Genomes project “Rareservoir” using a Bayesian statistical method - BeviMed. 2 splice site variants enriched in a renal and urinary tract disorders cohort (n=6).
Sources: Literature
Incidentalome v0.314 SCN3B Bryony Thompson Classified gene: SCN3B as Red List (low evidence)
Incidentalome v0.314 SCN3B Bryony Thompson Added comment: Comment on list classification: Disputed Brugada syndrome gene
Incidentalome v0.314 SCN3B Bryony Thompson Gene: scn3b has been classified as Red List (Low Evidence).
Incidentalome v0.313 RNASEL Bryony Thompson Marked gene: RNASEL as ready
Incidentalome v0.313 RNASEL Bryony Thompson Gene: rnasel has been classified as Red List (Low Evidence).
Incidentalome v0.313 RNASEL Bryony Thompson Classified gene: RNASEL as Red List (low evidence)
Incidentalome v0.313 RNASEL Bryony Thompson Added comment: Comment on list classification: Reportedly a prostate cancer risk factor. Not associated with Mendelian disease
Incidentalome v0.313 RNASEL Bryony Thompson Gene: rnasel has been classified as Red List (Low Evidence).
Incidentalome v0.312 RBM12 Bryony Thompson Marked gene: RBM12 as ready
Incidentalome v0.312 RBM12 Bryony Thompson Gene: rbm12 has been classified as Amber List (Moderate Evidence).
Incidentalome v0.312 RBM12 Bryony Thompson Classified gene: RBM12 as Amber List (moderate evidence)
Incidentalome v0.312 RBM12 Bryony Thompson Gene: rbm12 has been classified as Amber List (Moderate Evidence).
Incidentalome v0.311 RABL3 Bryony Thompson Publications for gene: RABL3 were set to 31406347
Incidentalome v0.310 RABL3 Bryony Thompson Classified gene: RABL3 as Red List (low evidence)
Incidentalome v0.310 RABL3 Bryony Thompson Added comment: Comment on list classification: One family reported and no replication in other pancreatic cancer cohorts at this point.
Incidentalome v0.310 RABL3 Bryony Thompson Gene: rabl3 has been classified as Red List (Low Evidence).
Incidentalome v0.309 RABL3 Bryony Thompson Classified gene: RABL3 as Red List (low evidence)
Incidentalome v0.309 RABL3 Bryony Thompson Added comment: Comment on list classification: One family reported and no replication in other pancreatic cancer cohorts at this point.
Incidentalome v0.309 RABL3 Bryony Thompson Gene: rabl3 has been classified as Red List (Low Evidence).
Mendeliome v1.2158 UCHL1 Bryony Thompson Marked gene: UCHL1 as ready
Mendeliome v1.2158 UCHL1 Bryony Thompson Gene: uchl1 has been classified as Green List (High Evidence).
Mendeliome v1.2158 UCHL1 Bryony Thompson Classified gene: UCHL1 as Green List (high evidence)
Mendeliome v1.2158 UCHL1 Bryony Thompson Gene: uchl1 has been classified as Green List (High Evidence).
Mendeliome v1.2157 UCHL1 Bryony Thompson reviewed gene: UCHL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23359680, 3340629, 28007905, 32656641, 29735986, 28007905, 35986737, 39030458; Phenotypes: Spastic paraplegia 79A, autosomal dominant, MIM# 620221, Spastic paraplegia 79, autosomal recessive, 615491, MONDO:0014209, Neurodegenerative disease, MONDO:0005559, UCHL1-related; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v1.2157 UCHL1 Bryony Thompson gene: UCHL1 was added
gene: UCHL1 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: UCHL1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: UCHL1 were set to 23359680; 3340629; 28007905; 32656641; 29735986; 28007905; 35986737; 39030458
Phenotypes for gene: UCHL1 were set to Spastic paraplegia 79A, autosomal dominant, MIM# 620221; Spastic paraplegia 79, autosomal recessive, 615491; MONDO:0014209; Neurodegenerative disease, MONDO:0005559, UCHL1-related
Neurodegeneration with brain iron accumulation v0.35 DCAF17 Sangavi Sivagnanasundram reviewed gene: DCAF17: Rating: GREEN; Mode of pathogenicity: None; Publications: 28542792, 38320940, 30409855, 35876063; Phenotypes: Woodhouse-Sakati syndrome MONDO:0009419; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Epidermolysis bullosa v1.20 TUFT1 Bryony Thompson Classified gene: TUFT1 as Amber List (moderate evidence)
Epidermolysis bullosa v1.20 TUFT1 Bryony Thompson Gene: tuft1 has been classified as Amber List (Moderate Evidence).
Epidermolysis bullosa v1.18 TUFT1 Bryony Thompson gene: TUFT1 was added
gene: TUFT1 was added to Epidermolysis bullosa. Sources: Literature
Mode of inheritance for gene: TUFT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TUFT1 were set to 36689522; 36928819
Phenotypes for gene: TUFT1 were set to Woolly hair-skin fragility syndrome, MIM# 620415
Deafness_IsolatedAndComplex v1.208 FMN1 Bryony Thompson Marked gene: FMN1 as ready
Deafness_IsolatedAndComplex v1.208 FMN1 Bryony Thompson Gene: fmn1 has been classified as Amber List (Moderate Evidence).
Deafness_IsolatedAndComplex v1.208 FMN1 Bryony Thompson Classified gene: FMN1 as Amber List (moderate evidence)
Deafness_IsolatedAndComplex v1.208 FMN1 Bryony Thompson Gene: fmn1 has been classified as Amber List (Moderate Evidence).
Deafness_IsolatedAndComplex v1.207 FMN1 Bryony Thompson gene: FMN1 was added
gene: FMN1 was added to Deafness_IsolatedAndComplex. Sources: Literature
SV/CNV tags were added to gene: FMN1.
Mode of inheritance for gene: FMN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FMN1 were set to 20610440; 19383632; 15202026; 36928819
Phenotypes for gene: FMN1 were set to Hearing loss disorder MONDO:0005365
Review for gene: FMN1 was set to AMBER
Added comment: PMID: 36928819 - Posterior probability association (PPA) between 0.95-0.96 for congenital hearing impairment under a recessive MOI in the 100,000 Genomes project “Rareservoir” using a Bayesian statistical method - BeviMed. A splice variant (n=3) & frameshift variant (n=1), possibly in 2 cases and possibly in trans (cosegregation in 2 unaffected relatives mentioned)

PMID: 20610440; 19383632; 15202026 - A 263 Kb homozygous deletion of FMN1 has been identified in a single case with oligosyndactyly, radioulnar synostosis, hearing loss and renal defects. Also, a supporting null mouse model with oligosyndactyly. Also, a large duplication including GREM1 reported in association with Cenani–Lenz syndrome.
Sources: Literature
Neurodegeneration with brain iron accumulation v0.35 CP Sangavi Sivagnanasundram reviewed gene: CP: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301666, 32235485, 11756598, 10997552; Phenotypes: aceruloplasminemia MONDO:0011426; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.2156 FMN1 Bryony Thompson Publications for gene: FMN1 were set to 20610440; 19383632; 15202026
Mendeliome v1.2155 FMN1 Bryony Thompson Phenotypes for gene: FMN1 were changed from oligosyndactyly; radioulnar synostosis; hearing loss; renal defects to Hearing loss disorder MONDO:0005365
Mendeliome v1.2154 FMN1 Bryony Thompson edited their review of gene: FMN1: Added comment: PMID: 36928819 - Posterior probability association (PPA) between 0.95-0.96 for congenital hearing impairment under a recessive MOI in the 100,000 Genomes project “Rareservoir” using a Bayesian statistical method - BeviMed. A splice variant (n=3) & frameshift variant (n=1), possibly in 2 cases and possibly in trans (cosegregation in 2 unaffected relatives mentioned); Changed publications: 20610440, 19383632, 15202026, 36928819; Changed phenotypes: Hearing loss disorder MONDO:0005365
Neurodegeneration with brain iron accumulation v0.35 COASY Sangavi Sivagnanasundram reviewed gene: COASY: Rating: GREEN; Mode of pathogenicity: None; Publications: 27021474, 24360804, 28489334; Phenotypes: neurodegeneration with brain iron accumulation 6 MONDO:0014290; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Neurodegeneration with brain iron accumulation v0.35 ATP13A2 Sangavi Sivagnanasundram reviewed gene: ATP13A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22743658, 23447832, 29325618, 20310007; Phenotypes: Kufor-Rakeb syndrome MONDO:0011706; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteopetrosis v0.34 TYROBP Sangavi Sivagnanasundram reviewed gene: TYROBP: Rating: RED; Mode of pathogenicity: None; Publications: 20301376, 25547154; Phenotypes: polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1 MONDO:0020749; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteopetrosis v0.34 TGFB1 Sangavi Sivagnanasundram reviewed gene: TGFB1: Rating: GREEN; Mode of pathogenicity: Other; Publications: 20301335, 30034812, 39014191; Phenotypes: Camurati-Engelmann disease MONDO:0007542; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Osteopetrosis v0.34 SOST Sangavi Sivagnanasundram reviewed gene: SOST: Rating: GREEN; Mode of pathogenicity: None; Publications: 23079137, 36481973, 33078679, 35208525, 36508511; Phenotypes: sclerosteosis 1 MONDO:0010016; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteopetrosis v0.34 PTH1R Sangavi Sivagnanasundram reviewed gene: PTH1R: Rating: GREEN; Mode of pathogenicity: None; Publications: 36159186, 37448157, 39327493; Phenotypes: primary failure of tooth eruption MONDO:0007434; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Prepair 1000+ v1.633 LHX3 Ee Ming Wong reviewed gene: LHX3: Rating: GREEN; Mode of pathogenicity: None; Publications: 30759489; Phenotypes: Pituitary hormone deficiency, combined, 3 (MIM# 221750); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.633 KY Ee Ming Wong reviewed gene: KY: Rating: GREEN; Mode of pathogenicity: None; Publications: 27484770, 27485408, 30591934; Phenotypes: Myopathy, myofibrillar, 7 (MIM#617114); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.633 KLHL7 Ee Ming Wong reviewed gene: KLHL7: Rating: GREEN; Mode of pathogenicity: None; Publications: 31953236, 30300710, 31856884; Phenotypes: PERCHING syndrome (MIM#617055); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.633 POP1 Crystle Lee reviewed gene: POP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27380734, 28067412; Phenotypes: Anauxetic dysplasia 2, MIM#617396; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 POMGNT2 Crystle Lee edited their review of gene: POMGNT2: Changed rating: GREEN
Prepair 1000+ v1.633 POMGNT2 Crystle Lee reviewed gene: POMGNT2: Rating: ; Mode of pathogenicity: None; Publications: 34301702; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 8, 618135, Muscular dystrophy-dystroglycanopathy (limb-girdle) type C, 8, MIM#618135; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 POMC Crystle Lee reviewed gene: POMC: Rating: GREEN; Mode of pathogenicity: None; Publications: 34177811; Phenotypes: Obesity, adrenal insufficiency, and red hair due to POMC deficiency, MIM#609734; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 IARS2 Crystle Lee reviewed gene: IARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30419932; Phenotypes: Cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia, MIM#616007; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 HINT1 Crystle Lee reviewed gene: HINT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuromyotonia and axonal neuropathy, autosomal recessive, MIM#137200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 HGSNAT Crystle Lee reviewed gene: HGSNAT: Rating: GREEN; Mode of pathogenicity: None; Publications: 32770643; Phenotypes: Mucopolysaccharidosis type IIIC (Sanfilippo C), MIM#252930, Retinitis pigmentosa 73, MIM#616544; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 PDE6C Crystle Lee reviewed gene: PDE6C: Rating: GREEN; Mode of pathogenicity: None; Publications: 33001157, 34720973; Phenotypes: Cone dystrophy 4, MIM#613093; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 NDUFAF2 Crystle Lee reviewed gene: NDUFAF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 38419071; Phenotypes: Mitochondrial complex I deficiency, nuclear type 10, MIM#618233; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 LPIN1 Crystle Lee reviewed gene: LPIN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18817903, 32549891; Phenotypes: Myoglobinuria, acute recurrent, autosomal recessive, MIM#268200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 L2HGDH Crystle Lee edited their review of gene: L2HGDH: Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 L2HGDH Crystle Lee changed review comment from: Well established gene-disease association.

Onset typically in infancy or early childhood, however, reports of milder, adult onset cases have been reported. Patients may present with a wide variety of clinical manifestations.; to: Well established gene-disease association.

Onset typically in infancy or early childhood, however, reports of milder, adult onset cases have been reported. Patients may present with a wide variety of clinical manifestations.
Prepair 1000+ v1.633 L2HGDH Crystle Lee reviewed gene: L2HGDH: Rating: ; Mode of pathogenicity: None; Publications: 39262645, 10399870; Phenotypes: L-2-hydroxyglutaric aciduria, MIM#236792; Mode of inheritance: None
Prepair 1000+ v1.633 HEXB Crystle Lee reviewed gene: HEXB: Rating: GREEN; Mode of pathogenicity: None; Publications: 35711818; Phenotypes: Sandhoff disease, infantile, juvenile, and adult forms, MIM#268800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 HEPACAM Crystle Lee reviewed gene: HEPACAM: Rating: GREEN; Mode of pathogenicity: None; Publications: 21419380; Phenotypes: Megalencephalic leukoencephalopathy with subcortical cysts 2A, MIM#613925; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 HCFC1 Crystle Lee reviewed gene: HCFC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34164576; Phenotypes: Methylmalonic aciduria and homocysteinemia, cblX type, MIM#309541; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.633 GPR143 Crystle Lee reviewed gene: GPR143: Rating: AMBER; Mode of pathogenicity: None; Publications: 30555098, 29761529; Phenotypes: Nystagmus 6, congenital, X-linked, MIM#300814, Ocular albinism, type I, Nettleship-Falls type, MIM#300500; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.633 POLR1C Andrew Coventry reviewed gene: POLR1C: Rating: GREEN; Mode of pathogenicity: None; Publications: 26151409, 21131976, 30957429, 32042905; Phenotypes: Leukodystrophy, hypomyelinating, 11 MIM#616494, Treacher Collins syndrome 3 MIM#248390; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 PEX11B Andrew Coventry reviewed gene: PEX11B: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301621, 22581968, 31724321, 38423277, 39092477, 28129423, 33558817; Phenotypes: Peroxisome biogenesis disorder 14B MIM#614920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 PEX10 Andrew Coventry reviewed gene: PEX10: Rating: GREEN; Mode of pathogenicity: None; Publications: 10862081, 21031596, 30640048; Phenotypes: Peroxisome biogenesis disorder 6A (Zellweger) MIM#614870, Peroxisome biogenesis disorder 6B MIM#614871; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 JAGN1 Ee Ming Wong reviewed gene: JAGN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25129144, 37528877; Phenotypes: Severe congenital neutropenia 6, MIM# 616022; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.633 NUP93 Andrew Coventry reviewed gene: NUP93: Rating: GREEN; Mode of pathogenicity: None; Publications: 26878725, 26878725, 33578576, 30741391, 37762751, 38650033, 37692026, 37845138; Phenotypes: Nephrotic syndrome, type 12 MIM#616892; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteopetrosis v0.34 LRP5 Sangavi Sivagnanasundram reviewed gene: LRP5: Rating: GREEN; Mode of pathogenicity: None; Publications: 37659026, 26348019, 12054167, 12579474; Phenotypes: autosomal dominant osteopetrosis 1 MONDO:0011877; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Prepair 1000+ v1.633 IL10RA Ee Ming Wong reviewed gene: IL10RA: Rating: GREEN; Mode of pathogenicity: None; Publications: 19890111, 21519361, 22476154; Phenotypes: Early onset inflammatory bowel disease 28 (MIM# 613148); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.633 IFT140 Ee Ming Wong reviewed gene: IFT140: Rating: GREEN; Mode of pathogenicity: None; Publications: 22503633, 23418020, 28288023, 28724397; Phenotypes: Short-rib thoracic dysplasia 9 with of without polydactyly (MIM#266920); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.633 NPHP4 Andrew Coventry reviewed gene: NPHP4: Rating: GREEN; Mode of pathogenicity: None; Publications: 12244321, 12205563, 34013113, 23354436, 1577426, 23188109, 23559409; Phenotypes: Nephronophthisis 4 MONDO:0011752, Nephronophthisis 4 MIM#606966, Senior-Loken syndrome 4 MIM#606996; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 NDUFAF6 Andrew Coventry reviewed gene: NDUFAF6: Rating: GREEN; Mode of pathogenicity: None; Publications: 30642748, 18614015, 30642748, 29531337, 27623250, 28639102, 31967322, 32020600, 22019594, 25613900, 26741492, 35664867; Phenotypes: Leigh syndrome MONDO:0009723, Mitochondrial complex I deficiency, nuclear type 17 MIM#618239; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteopetrosis v0.34 IKBKG Sangavi Sivagnanasundram changed review comment from: A condition that typically only affects males. Variants associated with osteopetrosis are primarily located in exon 10. Reported individuals also presented with mild skin features consistent with IP.

PMID: 20499091 - 6yr boy with multiple phenotypes including mild osteopetrosis.

PMID: 11242109 - 2 unrelated males with osteopetrosis as a presenting phenotype and X420W mutation. In vitro functional assay showed that this variant does not completely abolish IKBKG activity/protein however impairs the function.; to: A condition that typically only affects males. Variants associated with osteopetrosis are primarily located in exon 10. Reported individuals also presented with mild skin features consistent with IP.

PMID: 20499091 - 6yr boy with multiple phenotypes including mild osteopetrosis.

PMID: 11242109 - 2 unrelated males with osteopetrosis as a presenting phenotype and X420W mutation was identified. In vitro functional assay showed that this variant does not completely abolish IKBKG activity/protein however impairs the function.
Osteopetrosis v0.34 IKBKG Sangavi Sivagnanasundram reviewed gene: IKBKG: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301645, 20499091, 11242109; Phenotypes: IKBKG-related immunodeficiency with or without ectodermal dysplasia MONDO:0100162, incontinentia pigmenti MONDO:0010631; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Prepair 1000+ v1.633 IDS Ee Ming Wong reviewed gene: IDS: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301451; Phenotypes: Mucopolysaccharidosis II, MIM# 309900, Hunter syndrome, MONDO:0010674; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Prepair 1000+ v1.633 NAGLU Andrew Coventry reviewed gene: NAGLU: Rating: GREEN; Mode of pathogenicity: None; Publications: 25818867, 8650226, 14518829, 18392742, 11668611; Phenotypes: Mucopolysaccharidosis type IIIB (Sanfilippo B) MIM#252920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 MTM1 Andrew Coventry reviewed gene: MTM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 10790201, 8640223, 27017278, 26938784, 15725586, 30232666, 37176116, 32805447, 31541013; Phenotypes: Myopathy, centronuclear, X-linked MIM#310400; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Prepair 1000+ v1.633 HPRT1 Ee Ming Wong reviewed gene: HPRT1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301328; Phenotypes: Lesch-Nyhan syndrome (MIM#300322); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Mendeliome v1.2154 PPP5C Lucy Spencer gene: PPP5C was added
gene: PPP5C was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PPP5C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPP5C were set to 35361529; 25363768; 33057194
Phenotypes for gene: PPP5C were set to Neurodevelopmental disorder, MONDO:0700092, PPP5C-related
Review for gene: PPP5C was set to AMBER
Added comment: PMID: 35361529 - reported a de novo missense in a proband with microcephaly, developmental delay and epilepsy. However, after personal communication with the undiagnosed disease network this proband has since been found to have a different diagnosis with a nonsense and a missense in VARS1 identified, so unclear if the PPP5C variant is contributing to their phenotype.

3 more probands with de novo missense variants have been published in large autism or developmental disorder cohort with limited information (PMIDs: 25363768, 33057194)

An internal VCGS proband with intellectual disability and failure to thrive was also found to have a de novo missense variant in this gene.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.3 PPP5C Lucy Spencer gene: PPP5C was added
gene: PPP5C was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PPP5C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPP5C were set to 35361529; 25363768; 33057194
Phenotypes for gene: PPP5C were set to Neurodevelopmental disorder, MONDO:0700092, PPP5C-related
Review for gene: PPP5C was set to AMBER
Added comment: PMID: 35361529 - reported a de novo missense in a proband with microcephaly, developmental delay and epilepsy. However, after personal communication with the undiagnosed disease network this proband has since been found to have a different diagnosis with a nonsense and a missense in VARS1 identified, so unclear if the PPP5C variant is contributing to their phenotype.

3 more probands with de novo missense variants have been published in large autism or developmental disorder cohort with limited information (PMIDs: 25363768, 33057194)

An internal VCGS proband with intellectual disability and failure to thrive was also found to have a de novo missense variant in this gene.
Sources: Literature
Osteopetrosis v0.34 AMER1 Sangavi Sivagnanasundram reviewed gene: AMER1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27369646, 33856753, 35186393; Phenotypes: osteopathia striata with cranial sclerosis MONDO:0010310; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral vascular malformations v1.0 Bryony Thompson promoted panel to version 1.0
Cerebral vascular malformations v0.116 COL4A2 Sangavi Sivagnanasundram changed review comment from: 22209247 - COL4A1 form heterotrimers with COL4A2 which results in the cerebral vascular phenotype. No pathogenic variants in COL1A2 have been reported in individuals with a cerebral vascular phenotype.

COL4A2 is typically associated with haemorrhagic strokes with no evidence of any cerebral vascular malformations.; to: 22209247 - COL4A1 form heterotrimers with COL4A2 which results in the cerebral vascular phenotype. No pathogenic variants in COL4A2 have been reported in individuals with a cerebral vascular phenotype.

COL4A2 is typically associated with haemorrhagic strokes with no evidence of any cerebral vascular malformations.
Cerebral vascular malformations v0.116 COL4A2 Sangavi Sivagnanasundram changed review comment from: 22209247 - COL1A1 form heterotrimers with COL2A2 which results in the cerebral vascular phenotype. No pathogenic variants in COL1A2 have been reported in individuals with a cerebral vascular phenotype.

COL2A2 is typically associated with haemorrhagic strokes with no evidence of any cerebral vascular malformations.; to: 22209247 - COL4A1 form heterotrimers with COL4A2 which results in the cerebral vascular phenotype. No pathogenic variants in COL1A2 have been reported in individuals with a cerebral vascular phenotype.

COL4A2 is typically associated with haemorrhagic strokes with no evidence of any cerebral vascular malformations.
Cerebral vascular malformations v0.116 PKD1 Bryony Thompson Classified gene: PKD1 as Green List (high evidence)
Cerebral vascular malformations v0.116 PKD1 Bryony Thompson Gene: pkd1 has been classified as Green List (High Evidence).
Cerebral vascular malformations v0.115 PKD1 Bryony Thompson Classified gene: PKD1 as Amber List (moderate evidence)
Cerebral vascular malformations v0.115 PKD1 Bryony Thompson Gene: pkd1 has been classified as Amber List (Moderate Evidence).
Cerebral vascular malformations v0.114 PCNT Bryony Thompson Marked gene: PCNT as ready
Cerebral vascular malformations v0.114 PCNT Bryony Thompson Gene: pcnt has been classified as Green List (High Evidence).
Cerebral vascular malformations v0.114 PCNT Bryony Thompson Classified gene: PCNT as Green List (high evidence)
Cerebral vascular malformations v0.114 PCNT Bryony Thompson Gene: pcnt has been classified as Green List (High Evidence).
Cerebral vascular malformations v0.113 PCNT Bryony Thompson Publications for gene: PCNT were set to 15368497
Cerebral vascular malformations v0.112 MYH11 Bryony Thompson Marked gene: MYH11 as ready
Cerebral vascular malformations v0.112 MYH11 Bryony Thompson Gene: myh11 has been classified as Red List (Low Evidence).
Cerebral vascular malformations v0.112 MYH11 Bryony Thompson Publications for gene: MYH11 were set to 16444274; 29263223
Cerebral vascular malformations v0.111 MYH11 Bryony Thompson Classified gene: MYH11 as Red List (low evidence)
Cerebral vascular malformations v0.111 MYH11 Bryony Thompson Gene: myh11 has been classified as Red List (Low Evidence).
Mendeliome v1.2154 MRVI1 Bryony Thompson Marked gene: MRVI1 as ready
Mendeliome v1.2154 MRVI1 Bryony Thompson Gene: mrvi1 has been classified as Red List (Low Evidence).
Mendeliome v1.2154 MRVI1 Bryony Thompson Phenotypes for gene: MRVI1 were changed from moyamoya syndrome to Moyamoya disease MONDO:0016820
Mendeliome v1.2153 MRVI1 Bryony Thompson edited their review of gene: MRVI1: Changed phenotypes: Moyamoya disease MONDO:0016820
Mendeliome v1.2153 MRVI1 Bryony Thompson gene: MRVI1 was added
gene: MRVI1 was added to Mendeliome. Sources: NHS GMS
new gene name tags were added to gene: MRVI1.
Mode of inheritance for gene: MRVI1 was set to Unknown
Publications for gene: MRVI1 were set to 30001348
Phenotypes for gene: MRVI1 were set to moyamoya syndrome
Review for gene: MRVI1 was set to RED
Added comment: A single report of a variant as a possible modifier of NF1-related Moyamoya disease. The SNP rs35857561 segregates co-occurring with NF1 in 2 families and Moyamoya disease. rs35857561 is a common SNP and IRAG1 (new gene name) hasn't been reported in association with Mendelian disease.
Sources: NHS GMS
Cerebral vascular malformations v0.110 MRVI1 Bryony Thompson Marked gene: MRVI1 as ready
Cerebral vascular malformations v0.110 MRVI1 Bryony Thompson Gene: mrvi1 has been classified as Red List (Low Evidence).
Cerebral vascular malformations v0.110 MRVI1 Bryony Thompson Classified gene: MRVI1 as Red List (low evidence)
Cerebral vascular malformations v0.110 MRVI1 Bryony Thompson Gene: mrvi1 has been classified as Red List (Low Evidence).
Cerebral vascular malformations v0.109 FLVCR2 Bryony Thompson Classified gene: FLVCR2 as Green List (high evidence)
Cerebral vascular malformations v0.109 FLVCR2 Bryony Thompson Gene: flvcr2 has been classified as Green List (High Evidence).
Cerebral vascular malformations v0.108 FLVCR2 Bryony Thompson reviewed gene: FLVCR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 38693257, 32333401, 20206334; Phenotypes: Proliferative vasculopathy and hydranencephaly/hydrocephaly MONDO:0009168; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Cerebral vascular malformations v0.108 CEP152 Bryony Thompson Marked gene: CEP152 as ready
Cerebral vascular malformations v0.108 CEP152 Bryony Thompson Gene: cep152 has been classified as Red List (Low Evidence).
Cerebral vascular malformations v0.108 CEP152 Bryony Thompson Classified gene: CEP152 as Red List (low evidence)
Cerebral vascular malformations v0.108 CEP152 Bryony Thompson Gene: cep152 has been classified as Red List (Low Evidence).
Cerebral vascular malformations v0.107 ATR Bryony Thompson Classified gene: ATR as Red List (low evidence)
Cerebral vascular malformations v0.107 ATR Bryony Thompson Gene: atr has been classified as Red List (Low Evidence).
Cerebral vascular malformations v0.106 NF1 Bryony Thompson Marked gene: NF1 as ready
Cerebral vascular malformations v0.106 NF1 Bryony Thompson Gene: nf1 has been classified as Green List (High Evidence).
Cerebral vascular malformations v0.106 NF1 Bryony Thompson Classified gene: NF1 as Green List (high evidence)
Cerebral vascular malformations v0.106 NF1 Bryony Thompson Gene: nf1 has been classified as Green List (High Evidence).
Cerebral vascular malformations v0.105 NF1 Bryony Thompson reviewed gene: NF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 39367156, 39380389, 20301288; Phenotypes: Neurofibromatosis type 1 MONDO:0018975; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v1.2152 DHDDS Zornitza Stark Publications for gene: DHDDS were set to 27343064; 29100083; 21295283; 34382076
Mendeliome v1.2151 DHDDS Zornitza Stark edited their review of gene: DHDDS: Added comment: Bi-allelic variants: ClinGen have lumped the CDG together with the RP -- likely represent a continuum of severity rather than distinct disorders.; Changed publications: 27343064, 29100083, 21295283, 27343064, 21295283, 28130426, 29276052, 32483926, 36046393, 24078709, 28005406, 36046393
Retinitis pigmentosa v0.155 DHDDS Zornitza Stark Phenotypes for gene: DHDDS were changed from Retinitis pigmentosa 59, 613861 to Congenital disorder of glycosylation, type 1bb, MIM# 613861
Retinitis pigmentosa v0.154 DHDDS Zornitza Stark Publications for gene: DHDDS were set to
Retinitis pigmentosa v0.153 DHDDS Zornitza Stark Classified gene: DHDDS as Green List (high evidence)
Retinitis pigmentosa v0.153 DHDDS Zornitza Stark Gene: dhdds has been classified as Green List (High Evidence).
Retinitis pigmentosa v0.152 DHDDS Zornitza Stark edited their review of gene: DHDDS: Added comment: ClinGen have lumped the CDG together with the RP -- likely represent a continuum of severity rather than distinct disorders.; Changed rating: GREEN; Changed publications: 27343064, 21295283, 28130426, 29276052, 32483926, 36046393, 24078709, 28005406, 36046393; Changed phenotypes: Congenital disorder of glycosylation, type 1bb, MIM# 613861; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v1.58 DHDDS Zornitza Stark Publications for gene: DHDDS were set to 27343064
Congenital Disorders of Glycosylation v1.57 DHDDS Zornitza Stark Classified gene: DHDDS as Green List (high evidence)
Congenital Disorders of Glycosylation v1.57 DHDDS Zornitza Stark Gene: dhdds has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v1.56 DHDDS Zornitza Stark edited their review of gene: DHDDS: Added comment: ClinGen have lumped the CDG together with the RP -- likely represent a continuum of severity rather than distinct disorders.; Changed rating: GREEN; Changed publications: 27343064, 21295283, 28130426, 29276052, 32483926, 36046393, 24078709, 28005406, 36046393
Osteopetrosis v0.34 FERMT3 Sangavi Sivagnanasundram reviewed gene: FERMT3: Rating: GREEN; Mode of pathogenicity: None; Publications: 19234460, 20357244, 18278053; Phenotypes: leukocyte adhesion deficiency 3 MONDO:0013016; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteopetrosis v0.34 CTSK Sangavi Sivagnanasundram reviewed gene: CTSK: Rating: GREEN; Mode of pathogenicity: None; Publications: 19232111, 34777883, 32984533, 24269275; Phenotypes: pycnodysostosis MONDO:0009940; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteopetrosis v0.34 ANKH Sangavi Sivagnanasundram reviewed gene: ANKH: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301634, 20358596; Phenotypes: craniometaphyseal dysplasia MONDO:0015465; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pneumothorax v0.11 SMAD3 Sangavi Sivagnanasundram reviewed gene: SMAD3: Rating: AMBER; Mode of pathogenicity: None; Publications: 29392890, 26247899; Phenotypes: Loeys-Dietz syndrome 3 MIM#613795; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pneumothorax v0.11 SMAD2 Sangavi Sivagnanasundram reviewed gene: SMAD2: Rating: RED; Mode of pathogenicity: None; Publications: 26247899; Phenotypes: Loeys-Dietz syndrome 6 MONDO:0030500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pneumothorax v0.11 TSC2 Sangavi Sivagnanasundram reviewed gene: TSC2: Rating: AMBER; Mode of pathogenicity: None; Publications: 36117164, 37800821; Phenotypes: lymphangioleiomyomatosis MONDO:0011705, tuberous sclerosis 2 MONDO:0013199; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pneumothorax v0.11 TSC1 Sangavi Sivagnanasundram edited their review of gene: TSC1: Changed rating: AMBER
Pneumothorax v0.11 TSC1 Sangavi Sivagnanasundram changed review comment from: Lymphangioleiomyomatosis (LAM) is the primary pulmonary manifestation of tuberous sclerosis. LAM can cause other pulmonary phenotypes including pneumothorax.
The reported cases in the literature have reported a pneumothorax phenotype secondary to LAM and not as a primary cause when looking at tuberous sclerosis.
There are many reported individuals with a diagnosis of LAM has been reported with pneumothorax. ; to: Lymphangioleiomyomatosis (LAM) is the primary pulmonary manifestation of tuberous sclerosis. LAM can cause other pulmonary phenotypes including pneumothorax.
The reported cases in the literature have reported a pneumothorax phenotype secondary to LAM and not as a primary cause when looking at tuberous sclerosis.
There are many reported individuals with a diagnosis of LAM has been reported with pneumothorax.

This gene would be green when curated against LAM however red when curated against TSC as pneumothorax is a secondary feature.
Pneumothorax v0.11 TSC1 Sangavi Sivagnanasundram edited their review of gene: TSC1: Changed rating: GREEN
Pneumothorax v0.11 TSC1 Sangavi Sivagnanasundram changed review comment from: Lymphangioleiomyomatosis (LAM) is the primary pulmonary manifestation of tuberous sclerosis. LAM can cause other pulmonary phenotypes including pneumothorax.
The reported cases in the literature have reported a pneumothorax phenotype secondary to LAM and not as a primary cause.; to: Lymphangioleiomyomatosis (LAM) is the primary pulmonary manifestation of tuberous sclerosis. LAM can cause other pulmonary phenotypes including pneumothorax.
The reported cases in the literature have reported a pneumothorax phenotype secondary to LAM and not as a primary cause when looking at tuberous sclerosis.
There are many reported individuals with a diagnosis of LAM has been reported with pneumothorax.
Pneumothorax v0.11 TSC1 Sangavi Sivagnanasundram edited their review of gene: TSC1: Changed rating: AMBER
Pneumothorax v0.11 TSC1 Sangavi Sivagnanasundram reviewed gene: TSC1: Rating: RED; Mode of pathogenicity: None; Publications: 27226234, 23729718, 19318672; Phenotypes: tuberous sclerosis 1 MONDO:0008612, lung lymphangioleiomyomatosis MONDO:0006277; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pneumothorax v0.11 TGFB2 Sangavi Sivagnanasundram reviewed gene: TGFB2: Rating: AMBER; Mode of pathogenicity: None; Publications: 22772371, 29392890; Phenotypes: Loeys-Dietz syndrome 4 MONDO:0013897; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pneumothorax v0.11 TGFBR2 Sangavi Sivagnanasundram reviewed gene: TGFBR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22488992, 26493799; Phenotypes: Loeys-Dietz syndrome 2 MONDO:0012427; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pneumothorax v0.11 TGFB2 Sangavi Sivagnanasundram Deleted their review
Pneumothorax v0.11 TGFB2 Sangavi Sivagnanasundram Deleted their comment
Pneumothorax v0.11 TGFB3 Sangavi Sivagnanasundram reviewed gene: TGFB3: Rating: RED; Mode of pathogenicity: None; Publications: 25835445, 31898322; Phenotypes: Loeys-Dietz syndrome MONDO:0018954; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pneumothorax v0.11 TGFBR1 Sangavi Sivagnanasundram reviewed gene: TGFBR1: Rating: RED; Mode of pathogenicity: None; Publications: 16799921, 25835445; Phenotypes: Loeys-Dietz syndrome MONDO:0018954; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pneumothorax v0.11 TGFB2 Sangavi Sivagnanasundram reviewed gene: TGFB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26493799, 22488992, 24577266; Phenotypes: Loeys-Dietz syndrome 4 MONDO:0013897; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Prepair 1000+ v1.633 COG6 Lauren Thomas reviewed gene: COG6: Rating: GREEN; Mode of pathogenicity: None; Publications: 20605848, 23430903, 26260076, 32905044, 32683677, 31420886; Phenotypes: Congenital disorder of glycosylation, type IIl (MIM# 614576); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 GPT2 Kate Scarff reviewed gene: GPT2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27601654, 25758935, 31471722; Phenotypes: Neurodevelopmental disorder with microcephaly and spastic paraplegia, MIM #616281; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 MTFMT Andrew Coventry reviewed gene: MTFMT: Rating: GREEN; Mode of pathogenicity: None; Publications: 21907147, 23499752, 24461907, 22499348, 30911575; Phenotypes: Leigh Syndrome MONDO:0009723; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 GPC3 Kate Scarff reviewed gene: GPC3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301398, 38766979; Phenotypes: Simpson-Golabi-Behmel syndrome, type 1, MIM #312870; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Prepair 1000+ v1.633 DPH1 Lilian Downie Marked gene: DPH1 as ready
Prepair 1000+ v1.633 DPH1 Lilian Downie Gene: dph1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.633 DPH1 Lilian Downie Publications for gene: DPH1 were set to
Pneumothorax v0.11 SERPINA1 Sangavi Sivagnanasundram reviewed gene: SERPINA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 38633947, 20301692; Phenotypes: alpha 1-antitrypsin deficiency MONDO:0013282; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.632 EIF2B5 Lilian Downie Marked gene: EIF2B5 as ready
Prepair 1000+ v1.632 EIF2B5 Lilian Downie Gene: eif2b5 has been classified as Green List (High Evidence).
Prepair 1000+ v1.632 EIF2B5 Lilian Downie Publications for gene: EIF2B5 were set to
Prepair 1000+ v1.631 ESCO2 Lilian Downie Marked gene: ESCO2 as ready
Prepair 1000+ v1.631 ESCO2 Lilian Downie Added comment: Comment when marking as ready: ClinGen review
Prepair 1000+ v1.631 ESCO2 Lilian Downie Gene: esco2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.631 ESCO2 Lilian Downie Added comment: Comment on phenotypes: ClinGen review for Roberts-SC phocolmelia MONDO:0100253 but no reference to Juberg-Hayward syndrome
Prepair 1000+ v1.631 ESCO2 Lilian Downie Phenotypes for gene: ESCO2 were changed from SC phocomelia syndrome, 269000 (3) to Juberg-Hayward syndrome (MIM#216100); Roberts-SC phocomelia syndrome (MIM#268300)
Prepair 1000+ v1.630 ESCO2 Lilian Downie Publications for gene: ESCO2 were set to
Prepair 1000+ v1.629 GAMT Lilian Downie Marked gene: GAMT as ready
Prepair 1000+ v1.629 GAMT Lilian Downie Gene: gamt has been classified as Green List (High Evidence).
Prepair 1000+ v1.629 GAMT Lilian Downie Publications for gene: GAMT were set to
Prepair 1000+ v1.628 GLDC Lilian Downie Marked gene: GLDC as ready
Prepair 1000+ v1.628 GLDC Lilian Downie Gene: gldc has been classified as Green List (High Evidence).
Prepair 1000+ v1.628 GLDC Lilian Downie Publications for gene: GLDC were set to
Prepair 1000+ v1.627 GNS Lilian Downie Marked gene: GNS as ready
Prepair 1000+ v1.627 GNS Lilian Downie Gene: gns has been classified as Green List (High Evidence).
Prepair 1000+ v1.627 GNS Lilian Downie Publications for gene: GNS were set to
Prepair 1000+ v1.626 GPAA1 Lilian Downie Marked gene: GPAA1 as ready
Prepair 1000+ v1.626 GPAA1 Lilian Downie Gene: gpaa1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.626 GPAA1 Lilian Downie Phenotypes for gene: GPAA1 were changed from Glycosylphosphatidylinositol biosynthesis defect 15, 617810 (3), Autosomal recessive to Glycosylphosphatidylinositol biosynthesis defect 15, MIM#617810
Prepair 1000+ v1.625 GPAA1 Lilian Downie Publications for gene: GPAA1 were set to
Prepair 1000+ v1.624 GRM1 Lilian Downie Marked gene: GRM1 as ready
Prepair 1000+ v1.624 GRM1 Lilian Downie Gene: grm1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.624 GRM1 Lilian Downie Publications for gene: GRM1 were set to 22901947; 26308914; 31319223
Prepair 1000+ v1.624 GRM1 Lilian Downie Publications for gene: GRM1 were set to
Prepair 1000+ v1.623 GTF2H5 Lilian Downie Marked gene: GTF2H5 as ready
Prepair 1000+ v1.623 GTF2H5 Lilian Downie Gene: gtf2h5 has been classified as Green List (High Evidence).
Prepair 1000+ v1.623 GTF2H5 Lilian Downie Phenotypes for gene: GTF2H5 were changed from Trichothiodystrophy 3, photosensitive, 616395 (3) to Trichothiodystrophy 3, photosensitive, MIM# 616395
Prepair 1000+ v1.622 GTF2H5 Lilian Downie Publications for gene: GTF2H5 were set to
Prepair 1000+ v1.621 GUCY1A3 Lilian Downie Marked gene: GUCY1A3 as ready
Prepair 1000+ v1.621 GUCY1A3 Lilian Downie Gene: gucy1a3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.621 GUCY1A3 Lilian Downie Publications for gene: GUCY1A3 were set to
Prepair 1000+ v1.620 ATF6 Lilian Downie Marked gene: ATF6 as ready
Prepair 1000+ v1.620 ATF6 Lilian Downie Gene: atf6 has been classified as Green List (High Evidence).
Prepair 1000+ v1.620 ATF6 Lilian Downie Phenotypes for gene: ATF6 were changed from Achromatopsia 7, 616517 (3), Autosomal recessive to Achromatopsia 7, MIM# 616517
Prepair 1000+ v1.619 ATF6 Lilian Downie Publications for gene: ATF6 were set to
Prepair 1000+ v1.618 B4GALNT1 Lilian Downie Marked gene: B4GALNT1 as ready
Prepair 1000+ v1.618 B4GALNT1 Lilian Downie Gene: b4galnt1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.618 B4GALNT1 Lilian Downie Phenotypes for gene: B4GALNT1 were changed from Spastic paraplegia 26, MIM# 609195 to Spastic paraplegia 26, MIM# 609195
Prepair 1000+ v1.617 B4GALNT1 Lilian Downie Phenotypes for gene: B4GALNT1 were changed from Spastic paraplegia 26, autosomal recessive, 609195 (3) to Spastic paraplegia 26, MIM# 609195
Prepair 1000+ v1.616 B4GALNT1 Lilian Downie Publications for gene: B4GALNT1 were set to
Prepair 1000+ v1.615 LARP7 Lilian Downie Marked gene: LARP7 as ready
Prepair 1000+ v1.615 LARP7 Lilian Downie Gene: larp7 has been classified as Green List (High Evidence).
Prepair 1000+ v1.615 LARP7 Lilian Downie Phenotypes for gene: LARP7 were changed from Alazami syndrome, 615071 (3) to Alazami syndrome MIM#615071
Prepair 1000+ v1.614 LARP7 Lilian Downie Publications for gene: LARP7 were set to
Prepair 1000+ v1.613 MMAB Andrew Coventry reviewed gene: MMAB: Rating: GREEN; Mode of pathogenicity: None; Publications: 12471062, 24813872, 16410054; Phenotypes: Methylmalonic aciduria, vitamin B12-responsive, cblB type MIM#251110; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.613 FKBP10 Lilian Downie Marked gene: FKBP10 as ready
Prepair 1000+ v1.613 FKBP10 Lilian Downie Gene: fkbp10 has been classified as Green List (High Evidence).
Prepair 1000+ v1.613 FKBP10 Lilian Downie Phenotypes for gene: FKBP10 were changed from Bruck syndrome 1, 259450 (3) to Bruck syndrome MIM#259450; osteogenesis imperfecta, type XI, MIM#610968
Prepair 1000+ v1.612 FKBP10 Lilian Downie Publications for gene: FKBP10 were set to
Prepair 1000+ v1.611 LBR Lilian Downie Marked gene: LBR as ready
Prepair 1000+ v1.611 LBR Lilian Downie Gene: lbr has been classified as Green List (High Evidence).
Prepair 1000+ v1.611 LBR Lilian Downie Added comment: Comment on phenotypes: See detailed ClinGen curation these phenotypes have been split.
Prepair 1000+ v1.611 LBR Lilian Downie Phenotypes for gene: LBR were changed from Greenberg skeletal dysplasia MIM#215140; Rhizomelic skeletal dysplasia with or without Pelger-Huet anomaly MIM#618019 to Greenberg skeletal dysplasia MIM#215140; Regressive Spondylometaphyseal Dysplasia MIM#618019)
Prepair 1000+ v1.610 LBR Lilian Downie Phenotypes for gene: LBR were changed from Greenberg skeletal dysplasia, 215140 (3) to Greenberg skeletal dysplasia MIM#215140; Rhizomelic skeletal dysplasia with or without Pelger-Huet anomaly MIM#618019
Prepair 1000+ v1.609 LBR Lilian Downie Publications for gene: LBR were set to
Prepair 1000+ v1.608 GM2A Kate Scarff reviewed gene: GM2A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28417072, 28192816, 27402091, 33819415; Phenotypes: GM2-gangliosidosis, AB variant MIM #272750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.608 MBTPS1 Lilian Downie Marked gene: MBTPS1 as ready
Prepair 1000+ v1.608 MBTPS1 Lilian Downie Added comment: Comment when marking as ready: UPGRADE TO GREEN
Prepair 1000+ v1.608 MBTPS1 Lilian Downie Gene: mbtps1 has been classified as Amber List (Moderate Evidence).
Pneumothorax v0.11 FLCN Sangavi Sivagnanasundram reviewed gene: FLCN: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301695, 22146830; Phenotypes: Obsolete Birt-Hogg-Dube syndrome MONDO:0007607; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Prepair 1000+ v1.608 MGP Lilian Downie Marked gene: MGP as ready
Prepair 1000+ v1.608 MGP Lilian Downie Gene: mgp has been classified as Green List (High Evidence).
Prepair 1000+ v1.608 MGP Lilian Downie Publications for gene: MGP were set to
Prepair 1000+ v1.607 BIN1 Lilian Downie Marked gene: BIN1 as ready
Prepair 1000+ v1.607 BIN1 Lilian Downie Gene: bin1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.607 BIN1 Lilian Downie Phenotypes for gene: BIN1 were changed from Myopathy, centronuclear, autosomal recessive, 255200 (3) to Centronuclear myopathy 2, MIM# 255200
Prepair 1000+ v1.606 BIN1 Lilian Downie Publications for gene: BIN1 were set to
Prepair 1000+ v1.605 FREM2 Lilian Downie Marked gene: FREM2 as ready
Prepair 1000+ v1.605 FREM2 Lilian Downie Gene: frem2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.605 FREM2 Lilian Downie Publications for gene: FREM2 were set to
Prepair 1000+ v1.604 BMPER Lilian Downie Marked gene: BMPER as ready
Prepair 1000+ v1.604 BMPER Lilian Downie Gene: bmper has been classified as Green List (High Evidence).
Prepair 1000+ v1.604 BMPER Lilian Downie Publications for gene: BMPER were set to
Prepair 1000+ v1.603 ATP6AP1 Lilian Downie Marked gene: ATP6AP1 as ready
Prepair 1000+ v1.603 ATP6AP1 Lilian Downie Gene: atp6ap1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.603 ATP6AP1 Lilian Downie Phenotypes for gene: ATP6AP1 were changed from Immunodeficiency 47, 300972 (3), X-linked recessive to Immunodeficiency 47, MIM#300972
Prepair 1000+ v1.602 ATP6AP1 Lilian Downie Publications for gene: ATP6AP1 were set to
Prepair 1000+ v1.601 BBS5 Lilian Downie Marked gene: BBS5 as ready
Prepair 1000+ v1.601 BBS5 Lilian Downie Gene: bbs5 has been classified as Green List (High Evidence).
Prepair 1000+ v1.601 BBS5 Lilian Downie Phenotypes for gene: BBS5 were changed from Bardet-Biedl syndrome 5, MIM#615983 to Bardet-Biedl syndrome 5, MIM#615983
Prepair 1000+ v1.600 BBS5 Lilian Downie Phenotypes for gene: BBS5 were changed from Bardet-Biedl syndrome 5, 615983 (3) to Bardet-Biedl syndrome 5, MIM#615983
Prepair 1000+ v1.599 BBS5 Lilian Downie Publications for gene: BBS5 were set to
Prepair 1000+ v1.598 BCKDHA Lilian Downie Marked gene: BCKDHA as ready
Prepair 1000+ v1.598 BCKDHA Lilian Downie Gene: bckdha has been classified as Green List (High Evidence).
Prepair 1000+ v1.598 BCKDHA Lilian Downie Phenotypes for gene: BCKDHA were changed from Maple syrup urine disease, type Ia, 248600 (3) to Maple syrup urine disease, type Ia, MIM# 248600
Prepair 1000+ v1.597 BCKDHA Lilian Downie Publications for gene: BCKDHA were set to
Prepair 1000+ v1.596 CA2 Lilian Downie Marked gene: CA2 as ready
Prepair 1000+ v1.596 CA2 Lilian Downie Gene: ca2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.596 CA2 Lilian Downie Phenotypes for gene: CA2 were changed from Osteopetrosis, autosomal recessive 3, with renal tubular acidosis, 259730 (3) to Osteopetrosis, autosomal recessive 3, with renal tubular acidosis, MIM#259730
Cerebral vascular malformations v0.105 Bryony Thompson removed gene:ELN from the panel
Prepair 1000+ v1.595 CA2 Lilian Downie Publications for gene: CA2 were set to
Cerebral vascular malformations v0.104 Bryony Thompson removed gene:FBN1 from the panel
Prepair 1000+ v1.594 CCDC115 Lilian Downie Marked gene: CCDC115 as ready
Prepair 1000+ v1.594 CCDC115 Lilian Downie Gene: ccdc115 has been classified as Green List (High Evidence).
Prepair 1000+ v1.594 CCDC115 Lilian Downie Phenotypes for gene: CCDC115 were changed from Congenital disorder of glycosylation, type IIo, 616828 (3), Autosomal recessive to Congenital disorder of glycosylation, type IIo, MIM#616828
Prepair 1000+ v1.593 CCDC115 Lilian Downie Publications for gene: CCDC115 were set to
Cerebral vascular malformations v0.103 Bryony Thompson removed gene:FLT4 from the panel
Pneumothorax v0.11 FBN1 Sangavi Sivagnanasundram reviewed gene: FBN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301510, 12598898, 22772371, 34795948; Phenotypes: Marfan syndrome MONDO:0007947; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral vascular malformations v0.102 Bryony Thompson removed gene:FOXF1 from the panel
Cerebral vascular malformations v0.101 Bryony Thompson removed gene:GLA from the panel
Cerebral vascular malformations v0.100 Bryony Thompson removed gene:GLMN from the panel
Cerebral vascular malformations v0.99 Bryony Thompson removed gene:GNAQ from the panel
Cerebral vascular malformations v0.98 Bryony Thompson removed gene:HLA-B from the panel
Cerebral vascular malformations v0.97 Bryony Thompson removed gene:HLA-DQB1 from the panel
Cerebral vascular malformations v0.96 Bryony Thompson removed gene:HLA-DRB1 from the panel
Cerebral vascular malformations v0.95 Bryony Thompson removed gene:HTRA1 from the panel
Cerebral vascular malformations v0.94 Bryony Thompson removed gene:IL6 from the panel
Cerebral vascular malformations v0.93 Bryony Thompson removed gene:JAG1 from the panel
Cerebral vascular malformations v0.92 Bryony Thompson removed gene:KDR from the panel
Cerebral vascular malformations v0.91 Bryony Thompson removed gene:LAMB1 from the panel
Cerebral vascular malformations v0.90 Bryony Thompson removed gene:LAMC3 from the panel
Cerebral vascular malformations v0.89 Bryony Thompson removed gene:LARGE1 from the panel
Cerebral vascular malformations v0.88 Bryony Thompson removed gene:MEF2C from the panel
Cerebral vascular malformations v0.87 Bryony Thompson removed gene:NDE1 from the panel
Cerebral vascular malformations v0.86 Bryony Thompson removed gene:NIN from the panel
Cerebral vascular malformations v0.85 Bryony Thompson removed gene:NOTCH3 from the panel
Cerebral vascular malformations v0.84 Bryony Thompson removed gene:OCLN from the panel
Cerebral vascular malformations v0.83 Bryony Thompson removed gene:OPHN1 from the panel
Cerebral vascular malformations v0.82 Bryony Thompson removed gene:PAFAH1B1 from the panel
Cerebral vascular malformations v0.81 Bryony Thompson removed gene:PIK3R2 from the panel
Cerebral vascular malformations v0.80 Bryony Thompson removed gene:POMGNT1 from the panel
Cerebral vascular malformations v0.79 Bryony Thompson removed gene:POMT1 from the panel
Cerebral vascular malformations v0.78 Bryony Thompson removed gene:POMT2 from the panel
Cerebral vascular malformations v0.77 Bryony Thompson removed gene:PTEN from the panel
Cerebral vascular malformations v0.76 Bryony Thompson removed gene:RBBP8 from the panel
Cerebral vascular malformations v0.75 Bryony Thompson removed gene:RELN from the panel
Cerebral vascular malformations v0.74 Bryony Thompson removed gene:RTTN from the panel
Prepair 1000+ v1.592 CCDC115 Melanie Marty reviewed gene: CCDC115: Rating: GREEN; Mode of pathogenicity: None; Publications: 26833332; Phenotypes: Congenital disorder of glycosylation, type IIo (MIM# 616828); Mode of inheritance: None
Pneumothorax v0.11 COL3A1 Sangavi Sivagnanasundram reviewed gene: COL3A1: Rating: GREEN; Mode of pathogenicity: Other; Publications: 20301667, 24591672, 22610159, 19420820; Phenotypes: Ehlers-Danlos syndrome, vascular type MONDO:0017314; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Bone Marrow Failure v1.106 ERG Bryony Thompson Publications for gene: ERG were set to https://ash.confex.com/ash/2023/webprogram/Paper191986.html
Lymphoedema_nonsyndromic v0.40 MDFIC Krithika Murali gene: MDFIC was added
gene: MDFIC was added to Lymphoedema_nonsyndromic. Sources: Literature
Mode of inheritance for gene: MDFIC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MDFIC were set to PMID: 35235341
Phenotypes for gene: MDFIC were set to Lymphatic malformation 12 - MIM#620014
Review for gene: MDFIC was set to GREEN
Added comment: Biallelic LoF variants associated with central conducting lymphatic anomaly.
Sources: Literature
Lymphoedema_nonsyndromic v0.40 MDFIC Krithika Murali gene: MDFIC was added
gene: MDFIC was added to Lymphoedema_nonsyndromic. Sources: Literature
Mode of inheritance for gene: MDFIC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MDFIC were set to PMID: 35235341
Phenotypes for gene: MDFIC were set to Lymphatic malformation 12 - MIM#620014
Review for gene: MDFIC was set to GREEN
Added comment: Biallelic LoF variants associated with central conducting lymphatic anomaly.
Sources: Literature
Cerebral vascular malformations v0.73 Bryony Thompson removed gene:SMAD3 from the panel
Cerebral vascular malformations v0.72 Bryony Thompson removed gene:SMARCAL1 from the panel
Cerebral vascular malformations v0.71 Bryony Thompson removed gene:SRPX2 from the panel
Cerebral vascular malformations v0.70 Bryony Thompson removed gene:STAMBP from the panel
Cerebral vascular malformations v0.69 Bryony Thompson removed gene:TEK from the panel
Cerebral vascular malformations v0.68 Bryony Thompson removed gene:TGFB2 from the panel
Cerebral vascular malformations v0.67 Bryony Thompson removed gene:TGFBR1 from the panel
Cerebral vascular malformations v0.66 Bryony Thompson removed gene:TGFBR2 from the panel
Cerebral vascular malformations v0.65 Bryony Thompson removed gene:TMEM5 from the panel
Cerebral vascular malformations v0.64 Bryony Thompson removed gene:TRAIP from the panel
Cerebral vascular malformations v0.63 Bryony Thompson removed gene:TUBA1A from the panel
Cerebral vascular malformations v0.62 Bryony Thompson removed gene:TUBA8 from the panel
Cerebral vascular malformations v0.61 Bryony Thompson removed gene:TUBB from the panel
Cerebral vascular malformations v0.60 Bryony Thompson removed gene:TUBB2A from the panel
Cerebral vascular malformations v0.59 Bryony Thompson removed gene:TUBB2B from the panel
Cerebral vascular malformations v0.58 Bryony Thompson removed gene:TUBB3 from the panel
Cerebral vascular malformations v0.57 Bryony Thompson removed gene:TUBG1 from the panel
Cerebral vascular malformations v0.56 Bryony Thompson removed gene:VLDLR from the panel
Cerebral vascular malformations v0.55 Bryony Thompson removed gene:WDR62 from the panel
Cerebral vascular malformations v0.54 Bryony Thompson removed gene:DNA2 from the panel
Cerebral vascular malformations v0.53 Bryony Thompson removed gene:ATP7A from the panel
Cerebral vascular malformations v0.52 PKD1 Bryony Thompson Classified gene: PKD1 as Green List (high evidence)
Cerebral vascular malformations v0.52 PKD1 Bryony Thompson Gene: pkd1 has been classified as Green List (High Evidence).
Cerebral vascular malformations v0.51 EPHB4 Bryony Thompson Classified gene: EPHB4 as Green List (high evidence)
Cerebral vascular malformations v0.51 EPHB4 Bryony Thompson Gene: ephb4 has been classified as Green List (High Evidence).
Familial hypercholesterolaemia v0.27 PCSK9 Sangavi Sivagnanasundram changed review comment from: Classified as Definitive by ClinGen GCEP on 14/11/2018 - https://search.clinicalgenome.org/CCID:005746

Mechanism of disease is GoF.
Heterozygous LoF variants in this gene are associated with low levels of LDL cholesterol - PMID: 15654334; to: Classified as Definitive by ClinGen General Gene Curation GCEP on 14/11/2018 - https://search.clinicalgenome.org/CCID:005746

Mechanism of disease is GoF.
Heterozygous LoF variants in this gene are associated with low levels of LDL cholesterol - PMID: 15654334
Familial hypercholesterolaemia v0.27 PCSK9 Sangavi Sivagnanasundram reviewed gene: PCSK9: Rating: GREEN; Mode of pathogenicity: Other; Publications: 24404629, 16577715, 15654334; Phenotypes: hypercholesterolemia, autosomal dominant, 3 MONDO:0011369; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Familial hypercholesterolaemia v0.27 APOB Sangavi Sivagnanasundram reviewed gene: APOB: Rating: GREEN; Mode of pathogenicity: None; Publications: 24404629; Phenotypes: hypercholesterolemia, autosomal dominant, type B MONDO:0007751; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.2151 SLC35F1 Lucy Spencer changed review comment from: Probable 2nd internal VCGS case 24W004707 with intellectual disability and seizures and a de novo Gly226Arg variant.; to: Probable 2nd internal VCGS case with intellectual disability and seizures and a de novo Gly226Arg variant.
Prepair 1000+ v1.592 PIEZO1 Zornitza Stark Tag for review tag was added to gene: PIEZO1.
Intellectual disability syndromic and non-syndromic v1.3 WDR83OS Zornitza Stark Phenotypes for gene: WDR83OS were changed from complex neurodevelopmental disorder MONDO:0100038; neurodevelopmental disorder with hypercholanemia to Neurodevelopmental disorder with variable familial hypercholanemia, MIM# 621016
Intellectual disability syndromic and non-syndromic v1.2 WDR83OS Zornitza Stark reviewed gene: WDR83OS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with variable familial hypercholanemia, MIM# 621016; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2151 WDR83OS Zornitza Stark Phenotypes for gene: WDR83OS were changed from complex neurodevelopmental disorder MONDO:0100038; neurodevelopmental disorder with hypercholanemia to Neurodevelopmental disorder with variable familial hypercholanemia, MIM# 621016
Cholestasis v0.250 WDR83OS Zornitza Stark Phenotypes for gene: WDR83OS were changed from complex neurodevelopmental disorder MONDO:0100038; neurodevelopmental disorder with hypercholanemia to Neurodevelopmental disorder with variable familial hypercholanemia, MIM# 621016
Cerebral vascular malformations v0.50 CEP63 Zornitza Stark Marked gene: CEP63 as ready
Cerebral vascular malformations v0.50 CEP63 Zornitza Stark Gene: cep63 has been classified as Red List (Low Evidence).
Cerebral vascular malformations v0.50 COL4A2 Zornitza Stark Marked gene: COL4A2 as ready
Cerebral vascular malformations v0.50 COL4A2 Zornitza Stark Gene: col4a2 has been classified as Red List (Low Evidence).
Cerebral vascular malformations v0.50 COL4A2 Zornitza Stark Phenotypes for gene: COL4A2 were changed from {Hemorrhage, intracerebral, susceptibility to}, 614519; {Hemorrhage, intracerebral, susceptibility to} to Stroke, hemorrhagic MIM#614519
Cerebral vascular malformations v0.49 COL4A2 Zornitza Stark Publications for gene: COL4A2 were set to
Cerebral vascular malformations v0.48 COL4A2 Zornitza Stark Mode of inheritance for gene: COL4A2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral vascular malformations v0.47 CRB1 Zornitza Stark Marked gene: CRB1 as ready
Cerebral vascular malformations v0.47 CRB1 Zornitza Stark Gene: crb1 has been classified as Red List (Low Evidence).
Cerebral vascular malformations v0.47 CRB1 Zornitza Stark Phenotypes for gene: CRB1 were changed from Pigmented Paravenous Chorioretinal Atrophy to Pigmented paravenous chorioretinal atrophy MIM#172870
Cerebral vascular malformations v0.46 CTSA Zornitza Stark Marked gene: CTSA as ready
Cerebral vascular malformations v0.46 CTSA Zornitza Stark Gene: ctsa has been classified as Red List (Low Evidence).
Cerebral vascular malformations v0.46 CTSA Zornitza Stark Phenotypes for gene: CTSA were changed from to galactosialidosis MONDO:0009737
Cerebral vascular malformations v0.45 CTSA Zornitza Stark Mode of inheritance for gene: CTSA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cerebral vascular malformations v0.44 DCX Zornitza Stark Marked gene: DCX as ready
Cerebral vascular malformations v0.44 DCX Zornitza Stark Gene: dcx has been classified as Red List (Low Evidence).
Cerebral vascular malformations v0.44 DCX Zornitza Stark Phenotypes for gene: DCX were changed from Cerebral Malformation Disorders to lissencephaly spectrum disorders MONDO:0018838
Cerebral vascular malformations v0.43 ADGRG1 Zornitza Stark Marked gene: ADGRG1 as ready
Cerebral vascular malformations v0.43 ADGRG1 Zornitza Stark Gene: adgrg1 has been classified as Red List (Low Evidence).
Cerebral vascular malformations v0.43 ADGRG1 Zornitza Stark Phenotypes for gene: ADGRG1 were changed from Cerebral Malformation Disorders to bilateral frontoparietal polymicrogyria MONDO:0011738
Mendeliome v1.2150 GARS Zornitza Stark Phenotypes for gene: GARS were changed from Spinal muscular atrophy, infantile, James type, MIM# 619042; Charcot-Marie-Tooth disease, type 2D, MIM# 601472; Neuronopathy, distal hereditary motor, type VA, MIM# 600794; Multi-system mitochondrial disorder to Mitochondrial disease (MONDO:0044970), GARS1-related; Spinal muscular atrophy, infantile, James type, MIM# 619042; Charcot-Marie-Tooth disease, type 2D, MIM# 601472; Neuronopathy, distal hereditary motor, type VA, MIM# 600794; Multi-system mitochondrial disorder
Mendeliome v1.2149 GARS Zornitza Stark edited their review of gene: GARS: Changed phenotypes: Mitochondrial disease (MONDO:0044970), GARS1-related, Spinal muscular atrophy, infantile, James type, MIM# 619042, Charcot-Marie-Tooth disease, type 2D, MIM# 601472, Neuronopathy, distal hereditary motor, type VA, MIM# 600794, Multi-system mitochondrial disorder
Mitochondrial disease v0.954 GARS Zornitza Stark Phenotypes for gene: GARS were changed from Spinal muscular atrophy, infantile, James type, MIM# 619042; Charcot-Marie-Tooth disease, type 2D, MIM# 601472; Neuronopathy, distal hereditary motor, type VA, MIM# 600794; Multi-system mitochondrial disorder to Mitochondrial disease (MONDO:0044970), GARS1-related; Spinal muscular atrophy, infantile, James type, MIM# 619042; Charcot-Marie-Tooth disease, type 2D, MIM# 601472; Neuronopathy, distal hereditary motor, type VA, MIM# 600794; Multi-system mitochondrial disorder
Intellectual disability syndromic and non-syndromic v1.2 SLC35F1 Zornitza Stark Classified gene: SLC35F1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v1.2 SLC35F1 Zornitza Stark Gene: slc35f1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.1 SLC35F1 Zornitza Stark edited their review of gene: SLC35F1: Added comment: Likely second individual identified internally at VCGS, AS/Rett-like phenotype and de novo Gly226Arg variant.; Changed rating: AMBER
Angelman Rett like syndromes v1.11 SLC35F1 Zornitza Stark Classified gene: SLC35F1 as Amber List (moderate evidence)
Angelman Rett like syndromes v1.11 SLC35F1 Zornitza Stark Gene: slc35f1 has been classified as Amber List (Moderate Evidence).
Angelman Rett like syndromes v1.10 SLC35F1 Zornitza Stark edited their review of gene: SLC35F1: Added comment: Likely second individual identified internally at VCGS, AS/Rett-like phenotype and de novo Gly226Arg variant.; Changed rating: AMBER
Mendeliome v1.2149 SLC35F1 Zornitza Stark Classified gene: SLC35F1 as Amber List (moderate evidence)
Mendeliome v1.2149 SLC35F1 Zornitza Stark Gene: slc35f1 has been classified as Amber List (Moderate Evidence).
Cerebral vascular malformations v0.42 ANTXR1 Zornitza Stark Marked gene: ANTXR1 as ready
Cerebral vascular malformations v0.42 ANTXR1 Zornitza Stark Gene: antxr1 has been classified as Red List (Low Evidence).
Cerebral vascular malformations v0.42 ANTXR1 Zornitza Stark Phenotypes for gene: ANTXR1 were changed from {Hemangioma, capillary infantile, susceptibility to}, 602089; {Hemangioma, capillary infantile, susceptibility to} to GAPO syndrome MONDO:0009263
Cerebral vascular malformations v0.41 ANTXR1 Zornitza Stark Publications for gene: ANTXR1 were set to
Cerebral vascular malformations v0.40 ANTXR1 Zornitza Stark Mode of inheritance for gene: ANTXR1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal
Cerebral vascular malformations v0.39 ARX Zornitza Stark Marked gene: ARX as ready
Cerebral vascular malformations v0.39 ARX Zornitza Stark Gene: arx has been classified as Red List (Low Evidence).
Prepair 1000+ v1.592 CA2 Melanie Marty reviewed gene: CA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34624559, 33555497, 12566520, 7627193; Phenotypes: Osteopetrosis, autosomal recessive 3, with renal tubular acidosis, MIM#259730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.592 BCKDHA Melanie Marty reviewed gene: BCKDHA: Rating: GREEN; Mode of pathogenicity: None; Publications: 7883996, 7672509, 34288399; Phenotypes: Maple syrup urine disease, type Ia, MIM# 248600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.592 BBS5 Melanie Marty reviewed gene: BBS5: Rating: GREEN; Mode of pathogenicity: None; Publications: 19252258, 15137946, 10053027, 15637713; Phenotypes: Bardet-Biedl syndrome 5, MIM#615983, MONDO:0014434; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.592 ATP6AP1 Melanie Marty reviewed gene: ATP6AP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27231034, 32048120; Phenotypes: Immunodeficiency 47, MIM#300972; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.592 ALDOB Melanie Marty reviewed gene: ALDOB: Rating: GREEN; Mode of pathogenicity: None; Publications: 3083321; Phenotypes: Fructose intolerance, hereditary, MIM# 229600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral vascular malformations v0.39 ARX Sangavi Sivagnanasundram reviewed gene: ARX: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Cerebral vascular malformations v0.39 ANTXR1 Sangavi Sivagnanasundram reviewed gene: ANTXR1: Rating: RED; Mode of pathogenicity: None; Publications: 24664815; Phenotypes: GAPO syndrome MONDO:0009263; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2148 SLC35F1 Lucy Spencer reviewed gene: SLC35F1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, SLC35F1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Motor Neurone Disease v1.24 SQSTM1 Bryony Thompson Deleted their review
Cerebral vascular malformations v0.39 ADGRG1 Sangavi Sivagnanasundram reviewed gene: ADGRG1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: bilateral frontoparietal polymicrogyria MONDO:0011738; Mode of inheritance: None
Cerebral vascular malformations v0.39 DCX Sangavi Sivagnanasundram reviewed gene: DCX: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: lissencephaly spectrum disorders MONDO:0018838; Mode of inheritance: None
Cerebral vascular malformations v0.39 CTSA Sangavi Sivagnanasundram reviewed gene: CTSA: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: galactosialidosis MONDO:0009737; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.953 GARS Chris Ciotta reviewed gene: GARS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial disease (MONDO:0044970), GARS1-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cerebral vascular malformations v0.39 CRB1 Sangavi Sivagnanasundram reviewed gene: CRB1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Cerebral vascular malformations v0.39 COL4A2 Sangavi Sivagnanasundram reviewed gene: COL4A2: Rating: RED; Mode of pathogenicity: None; Publications: 22209247; Phenotypes: Stroke, hemorrhagic MIM#614519; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral vascular malformations v0.39 CEP63 Sangavi Sivagnanasundram reviewed gene: CEP63: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v1.1 LINC01578 Zornitza Stark Phenotypes for gene: LINC01578 were changed from Neurodevelopmental disorder, MONDO:0700092, CHASERR-related to Neurodevelopmental disorder with dysmorphic facies, absent speech and ambulation, and brain abnormalities, MIM# 621012
Intellectual disability syndromic and non-syndromic v1.0 LINC01578 Zornitza Stark edited their review of gene: LINC01578: Changed phenotypes: Neurodevelopmental disorder with dysmorphic facies, absent speech and ambulation, and brain abnormalities, MIM# 621012
Mendeliome v1.2148 LINC01578 Zornitza Stark Phenotypes for gene: LINC01578 were changed from Neurodevelopmental disorder, MONDO:0700092, CHASERR-related to Neurodevelopmental disorder with dysmorphic facies, absent speech and ambulation, and brain abnormalities, MIM# 621012
Mendeliome v1.2147 LINC01578 Zornitza Stark edited their review of gene: LINC01578: Changed phenotypes: Neurodevelopmental disorder with dysmorphic facies, absent speech and ambulation, and brain abnormalities, MIM# 621012
Cerebral vascular malformations v0.39 CENPJ Sangavi Sivagnanasundram reviewed gene: CENPJ: Rating: RED; Mode of pathogenicity: None; Publications: 20522431; Phenotypes: Seckel syndrome MONDO:0019342; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral vascular malformations v0.39 ACE Sangavi Sivagnanasundram reviewed gene: ACE: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Cerebral vascular malformations v0.39 THSD1 Sangavi Sivagnanasundram reviewed gene: THSD1: Rating: AMBER; Mode of pathogenicity: None; Publications: 27895300; Phenotypes: intracranial berry aneurysm MONDO:0016483; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Autoimmune Lymphoproliferative Syndrome v0.16 MAGT1 Ain Roesley Marked gene: MAGT1 as ready
Autoimmune Lymphoproliferative Syndrome v0.16 MAGT1 Ain Roesley Gene: magt1 has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.16 MAGT1 Ain Roesley Classified gene: MAGT1 as Green List (high evidence)
Autoimmune Lymphoproliferative Syndrome v0.16 MAGT1 Ain Roesley Gene: magt1 has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.15 MAGT1 Ain Roesley gene: MAGT1 was added
gene: MAGT1 was added to Autoimmune Lymphoproliferative Syndrome. Sources: Literature
Mode of inheritance for gene: MAGT1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: MAGT1 were set to 39060684; 25956530; 34447369
Phenotypes for gene: MAGT1 were set to Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia MIM#300853
Review for gene: MAGT1 was set to GREEN
gene: MAGT1 was marked as current diagnostic
Added comment: >5 unrelated males with ALPS-like
Sources: Literature
Autoimmune Lymphoproliferative Syndrome v0.14 KRAS Ain Roesley Marked gene: KRAS as ready
Autoimmune Lymphoproliferative Syndrome v0.14 KRAS Ain Roesley Gene: kras has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.14 KRAS Ain Roesley Classified gene: KRAS as Green List (high evidence)
Autoimmune Lymphoproliferative Syndrome v0.14 KRAS Ain Roesley Gene: kras has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.13 KRAS Ain Roesley gene: KRAS was added
gene: KRAS was added to Autoimmune Lymphoproliferative Syndrome. Sources: Literature
Mode of inheritance for gene: KRAS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KRAS were set to 27577878; 39060684; 21079152
Phenotypes for gene: KRAS were set to RAS-associated autoimmune leukoproliferative disorder MIM#614470
Review for gene: KRAS was set to GREEN
gene: KRAS was marked as current diagnostic
Added comment: Recurrent variant Gly13Cys

PMID:39060684
2x individuals with atypical ALPS - Gly13Cys

PMID:27577878
1x de novo mosaic in blood individual with ALPS - Gly13Cys

PMID:21079152
1x individual with ALPS-like syndrome somatic for Gly13Cys
1x individual with ALPS-like syndrome somatic for Gly12Asp
Sources: Literature
Autoimmune Lymphoproliferative Syndrome v0.12 ITK Ain Roesley Marked gene: ITK as ready
Autoimmune Lymphoproliferative Syndrome v0.12 ITK Ain Roesley Gene: itk has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.12 ITK Ain Roesley Classified gene: ITK as Green List (high evidence)
Autoimmune Lymphoproliferative Syndrome v0.12 ITK Ain Roesley Gene: itk has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.11 ITK Ain Roesley gene: ITK was added
gene: ITK was added to Autoimmune Lymphoproliferative Syndrome. Sources: Literature
Mode of inheritance for gene: ITK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ITK were set to 19425169; 22289921; 25061172; 26056787; 9311799; 10213685
Phenotypes for gene: ITK were set to Lymphoproliferative syndrome 1 MIM#613011
Review for gene: ITK was set to GREEN
gene: ITK was marked as current diagnostic
Added comment: 7 individuals from 5 unrelated families reported homozygous (missense/ nonsense) ITK variants consistent with Lymphoproliferative syndrome phenotype.

Two ITK-deficient mouse models demonstrated reduced T cells (CD4+), causing decreased CD4 to CD8 ratio.

Patients displayed early onset of features typically including fever, lymphadenopathy, autoimmune disorders, low immunoglobulins and high EBV viral load.
Sources: Literature
Autoimmune Lymphoproliferative Syndrome v0.10 FASLG Ain Roesley Classified gene: FASLG as Green List (high evidence)
Autoimmune Lymphoproliferative Syndrome v0.10 FASLG Ain Roesley Gene: faslg has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.9 FASLG Ain Roesley gene: FASLG was added
gene: FASLG was added to Autoimmune Lymphoproliferative Syndrome. Sources: Literature
Mode of inheritance for gene: FASLG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FASLG were set to 16627752; 17605793; 19794494; 8787672; 22857792; 33356695; 26334989; 25451160
Phenotypes for gene: FASLG were set to Autoimmune lymphoproliferative syndrome, type IB MIM#601859
Review for gene: FASLG was set to GREEN
gene: FASLG was marked as current diagnostic
Added comment: Sufficient evidence for AR gene-disease association. Limited evidence for AD gene-disease association
PMID: 22857792, 16627752, 26334989, 25451160 - 4 unrelated ALPS families reported with biallelic variants with a loss of function mechanism
PMID: 11457890, 19794494 - supporting deficient mouse models
PMID: 8787672, 17605793 - a single case (p.Met158_Glu185del) and a single family (p.Arg156Gly) reported with heterozygous variants, supporting dominant inheritance of dominant-negative variants. Another case reported with a rare VUS (p.Met86Val) that didn't alter protein function.
Sources: Literature
Autoimmune Lymphoproliferative Syndrome v0.8 FADD Ain Roesley Marked gene: FADD as ready
Autoimmune Lymphoproliferative Syndrome v0.8 FADD Ain Roesley Gene: fadd has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.8 FADD Ain Roesley Classified gene: FADD as Green List (high evidence)
Autoimmune Lymphoproliferative Syndrome v0.8 FADD Ain Roesley Gene: fadd has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.7 FADD Ain Roesley gene: FADD was added
gene: FADD was added to Autoimmune Lymphoproliferative Syndrome. Sources: Literature
Mode of inheritance for gene: FADD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FADD were set to 21109225; 25794656; 32350755; 32971525
Phenotypes for gene: FADD were set to FADD-related immunodeficiency MONDO:0013408
Review for gene: FADD was set to GREEN
gene: FADD was marked as current diagnostic
Added comment: 3 families reported so far. 2 apparently unrelated consanguineous Pakistani families with autoimmune lymphoproliferative syndrome both segregating homozygous p.Cys105Trp. A single compound het case with p.Cys105Arg and a frameshift variant. Also, FADD deficient mouse models support a role in immunodeficiency. Null mice are embryonic lethal.
Sources: Literature
Autoimmune Lymphoproliferative Syndrome v0.6 CASP10 Ain Roesley Marked gene: CASP10 as ready
Autoimmune Lymphoproliferative Syndrome v0.6 CASP10 Ain Roesley Gene: casp10 has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.6 CASP10 Ain Roesley Classified gene: CASP10 as Green List (high evidence)
Autoimmune Lymphoproliferative Syndrome v0.6 CASP10 Ain Roesley Gene: casp10 has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.5 CASP10 Ain Roesley gene: CASP10 was added
gene: CASP10 was added to Autoimmune Lymphoproliferative Syndrome. Sources: Literature
Mode of inheritance for gene: CASP10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CASP10 were set to 34329798; 34384744; 20301287
Phenotypes for gene: CASP10 were set to Autoimmune lymphoproliferative syndrome, type II MIM#603909
Review for gene: CASP10 was set to GREEN
gene: CASP10 was marked as current diagnostic
Added comment: Total of 15 individuals included in the review.

Asymptomatic carriers noted.
Sources: Literature
Autoimmune Lymphoproliferative Syndrome v0.4 CASP8 Ain Roesley Marked gene: CASP8 as ready
Autoimmune Lymphoproliferative Syndrome v0.4 CASP8 Ain Roesley Gene: casp8 has been classified as Amber List (Moderate Evidence).
Autoimmune Lymphoproliferative Syndrome v0.4 CASP8 Ain Roesley Classified gene: CASP8 as Amber List (moderate evidence)
Autoimmune Lymphoproliferative Syndrome v0.4 CASP8 Ain Roesley Gene: casp8 has been classified as Amber List (Moderate Evidence).
Autoimmune Lymphoproliferative Syndrome v0.3 CASP8 Ain Roesley gene: CASP8 was added
gene: CASP8 was added to Autoimmune Lymphoproliferative Syndrome. Sources: Literature
Mode of inheritance for gene: CASP8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CASP8 were set to 12353035; 25814141; 12654726; 17213198; 16148088
Phenotypes for gene: CASP8 were set to Autoimmune lymphoproliferative syndrome, type IIB MIM#607271
Review for gene: CASP8 was set to AMBER
gene: CASP8 was marked as current diagnostic
Added comment: Amber due to functional studies

1 family (the 2nd family reported in PMID:25814141 was found to be distantly related to the one in PMID:12353035)

Mice with targeted T cell and B cell caspase-8 deficiency present normal thymocyte development but a marked decrease in peripheral blood T-cells. Besides, when challenged with the lymphocytic choriomeningitis virus (LCMV), these animals showed a significantly impaired immune response to the infection that included impaired CD8 cell expansion and an abrogated ability to generate virus-specific CD8+ cytotoxic T-cells.
Sources: Literature
Autoimmune Lymphoproliferative Syndrome v0.2 FAS Ain Roesley Marked gene: FAS as ready
Autoimmune Lymphoproliferative Syndrome v0.2 FAS Ain Roesley Gene: fas has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.2 FAS Ain Roesley Classified gene: FAS as Green List (high evidence)
Autoimmune Lymphoproliferative Syndrome v0.2 FAS Ain Roesley Gene: fas has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.1 FAS Ain Roesley gene: FAS was added
gene: FAS was added to Autoimmune Lymphoproliferative Syndrome. Sources: Literature
Mode of inheritance for gene: FAS was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for gene: FAS were set to Autoimmune lymphoproliferative syndrome, type IA MIM#601859
Review for gene: FAS was set to GREEN
gene: FAS was marked as current diagnostic
Added comment: Well established association
Sources: Literature
Autoimmune Lymphoproliferative Syndrome v0.0 Ain Roesley Added Panel Autoimmune Lymphoproliferative Syndrome
Defects of intrinsic and innate immunity v0.159 IFIH1 Bryony Thompson Marked gene: IFIH1 as ready
Defects of intrinsic and innate immunity v0.159 IFIH1 Bryony Thompson Gene: ifih1 has been classified as Green List (High Evidence).
Defects of intrinsic and innate immunity v0.159 IFIH1 Bryony Thompson Classified gene: IFIH1 as Green List (high evidence)
Defects of intrinsic and innate immunity v0.159 IFIH1 Bryony Thompson Gene: ifih1 has been classified as Green List (High Evidence).
Defects of intrinsic and innate immunity v0.158 IFIH1 Bryony Thompson gene: IFIH1 was added
gene: IFIH1 was added to Defects of innate immunity. Sources: Expert list
Mode of inheritance for gene: IFIH1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IFIH1 were set to 28606988; 29018476; 28716935; 34185153
Phenotypes for gene: IFIH1 were set to Immunodeficiency 95 MIM#619773
Review for gene: IFIH1 was set to GREEN
Added comment: Biallelic loss of function variants cause a predisposition to severe viral infections. IUIS IEI committee classify the condition as a defect in intrinsic and innate immunity.
Sources: Expert list
Prepair 1000+ v1.592 GCH1 Lilian Downie Marked gene: GCH1 as ready
Prepair 1000+ v1.592 GCH1 Lilian Downie Added comment: Comment when marking as ready: Biallelic variants in GCH1 typically result in severe deficiency of GTPCH activity, and result in hyperphenylalaninemia due to secondary PAH deficiency. This can be identified by newborn screening. However, patients with phenotypes that are intermediate between the classic DRD and severe GTPCH deficiency symptoms have been described, such those with severe DRD and additional neurological features but without hyperphenylalaninemia (for review, see Table in Brüggemann et al 2012, PMID 22473768). Because the mechanism of disease in both the monoallelic and biallelic cases is loss of function of GTPCH, and there is a range of GTPCH activity that can cause disease, the decision was made to curate GCH1 for GTPCH deficiency with semi-dominant inheritance. Note that heterozygous parents of biallelic individuals are usually reported as unaffected, although there are some exceptions (Furukawa et al, 1998, PMID 9667588; Bodzioch et al, 2010, PMID 20842687). Reduced penetrance has been reported for individuals with monoallelic GCH1 variants, with penetrance varying according to age and diagnostic criteria. In addition, some variants (e.g. p.Arg184His and p.Lys224Arg) have been reported in monallelic and biallelic individuals. This data was presented to the ClinGen Lumping and Splitting Working Group on November 3, 2020 and there was agreement that GTPCH deficiency should be curated as a semi-dominant trait, including individuals with monoallelic and biallelic GCH1 variants.
Prepair 1000+ v1.592 GCH1 Lilian Downie Gene: gch1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.592 GCH1 Lilian Downie Phenotypes for gene: GCH1 were changed from Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, 128230 (3) to GTP cyclohydrolase I deficiency MONDO:0100184
Prepair 1000+ v1.591 GCH1 Lilian Downie Publications for gene: GCH1 were set to
Prepair 1000+ v1.590 ALS2 Lilian Downie Marked gene: ALS2 as ready
Prepair 1000+ v1.590 ALS2 Lilian Downie Gene: als2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.590 ALS2 Lilian Downie Phenotypes for gene: ALS2 were changed from Primary lateral sclerosis, juvenile, 606353 (3) to ALS2-related motor neuron disease (MONDO:0100227)
Prepair 1000+ v1.589 ALS2 Lilian Downie Publications for gene: ALS2 were set to
Prepair 1000+ v1.588 F7 Lilian Downie Marked gene: F7 as ready
Prepair 1000+ v1.588 F7 Lilian Downie Gene: f7 has been classified as Green List (High Evidence).
Prepair 1000+ v1.588 FARS2 Lilian Downie Marked gene: FARS2 as ready
Prepair 1000+ v1.588 FARS2 Lilian Downie Gene: fars2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.588 FARS2 Lilian Downie Phenotypes for gene: FARS2 were changed from Combined oxidative phosphorylation deficiency 14, 614946 (3) to Combined oxidative phosphorylation deficiency 14 (MIM#614946); Spastic paraplegia 77 (MIM#617046)
Prepair 1000+ v1.587 FARS2 Lilian Downie Publications for gene: FARS2 were set to
Prepair 1000+ v1.586 FKRP Lilian Downie Marked gene: FKRP as ready
Prepair 1000+ v1.586 FKRP Lilian Downie Gene: fkrp has been classified as Green List (High Evidence).
Prepair 1000+ v1.586 FKRP Lilian Downie Phenotypes for gene: FKRP were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 5, 613153 (3) to Myopathy caused by variation in FKRP MONDO:0700066
Prepair 1000+ v1.585 FKRP Lilian Downie Publications for gene: FKRP were set to 38277301
Prepair 1000+ v1.584 FKRP Lilian Downie Publications for gene: FKRP were set to
Prepair 1000+ v1.583 FLVCR1 Lilian Downie Marked gene: FLVCR1 as ready
Prepair 1000+ v1.583 FLVCR1 Lilian Downie Gene: flvcr1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.583 FLVCR1 Lilian Downie Phenotypes for gene: FLVCR1 were changed from Ataxia, posterior column, with retinitis pigmentosa, 609033 (3) to Ataxia, posterior column, with retinitis pigmentosa, 609033, Neurodevelopmental disorder MONDO:0700092, FLVCR1-related
Prepair 1000+ v1.582 FLVCR1 Lilian Downie Publications for gene: FLVCR1 were set to
Prepair 1000+ v1.581 C8B Lauren Thomas reviewed gene: C8B: Rating: AMBER; Mode of pathogenicity: None; Publications: 7980680, 27183977, 15565265; Phenotypes: C8 deficiency, type II MIM#613789; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.581 GCH1 Cassandra Muller reviewed gene: GCH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 10737119, 9667588; Phenotypes: Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, 128230 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.581 BMPER Lauren Thomas reviewed gene: BMPER: Rating: GREEN; Mode of pathogenicity: None; Publications: 20869035, 30006055, 15988748, 17764081; Phenotypes: Diaphanospondylodysostosis, MIM# 608022; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.581 FREM2 Cassandra Muller reviewed gene: FREM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 15838507, 8203166, 36720431, 33082983; Phenotypes: Fraser syndrome, 219000 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.581 BIN1 Lauren Thomas reviewed gene: BIN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 17676042, 20142620; Phenotypes: Centronuclear myopathy 2, MIM# 255200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.581 CD27 Zornitza Stark Marked gene: CD27 as ready
Prepair 1000+ v1.581 CD27 Zornitza Stark Gene: cd27 has been classified as Green List (High Evidence).
Prepair 1000+ v1.581 CD27 Zornitza Stark Phenotypes for gene: CD27 were changed from Lymphoproliferative syndrome 2, 615122 (3) to Lymphoproliferative syndrome 2, MIM# 615122
Prepair 1000+ v1.580 CD27 Zornitza Stark Publications for gene: CD27 were set to
Prepair 1000+ v1.579 CD27 Zornitza Stark reviewed gene: CD27: Rating: GREEN; Mode of pathogenicity: None; Publications: 22197273, 22801960, 22365582, 25843314, 11062504; Phenotypes: Lymphoproliferative syndrome 2, MIM# 615122; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.579 MGP Andrew Coventry reviewed gene: MGP: Rating: GREEN; Mode of pathogenicity: None; Publications: 37675773; Phenotypes: Keutel syndrome MIM#245150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.579 CAVIN1 Zornitza Stark Marked gene: CAVIN1 as ready
Prepair 1000+ v1.579 CAVIN1 Zornitza Stark Gene: cavin1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.579 CAVIN1 Zornitza Stark Phenotypes for gene: CAVIN1 were changed from Lipodystrophy, congenital generalized, type 4, 613327 (3) to Lipodystrophy, congenital generalized, type 4, MIM# 613327; MONDO:0013225
Prepair 1000+ v1.578 CAVIN1 Zornitza Stark Publications for gene: CAVIN1 were set to
Prepair 1000+ v1.577 CAVIN1 Zornitza Stark reviewed gene: CAVIN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19726876, 20300641, 20684003, 18840361; Phenotypes: Lipodystrophy, congenital generalized, type 4, MIM# 613327, MONDO:0013225; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.577 ABCB4 Zornitza Stark Marked gene: ABCB4 as ready
Prepair 1000+ v1.577 ABCB4 Zornitza Stark Gene: abcb4 has been classified as Green List (High Evidence).
Prepair 1000+ v1.577 ABCB4 Zornitza Stark Phenotypes for gene: ABCB4 were changed from Cholestasis, progressive familial intrahepatic 3, 602347 (3) to Cholestasis, progressive familial intrahepatic 3 MIM#602347
Prepair 1000+ v1.576 ABCB4 Zornitza Stark Publications for gene: ABCB4 were set to
Prepair 1000+ v1.575 ABCB4 Zornitza Stark reviewed gene: ABCB4: Rating: GREEN; Mode of pathogenicity: None; Publications: 17726488; Phenotypes: Cholestasis, progressive familial intrahepatic 3 MIM#602347; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.575 MBTPS1 Andrew Coventry reviewed gene: MBTPS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32420688, 30046013, 32857899, 36330313, 36816387, 36714646; Phenotypes: Spondyloepiphyseal dysplasia, Kondo-Fu type MIM#618392; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.575 CANT1 Zornitza Stark Marked gene: CANT1 as ready
Prepair 1000+ v1.575 CANT1 Zornitza Stark Gene: cant1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.575 CANT1 Zornitza Stark Phenotypes for gene: CANT1 were changed from Desbuquois dysplasia, 251450 (3) to Desbuquois dysplasia 1, MIM# 251450; Epiphyseal dysplasia, multiple, 7, MIM# 617719
Prepair 1000+ v1.574 CANT1 Zornitza Stark Publications for gene: CANT1 were set to
Prepair 1000+ v1.573 CANT1 Zornitza Stark reviewed gene: CANT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19853239, 21037275, 28742282; Phenotypes: Desbuquois dysplasia 1, MIM# 251450, Epiphyseal dysplasia, multiple, 7, MIM# 617719; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.573 C2CD3 Zornitza Stark Marked gene: C2CD3 as ready
Prepair 1000+ v1.573 C2CD3 Zornitza Stark Gene: c2cd3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.573 C2CD3 Zornitza Stark Phenotypes for gene: C2CD3 were changed from Orofaciodigital syndrome XIV to Orofaciodigital syndrome XIV, MIM# 615948; MONDO:0014413
Prepair 1000+ v1.572 LBR Marta Cifuentes Ochoa reviewed gene: LBR: Rating: GREEN; Mode of pathogenicity: None; Publications: 12618959, 27604308, 29068549, 32304187; Phenotypes: Greenberg skeletal dysplasia MIM#215140, MONDO:0008974 & Rhizomelic skeletal dysplasia with or without Pelger-Huet anomaly MIM#618019; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.572 C2CD3 Zornitza Stark Publications for gene: C2CD3 were set to
Prepair 1000+ v1.571 C2CD3 Zornitza Stark reviewed gene: C2CD3: Rating: GREEN; Mode of pathogenicity: None; Publications: 24997988, 26477546, 27094867, 30097616, 33875766; Phenotypes: Orofaciodigital syndrome XIV, MIM# 615948, MONDO:0014413; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.571 FKBP10 Cassandra Muller Deleted their comment
Prepair 1000+ v1.571 FKBP10 Cassandra Muller edited their review of gene: FKBP10: Added comment: Severe, early onset. Early-onset bone fractures and progressive skeletal deformities. Well established gene-disease association.; Changed phenotypes: Bruck syndrome 1, 259450 (3), osteogenesis imperfecta, type XI, 610968 (3)
Prepair 1000+ v1.571 C12orf65 Zornitza Stark Marked gene: C12orf65 as ready
Prepair 1000+ v1.571 C12orf65 Zornitza Stark Gene: c12orf65 has been classified as Green List (High Evidence).
Prepair 1000+ v1.571 C12orf65 Zornitza Stark Phenotypes for gene: C12orf65 were changed from Combined oxidative phosphorylation deficiency 7, 613559 (3) to Combined oxidative phosphorylation deficiency 7, MIM# 613559; Spastic paraplegia 55, autosomal recessive, MIM#615035
Prepair 1000+ v1.570 C12orf65 Zornitza Stark Publications for gene: C12orf65 were set to
Prepair 1000+ v1.569 C12orf65 Zornitza Stark Tag new gene name tag was added to gene: C12orf65.
Prepair 1000+ v1.569 C12orf65 Zornitza Stark reviewed gene: C12orf65: Rating: GREEN; Mode of pathogenicity: None; Publications: 23188110, 24080142, 24198383, 20598281, 32808965, 32478789, 28804760; Phenotypes: Combined oxidative phosphorylation deficiency 7, MIM# 613559, Spastic paraplegia 55, autosomal recessive, MIM#615035; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.569 FKBP10 Cassandra Muller reviewed gene: FKBP10: Rating: GREEN; Mode of pathogenicity: None; Publications: 20362275, 22718341, 22689593, 22718341; Phenotypes: Bruck syndrome 1, 259450 (3), steogenesis imperfecta, type XI, 610968 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.569 BMPR1B Zornitza Stark Marked gene: BMPR1B as ready
Prepair 1000+ v1.569 BMPR1B Zornitza Stark Gene: bmpr1b has been classified as Green List (High Evidence).
Prepair 1000+ v1.569 BMPR1B Zornitza Stark Phenotypes for gene: BMPR1B were changed from Acromesomelic dysplasia, Demirhan type, 609441 (3), Autosomal recessive to Acromesomelic dysplasia 3, MIM# 609441
Prepair 1000+ v1.568 BMPR1B Zornitza Stark Publications for gene: BMPR1B were set to
Prepair 1000+ v1.567 BMPR1B Zornitza Stark reviewed gene: BMPR1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 15805157, 24129431, 26105076; Phenotypes: Acromesomelic dysplasia 3, MIM# 609441; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.567 MALT1 Andrew Coventry reviewed gene: MALT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 3727036, 24332264, 14576442, 31037583; Phenotypes: Immunodeficiency 12 MIM#615468; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.567 BLM Zornitza Stark Marked gene: BLM as ready
Prepair 1000+ v1.567 BLM Zornitza Stark Gene: blm has been classified as Green List (High Evidence).
Prepair 1000+ v1.567 BLM Zornitza Stark Phenotypes for gene: BLM were changed from Bloom syndrome, 210900 (3) to Bloom Syndrome MIM# 210900
Prepair 1000+ v1.566 BLM Zornitza Stark Publications for gene: BLM were set to
Prepair 1000+ v1.565 BLM Zornitza Stark reviewed gene: BLM: Rating: GREEN; Mode of pathogenicity: None; Publications: 17407155, 9285778, 7585968, 8079989, 12242442, 11101838; Phenotypes: Bloom Syndrome MIM# 210900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.565 APTX Zornitza Stark Marked gene: APTX as ready
Prepair 1000+ v1.565 APTX Zornitza Stark Gene: aptx has been classified as Green List (High Evidence).
Prepair 1000+ v1.565 APTX Zornitza Stark Phenotypes for gene: APTX were changed from Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia, 208920 (3) to Ataxia, early-onset, with oculomotor apraxia and hypoalbuminaemia MIM#208920
Prepair 1000+ v1.564 APTX Zornitza Stark Publications for gene: APTX were set to
Prepair 1000+ v1.563 APTX Zornitza Stark reviewed gene: APTX: Rating: GREEN; Mode of pathogenicity: None; Publications: 30986824, 26256098, 11586299; Phenotypes: Ataxia, early-onset, with oculomotor apraxia and hypoalbuminaemia MIM#208920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.563 ALG6 Zornitza Stark Marked gene: ALG6 as ready
Prepair 1000+ v1.563 ALG6 Zornitza Stark Gene: alg6 has been classified as Green List (High Evidence).
Prepair 1000+ v1.563 ALG6 Zornitza Stark Phenotypes for gene: ALG6 were changed from Congenital disorder of glycosylation, type Ic, 603147 (3) to Congenital disorder of glycosylation, type Ic (MIM#603147)
Prepair 1000+ v1.562 ALG6 Zornitza Stark Publications for gene: ALG6 were set to
Prepair 1000+ v1.561 ALG6 Zornitza Stark reviewed gene: ALG6: Rating: GREEN; Mode of pathogenicity: None; Publications: 27498540; Phenotypes: Congenital disorder of glycosylation, type Ic (MIM#603147); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.561 LARP7 Andrew Coventry reviewed gene: LARP7: Rating: GREEN; Mode of pathogenicity: None; Publications: 22865833, 21937992, 30006060, 33569879, 36126956, 37529055; Phenotypes: Alazami syndrome MIM#615071; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.561 AGPS Zornitza Stark Marked gene: AGPS as ready
Prepair 1000+ v1.561 AGPS Zornitza Stark Gene: agps has been classified as Green List (High Evidence).
Prepair 1000+ v1.561 AGPS Zornitza Stark Phenotypes for gene: AGPS were changed from Chondrodysplasia punctata, rhizomelic, type 3, 600121 (3) to Rhizomelic chondrodysplasia punctata, type 3, MIM# 600121
Prepair 1000+ v1.560 AGPS Zornitza Stark Publications for gene: AGPS were set to
Prepair 1000+ v1.559 AGPS Zornitza Stark reviewed gene: AGPS: Rating: GREEN; Mode of pathogenicity: None; Publications: 9553082, 8611652, 21990100; Phenotypes: Rhizomelic chondrodysplasia punctata, type 3, MIM# 600121; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.559 FA2H Cassandra Muller reviewed gene: FA2H: Rating: GREEN; Mode of pathogenicity: None; Publications: 31135052, 31837835, 22146942, 19068277; Phenotypes: Spastic paraplegia 35, autosomal recessive, 612319 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.559 ACAT1 Zornitza Stark Marked gene: ACAT1 as ready
Prepair 1000+ v1.559 ACAT1 Zornitza Stark Gene: acat1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.559 ACAT1 Zornitza Stark Phenotypes for gene: ACAT1 were changed from Alpha-methylacetoacetic aciduria, 203750 (3) to Alpha-methylacetoacetic aciduria, MIM#203750
Prepair 1000+ v1.558 ACAT1 Zornitza Stark Publications for gene: ACAT1 were set to
Prepair 1000+ v1.557 ACAT1 Zornitza Stark reviewed gene: ACAT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 17236799, 1715688; Phenotypes: Alpha-methylacetoacetic aciduria, MIM#203750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.557 B4GALNT1 Lauren Thomas reviewed gene: B4GALNT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23746551, 24103911; Phenotypes: Spastic paraplegia 26, MIM# 609195; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.557 ATF6 Lauren Thomas reviewed gene: ATF6: Rating: GREEN; Mode of pathogenicity: None; Publications: 26063662, 26029869; Phenotypes: Achromatopsia 7, MIM# 616517; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2147 ATP5A1 Lucy Spencer reviewed gene: ATP5A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34483339, 34954817, 23599390, 23596069; Phenotypes: Mitochondrial complex V (ATP synthase) deficiency, nuclear type 4A (MIM#620358), AD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Prepair 1000+ v1.557 FOXP3 Lilian Downie Marked gene: FOXP3 as ready
Prepair 1000+ v1.557 FOXP3 Lilian Downie Gene: foxp3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.557 FOXP3 Lilian Downie Publications for gene: FOXP3 were set to
Prepair 1000+ v1.556 ACE Lilian Downie Marked gene: ACE as ready
Prepair 1000+ v1.556 ACE Lilian Downie Gene: ace has been classified as Green List (High Evidence).
Prepair 1000+ v1.556 ACE Lilian Downie Publications for gene: ACE were set to
Prepair 1000+ v1.555 EYS Lilian Downie Publications for gene: EYS were set to 31074760; 20537394; 31074760
Prepair 1000+ v1.554 EYS Lilian Downie Publications for gene: EYS were set to 31074760
Prepair 1000+ v1.553 GUCY1A3 Ee Ming Wong reviewed gene: GUCY1A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 36941667; Phenotypes: Moyamoya 6 with achalasia, MIM#615750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Ichthyosis and Porokeratosis v1.11 GTF2H5 Ee Ming Wong reviewed gene: GTF2H5: Rating: GREEN; Mode of pathogenicity: None; Publications: 24986372, 30359777, 37356817; Phenotypes: Trichothiodystrophy 3, photosensitive, MIM# 616395; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.553 GTF2H5 Ee Ming Wong reviewed gene: GTF2H5: Rating: GREEN; Mode of pathogenicity: None; Publications: 30359777, 24986372, 37356817; Phenotypes: Trichothiodystrophy 3, photosensitive, MIM# 616395; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.553 GRM1 Ee Ming Wong reviewed gene: GRM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22901947, 26308914, 31319223; Phenotypes: Spinocerebellar ataxia, autosomal recessive 13, 614831; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.553 GPAA1 Ee Ming Wong reviewed gene: GPAA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29100095; Phenotypes: Glycosylphosphatidylinositol biosynthesis defect 15, MIM#617810; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.553 GNS Ee Ming Wong reviewed gene: GNS: Rating: GREEN; Mode of pathogenicity: None; Publications: 31536183; Phenotypes: Mucopolysaccharidosis type IIID, MIM# 252940, Sanfilippo syndrome type D, MONDO:0009658; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Defects of intrinsic and innate immunity v0.157 GTF3A Bryony Thompson Marked gene: GTF3A as ready
Defects of intrinsic and innate immunity v0.157 GTF3A Bryony Thompson Gene: gtf3a has been classified as Red List (Low Evidence).
Defects of intrinsic and innate immunity v0.157 GTF3A Bryony Thompson gene: GTF3A was added
gene: GTF3A was added to Defects of innate immunity. Sources: Expert list
Mode of inheritance for gene: GTF3A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTF3A were set to 36399538
Phenotypes for gene: GTF3A were set to herpes simplex encephalitis MONDO:0012521
Review for gene: GTF3A was set to RED
Added comment: A single case is reported with common variable immunodeficiency and HSE, and some supporting functional assays.
Sources: Expert list
Defects of intrinsic and innate immunity v0.156 DBR1 Bryony Thompson Marked gene: DBR1 as ready
Defects of intrinsic and innate immunity v0.156 DBR1 Bryony Thompson Gene: dbr1 has been classified as Green List (High Evidence).
Defects of intrinsic and innate immunity v0.156 DBR1 Bryony Thompson Classified gene: DBR1 as Green List (high evidence)
Defects of intrinsic and innate immunity v0.156 DBR1 Bryony Thompson Gene: dbr1 has been classified as Green List (High Evidence).
Defects of intrinsic and innate immunity v0.155 DBR1 Bryony Thompson gene: DBR1 was added
gene: DBR1 was added to Defects of innate immunity. Sources: Expert list
Mode of inheritance for gene: DBR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DBR1 were set to 39023559; 29474921
Phenotypes for gene: DBR1 were set to encephalitis, acute, infection (viral)-induced, susceptibility to, 11 MONDO:0030334
Review for gene: DBR1 was set to GREEN
gene: DBR1 was marked as current diagnostic
Added comment: IUIS IEI committee classification as a defect in innate and intrinsic immunity in the subcategory of herpes simplex encephalitis. At least 4 families reported.
Sources: Expert list
Cerebral vascular malformations v0.39 SMAD9 Sangavi Sivagnanasundram reviewed gene: SMAD9: Rating: AMBER; Mode of pathogenicity: None; Publications: 29844917; Phenotypes: arteriovenous malformations of the brain MONDO:0007154; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Cerebral vascular malformations v0.39 PKD2 Sangavi Sivagnanasundram reviewed gene: PKD2: Rating: AMBER; Mode of pathogenicity: None; Publications: 20301424; Phenotypes: polycystic kidney disease 2 MONDO:0013131; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Cerebral vascular malformations v0.39 PKD1 Sangavi Sivagnanasundram reviewed gene: PKD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301424, 35108395, 26260542; Phenotypes: polycystic kidney disease 1 MONDO:0008263; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Cerebral vascular malformations v0.39 PCNT Sangavi Sivagnanasundram reviewed gene: PCNT: Rating: AMBER; Mode of pathogenicity: None; Publications: 34978779, 19839044, 37234811, 34923567; Phenotypes: microcephalic osteodysplastic primordial dwarfism type II MONDO:0008872, Moyamoya disease MONDO:0016820; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.553 GLDC Crystle Lee reviewed gene: GLDC: Rating: GREEN; Mode of pathogenicity: None; Publications: 36817643, 34513771; Phenotypes: Glycine encephalopathy1 (MIM#605899); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral vascular malformations v0.39 NF1 Sangavi Sivagnanasundram reviewed gene: NF1: Rating: RED; Mode of pathogenicity: None; Publications: 20301288; Phenotypes: neurofibromatosis type 1 MONDO:0018975; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Prepair 1000+ v1.553 GAMT Crystle Lee reviewed gene: GAMT: Rating: GREEN; Mode of pathogenicity: None; Publications: 33996490, 38469086; Phenotypes: Cerebral creatine deficiency syndrome 2 (MIM#612736); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.553 ESCO2 Crystle Lee reviewed gene: ESCO2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32977150; Phenotypes: Juberg-Hayward syndrome (MIM#216100), Roberts-SC phocomelia syndrome (MIM#268300); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral vascular malformations v0.39 MYH11 Sangavi Sivagnanasundram reviewed gene: MYH11: Rating: RED; Mode of pathogenicity: None; Publications: 32081817, 29263223, 27367753; Phenotypes: cerebrovascular disorder MONDO:0011057; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Prepair 1000+ v1.553 EIF2B5 Crystle Lee reviewed gene: EIF2B5: Rating: GREEN; Mode of pathogenicity: None; Publications: 20975056, 37674283, 25761052; Phenotypes: Leukoencephalopathy with vanishing white matter 5, with or without ovarian failure (MIM#620315); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.553 DPH1 Crystle Lee reviewed gene: DPH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 39166428, 33704902; Phenotypes: Developmental delay with short stature, dysmorphic facial features, and sparse hair (MIM#616901); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral vascular malformations v0.39 MRVI1 Sangavi Sivagnanasundram reviewed gene: MRVI1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: Unknown
Cerebral vascular malformations v0.39 HBB Sangavi Sivagnanasundram reviewed gene: HBB: Rating: RED; Mode of pathogenicity: None; Publications: 27301940; Phenotypes: sickle cell anemia MONDO:0011382; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral vascular malformations v0.39 FLVCR2 Sangavi Sivagnanasundram reviewed gene: FLVCR2: Rating: RED; Mode of pathogenicity: None; Publications: 4555262; Phenotypes: Fowler syndrome MONDO:0009168; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral vascular malformations v0.39 CEP152 Sangavi Sivagnanasundram reviewed gene: CEP152: Rating: RED; Mode of pathogenicity: None; Publications: 19338412; Phenotypes: Seckel syndrome MONDO:0019342; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral vascular malformations v0.39 ATR Sangavi Sivagnanasundram reviewed gene: ATR: Rating: RED; Mode of pathogenicity: None; Publications: 19338412; Phenotypes: Seckel syndrome 1 MONDO:0008869; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral vascular malformations v0.39 ADA2 Sangavi Sivagnanasundram reviewed gene: ADA2: Rating: AMBER; Mode of pathogenicity: None; Publications: 24552284; Phenotypes: vasculitis due to ADA2 deficiency MONDO:0014306; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral vascular malformations v0.39 COL3A1 Sangavi Sivagnanasundram reviewed gene: COL3A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28742248, 25205403, 19455184; Phenotypes: polymicrogyria with or without vascular-type Ehlers-Danlos syndrome MONDO:0032688; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.553 G6PC Lilian Downie Marked gene: G6PC as ready
Prepair 1000+ v1.553 G6PC Lilian Downie Gene: g6pc has been classified as Green List (High Evidence).
Prepair 1000+ v1.553 G6PC Lilian Downie Publications for gene: G6PC were set to
Prepair 1000+ v1.552 GNB5 Lilian Downie Marked gene: GNB5 as ready
Prepair 1000+ v1.552 GNB5 Lilian Downie Gene: gnb5 has been classified as Green List (High Evidence).
Prepair 1000+ v1.552 GNB5 Lilian Downie Phenotypes for gene: GNB5 were changed from Intellectual developmental disorder with cardiac arrhythmia, 617173 (3), Autosomal recessive to Lodder-Merla syndrome, type 1, with impaired intellectual development and cardiac arrhythmia (MIM#617173); Lodder-Merla syndrome, type 2, with developmental delay and with or without cardiac arrhythmia (MIM#617182)
Prepair 1000+ v1.551 GNB5 Lilian Downie Publications for gene: GNB5 were set to
Prepair 1000+ v1.550 GNPAT Lilian Downie Marked gene: GNPAT as ready
Prepair 1000+ v1.550 GNPAT Lilian Downie Gene: gnpat has been classified as Green List (High Evidence).
Prepair 1000+ v1.550 GNPAT Lilian Downie Phenotypes for gene: GNPAT were changed from Chondrodysplasia punctata, rhizomelic, type 2, 222765 (3) to Rhizomelic chondrodysplasia punctata, type 2 (MIM# 22276)5)
Prepair 1000+ v1.549 GNPAT Lilian Downie Publications for gene: GNPAT were set to
Prepair 1000+ v1.548 CLN3 Lilian Downie Publications for gene: CLN3 were set to 7553855; 31926949
Prepair 1000+ v1.547 CLN3 Lilian Downie Tag SV/CNV tag was added to gene: CLN3.
Cerebral vascular malformations v0.39 EPHB4 Sangavi Sivagnanasundram reviewed gene: EPHB4: Rating: GREEN; Mode of pathogenicity: None; Publications: 33864021, 27400125, 29444212; Phenotypes: EPHB4-associated vascular malformation spectrum MONDO:0700080; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral vascular malformations v0.39 ANO1 Sangavi Sivagnanasundram reviewed gene: ANO1: Rating: AMBER; Mode of pathogenicity: None; Publications: 37253099; Phenotypes: Moyamoya disease 7 MONDO:0958202; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cerebral vascular malformations v0.39 YY1AP1 Sangavi Sivagnanasundram reviewed gene: YY1AP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9489789, 11241488, 31633303; Phenotypes: grange syndrome MONDO:0011243; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral vascular malformations v0.39 SMAD4 Sangavi Sivagnanasundram reviewed gene: SMAD4: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301525; Phenotypes: Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome MONDO:0008278; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral vascular malformations v0.39 SLC2A10 Sangavi Sivagnanasundram reviewed gene: SLC2A10: Rating: GREEN; Mode of pathogenicity: None; Publications: 16550171, 17935213; Phenotypes: arterial tortuosity syndrome MONDO:0008818; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral vascular malformations v0.39 SAMHD1 Sangavi Sivagnanasundram reviewed gene: SAMHD1: Rating: ; Mode of pathogenicity: None; Publications: 20653736, 21402907; Phenotypes: Moyamoya disease MONDO:0016820, Aicardi-Goutieres syndrome 5 MONDO:0013059; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral vascular malformations v0.39 RASA1 Sangavi Sivagnanasundram reviewed gene: RASA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21348050, 24038909; Phenotypes: Capillary Malformation-Arteriovenous Malformation Syndrome MONDO:0012016; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral vascular malformations v0.39 PDCD10 Sangavi Sivagnanasundram changed review comment from: CCM is a feature in affected individuals; to: CCM is a feature in affected individuals.
Cerebral vascular malformations v0.39 PDCD10 Sangavi Sivagnanasundram reviewed gene: PDCD10: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301470; Phenotypes: Familial cerebral cavernous malformations MONDO:0031037; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Prepair 1000+ v1.547 CLN3 Marta Cifuentes Ochoa reviewed gene: CLN3: Rating: GREEN; Mode of pathogenicity: None; Publications: 7553855, 9004140, 9311735, 31926949; Phenotypes: Ceroid lipofuscinosis, neuronal, 3, MIM# 204200, MONDO:0008767; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.547 CLN3 Marta Cifuentes Ochoa Deleted their review
Cerebral vascular malformations v0.39 GUCY1A3 Sangavi Sivagnanasundram reviewed gene: GUCY1A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 24581742, 26777256; Phenotypes: Moyamoya disease with early-onset achalasia MONDO:0014331; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral vascular malformations v0.39 ENG Sangavi Sivagnanasundram reviewed gene: ENG: Rating: GREEN; Mode of pathogenicity: None; Publications: 7894484, 20414677, 30763665, 17384219, 20364125; Phenotypes: telangiectasia, hereditary hemorrhagic, type 1 MONDO:0008535; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral vascular malformations v0.39 CCM2 Sangavi Sivagnanasundram reviewed gene: CCM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301470; Phenotypes: famililal cerebral cavernous malformations MONDO:0031037; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral vascular malformations v0.39 ACVRL1 Sangavi Sivagnanasundram reviewed gene: ACVRL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 86402252, 17384219, 26176610, 9245985 20364125, 20414677; Phenotypes: telangiectasia, hereditary hemorrhagic, type 2 MONDO:0010880; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral vascular malformations v0.39 ACTA2 Sangavi Sivagnanasundram reviewed gene: ACTA2: Rating: AMBER; Mode of pathogenicity: None; Publications: 19409525, 24621862, 20970362; Phenotypes: Moyamoya disease 5 MONDO:0013542; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Prepair 1000+ v1.547 GNPAT Ee Ming Wong reviewed gene: GNPAT: Rating: GREEN; Mode of pathogenicity: None; Publications: 9536089, 11152660, 21990100; Phenotypes: Rhizomelic chondrodysplasia punctata, type 2 (MIM# 222765); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.547 GNB5 Ee Ming Wong reviewed gene: GNB5: Rating: GREEN; Mode of pathogenicity: None; Publications: 34436834; Phenotypes: Lodder-Merla syndrome, type 1, with impaired intellectual development and cardiac arrhythmia (MIM#617173), Lodder-Merla syndrome, type 2, with developmental delay and with or without cardiac arrhythmia (MIM#617182); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.547 G6PC Ee Ming Wong reviewed gene: G6PC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Glycogen storage disease Ia (MIM# 232200); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Predominantly Antibody Deficiency v0.150 Bryony Thompson Panel types changed to Melbourne Genomics; Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Phagocyte Defects v1.32 DBF4 Bryony Thompson Marked gene: DBF4 as ready
Phagocyte Defects v1.32 DBF4 Bryony Thompson Gene: dbf4 has been classified as Red List (Low Evidence).
Phagocyte Defects v1.32 DBF4 Bryony Thompson gene: DBF4 was added
gene: DBF4 was added to Phagocyte Defects. Sources: Expert list
Mode of inheritance for gene: DBF4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DBF4 were set to 36841265
Phenotypes for gene: DBF4 were set to severe congenital neutropenia MONDO:0018542
Review for gene: DBF4 was set to RED
Added comment: A single case with a homozygous variant & some supporting in vitro functional assay.
Sources: Expert list
Disorders of immune dysregulation v0.216 TNFSF9 Bryony Thompson Marked gene: TNFSF9 as ready
Disorders of immune dysregulation v0.216 TNFSF9 Bryony Thompson Gene: tnfsf9 has been classified as Red List (Low Evidence).
Disorders of immune dysregulation v0.215 TNFSF9 Bryony Thompson gene: TNFSF9 was added
gene: TNFSF9 was added to Disorders of immune dysregulation. Sources: Expert list
Mode of inheritance for gene: TNFSF9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TNFSF9 were set to 35657354
Phenotypes for gene: TNFSF9 were set to Hereditary susceptibility to infections, MONDO:0015979, TNFSF9-related
Susceptibility to Viral Infections v0.131 NFATC2 Bryony Thompson Publications for gene: NFATC2 were set to PMID: 38427060
Susceptibility to Viral Infections v0.130 NFATC2 Bryony Thompson Classified gene: NFATC2 as Amber List (moderate evidence)
Susceptibility to Viral Infections v0.130 NFATC2 Bryony Thompson Gene: nfatc2 has been classified as Amber List (Moderate Evidence).
Susceptibility to Viral Infections v0.129 NFATC2 Bryony Thompson reviewed gene: NFATC2: Rating: AMBER; Mode of pathogenicity: None; Publications: 35789258, 38427060; Phenotypes: Lymphoproliferative syndrome, MONDO:0016537, NFATC2-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2147 NFATC2 Bryony Thompson Classified gene: NFATC2 as Amber List (moderate evidence)
Mendeliome v1.2147 NFATC2 Bryony Thompson Gene: nfatc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2146 NFATC2 Bryony Thompson reviewed gene: NFATC2: Rating: AMBER; Mode of pathogenicity: None; Publications: 35789258, 38427060; Phenotypes: Lymphoproliferative syndrome, MONDO:0016537, NFATC2-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Disorders of immune dysregulation v0.214 NFATC2 Bryony Thompson Marked gene: NFATC2 as ready
Disorders of immune dysregulation v0.214 NFATC2 Bryony Thompson Gene: nfatc2 has been classified as Amber List (Moderate Evidence).
Disorders of immune dysregulation v0.214 NFATC2 Bryony Thompson Classified gene: NFATC2 as Amber List (moderate evidence)
Disorders of immune dysregulation v0.214 NFATC2 Bryony Thompson Gene: nfatc2 has been classified as Amber List (Moderate Evidence).
Disorders of immune dysregulation v0.213 NFATC2 Bryony Thompson gene: NFATC2 was added
gene: NFATC2 was added to Disorders of immune dysregulation. Sources: Expert list
Mode of inheritance for gene: NFATC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NFATC2 were set to 35789258; 38427060
Phenotypes for gene: NFATC2 were set to Lymphoproliferative syndrome, MONDO:0016537, NFATC2-related
Review for gene: NFATC2 was set to AMBER
Added comment: 2 consanguineous families are reported with homozygous variants (a frameshift & an in-frame deletion). Both families have a lymphoproliferative disorder and one family also had soft tissue and cartilage abnormalities. IUIS IEI committee classify NFATC2-deficiency as a disease of immune dysregulation.
Sources: Expert list
Autoinflammatory Disorders v1.57 Bryony Thompson removed gene:LACC1 from the panel
Disorders of immune dysregulation v0.212 LACC1 Bryony Thompson Marked gene: LACC1 as ready
Disorders of immune dysregulation v0.212 LACC1 Bryony Thompson Gene: lacc1 has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.212 LACC1 Bryony Thompson Classified gene: LACC1 as Green List (high evidence)
Disorders of immune dysregulation v0.212 LACC1 Bryony Thompson Added comment: Comment on list classification: IUIS IEI classifies LACC1-deficiency as a disease of immune dysregulation
Disorders of immune dysregulation v0.212 LACC1 Bryony Thompson Gene: lacc1 has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.210 LACC1 Bryony Thompson gene: LACC1 was added
gene: LACC1 was added to Disorders of immune dysregulation. Sources: Expert list
Mode of inheritance for gene: LACC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LACC1 were set to 25220867; 27881174; 30872671; 33718577
Phenotypes for gene: LACC1 were set to juvenile arthritis due to defect in LACC1 MONDO:0032920
Disorders of immune dysregulation v0.209 IL27RA Bryony Thompson Marked gene: IL27RA as ready
Disorders of immune dysregulation v0.209 IL27RA Bryony Thompson Gene: il27ra has been classified as Amber List (Moderate Evidence).
Disorders of immune dysregulation v0.209 IL27RA Bryony Thompson Classified gene: IL27RA as Amber List (moderate evidence)
Disorders of immune dysregulation v0.209 IL27RA Bryony Thompson Gene: il27ra has been classified as Amber List (Moderate Evidence).
Disorders of immune dysregulation v0.208 IL27RA Bryony Thompson gene: IL27RA was added
gene: IL27RA was added to Disorders of immune dysregulation. Sources: Expert list
Mode of inheritance for gene: IL27RA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL27RA were set to 38509369
Phenotypes for gene: IL27RA were set to Epstein-Barr virus infection MONDO:0005111 , IL27RA-related
Review for gene: IL27RA was set to AMBER
Added comment: 2 families reported. IL27RA-deficiency is classified as a disease of immune dysregulation by the IUIS IEI committee, under the Susceptibility to EBV and Lymphoproliferative Conditions subcategory.
Sources: Expert list
Disorders of immune dysregulation v0.207 GIMAP5 Bryony Thompson Marked gene: GIMAP5 as ready
Disorders of immune dysregulation v0.207 GIMAP5 Bryony Thompson Gene: gimap5 has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.207 GIMAP5 Bryony Thompson Classified gene: GIMAP5 as Green List (high evidence)
Disorders of immune dysregulation v0.207 GIMAP5 Bryony Thompson Gene: gimap5 has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.206 GIMAP5 Bryony Thompson gene: GIMAP5 was added
gene: GIMAP5 was added to Disorders of immune dysregulation. Sources: Expert list
Mode of inheritance for gene: GIMAP5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GIMAP5 were set to 33956074
Phenotypes for gene: GIMAP5 were set to portal hypertension, noncirrhotic, 2 MONDO:0030397
Review for gene: GIMAP5 was set to GREEN
gene: GIMAP5 was marked as current diagnostic
Added comment: At least 4 families reported. GIMAP5-deficiency is classified as a disease of immune dysregulation by the IUIS IEI committee, under the Autoimmunity with or without Lymphoproliferation subcategory.
Sources: Expert list
Disorders of immune dysregulation v0.205 FERMT1 Bryony Thompson Marked gene: FERMT1 as ready
Disorders of immune dysregulation v0.205 FERMT1 Bryony Thompson Gene: fermt1 has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.205 FERMT1 Bryony Thompson Classified gene: FERMT1 as Green List (high evidence)
Disorders of immune dysregulation v0.205 FERMT1 Bryony Thompson Gene: fermt1 has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.204 FERMT1 Bryony Thompson gene: FERMT1 was added
gene: FERMT1 was added to Disorders of immune dysregulation. Sources: Expert list
Mode of inheritance for gene: FERMT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FERMT1 were set to 34512655
Phenotypes for gene: FERMT1 were set to Kindler syndrome MONDO:0008260
Review for gene: FERMT1 was set to GREEN
gene: FERMT1 was marked as current diagnostic
Added comment: The IUIS IEI committee classifies FERMT1 deficiency (aka Kindler syndrome) as a disease of immune dysregulation under the Regulatory T Cell Defects subcategory.
Sources: Expert list
Disorders of immune dysregulation v0.203 FAAP24 Bryony Thompson Classified gene: FAAP24 as Red List (low evidence)
Disorders of immune dysregulation v0.203 FAAP24 Bryony Thompson Added comment: Comment on list classification: Disputed gene-disease association by the Primary Immune Regulatory Disorders GCEP (https://search.clinicalgenome.org/CCID:008245).
Disorders of immune dysregulation v0.203 FAAP24 Bryony Thompson Gene: faap24 has been classified as Red List (Low Evidence).
Disorders of immune dysregulation v0.202 ERN1 Bryony Thompson Marked gene: ERN1 as ready
Disorders of immune dysregulation v0.202 ERN1 Bryony Thompson Gene: ern1 has been classified as Red List (Low Evidence).
Disorders of immune dysregulation v0.202 ERN1 Bryony Thompson gene: ERN1 was added
gene: ERN1 was added to Disorders of immune dysregulation. Sources: Expert list
Mode of inheritance for gene: ERN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ERN1 were set to Immune dysregulation
Review for gene: ERN1 was set to RED
Added comment: On the IUIS 2024 update for IEIs as a gene associated with an AD disease of immune dysregulation, I cannot find any evidence of Mendelian disease.
Sources: Expert list
Disorders of immune dysregulation v0.201 DPP9 Bryony Thompson Marked gene: DPP9 as ready
Disorders of immune dysregulation v0.201 DPP9 Bryony Thompson Gene: dpp9 has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.201 DPP9 Bryony Thompson Classified gene: DPP9 as Green List (high evidence)
Disorders of immune dysregulation v0.201 DPP9 Bryony Thompson Gene: dpp9 has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.200 DPP9 Bryony Thompson gene: DPP9 was added
gene: DPP9 was added to Disorders of immune dysregulation. Sources: Expert Review
Mode of inheritance for gene: DPP9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DPP9 were set to 36112693
Phenotypes for gene: DPP9 were set to hatipoglu immunodeficiency syndrome MONDO:0957229
Review for gene: DPP9 was set to GREEN
gene: DPP9 was marked as current diagnostic
Added comment: 3 unrelated families and supporting null mouse model. IUIS IEI committee assign the condition to diseases of immune dysregulation in the subcategory of Familial Hemophagocytic Lymphohistiocytosis (FHL syndromes).
Sources: Expert Review
Disorders of immune dysregulation v0.199 ARPC5 Bryony Thompson Marked gene: ARPC5 as ready
Disorders of immune dysregulation v0.199 ARPC5 Bryony Thompson Gene: arpc5 has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.199 ARPC5 Bryony Thompson Classified gene: ARPC5 as Green List (high evidence)
Disorders of immune dysregulation v0.199 ARPC5 Bryony Thompson Gene: arpc5 has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.198 ARPC5 Bryony Thompson gene: ARPC5 was added
gene: ARPC5 was added to Disorders of immune dysregulation. Sources: Expert list
Mode of inheritance for gene: ARPC5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARPC5 were set to 37382373; 37349293
Phenotypes for gene: ARPC5 were set to Immunodeficiency 133 with autoimmunity and autoinflammation MIM#620565
Review for gene: ARPC5 was set to GREEN
gene: ARPC5 was marked as current diagnostic
Added comment: 3 unrelated consanguineous families with homozygous variants and supporting in vitro functional assays. Immune dysregulation is a prominent feature of the condition. The IUIS IEI committee classify it as a disease of immune dysregulation in the subcategory of autoimmunity with or without lymphoproliferation.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v1.0 Zornitza Stark promoted panel to version 1.0
Intellectual disability syndromic and non-syndromic v0.6911 FMR1 Zornitza Stark Marked gene: FMR1 as ready
Intellectual disability syndromic and non-syndromic v0.6911 FMR1 Zornitza Stark Gene: fmr1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6911 FMR1 Zornitza Stark Phenotypes for gene: FMR1 were changed from to fragile X syndrome MONDO:0010383
Intellectual disability syndromic and non-syndromic v0.6910 FMR1 Zornitza Stark Publications for gene: FMR1 were set to
Intellectual disability syndromic and non-syndromic v0.6909 FMR1 Zornitza Stark Mode of inheritance for gene: FMR1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.6908 FRAXE Zornitza Stark Marked STR: FRAXE as ready
Intellectual disability syndromic and non-syndromic v0.6908 FRAXE Zornitza Stark Str: fraxe has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6908 FRAXE Zornitza Stark Tag STR tag was added to STR: FRAXE.
Intellectual disability syndromic and non-syndromic v0.6908 HADHA Zornitza Stark Marked gene: HADHA as ready
Intellectual disability syndromic and non-syndromic v0.6908 HADHA Zornitza Stark Gene: hadha has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6908 HADHA Zornitza Stark Phenotypes for gene: HADHA were changed from to long chain 3-hydroxyacyl-CoA dehydrogenase deficiency MONDO:0012173
Intellectual disability syndromic and non-syndromic v0.6907 HADHA Zornitza Stark Publications for gene: HADHA were set to
Intellectual disability syndromic and non-syndromic v0.6906 HADHA Zornitza Stark Mode of inheritance for gene: HADHA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6905 PEX14 Zornitza Stark Marked gene: PEX14 as ready
Intellectual disability syndromic and non-syndromic v0.6905 PEX14 Zornitza Stark Gene: pex14 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6905 AHSG Zornitza Stark Marked gene: AHSG as ready
Intellectual disability syndromic and non-syndromic v0.6905 AHSG Zornitza Stark Gene: ahsg has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.6905 STN1 Zornitza Stark Marked gene: STN1 as ready
Intellectual disability syndromic and non-syndromic v0.6905 STN1 Zornitza Stark Gene: stn1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6905 STN1 Zornitza Stark Phenotypes for gene: STN1 were changed from cerebral calcification; premature ageing; bone marrow failure; retinal telangiactasia; hepatic fibrosis to Cerebroretinal microangiopathy with calcification and cysts 2, MIM#617341
Intellectual disability syndromic and non-syndromic v0.6904 PCNT Zornitza Stark Marked gene: PCNT as ready
Intellectual disability syndromic and non-syndromic v0.6904 PCNT Zornitza Stark Gene: pcnt has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6904 PCNT Zornitza Stark Phenotypes for gene: PCNT were changed from to Microcephalic osteodysplastic primordial dwarfism, type II MIM#210720
Intellectual disability syndromic and non-syndromic v0.6903 PCNT Zornitza Stark Publications for gene: PCNT were set to
Intellectual disability syndromic and non-syndromic v0.6902 PCNT Zornitza Stark Mode of inheritance for gene: PCNT was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6901 PCNT Zornitza Stark Mode of inheritance for gene: PCNT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6901 PCNT Zornitza Stark Classified gene: PCNT as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.6901 PCNT Zornitza Stark Gene: pcnt has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6900 PCNT Zornitza Stark Classified gene: PCNT as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.6900 PCNT Zornitza Stark Gene: pcnt has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6899 PC Zornitza Stark Marked gene: PC as ready
Intellectual disability syndromic and non-syndromic v0.6899 PC Zornitza Stark Gene: pc has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6899 PC Zornitza Stark Phenotypes for gene: PC were changed from to Pyruvate carboxylase deficiency - MIM#266150
Intellectual disability syndromic and non-syndromic v0.6898 PC Zornitza Stark Publications for gene: PC were set to
Intellectual disability syndromic and non-syndromic v0.6897 PC Zornitza Stark Mode of inheritance for gene: PC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6896 PAX8 Zornitza Stark Marked gene: PAX8 as ready
Intellectual disability syndromic and non-syndromic v0.6896 PAX8 Zornitza Stark Gene: pax8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6896 PAX8 Zornitza Stark Phenotypes for gene: PAX8 were changed from to Hypothyroidism, congenital, due to thyroid dysgenesis or hypoplasia, MIM# 218700
Intellectual disability syndromic and non-syndromic v0.6895 PAX8 Zornitza Stark Publications for gene: PAX8 were set to
Intellectual disability syndromic and non-syndromic v0.6894 PAX8 Zornitza Stark Mode of inheritance for gene: PAX8 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6893 PAX6 Zornitza Stark Marked gene: PAX6 as ready
Intellectual disability syndromic and non-syndromic v0.6893 PAX6 Zornitza Stark Gene: pax6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6893 PAX6 Zornitza Stark Phenotypes for gene: PAX6 were changed from Microphthalmia/coloboma 12, OMIM #120200 to Microphthalmia/coloboma 12, OMIM #120200
Intellectual disability syndromic and non-syndromic v0.6892 PAX6 Zornitza Stark Phenotypes for gene: PAX6 were changed from to Microphthalmia/coloboma 12, OMIM #120200
Intellectual disability syndromic and non-syndromic v0.6891 PAX6 Zornitza Stark Publications for gene: PAX6 were set to
Intellectual disability syndromic and non-syndromic v0.6890 PAX6 Zornitza Stark Mode of inheritance for gene: PAX6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6889 PARN Zornitza Stark Marked gene: PARN as ready
Intellectual disability syndromic and non-syndromic v0.6889 PARN Zornitza Stark Gene: parn has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6889 PARN Zornitza Stark Phenotypes for gene: PARN were changed from to Dyskeratosis congenita, autosomal recessive 6, MIM# 616353
Intellectual disability syndromic and non-syndromic v0.6888 PARN Zornitza Stark Publications for gene: PARN were set to
Intellectual disability syndromic and non-syndromic v0.6887 PARN Zornitza Stark Mode of inheritance for gene: PARN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6886 OTX2 Zornitza Stark Marked gene: OTX2 as ready
Intellectual disability syndromic and non-syndromic v0.6886 OTX2 Zornitza Stark Gene: otx2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6886 OTX2 Zornitza Stark Phenotypes for gene: OTX2 were changed from to Microphthalmia, syndromic 5, MIM# 610125; Pituitary hormone deficiency, combined, 6, MIM# 613986; Retinal dystrophy, early-onset, with or without pituitary dysfunction, MIM# 610125; Otocephaly-dysgnathia complex
Intellectual disability syndromic and non-syndromic v0.6885 OTX2 Zornitza Stark Publications for gene: OTX2 were set to
Intellectual disability syndromic and non-syndromic v0.6884 OTX2 Zornitza Stark Mode of inheritance for gene: OTX2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6883 OPA3 Zornitza Stark Marked gene: OPA3 as ready
Intellectual disability syndromic and non-syndromic v0.6883 OPA3 Zornitza Stark Gene: opa3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6883 OPA3 Zornitza Stark Phenotypes for gene: OPA3 were changed from to 3-methylglutaconic aciduria, type III (MGA3) (MIM#258501), AR; Optic atrophy 3 with cataract (MIM#165300), AD
Intellectual disability syndromic and non-syndromic v0.6882 OPA3 Zornitza Stark Publications for gene: OPA3 were set to 25159689; 31119193; 31928268
Intellectual disability syndromic and non-syndromic v0.6881 OPA3 Zornitza Stark Publications for gene: OPA3 were set to
Intellectual disability syndromic and non-syndromic v0.6880 OPA3 Zornitza Stark Mode of inheritance for gene: OPA3 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6879 OPA3 Zornitza Stark Mode of inheritance for gene: OPA3 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 v0.6878 OCLN Zornitza Stark Marked gene: OCLN as ready
Intellectual disability syndromic and non-syndromic v0.6878 OCLN Zornitza Stark Gene: ocln has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6878 OCLN Zornitza Stark Phenotypes for gene: OCLN were changed from to Pseudo-TORCH syndrome 1, MIM#251290
Intellectual disability syndromic and non-syndromic v0.6877 OCLN Zornitza Stark Publications for gene: OCLN were set to
Intellectual disability syndromic and non-syndromic v0.6876 OCLN Zornitza Stark Mode of inheritance for gene: OCLN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6875 NRAS Zornitza Stark Marked gene: NRAS as ready
Intellectual disability syndromic and non-syndromic v0.6875 NRAS Zornitza Stark Gene: nras has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6875 NRAS Zornitza Stark Phenotypes for gene: NRAS were changed from to Noonan syndrome 6, MIM# 613224
Intellectual disability syndromic and non-syndromic v0.6874 NRAS Zornitza Stark Publications for gene: NRAS were set to
Intellectual disability syndromic and non-syndromic v0.6873 NRAS Zornitza Stark Mode of pathogenicity for gene: NRAS was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability syndromic and non-syndromic v0.6872 NRAS Zornitza Stark Mode of pathogenicity for gene: NRAS was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability syndromic and non-syndromic v0.6871 NRAS Zornitza Stark Mode of inheritance for gene: NRAS was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6870 NPHP1 Zornitza Stark Marked gene: NPHP1 as ready
Intellectual disability syndromic and non-syndromic v0.6870 NPHP1 Zornitza Stark Gene: nphp1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6870 NPHP1 Zornitza Stark Phenotypes for gene: NPHP1 were changed from to Joubert syndrome 4, MIM# 609583; Nephronophthisis 1, juvenile, MIM# 256100; Senior-Loken syndrome-1, MIM# 266900
Intellectual disability syndromic and non-syndromic v0.6869 NPHP1 Zornitza Stark Publications for gene: NPHP1 were set to 15138899; 32139166; 28347285; 8852662; 9856524
Intellectual disability syndromic and non-syndromic v0.6868 NPHP1 Zornitza Stark Publications for gene: NPHP1 were set to
Intellectual disability syndromic and non-syndromic v0.6867 NPHP1 Zornitza Stark Mode of inheritance for gene: NPHP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6866 NF1 Zornitza Stark Marked gene: NF1 as ready
Intellectual disability syndromic and non-syndromic v0.6866 NF1 Zornitza Stark Gene: nf1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6866 NF1 Zornitza Stark Phenotypes for gene: NF1 were changed from to Neurofibromatosis, type 1 (MIM#162200)
Intellectual disability syndromic and non-syndromic v0.6865 NF1 Zornitza Stark Publications for gene: NF1 were set to 23931823; 10762507
Intellectual disability syndromic and non-syndromic v0.6864 NF1 Zornitza Stark Publications for gene: NF1 were set to
Intellectual disability syndromic and non-syndromic v0.6863 NF1 Zornitza Stark Mode of inheritance for gene: NF1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6862 NDUFS8 Zornitza Stark Marked gene: NDUFS8 as ready
Intellectual disability syndromic and non-syndromic v0.6862 NDUFS8 Zornitza Stark Gene: ndufs8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6862 NDUFS8 Zornitza Stark Phenotypes for gene: NDUFS8 were changed from Mitochondrial complex I deficiency, nuclear type 2 MIM#618222 to Mitochondrial complex I deficiency, nuclear type 2 MIM#618222
Intellectual disability syndromic and non-syndromic v0.6861 NDUFS8 Zornitza Stark Phenotypes for gene: NDUFS8 were changed from to Mitochondrial complex I deficiency, nuclear type 2 MIM#618222
Intellectual disability syndromic and non-syndromic v0.6861 NDUFS8 Zornitza Stark Publications for gene: NDUFS8 were set to 23430795; 9837812; 15159508; 22499348; 20818383; 20819849
Intellectual disability syndromic and non-syndromic v0.6860 NDUFS8 Zornitza Stark Publications for gene: NDUFS8 were set to 23430795; 9837812; 15159508; 22499348; 20818383; 20819849
Intellectual disability syndromic and non-syndromic v0.6859 NDUFS8 Zornitza Stark Publications for gene: NDUFS8 were set to
Intellectual disability syndromic and non-syndromic v0.6858 NDUFS8 Zornitza Stark Mode of inheritance for gene: NDUFS8 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6857 NDUFS8 Zornitza Stark Mode of inheritance for gene: NDUFS8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6856 NDUFS4 Zornitza Stark Phenotypes for gene: NDUFS4 were changed from Mitochondrial complex I deficiency, nuclear type 1, 252010; Leigh syndrome, MIM#252010 to Mitochondrial complex I deficiency, nuclear type 1, 252010; Leigh syndrome, MIM#252010
Intellectual disability syndromic and non-syndromic v0.6856 NDUFS4 Zornitza Stark Marked gene: NDUFS4 as ready
Intellectual disability syndromic and non-syndromic v0.6856 NDUFS4 Zornitza Stark Gene: ndufs4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6856 NDUFS4 Zornitza Stark Phenotypes for gene: NDUFS4 were changed from to Mitochondrial complex I deficiency, nuclear type 1, 252010; Leigh syndrome, MIM#252010
Intellectual disability syndromic and non-syndromic v0.6855 NDUFS4 Zornitza Stark Publications for gene: NDUFS4 were set to
Intellectual disability syndromic and non-syndromic v0.6854 NDUFS4 Zornitza Stark Mode of inheritance for gene: NDUFS4 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6853 NDUFS4 Zornitza Stark Mode of inheritance for gene: NDUFS4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6852 NACC1 Zornitza Stark Marked gene: NACC1 as ready
Intellectual disability syndromic and non-syndromic v0.6852 NACC1 Zornitza Stark Gene: nacc1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6852 MYCN Zornitza Stark Marked gene: MYCN as ready
Intellectual disability syndromic and non-syndromic v0.6852 MYCN Zornitza Stark Gene: mycn has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6852 MYCN Zornitza Stark Phenotypes for gene: MYCN were changed from to Feingold syndrome 1 MIM#164280; Megalencephaly-polydactyly syndrome, MIM# 620748
Intellectual disability syndromic and non-syndromic v0.6851 MYCN Zornitza Stark reviewed gene: MYCN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Feingold syndrome 1 MIM#164280; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6851 MYCN Zornitza Stark Publications for gene: MYCN were set to
Intellectual disability syndromic and non-syndromic v0.6850 MYCN Zornitza Stark Mode of inheritance for gene: MYCN was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.2146 MED12L Zornitza Stark Phenotypes for gene: MED12L were changed from Intellectual disability; Seizures; Autism to Neurodevelopmental disorder, MONDO:0700092, MED12L-related; Intellectual disability; Seizures; Autism
Mendeliome v1.2145 MED12L Zornitza Stark edited their review of gene: MED12L: Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, MED12L-related, Intellectual disability, Seizures, Autism
Intellectual disability syndromic and non-syndromic v0.6849 MED12L Zornitza Stark Marked gene: MED12L as ready
Intellectual disability syndromic and non-syndromic v0.6849 MED12L Zornitza Stark Gene: med12l has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6849 MED12L Zornitza Stark Phenotypes for gene: MED12L were changed from Intellectual disability; Seizures; Autism to Neurodevelopmental disorder, MONDO:0700092, MED12L-related; Intellectual disability; Seizures; Autism
Intellectual disability syndromic and non-syndromic v0.6848 LARS2 Zornitza Stark Marked gene: LARS2 as ready
Intellectual disability syndromic and non-syndromic v0.6848 LARS2 Zornitza Stark Gene: lars2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6848 LARS2 Zornitza Stark Phenotypes for gene: LARS2 were changed from to Perrault syndrome 4, MIM# 615300; Hydrops, lactic acidosis, and sideroblastic anemia, MIM# 617021
Intellectual disability syndromic and non-syndromic v0.6847 LARS2 Zornitza Stark Publications for gene: LARS2 were set to
Intellectual disability syndromic and non-syndromic v0.6846 LARS2 Zornitza Stark Mode of inheritance for gene: LARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6845 LARGE1 Zornitza Stark Marked gene: LARGE1 as ready
Intellectual disability syndromic and non-syndromic v0.6845 LARGE1 Zornitza Stark Gene: large1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6845 LARGE1 Zornitza Stark Phenotypes for gene: LARGE1 were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 6, MIM# 613154; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 6, MIM# 608840
Intellectual disability syndromic and non-syndromic v0.6844 LARGE1 Zornitza Stark Publications for gene: LARGE1 were set to
Intellectual disability syndromic and non-syndromic v0.6843 LARGE1 Zornitza Stark Mode of inheritance for gene: LARGE1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6842 LAMP2 Zornitza Stark Marked gene: LAMP2 as ready
Intellectual disability syndromic and non-syndromic v0.6842 LAMP2 Zornitza Stark Gene: lamp2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6842 LAMP2 Zornitza Stark Phenotypes for gene: LAMP2 were changed from Danon disease, MIM# 300257; MONDO:0010281 to Danon disease, MIM# 300257; MONDO:0010281
Intellectual disability syndromic and non-syndromic v0.6841 LAMP2 Zornitza Stark Phenotypes for gene: LAMP2 were changed from to Danon disease, MIM# 300257; MONDO:0010281
Intellectual disability syndromic and non-syndromic v0.6840 LAMP2 Zornitza Stark Publications for gene: LAMP2 were set to
Intellectual disability syndromic and non-syndromic v0.6839 LAMP2 Zornitza Stark Mode of inheritance for gene: LAMP2 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.6838 KRAS Zornitza Stark Marked gene: KRAS as ready
Intellectual disability syndromic and non-syndromic v0.6838 KRAS Zornitza Stark Gene: kras has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6838 KRAS Zornitza Stark Phenotypes for gene: KRAS were changed from to Noonan syndrome 3, MIM# 609942; Cardiofaciocutaneous syndrome 2, MIM# 615278
Intellectual disability syndromic and non-syndromic v0.6837 KRAS Zornitza Stark Publications for gene: KRAS were set to
Intellectual disability syndromic and non-syndromic v0.6836 KRAS Zornitza Stark Mode of pathogenicity for gene: KRAS was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability syndromic and non-syndromic v0.6835 KRAS Zornitza Stark Mode of inheritance for gene: KRAS was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6834 KMT2E Zornitza Stark Marked gene: KMT2E as ready
Intellectual disability syndromic and non-syndromic v0.6834 KMT2E Zornitza Stark Gene: kmt2e has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6834 KMT2E Zornitza Stark Phenotypes for gene: KMT2E were changed from to O'Donnell-Luria-Rodan syndrome, MIM# 618512; Intellectual disability; Autism; Seizures
Intellectual disability syndromic and non-syndromic v0.6833 KMT2E Zornitza Stark Publications for gene: KMT2E were set to
Intellectual disability syndromic and non-syndromic v0.6832 KMT2E Zornitza Stark Mode of inheritance for gene: KMT2E was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6831 KAT6B Zornitza Stark Marked gene: KAT6B as ready
Intellectual disability syndromic and non-syndromic v0.6831 KAT6B Zornitza Stark Gene: kat6b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6831 KAT6B Zornitza Stark Phenotypes for gene: KAT6B were changed from KAT6B-related multiple congenital anomalies syndrome MONDO:0036042 to KAT6B-related multiple congenital anomalies syndrome MONDO:0036042
Intellectual disability syndromic and non-syndromic v0.6830 KAT6B Zornitza Stark Phenotypes for gene: KAT6B were changed from to KAT6B-related multiple congenital anomalies syndrome MONDO:0036042
Intellectual disability syndromic and non-syndromic v0.6829 KAT6B Zornitza Stark Publications for gene: KAT6B were set to
Intellectual disability syndromic and non-syndromic v0.6828 KAT6B Zornitza Stark Mode of inheritance for gene: KAT6B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6827 KAT6A Zornitza Stark Marked gene: KAT6A as ready
Intellectual disability syndromic and non-syndromic v0.6827 KAT6A Zornitza Stark Gene: kat6a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6827 KAT6A Zornitza Stark Phenotypes for gene: KAT6A were changed from to syndromic intellectual disability MONDO:0000508
Intellectual disability syndromic and non-syndromic v0.6826 KAT6A Zornitza Stark Publications for gene: KAT6A were set to
Intellectual disability syndromic and non-syndromic v0.6825 KAT6A Zornitza Stark Mode of inheritance for gene: KAT6A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6824 INPP5K Zornitza Stark Marked gene: INPP5K as ready
Intellectual disability syndromic and non-syndromic v0.6824 INPP5K Zornitza Stark Gene: inpp5k has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6824 INPP5K Zornitza Stark Phenotypes for gene: INPP5K were changed from to congenital muscular dystrophy with cataracts and intellectual disability MONDO:0024607
Intellectual disability syndromic and non-syndromic v0.6823 INPP5K Zornitza Stark Publications for gene: INPP5K were set to
Intellectual disability syndromic and non-syndromic v0.6822 INPP5K Zornitza Stark Mode of inheritance for gene: INPP5K was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6821 IKBKG Zornitza Stark Marked gene: IKBKG as ready
Intellectual disability syndromic and non-syndromic v0.6821 IKBKG Zornitza Stark Gene: ikbkg has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6821 IKBKG Zornitza Stark Phenotypes for gene: IKBKG were changed from to Incontinentia pigmenti MONDO:0010631
Intellectual disability syndromic and non-syndromic v0.6820 IKBKG Zornitza Stark Publications for gene: IKBKG were set to
Intellectual disability syndromic and non-syndromic v0.6819 IKBKG Zornitza Stark Mode of inheritance for gene: IKBKG was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.547 EYS Cassandra Muller reviewed gene: EYS: Rating: RED; Mode of pathogenicity: None; Publications: 20537394, 31074760; Phenotypes: Retinitis pigmentosa 25 (MIM#602772); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.547 ACE Lauren Rogers reviewed gene: ACE: Rating: GREEN; Mode of pathogenicity: None; Publications: 16116425, 22095942; Phenotypes: Renal tubular dysgenesis, MIM# 267430; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v1.79 RFC4 Zornitza Stark Marked gene: RFC4 as ready
Muscular dystrophy and myopathy_Paediatric v1.79 RFC4 Zornitza Stark Gene: rfc4 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.79 RFC4 Zornitza Stark Phenotypes for gene: RFC4 were changed from Morimoto-Ryu-Malicdan neuromuscular syndrome, MIM# 621010 to Morimoto-Ryu-Malicdan neuromuscular syndrome, MIM# 621010
Muscular dystrophy and myopathy_Paediatric v1.79 RFC4 Zornitza Stark Phenotypes for gene: RFC4 were changed from RFC4-related multisystem disorder to Morimoto-Ryu-Malicdan neuromuscular syndrome, MIM# 621010
Muscular dystrophy and myopathy_Paediatric v1.78 RFC4 Zornitza Stark reviewed gene: RFC4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Morimoto-Ryu-Malicdan neuromuscular syndrome, MIM# 621010; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2145 RFC4 Zornitza Stark Marked gene: RFC4 as ready
Mendeliome v1.2145 RFC4 Zornitza Stark Gene: rfc4 has been classified as Green List (High Evidence).
Mendeliome v1.2145 RFC4 Zornitza Stark Phenotypes for gene: RFC4 were changed from RFC4-related multisystem disorder to Morimoto-Ryu-Malicdan neuromuscular syndrome, MIM# 621010
Cerebellar and Pontocerebellar Hypoplasia v1.73 RFC4 Zornitza Stark Marked gene: RFC4 as ready
Cerebellar and Pontocerebellar Hypoplasia v1.73 RFC4 Zornitza Stark Gene: rfc4 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v1.73 RFC4 Zornitza Stark Phenotypes for gene: RFC4 were changed from RFC4-related multisystem disorder to Morimoto-Ryu-Malicdan neuromuscular syndrome, MIM# 621010
Cerebellar and Pontocerebellar Hypoplasia v1.72 RFC4 Zornitza Stark reviewed gene: RFC4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Morimoto-Ryu-Malicdan neuromuscular syndrome, MIM# 621010; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.294 DHRSX Zornitza Stark Phenotypes for gene: DHRSX were changed from congenital disorder of glycosylation, MONDO:0015286, DHRSX-related to Congenital disorder of glycosylation, type 1DD, MIM# 301133
Fetal anomalies v1.293 DHRSX Zornitza Stark edited their review of gene: DHRSX: Changed phenotypes: Congenital disorder of glycosylation, type 1DD, MIM# 301133
Intellectual disability syndromic and non-syndromic v0.6818 DHRSX Zornitza Stark Phenotypes for gene: DHRSX were changed from congenital disorder of glycosylation, MONDO:0015286, DHRSX-related to Congenital disorder of glycosylation, type 1DD, MIM# 301133
Intellectual disability syndromic and non-syndromic v0.6817 DHRSX Zornitza Stark edited their review of gene: DHRSX: Changed phenotypes: Congenital disorder of glycosylation, type 1DD, MIM# 301133
Deafness_IsolatedAndComplex v1.206 DHRSX Zornitza Stark Phenotypes for gene: DHRSX were changed from congenital disorder of glycosylation, MONDO:0015286, DHRSX-related to Congenital disorder of glycosylation, type 1DD, MIM# 301133
Deafness_IsolatedAndComplex v1.205 DHRSX Zornitza Stark edited their review of gene: DHRSX: Changed phenotypes: Congenital disorder of glycosylation, type 1DD, MIM# 301133
Genetic Epilepsy v1.73 DHRSX Zornitza Stark Phenotypes for gene: DHRSX were changed from congenital disorder of glycosylation, MONDO:0015286, DHRSX-related to Congenital disorder of glycosylation, type 1DD, MIM# 301133
Genetic Epilepsy v1.72 DHRSX Zornitza Stark edited their review of gene: DHRSX: Changed phenotypes: Congenital disorder of glycosylation, type 1DD, MIM# 301133
Mendeliome v1.2144 DHRSX Zornitza Stark Phenotypes for gene: DHRSX were changed from congenital disorder of glycosylation, MONDO:0015286 to Congenital disorder of glycosylation, type 1DD, MIM# 301133
Congenital Disorders of Glycosylation v1.56 DHRSX Zornitza Stark Phenotypes for gene: DHRSX were changed from congenital disorder of glycosylation, MONDO:0015286, DHRSX-related to Congenital disorder of glycosylation, type 1DD, MIM# 301133
Intellectual disability syndromic and non-syndromic v0.6817 IFT172 Zornitza Stark Marked gene: IFT172 as ready
Intellectual disability syndromic and non-syndromic v0.6817 IFT172 Zornitza Stark Gene: ift172 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6817 IFT172 Zornitza Stark Phenotypes for gene: IFT172 were changed from to Bardet-Biedl syndrome MONDO:0015229
Intellectual disability syndromic and non-syndromic v0.6816 IFT172 Zornitza Stark Publications for gene: IFT172 were set to
Intellectual disability syndromic and non-syndromic v0.6815 IFT172 Zornitza Stark Mode of inheritance for gene: IFT172 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6814 IFIH1 Zornitza Stark Marked gene: IFIH1 as ready
Intellectual disability syndromic and non-syndromic v0.6814 IFIH1 Zornitza Stark Gene: ifih1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6814 IFIH1 Zornitza Stark Phenotypes for gene: IFIH1 were changed from to IFIH1-related type 1 interferonopathy MONDO:0700262
Intellectual disability syndromic and non-syndromic v0.6813 IFIH1 Zornitza Stark Publications for gene: IFIH1 were set to
Intellectual disability syndromic and non-syndromic v0.6812 IFIH1 Zornitza Stark Mode of inheritance for gene: IFIH1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6811 IDUA Zornitza Stark Marked gene: IDUA as ready
Intellectual disability syndromic and non-syndromic v0.6811 IDUA Zornitza Stark Gene: idua has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6811 IDUA Zornitza Stark Phenotypes for gene: IDUA were changed from to mucopolysaccharidosis type 1 MONDO:0001586
Intellectual disability syndromic and non-syndromic v0.6810 IDUA Zornitza Stark Publications for gene: IDUA were set to 20301341
Intellectual disability syndromic and non-syndromic v0.6809 IDUA Zornitza Stark Publications for gene: IDUA were set to
Intellectual disability syndromic and non-syndromic v0.6808 IDUA Zornitza Stark Mode of inheritance for gene: IDUA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6807 IDS Zornitza Stark Marked gene: IDS as ready
Intellectual disability syndromic and non-syndromic v0.6807 IDS Zornitza Stark Gene: ids has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6807 IDS Zornitza Stark Phenotypes for gene: IDS were changed from to mucopolysaccharidosis type 2 MONDO:0010674
Intellectual disability syndromic and non-syndromic v0.6806 IDS Zornitza Stark Publications for gene: IDS were set to
Intellectual disability syndromic and non-syndromic v0.6805 IDS Zornitza Stark Mode of inheritance for gene: IDS was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.6804 IDH2 Zornitza Stark Marked gene: IDH2 as ready
Intellectual disability syndromic and non-syndromic v0.6804 IDH2 Zornitza Stark Gene: idh2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6804 IDH2 Zornitza Stark Phenotypes for gene: IDH2 were changed from to mitochondrial disease MONDO:0044970
Intellectual disability syndromic and non-syndromic v0.6803 IDH2 Zornitza Stark Publications for gene: IDH2 were set to
Intellectual disability syndromic and non-syndromic v0.6802 IDH2 Zornitza Stark Mode of inheritance for gene: IDH2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6801 HTRA2 Zornitza Stark Marked gene: HTRA2 as ready
Intellectual disability syndromic and non-syndromic v0.6801 HTRA2 Zornitza Stark Gene: htra2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6801 HTRA2 Zornitza Stark Phenotypes for gene: HTRA2 were changed from to 3-methylglutaconic aciduria type 8 MONDO:0044723
Intellectual disability syndromic and non-syndromic v0.6800 HTRA2 Zornitza Stark Publications for gene: HTRA2 were set to
Intellectual disability syndromic and non-syndromic v0.6799 HTRA2 Zornitza Stark Mode of inheritance for gene: HTRA2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6798 HSPD1 Zornitza Stark Marked gene: HSPD1 as ready
Intellectual disability syndromic and non-syndromic v0.6798 HSPD1 Zornitza Stark Gene: hspd1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6798 HSPD1 Zornitza Stark Phenotypes for gene: HSPD1 were changed from Leukodystrophy, hypomyelinating, 4, MIM# 612233 to Leukodystrophy, hypomyelinating, 4, MIM# 612233
Intellectual disability syndromic and non-syndromic v0.6797 HSPD1 Zornitza Stark Phenotypes for gene: HSPD1 were changed from Leukodystrophy, hypomyelinating, 4, MIM# 612233 to Leukodystrophy, hypomyelinating, 4, MIM# 612233
Intellectual disability syndromic and non-syndromic v0.6796 HSPD1 Zornitza Stark Phenotypes for gene: HSPD1 were changed from to Leukodystrophy, hypomyelinating, 4, MIM# 612233
Intellectual disability syndromic and non-syndromic v0.6795 HSPD1 Zornitza Stark Publications for gene: HSPD1 were set to
Intellectual disability syndromic and non-syndromic v0.6794 HSPD1 Zornitza Stark Mode of inheritance for gene: HSPD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6793 HSPD1 Zornitza Stark reviewed gene: HSPD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18571143, 27405012, 32532876, 28377887, 27405012, 11898127, 17420924; Phenotypes: Leukodystrophy, hypomyelinating, 4, MIM# 612233; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6793 HSD17B10 Zornitza Stark Phenotypes for gene: HSD17B10 were changed from HSD10 mitochondrial disease MONDO:0010327 to HSD10 mitochondrial disease MONDO:0010327
Intellectual disability syndromic and non-syndromic v0.6792 HSD17B10 Zornitza Stark Marked gene: HSD17B10 as ready
Intellectual disability syndromic and non-syndromic v0.6792 HSD17B10 Zornitza Stark Gene: hsd17b10 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6792 HSD17B10 Zornitza Stark Phenotypes for gene: HSD17B10 were changed from to HSD10 mitochondrial disease MONDO:0010327
Intellectual disability syndromic and non-syndromic v0.6791 HSD17B10 Zornitza Stark Publications for gene: HSD17B10 were set to
Intellectual disability syndromic and non-syndromic v0.6790 HSD17B10 Zornitza Stark Mode of inheritance for gene: HSD17B10 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.6789 HPRT1 Zornitza Stark Marked gene: HPRT1 as ready
Intellectual disability syndromic and non-syndromic v0.6789 HPRT1 Zornitza Stark Gene: hprt1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6789 HPRT1 Zornitza Stark Phenotypes for gene: HPRT1 were changed from to Lesch-Nyhan syndrome MONDO:0010298
Intellectual disability syndromic and non-syndromic v0.6788 HPRT1 Zornitza Stark Publications for gene: HPRT1 were set to
Intellectual disability syndromic and non-syndromic v0.6787 HPRT1 Zornitza Stark Mode of inheritance for gene: HPRT1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.6786 HPD Zornitza Stark Marked gene: HPD as ready
Intellectual disability syndromic and non-syndromic v0.6786 HPD Zornitza Stark Gene: hpd has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6786 HPD Zornitza Stark Phenotypes for gene: HPD were changed from to tyrosinemia type III MONDO:0010162
Intellectual disability syndromic and non-syndromic v0.6785 HPD Zornitza Stark Publications for gene: HPD were set to
Intellectual disability syndromic and non-syndromic v0.6784 HPD Zornitza Stark Mode of inheritance for gene: HPD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6783 HPD Zornitza Stark reviewed gene: HPD: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: tyrosinemia type III MONDO:0010162; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6783 HOXA1 Zornitza Stark Marked gene: HOXA1 as ready
Intellectual disability syndromic and non-syndromic v0.6783 HOXA1 Zornitza Stark Gene: hoxa1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6783 HOXA1 Zornitza Stark Mode of inheritance for gene: HOXA1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6782 HOXA1 Zornitza Stark Publications for gene: HOXA1 were set to
Intellectual disability syndromic and non-syndromic v0.6781 HOXA1 Zornitza Stark Phenotypes for gene: HOXA1 were changed from to Bosley-Salih-Alorainy syndrome, MIM#601536 and Athabaskan brainstem dysgenesis syndrome, MIM#601536
Intellectual disability syndromic and non-syndromic v0.6780 HNRNPK Zornitza Stark Marked gene: HNRNPK as ready
Intellectual disability syndromic and non-syndromic v0.6780 HNRNPK Zornitza Stark Gene: hnrnpk has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6780 HNRNPK Zornitza Stark Phenotypes for gene: HNRNPK were changed from to neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome (Au-Kline syndrome) MONDO:0018681
Intellectual disability syndromic and non-syndromic v0.6779 HNRNPK Zornitza Stark Publications for gene: HNRNPK were set to
Intellectual disability syndromic and non-syndromic v0.6778 HNRNPK Zornitza Stark Mode of inheritance for gene: HNRNPK was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Prepair 1000+ v1.547 FOXP3 Ee Ming Wong reviewed gene: FOXP3: Rating: GREEN; Mode of pathogenicity: None; Publications: 11295725, 11137993, 33668198, 33614561, 33330291, 32234571; Phenotypes: Immunodysregulation, polyendocrinopathy, and enteropathy, X-linked (MIM#304790); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Prepair 1000+ v1.547 FLVCR1 Ee Ming Wong reviewed gene: FLVCR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 39306721; Phenotypes: Neurodevelopmental disorder MONDO:0700092, FLVCR1-related, Ataxia, posterior column, with retinitis pigmentosa, MIM#609033; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6777 HMGCL Zornitza Stark Marked gene: HMGCL as ready
Intellectual disability syndromic and non-syndromic v0.6777 HMGCL Zornitza Stark Gene: hmgcl has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6777 HMGCL Zornitza Stark Phenotypes for gene: HMGCL were changed from to 3-hydroxy-3-methylglutaric aciduria MONDO:0009520
Intellectual disability syndromic and non-syndromic v0.6776 HMGCL Zornitza Stark Publications for gene: HMGCL were set to
Intellectual disability syndromic and non-syndromic v0.6775 HMGCL Zornitza Stark Mode of inheritance for gene: HMGCL was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6774 HLCS Zornitza Stark Marked gene: HLCS as ready
Intellectual disability syndromic and non-syndromic v0.6774 HLCS Zornitza Stark Gene: hlcs has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6774 HLCS Zornitza Stark Phenotypes for gene: HLCS were changed from to holocarboxylase synthetase deficiency MONDO:0009666
Intellectual disability syndromic and non-syndromic v0.6773 HLCS Zornitza Stark Publications for gene: HLCS were set to
Intellectual disability syndromic and non-syndromic v0.6772 HLCS Zornitza Stark Mode of inheritance for gene: HLCS was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6771 HLCS Zornitza Stark Mode of inheritance for gene: HLCS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.547 FKRP Ee Ming Wong reviewed gene: FKRP: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38277301; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 5 (MIM#613153), Muscular dystrophy-dystroglycanopathy (congenital with or without intellectual development), type B, 5 (MIM#606612), Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 5 (MIM#607155); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6770 HIBCH Zornitza Stark Marked gene: HIBCH as ready
Intellectual disability syndromic and non-syndromic v0.6770 HIBCH Zornitza Stark Gene: hibch has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6770 HIBCH Zornitza Stark Phenotypes for gene: HIBCH were changed from 3-hydroxyisobutyryl-CoA hydrolase deficiency MONDO:0009603; Leigh syndrome MONDO:0009723 to 3-hydroxyisobutyryl-CoA hydrolase deficiency MONDO:0009603; Leigh syndrome MONDO:0009723
Intellectual disability syndromic and non-syndromic v0.6769 HIBCH Zornitza Stark Phenotypes for gene: HIBCH were changed from to 3-hydroxyisobutyryl-CoA hydrolase deficiency MONDO:0009603; Leigh syndrome MONDO:0009723
Intellectual disability syndromic and non-syndromic v0.6768 HIBCH Zornitza Stark Publications for gene: HIBCH were set to
Intellectual disability syndromic and non-syndromic v0.6767 HIBCH Zornitza Stark Mode of inheritance for gene: HIBCH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6766 HEXB Zornitza Stark Marked gene: HEXB as ready
Intellectual disability syndromic and non-syndromic v0.6766 HEXB Zornitza Stark Gene: hexb has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6766 HEXB Zornitza Stark Phenotypes for gene: HEXB were changed from Sandhoff disease MONDO:0010006 to Sandhoff disease MONDO:0010006
Intellectual disability syndromic and non-syndromic v0.6765 HEXB Zornitza Stark Phenotypes for gene: HEXB were changed from to Sandhoff disease MONDO:0010006
Intellectual disability syndromic and non-syndromic v0.6764 HEXB Zornitza Stark Publications for gene: HEXB were set to 35420740
Intellectual disability syndromic and non-syndromic v0.6764 HEXB Zornitza Stark Publications for gene: HEXB were set to
Intellectual disability syndromic and non-syndromic v0.6763 HEXB Zornitza Stark Mode of inheritance for gene: HEXB was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6762 HEXB Zornitza Stark Mode of inheritance for gene: HEXB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6761 HEXA Zornitza Stark Marked gene: HEXA as ready
Intellectual disability syndromic and non-syndromic v0.6761 HEXA Zornitza Stark Gene: hexa has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6761 HEXA Zornitza Stark Phenotypes for gene: HEXA were changed from to Tay-Sachs disease MONDO:0010100
Intellectual disability syndromic and non-syndromic v0.6760 HEXA Zornitza Stark Publications for gene: HEXA were set to
Intellectual disability syndromic and non-syndromic v0.6759 HEXA Zornitza Stark Mode of inheritance for gene: HEXA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6758 HESX1 Zornitza Stark Phenotypes for gene: HESX1 were changed from septooptic dysplasia MONDO:0008428, Pituitary hormone deficiency, combined, 5 MONDO:0013099 to septooptic dysplasia MONDO:0008428, Pituitary hormone deficiency, combined, 5 MONDO:0013099
Intellectual disability syndromic and non-syndromic v0.6758 HESX1 Zornitza Stark Marked gene: HESX1 as ready
Intellectual disability syndromic and non-syndromic v0.6758 HESX1 Zornitza Stark Gene: hesx1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6758 HESX1 Zornitza Stark Phenotypes for gene: HESX1 were changed from to septooptic dysplasia MONDO:0008428, Pituitary hormone deficiency, combined, 5 MONDO:0013099
Intellectual disability syndromic and non-syndromic v0.6757 HESX1 Zornitza Stark Publications for gene: HESX1 were set to
Intellectual disability syndromic and non-syndromic v0.6756 HESX1 Zornitza Stark Mode of inheritance for gene: HESX1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6755 HESX1 Zornitza Stark reviewed gene: HESX1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: septooptic dysplasia MONDO:0008428, Pituitary hormone deficiency, combined, 5 MONDO:0013099; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6755 HEPACAM Zornitza Stark Marked gene: HEPACAM as ready
Intellectual disability syndromic and non-syndromic v0.6755 HEPACAM Zornitza Stark Gene: hepacam has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6755 HEPACAM Zornitza Stark Phenotypes for gene: HEPACAM were changed from to Megalencephalic leukoencephalopathy with subcortical cysts 2A MONDO:0013490; Megalencephalic leukoencephalopathy with subcortical cysts 2B, remitting, with or without intellectual disability MONDO:0013491
Intellectual disability syndromic and non-syndromic v0.6754 HEPACAM Zornitza Stark Publications for gene: HEPACAM were set to
Intellectual disability syndromic and non-syndromic v0.6753 HEPACAM Zornitza Stark Mode of inheritance for gene: HEPACAM 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 v0.6752 HCCS Zornitza Stark Marked gene: HCCS as ready
Intellectual disability syndromic and non-syndromic v0.6752 HCCS Zornitza Stark Gene: hccs has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6752 HCCS Zornitza Stark Phenotypes for gene: HCCS were changed from to linear skin defects with multiple congenital anomalies 1 (MONDO:0024552)
Intellectual disability syndromic and non-syndromic v0.6751 HCCS Zornitza Stark Publications for gene: HCCS were set to
Intellectual disability syndromic and non-syndromic v0.6750 HCCS Zornitza Stark Mode of inheritance for gene: HCCS was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.6749 HCCS Zornitza Stark reviewed gene: HCCS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: linear skin defects with multiple congenital anomalies 1 (MONDO:0024552); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.6749 GTF2H5 Zornitza Stark Marked gene: GTF2H5 as ready
Intellectual disability syndromic and non-syndromic v0.6749 GTF2H5 Zornitza Stark Gene: gtf2h5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6749 GTF2H5 Zornitza Stark Phenotypes for gene: GTF2H5 were changed from to Trichothiodystrophy 3, photosensitive MIM#616395
Intellectual disability syndromic and non-syndromic v0.6748 GTF2H5 Zornitza Stark Publications for gene: GTF2H5 were set to
Intellectual disability syndromic and non-syndromic v0.6747 GTF2H5 Zornitza Stark Mode of inheritance for gene: GTF2H5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6746 GTF2H5 Zornitza Stark reviewed gene: GTF2H5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Trichothiodystrophy 3, photosensitive MIM#616395; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6746 GRM1 Zornitza Stark Marked gene: GRM1 as ready
Intellectual disability syndromic and non-syndromic v0.6746 GRM1 Zornitza Stark Gene: grm1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6746 GRM1 Zornitza Stark Phenotypes for gene: GRM1 were changed from to autosomal recessive spinocerebellar ataxia 13 MONDO:0013905
Intellectual disability syndromic and non-syndromic v0.6745 GRM1 Zornitza Stark Publications for gene: GRM1 were set to
Intellectual disability syndromic and non-syndromic v0.6744 GRM1 Zornitza Stark Mode of inheritance for gene: GRM1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6743 GRM1 Zornitza Stark reviewed gene: GRM1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: autosomal recessive spinocerebellar ataxia 13 MONDO:0013905; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6743 GPC3 Zornitza Stark Marked gene: GPC3 as ready
Intellectual disability syndromic and non-syndromic v0.6743 GPC3 Zornitza Stark Gene: gpc3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6743 GPC3 Zornitza Stark Phenotypes for gene: GPC3 were changed from to Simpson-Golabi-Behmel syndrome MONDO:0010731
Intellectual disability syndromic and non-syndromic v0.6742 GPC3 Zornitza Stark Publications for gene: GPC3 were set to
Intellectual disability syndromic and non-syndromic v0.6741 GPC3 Zornitza Stark Mode of inheritance for gene: GPC3 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.6740 GNS Zornitza Stark Marked gene: GNS as ready
Intellectual disability syndromic and non-syndromic v0.6740 GNS Zornitza Stark Gene: gns has been classified as Green List (High Evidence).
Prepair 1000+ v1.547 FARS2 Ee Ming Wong reviewed gene: FARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30869852; Phenotypes: Combined oxidative phosphorylation deficiency 14 (MIM#614946), Spastic paraplegia 77 (MIM#617046); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6740 GNS Zornitza Stark Phenotypes for gene: GNS were changed from to mucopolysaccharidosis type 3D MONDO:0009658
Intellectual disability syndromic and non-syndromic v0.6739 GNS Zornitza Stark Publications for gene: GNS were set to
Intellectual disability syndromic and non-syndromic v0.6738 GNS Zornitza Stark Mode of inheritance for gene: GNS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.547 F7 Ee Ming Wong reviewed gene: F7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Factor VII deficiency, MIM# 227500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6737 GNPTAB Zornitza Stark Marked gene: GNPTAB as ready
Intellectual disability syndromic and non-syndromic v0.6737 GNPTAB Zornitza Stark Gene: gnptab has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6737 GNPTAB Zornitza Stark Phenotypes for gene: GNPTAB were changed from to GNPTAB-mucolipidosis MONDO:0100122
Intellectual disability syndromic and non-syndromic v0.6736 GNPTAB Zornitza Stark Publications for gene: GNPTAB were set to
Intellectual disability syndromic and non-syndromic v0.6735 GNPTAB Zornitza Stark Mode of inheritance for gene: GNPTAB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6734 GNPAT Zornitza Stark Marked gene: GNPAT as ready
Intellectual disability syndromic and non-syndromic v0.6734 GNPAT Zornitza Stark Gene: gnpat has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6734 GNPAT Zornitza Stark Phenotypes for gene: GNPAT were changed from to glyceronephosphate O-acyltransferase deficiency MONDO:0100273
Intellectual disability syndromic and non-syndromic v0.6733 GNPAT Zornitza Stark Publications for gene: GNPAT were set to
Intellectual disability syndromic and non-syndromic v0.6732 GNPAT Zornitza Stark Mode of inheritance for gene: GNPAT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6731 GMPPB Zornitza Stark Marked gene: GMPPB as ready
Intellectual disability syndromic and non-syndromic v0.6731 GMPPB Zornitza Stark Gene: gmppb has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6731 GMPPB Zornitza Stark Phenotypes for gene: GMPPB were changed from to myopathy caused by variation in GMPPB MONDO:0700084
Intellectual disability syndromic and non-syndromic v0.6730 GMPPB Zornitza Stark Publications for gene: GMPPB were set to
Intellectual disability syndromic and non-syndromic v0.6729 GMPPB Zornitza Stark Mode of inheritance for gene: GMPPB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6728 GMPPA Zornitza Stark Marked gene: GMPPA as ready
Intellectual disability syndromic and non-syndromic v0.6728 GMPPA Zornitza Stark Gene: gmppa has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6728 GMPPA Zornitza Stark Phenotypes for gene: GMPPA were changed from to alacrima, achalasia, and intellectual disability syndrome MONDO:0014219
Intellectual disability syndromic and non-syndromic v0.6727 GMPPA Zornitza Stark Publications for gene: GMPPA were set to
Intellectual disability syndromic and non-syndromic v0.6726 GMPPA Zornitza Stark Mode of inheritance for gene: GMPPA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6725 GM2A Zornitza Stark Marked gene: GM2A as ready
Intellectual disability syndromic and non-syndromic v0.6725 GM2A Zornitza Stark Gene: gm2a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6725 GM2A Zornitza Stark Phenotypes for gene: GM2A were changed from to Tay-Sachs disease AB variant MONDO:0010099
Intellectual disability syndromic and non-syndromic v0.6724 GM2A Zornitza Stark Publications for gene: GM2A were set to
Intellectual disability syndromic and non-syndromic v0.6723 GM2A Zornitza Stark Mode of inheritance for gene: GM2A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6722 PSPH Ain Roesley Marked gene: PSPH as ready
Intellectual disability syndromic and non-syndromic v0.6722 PSPH Ain Roesley Gene: psph has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6722 PSPH Ain Roesley Phenotypes for gene: PSPH were changed from Phosphoserine phosphatase deficiency MIM#614023 to Phosphoserine phosphatase deficiency MIM#614023
Intellectual disability syndromic and non-syndromic v0.6722 PSPH Ain Roesley Phenotypes for gene: PSPH were changed from to Phosphoserine phosphatase deficiency MIM#614023
Intellectual disability syndromic and non-syndromic v0.6721 PSPH Ain Roesley Publications for gene: PSPH were set to
Intellectual disability syndromic and non-syndromic v0.6721 PSPH Ain Roesley Mode of inheritance for gene: PSPH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6720 PSPH Ain Roesley reviewed gene: PSPH: Rating: GREEN; Mode of pathogenicity: None; Publications: 37347880; Phenotypes: Phosphoserine phosphatase deficiency MIM#614023; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6720 PRPS1 Ain Roesley Phenotypes for gene: PRPS1 were changed from PRPS1 deficiency disorder MONDO:0100061 to PRPS1 deficiency disorder MONDO:0100061
Intellectual disability syndromic and non-syndromic v0.6720 PRPS1 Ain Roesley Publications for gene: PRPS1 were set to 24961627
Intellectual disability syndromic and non-syndromic v0.6719 PRPS1 Ain Roesley Marked gene: PRPS1 as ready
Intellectual disability syndromic and non-syndromic v0.6719 PRPS1 Ain Roesley Gene: prps1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6719 PRPS1 Ain Roesley Phenotypes for gene: PRPS1 were changed from to PRPS1 deficiency disorder MONDO:0100061
Intellectual disability syndromic and non-syndromic v0.6719 PRPS1 Ain Roesley Publications for gene: PRPS1 were set to
Intellectual disability syndromic and non-syndromic v0.6719 PRPS1 Ain Roesley Mode of inheritance for gene: PRPS1 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.6718 PRPS1 Ain Roesley reviewed gene: PRPS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24961627; Phenotypes: PRPS1 deficiency disorder MONDO:0100061; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males); Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6718 PRODH Ain Roesley Mode of inheritance for gene: PRODH was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6718 PRODH Ain Roesley Marked gene: PRODH as ready
Intellectual disability syndromic and non-syndromic v0.6718 PRODH Ain Roesley Gene: prodh has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6718 PRODH Ain Roesley Mode of inheritance for gene: PRODH was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6718 PRODH Ain Roesley Publications for gene: PRODH were set to 17412540; 12217952
Intellectual disability syndromic and non-syndromic v0.6717 PRODH Ain Roesley Mode of inheritance for gene: PRODH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6717 PRODH Ain Roesley Publications for gene: PRODH were set to
Intellectual disability syndromic and non-syndromic v0.6717 PRODH Ain Roesley Phenotypes for gene: PRODH were changed from to Hyperprolinemia, type I MIM#239500
Intellectual disability syndromic and non-syndromic v0.6716 PRODH Ain Roesley reviewed gene: PRODH: Rating: GREEN; Mode of pathogenicity: None; Publications: 17412540, 12217952; Phenotypes: Hyperprolinemia, type I MIM#239500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6716 PPT1 Ain Roesley Phenotypes for gene: PPT1 were changed from Ceroid lipofuscinosis, neuronal, 1 MIM#256730 to Ceroid lipofuscinosis, neuronal, 1 MIM#256730
Intellectual disability syndromic and non-syndromic v0.6716 PPT1 Ain Roesley Mode of inheritance for gene: PPT1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6715 PPT1 Ain Roesley Marked gene: PPT1 as ready
Intellectual disability syndromic and non-syndromic v0.6715 PPT1 Ain Roesley Gene: ppt1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6715 PPT1 Ain Roesley Phenotypes for gene: PPT1 were changed from to Ceroid lipofuscinosis, neuronal, 1 MIM#256730
Intellectual disability syndromic and non-syndromic v0.6715 PPT1 Ain Roesley Mode of inheritance for gene: PPT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6715 PPT1 Ain Roesley Publications for gene: PPT1 were set to
Intellectual disability syndromic and non-syndromic v0.6714 PPT1 Ain Roesley reviewed gene: PPT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 7637805, 9425237, 9664077; Phenotypes: Ceroid lipofuscinosis, neuronal, 1 MIM#256730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6714 FTSJ1 Zornitza Stark Marked gene: FTSJ1 as ready
Intellectual disability syndromic and non-syndromic v0.6714 FTSJ1 Zornitza Stark Gene: ftsj1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6714 FTSJ1 Zornitza Stark Phenotypes for gene: FTSJ1 were changed from Intellectual developmental disorder, X-linked 9, MIM# 309549 to Intellectual developmental disorder, X-linked 9, MIM# 309549; X-linked complex neurodevelopmental disorder MONDO:0100148
Intellectual disability syndromic and non-syndromic v0.6713 FTSJ1 Zornitza Stark Phenotypes for gene: FTSJ1 were changed from to Intellectual developmental disorder, X-linked 9, MIM# 309549
Intellectual disability syndromic and non-syndromic v0.6712 FTSJ1 Zornitza Stark Publications for gene: FTSJ1 were set to
Intellectual disability syndromic and non-syndromic v0.6711 FTSJ1 Zornitza Stark Mode of inheritance for gene: FTSJ1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.6710 PPP3CA Ain Roesley Marked gene: PPP3CA as ready
Intellectual disability syndromic and non-syndromic v0.6710 PPP3CA Ain Roesley Gene: ppp3ca has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6710 PPP3CA Ain Roesley Publications for gene: PPP3CA were set to
Intellectual disability syndromic and non-syndromic v0.6710 PPP3CA Ain Roesley Phenotypes for gene: PPP3CA were changed from to Arthrogryposis, cleft palate, craniosynostosis, and impaired intellectual development MIM#618265; Developmental and epileptic encephalopathy 91 MIM617711
Intellectual disability syndromic and non-syndromic v0.6710 PPP3CA Ain Roesley Mode of inheritance for gene: PPP3CA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6709 PPP3CA Ain Roesley reviewed gene: PPP3CA: Rating: GREEN; Mode of pathogenicity: None; Publications: 29432562, 32593294; Phenotypes: Arthrogryposis, cleft palate, craniosynostosis, and impaired intellectual development MIM#618265, Developmental and epileptic encephalopathy 91 MIM617711; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6709 POMT2 Ain Roesley Marked gene: POMT2 as ready
Intellectual disability syndromic and non-syndromic v0.6709 POMT2 Ain Roesley Gene: pomt2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6709 POMT2 Ain Roesley Phenotypes for gene: POMT2 were changed from myopathy caused by variation in POMT2 MONDO:0700071 to myopathy caused by variation in POMT2 MONDO:0700071
Intellectual disability syndromic and non-syndromic v0.6708 POMT2 Ain Roesley Phenotypes for gene: POMT2 were changed from to myopathy caused by variation in POMT2 MONDO:0700071
Intellectual disability syndromic and non-syndromic v0.6708 POMT2 Ain Roesley Mode of inheritance for gene: POMT2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6707 POMT1 Ain Roesley Marked gene: POMT1 as ready
Intellectual disability syndromic and non-syndromic v0.6707 POMT1 Ain Roesley Gene: pomt1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6707 POMT2 Ain Roesley reviewed gene: POMT2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: myopathy caused by variation in POMT2 MONDO:0700071; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6707 POMT1 Ain Roesley Phenotypes for gene: POMT1 were changed from to myopathy caused by variation in POMT1 MONDO:0700070
Intellectual disability syndromic and non-syndromic v0.6707 POMT1 Ain Roesley Mode of inheritance for gene: POMT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6706 POMT1 Ain Roesley reviewed gene: POMT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: myopathy caused by variation in POMT1 MONDO:0700070; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6706 POMGNT2 Ain Roesley Marked gene: POMGNT2 as ready
Intellectual disability syndromic and non-syndromic v0.6706 POMGNT2 Ain Roesley Gene: pomgnt2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6706 POMGNT2 Ain Roesley Phenotypes for gene: POMGNT2 were changed from to myopathy caused by variation in POMGNT2 MONDO:0700069
Intellectual disability syndromic and non-syndromic v0.6706 POMGNT2 Ain Roesley Mode of inheritance for gene: POMGNT2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6705 POMGNT2 Ain Roesley reviewed gene: POMGNT2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: myopathy caused by variation in POMGNT2 MONDO:0700069; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6705 POMGNT1 Ain Roesley Marked gene: POMGNT1 as ready
Intellectual disability syndromic and non-syndromic v0.6705 POMGNT1 Ain Roesley Gene: pomgnt1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6705 POMGNT1 Ain Roesley Phenotypes for gene: POMGNT1 were changed from myopathy caused by variation in POMGNT1 MONDO:0700068 to myopathy caused by variation in POMGNT1 MONDO:0700068
Intellectual disability syndromic and non-syndromic v0.6705 POMGNT1 Ain Roesley Mode of inheritance for gene: POMGNT1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6704 POMGNT1 Ain Roesley Phenotypes for gene: POMGNT1 were changed from myopathy caused by variation in POMGNT1 MONDO:0700068 to myopathy caused by variation in POMGNT1 MONDO:0700068
Intellectual disability syndromic and non-syndromic v0.6704 POMGNT1 Ain Roesley Mode of inheritance for gene: POMGNT1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6704 POMGNT1 Ain Roesley Phenotypes for gene: POMGNT1 were changed from to myopathy caused by variation in POMGNT1 MONDO:0700068
Intellectual disability syndromic and non-syndromic v0.6704 POMGNT1 Ain Roesley Mode of inheritance for gene: POMGNT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6703 POMGNT1 Ain Roesley changed review comment from: DD/ID is a feature

the following has been lumped by clingen as one entity

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 3 MIM#253280
Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 3 MIM#613151
Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 3 MIM#613157; to: DD/ID is a feature

the following has been lumped by clingen as one entity

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 3 MIM#253280
Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 3 MIM#613151
Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 3 MIM#613157

https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_03bb8479-2ed3-4b15-9e54-378ea0729ab2-2024-08-14T190000.000Z?page=1&size=25&search=
Intellectual disability syndromic and non-syndromic v0.6703 POMGNT1 Ain Roesley reviewed gene: POMGNT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: myopathy caused by variation in POMGNT1 MONDO:0700068; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6703 POLR3B Ain Roesley Marked gene: POLR3B as ready
Intellectual disability syndromic and non-syndromic v0.6703 POLR3B Ain Roesley Gene: polr3b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6703 POLR3B Ain Roesley Mode of inheritance for gene: POLR3B was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6702 POLR3B Ain Roesley Mode of inheritance for gene: POLR3B was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6702 POLR3K Ain Roesley Marked gene: POLR3K as ready
Intellectual disability syndromic and non-syndromic v0.6702 POLR3K Ain Roesley Gene: polr3k has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6702 POLR3B Ain Roesley Phenotypes for gene: POLR3B were changed from to POLR3B-related disorder MONDO:0700277; Charcot-Marie-Tooth disease, demyelinating, type 1I MIM#619742; Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism MIM#614381
Intellectual disability syndromic and non-syndromic v0.6702 POLR3B Ain Roesley Publications for gene: POLR3B were set to
Intellectual disability syndromic and non-syndromic v0.6701 POLR3B Ain Roesley reviewed gene: POLR3B: Rating: GREEN; Mode of pathogenicity: None; Publications: 33417887; Phenotypes: POLR3B-related disorder MONDO:0700277, Charcot-Marie-Tooth disease, demyelinating, type 1I MIM#619742, Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism MIM#614381; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Disorders of immune dysregulation v0.197 PDCD1 Zornitza Stark Phenotypes for gene: PDCD1 were changed from Autoimmune disease with susceptibility to mycobacterium tuberculosis, MIM# 621004 to Autoimmune disease with susceptibility to mycobacterium tuberculosis, MIM# 621004
Intellectual disability syndromic and non-syndromic v0.6701 POLR3A Ain Roesley Marked gene: POLR3A as ready
Intellectual disability syndromic and non-syndromic v0.6701 POLR3A Ain Roesley Gene: polr3a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6701 POLR3A Ain Roesley Phenotypes for gene: POLR3A were changed from POLR3A-related disorder MONDO:0700276 to POLR3A-related disorder MONDO:0700276
Disorders of immune dysregulation v0.196 PDCD1 Zornitza Stark Phenotypes for gene: PDCD1 were changed from Complex Autoimmunity; Inborn errors of immunity, MONDO:0003778 to Autoimmune disease with susceptibility to mycobacterium tuberculosis, MIM# 621004
Intellectual disability syndromic and non-syndromic v0.6700 POLR3A Ain Roesley Phenotypes for gene: POLR3A were changed from to POLR3A-related disorder MONDO:0700276
Intellectual disability syndromic and non-syndromic v0.6700 POLR3A Ain Roesley Mode of inheritance for gene: POLR3A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2143 PDCD1 Zornitza Stark Phenotypes for gene: PDCD1 were changed from PDCD1 deficiency; Inborn errors of immunity, MONDO:0003778 to Autoimmune disease with susceptibility to mycobacterium tuberculosis, MIM# 621004
Intellectual disability syndromic and non-syndromic v0.6699 POLR3A Ain Roesley reviewed gene: POLR3A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: POLR3A-related disorder MONDO:0700276; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6699 POLG Ain Roesley Phenotypes for gene: POLG were changed from Mitochondrial DNA depletion syndrome 4A (Alpers type) MIM#203700; Mitochondrial DNA depletion syndrome 4B (MNGIE type) MIM#613662; Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE) MIM#607459; Progressive external ophthalmoplegia, autosomal recessive 1 MIM#258450; Progressive external ophthalmoplegia, autosomal dominant 1, MIM# 157640 to Mitochondrial DNA depletion syndrome 4A (Alpers type) MIM#203700; Mitochondrial DNA depletion syndrome 4B (MNGIE type) MIM#613662; Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE) MIM#607459; Progressive external ophthalmoplegia, autosomal recessive 1 MIM#258450; Progressive external ophthalmoplegia, autosomal dominant 1, MIM# 157640
Intellectual disability syndromic and non-syndromic v0.6699 POLG Ain Roesley Marked gene: POLG as ready
Intellectual disability syndromic and non-syndromic v0.6699 POLG Ain Roesley Gene: polg has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6699 POLG Ain Roesley Publications for gene: POLG were set to 20301791
Intellectual disability syndromic and non-syndromic v0.6698 POLG Ain Roesley Publications for gene: POLG were set to 20301791
Intellectual disability syndromic and non-syndromic v0.6698 POLG Ain Roesley Publications for gene: POLG were set to
Intellectual disability syndromic and non-syndromic v0.6698 POLG Ain Roesley Phenotypes for gene: POLG were changed from to Mitochondrial DNA depletion syndrome 4A (Alpers type) MIM#203700; Mitochondrial DNA depletion syndrome 4B (MNGIE type) MIM#613662; Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE) MIM#607459; Progressive external ophthalmoplegia, autosomal recessive 1 MIM#258450; Progressive external ophthalmoplegia, autosomal dominant 1, MIM# 157640
Intellectual disability syndromic and non-syndromic v0.6698 POLG Ain Roesley Mode of inheritance for gene: POLG was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6697 POLG Ain Roesley reviewed gene: POLG: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301791; Phenotypes: Mitochondrial DNA depletion syndrome 4A (Alpers type) MIM#203700, Mitochondrial DNA depletion syndrome 4B (MNGIE type) MIM#613662, Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE) MIM#607459, Progressive external ophthalmoplegia, autosomal recessive 1 MIM#258450, Progressive external ophthalmoplegia, autosomal dominant 1, MIM# 157640; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6697 PNPLA6 Ain Roesley Publications for gene: PNPLA6 were set to 25299038
Intellectual disability syndromic and non-syndromic v0.6697 PNPLA6 Ain Roesley Phenotypes for gene: PNPLA6 were changed from retinal dystrophy-ataxia-pituitary hormone abnormality-hypogonadism syndrome MONDO:0100155 to retinal dystrophy-ataxia-pituitary hormone abnormality-hypogonadism syndrome MONDO:0100155
Intellectual disability syndromic and non-syndromic v0.6697 PNPLA6 Ain Roesley Phenotypes for gene: PNPLA6 were changed from retinal dystrophy-ataxia-pituitary hormone abnormality-hypogonadism syndrome MONDO:0100155 to retinal dystrophy-ataxia-pituitary hormone abnormality-hypogonadism syndrome MONDO:0100155
Intellectual disability syndromic and non-syndromic v0.6696 PNPLA6 Ain Roesley Mode of inheritance for gene: PNPLA6 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6696 PNPLA6 Ain Roesley Marked gene: PNPLA6 as ready
Intellectual disability syndromic and non-syndromic v0.6696 PNPLA6 Ain Roesley Gene: pnpla6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6696 PNPLA6 Ain Roesley Phenotypes for gene: PNPLA6 were changed from to retinal dystrophy-ataxia-pituitary hormone abnormality-hypogonadism syndrome MONDO:0100155
Intellectual disability syndromic and non-syndromic v0.6696 PNPLA6 Ain Roesley Publications for gene: PNPLA6 were set to
Intellectual disability syndromic and non-syndromic v0.6696 PNPLA6 Ain Roesley Mode of inheritance for gene: PNPLA6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6695 PNPLA6 Ain Roesley reviewed gene: PNPLA6: Rating: GREEN; Mode of pathogenicity: None; Publications: 25299038; Phenotypes: retinal dystrophy-ataxia-pituitary hormone abnormality-hypogonadism syndrome MONDO:0100155; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6695 PMM2 Ain Roesley Mode of inheritance for gene: PMM2 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6695 PMM2 Ain Roesley Publications for gene: PMM2 were set to 20301289
Intellectual disability syndromic and non-syndromic v0.6695 PMM2 Ain Roesley Phenotypes for gene: PMM2 were changed from Congenital disorder of glycosylation, type Ia MIM#212065 to Congenital disorder of glycosylation, type Ia MIM#212065
Intellectual disability syndromic and non-syndromic v0.6695 PMM2 Ain Roesley Mode of inheritance for gene: PMM2 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6695 PMM2 Ain Roesley Phenotypes for gene: PMM2 were changed from Congenital disorder of glycosylation, type Ia MIM#212065 to Congenital disorder of glycosylation, type Ia MIM#212065
Intellectual disability syndromic and non-syndromic v0.6695 PMM2 Ain Roesley Marked gene: PMM2 as ready
Intellectual disability syndromic and non-syndromic v0.6695 PMM2 Ain Roesley Gene: pmm2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6695 PMM2 Ain Roesley Mode of inheritance for gene: PMM2 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6694 PMM2 Ain Roesley Mode of inheritance for gene: PMM2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6694 PMM2 Ain Roesley Phenotypes for gene: PMM2 were changed from to Congenital disorder of glycosylation, type Ia MIM#212065
Intellectual disability syndromic and non-syndromic v0.6694 PMM2 Ain Roesley Publications for gene: PMM2 were set to
Intellectual disability syndromic and non-syndromic v0.6693 PLA2G6 Ain Roesley Phenotypes for gene: PLA2G6 were changed from Infantile neuroaxonal dystrophy 1 MIM#256600; Neurodegeneration with brain iron accumulation 2B MIM#610217 to Infantile neuroaxonal dystrophy 1 MIM#256600; Neurodegeneration with brain iron accumulation 2B MIM#610217
Intellectual disability syndromic and non-syndromic v0.6693 PLA2G6 Ain Roesley Publications for gene: PLA2G6 were set to 20301718
Intellectual disability syndromic and non-syndromic v0.6692 PLA2G6 Ain Roesley Marked gene: PLA2G6 as ready
Intellectual disability syndromic and non-syndromic v0.6692 PLA2G6 Ain Roesley Gene: pla2g6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6692 PLA2G6 Ain Roesley Phenotypes for gene: PLA2G6 were changed from to Infantile neuroaxonal dystrophy 1 MIM#256600; Neurodegeneration with brain iron accumulation 2B MIM#610217
Intellectual disability syndromic and non-syndromic v0.6692 PMM2 Ain Roesley reviewed gene: PMM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301289; Phenotypes: Congenital disorder of glycosylation, type Ia MIM#212065; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6692 PLA2G6 Ain Roesley Publications for gene: PLA2G6 were set to
Intellectual disability syndromic and non-syndromic v0.6692 PLA2G6 Ain Roesley Mode of inheritance for gene: PLA2G6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6691 PLA2G6 Ain Roesley reviewed gene: PLA2G6: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301718; Phenotypes: nfantile neuroaxonal dystrophy 1 MIM#256600, Neurodegeneration with brain iron accumulation 2B MIM#610217; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6691 PIK3CA Ain Roesley Marked gene: PIK3CA as ready
Intellectual disability syndromic and non-syndromic v0.6691 PIK3CA Ain Roesley Gene: pik3ca has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6691 PIK3CA Ain Roesley Phenotypes for gene: PIK3CA were changed from PIK3CA-related overgrowth spectrum MONDO:1040002 to PIK3CA-related overgrowth spectrum MONDO:1040002
Intellectual disability syndromic and non-syndromic v0.6691 PIK3CA Ain Roesley Publications for gene: PIK3CA were set to 23946963
Intellectual disability syndromic and non-syndromic v0.6691 PIK3CA Ain Roesley Phenotypes for gene: PIK3CA were changed from PIK3CA-related overgrowth spectrum MONDO:1040002 to PIK3CA-related overgrowth spectrum MONDO:1040002
Intellectual disability syndromic and non-syndromic v0.6690 PIK3CA Ain Roesley Phenotypes for gene: PIK3CA were changed from to PIK3CA-related overgrowth spectrum MONDO:1040002
Intellectual disability syndromic and non-syndromic v0.6690 PIK3CA Ain Roesley Publications for gene: PIK3CA were set to
Intellectual disability syndromic and non-syndromic v0.6690 PIK3CA Ain Roesley Mode of inheritance for gene: PIK3CA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6689 PIK3CA Ain Roesley reviewed gene: PIK3CA: Rating: GREEN; Mode of pathogenicity: None; Publications: 23946963; Phenotypes: PIK3CA-related overgrowth spectrum MONDO:1040002; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6689 PHGDH Ain Roesley Phenotypes for gene: PHGDH were changed from Neu-Laxova syndrome 1 MIM#256520; Phosphoglycerate dehydrogenase deficiency MIM#601815 to Neu-Laxova syndrome 1 MIM#256520; Phosphoglycerate dehydrogenase deficiency MIM#601815
Intellectual disability syndromic and non-syndromic v0.6688 PHGDH Ain Roesley Marked gene: PHGDH as ready
Intellectual disability syndromic and non-syndromic v0.6688 PHGDH Ain Roesley Gene: phgdh has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6689 PHGDH Ain Roesley Publications for gene: PHGDH were set to 37347880
Intellectual disability syndromic and non-syndromic v0.6688 PHGDH Ain Roesley Phenotypes for gene: PHGDH were changed from to Neu-Laxova syndrome 1 MIM#256520; Phosphoglycerate dehydrogenase deficiency MIM#601815
Intellectual disability syndromic and non-syndromic v0.6688 PHGDH Ain Roesley Publications for gene: PHGDH were set to
Intellectual disability syndromic and non-syndromic v0.6688 PHGDH Ain Roesley Mode of inheritance for gene: PHGDH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6687 PHGDH Ain Roesley reviewed gene: PHGDH: Rating: GREEN; Mode of pathogenicity: None; Publications: 37347880; Phenotypes: Neu-Laxova syndrome 1 MIM#256520, Phosphoglycerate dehydrogenase deficiency MIM#601815; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6687 PEX7 Ain Roesley Phenotypes for gene: PEX7 were changed from Peroxisome biogenesis disorder 9B MIM#614879; Rhizomelic chondrodysplasia punctata, type 1 MIM#215100 to Peroxisome biogenesis disorder 9B MIM#614879; Rhizomelic chondrodysplasia punctata, type 1 MIM#215100
Intellectual disability syndromic and non-syndromic v0.6687 PEX7 Ain Roesley Publications for gene: PEX7 were set to 20301447
Intellectual disability syndromic and non-syndromic v0.6686 PEX7 Ain Roesley Marked gene: PEX7 as ready
Intellectual disability syndromic and non-syndromic v0.6686 PEX7 Ain Roesley Gene: pex7 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6686 PEX7 Ain Roesley Phenotypes for gene: PEX7 were changed from to Peroxisome biogenesis disorder 9B MIM#614879; Rhizomelic chondrodysplasia punctata, type 1 MIM#215100
Intellectual disability syndromic and non-syndromic v0.6686 PEX7 Ain Roesley Publications for gene: PEX7 were set to
Intellectual disability syndromic and non-syndromic v0.6686 PEX7 Ain Roesley Mode of inheritance for gene: PEX7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6685 PEX7 Ain Roesley reviewed gene: PEX7: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301447; Phenotypes: Peroxisome biogenesis disorder 9B MIM#614879, Rhizomelic chondrodysplasia punctata, type 1 MIM#215100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6685 PEX6 Ain Roesley Marked gene: PEX6 as ready
Intellectual disability syndromic and non-syndromic v0.6685 PEX6 Ain Roesley Gene: pex6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6685 PEX6 Ain Roesley Publications for gene: PEX6 were set to
Intellectual disability syndromic and non-syndromic v0.6684 PEX6 Ain Roesley Phenotypes for gene: PEX6 were changed from to Peroxisome biogenesis disorder 4A (Zellweger) MIM#614862; Peroxisome biogenesis disorder 4B MIM#614863
Intellectual disability syndromic and non-syndromic v0.6684 PEX6 Ain Roesley edited their review of gene: PEX6: Changed publications: 29220678, 20301621
Intellectual disability syndromic and non-syndromic v0.6684 PEX6 Ain Roesley Mode of inheritance for gene: PEX6 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6683 PEX6 Ain Roesley edited their review of gene: PEX6: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6683 PEX6 Ain Roesley edited their review of gene: PEX6: Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6683 PEX5 Ain Roesley Phenotypes for gene: PEX5 were changed from Peroxisome biogenesis disorder 2A (Zellweger) MIM#214110; Peroxisome biogenesis disorder 2B MIM#202370 to Peroxisome biogenesis disorder 2A (Zellweger) MIM#214110; Peroxisome biogenesis disorder 2B MIM#202370
Intellectual disability syndromic and non-syndromic v0.6683 PEX5 Ain Roesley Marked gene: PEX5 as ready
Intellectual disability syndromic and non-syndromic v0.6683 PEX5 Ain Roesley Gene: pex5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6683 PEX6 Ain Roesley reviewed gene: PEX6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 4A (Zellweger) MIM#614862, Peroxisome biogenesis disorder 4B MIM#614863; Mode of inheritance: None; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6683 PEX5 Ain Roesley Mode of inheritance for gene: PEX5 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6683 PEX5 Ain Roesley Publications for gene: PEX5 were set to 20301621
Intellectual disability syndromic and non-syndromic v0.6682 PEX5 Ain Roesley Publications for gene: PEX5 were set to
Intellectual disability syndromic and non-syndromic v0.6682 PEX5 Ain Roesley Phenotypes for gene: PEX5 were changed from to Peroxisome biogenesis disorder 2A (Zellweger) MIM#214110; Peroxisome biogenesis disorder 2B MIM#202370
Intellectual disability syndromic and non-syndromic v0.6682 PEX5 Ain Roesley Mode of inheritance for gene: PEX5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6682 PEX3 Ain Roesley Marked gene: PEX3 as ready
Intellectual disability syndromic and non-syndromic v0.6682 PEX3 Ain Roesley Gene: pex3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6682 PEX3 Ain Roesley Phenotypes for gene: PEX3 were changed from Peroxisome biogenesis disorder 10A (Zellweger), MIM# 614882; Peroxisome biogenesis disorder 10B , MIM# 617370 to Peroxisome biogenesis disorder 10A (Zellweger), MIM# 614882; Peroxisome biogenesis disorder 10B , MIM# 617370
Intellectual disability syndromic and non-syndromic v0.6681 PEX3 Ain Roesley Phenotypes for gene: PEX3 were changed from to Peroxisome biogenesis disorder 10A (Zellweger), MIM# 614882; Peroxisome biogenesis disorder 10B , MIM# 617370
Intellectual disability syndromic and non-syndromic v0.6681 PEX5 Ain Roesley reviewed gene: PEX5: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301621; Phenotypes: Peroxisome biogenesis disorder 2A (Zellweger) MIM#214110, Peroxisome biogenesis disorder 2B MIM#202370; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6681 PEX3 Ain Roesley Publications for gene: PEX3 were set to
Intellectual disability syndromic and non-syndromic v0.6681 PEX3 Ain Roesley Mode of inheritance for gene: PEX3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6680 PEX26 Ain Roesley Marked gene: PEX26 as ready
Intellectual disability syndromic and non-syndromic v0.6680 PEX26 Ain Roesley Gene: pex26 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6680 PEX3 Ain Roesley reviewed gene: PEX3: Rating: GREEN; Mode of pathogenicity: None; Publications: 10942428, 10958759, 10968777, 27557811, 33101983, 20301621; Phenotypes: Peroxisome biogenesis disorder 10A (Zellweger), MIM# 614882, Peroxisome biogenesis disorder 10B , MIM# 617370; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6680 PEX26 Ain Roesley Phenotypes for gene: PEX26 were changed from Peroxisome biogenesis disorder 7A (Zellweger) MIM#614872; Peroxisome biogenesis disorder 7B MIM614873 to Peroxisome biogenesis disorder 7A (Zellweger) MIM#614872; Peroxisome biogenesis disorder 7B MIM614873
Intellectual disability syndromic and non-syndromic v0.6679 PEX26 Ain Roesley Phenotypes for gene: PEX26 were changed from to Peroxisome biogenesis disorder 7A (Zellweger) MIM#614872; Peroxisome biogenesis disorder 7B MIM614873
Intellectual disability syndromic and non-syndromic v0.6679 PEX26 Ain Roesley Mode of inheritance for gene: PEX26 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6679 PEX26 Ain Roesley Publications for gene: PEX26 were set to
Intellectual disability syndromic and non-syndromic v0.6678 PEX2 Ain Roesley Phenotypes for gene: PEX2 were changed from Peroxisome biogenesis disorder 5A (Zellweger) MIM#614866; Peroxisome biogenesis disorder 5B MIM#614867 to Peroxisome biogenesis disorder 5A (Zellweger) MIM#614866; Peroxisome biogenesis disorder 5B MIM#614867
Intellectual disability syndromic and non-syndromic v0.6678 PEX26 Ain Roesley Deleted their comment
Intellectual disability syndromic and non-syndromic v0.6678 PEX2 Ain Roesley Marked gene: PEX2 as ready
Intellectual disability syndromic and non-syndromic v0.6678 PEX2 Ain Roesley Gene: pex2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6678 PEX2 Ain Roesley Publications for gene: PEX2 were set to 20301621
Intellectual disability syndromic and non-syndromic v0.6677 PEX26 Ain Roesley commented on gene: PEX26: ID/DD is part of the Zellweger spectrum
Intellectual disability syndromic and non-syndromic v0.6677 PEX2 Ain Roesley Phenotypes for gene: PEX2 were changed from to Peroxisome biogenesis disorder 5A (Zellweger) MIM#614866; Peroxisome biogenesis disorder 5B MIM#614867
Intellectual disability syndromic and non-syndromic v0.6677 PEX2 Ain Roesley Publications for gene: PEX2 were set to
Intellectual disability syndromic and non-syndromic v0.6677 PEX26 Ain Roesley reviewed gene: PEX26: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301621; Phenotypes: Peroxisome biogenesis disorder 7A (Zellweger) MIM#614872, Peroxisome biogenesis disorder 7B MIM614873; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6677 PEX2 Ain Roesley Mode of inheritance for gene: PEX2 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6677 PEX2 Ain Roesley Mode of inheritance for gene: PEX2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6676 PEX2 Ain Roesley changed review comment from: Few individuals reported with variants in PEX19 however,; to: ID/DD is part of the Zellweger spectrum
Intellectual disability syndromic and non-syndromic v0.6676 PEX2 Ain Roesley commented on gene: PEX2: Few individuals reported with variants in PEX19 however,
Intellectual disability syndromic and non-syndromic v0.6676 PEX2 Ain Roesley reviewed gene: PEX2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301621; Phenotypes: Peroxisome biogenesis disorder 5A (Zellweger) MIM#614866, Peroxisome biogenesis disorder 5B MIM#614867; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6676 PEX19 Ain Roesley Marked gene: PEX19 as ready
Intellectual disability syndromic and non-syndromic v0.6676 PEX19 Ain Roesley Gene: pex19 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6676 PEX19 Ain Roesley Phenotypes for gene: PEX19 were changed from Peroxisome biogenesis disorder 12A (Zellweger) MIM#614886 to Peroxisome biogenesis disorder 12A (Zellweger) MIM#614886
Intellectual disability syndromic and non-syndromic v0.6675 PEX19 Ain Roesley Phenotypes for gene: PEX19 were changed from to Peroxisome biogenesis disorder 12A (Zellweger) MIM#614886
Intellectual disability syndromic and non-syndromic v0.6675 PEX19 Ain Roesley Publications for gene: PEX19 were set to
Intellectual disability syndromic and non-syndromic v0.6675 PEX19 Ain Roesley Mode of inheritance for gene: PEX19 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6674 PEX19 Ain Roesley reviewed gene: PEX19: Rating: GREEN; Mode of pathogenicity: None; Publications: 10051604, 20683989, 11883941, 28391327; Phenotypes: Peroxisome biogenesis disorder 12A (Zellweger) MIM#614886; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6674 PEX16 Ain Roesley Mode of inheritance for gene: PEX16 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6673 PEX16 Ain Roesley Marked gene: PEX16 as ready
Intellectual disability syndromic and non-syndromic v0.6673 PEX16 Ain Roesley Gene: pex16 has been classified as Green List (High Evidence).
Prepair 1000+ v1.547 ITCH Zornitza Stark Marked gene: ITCH as ready
Prepair 1000+ v1.547 ITCH Zornitza Stark Gene: itch has been classified as Green List (High Evidence).
Prepair 1000+ v1.547 ITCH Zornitza Stark Publications for gene: ITCH were set to
Intellectual disability syndromic and non-syndromic v0.6673 PEX16 Ain Roesley Mode of inheritance for gene: PEX16 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.546 ITCH Zornitza Stark reviewed gene: ITCH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Autoimmune disease, multisystem, with facial dysmorphism MIM#613385; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6673 PEX16 Ain Roesley Publications for gene: PEX16 were set to
Intellectual disability syndromic and non-syndromic v0.6673 PEX16 Ain Roesley Phenotypes for gene: PEX16 were changed from to Peroxisome biogenesis disorder 8A (Zellweger) MIM#614876; Peroxisome biogenesis disorder 8B MIM#614877
Intellectual disability syndromic and non-syndromic v0.6672 PEX16 Ain Roesley edited their review of gene: PEX16: Changed rating: GREEN
Intellectual disability syndromic and non-syndromic v0.6672 PEX14 Ain Roesley Publications for gene: PEX14 were set to 37493040; 20301621
Intellectual disability syndromic and non-syndromic v0.6672 PEX16 Ain Roesley reviewed gene: PEX16: Rating: ; Mode of pathogenicity: None; Publications: 20301621; Phenotypes: Peroxisome biogenesis disorder 8A (Zellweger) MIM#614876, Peroxisome biogenesis disorder 8B MIM#614877; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.546 ALS2 Lauren Thomas edited their review of gene: ALS2: Changed phenotypes: ALS2-related motor neuron disease (MONDO:0100227)
Intellectual disability syndromic and non-syndromic v0.6672 PEX14 Ain Roesley Phenotypes for gene: PEX14 were changed from Peroxisome biogenesis disorder 13A (Zellweger) MIM#614887; peroxisome biogenesis disorder due to PEX14 defect MONDO:0100268 to Peroxisome biogenesis disorder 13A (Zellweger) MIM#614887; peroxisome biogenesis disorder due to PEX14 defect MONDO:0100268
Intellectual disability syndromic and non-syndromic v0.6671 PEX14 Ain Roesley Phenotypes for gene: PEX14 were changed from to Peroxisome biogenesis disorder 13A (Zellweger) MIM#614887; peroxisome biogenesis disorder due to PEX14 defect MONDO:0100268
Intellectual disability syndromic and non-syndromic v0.6671 PEX14 Ain Roesley Publications for gene: PEX14 were set to
Intellectual disability syndromic and non-syndromic v0.6671 PEX14 Ain Roesley Mode of inheritance for gene: PEX14 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 v0.6670 PEX14 Ain Roesley reviewed gene: PEX14: Rating: GREEN; Mode of pathogenicity: None; Publications: 37493040, 20301621; Phenotypes: Peroxisome biogenesis disorder 13A (Zellweger) MIM#614887, peroxisome biogenesis disorder due to PEX14 defect MONDO:0100268; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.546 IMPG2 Zornitza Stark Tag for review tag was added to gene: IMPG2.
Intellectual disability syndromic and non-syndromic v0.6670 PEX13 Ain Roesley Mode of inheritance for gene: PEX13 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6669 PEX13 Ain Roesley Marked gene: PEX13 as ready
Intellectual disability syndromic and non-syndromic v0.6669 PEX13 Ain Roesley Gene: pex13 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6669 PEX13 Ain Roesley Mode of inheritance for gene: PEX13 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6669 PEX13 Ain Roesley Publications for gene: PEX13 were set to
Intellectual disability syndromic and non-syndromic v0.6669 PEX13 Ain Roesley Phenotypes for gene: PEX13 were changed from to Peroxisome biogenesis disorder 11A (Zellweger) MIM#614883; Peroxisome biogenesis disorder 11B MIM#614885
Intellectual disability syndromic and non-syndromic v0.6668 PEX13 Ain Roesley reviewed gene: PEX13: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301621; Phenotypes: Peroxisome biogenesis disorder 11A (Zellweger) MIM#614883, Peroxisome biogenesis disorder 11B MIM#614885; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6668 PEX12 Ain Roesley Phenotypes for gene: PEX12 were changed from Peroxisome biogenesis disorder 3A (Zellweger) MIM#614859; Peroxisome biogenesis disorder 3B MIM#266510 to Peroxisome biogenesis disorder 3A (Zellweger) MIM#614859; Peroxisome biogenesis disorder 3B MIM#266510
Intellectual disability syndromic and non-syndromic v0.6668 PEX12 Ain Roesley Marked gene: PEX12 as ready
Intellectual disability syndromic and non-syndromic v0.6668 PEX12 Ain Roesley Gene: pex12 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6668 PEX12 Ain Roesley Phenotypes for gene: PEX12 were changed from Peroxisome biogenesis disorder 3A (Zellweger) MIM#614859; Peroxisome biogenesis disorder 3B MIM#266510 to Peroxisome biogenesis disorder 3A (Zellweger) MIM#614859; Peroxisome biogenesis disorder 3B MIM#266510
Intellectual disability syndromic and non-syndromic v0.6667 PEX12 Ain Roesley Phenotypes for gene: PEX12 were changed from to Peroxisome biogenesis disorder 3A (Zellweger) MIM#614859; Peroxisome biogenesis disorder 3B MIM#266510
Intellectual disability syndromic and non-syndromic v0.6667 PEX12 Ain Roesley Publications for gene: PEX12 were set to
Intellectual disability syndromic and non-syndromic v0.6667 PEX12 Ain Roesley Mode of inheritance for gene: PEX12 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6666 PEX12 Ain Roesley reviewed gene: PEX12: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301621; Phenotypes: Peroxisome biogenesis disorder 3A (Zellweger) MIM#614859, Peroxisome biogenesis disorder 3B MIM#266510; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.546 FAM161A Lisa Norbart reviewed gene: FAM161A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Retinitis pigmentosa 28, MIM #606068; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.546 ARX Lisa Norbart reviewed gene: ARX: Rating: GREEN; Mode of pathogenicity: None; Publications: 14722918, 12379852, 19738637, 32519823, 28150386; Phenotypes: Developmental and epileptic encephalopathy 1, MIM#30835, Hydranencephaly with abnormal genitalia, MIM#300215, Intellectual developmental disorder, X-linked 29, MIM#300419, Lissencephaly, X-linked 2, MIM#300215, Partington syndrome, MIM#309510, Proud syndrome, MIM#300004; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2142 POMT1 Ain Roesley Phenotypes for gene: POMT1 were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1 236670; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 1 613155; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 1 609308 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1 236670; Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 1 613155; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 1 609308
Cerebellar and Pontocerebellar Hypoplasia v1.72 POMT1 Ain Roesley Phenotypes for gene: POMT1 were changed from 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) to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1 (MIM#236670); Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 1 (MIM#613155)
Congenital Disorders of Glycosylation v1.55 POMT1 Ain Roesley Phenotypes for gene: POMT1 were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1 236670; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 1 613155; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 1 609308 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1 236670; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 1 609308; Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 1 613155
Mendeliome v1.2141 SH3KBP1 Bryony Thompson Classified gene: SH3KBP1 as Amber List (moderate evidence)
Mendeliome v1.2141 SH3KBP1 Bryony Thompson Gene: sh3kbp1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2140 SH3KBP1 Bryony Thompson edited their review of gene: SH3KBP1: Changed phenotypes: immunodeficiency 61 MONDO:0010296
Predominantly Antibody Deficiency v0.149 SH3KBP1 Bryony Thompson edited their review of gene: SH3KBP1: Changed phenotypes: immunodeficiency 61 MONDO:0010296
Mendeliome v1.2140 SH3KBP1 Bryony Thompson reviewed gene: SH3KBP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 29636373, 21708930; Phenotypes: Immunodeficiency, common variable, 4 MONDO:0013284; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Predominantly Antibody Deficiency v0.149 SH3KBP1 Bryony Thompson Classified gene: SH3KBP1 as Amber List (moderate evidence)
Predominantly Antibody Deficiency v0.149 SH3KBP1 Bryony Thompson Gene: sh3kbp1 has been classified as Amber List (Moderate Evidence).
Predominantly Antibody Deficiency v0.148 SH3KBP1 Bryony Thompson reviewed gene: SH3KBP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 29636373, 21708930; Phenotypes: Immunodeficiency, common variable, 4 MONDO:0013284; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Predominantly Antibody Deficiency v0.148 PTEN Bryony Thompson Classified gene: PTEN as Green List (high evidence)
Predominantly Antibody Deficiency v0.148 PTEN Bryony Thompson Gene: pten has been classified as Green List (High Evidence).
Predominantly Antibody Deficiency v0.148 PTEN Bryony Thompson Classified gene: PTEN as Green List (high evidence)
Predominantly Antibody Deficiency v0.148 PTEN Bryony Thompson Gene: pten has been classified as Green List (High Evidence).
Predominantly Antibody Deficiency v0.147 PTEN Bryony Thompson Marked gene: PTEN as ready
Predominantly Antibody Deficiency v0.147 PTEN Bryony Thompson Gene: pten has been classified as Red List (Low Evidence).
Predominantly Antibody Deficiency v0.147 PTEN Bryony Thompson gene: PTEN was added
gene: PTEN was added to Predominantly Antibody Deficiency. 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 30504085; 33532886; 26246517
Phenotypes for gene: PTEN were set to PTEN hamartoma tumor syndrome MONDO:0017623
Review for gene: PTEN was set to GREEN
gene: PTEN was marked as current diagnostic
Added comment: Hypogammaglobulinaemia can be a feature of the condition.
Sources: Expert list
Hereditary Neuropathy - complex v1.19 RFC1 Bryony Thompson Classified gene: RFC1 as Green List (high evidence)
Hereditary Neuropathy - complex v1.19 RFC1 Bryony Thompson Gene: rfc1 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v1.18 RFC1 Bryony Thompson Publications for gene: RFC1 were set to 30926972
Mendeliome v1.2140 RFC1 Bryony Thompson Publications for gene: RFC1 were set to 30926972; 33103729; 35883251
Mendeliome v1.2139 RFC1 Bryony Thompson Classified gene: RFC1 as Green List (high evidence)
Mendeliome v1.2139 RFC1 Bryony Thompson Gene: rfc1 has been classified as Green List (High Evidence).
Mendeliome v1.2138 ANAPC1 Zornitza Stark Tag founder tag was added to gene: ANAPC1.
Mendeliome v1.2138 WASHC5 Zornitza Stark Mode of inheritance for gene: WASHC5 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.2137 WASHC5 Zornitza Stark edited their review of gene: WASHC5: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pulmonary Fibrosis_Interstitial Lung Disease v0.82 ZCCHC8 Zornitza Stark Publications for gene: ZCCHC8 were set to 31488579
Pulmonary Fibrosis_Interstitial Lung Disease v0.81 ZCCHC8 Zornitza Stark Classified gene: ZCCHC8 as Green List (high evidence)
Pulmonary Fibrosis_Interstitial Lung Disease v0.81 ZCCHC8 Zornitza Stark Gene: zcchc8 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.105 ZCCHC8 Zornitza Stark Publications for gene: ZCCHC8 were set to 31488579; 38375433
Pulmonary Fibrosis_Interstitial Lung Disease v0.80 ZCCHC8 Zornitza Stark reviewed gene: ZCCHC8: Rating: GREEN; Mode of pathogenicity: None; Publications: 31488579, 38375433; Phenotypes: Pulmonary fibrosis and/or bone marrow failure, telomere-related MONDO:0000148; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Bone Marrow Failure v1.104 ZCCHC8 Zornitza Stark Publications for gene: ZCCHC8 were set to 31488579
Bone Marrow Failure v1.103 ZCCHC8 Zornitza Stark Classified gene: ZCCHC8 as Green List (high evidence)
Bone Marrow Failure v1.103 ZCCHC8 Zornitza Stark Gene: zcchc8 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.102 ZCCHC8 Zornitza Stark reviewed gene: ZCCHC8: Rating: GREEN; Mode of pathogenicity: None; Publications: 31488579, 38375433; Phenotypes: pulmonary fibrosis and/or bone marrow failure, telomere-related, 5 MONDO:0032865; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.2137 ZCCHC8 Zornitza Stark Classified gene: ZCCHC8 as Green List (high evidence)
Mendeliome v1.2137 ZCCHC8 Zornitza Stark Gene: zcchc8 has been classified as Green List (High Evidence).
Mendeliome v1.2136 ZCCHC8 Zornitza Stark reviewed gene: ZCCHC8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: pulmonary fibrosis and/or bone marrow failure, telomere-related, 5 MONDO:0032865; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.2136 RTTN Zornitza Stark Phenotypes for gene: RTTN were changed from Microcephaly, short stature, and polymicrogyria with seizures, MIM# 614833; Intellectual disability; cerebral polymicrogyria; primary microcephaly; growth defects; congenital anomalies to Microcephaly, short stature, and polymicrogyria with seizures, MIM# 614833; microcephalic primordial dwarfism due to RTTN deficiency MONDO:0018764
Mendeliome v1.2135 PLA2G4A Sangavi Sivagnanasundram reviewed gene: PLA2G4A: Rating: GREEN; Mode of pathogenicity: None; Publications: 18451993, 23268370, 25102815; Phenotypes: cytosolic phospholipase-A2 alpha deficiency associated bleeding disorder MONDO:0018794; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2135 RTTN Sangavi Sivagnanasundram reviewed gene: RTTN: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008471; Phenotypes: microcephalic primordial dwarfism due to RTTN deficiency MONDO:0018764; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2135 ZCCHC8 Sangavi Sivagnanasundram reviewed gene: ZCCHC8: Rating: GREEN; Mode of pathogenicity: None; Publications: 31488579, 38375433; Phenotypes: pulmonary fibrosis and/or bone marrow failure, telomere-related, 5 MONDO:0032865; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.2135 SLC18A2 Sangavi Sivagnanasundram reviewed gene: SLC18A2: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008459; Phenotypes: brain dopamine-serotonin vesicular transport disease MONDO:0018130; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2135 RFC1 Sangavi Sivagnanasundram reviewed gene: RFC1: Rating: AMBER; Mode of pathogenicity: None; Publications: 35883251, 36478048, 36289003; Phenotypes: cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome MONDO:0044720; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2135 IQCB1 Sangavi Sivagnanasundram reviewed gene: IQCB1: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008440; Phenotypes: ciliopathy MONDO:0005308; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2135 WASHC5 Sangavi Sivagnanasundram reviewed gene: WASHC5: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:006537, https://search.clinicalgenome.org/CCID:006538; Phenotypes: hereditary spastic paraplegia 8 MONDO:0011339, Ritscher-Schinzel syndrome 1 MONDO:0009073; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.2135 G6PC Sangavi Sivagnanasundram reviewed gene: G6PC: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008420; Phenotypes: glycogen storage disease I MONDO:0002413; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2135 PYGL Sangavi Sivagnanasundram reviewed gene: PYGL: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008478; Phenotypes: glycogen storage disease VI MONDO:0009294; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2135 CAMLG Sangavi Sivagnanasundram reviewed gene: CAMLG: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008383; Phenotypes: congenital disorder of glycosylation, type IIz MONDO:0859357; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v1.54 CAMLG Sangavi Sivagnanasundram reviewed gene: CAMLG: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008383; Phenotypes: congenital disorder of glycosylation, type IIz MONDO:0859357; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2135 CYP27A1 Sangavi Sivagnanasundram reviewed gene: CYP27A1: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008400; Phenotypes: cerebrotendinous xanthomatosis MONDO:0008948; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2135 DEGS1 Sangavi Sivagnanasundram reviewed gene: DEGS1: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008468; Phenotypes: leukodystrophy, hypomyelinating, 18 MONDO:0032730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2135 ANAPC1 Sangavi Sivagnanasundram reviewed gene: ANAPC1: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008429; Phenotypes: Rothmund-Thomson syndrome type 1 MONDO:0016368; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v1.54 COG3 Sangavi Sivagnanasundram reviewed gene: COG3: Rating: AMBER; Mode of pathogenicity: Other; Publications: https://search.clinicalgenome.org/CCID:008379; Phenotypes: congenital disorder of glycosylation MONDO:0015286; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2135 COG3 Sangavi Sivagnanasundram reviewed gene: COG3: Rating: AMBER; Mode of pathogenicity: Other; Publications: https://search.clinicalgenome.org/CCID:008379; Phenotypes: congenital disorder of glycosylation MONDO:0015286; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Predominantly Antibody Deficiency v0.146 POU2AF1 Bryony Thompson changed review comment from: A single case has been reported and a supporting null mouse model.; to: A single case has been reported and a supporting null mouse model.
https://search.clinicalgenome.org/CCID:005865
Mendeliome v1.2135 POU2AF1 Bryony Thompson Classified gene: POU2AF1 as Amber List (moderate evidence)
Mendeliome v1.2135 POU2AF1 Bryony Thompson Gene: pou2af1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2134 POU2AF1 Bryony Thompson reviewed gene: POU2AF1: Rating: AMBER; Mode of pathogenicity: None; Publications: 35603192, 33571536; Phenotypes: Agammaglobulinemia MONDO:0015977; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Predominantly Antibody Deficiency v0.146 POU2AF1 Bryony Thompson Classified gene: POU2AF1 as Amber List (moderate evidence)
Predominantly Antibody Deficiency v0.146 POU2AF1 Bryony Thompson Gene: pou2af1 has been classified as Amber List (Moderate Evidence).
Predominantly Antibody Deficiency v0.145 POU2AF1 Bryony Thompson reviewed gene: POU2AF1: Rating: AMBER; Mode of pathogenicity: None; Publications: 35603192, 33571536; Phenotypes: Agammaglobulinemia MONDO:0015977; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Predominantly Antibody Deficiency v0.145 KARS Bryony Thompson Marked gene: KARS as ready
Predominantly Antibody Deficiency v0.145 KARS Bryony Thompson Gene: kars has been classified as Green List (High Evidence).
Predominantly Antibody Deficiency v0.145 KARS Bryony Thompson Classified gene: KARS as Green List (high evidence)
Predominantly Antibody Deficiency v0.145 KARS Bryony Thompson Gene: kars has been classified as Green List (High Evidence).
Predominantly Antibody Deficiency v0.144 KARS Bryony Thompson gene: KARS was added
gene: KARS was added to Predominantly Antibody Deficiency. Sources: Expert list
Mode of inheritance for gene: KARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KARS were set to 37770806
Phenotypes for gene: KARS were set to leukoencephalopathy, progressive, infantile-onset, with or without deafness MONDO:0030893
Review for gene: KARS was set to GREEN
gene: KARS was marked as current diagnostic
Added comment: Recurrent/severe infections (9/17) and B cell abnormalities (either B cell lymphopenia [3/9], hypogammaglobulinemia [either IgG, IgA or IgM; 6/15] or impaired vaccine responses [4/7]) have been reported in cases with KARS1-related disease.
Sources: Expert list
Predominantly Antibody Deficiency v0.143 IGKC Bryony Thompson Marked gene: IGKC as ready
Predominantly Antibody Deficiency v0.143 IGKC Bryony Thompson Gene: igkc has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2134 IGKC Bryony Thompson Marked gene: IGKC as ready
Mendeliome v1.2134 IGKC Bryony Thompson Gene: igkc has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2134 IGKC Bryony Thompson Classified gene: IGKC as Amber List (moderate evidence)
Mendeliome v1.2134 IGKC Bryony Thompson Gene: igkc has been classified as Amber List (Moderate Evidence).
Predominantly Antibody Deficiency v0.143 IGKC Bryony Thompson Classified gene: IGKC as Amber List (moderate evidence)
Predominantly Antibody Deficiency v0.143 IGKC Bryony Thompson Gene: igkc has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2133 IGKC Bryony Thompson gene: IGKC was added
gene: IGKC was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: IGKC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IGKC were set to https://search.clinicalgenome.org/CCID:005121
Phenotypes for gene: IGKC were set to recurrent infections associated with rare immunoglobulin isotypes deficiency MONDO:0013576
Review for gene: IGKC was set to AMBER
Added comment: Antibody Deficiencies GCEP classify gene-disease association as Limited (18/05/2021) - at least 6 probands https://search.clinicalgenome.org/CCID:005121
Sources: Expert list
Predominantly Antibody Deficiency v0.142 IGKC Bryony Thompson gene: IGKC was added
gene: IGKC was added to Predominantly Antibody Deficiency. Sources: Expert list
Mode of inheritance for gene: IGKC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IGKC were set to https://search.clinicalgenome.org/CCID:005121
Phenotypes for gene: IGKC were set to recurrent infections associated with rare immunoglobulin isotypes deficiency MONDO:0013576
Review for gene: IGKC was set to AMBER
Added comment: Antibody Deficiencies GCEP classify gene-disease association as Limited (18/05/2021)
- at least 6 probands
https://search.clinicalgenome.org/CCID:005121
Sources: Expert list
Predominantly Antibody Deficiency v0.141 CTNNBL1 Bryony Thompson Marked gene: CTNNBL1 as ready
Predominantly Antibody Deficiency v0.141 CTNNBL1 Bryony Thompson Gene: ctnnbl1 has been classified as Amber List (Moderate Evidence).
Predominantly Antibody Deficiency v0.141 CTNNBL1 Bryony Thompson Classified gene: CTNNBL1 as Amber List (moderate evidence)
Predominantly Antibody Deficiency v0.141 CTNNBL1 Bryony Thompson Gene: ctnnbl1 has been classified as Amber List (Moderate Evidence).
Predominantly Antibody Deficiency v0.140 CTNNBL1 Bryony Thompson gene: CTNNBL1 was added
gene: CTNNBL1 was added to Predominantly Antibody Deficiency. Sources: Expert list
Mode of inheritance for gene: CTNNBL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTNNBL1 were set to 23343763; 32484799
Phenotypes for gene: CTNNBL1 were set to common variable immunodeficiency MONDO:0015517
Review for gene: CTNNBL1 was set to AMBER
Added comment: A single case has been reported and a supporting null mouse model.
https://search.clinicalgenome.org/CCID:004601
Sources: Expert list
Combined Immunodeficiency v1.109 PTCRA Bryony Thompson Marked gene: PTCRA as ready
Combined Immunodeficiency v1.109 PTCRA Bryony Thompson Gene: ptcra has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.109 PTCRA Bryony Thompson Classified gene: PTCRA as Green List (high evidence)
Combined Immunodeficiency v1.109 PTCRA Bryony Thompson Gene: ptcra has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.108 PTCRA Bryony Thompson reviewed gene: PTCRA: Rating: GREEN; Mode of pathogenicity: None; Publications: 38422122; Phenotypes: Immunodeficiency 126, MIM# 620931; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v1.108 PTCRA Bryony Thompson gene: PTCRA was added
gene: PTCRA was added to Combined Immunodeficiency. Sources: Expert list
Mode of inheritance for gene: PTCRA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTCRA were set to 38422122
Phenotypes for gene: PTCRA were set to Immunodeficiency 126, MIM# 620931
Bone Marrow Failure v1.102 FLT3LG Bryony Thompson Classified gene: FLT3LG as Amber List (moderate evidence)
Bone Marrow Failure v1.102 FLT3LG Bryony Thompson Gene: flt3lg has been classified as Amber List (Moderate Evidence).
Combined Immunodeficiency v1.107 FLT3LG Bryony Thompson Marked gene: FLT3LG as ready
Combined Immunodeficiency v1.107 FLT3LG Bryony Thompson Gene: flt3lg has been classified as Amber List (Moderate Evidence).
Combined Immunodeficiency v1.107 FLT3LG Bryony Thompson Classified gene: FLT3LG as Amber List (moderate evidence)
Combined Immunodeficiency v1.107 FLT3LG Bryony Thompson Gene: flt3lg has been classified as Amber List (Moderate Evidence).
Bone Marrow Failure v1.101 FLT3LG Bryony Thompson reviewed gene: FLT3LG: Rating: AMBER; Mode of pathogenicity: None; Publications: 10828034, 38701783; Phenotypes: ?Immunodeficiency 125 MIM#620926; Mode of inheritance: None
Combined Immunodeficiency v1.106 FLT3LG Bryony Thompson gene: FLT3LG was added
gene: FLT3LG was added to Combined Immunodeficiency. Sources: Expert list
Mode of inheritance for gene: FLT3LG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FLT3LG were set to 10828034; 38701783
Phenotypes for gene: FLT3LG were set to ?Immunodeficiency 125 MIM#620926
Review for gene: FLT3LG was set to AMBER
Added comment: One family reported and mouse models. IUIS IEI committee classify this gene as a Combined immunodeficiency with associated or syndromic features.
Sources: Expert list
Mendeliome v1.2132 FLT3LG Bryony Thompson Classified gene: FLT3LG as Amber List (moderate evidence)
Mendeliome v1.2132 FLT3LG Bryony Thompson Gene: flt3lg has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2131 FLT3LG Bryony Thompson reviewed gene: FLT3LG: Rating: AMBER; Mode of pathogenicity: None; Publications: 10828034, 38701783; Phenotypes: ?Immunodeficiency 125 MIM#620926; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v1.105 CD28 Bryony Thompson Marked gene: CD28 as ready
Combined Immunodeficiency v1.105 CD28 Bryony Thompson Gene: cd28 has been classified as Amber List (Moderate Evidence).
Combined Immunodeficiency v1.105 CD28 Bryony Thompson Classified gene: CD28 as Amber List (moderate evidence)
Combined Immunodeficiency v1.105 CD28 Bryony Thompson Gene: cd28 has been classified as Amber List (Moderate Evidence).
Combined Immunodeficiency v1.104 CD28 Bryony Thompson gene: CD28 was added
gene: CD28 was added to Combined Immunodeficiency. Sources: Expert list
Mode of inheritance for gene: CD28 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CD28 were set to 34214472
Phenotypes for gene: CD28 were set to Immunodeficiency-123 with HPV-related verrucosis (IMD123), MIM#620901
Review for gene: CD28 was set to AMBER
Added comment: A single family reported and supporting mouse model. IUIS IEI committee classify the gene as a Combined immunodeficiency with associated or syndromic features.
Sources: Expert list
Mendeliome v1.2131 TNFSF9 Zornitza Stark Marked gene: TNFSF9 as ready
Mendeliome v1.2131 TNFSF9 Zornitza Stark Gene: tnfsf9 has been classified as Red List (Low Evidence).
Mendeliome v1.2131 TNFSF9 Zornitza Stark gene: TNFSF9 was added
gene: TNFSF9 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TNFSF9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TNFSF9 were set to 35657354
Phenotypes for gene: TNFSF9 were set to Hereditary susceptibility to infections, MONDO:0015979, TNFSF9-related
Review for gene: TNFSF9 was set to RED
Added comment: Fournier et al. described one patient with DiGeorge syndrome with a unique susceptibility to EBV with broad EBV infection and smooth muscle tumors. He was found to have a homozygous missense variant (p.V140G) in TNFSF9 coding for CD137L/4-1BBL, the ligand of the T cell co-stimulatory molecule CD137/4-1BB, whose deficiency predisposes to EBV infection.

They show that CD137LV140G mutant was weakly expressed on patient cells or when ectopically expressed in HEK and P815 cells. Importantly, patient EBV-infected B cells failed to trigger the expansion of EBV-specific T cells, resulting in decreased T cell effector responses. T cell expansion was recovered when CD137L expression was restored on B cells.
Sources: Literature
Susceptibility to Viral Infections v0.129 TNFSF9 Zornitza Stark changed review comment from: Fournier et al. described one patient with DiGeorge syndrome with a unique susceptibility to EBV with broad EBV infection and smooth muscle tumors. He was found to have a homozygous missense mutation (p.V140G) in TNFSF9 coding for CD137L/4-1BBL, the ligand of the T cell co-stimulatory molecule CD137/4-1BB, whose deficiency predisposes to EBV infection.

They show that CD137LV140G mutant was weakly expressed on patient cells or when ectopically expressed in HEK and P815 cells. Importantly, patient EBV-infected B cells failed to trigger the expansion of EBV-specific T cells, resulting in decreased T cell effector responses. T cell expansion was recovered when CD137L expression was restored on B cells.
Sources: Literature; to: Fournier et al. described one patient with DiGeorge syndrome with a unique susceptibility to EBV with broad EBV infection and smooth muscle tumors. He was found to have a homozygous missense variant (p.V140G) in TNFSF9 coding for CD137L/4-1BBL, the ligand of the T cell co-stimulatory molecule CD137/4-1BB, whose deficiency predisposes to EBV infection.

They show that CD137LV140G mutant was weakly expressed on patient cells or when ectopically expressed in HEK and P815 cells. Importantly, patient EBV-infected B cells failed to trigger the expansion of EBV-specific T cells, resulting in decreased T cell effector responses. T cell expansion was recovered when CD137L expression was restored on B cells.
Sources: Literature
Susceptibility to Viral Infections v0.129 TNFSF9 Zornitza Stark Marked gene: TNFSF9 as ready
Susceptibility to Viral Infections v0.129 TNFSF9 Zornitza Stark Gene: tnfsf9 has been classified as Red List (Low Evidence).
Susceptibility to Viral Infections v0.129 TNFSF9 Zornitza Stark gene: TNFSF9 was added
gene: TNFSF9 was added to Susceptibility to Viral Infections. Sources: Literature
Mode of inheritance for gene: TNFSF9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TNFSF9 were set to 35657354
Phenotypes for gene: TNFSF9 were set to Hereditary susceptibility to infections, MONDO:0015979, TNFSF9-related
Review for gene: TNFSF9 was set to RED
Added comment: Fournier et al. described one patient with DiGeorge syndrome with a unique susceptibility to EBV with broad EBV infection and smooth muscle tumors. He was found to have a homozygous missense mutation (p.V140G) in TNFSF9 coding for CD137L/4-1BBL, the ligand of the T cell co-stimulatory molecule CD137/4-1BB, whose deficiency predisposes to EBV infection.

They show that CD137LV140G mutant was weakly expressed on patient cells or when ectopically expressed in HEK and P815 cells. Importantly, patient EBV-infected B cells failed to trigger the expansion of EBV-specific T cells, resulting in decreased T cell effector responses. T cell expansion was recovered when CD137L expression was restored on B cells.
Sources: Literature
Mendeliome v1.2130 APOA4 Zornitza Stark Marked gene: APOA4 as ready
Mendeliome v1.2130 APOA4 Zornitza Stark Gene: apoa4 has been classified as Green List (High Evidence).
Mendeliome v1.2130 APOA4 Zornitza Stark Classified gene: APOA4 as Green List (high evidence)
Mendeliome v1.2130 APOA4 Zornitza Stark Gene: apoa4 has been classified as Green List (High Evidence).
Mendeliome v1.2129 APOA4 Zornitza Stark gene: APOA4 was added
gene: APOA4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: APOA4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: APOA4 were set to 38096951
Phenotypes for gene: APOA4 were set to Hereditary amyloidosis, MONDO:0018634, APOA4-related
Review for gene: APOA4 was set to GREEN
Added comment: 5 families with autosomal dominant medullary amyloidosis. WGS/WES identified 2 different variants in the APOA4 gene (p.D33N in 3 families and p.L66V in 2 families). The variants were absent in gnomAD, located at the structurally flexible N-terminal domain of APOA4, and segregated with disease. There were 48 genotype +ve individuals with 44/48 having an eGFR <60. All clinically affected individuals presented with a bland urinary sediment, CKD, and no clinical evidence of systemic amyloidosis. Mean age of dialysis/transplantation was 58+/-11yrs. Routine kidney biopsies limited to the kidney cortex showed tubulointerstitial fibrosis and secondary glomerulosclerosis and no amyloid deposition. Four affected individuals were shown to have isolated medullary deposition of amyloid, with mass spectrometry showing the mutated Apoa4 as the primary constituent in 3 available cases. Plasma total ApoA4 levels were increased for patients (n=15) with ApoA4 mutations versus controls (n=49). They hypothesize that the amino acid substitutions alter the tertiary or quaternary structure of the mutated ApoA4, leading to increased plasma and primary urine concentrations and isolated medullary amyloid deposition.
Sources: Literature
Amyloidosis v0.31 APOA4 Zornitza Stark Marked gene: APOA4 as ready
Amyloidosis v0.31 APOA4 Zornitza Stark Gene: apoa4 has been classified as Green List (High Evidence).
Amyloidosis v0.31 APOA4 Zornitza Stark Phenotypes for gene: APOA4 were changed from Autosomal dominant renal medullary amyloidosis to Hereditary amyloidosis, MONDO:0018634, APOA4-related
Mitochondrial disease v0.953 TYMP Zornitza Stark Marked gene: TYMP as ready
Mitochondrial disease v0.953 TYMP Zornitza Stark Gene: tymp has been classified as Green List (High Evidence).
Mitochondrial disease v0.953 TYMP Zornitza Stark Phenotypes for gene: TYMP were changed from Mitochondrial DNA depletion syndrome 1 (MNGIE type), MIM# 603041 to Mitochondrial DNA depletion syndrome 1 (MNGIE type), MIM# 603041
Mitochondrial disease v0.952 TYMP Zornitza Stark Phenotypes for gene: TYMP were changed from to Mitochondrial DNA depletion syndrome 1 (MNGIE type), MIM# 603041
Mitochondrial disease v0.951 TYMP Zornitza Stark Publications for gene: TYMP were set to
Mitochondrial disease v0.950 TYMP Zornitza Stark Mode of inheritance for gene: TYMP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Calcium and Phosphate disorders v1.24 HRAS Zornitza Stark Tag somatic tag was added to gene: HRAS.
Amyloidosis v0.30 APOA4 Chirag Patel Classified gene: APOA4 as Green List (high evidence)
Amyloidosis v0.30 APOA4 Chirag Patel Gene: apoa4 has been classified as Green List (High Evidence).
Amyloidosis v0.29 APOA4 Chirag Patel gene: APOA4 was added
gene: APOA4 was added to Amyloidosis. Sources: Literature
Mode of inheritance for gene: APOA4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: APOA4 were set to PMID: 38096951
Phenotypes for gene: APOA4 were set to Autosomal dominant renal medullary amyloidosis
Review for gene: APOA4 was set to GREEN
Added comment: 5 families with autosomal dominant medullary amyloidosis. WGS/WES identified 2 different variants in the APOA4 gene (p.D33N in 3 families and p.L66V in 2 families). The variants were absent in gnomAD, located at the structurally flexible N-terminal domain of APOA4, and segregated with disease. There were 48 genotype +ve individuals with 44/48 having an eGFR <60. All clinically affected individuals presented with a bland urinary sediment, CKD, and no clinical evidence of systemic amyloidosis. Mean age of dialysis/transplantation was 58+/-11yrs. Routine kidney biopsies limited to the kidney cortex showed tubulointerstitial fibrosis and secondary glomerulosclerosis and no amyloid deposition. Four affected individuals were shown to have isolated medullary deposition of amyloid, with mass spectrometry showing the mutated Apoa4 as the primary constituent in 3 available cases.
Plasma total ApoA4 levels were increased for patients (n=15) with ApoA4 mutations versus controls (n=49). They hypothesize that the amino acid substitutions alter the tertiary or quaternary structure of the mutated ApoA4, leading to increased plasma and primary urine concentrations and isolated medullary amyloid deposition.
Sources: Literature
Combined Immunodeficiency v1.103 DSG1 Bryony Thompson Marked gene: DSG1 as ready
Combined Immunodeficiency v1.103 DSG1 Bryony Thompson Gene: dsg1 has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.103 DSG1 Bryony Thompson Classified gene: DSG1 as Green List (high evidence)
Combined Immunodeficiency v1.103 DSG1 Bryony Thompson Gene: dsg1 has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.101 DSG1 Bryony Thompson gene: DSG1 was added
gene: DSG1 was added to Combined Immunodeficiency. Sources: Literature
Mode of inheritance for gene: DSG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DSG1 were set to 23974871; 32126589; 29604126
Phenotypes for gene: DSG1 were set to severe dermatitis-multiple allergies-metabolic wasting syndrome MONDO:0014218
Combined Immunodeficiency v1.100 STAT6 Bryony Thompson Marked gene: STAT6 as ready
Combined Immunodeficiency v1.100 STAT6 Bryony Thompson Gene: stat6 has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.100 STAT6 Bryony Thompson Classified gene: STAT6 as Green List (high evidence)
Combined Immunodeficiency v1.100 STAT6 Bryony Thompson Gene: stat6 has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.99 STAT6 Bryony Thompson gene: STAT6 was added
gene: STAT6 was added to Combined Immunodeficiency. Sources: Expert list
Mode of inheritance for gene: STAT6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: STAT6 were set to 36884218; 36758835
Phenotypes for gene: STAT6 were set to hyper-IgE syndrome MONDO:0018037
Mode of pathogenicity for gene: STAT6 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: STAT6 was set to GREEN
gene: STAT6 was marked as current diagnostic
Added comment: Gain of function variants cause early-onset allergies. IUIS IEI committee classify this gene as a Combined immunodeficiency with associated or syndromic features.
Sources: Expert list
Combined Immunodeficiency v1.98 RECQL4 Bryony Thompson Marked gene: RECQL4 as ready
Combined Immunodeficiency v1.98 RECQL4 Bryony Thompson Gene: recql4 has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.98 RECQL4 Bryony Thompson Classified gene: RECQL4 as Green List (high evidence)
Combined Immunodeficiency v1.98 RECQL4 Bryony Thompson Gene: recql4 has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.97 RECQL4 Bryony Thompson gene: RECQL4 was added
gene: RECQL4 was added to Combined Immunodeficiency. Sources: Expert list
Mode of inheritance for gene: RECQL4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RECQL4 were set to 21143835; 26064716
Phenotypes for gene: RECQL4 were set to Rothmund-Thomson syndrome MONDO:0010002
Review for gene: RECQL4 was set to GREEN
gene: RECQL4 was marked as current diagnostic
Added comment: Immunodeficiency can be a feature of RTS, but is not always present. IUIS IEI committee classify this gene as a Combined immunodeficiency with associated or syndromic features.
Sources: Expert list
Combined Immunodeficiency v1.96 POLA1 Bryony Thompson Marked gene: POLA1 as ready
Combined Immunodeficiency v1.96 POLA1 Bryony Thompson Gene: pola1 has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.96 POLA1 Bryony Thompson Classified gene: POLA1 as Green List (high evidence)
Combined Immunodeficiency v1.96 POLA1 Bryony Thompson Gene: pola1 has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.95 POLA1 Bryony Thompson gene: POLA1 was added
gene: POLA1 was added to Combined Immunodeficiency. Sources: Expert list
Mode of inheritance for gene: POLA1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: POLA1 were set to 27019227
Phenotypes for gene: POLA1 were set to X-linked reticulate pigmentary disorder MONDO:0010523
Review for gene: POLA1 was set to GREEN
gene: POLA1 was marked as current diagnostic
Added comment: An intronic variant that alters splicing causes a combined primary immunodeficiency with autoinflammatory features. IUIS IEI committee classifies the gene as a Combined immunodeficiency with associated or syndromic features.
Sources: Expert list
Combined Immunodeficiency v1.94 MCM10 Bryony Thompson Marked gene: MCM10 as ready
Combined Immunodeficiency v1.94 MCM10 Bryony Thompson Gene: mcm10 has been classified as Amber List (Moderate Evidence).
Combined Immunodeficiency v1.94 MCM10 Bryony Thompson Classified gene: MCM10 as Amber List (moderate evidence)
Combined Immunodeficiency v1.94 MCM10 Bryony Thompson Gene: mcm10 has been classified as Amber List (Moderate Evidence).
Combined Immunodeficiency v1.93 MCM10 Bryony Thompson gene: MCM10 was added
gene: MCM10 was added to Combined Immunodeficiency. Sources: Expert list
Mode of inheritance for gene: MCM10 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MCM10 were set to Immunodeficiency 80 with or without congenital cardiomyopathy MONDO:0030266
Review for gene: MCM10 was set to AMBER
Added comment: 2 families reported with supporting functional studies
Moderate gene-disease classification - https://search.clinicalgenome.org/CCID:008284
Sources: Expert list
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.143 TSHZ3 Zornitza Stark Marked gene: TSHZ3 as ready
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.143 TSHZ3 Zornitza Stark Gene: tshz3 has been classified as Amber List (Moderate Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.143 TSHZ3 Zornitza Stark Classified gene: TSHZ3 as Amber List (moderate evidence)
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.143 TSHZ3 Zornitza Stark Gene: tshz3 has been classified as Amber List (Moderate Evidence).
Combined Immunodeficiency v1.92 GINS4 Bryony Thompson Marked gene: GINS4 as ready
Combined Immunodeficiency v1.92 GINS4 Bryony Thompson Gene: gins4 has been classified as Red List (Low Evidence).
Combined Immunodeficiency v1.92 GINS4 Bryony Thompson gene: GINS4 was added
gene: GINS4 was added to Combined Immunodeficiency. Sources: Expert list
Mode of inheritance for gene: GINS4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GINS4 were set to 36345943
Phenotypes for gene: GINS4 were set to combined immunodeficiency MONDO:0015131
Review for gene: GINS4 was set to RED
Added comment: 2 affected siblings with compound het variants are reported in a single family.
Sources: Expert list
Mendeliome v1.2128 TAPBP Bryony Thompson Publications for gene: TAPBP were set to 12149238
Mendeliome v1.2127 TAPBP Bryony Thompson Classified gene: TAPBP as Amber List (moderate evidence)
Mendeliome v1.2127 TAPBP Bryony Thompson Gene: tapbp has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2126 TAPBP Bryony Thompson reviewed gene: TAPBP: Rating: AMBER; Mode of pathogenicity: None; Publications: 38866210, 12149238; Phenotypes: MHC class I deficiency MONDO:0011476; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v1.91 TAPBP Bryony Thompson Publications for gene: TAPBP were set to 12149238
Combined Immunodeficiency v1.90 TAPBP Bryony Thompson Classified gene: TAPBP as Amber List (moderate evidence)
Combined Immunodeficiency v1.90 TAPBP Bryony Thompson Gene: tapbp has been classified as Amber List (Moderate Evidence).
Combined Immunodeficiency v1.89 TAPBP Bryony Thompson reviewed gene: TAPBP: Rating: AMBER; Mode of pathogenicity: None; Publications: 38866210, 12149238; Phenotypes: MHC class I deficiency MONDO:0011476; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2126 RHOH Bryony Thompson Publications for gene: RHOH were set to 22850876; 27574848
Combined Immunodeficiency v1.89 RHOH Bryony Thompson Publications for gene: RHOH were set to 38775840; 22850876; 27574848
Combined Immunodeficiency v1.88 RHOH Bryony Thompson Publications for gene: RHOH were set to 22850876; 27574848
Mendeliome v1.2125 RHOH Bryony Thompson Classified gene: RHOH as Amber List (moderate evidence)
Mendeliome v1.2125 RHOH Bryony Thompson Gene: rhoh has been classified as Amber List (Moderate Evidence).
Combined Immunodeficiency v1.87 RHOH Bryony Thompson Classified gene: RHOH as Amber List (moderate evidence)
Combined Immunodeficiency v1.87 RHOH Bryony Thompson Gene: rhoh has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2124 RHOH Bryony Thompson reviewed gene: RHOH: Rating: AMBER; Mode of pathogenicity: None; Publications: 38775840, 22850876; Phenotypes: epidermodysplasia verruciformis, susceptibility to, 4 MONDO:0032666; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v1.86 RHOH Bryony Thompson reviewed gene: RHOH: Rating: AMBER; Mode of pathogenicity: None; Publications: 38775840, 22850876; Phenotypes: epidermodysplasia verruciformis, susceptibility to, 4 MONDO:0032666; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2124 PRIM1 Bryony Thompson Classified gene: PRIM1 as Green List (high evidence)
Mendeliome v1.2124 PRIM1 Bryony Thompson Gene: prim1 has been classified as Green List (High Evidence).
Mendeliome v1.2123 PRIM1 Bryony Thompson reviewed gene: PRIM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33060134, 38773012; Phenotypes: primordial dwarfism-immunodeficiency-lipodystrophy syndrome MONDO:0859276; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v1.86 PRIM1 Bryony Thompson Marked gene: PRIM1 as ready
Combined Immunodeficiency v1.86 PRIM1 Bryony Thompson Gene: prim1 has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.86 PRIM1 Bryony Thompson changed review comment from: 8 cases from 6 families with combined immunodeficiency a feature of the condition.
Sources: Expert list; to: 8 cases from 6 families with combined immunodeficiency a feature of the condition. IUIS IEI committee classify the gene in the subcategory Combined Immunodeficiencies Generally Less Profound than Severe Combined Immunodeficiency.
Sources: Expert list
Combined Immunodeficiency v1.86 PRIM1 Bryony Thompson Classified gene: PRIM1 as Green List (high evidence)
Combined Immunodeficiency v1.86 PRIM1 Bryony Thompson Gene: prim1 has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.85 PRIM1 Bryony Thompson gene: PRIM1 was added
gene: PRIM1 was added to Combined Immunodeficiency. Sources: Expert list
Mode of inheritance for gene: PRIM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRIM1 were set to 33060134; 38773012
Phenotypes for gene: PRIM1 were set to primordial dwarfism-immunodeficiency-lipodystrophy syndrome MONDO:0859276
Review for gene: PRIM1 was set to GREEN
Added comment: 8 cases from 6 families with combined immunodeficiency a feature of the condition.
Sources: Expert list
Combined Immunodeficiency v1.84 POLD3 Bryony Thompson Marked gene: POLD3 as ready
Combined Immunodeficiency v1.84 POLD3 Bryony Thompson Gene: pold3 has been classified as Amber List (Moderate Evidence).
Combined Immunodeficiency v1.84 POLD3 Bryony Thompson Classified gene: POLD3 as Amber List (moderate evidence)
Combined Immunodeficiency v1.84 POLD3 Bryony Thompson Gene: pold3 has been classified as Amber List (Moderate Evidence).
Combined Immunodeficiency v1.83 POLD3 Bryony Thompson gene: POLD3 was added
gene: POLD3 was added to Combined Immunodeficiency. Sources: Expert list
Mode of inheritance for gene: POLD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLD3 were set to 38099988; 37030525
Phenotypes for gene: POLD3 were set to Immunodeficiency 122, MIM# 620869
Review for gene: POLD3 was set to AMBER
Added comment: Two reported cases. IUIS IEI committee classify the gene in the subcategory Combined Immunodeficiencies Generally Less Profound than Severe Combined Immunodeficiency.
Sources: Expert list
Congenital Disorders of Glycosylation v1.54 MAN2B2 Bryony Thompson Phenotypes for gene: MAN2B2 were changed from ongenital disorder of glycosylation, MONDO:0015286, MAN2B2-related to Congenital disorder of glycosylation, MONDO:0015286, MAN2B2-related
Mendeliome v1.2123 MAN2B2 Bryony Thompson Publications for gene: MAN2B2 were set to 31775018; 35637269
Mendeliome v1.2122 MAN2B2 Bryony Thompson reviewed gene: MAN2B2: Rating: AMBER; Mode of pathogenicity: None; Publications: 38622837, 35637269, 31775018; Phenotypes: Congenital disorder of glycosylation, MONDO:0015286, MAN2B2-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v1.53 MAN2B2 Bryony Thompson Publications for gene: MAN2B2 were set to 31775018; 35637269
Congenital Disorders of Glycosylation v1.52 MAN2B2 Bryony Thompson reviewed gene: MAN2B2: Rating: AMBER; Mode of pathogenicity: None; Publications: 38622837, 35637269, 31775018; Phenotypes: Congenital disorder of glycosylation, MONDO:0015286, MAN2B2-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v1.82 MAN2B2 Bryony Thompson Publications for gene: MAN2B2 were set to PMID: 31775018
Combined Immunodeficiency v1.81 MAN2B2 Bryony Thompson Classified gene: MAN2B2 as Amber List (moderate evidence)
Combined Immunodeficiency v1.81 MAN2B2 Bryony Thompson Gene: man2b2 has been classified as Amber List (Moderate Evidence).
Combined Immunodeficiency v1.80 MAN2B2 Bryony Thompson reviewed gene: MAN2B2: Rating: AMBER; Mode of pathogenicity: None; Publications: 38622837, 35637269, 31775018; Phenotypes: Congenital disorder of glycosylation, MONDO:0015286, MAN2B2-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Inflammatory bowel disease v0.122 IL21 Bryony Thompson Classified gene: IL21 as Red List (low evidence)
Inflammatory bowel disease v0.122 IL21 Bryony Thompson Added comment: Comment on list classification: Only a single case reported
Inflammatory bowel disease v0.122 IL21 Bryony Thompson Gene: il21 has been classified as Red List (Low Evidence).
Combined Immunodeficiency v1.80 IKZF2 Bryony Thompson Marked gene: IKZF2 as ready
Combined Immunodeficiency v1.80 IKZF2 Bryony Thompson Gene: ikzf2 has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.80 IKZF2 Bryony Thompson Classified gene: IKZF2 as Green List (high evidence)
Combined Immunodeficiency v1.80 IKZF2 Bryony Thompson Gene: ikzf2 has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.79 IKZF2 Bryony Thompson gene: IKZF2 was added
gene: IKZF2 was added to Combined Immunodeficiency. Sources: Expert list
Mode of inheritance for gene: IKZF2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: IKZF2 were set to 34826260; 34826259; 34920454
Phenotypes for gene: IKZF2 were set to HELIOS deficiency MONDO:0800139
Review for gene: IKZF2 was set to GREEN
Added comment: Cases present with a combined immunodeficiency phenotype characterised by recurrent upper respiratory infections, thrush and mucosal ulcers, and chronic lymphadenopathy. Incomplete penetrance is reported. IUIS IEI committee include this gene in the Combined Immunodeficiencies Generally Less Profound than Severe Combined Immunodeficiency subcategory of Immunodeficiencies affecting cellular and humoral immunity.
Sources: Expert list
Combined Immunodeficiency v1.78 FOXI3 Bryony Thompson Marked gene: FOXI3 as ready
Combined Immunodeficiency v1.78 FOXI3 Bryony Thompson Gene: foxi3 has been classified as Amber List (Moderate Evidence).
Combined Immunodeficiency v1.78 FOXI3 Bryony Thompson Classified gene: FOXI3 as Amber List (moderate evidence)
Combined Immunodeficiency v1.78 FOXI3 Bryony Thompson Gene: foxi3 has been classified as Amber List (Moderate Evidence).
Combined Immunodeficiency v1.77 FOXI3 Bryony Thompson gene: FOXI3 was added
gene: FOXI3 was added to Combined Immunodeficiency. Sources: Expert list
Mode of inheritance for gene: FOXI3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOXI3 were set to 35987349; 31600545
Phenotypes for gene: FOXI3 were set to thymic dysplasia MONDO:0004195
Review for gene: FOXI3 was set to AMBER
Added comment: 2 cases with loss of function variants in FOXI3 that resulted in abnormal TRECs and T cell lymphopenia. Incomplete penetrance in both families (4 unaffected individuals with variant & 2 affected with variant). Also, 5 families with overlapping microdeletions at chromosome 2p11.2 that spanned FOXI3 with similar immunophenotypes that included selective T cell lymphopenia. Also, supporting mouse models. However, due to the incomplete penetrance the gene-disease association remains uncertain.
Sources: Expert list
Mendeliome v1.2122 NUDCD3 Bryony Thompson Marked gene: NUDCD3 as ready
Mendeliome v1.2122 NUDCD3 Bryony Thompson Gene: nudcd3 has been classified as Green List (High Evidence).
Mendeliome v1.2122 NUDCD3 Bryony Thompson Classified gene: NUDCD3 as Green List (high evidence)
Mendeliome v1.2122 NUDCD3 Bryony Thompson Gene: nudcd3 has been classified as Green List (High Evidence).
Mendeliome v1.2120 NUDCD3 Bryony Thompson gene: NUDCD3 was added
gene: NUDCD3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: NUDCD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUDCD3 were set to 38787962
Phenotypes for gene: NUDCD3 were set to severe combined immunodeficiency MONDO:0015974
Defects of intrinsic and innate immunity v0.154 MCTS1 Bryony Thompson Marked gene: MCTS1 as ready
Defects of intrinsic and innate immunity v0.154 MCTS1 Bryony Thompson Gene: mcts1 has been classified as Green List (High Evidence).
Defects of intrinsic and innate immunity v0.154 MCTS1 Bryony Thompson Phenotypes for gene: MCTS1 were changed from to Inherited susceptibility to mycobacterial diseases, MONDO:0019146, MCTS1-related
Defects of intrinsic and innate immunity v0.153 MCTS1 Bryony Thompson Publications for gene: MCTS1 were set to
Defects of intrinsic and innate immunity v0.152 MCTS1 Bryony Thompson Classified gene: MCTS1 as Green List (high evidence)
Defects of intrinsic and innate immunity v0.152 MCTS1 Bryony Thompson Gene: mcts1 has been classified as Green List (High Evidence).
Defects of intrinsic and innate immunity v0.151 MAPK8 Bryony Thompson Marked gene: MAPK8 as ready
Defects of intrinsic and innate immunity v0.151 MAPK8 Bryony Thompson Gene: mapk8 has been classified as Amber List (Moderate Evidence).
Defects of intrinsic and innate immunity v0.151 MAPK8 Bryony Thompson Phenotypes for gene: MAPK8 were changed from to Chronic mucocutaneous candidiasis; Connective tissue disorders
Defects of intrinsic and innate immunity v0.150 MAPK8 Bryony Thompson Publications for gene: MAPK8 were set to
Defects of intrinsic and innate immunity v0.149 MAPK8 Bryony Thompson Classified gene: MAPK8 as Amber List (moderate evidence)
Defects of intrinsic and innate immunity v0.149 MAPK8 Bryony Thompson Gene: mapk8 has been classified as Amber List (Moderate Evidence).
Defects of intrinsic and innate immunity v0.148 IRF1 Bryony Thompson Marked gene: IRF1 as ready
Defects of intrinsic and innate immunity v0.148 IRF1 Bryony Thompson Gene: irf1 has been classified as Green List (High Evidence).
Defects of intrinsic and innate immunity v0.148 IRF1 Bryony Thompson Phenotypes for gene: IRF1 were changed from to Immunodeficiency 117, mycobacteriosis, autosomal recessive, MIM# 620668
Defects of intrinsic and innate immunity v0.147 IRF1 Bryony Thompson Publications for gene: IRF1 were set to
Defects of intrinsic and innate immunity v0.146 IRF1 Bryony Thompson Classified gene: IRF1 as Green List (high evidence)
Defects of intrinsic and innate immunity v0.146 IRF1 Bryony Thompson Gene: irf1 has been classified as Green List (High Evidence).
Defects of intrinsic and innate immunity v0.144 IRF1 Bryony Thompson gene: IRF1 was added
gene: IRF1 was added to Defects of innate immunity. Sources: Expert list
Mode of inheritance for gene: IRF1 was set to BIALLELIC, autosomal or pseudoautosomal
Defects of intrinsic and innate immunity v0.143 MAPK8 Bryony Thompson gene: MAPK8 was added
gene: MAPK8 was added to Defects of innate immunity. Sources: Expert list
Mode of inheritance for gene: MAPK8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Defects of intrinsic and innate immunity v0.142 MCTS1 Bryony Thompson gene: MCTS1 was added
gene: MCTS1 was added to Defects of innate immunity. Sources: Expert list
Mode of inheritance for gene: MCTS1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Disorders of immune dysregulation v0.195 ATG9A Bryony Thompson Marked gene: ATG9A as ready
Disorders of immune dysregulation v0.195 ATG9A Bryony Thompson Gene: atg9a has been classified as Red List (Low Evidence).
Disorders of immune dysregulation v0.195 ATG9A Bryony Thompson gene: ATG9A was added
gene: ATG9A was added to Disorders of immune dysregulation. Sources: Literature
Mode of inheritance for gene: ATG9A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATG9A were set to 35838483
Phenotypes for gene: ATG9A were set to Autophagy-associated immune dysregulation and hyperplasia
Review for gene: ATG9A was set to RED
Added comment: A single case with compound heterozygous variants was reported. After infection with Epstein-Barr virus (EBV), the patient developed hyperplastic proliferation of T and B cells in the lung and brain and exhibited defects in lymphocyte memory cell populations. In vitro functional assays.
Sources: Literature
Mendeliome v1.2119 ATG9A Bryony Thompson Marked gene: ATG9A as ready
Mendeliome v1.2119 ATG9A Bryony Thompson Gene: atg9a has been classified as Red List (Low Evidence).
Mendeliome v1.2119 ATG9A Bryony Thompson gene: ATG9A was added
gene: ATG9A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATG9A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATG9A were set to 35838483
Phenotypes for gene: ATG9A were set to Autophagy-associated immune dysregulation and hyperplasia
Review for gene: ATG9A was set to RED
Added comment: A single case with compound heterozygous variants was reported. After infection with Epstein-Barr virus (EBV), the patient developed hyperplastic proliferation of T and B cells in the lung and brain and exhibited defects in lymphocyte memory cell populations. In vitro functional assays.
Sources: Literature
Predominantly Antibody Deficiency v0.139 MS4A1 Bryony Thompson Classified gene: MS4A1 as Amber List (moderate evidence)
Predominantly Antibody Deficiency v0.139 MS4A1 Bryony Thompson Gene: ms4a1 has been classified as Amber List (Moderate Evidence).
Phagocyte Defects v1.31 CCR2 Bryony Thompson Marked gene: CCR2 as ready
Phagocyte Defects v1.31 CCR2 Bryony Thompson Gene: ccr2 has been classified as Green List (High Evidence).
Phagocyte Defects v1.31 CCR2 Bryony Thompson Classified gene: CCR2 as Green List (high evidence)
Phagocyte Defects v1.31 CCR2 Bryony Thompson Gene: ccr2 has been classified as Green List (High Evidence).
Mendeliome v1.2118 CCR2 Bryony Thompson Phenotypes for gene: CCR2 were changed from {HIV infection, susceptibility/resistance to} to {HIV infection, susceptibility/resistance to}; Polycystic lung disease MIM#219600
Phagocyte Defects v1.30 CCR2 Bryony Thompson gene: CCR2 was added
gene: CCR2 was added to Phagocyte Defects. Sources: Expert list
Mode of inheritance for gene: CCR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCR2 were set to 38157855
Phenotypes for gene: CCR2 were set to Polycystic lung disease MIM#219600
Review for gene: CCR2 was set to GREEN
Added comment: CCR2 deficiency was found to cause pulmonary alveolar proteinosis (PAP), polycystic lung disease, and recurrent infections caused by impaired CCL2-dependent monocyte migration to the lungs and infected tissues. 9 children from 5 independent kindreds with biallelic variants, homozygous in 6 cases & compound heterozygous in 3 were identified. Classified as a congenital defect of phagocyte number or function (subcategory defects of motility) by the IUIS IEI committee.
Sources: Expert list
Mendeliome v1.2117 CCR2 Bryony Thompson Publications for gene: CCR2 were set to 34516427; 17504215; 15167933; 17604544
Mendeliome v1.2116 CCR2 Bryony Thompson Mode of inheritance for gene: CCR2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2115 CCR2 Bryony Thompson Classified gene: CCR2 as Green List (high evidence)
Mendeliome v1.2115 CCR2 Bryony Thompson Gene: ccr2 has been classified as Green List (High Evidence).
Mendeliome v1.2114 CCR2 Bryony Thompson reviewed gene: CCR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 38157855; Phenotypes: Polycystic lung disease MIM#219600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Defects of intrinsic and innate immunity v0.141 ATG4A Bryony Thompson Marked gene: ATG4A as ready
Defects of intrinsic and innate immunity v0.141 ATG4A Bryony Thompson Gene: atg4a has been classified as Red List (Low Evidence).
Defects of intrinsic and innate immunity v0.141 ATG4A Bryony Thompson changed review comment from: Single case with recurrent HSV2 lymphocytic Mollaret’s meningitis heterozygous for a missense variant (p.Leu90Ile).
Sources: Expert list; to: Single case with recurrent HSV2 lymphocytic Mollaret’s meningitis heterozygous for a missense variant (p.Leu90Ile). Classified as a defect of intrinsic and innate immunity by IUIS and included on their list of IEIs.
Sources: Expert list
Defects of intrinsic and innate immunity v0.141 ATG4A Bryony Thompson gene: ATG4A was added
gene: ATG4A was added to Defects of innate immunity. Sources: Expert list
Mode of inheritance for gene: ATG4A 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: ATG4A were set to 33310865
Phenotypes for gene: ATG4A were set to infectious meningitis MONDO:0004796
Review for gene: ATG4A was set to RED
Added comment: Single case with recurrent HSV2 lymphocytic Mollaret’s meningitis heterozygous for a missense variant (p.Leu90Ile).
Sources: Expert list
Autoinflammatory Disorders v1.56 ATAD3A Bryony Thompson Marked gene: ATAD3A as ready
Autoinflammatory Disorders v1.56 ATAD3A Bryony Thompson Gene: atad3a has been classified as Green List (High Evidence).
Autoinflammatory Disorders v1.56 ATAD3A Bryony Thompson Classified gene: ATAD3A as Green List (high evidence)
Autoinflammatory Disorders v1.56 ATAD3A Bryony Thompson Gene: atad3a has been classified as Green List (High Evidence).
Autoinflammatory Disorders v1.55 ATAD3A Bryony Thompson gene: ATAD3A was added
gene: ATAD3A was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Expert list
Mode of inheritance for gene: ATAD3A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ATAD3A were set to 34387651
Phenotypes for gene: ATAD3A were set to inborn error of immunity MONDO:0003778; Harel-Yoon syndrome MONDO:0014958
Review for gene: ATAD3A was set to GREEN
gene: ATAD3A was marked as current diagnostic
Added comment: Elevated interferon-stimulated gene expression and increased serum type 1 IFNs were identified in both cases with monoallelic and biallelic variants. Classified as an inborn error of immunity (type 1 interferonopathy) by IUIS in the July 2024 IEI update.
Sources: Expert list
Predominantly Antibody Deficiency v0.138 ARHGEF1 Bryony Thompson Publications for gene: ARHGEF1 were set to 30521495
Predominantly Antibody Deficiency v0.137 ARHGEF1 Bryony Thompson Classified gene: ARHGEF1 as Amber List (moderate evidence)
Predominantly Antibody Deficiency v0.137 ARHGEF1 Bryony Thompson Gene: arhgef1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2114 ARHGEF1 Bryony Thompson Classified gene: ARHGEF1 as Amber List (moderate evidence)
Mendeliome v1.2114 ARHGEF1 Bryony Thompson Gene: arhgef1 has been classified as Amber List (Moderate Evidence).
Defects of intrinsic and innate immunity v0.140 APOL1 Bryony Thompson Classified gene: APOL1 as Red List (low evidence)
Defects of intrinsic and innate immunity v0.140 APOL1 Bryony Thompson Added comment: Comment on list classification: Included on the IUIS inborn errors of immunity
Defects of intrinsic and innate immunity v0.140 APOL1 Bryony Thompson Gene: apol1 has been classified as Red List (Low Evidence).
Rhabdomyolysis and Metabolic Myopathy v1.17 DTNA Bryony Thompson Classified gene: DTNA as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v1.17 DTNA Bryony Thompson Added comment: Comment on list classification: Exercise intolerance is a prominent feature of the myopathy
Rhabdomyolysis and Metabolic Myopathy v1.17 DTNA Bryony Thompson Gene: dtna has been classified as Green List (High Evidence).
Mitochondrial disease v0.949 ME2 Bryony Thompson Marked gene: ME2 as ready
Mitochondrial disease v0.949 ME2 Bryony Thompson Gene: me2 has been classified as Red List (Low Evidence).
Mitochondrial disease v0.949 ME2 Bryony Thompson gene: ME2 was added
gene: ME2 was added to Mitochondrial disease. Sources: Literature
Mode of inheritance for gene: ME2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ME2 were set to 39401966
Phenotypes for gene: ME2 were set to inborn disorder of energy metabolism MONDO:0019243
Review for gene: ME2 was set to RED
Added comment: A single individual with a homozygous frameshift variant from a consanguineous family. The phenotype included developmental delay, microcephaly, mild brain atrophy, peripheral hypotonia, subtle dysmorphic features, ectopic kidney, and mild lactate elevation. Deletion of yeast ortholog of the gene resulted in growth arrest (which could be rescued).
Sources: Literature
Mendeliome v1.2113 ME2 Bryony Thompson Marked gene: ME2 as ready
Mendeliome v1.2113 ME2 Bryony Thompson Gene: me2 has been classified as Red List (Low Evidence).
Mendeliome v1.2113 ME2 Bryony Thompson gene: ME2 was added
gene: ME2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ME2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ME2 were set to 39401966
Phenotypes for gene: ME2 were set to inborn disorder of energy metabolism MONDO:0019243
Review for gene: ME2 was set to RED
Added comment: A single individual with a homozygous frameshift variant from a consanguineous family. The phenotype included developmental delay, microcephaly, mild brain atrophy, peripheral
hypotonia, subtle dysmorphic features, ectopic kidney, and mild lactate elevation. Deletion of yeast ortholog of the gene resulted in growth arrest (which could be rescued).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6666 TSHZ3 Bryony Thompson Marked gene: TSHZ3 as ready
Intellectual disability syndromic and non-syndromic v0.6666 TSHZ3 Bryony Thompson Gene: tshz3 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6666 TSHZ3 Bryony Thompson Classified gene: TSHZ3 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.6666 TSHZ3 Bryony Thompson Gene: tshz3 has been classified as Amber List (Moderate Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.140 TSHZ3 Bryony Thompson gene: TSHZ3 was added
gene: TSHZ3 was added to Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic. Sources: Literature
Mode of inheritance for gene: TSHZ3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TSHZ3 were set to 27668656; 34919690; 36553458; 39420202
Phenotypes for gene: TSHZ3 were set to congenital anomaly of kidney and urinary tract MONDO:0019719
Review for gene: TSHZ3 was set to AMBER
Added comment: More evidence for the gene-disease association is required
PMID: 27668656 - TSHZ3 is included in the region deleted in chromosome 19q13.11 Deletion Syndrome, which includes intellectual disability and behavioural issues, congenital anomalies of the kidney and urinary tract (CAKUT)
PMID: 34919690 - haploinsufficient mouse model leads to kidney defects
PMID: 36553458 - heterozygous frameshift variant c.119_120dup p.Pro41SerfsTer79 in a case with intellectual disability, behavioural issues, pyelocaliceal dilatation, and mild urethral stenosis.
PMID: 39420202 - 12 CAKUT patients from 9/301 (3%) families carried 5 different rare heterozygous TSHZ3 missense variants. However, 1 of the variants (p.Ser58Gly) present in 5 of the families is more common in gnomAD v4.1 than you would expect for a dominant disease including 5 homozygotes (1,408/1,612,114 alleles, 5 hom, AF=0.0008734). The authors state this is not unexpected in a condition, such as CAKUT. However, the different missense variants are inherited from unaffected parents in at least 2/9 families (there was no phenotype information available for an additional 3 parents).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6666 TSHZ3 Bryony Thompson Classified gene: TSHZ3 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.6666 TSHZ3 Bryony Thompson Gene: tshz3 has been classified as Amber List (Moderate Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.140 TSHZ3 Bryony Thompson gene: TSHZ3 was added
gene: TSHZ3 was added to Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic. Sources: Literature
Mode of inheritance for gene: TSHZ3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TSHZ3 were set to 27668656; 34919690; 36553458; 39420202
Phenotypes for gene: TSHZ3 were set to congenital anomaly of kidney and urinary tract MONDO:0019719
Review for gene: TSHZ3 was set to AMBER
Added comment: More evidence for the gene-disease association is required
PMID: 27668656 - TSHZ3 is included in the region deleted in chromosome 19q13.11 Deletion Syndrome, which includes intellectual disability and behavioural issues, congenital anomalies of the kidney and urinary tract (CAKUT)
PMID: 34919690 - haploinsufficient mouse model leads to kidney defects
PMID: 36553458 - heterozygous frameshift variant c.119_120dup p.Pro41SerfsTer79 in a case with intellectual disability, behavioural issues, pyelocaliceal dilatation, and mild urethral stenosis.
PMID: 39420202 - 12 CAKUT patients from 9/301 (3%) families carried 5 different rare heterozygous TSHZ3 missense variants. However, 1 of the variants (p.Ser58Gly) present in 5 of the families is more common in gnomAD v4.1 than you would expect for a dominant disease including 5 homozygotes (1,408/1,612,114 alleles, 5 hom, AF=0.0008734). The authors state this is not unexpected in a condition, such as CAKUT. However, the different missense variants are inherited from unaffected parents in at least 2/9 families (there was no phenotype information available for an additional 3 parents).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6665 TSHZ3 Bryony Thompson gene: TSHZ3 was added
gene: TSHZ3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: TSHZ3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TSHZ3 were set to 27668656; 34919690; 36553458; 39420202
Phenotypes for gene: TSHZ3 were set to congenital anomaly of kidney and urinary tract MONDO:0019719
Review for gene: TSHZ3 was set to AMBER
Added comment: More evidence for the gene-disease association is required
PMID: 27668656 - TSHZ3 is included in the region deleted in chromosome 19q13.11 Deletion Syndrome, which includes intellectual disability and behavioural issues, congenital anomalies of the kidney and urinary tract (CAKUT)
PMID: 34919690 - haploinsufficient mouse model leads to kidney defects
PMID: 36553458 - heterozygous frameshift variant c.119_120dup p.Pro41SerfsTer79 in a case with intellectual disability, behavioural issues, pyelocaliceal dilatation, and mild urethral stenosis.
PMID: 39420202 - 12 CAKUT patients from 9/301 (3%) families carried 5 different rare heterozygous TSHZ3 missense variants. However, 1 of the variants (p.Ser58Gly) present in 5 of the families is more common in gnomAD v4.1 than you would expect for a dominant disease including 5 homozygotes (1,408/1,612,114 alleles, 5 hom, AF=0.0008734). The authors state this is not unexpected in a condition, such as CAKUT. However, the different missense variants are inherited from unaffected parents in at least 2/9 families (there was no phenotype information available for an additional 3 parents).
Sources: Literature
Mendeliome v1.2112 TSHZ3 Bryony Thompson Marked gene: TSHZ3 as ready
Mendeliome v1.2112 TSHZ3 Bryony Thompson Gene: tshz3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2112 TSHZ3 Bryony Thompson Classified gene: TSHZ3 as Amber List (moderate evidence)
Mendeliome v1.2112 TSHZ3 Bryony Thompson Gene: tshz3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2111 TSHZ3 Bryony Thompson gene: TSHZ3 was added
gene: TSHZ3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TSHZ3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TSHZ3 were set to 27668656; 34919690; 36553458; 39420202
Phenotypes for gene: TSHZ3 were set to congenital anomaly of kidney and urinary tract MONDO:0019719
Review for gene: TSHZ3 was set to AMBER
Added comment: More evidence for the gene-disease association is required
PMID: 27668656 - TSHZ3 is included in the region deleted in chromosome 19q13.11 Deletion Syndrome, which includes intellectual disability and behavioural issues, congenital anomalies of the kidney and urinary tract (CAKUT)
PMID: 34919690 - haploinsufficient mouse model leads to kidney defects
PMID: 36553458 - heterozygous frameshift variant c.119_120dup p.Pro41SerfsTer79 in a case with intellectual disability, behavioural issues, pyelocaliceal dilatation, and mild urethral stenosis.
PMID: 39420202 - 12 CAKUT patients from 9/301 (3%) families carried 5 different rare heterozygous TSHZ3 missense variants. However, 1 of the variants (p.Ser58Gly) present in 5 of the families is more common in gnomAD v4.1 than you would expect for a dominant disease including 5 homozygotes (1,408/1,612,114 alleles, 5 hom, AF=0.0008734). The authors state this is not unexpected in a condition, such as CAKUT. However, the different missense variants are inherited from unaffected parents in at least 2/9 families (there was no phenotype information available for an additional 3 parents).
Sources: Literature
Cholestasis v0.249 WDR83OS Bryony Thompson Phenotypes for gene: WDR83OS were changed from Cholestasis to complex neurodevelopmental disorder MONDO:0100038; neurodevelopmental disorder with hypercholanemia
Cholestasis v0.248 WDR83OS Bryony Thompson Publications for gene: WDR83OS were set to 39471804; 30250217
Cholestasis v0.247 WDR83OS Bryony Thompson Publications for gene: WDR83OS were set to 30250217
Mendeliome v1.2110 WDR83OS Bryony Thompson Phenotypes for gene: WDR83OS were changed from Cholestasis to complex neurodevelopmental disorder MONDO:0100038; neurodevelopmental disorder with hypercholanemia
Intellectual disability syndromic and non-syndromic v0.6664 WDR83OS Bryony Thompson Marked gene: WDR83OS as ready
Intellectual disability syndromic and non-syndromic v0.6664 WDR83OS Bryony Thompson Gene: wdr83os has been classified as Green List (High Evidence).
Mendeliome v1.2109 WDR83OS Bryony Thompson Publications for gene: WDR83OS were set to 30250217
Intellectual disability syndromic and non-syndromic v0.6664 WDR83OS Bryony Thompson Classified gene: WDR83OS as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6664 WDR83OS Bryony Thompson Gene: wdr83os has been classified as Green List (High Evidence).
Cholestasis v0.246 WDR83OS Bryony Thompson Classified gene: WDR83OS as Green List (high evidence)
Cholestasis v0.246 WDR83OS Bryony Thompson Gene: wdr83os has been classified as Green List (High Evidence).
Cholestasis v0.245 WDR83OS Bryony Thompson reviewed gene: WDR83OS: Rating: GREEN; Mode of pathogenicity: None; Publications: 39471804, 30250217; Phenotypes: complex neurodevelopmental disorder MONDO:0100038, neurodevelopmental disorder with hypercholanemia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6663 WDR83OS Bryony Thompson gene: WDR83OS was added
gene: WDR83OS was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: WDR83OS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR83OS were set to 39471804; 30250217
Phenotypes for gene: WDR83OS were set to complex neurodevelopmental disorder MONDO:0100038; neurodevelopmental disorder with hypercholanemia
Review for gene: WDR83OS was set to GREEN
Added comment: Now 14 cases from 9 unrelated families with homozygous LoF variants, including the family reported in 2019. Consistent clinical features include NDD (14/14), facial dysmorphism (13/14), intractable itching (9/14), and elevated bile acids (5/6). Also, supporting null zebrafish model that recapitulates the human phenotype.
Sources: Literature
Mendeliome v1.2108 WDR83OS Bryony Thompson edited their review of gene: WDR83OS: Changed phenotypes: complex neurodevelopmental disorder MONDO:0100038, neurodevelopmental disorder with hypercholanemia
Mendeliome v1.2108 WDR83OS Bryony Thompson changed review comment from: Now 14 cases from 9 unrelated families with homozygous LoF variants. Consistent clinical features include NDD (14/14), facial dysmorphism (13/14), intractable itching (9/14), and elevated bile acids (5/6). Also, supporting null zebrafish model that recapitulates the human phenotype.; to: Now 14 cases from 9 unrelated families with homozygous LoF variants, including the family reported in 2019. Consistent clinical features include NDD (14/14), facial dysmorphism (13/14), intractable itching (9/14), and elevated bile acids (5/6). Also, supporting null zebrafish model that recapitulates the human phenotype.
Mendeliome v1.2108 WDR83OS Bryony Thompson Classified gene: WDR83OS as Green List (high evidence)
Mendeliome v1.2108 WDR83OS Bryony Thompson Gene: wdr83os has been classified as Green List (High Evidence).
Mendeliome v1.2107 WDR83OS Bryony Thompson reviewed gene: WDR83OS: Rating: GREEN; Mode of pathogenicity: None; Publications: 39471804, 30250217; Phenotypes: complex neurodevelopmental disorder MONDO:0100038; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6662 GON4L Bryony Thompson Marked gene: GON4L as ready
Intellectual disability syndromic and non-syndromic v0.6662 GON4L Bryony Thompson Gene: gon4l has been classified as Green List (High Evidence).
Fetal anomalies v1.293 GON4L Bryony Thompson Marked gene: GON4L as ready
Fetal anomalies v1.293 GON4L Bryony Thompson Gene: gon4l has been classified as Green List (High Evidence).
Fetal anomalies v1.293 GON4L Bryony Thompson Classified gene: GON4L as Green List (high evidence)
Fetal anomalies v1.293 GON4L Bryony Thompson Gene: gon4l has been classified as Green List (High Evidence).
Fetal anomalies v1.292 GON4L Bryony Thompson gene: GON4L was added
gene: GON4L was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: GON4L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GON4L were set to 39500882; 21937992
Phenotypes for gene: GON4L were set to complex neurodevelopmental disorder MONDO:0100038
Review for gene: GON4L was set to GREEN
Added comment: 2 LoF variants in 4 cases from 3 unrelated consanguineous families, and supporting null zebrafish model
PMID: 39500882 - 2 homozygous truncating GON4L variants [NM_001282860.2: c.62_63del, p.(Gln21Argfs*12) and c.5517+1G>A] in 3 patients from 2 consanguineous families with prenatal-onset growth impairment, developmental delay, mild intellectual disability, speech impairment, progressive and disproportionate microcephaly, facial asymmetry, congenital heart anomaly, and brain structure abnormalities.
Null zebrafish model had distinct morphological and size abnormalities in the craniofacial cartilage of zebrafish larvae
Heterozygous carriers in biallelic families were unaffected
PMID: 21937992 - a case from Iran from a consanguineous family homozygous for c.5517+1G>A with syndromic ID. No other clinical details provided
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6662 GON4L Bryony Thompson Classified gene: GON4L as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6662 GON4L Bryony Thompson Gene: gon4l has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6661 GON4L Bryony Thompson gene: GON4L was added
gene: GON4L was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: GON4L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GON4L were set to 39500882; 21937992
Phenotypes for gene: GON4L were set to complex neurodevelopmental disorder MONDO:0100038
Review for gene: GON4L was set to GREEN
Added comment: 2 LoF variants in 4 cases from 3 unrelated consanguineous families, and supporting null zebrafish model
PMID: 39500882 - 2 homozygous truncating GON4L variants [NM_001282860.2: c.62_63del, p.(Gln21Argfs*12) and c.5517+1G>A] in 3 patients from 2 consanguineous families with prenatal-onset growth impairment, developmental delay, mild intellectual disability, speech impairment, progressive and disproportionate microcephaly, facial asymmetry, congenital heart anomaly, and brain structure abnormalities.
Null zebrafish model had distinct morphological and size abnormalities in the craniofacial cartilage of zebrafish larvae
Heterozygous carriers in biallelic families were unaffected
PMID: 21937992 - a case from Iran from a consanguineous family homozygous for c.5517+1G>A with syndromic ID. No other clinical details provided
Sources: Literature
Mendeliome v1.2107 GON4L Bryony Thompson Marked gene: GON4L as ready
Mendeliome v1.2107 GON4L Bryony Thompson Gene: gon4l has been classified as Green List (High Evidence).
Mendeliome v1.2107 GON4L Bryony Thompson Classified gene: GON4L as Green List (high evidence)
Mendeliome v1.2107 GON4L Bryony Thompson Gene: gon4l has been classified as Green List (High Evidence).
Mendeliome v1.2106 GON4L Bryony Thompson gene: GON4L was added
gene: GON4L was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GON4L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GON4L were set to 39500882; 21937992; 31785789; 34011629; 33077954
Phenotypes for gene: GON4L were set to complex neurodevelopmental disorder MONDO:0100038
Review for gene: GON4L was set to GREEN
Added comment: 2 LoF variants in 4 cases from 3 unrelated consanguineous families, and supporting null zebrafish model
PMID: 39500882 - 2 homozygous truncating GON4L variants [NM_001282860.2: c.62_63del, p.(Gln21Argfs*12) and c.5517+1G>A] in 3 patients from 2 consanguineous families with prenatal-onset growth impairment, developmental delay, mild intellectual disability, speech impairment, progressive and disproportionate microcephaly, facial asymmetry, congenital heart anomaly, and brain structure abnormalities.
Null zebrafish model had distinct morphological and size abnormalities in the craniofacial cartilage of zebrafish larvae
Heterozygous carriers in biallelic families were unaffected
PMID: 21937992 - a case from Iran from a consanguineous family homozygous for c.5517+1G>A with syndromic ID. No other clinical details provided

Limited evidence for AD gene-disease association - heterozygous de novo variants identified in autism studies and a congenital hydrocephalus study. But, heterozygous carriers in families with biallelic LoF variants are healthy
PMID: 31785789 - 4 (3 NS & 1 Silent) de novo GON4L variants in cases with autism (n=3) & neurodevelopmental disorder
PMID: 34011629 - 2 cases with autism spectrum disorder and de novo missense
PMID: 33077954 - a de novo splice site variant identified in a single case with congenital hydrocephalus
Sources: Literature
Prepair 1000+ v1.546 LAMB3 Andrew Coventry reviewed gene: LAMB3: Rating: GREEN; Mode of pathogenicity: None; Publications: 7706760, 10577906, 17476356, 7698759, 11023379; Phenotypes: Epidermolysis bullosa, junctional 1A, intermediate MIM#226650, Epidermolysis bullosa, junctional 1B, severe MIM#226700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.546 KLHL40 Andrew Coventry reviewed gene: KLHL40: Rating: GREEN; Mode of pathogenicity: None; Publications: 23746549, 24960163, 32352246, 31908664, 27528495; Phenotypes: Nemaline myopathy 8, autosomal recessive MIM#615348; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.546 KCNQ1 Andrew Coventry changed review comment from: Characterised by congenital deafness, prolongation of the QT interval, syncopal attacks due to ventricular arrhythmias, and a high risk of sudden death (including during childhood).
Definitive by ClinGen
Moue model present and functional studies.

Note: alterations have also been shown to cause other arrythmias, e.g. Romano-Ward Syndrome (type of Long QT Syndrome) in an AD manner (PMID: 29037160); to: Characterised by congenital deafness, prolongation of the QT interval, syncopal attacks due to ventricular arrhythmias, and a high risk of sudden death (including during childhood).
Definitive by ClinGen
Mouse model present and functional studies.

Note: alterations have also been shown to cause other arrythmias, e.g. Romano-Ward Syndrome (type of Long QT Syndrome) in an AD manner (PMID: 29037160)
Prepair 1000+ v1.546 KCNQ1 Andrew Coventry reviewed gene: KCNQ1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9020846, 29037160, 20301579; Phenotypes: Jervell and Lange-Nielsen syndrome MIM#220400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.546 JAM3 Andrew Coventry reviewed gene: JAM3: Rating: GREEN; Mode of pathogenicity: None; Publications: 23255084, 21109224, 34292449; Phenotypes: Hemorrhagic destruction of the brain, subependymal calcification, and cataracts MIM#613730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.546 ITCH Andrew Coventry reviewed gene: ITCH: Rating: AMBER; Mode of pathogenicity: None; Publications: 20170897, 31091003, 32356405, 9462731, 9462742; Phenotypes: Autoimmune disease, multisystem, with facial dysmorphism MIM#613385; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.546 IQCB1 Andrew Coventry reviewed gene: IQCB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15723066, 21220633, 20881296, 21901789, 33512896, 33535056, 29219953; Phenotypes: Senior-Loken syndrome 5 MIM#609254; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2105 SGSM3 Zornitza Stark Publications for gene: SGSM3 were set to PMID: 37833060
Mendeliome v1.2104 SGSM3 Zornitza Stark Classified gene: SGSM3 as Green List (high evidence)
Mendeliome v1.2104 SGSM3 Zornitza Stark Gene: sgsm3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6660 SGSM3 Zornitza Stark Publications for gene: SGSM3 were set to PMID: 37833060
Intellectual disability syndromic and non-syndromic v0.6659 SGSM3 Zornitza Stark Classified gene: SGSM3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6659 SGSM3 Zornitza Stark Gene: sgsm3 has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.318 LSM7 Zornitza Stark Publications for gene: LSM7 were set to https://doi.org/10.1016/j.xhgg.2021.100034
Leukodystrophy - paediatric v0.317 LSM7 Zornitza Stark Phenotypes for gene: LSM7 were changed from Leukodystrophy; fetal death to leukodystrophy MONDO:0019046, LRM7-related
Leukodystrophy - paediatric v0.316 LSM7 Zornitza Stark Classified gene: LSM7 as Amber List (moderate evidence)
Leukodystrophy - paediatric v0.316 LSM7 Zornitza Stark Gene: lsm7 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2103 LSM7 Zornitza Stark Phenotypes for gene: LSM7 were changed from Leukodystrophy; foetal death to leukodystrophy MONDO:0019046, LRM7-related
Genetic Epilepsy v1.72 DALRD3 Zornitza Stark Publications for gene: DALRD3 were set to 32427860
Mendeliome v1.2102 DALRD3 Zornitza Stark Publications for gene: DALRD3 were set to 32427860
Mendeliome v1.2101 UBTF Zornitza Stark Phenotypes for gene: UBTF were changed from Neurodegeneration, childhood-onset, with brain atrophy, MIM# 617672; MONDO:0044701 to Neurodegeneration, childhood-onset, with brain atrophy, MIM# 617672; MONDO:0044701; Neurodevelopmental disorder, MONDO:0700092, UBTF-related
Mendeliome v1.2100 UBTF Zornitza Stark Publications for gene: UBTF were set to 28777933; 29300972
Mendeliome v1.2099 UBTF Zornitza Stark edited their review of gene: UBTF: Added comment: PMID 39366741: 3 Chinese patients with global developmental delay, intellectual disability, social challenges and dysmorphism (wide forehead, sparse eyebrows, hypertelorism, narrow palpebral fissures, single-fold eyelids, flat nasal bridge, anteverted nares, a long philtrum and a thin upper lip), but no neuroregression (but aged 1.8yrs-4.8yrs). WES with SNV/CNV analysis showed:
-nonsense variant c.1327C>T p. (Arg443Ter) - parental segregation not possible
-de novo ~46 kb deletion at 17q21.31 containing 7 genes but UBTF as only OMIM Morbid gene
-de novo ~106kb deletion at 17q21.31 containing 10 genes but UBTF as only relevant OMIM Morbid gene (other one was SLC4A1)

Propose haploinsufficiency presents with different phenotype to CONDBA which is due to GOF variant.

AMBER for this mechanism and phenotype.; Changed publications: 28777933, 29300972, 39366741; Changed phenotypes: Neurodegeneration, childhood-onset, with brain atrophy, MIM# 617672, MONDO:0044701, Neurodevelopmental disorder, MONDO:0700092, UBTF-related
Intellectual disability syndromic and non-syndromic v0.6658 UBTF Zornitza Stark Phenotypes for gene: UBTF were changed from Neurodegeneration, childhood-onset, with brain atrophy, MIM# 617672; MONDO:0044701 to Neurodegeneration, childhood-onset, with brain atrophy, MIM# 617672; MONDO:0044701; Neurodevelopmental disorder, MONDO:0700092, UBTF-related
Intellectual disability syndromic and non-syndromic v0.6657 UBTF Zornitza Stark Publications for gene: UBTF were set to 28777933; 29300972
Intellectual disability syndromic and non-syndromic v0.6656 MARK2 Zornitza Stark Marked gene: MARK2 as ready
Intellectual disability syndromic and non-syndromic v0.6656 MARK2 Zornitza Stark Gene: mark2 has been classified as Green List (High Evidence).
Mendeliome v1.2099 MARK2 Zornitza Stark Marked gene: MARK2 as ready
Mendeliome v1.2099 MARK2 Zornitza Stark Gene: mark2 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.71 MARK2 Zornitza Stark Marked gene: MARK2 as ready
Genetic Epilepsy v1.71 MARK2 Zornitza Stark Gene: mark2 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.71 MARK2 Zornitza Stark Classified gene: MARK2 as Green List (high evidence)
Genetic Epilepsy v1.71 MARK2 Zornitza Stark Gene: mark2 has been classified as Green List (High Evidence).
Autism v0.201 MARK2 Zornitza Stark Marked gene: MARK2 as ready
Autism v0.201 MARK2 Zornitza Stark Gene: mark2 has been classified as Green List (High Evidence).
Autism v0.201 MARK2 Zornitza Stark Classified gene: MARK2 as Green List (high evidence)
Autism v0.201 MARK2 Zornitza Stark Gene: mark2 has been classified as Green List (High Evidence).
Mendeliome v1.2099 IRAK2 Zornitza Stark Marked gene: IRAK2 as ready
Mendeliome v1.2099 IRAK2 Zornitza Stark Gene: irak2 has been classified as Red List (Low Evidence).
Mendeliome v1.2099 IRAK2 Zornitza Stark Phenotypes for gene: IRAK2 were changed from Immune dysregulation, no OMIM # to Immune dysregulation, MONDO:0957790, IRAK2-related
Mendeliome v1.2098 IRAK2 Zornitza Stark reviewed gene: IRAK2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Immune dysregulation, MONDO:0957790, IRAK2-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Defects of intrinsic and innate immunity v0.139 IRAK2 Zornitza Stark Marked gene: IRAK2 as ready
Defects of intrinsic and innate immunity v0.139 IRAK2 Zornitza Stark Gene: irak2 has been classified as Red List (Low Evidence).
Defects of intrinsic and innate immunity v0.139 IRAK2 Zornitza Stark Phenotypes for gene: IRAK2 were changed from Immune dysregulation, no OMIM # to Immune dysregulation, MONDO:0957790, IRAK2-related
Defects of intrinsic and innate immunity v0.138 IRAK2 Zornitza Stark reviewed gene: IRAK2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Immune dysregulation, MONDO:0957790, IRAK2-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Autoinflammatory Disorders v1.54 IRAK2 Zornitza Stark Marked gene: IRAK2 as ready
Autoinflammatory Disorders v1.54 IRAK2 Zornitza Stark Gene: irak2 has been classified as Red List (Low Evidence).
Autoinflammatory Disorders v1.54 IRAK2 Zornitza Stark Phenotypes for gene: IRAK2 were changed from Immune dysregulation, no OMIM # to Immune dysregulation, MONDO:0957790, IRAK2-related
Autoinflammatory Disorders v1.53 IRAK2 Zornitza Stark reviewed gene: IRAK2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Immune dysregulation, MONDO:0957790, IRAK2-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rhabdomyolysis and Metabolic Myopathy v1.16 DTNA Zornitza Stark reviewed gene: DTNA: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy, MONDO:0020121, DTNA-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rhabdomyolysis and Metabolic Myopathy v1.16 DTNA Zornitza Stark Marked gene: DTNA as ready
Rhabdomyolysis and Metabolic Myopathy v1.16 DTNA Zornitza Stark Gene: dtna has been classified as Amber List (Moderate Evidence).
Rhabdomyolysis and Metabolic Myopathy v1.16 DTNA Zornitza Stark Phenotypes for gene: DTNA were changed from Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis MONDO:0859322 to Muscular dystrophy, MONDO:0020121, DTNA-related
Mendeliome v1.2098 DTNA Zornitza Stark Publications for gene: DTNA were set to 29118297; 11238270; 16427346
Mendeliome v1.2097 DTNA Zornitza Stark Phenotypes for gene: DTNA were changed from Left ventricular noncompaction 1, with or without congenital heart defects, MIM# 604169 to Muscular dystrophy, MONDO:0020121, DTNA-related; Left ventricular noncompaction 1, with or without congenital heart defects, MIM# 604169
Muscular dystrophy and myopathy_Paediatric v1.78 DTNA Zornitza Stark Marked gene: DTNA as ready
Muscular dystrophy and myopathy_Paediatric v1.78 DTNA Zornitza Stark Gene: dtna has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.78 DTNA Zornitza Stark Phenotypes for gene: DTNA were changed from Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis MONDO:0859322 to Muscular dystrophy, MONDO:0020121, DTNA-related
Mendeliome v1.2096 IKZF2 Zornitza Stark Phenotypes for gene: IKZF2 were changed from Immunodeficiency, MONDO:0021094, IKZF2-related; Immune dysregulation to Immunodeficiency, MONDO:0021094, IKZF2-related; Immune dysregulation; nonsyndromic genetic hearing loss MONDO:0019497, IKZF2-related
Mendeliome v1.2095 IKZF2 Zornitza Stark Publications for gene: IKZF2 were set to 34920454; 34826259
Mendeliome v1.2094 CRACR2A Sangavi Sivagnanasundram reviewed gene: CRACR2A: Rating: AMBER; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008378; Phenotypes: combined immunodeficiency MONDO:0015131; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2094 DNAH9 Sangavi Sivagnanasundram reviewed gene: DNAH9: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008406; Phenotypes: ciliary dyskinesia, primary, 40 MONDO:0032664; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2094 FUK Sangavi Sivagnanasundram reviewed gene: FUK: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008377; Phenotypes: congenital disorder of glycosylation with defective fucosylation 2 MONDO:0020777; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2094 CTPS1 Sangavi Sivagnanasundram reviewed gene: CTPS1: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008376; Phenotypes: severe combined immunodeficiency due to CTPS1 deficiency MONDO:0014391; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2094 SOX6 Sangavi Sivagnanasundram reviewed gene: SOX6: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008480; Phenotypes: complex neurodevelopmental disorder MONDO:0100038; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Callosome v0.538 BHLHE22 Zornitza Stark Marked gene: BHLHE22 as ready
Callosome v0.538 BHLHE22 Zornitza Stark Gene: bhlhe22 has been classified as Green List (High Evidence).
Callosome v0.538 BHLHE22 Zornitza Stark Classified gene: BHLHE22 as Green List (high evidence)
Callosome v0.538 BHLHE22 Zornitza Stark Gene: bhlhe22 has been classified as Green List (High Evidence).
Callosome v0.537 BHLHE22 Zornitza Stark gene: BHLHE22 was added
gene: BHLHE22 was added to Callosome. Sources: Literature
Mode of inheritance for gene: BHLHE22 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: BHLHE22 were set to 39502664
Phenotypes for gene: BHLHE22 were set to Neurodevelopmental disorder, MONDO:0700092, BHLHE22-related
Review for gene: BHLHE22 was set to GREEN
Added comment: Four individuals with de novo missense variants within the highly conserved helix-loop-helix domain and seven individuals from five unrelated families with a recurrent homozygous frameshift variant, p.(Gly74Alafs*18).

Individuals presented with absent or limited speech, severely impaired motor abilities, intellectual disability (ID), involuntary movements, autistic traits with stereotypies, abnormal muscle tone. The majority of individuals had partial or complete agenesis of the corpus callosum (ACC). Additional symptoms comprised epilepsy, variable dysmorphic features, and eye anomalies. One additional individual had spastic paraplegia without delayed development and ACC, expanding the phenotype to milder and later onset forms.

Mice lacking bhlhe22 show nearly complete loss of three brain comminsure, including the corpus callosum.
Sources: Literature
Mendeliome v1.2094 BHLHE22 Zornitza Stark Marked gene: BHLHE22 as ready
Mendeliome v1.2094 BHLHE22 Zornitza Stark Gene: bhlhe22 has been classified as Green List (High Evidence).
Mendeliome v1.2094 BHLHE22 Zornitza Stark Classified gene: BHLHE22 as Green List (high evidence)
Mendeliome v1.2094 BHLHE22 Zornitza Stark Gene: bhlhe22 has been classified as Green List (High Evidence).
Mendeliome v1.2093 BHLHE22 Zornitza Stark gene: BHLHE22 was added
gene: BHLHE22 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BHLHE22 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: BHLHE22 were set to 39502664
Phenotypes for gene: BHLHE22 were set to Neurodevelopmental disorder, MONDO:0700092, BHLHE22-related
Review for gene: BHLHE22 was set to GREEN
Added comment: Four individuals with de novo missense variants within the highly conserved helix-loop-helix domain and seven individuals from five unrelated families with a recurrent homozygous frameshift variant, p.(Gly74Alafs*18).

Individuals presented with absent or limited speech, severely impaired motor abilities, intellectual disability (ID), involuntary movements, autistic traits with stereotypies, abnormal muscle tone. The majority of individuals had partial or complete agenesis of the corpus callosum (ACC). Additional symptoms comprised epilepsy, variable dysmorphic features, and eye anomalies. One additional individual had spastic paraplegia without delayed development and ACC, expanding the phenotype to milder and later onset forms.

Mice lacking bhlhe22 show nearly complete loss of three brain comminsure, including the corpus callosum.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6656 BHLHE22 Zornitza Stark Classified gene: BHLHE22 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6656 BHLHE22 Zornitza Stark Gene: bhlhe22 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6655 BHLHE22 Zornitza Stark Marked gene: BHLHE22 as ready
Intellectual disability syndromic and non-syndromic v0.6655 BHLHE22 Zornitza Stark Gene: bhlhe22 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6655 BHLHE22 Zornitza Stark Classified gene: BHLHE22 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6655 BHLHE22 Zornitza Stark Gene: bhlhe22 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6654 BHLHE22 Zornitza Stark gene: BHLHE22 was added
gene: BHLHE22 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: BHLHE22 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: BHLHE22 were set to 39502664
Phenotypes for gene: BHLHE22 were set to Neurodevelopmental disorder, MONDO:0700092, BHLHE22-related
Review for gene: BHLHE22 was set to GREEN
Added comment: Four individuals with de novo missense variants within the highly conserved helix-loop-helix domain and seven individuals from five unrelated families with a recurrent homozygous frameshift variant, p.(Gly74Alafs*18).

Individuals presented with absent or limited speech, severely impaired motor abilities, intellectual disability (ID), involuntary movements, autistic traits with stereotypies, abnormal muscle tone. The majority of individuals had partial or complete agenesis of the corpus callosum (ACC). Additional symptoms comprised epilepsy, variable dysmorphic features, and eye anomalies. One additional individual had spastic paraplegia without delayed development and ACC, expanding the phenotype to milder and later onset forms.

Mice lacking bhlhe22 show nearly complete loss of three brain comminsure, including the corpus callosum.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6653 MRPL49 Zornitza Stark Marked gene: MRPL49 as ready
Intellectual disability syndromic and non-syndromic v0.6653 MRPL49 Zornitza Stark Gene: mrpl49 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6653 MRPL49 Zornitza Stark Classified gene: MRPL49 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6653 MRPL49 Zornitza Stark Gene: mrpl49 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6652 MRPL49 Zornitza Stark gene: MRPL49 was added
gene: MRPL49 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: MRPL49 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MRPL49 were set to 39417135
Phenotypes for gene: MRPL49 were set to Mitochondrial disease, MONDO:0044970, MRPL49-related
Review for gene: MRPL49 was set to GREEN
Added comment: Five unrelated families with presentations ranging from Perrault syndrome (primary ovarian insufficiency and sensorineural hearing loss) to severe childhood onset of leukodystrophy, learning disability, microcephaly and retinal dystrophy and bi-allelic variants in this gene.
Sources: Literature
Deafness_IsolatedAndComplex v1.205 MRPL49 Zornitza Stark Marked gene: MRPL49 as ready
Deafness_IsolatedAndComplex v1.205 MRPL49 Zornitza Stark Gene: mrpl49 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.205 MRPL49 Zornitza Stark Classified gene: MRPL49 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.205 MRPL49 Zornitza Stark Gene: mrpl49 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.204 MRPL49 Zornitza Stark gene: MRPL49 was added
gene: MRPL49 was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: MRPL49 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MRPL49 were set to 39417135
Phenotypes for gene: MRPL49 were set to Mitochondrial disease, MONDO:0044970, MRPL49-related
Review for gene: MRPL49 was set to GREEN
Added comment: Five unrelated families with presentations ranging from Perrault syndrome (primary ovarian insufficiency and sensorineural hearing loss) to severe childhood onset of leukodystrophy, learning disability, microcephaly and retinal dystrophy and bi-allelic variants in this gene.
Sources: Literature
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.335 MRPL49 Zornitza Stark Marked gene: MRPL49 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.335 MRPL49 Zornitza Stark Gene: mrpl49 has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.335 MRPL49 Zornitza Stark Classified gene: MRPL49 as Green List (high evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.335 MRPL49 Zornitza Stark Gene: mrpl49 has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.334 MRPL49 Zornitza Stark gene: MRPL49 was added
gene: MRPL49 was added to Primary Ovarian Insufficiency_Premature Ovarian Failure. Sources: Literature
Mode of inheritance for gene: MRPL49 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MRPL49 were set to 39417135
Phenotypes for gene: MRPL49 were set to Mitochondrial disease, MONDO:0044970, MRPL49-related
Review for gene: MRPL49 was set to GREEN
Added comment: Five unrelated families with presentations ranging from Perrault syndrome (primary ovarian insufficiency and sensorineural hearing loss) to severe childhood onset of leukodystrophy, learning disability, microcephaly and retinal dystrophy and bi-allelic variants in this gene.
Sources: Literature
Mendeliome v1.2092 MRPL49 Zornitza Stark Marked gene: MRPL49 as ready
Mendeliome v1.2092 MRPL49 Zornitza Stark Gene: mrpl49 has been classified as Green List (High Evidence).
Mendeliome v1.2092 MRPL49 Zornitza Stark Classified gene: MRPL49 as Green List (high evidence)
Mendeliome v1.2092 MRPL49 Zornitza Stark Gene: mrpl49 has been classified as Green List (High Evidence).
Mendeliome v1.2091 MRPL49 Zornitza Stark gene: MRPL49 was added
gene: MRPL49 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MRPL49 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MRPL49 were set to 39417135
Phenotypes for gene: MRPL49 were set to Mitochondrial disease, MONDO:0044970, MRPL49-related
Review for gene: MRPL49 was set to GREEN
Added comment: Five unrelated families with presentations ranging from Perrault syndrome (primary ovarian insufficiency and sensorineural hearing loss) to severe childhood onset of leukodystrophy, learning disability, microcephaly and retinal dystrophy and bi-allelic variants in this gene.
Sources: Literature
Mendeliome v1.2090 SATB1 Sangavi Sivagnanasundram reviewed gene: SATB1: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008481; Phenotypes: complex neurodevelopmental disorder MONDO:0100038; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6651 SATB1 Sangavi Sivagnanasundram reviewed gene: SATB1: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008481; Phenotypes: complex neurodevelopmental disorder MONDO:0100038; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.2090 NT5C2 Sangavi Sivagnanasundram reviewed gene: NT5C2: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008372; Phenotypes: complex hereditary spastic paraplegia MONDO:0015150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2090 NPTX1 Sangavi Sivagnanasundram reviewed gene: NPTX1: Rating: GREEN; Mode of pathogenicity: Other; Publications: https://search.clinicalgenome.org/CCID:008403; Phenotypes: autosomal dominant cerebellar ataxia MONDO:0020380; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
IBMDx study v0.33 ACKR1 Zornitza Stark edited their review of gene: ACKR1: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
IBMDx study v0.33 ACKR1 Zornitza Stark Mode of inheritance for gene: ACKR1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
IBMDx study v0.32 ACKR1 Zornitza Stark Marked gene: ACKR1 as ready
IBMDx study v0.32 ACKR1 Zornitza Stark Gene: ackr1 has been classified as Amber List (Moderate Evidence).
IBMDx study v0.32 ACKR1 Zornitza Stark Classified gene: ACKR1 as Amber List (moderate evidence)
IBMDx study v0.32 ACKR1 Zornitza Stark Gene: ackr1 has been classified as Amber List (Moderate Evidence).
IBMDx study v0.31 ACKR1 Zornitza Stark gene: ACKR1 was added
gene: ACKR1 was added to IBMDx study. Sources: Expert Review
Mode of inheritance for gene: ACKR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ACKR1 were set to [Blood group, Duffy system] 110700; Duffy null susceptibility allele
Review for gene: ACKR1 was set to AMBER
Added comment: c.-67T>C is associated with low neutrophil counts.
Sources: Expert Review
Arthrogryposis v0.414 MET Achchuthan Shanmugasundram reviewed gene: MET: Rating: GREEN; Mode of pathogenicity: None; Publications: 38429387; Phenotypes: ?Arthrogryposis, distal, type 11, OMIM:620019; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Prepair 1000+ v1.546 ASS1 Lauren Thomas reviewed gene: ASS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25135652, 15334737; Phenotypes: Citrullinaemia (MIM# 215700); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6651 PEX11B Ain Roesley Marked gene: PEX11B as ready
Intellectual disability syndromic and non-syndromic v0.6651 PEX11B Ain Roesley Gene: pex11b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6651 PEX11B Ain Roesley Publications for gene: PEX11B were set to 28129423; 22581968
Intellectual disability syndromic and non-syndromic v0.6650 PEX11B Ain Roesley Phenotypes for gene: PEX11B were changed from to Peroxisome biogenesis disorder 14B MIM#614920
Intellectual disability syndromic and non-syndromic v0.6649 PEX11B Ain Roesley Publications for gene: PEX11B were set to
Intellectual disability syndromic and non-syndromic v0.6648 PEX11B Ain Roesley Mode of inheritance for gene: PEX11B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6647 PEX11B Ain Roesley reviewed gene: PEX11B: Rating: GREEN; Mode of pathogenicity: None; Publications: 28129423, 22581968; Phenotypes: Peroxisome biogenesis disorder 14B MIM#614920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6647 PEX10 Ain Roesley Marked gene: PEX10 as ready
Intellectual disability syndromic and non-syndromic v0.6647 PEX10 Ain Roesley Gene: pex10 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6647 PEX10 Ain Roesley Publications for gene: PEX10 were set to 20301621
Intellectual disability syndromic and non-syndromic v0.6647 PEX10 Ain Roesley Phenotypes for gene: PEX10 were changed from to Peroxisome biogenesis disorder 6A (Zellweger) MIM#614870; Peroxisome biogenesis disorder 6B MIM#614871
Intellectual disability syndromic and non-syndromic v0.6646 PEX10 Ain Roesley Publications for gene: PEX10 were set to
Intellectual disability syndromic and non-syndromic v0.6646 PEX10 Ain Roesley Mode of inheritance for gene: PEX10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6645 PEX10 Ain Roesley reviewed gene: PEX10: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301621; Phenotypes: Peroxisome biogenesis disorder 6A (Zellweger) MIM#614870, Peroxisome biogenesis disorder 6B MIM#614871; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6645 PEX1 Ain Roesley Marked gene: PEX1 as ready
Intellectual disability syndromic and non-syndromic v0.6645 PEX1 Ain Roesley Gene: pex1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6645 PEX1 Ain Roesley Publications for gene: PEX1 were set to
Intellectual disability syndromic and non-syndromic v0.6645 PEX1 Ain Roesley Phenotypes for gene: PEX1 were changed from to Heimler syndrome 1 MIM#234580; Peroxisome biogenesis disorder 1A (Zellweger) MIM#214100; Peroxisome biogenesis disorder 1B (NALD/IRD) MIM#601539
Intellectual disability syndromic and non-syndromic v0.6645 PEX1 Ain Roesley Mode of inheritance for gene: PEX1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6644 PEX1 Ain Roesley edited their review of gene: PEX1: Changed rating: GREEN
Intellectual disability syndromic and non-syndromic v0.6644 PEX1 Ain Roesley reviewed gene: PEX1: Rating: ; Mode of pathogenicity: None; Publications: 20301621; Phenotypes: Heimler syndrome 1 MIM#234580, Peroxisome biogenesis disorder 1A (Zellweger) MIM#214100, Peroxisome biogenesis disorder 1B (NALD/IRD) MIM#601539; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6644 PEPD Ain Roesley Publications for gene: PEPD were set to 26110198; 32455636
Intellectual disability syndromic and non-syndromic v0.6644 PEPD Ain Roesley Phenotypes for gene: PEPD were changed from Prolidase deficiency MIM#170100 to Prolidase deficiency MIM#170100
Intellectual disability syndromic and non-syndromic v0.6643 PEPD Ain Roesley Marked gene: PEPD as ready
Intellectual disability syndromic and non-syndromic v0.6643 PEPD Ain Roesley Gene: pepd has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6643 PEPD Ain Roesley Phenotypes for gene: PEPD were changed from to Prolidase deficiency MIM#170100
Intellectual disability syndromic and non-syndromic v0.6643 PEPD Ain Roesley Publications for gene: PEPD were set to
Intellectual disability syndromic and non-syndromic v0.6643 PEPD Ain Roesley Mode of inheritance for gene: PEPD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6642 PEPD Ain Roesley reviewed gene: PEPD: Rating: GREEN; Mode of pathogenicity: None; Publications: 26110198, 32455636; Phenotypes: Prolidase deficiency MIM#170100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6642 PDSS2 Ain Roesley Phenotypes for gene: PDSS2 were changed from Coenzyme Q10 deficiency, primary, 3 MIM#614652 to Coenzyme Q10 deficiency, primary, 3 MIM#614652
Intellectual disability syndromic and non-syndromic v0.6641 PDSS2 Ain Roesley Marked gene: PDSS2 as ready
Intellectual disability syndromic and non-syndromic v0.6641 PDSS2 Ain Roesley Gene: pdss2 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.6641 PDSS2 Ain Roesley Phenotypes for gene: PDSS2 were changed from Coenzyme Q10 deficiency, primary, 3 MIM#614652 to Coenzyme Q10 deficiency, primary, 3 MIM#614652
Intellectual disability syndromic and non-syndromic v0.6640 PDSS2 Ain Roesley Phenotypes for gene: PDSS2 were changed from to Coenzyme Q10 deficiency, primary, 3 MIM#614652
Intellectual disability syndromic and non-syndromic v0.6640 PDSS2 Ain Roesley Publications for gene: PDSS2 were set to
Intellectual disability syndromic and non-syndromic v0.6639 PDSS2 Ain Roesley Mode of inheritance for gene: PDSS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6639 PDSS2 Ain Roesley Classified gene: PDSS2 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.6639 PDSS2 Ain Roesley Gene: pdss2 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.6638 PDSS2 Ain Roesley reviewed gene: PDSS2: Rating: RED; Mode of pathogenicity: None; Publications: 28125198, 29032433, 25349199, 17186472, 21723727, 10972372; Phenotypes: Coenzyme Q10 deficiency, primary, 3 MIM#614652; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6638 PDHX Ain Roesley Phenotypes for gene: PDHX were changed from Lacticacidemia due to PDX1 deficiency MIM#245349 to Lacticacidemia due to PDX1 deficiency MIM#245349
Intellectual disability syndromic and non-syndromic v0.6638 PDHX Ain Roesley Marked gene: PDHX as ready
Intellectual disability syndromic and non-syndromic v0.6638 PDHX Ain Roesley Gene: pdhx has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6638 PDHX Ain Roesley Phenotypes for gene: PDHX were changed from Lacticacidemia due to PDX1 deficiency MIM#245349 to Lacticacidemia due to PDX1 deficiency MIM#245349
Intellectual disability syndromic and non-syndromic v0.6638 PDHX Ain Roesley Phenotypes for gene: PDHX were changed from to Lacticacidemia due to PDX1 deficiency MIM#245349
Intellectual disability syndromic and non-syndromic v0.6637 PDHX Ain Roesley Publications for gene: PDHX were set to
Intellectual disability syndromic and non-syndromic v0.6637 PDHX Ain Roesley Mode of inheritance for gene: PDHX was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6636 PDHX Ain Roesley reviewed gene: PDHX: Rating: GREEN; Mode of pathogenicity: None; Publications: 34138529; Phenotypes: Lacticacidemia due to PDX1 deficiency MIM#245349; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.546 ALS2 Lauren Thomas reviewed gene: ALS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24315819, 12601111, 30128655, 33409823; Phenotypes: Infantile onset ascending spastic paralysis (MIM#607225), Juvenile amyotrophic lateral sclerosis 2 (MIM#205100), Juvenile primary lateral sclerosis (MIM#606353); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6636 PDHA1 Ain Roesley Publications for gene: PDHA1 were set to 23021068
Intellectual disability syndromic and non-syndromic v0.6636 PDHA1 Ain Roesley Marked gene: PDHA1 as ready
Intellectual disability syndromic and non-syndromic v0.6636 PDHA1 Ain Roesley Gene: pdha1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6636 PDHA1 Ain Roesley Phenotypes for gene: PDHA1 were changed from Pyruvate dehydrogenase E1-alpha deficiency MIM#312170 to Pyruvate dehydrogenase E1-alpha deficiency MIM#312170
Intellectual disability syndromic and non-syndromic v0.6635 PDHA1 Ain Roesley Phenotypes for gene: PDHA1 were changed from to Pyruvate dehydrogenase E1-alpha deficiency MIM#312170
Intellectual disability syndromic and non-syndromic v0.6635 PDHA1 Ain Roesley Publications for gene: PDHA1 were set to
Intellectual disability syndromic and non-syndromic v0.6635 PDHA1 Ain Roesley Mode of inheritance for gene: PDHA1 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.6634 PDHA1 Ain Roesley changed review comment from: In subjects surviving past 6 months, a broad range of intellectual outcomes was observed.; to: ID is a feature of this condition.

PMID:23021068 "In subjects surviving past 6 months, a broad range of intellectual outcomes was observed."
Intellectual disability syndromic and non-syndromic v0.6634 PDHA1 Ain Roesley reviewed gene: PDHA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23021068; Phenotypes: Pyruvate dehydrogenase E1-alpha deficiency MIM#312170; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males); Current diagnostic: yes
Mendeliome v1.2090 SLC24A1 Sangavi Sivagnanasundram reviewed gene: SLC24A1: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008419; Phenotypes: inherited retinal dystrophy MONDO:0019118; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2090 C1QTNF5 Sangavi Sivagnanasundram reviewed gene: C1QTNF5: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008422; Phenotypes: inherited retinal dystrophy MONDO:0019118; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6634 MED16 Zornitza Stark Marked gene: MED16 as ready
Intellectual disability syndromic and non-syndromic v0.6634 MED16 Zornitza Stark Gene: med16 has been classified as Green List (High Evidence).
Mendeliome v1.2090 EPHB2 Sangavi Sivagnanasundram reviewed gene: EPHB2: Rating: AMBER; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008367; Phenotypes: bleeding disorder, platelet-type, 22 MONDO:0032765; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.546 ALG1 Lauren Thomas reviewed gene: ALG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26931382, 24157261, 14973782; Phenotypes: Congenital disorder of glycosylation, type Ik, MIM# 608540; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2090 F12 Sangavi Sivagnanasundram reviewed gene: F12: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: hereditary angioedema type 3 MONDO:0012526; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.2090 HOXA11 Sangavi Sivagnanasundram reviewed gene: HOXA11: Rating: AMBER; Mode of pathogenicity: None; Publications: 11101832; Phenotypes: radioulnar synostosis with amegakaryocytic thrombocytopenia 1 MONDO:0024558; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.2090 CCDC115 Sangavi Sivagnanasundram reviewed gene: CCDC115: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008374; Phenotypes: CCDC115-CDG MONDO:0014789; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Defects of intrinsic and innate immunity v0.138 IRAK2 Chirag Patel Phenotypes for gene: IRAK2 were changed from Immune dysregulation, no OMIM # to Immune dysregulation, no OMIM #
Defects of intrinsic and innate immunity v0.138 IRAK2 Chirag Patel Phenotypes for gene: IRAK2 were changed from Immune dysregulation, no OMIM # to Immune dysregulation, no OMIM #
Defects of intrinsic and innate immunity v0.137 IRAK2 Chirag Patel Phenotypes for gene: IRAK2 were changed from Immune dysregulation, no OMIM # to Immune dysregulation, no OMIM #
Mendeliome v1.2090 IRAK2 Chirag Patel Phenotypes for gene: IRAK2 were changed from Immune dysregulation, no OMIM # to Immune dysregulation, no OMIM #
Mendeliome v1.2090 IRAK2 Chirag Patel Phenotypes for gene: IRAK2 were changed from Immunodeficiency, no OMIM # to Immune dysregulation, no OMIM #
Mendeliome v1.2089 IRAK2 Chirag Patel changed review comment from: 2 individuals with sequential or repeated invasive infections with 2 different variants in IRAK2 gene found on WES testing. The IRAK kinases function as downstream signal transductors following the activation of pathogen recognition receptors. IRAK4 gene has been associated with susceptibility to severe infections by common pyogenic bacteria.

Individual 1 had herpes simplex virus-triggered hemophagocytic lymphohistiocytosis with tuberculosis, and a homozygous missense variant (L78P). There are no homozygous individuals in gnomAD (MAF 0.003%). No segregation testing reported.

Individual 2 had Streptococcus pneumoniae bacteremia with candidemia, and a heterozygous missense variant (R506W) which straddles between the kinase and TRAF6-binding CTD of IRAK2. There are 15 heterozygous individuals in gnomAD for this rare variant with no homozygotes (MAF 0.012%). No segregation testing reported.

Both patients’ peripheral blood mononuclear cells showed tendencies for TNFα hypo-responsiveness to representative bacterial, fungal and viral ligands, in line with subjects with IRAK defects. Immunoprecipitation platform assay to pull down TRAF6 revealed that possession of L78P or R506W variants led to reduced TRAF6 ubiquitination. The led to TRAF6 accumulation and in turn decreased TNFα production (an inflammatory cytokine to invading pathogens).

Paper does not comment on reasons for disease in biallelic and mono-allelic form.
Sources: Literature; to: PMID: 39299377
2 individuals with sequential or repeated invasive infections with 2 different variants in IRAK2 gene found on WES testing. The IRAK kinases function as downstream signal transductors following the activation of pathogen recognition receptors. IRAK4 gene has been associated with susceptibility to severe infections by common pyogenic bacteria.

Individual 1 had herpes simplex virus-triggered hemophagocytic lymphohistiocytosis with tuberculosis, and a homozygous missense variant (L78P). There are no homozygous individuals in gnomAD (MAF 0.003%). No segregation testing reported. Individual 2 had Streptococcus pneumoniae bacteremia with candidemia, and a heterozygous missense variant (R506W) which straddles between the kinase and TRAF6-binding CTD of IRAK2. There are 15 heterozygous individuals in gnomAD for this rare variant with no homozygotes (MAF 0.012%). No segregation testing reported.

Both patients’ peripheral blood mononuclear cells showed tendencies for TNFα hypo-responsiveness to representative bacterial, fungal and viral ligands, in line with subjects with IRAK defects. Immunoprecipitation platform assay to pull down TRAF6 revealed that possession of L78P or R506W variants led to reduced TRAF6 ubiquitination. The led to TRAF6 accumulation and in turn decreased TNFα production (an inflammatory cytokine to invading pathogens). Paper does not comment on reasons for disease in biallelic and mono-allelic form.


Preprint paper:
2 individuals with immune dysregulation (1 x systemic lupus erythematosus and 1 x autoinflammatory disease) with same homozgyous exon 2 deletion in IRAK2 gene found on WES testing and confirmed with Sanger sequencing. Unaffected family members in trio were heterozygous for variant. Exon 2 encodes a proportion of the death domain, a critical protein domain for Myddosome assembly.

The patients exhibited aberrantly upregulated type I interferon (IFN) response following LPS stimulation, which was further confirmed in bone marrow-derived macrophages (BMDMs) in mice. RNA sequencing analysis indicated that PBMCs from the two patients consistently exhibited defects in activating NFkb signaling in response to LPS or R848 stimulation, as well as impaired activation of the MAPK signaling pathway. RNA sequencing demonstrated that BMDMs from Irak2 ∆ex2/∆ex2 mice exhibited defects in NFkb and MAPK signaling pathways, similar to patients’ PBMCs.
Autoinflammatory Disorders v1.53 IRAK2 Chirag Patel gene: IRAK2 was added
gene: IRAK2 was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Literature
Mode of inheritance for gene: IRAK2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: IRAK2 were set to PMID: 39299377
Phenotypes for gene: IRAK2 were set to Immune dysregulation, no OMIM #
Review for gene: IRAK2 was set to RED
Added comment: PMID: 39299377
2 individuals with sequential or repeated invasive infections with 2 different variants in IRAK2 gene found on WES testing. The IRAK kinases function as downstream signal transductors following the activation of pathogen recognition receptors. IRAK4 gene has been associated with susceptibility to severe infections by common pyogenic bacteria.

Individual 1 had herpes simplex virus-triggered hemophagocytic lymphohistiocytosis with tuberculosis, and a homozygous missense variant (L78P). There are no homozygous individuals in gnomAD (MAF 0.003%). No segregation testing reported. Individual 2 had Streptococcus pneumoniae bacteremia with candidemia, and a heterozygous missense variant (R506W) which straddles between the kinase and TRAF6-binding CTD of IRAK2. There are 15 heterozygous individuals in gnomAD for this rare variant with no homozygotes (MAF 0.012%). No segregation testing reported.

Both patients’ peripheral blood mononuclear cells showed tendencies for TNFα hypo-responsiveness to representative bacterial, fungal and viral ligands, in line with subjects with IRAK defects. Immunoprecipitation platform assay to pull down TRAF6 revealed that possession of L78P or R506W variants led to reduced TRAF6 ubiquitination. The led to TRAF6 accumulation and in turn decreased TNFα production (an inflammatory cytokine to invading pathogens). Paper does not comment on reasons for disease in biallelic and mono-allelic form.


Preprint paper:
2 individuals with immune dysregulation (1 x systemic lupus erythematosus and 1 x autoinflammatory disease) with same homozgyous exon 2 deletion in IRAK2 gene found on WES testing and confirmed with Sanger sequencing. Unaffected family members in trio were heterozygous for variant. Exon 2 encodes a proportion of the death domain, a critical protein domain for Myddosome assembly.

The patients exhibited aberrantly upregulated type I interferon (IFN) response following LPS stimulation, which was further confirmed in bone marrow-derived macrophages (BMDMs) in mice. RNA sequencing analysis indicated that PBMCs from the two patients consistently exhibited defects in activating NFkb signaling in response to LPS or R848 stimulation, as well as impaired activation of the MAPK signaling pathway. RNA sequencing demonstrated that BMDMs from Irak2 ∆ex2/∆ex2 mice exhibited defects in NFkb and MAPK signaling pathways, similar to patients’ PBMCs.
Sources: Literature
Defects of intrinsic and innate immunity v0.136 IRAK2 Chirag Patel Phenotypes for gene: IRAK2 were changed from to Immune dysregulation, no OMIM #
Defects of intrinsic and innate immunity v0.135 IRAK2 Chirag Patel changed review comment from: 2 individuals with sequential or repeated invasive infections with 2 different variants in IRAK2 gene found on WES testing. The IRAK kinases function as downstream signal transductors following the activation of pathogen recognition receptors. IRAK4 gene has been associated with susceptibility to severe infections by common pyogenic bacteria.

Individual 1 had herpes simplex virus-triggered hemophagocytic lymphohistiocytosis with tuberculosis, and a homozygous missense variant (L78P). There are no homozygous individuals in gnomAD (MAF 0.003%). No segregation testing reported.

Individual 2 had Streptococcus pneumoniae bacteremia with candidemia, and a heterozygous missense variant (R506W) which straddles between the kinase and TRAF6-binding CTD of IRAK2. There are 15 heterozygous individuals in gnomAD for this rare variant with no homozygotes (MAF 0.012%). No segregation testing reported.

Both patients’ peripheral blood mononuclear cells showed tendencies for TNFα hypo-responsiveness to representative bacterial, fungal and viral ligands, in line with subjects with IRAK defects. Immunoprecipitation platform assay to pull down TRAF6 revealed that possession of L78P or R506W variants led to reduced TRAF6 ubiquitination. The led to TRAF6 accumulation and in turn decreased TNFα production (an inflammatory cytokine to invading pathogens).

Paper does not comment on reasons for disease in biallelic and mono-allelic form.
Sources: Literature; to: PMID: 39299377
2 individuals with sequential or repeated invasive infections with 2 different variants in IRAK2 gene found on WES testing. The IRAK kinases function as downstream signal transductors following the activation of pathogen recognition receptors. IRAK4 gene has been associated with susceptibility to severe infections by common pyogenic bacteria.

Individual 1 had herpes simplex virus-triggered hemophagocytic lymphohistiocytosis with tuberculosis, and a homozygous missense variant (L78P). There are no homozygous individuals in gnomAD (MAF 0.003%). No segregation testing reported. Individual 2 had Streptococcus pneumoniae bacteremia with candidemia, and a heterozygous missense variant (R506W) which straddles between the kinase and TRAF6-binding CTD of IRAK2. There are 15 heterozygous individuals in gnomAD for this rare variant with no homozygotes (MAF 0.012%). No segregation testing reported.

Both patients’ peripheral blood mononuclear cells showed tendencies for TNFα hypo-responsiveness to representative bacterial, fungal and viral ligands, in line with subjects with IRAK defects. Immunoprecipitation platform assay to pull down TRAF6 revealed that possession of L78P or R506W variants led to reduced TRAF6 ubiquitination. The led to TRAF6 accumulation and in turn decreased TNFα production (an inflammatory cytokine to invading pathogens). Paper does not comment on reasons for disease in biallelic and mono-allelic form.


Preprint paper:
2 individuals with immune dysregulation (1 x systemic lupus erythematosus and 1 x autoinflammatory disease) with same homozgyous exon 2 deletion in IRAK2 gene found on WES testing and confirmed with Sanger sequencing. Unaffected family members in trio were heterozygous for variant. Exon 2 encodes a proportion of the death domain, a critical protein domain for Myddosome assembly.

The patients exhibited aberrantly upregulated type I interferon (IFN) response following LPS stimulation, which was further confirmed in bone marrow-derived macrophages (BMDMs) in mice. RNA sequencing analysis indicated that PBMCs from the two patients consistently exhibited defects in activating NFkb signaling in response to LPS or R848 stimulation, as well as impaired activation of the MAPK signaling pathway. RNA sequencing demonstrated that BMDMs from Irak2 ∆ex2/∆ex2 mice exhibited defects in NFkb and MAPK signaling pathways, similar to patients’ PBMCs.
Mendeliome v1.2089 WISP3 Sangavi Sivagnanasundram reviewed gene: WISP3: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008442; Phenotypes: progressive pseudorheumatoid arthropathy of childhood MONDO:0008827; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2089 WDR60 Sangavi Sivagnanasundram reviewed gene: WDR60: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008443; Phenotypes: short-rib thoracic dysplasia 8 with or without polydactyly MONDO:0014214; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.546 ALDH5A1 Lauren Thomas reviewed gene: ALDH5A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9683595, 14635103, 32402538, 32887777; Phenotypes: Succinic semialdehyde dehydrogenase deficiency, MIM# 271980; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.280 ICK Zornitza Stark Marked gene: ICK as ready
Polydactyly v0.280 ICK Zornitza Stark Gene: ick has been classified as Green List (High Evidence).
Polydactyly v0.280 ICK Zornitza Stark Phenotypes for gene: ICK were changed from to Endocrine-cerebroosteodysplasia, MIM# 612651
Polydactyly v0.279 ICK Zornitza Stark Mode of inheritance for gene: ICK was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.278 ICK Zornitza Stark edited their review of gene: ICK: Changed phenotypes: Endocrine-cerebroosteodysplasia, MIM# 612651
Polydactyly v0.278 ICK Zornitza Stark reviewed gene: ICK: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2089 IRAK2 Chirag Patel gene: IRAK2 was added
gene: IRAK2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: IRAK2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: IRAK2 were set to PMID: 39299377
Phenotypes for gene: IRAK2 were set to Immunodeficiency, no OMIM #
Review for gene: IRAK2 was set to RED
Added comment: 2 individuals with sequential or repeated invasive infections with 2 different variants in IRAK2 gene found on WES testing. The IRAK kinases function as downstream signal transductors following the activation of pathogen recognition receptors. IRAK4 gene has been associated with susceptibility to severe infections by common pyogenic bacteria.

Individual 1 had herpes simplex virus-triggered hemophagocytic lymphohistiocytosis with tuberculosis, and a homozygous missense variant (L78P). There are no homozygous individuals in gnomAD (MAF 0.003%). No segregation testing reported.

Individual 2 had Streptococcus pneumoniae bacteremia with candidemia, and a heterozygous missense variant (R506W) which straddles between the kinase and TRAF6-binding CTD of IRAK2. There are 15 heterozygous individuals in gnomAD for this rare variant with no homozygotes (MAF 0.012%). No segregation testing reported.

Both patients’ peripheral blood mononuclear cells showed tendencies for TNFα hypo-responsiveness to representative bacterial, fungal and viral ligands, in line with subjects with IRAK defects. Immunoprecipitation platform assay to pull down TRAF6 revealed that possession of L78P or R506W variants led to reduced TRAF6 ubiquitination. The led to TRAF6 accumulation and in turn decreased TNFα production (an inflammatory cytokine to invading pathogens).

Paper does not comment on reasons for disease in biallelic and mono-allelic form.
Sources: Literature
Defects of intrinsic and innate immunity v0.135 IRAK2 Chirag Patel edited their review of gene: IRAK2: Changed phenotypes: Immunodeficiency, no OMIM #
Defects of intrinsic and innate immunity v0.135 IRAK2 Chirag Patel gene: IRAK2 was added
gene: IRAK2 was added to Defects of innate immunity. Sources: Literature
Mode of inheritance for gene: IRAK2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: IRAK2 were set to PMID: 39299377
Review for gene: IRAK2 was set to RED
Added comment: 2 individuals with sequential or repeated invasive infections with 2 different variants in IRAK2 gene found on WES testing. The IRAK kinases function as downstream signal transductors following the activation of pathogen recognition receptors. IRAK4 gene has been associated with susceptibility to severe infections by common pyogenic bacteria.

Individual 1 had herpes simplex virus-triggered hemophagocytic lymphohistiocytosis with tuberculosis, and a homozygous missense variant (L78P). There are no homozygous individuals in gnomAD (MAF 0.003%). No segregation testing reported.

Individual 2 had Streptococcus pneumoniae bacteremia with candidemia, and a heterozygous missense variant (R506W) which straddles between the kinase and TRAF6-binding CTD of IRAK2. There are 15 heterozygous individuals in gnomAD for this rare variant with no homozygotes (MAF 0.012%). No segregation testing reported.

Both patients’ peripheral blood mononuclear cells showed tendencies for TNFα hypo-responsiveness to representative bacterial, fungal and viral ligands, in line with subjects with IRAK defects. Immunoprecipitation platform assay to pull down TRAF6 revealed that possession of L78P or R506W variants led to reduced TRAF6 ubiquitination. The led to TRAF6 accumulation and in turn decreased TNFα production (an inflammatory cytokine to invading pathogens).

Paper does not comment on reasons for disease in biallelic and mono-allelic form.
Sources: Literature
Prepair 1000+ v1.546 INSR Andrew Coventry reviewed gene: INSR: Rating: GREEN; Mode of pathogenicity: None; Publications: 34965699, 11735220, 12023989, 13302174, 10084586; Phenotypes: Donohue syndrome MIM#246200, Rabson-Mendenhall syndrome MIM#262190; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6634 PDGFRB Ain Roesley Publications for gene: PDGFRB were set to 31710779; 35221873
Intellectual disability syndromic and non-syndromic v0.6634 PDGFRB Ain Roesley Phenotypes for gene: PDGFRB were changed from Kosaki overgrowth syndrome MIM#616592 to Kosaki overgrowth syndrome MIM#616592
Intellectual disability syndromic and non-syndromic v0.6633 PDGFRB Ain Roesley Publications for gene: PDGFRB were set to
Intellectual disability syndromic and non-syndromic v0.6633 PDGFRB Ain Roesley Phenotypes for gene: PDGFRB were changed from to Kosaki overgrowth syndrome MIM#616592
Intellectual disability syndromic and non-syndromic v0.6633 PDGFRB Ain Roesley Mode of inheritance for gene: PDGFRB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6632 PDGFRB Ain Roesley Marked gene: PDGFRB as ready
Intellectual disability syndromic and non-syndromic v0.6632 PDGFRB Ain Roesley Gene: pdgfrb has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6632 PDGFRB Ain Roesley reviewed gene: PDGFRB: Rating: GREEN; Mode of pathogenicity: None; Publications: 31710779, 35221873; Phenotypes: Kosaki overgrowth syndrome MIM#616592; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v1.2088 MARK2 Chirag Patel Classified gene: MARK2 as Green List (high evidence)
Mendeliome v1.2088 MARK2 Chirag Patel Gene: mark2 has been classified as Green List (High Evidence).
Mendeliome v1.2087 MARK2 Chirag Patel gene: MARK2 was added
gene: MARK2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MARK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MARK2 were set to PMID: 39419027, 39436150
Phenotypes for gene: MARK2 were set to Neurodevelopmental disorder MONDO:0700092
Mode of pathogenicity for gene: MARK2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: MARK2 was set to GREEN
Added comment: 31 individuals with autism spectrum disorder (30/31), intellectual disability/developmental delay (100%), motor delay (62%), speech-language problems (100%), seizure/epilepsy (46%), behaviour disorders (ADHD, aggression, anxiety)(74%), and distinctive facial features (narrow face, abnormal or broad forehead, downslanting palpebral fissures, and large or dysplastic ears).

WES/WGS identified 25 LOF and 6 missense variants in MARK2 gene (Microtubule affinity-regulating kinase 2) which contributes to establishing neuronal polarity and developing dendritic spines. LOF variants were de novo (16/25), inherited (4/25), or unk (5/25). All 6 missense variants were de novo and clustered in the kinase or KA1 domains.

The mRNA and protein expression of MARK2 in PBMCs were significantly lower in affected individuals with LOF variants than in the control group. In vitro expression assay of missense variants supported the effect of MARK2 loss. Proband-derived and CRISPR-engineered isogenic induced pluripotent stem cells (iPSCs) showed MARK2 loss leads to early neuronal developmental and functional deficits, including anomalous polarity and disorganization in neural rosettes, as well as imbalanced proliferation and differentiation in neural progenitor cells (NPCs). Mark2+/- mice showed abnormal cortical formation and partition and ASD-like behaviour. Through the use of RNA sequencing (RNA-seq) and lithium treatment, they linked MARK2 loss to downregulation of the WNT/β-catenin signaling pathway and identified lithium as a potential drug for treating MARK2-associated ASD.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6632 PCNT Ain Roesley reviewed gene: PCNT: Rating: AMBER; Mode of pathogenicity: None; Publications: 34978779; Phenotypes: Microcephalic osteodysplastic primordial dwarfism, type II MIM#210720; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v1.2086 DTNA Chirag Patel Classified gene: DTNA as Green List (high evidence)
Mendeliome v1.2086 DTNA Chirag Patel Gene: dtna has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.77 DTNA Chirag Patel Classified gene: DTNA as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.77 DTNA Chirag Patel Gene: dtna has been classified as Green List (High Evidence).
Mendeliome v1.2085 DTNA Chirag Patel reviewed gene: DTNA: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 36799992; Phenotypes: Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis MONDO:0859322; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rhabdomyolysis and Metabolic Myopathy v1.15 DTNA Chirag Patel Classified gene: DTNA as Amber List (moderate evidence)
Rhabdomyolysis and Metabolic Myopathy v1.15 DTNA Chirag Patel Gene: dtna has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v1.76 DTNA Chirag Patel gene: DTNA was added
gene: DTNA was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: DTNA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DTNA were set to PMID: 36799992
Phenotypes for gene: DTNA were set to Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis MONDO:0859322
Mode of pathogenicity for gene: DTNA was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: DTNA was set to GREEN
Added comment: 12 individuals from 4 unrelated families with 2 different monoallelic DTNA variants in exon 18 and affecting the coiled-coil domain of α-dystrobrevin (DTNA). DTNA encodes α-dystrobrevin, a component of the macromolecular dystrophin-glycoprotein complex (DGC) that binds to dystrophin/utrophin and α-syntrophin. Mice lacking α-dystrobrevin have a muscular dystrophy phenotype.

Clinical features with onset between 1st and 4th decades included: myalgia, muscle cramps associated with physical activity, exercise intolerance, and increased serum CK (11/12). Most patients have mild symptoms, only 3 had mild proximal muscle weakness of the lower limbs, and 1 had episode of rhabdomyolysis @20yrs. Muscle biopsies in 8 individuals showed mild myopathic and/or dystrophic features.

The 2 variants (p.Glu529Lys and p.Gln523_Glu529del) were found by targeted exome sequencing and confirmed by Sanger sequencing. They segregated with the disorder in the families and were absent in gnomAD. Immunofluorescent analysis of patient muscle samples showed decreased DTNA immunoreactivity at the sarcolemma, as well as variably reduced immunoreactivity of several other dystrophin-glycoprotein complex (DGC) proteins, suggesting that the DTNA variants resulted in overall destabilization of the DG complex within skeletal muscle.
Sources: Literature
Rhabdomyolysis and Metabolic Myopathy v1.14 DTNA Chirag Patel gene: DTNA was added
gene: DTNA was added to Rhabdomyolysis and Metabolic Myopathy. Sources: Literature
Mode of inheritance for gene: DTNA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DTNA were set to PMID: 36799992
Phenotypes for gene: DTNA were set to Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis MONDO:0859322
Mode of pathogenicity for gene: DTNA was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: DTNA was set to GREEN
Added comment: 12 individuals from 4 unrelated families with 2 different monoallelic DTNA variants in exon 18 and affecting the coiled-coil domain of α-dystrobrevin (DTNA). DTNA encodes α-dystrobrevin, a component of the macromolecular dystrophin-glycoprotein complex (DGC) that binds to dystrophin/utrophin and α-syntrophin. Mice lacking α-dystrobrevin have a muscular dystrophy phenotype.

Clinical features with onset between 1st and 4th decades included: myalgia, muscle cramps associated with physical activity, exercise intolerance, and increased serum CK (11/12). Most patients have mild symptoms, only 3 had mild proximal muscle weakness of the lower limbs, and 1 had episode of rhabdomyolysis @20yrs. Muscle biopsies in 8 individuals showed mild myopathic and/or dystrophic features.

The 2 variants (p.Glu529Lys and p.Gln523_Glu529del) were found by targeted exome sequencing and confirmed by Sanger sequencing. They segregated with the disorder in the families and were absent in gnomAD. Immunofluorescent analysis of patient muscle samples showed decreased DTNA immunoreactivity at the sarcolemma, as well as variably reduced immunoreactivity of several other dystrophin-glycoprotein complex (DGC) proteins, suggesting that the DTNA variants resulted in overall destabilization of the DG complex within skeletal muscle.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6632 PCCA Ain Roesley Mode of inheritance for gene: PCCA was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6631 PCCA Ain Roesley Mode of inheritance for gene: PCCA was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6632 PCCB Ain Roesley Mode of inheritance for gene: PCCB was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6632 PCCB Ain Roesley Publications for gene: PCCB were set to 22593918
Intellectual disability syndromic and non-syndromic v0.6631 PCCB Ain Roesley Publications for gene: PCCB were set to
Intellectual disability syndromic and non-syndromic v0.6631 PCCA Ain Roesley Publications for gene: PCCA were set to 22593918
Intellectual disability syndromic and non-syndromic v0.6631 PCCA Ain Roesley Mode of inheritance for gene: PCCA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6631 PCCB Ain Roesley Phenotypes for gene: PCCB were changed from Propionicacidemia MIM#606054 to Propionicacidemia MIM#606054
Intellectual disability syndromic and non-syndromic v0.6631 PCCB Ain Roesley Phenotypes for gene: PCCB were changed from to Propionicacidemia MIM#606054
Intellectual disability syndromic and non-syndromic v0.6630 PCCB Ain Roesley Mode of inheritance for gene: PCCB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6631 PCDH19 Ain Roesley Publications for gene: PCDH19 were set to 28669061
Intellectual disability syndromic and non-syndromic v0.6630 PCCA Ain Roesley Publications for gene: PCCA were set to
Intellectual disability syndromic and non-syndromic v0.6630 PCDH19 Ain Roesley Marked gene: PCDH19 as ready
Intellectual disability syndromic and non-syndromic v0.6630 PCDH19 Ain Roesley Gene: pcdh19 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6630 PCCA Ain Roesley Phenotypes for gene: PCCA were changed from to Propionicacidemia MIM#606054
Intellectual disability syndromic and non-syndromic v0.6630 PCDH19 Ain Roesley Phenotypes for gene: PCDH19 were changed from to Developmental and epileptic encephalopathy 9 MIM#300088
Intellectual disability syndromic and non-syndromic v0.6630 PCDH19 Ain Roesley Publications for gene: PCDH19 were set to
Intellectual disability syndromic and non-syndromic v0.6630 PCDH19 Ain Roesley Mode of inheritance for gene: PCDH19 was changed from Unknown to Other
Intellectual disability syndromic and non-syndromic v0.6629 PCDH19 Ain Roesley reviewed gene: PCDH19: Rating: GREEN; Mode of pathogenicity: None; Publications: 28669061; Phenotypes: Developmental and epileptic encephalopathy 9 MIM#300088; Mode of inheritance: Other; Current diagnostic: yes
Genetic Epilepsy v1.69 MARK2 Chirag Patel gene: MARK2 was added
gene: MARK2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: MARK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MARK2 were set to PMID: 39419027, 39436150
Phenotypes for gene: MARK2 were set to Neurodevelopmental disorder MONDO:0700092
Review for gene: MARK2 was set to GREEN
Added comment: 31 individuals with autism spectrum disorder (30/31), intellectual disability/developmental delay (100%), motor delay (62%), speech-language problems (100%), seizure/epilepsy (46%), behaviour disorders (ADHD, aggression, anxiety)(74%), and distinctive facial features (narrow face, abnormal or broad forehead, downslanting palpebral fissures, and large or dysplastic ears).

WES/WGS identified 25 LOF and 6 missense variants in MARK2 gene (Microtubule affinity-regulating kinase 2) which contributes to establishing neuronal polarity and developing dendritic spines. LOF variants were de novo (16/25), inherited (4/25), or unk (5/25). All 6 missense variants were de novo and clustered in the kinase or KA1 domains.

The mRNA and protein expression of MARK2 in PBMCs were significantly lower in affected individuals with LOF variants than in the control group. In vitro expression assay of missense variants supported the effect of MARK2 loss. Proband-derived and CRISPR-engineered isogenic induced pluripotent stem cells (iPSCs) showed MARK2 loss leads to early neuronal developmental and functional deficits, including anomalous polarity and disorganization in neural rosettes, as well as imbalanced proliferation and differentiation in neural progenitor cells (NPCs). Mark2+/- mice showed abnormal cortical formation and partition and ASD-like behaviour. Through the use of RNA sequencing (RNA-seq) and lithium treatment, they linked MARK2 loss to downregulation of the WNT/β-catenin signaling pathway and identified lithium as a potential drug for treating MARK2-associated ASD.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6629 PCCB Ain Roesley Marked gene: PCCB as ready
Intellectual disability syndromic and non-syndromic v0.6629 PCCB Ain Roesley Gene: pccb has been classified as Green List (High Evidence).
Autism v0.200 MARK2 Chirag Patel gene: MARK2 was added
gene: MARK2 was added to Autism. Sources: Literature
Mode of inheritance for gene: MARK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MARK2 were set to PMID: 39419027, 39436150
Phenotypes for gene: MARK2 were set to Neurodevelopmental disorder MONDO:0700092
Review for gene: MARK2 was set to GREEN
Added comment: 31 individuals with autism spectrum disorder (30/31), intellectual disability/developmental delay (100%), motor delay (62%), speech-language problems (100%), seizure/epilepsy (46%), behaviour disorders (ADHD, aggression, anxiety)(74%), and distinctive facial features (narrow face, abnormal or broad forehead, downslanting palpebral fissures, and large or dysplastic ears).

WES/WGS identified 25 LOF and 6 missense variants in MARK2 gene (Microtubule affinity-regulating kinase 2) which contributes to establishing neuronal polarity and developing dendritic spines. LOF variants were de novo (16/25), inherited (4/25), or unk (5/25). All 6 missense variants were de novo and clustered in the kinase or KA1 domains.

The mRNA and protein expression of MARK2 in PBMCs were significantly lower in affected individuals with LOF variants than in the control group. In vitro expression assay of missense variants supported the effect of MARK2 loss. Proband-derived and CRISPR-engineered isogenic induced pluripotent stem cells (iPSCs) showed MARK2 loss leads to early neuronal developmental and functional deficits, including anomalous polarity and disorganization in neural rosettes, as well as imbalanced proliferation and differentiation in neural progenitor cells (NPCs). Mark2+/- mice showed abnormal cortical formation and partition and ASD-like behaviour. Through the use of RNA sequencing (RNA-seq) and lithium treatment, they linked MARK2 loss to downregulation of the WNT/β-catenin signaling pathway and identified lithium as a potential drug for treating MARK2-associated ASD.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6629 PCCB Ain Roesley reviewed gene: PCCB: Rating: GREEN; Mode of pathogenicity: None; Publications: 22593918; Phenotypes: Propionicacidemia MIM#606054; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Genetic Epilepsy v1.69 MARK2 Chirag Patel gene: MARK2 was added
gene: MARK2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: MARK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MARK2 were set to PMID: 39419027, 39436150
Phenotypes for gene: MARK2 were set to Neurodevelopmental disorder MONDO:0700092
Review for gene: MARK2 was set to GREEN
Added comment: 31 individuals with autism spectrum disorder (30/31), intellectual disability/developmental delay (100%), motor delay (62%), speech-language problems (100%), seizure/epilepsy (46%), behaviour disorders (ADHD, aggression, anxiety)(74%), and distinctive facial features (narrow face, abnormal or broad forehead, downslanting palpebral fissures, and large or dysplastic ears).

WES/WGS identified 25 LOF and 6 missense variants in MARK2 gene (Microtubule affinity-regulating kinase 2) which contributes to establishing neuronal polarity and developing dendritic spines. LOF variants were de novo (16/25), inherited (4/25), or unk (5/25). All 6 missense variants were de novo and clustered in the kinase or KA1 domains.

The mRNA and protein expression of MARK2 in PBMCs were significantly lower in affected individuals with LOF variants than in the control group. In vitro expression assay of missense variants supported the effect of MARK2 loss. Proband-derived and CRISPR-engineered isogenic induced pluripotent stem cells (iPSCs) showed MARK2 loss leads to early neuronal developmental and functional deficits, including anomalous polarity and disorganization in neural rosettes, as well as imbalanced proliferation and differentiation in neural progenitor cells (NPCs). Mark2+/- mice showed abnormal cortical formation and partition and ASD-like behaviour. Through the use of RNA sequencing (RNA-seq) and lithium treatment, they linked MARK2 loss to downregulation of the WNT/β-catenin signaling pathway and identified lithium as a potential drug for treating MARK2-associated ASD.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6629 MARK2 Chirag Patel Classified gene: MARK2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6629 MARK2 Chirag Patel Gene: mark2 has been classified as Green List (High Evidence).
Autism v0.200 MARK2 Chirag Patel gene: MARK2 was added
gene: MARK2 was added to Autism. Sources: Literature
Mode of inheritance for gene: MARK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MARK2 were set to PMID: 39419027, 39436150
Phenotypes for gene: MARK2 were set to Neurodevelopmental disorder MONDO:0700092
Review for gene: MARK2 was set to GREEN
Added comment: 31 individuals with autism spectrum disorder (30/31), intellectual disability/developmental delay (100%), motor delay (62%), speech-language problems (100%), seizure/epilepsy (46%), behaviour disorders (ADHD, aggression, anxiety)(74%), and distinctive facial features (narrow face, abnormal or broad forehead, downslanting palpebral fissures, and large or dysplastic ears).

WES/WGS identified 25 LOF and 6 missense variants in MARK2 gene (Microtubule affinity-regulating kinase 2) which contributes to establishing neuronal polarity and developing dendritic spines. LOF variants were de novo (16/25), inherited (4/25), or unk (5/25). All 6 missense variants were de novo and clustered in the kinase or KA1 domains.

The mRNA and protein expression of MARK2 in PBMCs were significantly lower in affected individuals with LOF variants than in the control group. In vitro expression assay of missense variants supported the effect of MARK2 loss. Proband-derived and CRISPR-engineered isogenic induced pluripotent stem cells (iPSCs) showed MARK2 loss leads to early neuronal developmental and functional deficits, including anomalous polarity and disorganization in neural rosettes, as well as imbalanced proliferation and differentiation in neural progenitor cells (NPCs). Mark2+/- mice showed abnormal cortical formation and partition and ASD-like behaviour. Through the use of RNA sequencing (RNA-seq) and lithium treatment, they linked MARK2 loss to downregulation of the WNT/β-catenin signaling pathway and identified lithium as a potential drug for treating MARK2-associated ASD.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6628 PCCA Ain Roesley Marked gene: PCCA as ready
Intellectual disability syndromic and non-syndromic v0.6628 PCCA Ain Roesley Gene: pcca has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6628 PCCA Ain Roesley reviewed gene: PCCA: Rating: GREEN; Mode of pathogenicity: None; Publications: 22593918; Phenotypes: Propionicacidemia MIM#606054; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6628 MARK2 Chirag Patel gene: MARK2 was added
gene: MARK2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: MARK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MARK2 were set to PMID: 39419027, 39436150
Phenotypes for gene: MARK2 were set to Neurodevelopmental disorder MONDO:0700092
Review for gene: MARK2 was set to GREEN
Added comment: 31 individuals with autism spectrum disorder (30/31), intellectual disability/developmental delay (100%), motor delay (62%), speech-language problems (100%), seizure/epilepsy (46%), behaviour disorders (ADHD, aggression, anxiety)(74%), and distinctive facial features (narrow face, abnormal or broad forehead, downslanting palpebral fissures, and large or dysplastic ears).

WES/WGS identified 25 LOF and 6 missense variants in MARK2 gene (Microtubule affinity-regulating kinase 2) which contributes to establishing neuronal polarity and developing dendritic spines. LOF variants were de novo (16/25), inherited (4/25), or unk (5/25). All 6 missense variants were de novo and clustered in the kinase or KA1 domains.

The mRNA and protein expression of MARK2 in PBMCs were significantly lower in affected individuals with LOF variants than in the control group. In vitro expression assay of missense variants supported the effect of MARK2 loss. Proband-derived and CRISPR-engineered isogenic induced pluripotent stem cells (iPSCs) showed MARK2 loss leads to early neuronal developmental and functional deficits, including anomalous polarity and disorganization in neural rosettes, as well as imbalanced proliferation and differentiation in neural progenitor cells (NPCs). Mark2+/- mice showed abnormal cortical formation and partition and ASD-like behaviour. Through the use of RNA sequencing (RNA-seq) and lithium treatment, they linked MARK2 loss to downregulation of the WNT/β-catenin signaling pathway and identified lithium as a potential drug for treating MARK2-associated ASD.
Sources: Literature
Congenital Heart Defect v0.420 ROCK2 Sangavi Sivagnanasundram gene: ROCK2 was added
gene: ROCK2 was added to Congenital Heart Defect. Sources: ClinGen
Mode of inheritance for gene: ROCK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ROCK2 were set to 28554332, 30622330, 31941532
Phenotypes for gene: ROCK2 were set to congenital heart disease MONDO:0005453
Review for gene: ROCK2 was set to AMBER
Added comment: Reported in 4 unrelated individuals however classified as LIMITED by ClinGen Congenital Heart Disease GCEP on 03/09/2024 - https://search.clinicalgenome.org/CCID:008432
Sources: ClinGen
Cataract v0.373 KAT2B Ain Roesley Marked gene: KAT2B as ready
Cataract v0.373 KAT2B Ain Roesley Gene: kat2b has been classified as Red List (Low Evidence).
Mendeliome v1.2085 KAT2B Ain Roesley Marked gene: KAT2B as ready
Mendeliome v1.2085 KAT2B Ain Roesley Gene: kat2b has been classified as Red List (Low Evidence).
Cataract v0.373 KAT2B Ain Roesley gene: KAT2B was added
gene: KAT2B was added to Cataract. Sources: Literature
Mode of inheritance for gene: KAT2B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KAT2B were set to 39366742
Phenotypes for gene: KAT2B were set to cataract MONDO:0005129, KAT2B-related
Review for gene: KAT2B was set to RED
gene: KAT2B was marked as current diagnostic
Added comment: 1 family with 2 affected siblings homozygous for an NMD-predicted variant

both have steroid-resistant nephrotic syndrome and bilateral cataract
only 1 has FSGS
Sources: Literature
Proteinuria v0.229 KAT2B Ain Roesley Marked gene: KAT2B as ready
Proteinuria v0.229 KAT2B Ain Roesley Gene: kat2b has been classified as Red List (Low Evidence).
Mendeliome v1.2085 KAT2B Ain Roesley Phenotypes for gene: KAT2B were changed from steroid-resistant nephrotic syndrome MONDO:0044765, KAT2B-related to steroid-resistant nephrotic syndrome MONDO:0044765, KAT2B-related; cataract MONDO:0005129, KAT2B-related
Mendeliome v1.2084 ROCK2 Sangavi Sivagnanasundram gene: ROCK2 was added
gene: ROCK2 was added to Mendeliome. Sources: ClinGen
Mode of inheritance for gene: ROCK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ROCK2 were set to 28554332, 30622330, 31941532
Phenotypes for gene: ROCK2 were set to congenital heart disease MONDO:0005453
Review for gene: ROCK2 was set to AMBER
Added comment: Reported in 4 unrelated individuals however classified as LIMITED by ClinGen Congenital Heart Disease GCEP on 03/09/2024 - https://search.clinicalgenome.org/CCID:008432
Sources: ClinGen
Proteinuria v0.229 KAT2B Ain Roesley gene: KAT2B was added
gene: KAT2B was added to Proteinuria. Sources: Literature
Mode of inheritance for gene: KAT2B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KAT2B were set to 39366742
Phenotypes for gene: KAT2B were set to steroid-resistant nephrotic syndrome MONDO:0044765, KAT2B-related
Review for gene: KAT2B was set to RED
gene: KAT2B was marked as current diagnostic
Added comment: 1 family with 2 affected siblings homozygous for an NMD-predicted variant

both have steroid-resistant nephrotic syndrome and bilateral cataract
only 1 has FSGS
Sources: Literature
Mendeliome v1.2084 KAT2B Ain Roesley gene: KAT2B was added
gene: KAT2B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KAT2B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KAT2B were set to 39366742
Phenotypes for gene: KAT2B were set to steroid-resistant nephrotic syndrome MONDO:0044765, KAT2B-related
Review for gene: KAT2B was set to RED
gene: KAT2B was marked as current diagnostic
Added comment: 1 family with 2 affected siblings homozygous for an NMD-predicted variant

both have steroid-resistant nephrotic syndrome and bilateral cataract
only 1 has FSGS
Sources: Literature
Mendeliome v1.2083 IKZF2 Ain Roesley edited their review of gene: IKZF2: Changed rating: GREEN
Mendeliome v1.2083 IKZF2 Ain Roesley reviewed gene: IKZF2: Rating: ; Mode of pathogenicity: None; Publications: PMID: 39406892; Phenotypes: nonsyndromic genetic hearing loss MONDO:0019497, IKZF2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6627 UBTF Chirag Patel reviewed gene: UBTF: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 39366741; Phenotypes: Global developmental delay without neuroregression; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Prepair 1000+ v1.546 IMPG2 Andrew Coventry changed review comment from: Retinitis pigmentosa 56 - is an early-onset form of RP with progressive visual-field loss and deterioration of visual acuity. Features include night blindness, progressive visual loss, macular retinal pigment epithelium (RPE) mottling / atrophy, decreased ERG amplitudes (affecting rods more severely than cones), colour vision defect, peripheral visual field loss, central scotoma, retinal blood vessel attenuation, and/or optic disc pallor. These features are largely distinct from the vitelliform macular dystrophy phenotype (MIM#616152).
- biallelic loss-of-function consistently associates with retinitis pigmentosa, while monoallelic loss-of-function consistently associates with vitelliform macular dystrophy.
PMID: 20673862 - 2 families each with 3 affected sibs. Additional 10 index cases identified.
- Those with nonsenses showed early-onset RP, patient with missense variants had a milder maculopathy phenotype.

Further studies and evidence:
Mouse models present exhibiting RP phenotype. (PMID: 38217426 - indicates missense variants had minimal retinal pathology in mice)
Functional study present using patient derived iPS (PMID: 36206764) - confirmed LoF due to lack of expression or lack os post-translational modifications - destabilising outer segments of rods and cones.

ClinGen - curation definitive for AR RP phenotype in association with gene IMPG2, with 10 suspected disease-causing variants scored as part of their curation (five nonsense, one frameshift, one canonical splice site disruption, one in-frame exon deletion, and two missense). Variants were in 8 probands (PMID: 24876279, PMID: 20673862, PMID: 31264916, PMID: 34990796).

RP genes already screened for by 1000+, consider above adequate evidence to upgrade to green status for inclusion in v2.; to: Retinitis pigmentosa 56 - is an early-onset form of RP with progressive visual-field loss and deterioration of visual acuity. Features include night blindness, progressive visual loss, macular retinal pigment epithelium (RPE) mottling / atrophy, decreased ERG amplitudes (affecting rods more severely than cones), colour vision defect, peripheral visual field loss, central scotoma, retinal blood vessel attenuation, and/or optic disc pallor. These features are largely distinct from the vitelliform macular dystrophy phenotype (MIM#616152).
- biallelic loss-of-function consistently associates with retinitis pigmentosa, while monoallelic loss-of-function consistently associates with vitelliform macular dystrophy.
PMID: 20673862 - 2 families each with 3 affected sibs. Additional 10 index cases identified.
- Those with nonsenses showed early-onset RP, patient with missense variants had a milder maculopathy phenotype.

Further studies and evidence:
Mouse models present exhibiting RP phenotype. (PMID: 38217426 - indicates missense variants had minimal retinal pathology in mice)
Functional study present using patient derived iPS (PMID: 36206764) - confirmed LoF due to lack of expression or lack os post-translational modifications - destabilising outer segments of rods and cones.

ClinGen - curation definitive for AR RP phenotype in association with gene IMPG2, with 10 suspected disease-causing variants scored as part of their curation (five nonsense, one frameshift, one canonical splice site disruption, one in-frame exon deletion, and two missense). Variants curated were in 8 probands (PMID: 24876279, PMID: 20673862, PMID: 31264916, PMID: 34990796).

RP genes already screened for by 1000+, consider above adequate evidence to upgrade to green status for inclusion in v2.
Prepair 1000+ v1.546 IMPG2 Andrew Coventry reviewed gene: IMPG2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20673862, 32242237, 37806544, 36206764, 38217426, 32817297, 24876279, 31264916, 34990796; Phenotypes: Retinitis pigmentosa 56 MIM#613581; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.546 LAMA3 Lisa Norbart reviewed gene: LAMA3: Rating: GREEN; Mode of pathogenicity: None; Publications: 7633458, 8530087, 11810295, 10366601; Phenotypes: Epidermolysis bullosa, junctional 2B, severe (MIM#619784), 3. Epidermolysis bullosa, junctional 2C, laryngoonychocutaneous (MIM#245660), Epidermolysis bullosa, junctional 2A, intermediate (MIM#619783); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.546 IFNGR1 Andrew Coventry changed review comment from: Multiple families with recessive disease reported, reviewed in PMID 15589309.
Patients with complete IFNGR1 deficiency have a severe clinical phenotype characterized by early and often fatal mycobacterial infections. The disorder can thus be categorized as a form of mendelian susceptibility to mycobacterial disease (MSMD). Bacillus Calmette-Guerin (BCG) and environmental mycobacteria are the most frequent pathogens, and infection typically begins before the age of 3 years. Recessive deficiency is thought to result in complete loss of cellular response to IFNG and absence of surface IFNGR1 expression. Animal models present.

Note: AD condition associated with this gene - Immunodeficiency 27B, mycobacteriosis, MIM#615978.
Dominant deficiency is typically due to cytoplasmic domain truncations resulting in accumulation of non-functional IFNGR1 proteins that may impede the function of molecules encoded by the wildtype allele, thereby leading to diminished but not absent responsiveness to IFNG. Common deletions at and around nucleotide 818. (PMID: 10192386); to: Multiple families with recessive disease reported, reviewed in PMID 15589309.
Patients with complete IFNGR1 deficiency have a severe clinical phenotype characterized by early and often fatal mycobacterial infections. The disorder can thus be categorized as a form of mendelian susceptibility to mycobacterial disease (MSMD). Bacillus Calmette-Guerin (BCG) and environmental mycobacteria are the most frequent pathogens, and infection typically begins before the age of 3 years. Recessive deficiency is thought to result in complete loss of cellular response to IFNG and absence of surface IFNGR1 expression. Animal models present.

Note: AD condition associated with this gene - Immunodeficiency 27B, mycobacteriosis, MIM#615978.
Dominant deficiency is typically due to cytoplasmic domain truncations resulting in accumulation of non-functional IFNGR1 proteins that may impede the function of molecules encoded by the wildtype allele, thereby leading to diminished but not absent responsiveness to IFNG. Deletions including nucleotide 818 reported. (PMID: 10192386)
Prepair 1000+ v1.546 IFNGR1 Andrew Coventry reviewed gene: IFNGR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15589309, 10192386, 7815885, 12244188, 10811850, 9389728; Phenotypes: Immunodeficiency 27A, mycobacteriosis, MIM#209950; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.546 GTPBP3 Andrew Coventry reviewed gene: GTPBP3: Rating: GREEN; Mode of pathogenicity: None; Publications: 34276756, 25434004; Phenotypes: Combined oxidative phosphorylation deficiency 23 MIM#616198; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2083 ANKRD24 Ain Roesley Marked gene: ANKRD24 as ready
Mendeliome v1.2083 ANKRD24 Ain Roesley Gene: ankrd24 has been classified as Red List (Low Evidence).
Mendeliome v1.2083 ANKRD24 Ain Roesley gene: ANKRD24 was added
gene: ANKRD24 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ANKRD24 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ANKRD24 were set to PMID: 39434538
Phenotypes for gene: ANKRD24 were set to sensorineural hearing loss disorder MONDO:0020678, ANKRD24-related
Review for gene: ANKRD24 was set to RED
gene: ANKRD24 was marked as current diagnostic
Added comment: 1 consanguineous family with postlingual, moderate-to-severe autosomal recessive SNHL

2 affecteds homozygous for c.1934_1937del; (p.Thr645Lysfs*52), which is NMD-predicted
Sources: Literature
Genetic Epilepsy v1.68 DALRD3 Sangavi Sivagnanasundram reviewed gene: DALRD3: Rating: AMBER; Mode of pathogenicity: None; Publications: 39482881; Phenotypes: developmental and epileptic encephalopathy, 86 MONDO:0030054; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2082 DALRD3 Sangavi Sivagnanasundram reviewed gene: DALRD3: Rating: AMBER; Mode of pathogenicity: None; Publications: 39482881; Phenotypes: developmental and epileptic encephalopathy, 86 MONDO:0030054; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2082 ZNF862 Ain Roesley Marked gene: ZNF862 as ready
Mendeliome v1.2082 ZNF862 Ain Roesley Gene: znf862 has been classified as Red List (Low Evidence).
Mendeliome v1.2082 ZNF862 Ain Roesley gene: ZNF862 was added
gene: ZNF862 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZNF862 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZNF862 were set to PMID: 35142290
Phenotypes for gene: ZNF862 were set to hereditary gingival fibromatosis MONDO:0016070 , ZNF862 -related
Review for gene: ZNF862 was set to RED
gene: ZNF862 was marked as current diagnostic
Added comment: 13 individuals in a large multi-generational family with hereditary gingival fibromatosis

missense variant with 5 hets in gnomad v4, very low conservation and benign REVEL score
Sources: Literature
Rhabdomyolysis and Metabolic Myopathy v1.13 SLC52A1 Bryony Thompson Marked gene: SLC52A1 as ready
Rhabdomyolysis and Metabolic Myopathy v1.13 SLC52A1 Bryony Thompson Gene: slc52a1 has been classified as Amber List (Moderate Evidence).
Leukodystrophy - paediatric v0.315 LSM7 Sangavi Sivagnanasundram reviewed gene: LSM7: Rating: AMBER; Mode of pathogenicity: None; Publications: 39420558; Phenotypes: leukodystrophy MONDO:0019046; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2081 LSM7 Sangavi Sivagnanasundram reviewed gene: LSM7: Rating: AMBER; Mode of pathogenicity: None; Publications: 39420558; Phenotypes: leukodystrophy MONDO:0019046; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.291 LAMA3 Ain Roesley Phenotypes for gene: LAMA3 were changed from Epidermolysis bullosa, junctional, Herlitz type (MIM#226700) to Epidermolysis bullosa, junctional 2A, intermediate MIM#619783; Epidermolysis bullosa, junctional 2B, severe MIM#619784; Epidermolysis bullosa, junctional 2C, laryngoonychocutaneous MIM#245660
Amelogenesis imperfecta v1.11 LAMA3 Ain Roesley Phenotypes for gene: LAMA3 were changed from Epidermolysis bullosa, generalized atrophic benign, MIM# 226650; Epidermolysis bullosa, junctional, Herlitz type, MIM# 226700; Laryngoonychocutaneous syndrome, MIM# 245660 to Epidermolysis bullosa, junctional 2A, intermediate MIM#619783; Epidermolysis bullosa, junctional 2B, severe MIM#619784; Epidermolysis bullosa, junctional 2C, laryngoonychocutaneous MIM#245660
Mendeliome v1.2081 LAMA3 Ain Roesley Phenotypes for gene: LAMA3 were changed from Epidermolysis bullosa, generalized atrophic benign, MIM# 226650; Epidermolysis bullosa, junctional, Herlitz type, MIM# 226700 to Epidermolysis bullosa, junctional 2A, intermediate MIM#619783; Epidermolysis bullosa, junctional 2B, severe MIM#619784; Epidermolysis bullosa, junctional 2C, laryngoonychocutaneous MIM#245660
Epidermolysis bullosa v1.17 LAMA3 Ain Roesley Phenotypes for gene: LAMA3 were changed from Epidermolysis bullosa, generalized atrophic benign, MIM# 226650; Epidermolysis bullosa, junctional, Herlitz type, MIM# 226700 to Epidermolysis bullosa, junctional 2A, intermediate MIM#619783; Epidermolysis bullosa, junctional 2B, severe MIM#619784; Epidermolysis bullosa, junctional 2C, laryngoonychocutaneous MIM#245660
Intellectual disability syndromic and non-syndromic v0.6627 SGSM3 Sangavi Sivagnanasundram reviewed gene: SGSM3: Rating: GREEN; Mode of pathogenicity: None; Publications: 39390489; Phenotypes: Neurodevelopmental disorder (MONDO:0700092), SGSM3-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2080 SGSM3 Sangavi Sivagnanasundram reviewed gene: SGSM3: Rating: GREEN; Mode of pathogenicity: None; Publications: 39390489; Phenotypes: Neurodevelopmental disorder (MONDO:0700092), SGSM3-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rhabdomyolysis and Metabolic Myopathy v1.13 SLC52A1 Bryony Thompson Classified gene: SLC52A1 as Amber List (moderate evidence)
Rhabdomyolysis and Metabolic Myopathy v1.13 SLC52A1 Bryony Thompson Added comment: Comment on list classification: MADD phenotype can mimic mitochondrial myopathy
Rhabdomyolysis and Metabolic Myopathy v1.13 SLC52A1 Bryony Thompson Gene: slc52a1 has been classified as Amber List (Moderate Evidence).
Rhabdomyolysis and Metabolic Myopathy v1.11 SLC52A1 Bryony Thompson gene: SLC52A1 was added
gene: SLC52A1 was added to Rhabdomyolysis and Metabolic Myopathy. Sources: Expert list
Mode of inheritance for gene: SLC52A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC52A1 were set to 37510312; 29122468; 21089064
Phenotypes for gene: SLC52A1 were set to Maternal riboflavin deficiency MONDO:0014013
Skeletal dysplasia v0.294 TNFRSF11A Zornitza Stark Marked gene: TNFRSF11A as ready
Skeletal dysplasia v0.294 TNFRSF11A Zornitza Stark Gene: tnfrsf11a has been classified as Green List (High Evidence).
Skeletal dysplasia v0.294 TNFRSF11A Zornitza Stark Publications for gene: TNFRSF11A were set to
Skeletal dysplasia v0.293 TNFRSF11A Zornitza Stark Mode of inheritance for gene: TNFRSF11A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v0.292 TNFRSF11A Zornitza Stark edited their review of gene: TNFRSF11A: Changed phenotypes: Osteopetrosis, autosomal recessive 7 - MIM# 612301, Osteolysis, familial expansile, MIM# 174810; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rhabdomyolysis and Metabolic Myopathy v1.10 SLC52A3 Bryony Thompson Marked gene: SLC52A3 as ready
Rhabdomyolysis and Metabolic Myopathy v1.10 SLC52A3 Bryony Thompson Gene: slc52a3 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v1.10 SLC52A3 Bryony Thompson Classified gene: SLC52A3 as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v1.10 SLC52A3 Bryony Thompson Gene: slc52a3 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v1.9 SLC52A3 Bryony Thompson gene: SLC52A3 was added
gene: SLC52A3 was added to Rhabdomyolysis and Metabolic Myopathy. Sources: Expert list
Mode of inheritance for gene: SLC52A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC52A3 were set to 29193829; 31868069; 29053833; 26072523
Phenotypes for gene: SLC52A3 were set to Brown-Vialetto-van Laere syndrome 1 MONDO:0024537
Review for gene: SLC52A3 was set to GREEN
gene: SLC52A3 was marked as current diagnostic
Added comment: Phenotype can resemble Multiple Acyl-CoA Dehydrogenase Deficiency and can mimic a mitochondrial myopathy.
Sources: Expert list
Rhabdomyolysis and Metabolic Myopathy v1.8 SLC52A2 Bryony Thompson Marked gene: SLC52A2 as ready
Rhabdomyolysis and Metabolic Myopathy v1.8 SLC52A2 Bryony Thompson Gene: slc52a2 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v1.8 SLC52A2 Bryony Thompson Classified gene: SLC52A2 as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v1.8 SLC52A2 Bryony Thompson Gene: slc52a2 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v1.7 SLC52A2 Bryony Thompson gene: SLC52A2 was added
gene: SLC52A2 was added to Rhabdomyolysis and Metabolic Myopathy. Sources: Expert list
Mode of inheritance for gene: SLC52A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC52A2 were set to 29193829; 31868069; 29053833; 26072523
Phenotypes for gene: SLC52A2 were set to Brown-Vialetto-van Laere syndrome 2 MONDO:0013867
Review for gene: SLC52A2 was set to GREEN
gene: SLC52A2 was marked as current diagnostic
Added comment: Phenotype can resemble Multiple Acyl-CoA Dehydrogenase Deficiency and can mimic a mitochondrial myopathy.
Sources: Expert list
Mendeliome v1.2080 GMNN Zornitza Stark changed review comment from: Three unrelated individuals reported, all variants in exon 2 (first coding exon).; to: Three unrelated individuals reported, all variants in exon 2 (first coding exon), leading to the expression of a stable truncated protein.
Immunological disorders_SuperPanel v9.325 Bryony Thompson Changed child panels to: Bone Marrow Failure; Combined Immunodeficiency; Systemic Autoinflammatory Disease_Periodic Fever; Phagocyte Defects; Common Variable Immunodeficiency; Severe Combined Immunodeficiency (absent T present B cells); Severe Combined Immunodeficiency (absent T absent B cells); Susceptibility to Fungal Infections; Hereditary angioedema; Hyper-IgE syndrome; Disorders of immune dysregulation; Predominantly Antibody Deficiency; Defects of innate immunity; Susceptibility to Viral Infections; Inflammatory bowel disease; Complement Deficiencies; Mendelian susceptibility to Immune Disorders
Mitochondrial disease v0.948 MRPL49 Zornitza Stark Marked gene: MRPL49 as ready
Mitochondrial disease v0.948 MRPL49 Zornitza Stark Gene: mrpl49 has been classified as Green List (High Evidence).
Mitochondrial disease v0.948 MRPL49 Zornitza Stark Classified gene: MRPL49 as Green List (high evidence)
Mitochondrial disease v0.948 MRPL49 Zornitza Stark Gene: mrpl49 has been classified as Green List (High Evidence).
Mitochondrial disease v0.947 MRPL49 Zornitza Stark gene: MRPL49 was added
gene: MRPL49 was added to Mitochondrial disease. Sources: Literature
Mode of inheritance for gene: MRPL49 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MRPL49 were set to 39417135
Phenotypes for gene: MRPL49 were set to Mitochondrial disease, MONDO:0044970, MRPL49-related
Review for gene: MRPL49 was set to GREEN
Added comment: Five unrelated families with presentations ranging from Perrault syndrome (primary ovarian insufficiency and sensorineural hearing loss) to severe childhood onset of leukodystrophy, learning disability, microcephaly and retinal dystrophy and bi-allelic variants in this gene.
Sources: Literature
Mendeliome v1.2080 LINC01578 Zornitza Stark Marked gene: LINC01578 as ready
Mendeliome v1.2080 LINC01578 Zornitza Stark Gene: linc01578 has been classified as Green List (High Evidence).
Mendeliome v1.2080 LINC01578 Zornitza Stark Publications for gene: LINC01578 were set to
Mendeliome v1.2079 LINC01578 Zornitza Stark edited their review of gene: LINC01578: Changed publications: 39442041
Mendeliome v1.2079 LINC01578 Zornitza Stark Classified gene: LINC01578 as Green List (high evidence)
Mendeliome v1.2079 LINC01578 Zornitza Stark Gene: linc01578 has been classified as Green List (High Evidence).
Mendeliome v1.2078 LINC01578 Zornitza Stark gene: LINC01578 was added
gene: LINC01578 was added to Mendeliome. Sources: Literature
SV/CNV, new gene name tags were added to gene: LINC01578.
Mode of inheritance for gene: LINC01578 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: LINC01578 were set to Neurodevelopmental disorder, MONDO:0700092, CHASERR-related
Review for gene: LINC01578 was set to GREEN
Added comment: CHASERR encodes a human long noncoding RNA (lncRNA) adjacent to CHD2, a coding gene in which de novo loss-of-function variants cause developmental and epileptic encephalopathy. Three unrelated children reported with a syndromic, early-onset neurodevelopmental disorder, each of whom had a de novo deletion in the CHASERR locus. The children had severe encephalopathy, shared facial dysmorphisms, cortical atrophy, and cerebral hypomyelination - a phenotype that is distinct from the phenotypes of patients with CHD2 haploinsufficiency. CHASERR deletion results in increased CHD2 protein abundance in patient-derived cell lines and increased expression of the CHD2 transcript in cis, indicating bidirectional dosage sensitivity in human disease.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6627 LINC01578 Zornitza Stark Tag SV/CNV tag was added to gene: LINC01578.
Intellectual disability syndromic and non-syndromic v0.6627 LINC01578 Zornitza Stark Marked gene: LINC01578 as ready
Intellectual disability syndromic and non-syndromic v0.6627 LINC01578 Zornitza Stark Gene: linc01578 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6627 LINC01578 Zornitza Stark Classified gene: LINC01578 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6627 LINC01578 Zornitza Stark Gene: linc01578 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6626 LINC01578 Zornitza Stark gene: LINC01578 was added
gene: LINC01578 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
new gene name tags were added to gene: LINC01578.
Mode of inheritance for gene: LINC01578 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LINC01578 were set to 39442041
Phenotypes for gene: LINC01578 were set to Neurodevelopmental disorder, MONDO:0700092, CHASERR-related
Review for gene: LINC01578 was set to GREEN
Added comment: CHASERR encodes a human long noncoding RNA (lncRNA) adjacent to CHD2, a coding gene in which de novo loss-of-function variants cause developmental and epileptic encephalopathy. Three unrelated children reported with a syndromic, early-onset neurodevelopmental disorder, each of whom had a de novo deletion in the CHASERR locus. The children had severe encephalopathy, shared facial dysmorphisms, cortical atrophy, and cerebral hypomyelination - a phenotype that is distinct from the phenotypes of patients with CHD2 haploinsufficiency. CHASERR deletion results in increased CHD2 protein abundance in patient-derived cell lines and increased expression of the CHD2 transcript in cis, indicating bidirectional dosage sensitivity in human disease.
Sources: Literature
Mendeliome v1.2077 RNU5B-1 Zornitza Stark Marked gene: RNU5B-1 as ready
Mendeliome v1.2077 RNU5B-1 Zornitza Stark Gene: rnu5b-1 has been classified as Green List (High Evidence).
Mendeliome v1.2077 RNU5B-1 Zornitza Stark Classified gene: RNU5B-1 as Green List (high evidence)
Mendeliome v1.2077 RNU5B-1 Zornitza Stark Gene: rnu5b-1 has been classified as Green List (High Evidence).
Mendeliome v1.2076 RNU5B-1 Zornitza Stark gene: RNU5B-1 was added
gene: RNU5B-1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RNU5B-1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RNU5B-1 were set to https://www.medrxiv.org/content/10.1101/2024.10.04.24314692v1.full.pdf; https://www.medrxiv.org/content/10.1101/2024.10.07.24314689v1
Phenotypes for gene: RNU5B-1 were set to Neurodevelopmental disorder, MONDO:0700092, RNU5B-1 related
Review for gene: RNU5B-1 was set to GREEN
Added comment: 20 individuals reported in two preprints with de novo variants in this gene and a neurodevelopmental phenotype.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6625 RNU5B-1 Zornitza Stark Marked gene: RNU5B-1 as ready
Intellectual disability syndromic and non-syndromic v0.6625 RNU5B-1 Zornitza Stark Gene: rnu5b-1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6625 RNU5B-1 Zornitza Stark Phenotypes for gene: RNU5B-1 were changed from to Neurodevelopmental disorder, MONDO:0700092, RNU5B-1 related
Intellectual disability syndromic and non-syndromic v0.6624 RNU5B-1 Zornitza Stark Classified gene: RNU5B-1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6624 RNU5B-1 Zornitza Stark Gene: rnu5b-1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6623 RNU5B-1 Zornitza Stark edited their review of gene: RNU5B-1: Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, RNU5B-1 related
Intellectual disability syndromic and non-syndromic v0.6623 RNU5B-1 Zornitza Stark gene: RNU5B-1 was added
gene: RNU5B-1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RNU5B-1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RNU5B-1 were set to https://www.medrxiv.org/content/10.1101/2024.10.04.24314692v1.full.pdf; https://www.medrxiv.org/content/10.1101/2024.10.07.24314689v1
Review for gene: RNU5B-1 was set to GREEN
Added comment: 20 individuals reported in two preprints with de novo variants in this gene and a neurodevelopmental phenotype.
Sources: Literature
Skeletal dysplasia v0.292 TBXAS1 Zornitza Stark Marked gene: TBXAS1 as ready
Skeletal dysplasia v0.292 TBXAS1 Zornitza Stark Gene: tbxas1 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.292 TBXAS1 Zornitza Stark Phenotypes for gene: TBXAS1 were changed from Ghosal hematodiaphyseal syndrome 231095 to Ghosal hematodiaphyseal syndrome MIM#231095
Skeletal dysplasia v0.291 TBXAS1 Zornitza Stark Publications for gene: TBXAS1 were set to
Skeletal dysplasia v0.290 TBXAS1 Zornitza Stark Mode of inheritance for gene: TBXAS1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6622 MBOAT7 Zornitza Stark Mode of inheritance for gene: MBOAT7 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6621 MBOAT7 Zornitza Stark reviewed gene: MBOAT7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual disability MIM#617188; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.546 GLE1 Kate Scarff reviewed gene: GLE1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 18204449, 22357925, 32537934; Phenotypes: Congenital arthrogryposis with anterior horn cell disease, MIM #611890, Lethal congenital contracture syndrome 1, MIM #253310; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.546 GDI1 Kate Scarff reviewed gene: GDI1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28863211, 22002931, 9620768, 9668174; Phenotypes: Intellectual developmental disorder, X-linked 41, MIM #300849; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Prepair 1000+ v1.546 GDF1 Kate Scarff reviewed gene: GDF1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32144877, 20413652, 28991257; Phenotypes: Right atrial isomerism (Ivemark), MIM #208530; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.546 GDAP1 Kate Scarff reviewed gene: GDAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301711, 16172208, 21753178, 21365284, 20232219, 11743580; Phenotypes: Charcot-Marie-Tooth disease, axonal, type 2K, MIM #607831, Charcot-Marie-Tooth disease, axonal, with vocal cord paresis, MIM #607706, Charcot-Marie-Tooth disease, recessive intermediate, A, MIM #608340, Charcot-Marie-Tooth disease, type 4A, MIM#214400; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Prepair 1000+ v1.546 FTCD Kate Scarff reviewed gene: FTCD: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 29178637; Phenotypes: Glutamate formiminotransferase deficiency, MIM #229100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.546 FMR1 Kate Scarff reviewed gene: FMR1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301558, 28176767, 29178241; Phenotypes: Fragile X syndrome, MIM #300624; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Optic Atrophy v1.45 KIF5A Bryony Thompson Marked gene: KIF5A as ready
Optic Atrophy v1.45 KIF5A Bryony Thompson Gene: kif5a has been classified as Green List (High Evidence).
Prepair 1000+ v1.546 FBXO7 Kate Scarff reviewed gene: FBXO7: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34396589, 20301402, 18513678, 34781237, 19038853; Phenotypes: Parkinson disease 15, autosomal recessive, MIM #260300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic Atrophy v1.45 KIF5A Bryony Thompson Classified gene: KIF5A as Green List (high evidence)
Optic Atrophy v1.45 KIF5A Bryony Thompson Gene: kif5a has been classified as Green List (High Evidence).
Optic Atrophy v1.44 KIF5A Bryony Thompson gene: KIF5A was added
gene: KIF5A was added to Optic Atrophy. Sources: Literature
Mode of inheritance for gene: KIF5A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF5A were set to 35921593; 27463701
Phenotypes for gene: KIF5A were set to myoclonus, intractable, neonatal MONDO:0014979; Leber hereditary optic neuropathy MONDO:0010788
Mode of pathogenicity for gene: KIF5A was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: KIF5A was set to GREEN
Added comment: Optic atrophy has been reported as a feature of the NEIMY phenotype, and a missense variant has been reported in a family with LHON. Dominant negative effects and toxic gain-of-function are the mechanism of disease for this gene.
Sources: Literature
Prepair 1000+ v1.546 EIF2B2 Kate Scarff reviewed gene: EIF2B2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 14566705, 21484434, 28041799, 11704758; Phenotypes: Leukoencephalopathy with vanishing white matter 2, with or without ovarian failure, MIM #620312; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2075 SPATA22 Zornitza Stark Phenotypes for gene: SPATA22 were changed from Premature ovarian insufficiency and nonobstructive azoospermia; Genetic infertility MONDO:0017143 to Spermatogenic failure 96, MIM#621001; Premature ovarian failure 25, MIM#621002
Mendeliome v1.2074 SPATA22 Zornitza Stark edited their review of gene: SPATA22: Changed phenotypes: Spermatogenic failure 96, MIM#621001, Premature ovarian failure 25, MIM#621002
Fetal anomalies v1.290 SRPK3 Zornitza Stark Phenotypes for gene: SRPK3 were changed from Neurodevelopmental disorder, MONDO:0700092, SRPK3-related to Intellectual developmental disorder, X-linked, 114, MIM#301134
Fetal anomalies v1.289 SRPK3 Zornitza Stark edited their review of gene: SRPK3: Changed phenotypes: Intellectual developmental disorder, X-linked, 114, MIM#301134
Intellectual disability syndromic and non-syndromic v0.6621 SRPK3 Zornitza Stark Phenotypes for gene: SRPK3 were changed from Neurodevelopmental disorder, MONDO:0700092, SRPK3-related to Intellectual developmental disorder, X-linked, 114, MIM#301134
Intellectual disability syndromic and non-syndromic v0.6620 SRPK3 Zornitza Stark edited their review of gene: SRPK3: Changed phenotypes: Intellectual developmental disorder, X-linked, 114, MIM#301134
Callosome v0.536 SRPK3 Zornitza Stark Phenotypes for gene: SRPK3 were changed from Neurodevelopmental disorder, MONDO:0700092, SRPK3-related to Intellectual developmental disorder, X-linked, 114, MIM#301134
Callosome v0.535 SRPK3 Zornitza Stark edited their review of gene: SRPK3: Changed phenotypes: Intellectual developmental disorder, X-linked, 114, MIM#301134
Mendeliome v1.2074 SRPK3 Zornitza Stark Phenotypes for gene: SRPK3 were changed from Myopathy, MONDO:0005336, digenic SRPK3- and TTN-related; Neurodevelopmental disorder, MONDO:0700092, SRPK3-related to Myopathy, MONDO:0005336, digenic SRPK3- and TTN-related; Intellectual developmental disorder, X-linked, 114, MIM#301134
Mendeliome v1.2073 SRPK3 Zornitza Stark edited their review of gene: SRPK3: Changed phenotypes: Myopathy, MONDO:0005336, digenic SRPK3- and TTN-related, Intellectual developmental disorder, X-linked, 114, MIM#301134
Prepair 1000+ v1.546 EFEMP2 Zornitza Stark Marked gene: EFEMP2 as ready
Prepair 1000+ v1.546 EFEMP2 Zornitza Stark Gene: efemp2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.546 EFEMP2 Zornitza Stark Publications for gene: EFEMP2 were set to
Prepair 1000+ v1.545 EFEMP2 Kate Scarff reviewed gene: EFEMP2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 21563328, 30140196; Phenotypes: Cutis laxa, autosomal recessive, type IB, MIM #614437; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Thyroid Cancer v1.1 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Genetic Health Queensland; Cancer Germline; Adult Genetics Unit, Royal Adelaide Hospital
Schwannoma v1.1 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Genetic Health Queensland; Cancer Germline; Adult Genetics Unit, Royal Adelaide Hospital
Sarcoma non-soft tissue v1.1 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Genetic Health Queensland; Cancer Germline; Adult Genetics Unit, Royal Adelaide Hospital
Prostate Cancer v1.1 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Genetic Health Queensland; Cancer Germline; Adult Genetics Unit, Royal Adelaide Hospital
Pituitary Tumour v1.1 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Genetic Health Queensland; Cancer Germline; Adult Genetics Unit, Royal Adelaide Hospital
Parathyroid Tumour v1.2 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Genetic Health Queensland; Cancer Germline; Adult Genetics Unit, Royal Adelaide Hospital
Paraganglioma_phaeochromocytoma v1.1 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Genetic Health Queensland; Cancer Germline; Adult Genetics Unit, Royal Adelaide Hospital
Melanoma v1.1 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Genetic Health Queensland; Cancer Germline; SA Pathology; Adult Genetics Unit, Royal Adelaide Hospital
Pancreatic Cancer v1.1 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Genetic Health Queensland; Cancer Germline; Adult Genetics Unit, Royal Adelaide Hospital
Medulloblastoma v1.1 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Genetic Health Queensland; Cancer Germline; SA Pathology; Adult Genetics Unit, Royal Adelaide Hospital
Ovarian Cancer v1.1 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Genetic Health Queensland; Cancer Germline; Adult Genetics Unit, Royal Adelaide Hospital
Neuroblastoma v1.1 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Genetic Health Queensland; Cancer Germline; Adult Genetics Unit, Royal Adelaide Hospital
Meningioma v1.1 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Genetic Health Queensland; Cancer Germline; Adult Genetics Unit, Royal Adelaide Hospital
Kidney Cancer v1.1 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Genetic Health Queensland; Cancer Germline; Adult Genetics Unit, Royal Adelaide Hospital
Endometrial Cancer v1.1 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Genetic Health Queensland; Cancer Germline; Adult Genetics Unit, Royal Adelaide Hospital
Diffuse Gastric Cancer v1.1 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Genetic Health Queensland; Cancer Germline; Adult Genetics Unit, Royal Adelaide Hospital
Colorectal Cancer and Polyposis v1.1 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Genetic Health Queensland; Cancer Germline; Adult Genetics Unit, Royal Adelaide Hospital
Breast Cancer v1.1 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Genetic Health Queensland; Cancer Germline; Adult Genetics Unit, Royal Adelaide Hospital
Basal Cell Cancer v1.1 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Genetic Health Queensland; Cancer Germline; Adult Genetics Unit, Royal Adelaide Hospital
Prepair 1000+ v1.545 TMEM94 Lucy Spencer edited their review of gene: TMEM94: Changed publications: 30526868, 32825426
Prepair 1000+ v1.545 TMEM94 Lucy Spencer reviewed gene: TMEM94: Rating: GREEN; Mode of pathogenicity: None; Publications: 30526868; Phenotypes: Intellectual developmental disorder with cardiac defects and dysmorphic facies MIM#618316; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.545 DCDC2 Kate Scarff reviewed gene: DCDC2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25557784, 31821705, 27319779, 27469900, 36938759, 34155636; Phenotypes: Nephronophthisis 19, MIM #616217, Sclerosing cholangitis, neonatal, MIM #617394; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.545 CWC27 Kate Scarff reviewed gene: CWC27: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 36718996, 28285769, 31481716, 38956876, 34828430; Phenotypes: Retinitis pigmentosa with or without skeletal anomalies, MIM# 250410; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.545 PFKM Lucy Spencer reviewed gene: PFKM: Rating: GREEN; Mode of pathogenicity: None; Publications: 22364848; Phenotypes: Glycogen storage disease VII MIM#232800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.545 OFD1 Lucy Spencer reviewed gene: OFD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22619378, 31373179, 23033313, 16783569; Phenotypes: Joubert syndrome 10 MIM#300804, Simpson-Golabi-Behmel syndrome, type 2 MIM#300209, Retinitis pigmentosa 23 MIM#300424; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.545 GLB1 Zornitza Stark Marked gene: GLB1 as ready
Prepair 1000+ v1.545 GLB1 Zornitza Stark Gene: glb1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.545 GLB1 Zornitza Stark Phenotypes for gene: GLB1 were changed from Mucopolysaccharidosis type IVB (Morquio), 253010 (3) to GM1-gangliosidosis, type I MIM#230500; GM1-gangliosidosis, type II MIM#230600; GM1-gangliosidosis, type III MIM#230650; Mucopolysaccharidosis type IVB (Morquio) MIM#253010
Prepair 1000+ v1.544 GLB1 Zornitza Stark Publications for gene: GLB1 were set to
Prepair 1000+ v1.543 GOSR2 Zornitza Stark Marked gene: GOSR2 as ready
Prepair 1000+ v1.543 GOSR2 Zornitza Stark Gene: gosr2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.543 GOSR2 Zornitza Stark Phenotypes for gene: GOSR2 were changed from Epilepsy, progressive myoclonic 6, 614018 (3) to Epilepsy, progressive myoclonic 6 MIM#614018; Muscular dystrophy, congenital, with or without seizures MIM#620166
Prepair 1000+ v1.542 GOSR2 Zornitza Stark Publications for gene: GOSR2 were set to
Prepair 1000+ v1.541 SPG11 Zornitza Stark Phenotypes for gene: SPG11 were changed from Spastic paraplegia 11, autosomal recessive, MIM# 604360 to Hereditary spastic paraplegia 11 MONDO:0011445
Prepair 1000+ v1.540 CTSA Zornitza Stark Marked gene: CTSA as ready
Prepair 1000+ v1.540 CTSA Zornitza Stark Gene: ctsa has been classified as Green List (High Evidence).
Prepair 1000+ v1.540 CTSA Zornitza Stark Phenotypes for gene: CTSA were changed from Galactosialidosis, 256540 (3) to Galactosialidosis MIM#256540
Prepair 1000+ v1.539 CTSA Zornitza Stark Publications for gene: CTSA were set to
Prepair 1000+ v1.538 DDR2 Zornitza Stark Marked gene: DDR2 as ready
Prepair 1000+ v1.538 DDR2 Zornitza Stark Gene: ddr2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.538 DDR2 Zornitza Stark Publications for gene: DDR2 were set to
Prepair 1000+ v1.537 AHI1 Zornitza Stark Marked gene: AHI1 as ready
Prepair 1000+ v1.537 AHI1 Zornitza Stark Gene: ahi1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.537 AHI1 Zornitza Stark Phenotypes for gene: AHI1 were changed from Joubert syndrome-3, 608629 (3) to Joubert syndrome 3 MIM#608629
Prepair 1000+ v1.536 AHI1 Zornitza Stark Publications for gene: AHI1 were set to
Prepair 1000+ v1.535 ANKS6 Zornitza Stark Marked gene: ANKS6 as ready
Prepair 1000+ v1.535 ANKS6 Zornitza Stark Gene: anks6 has been classified as Green List (High Evidence).
Prepair 1000+ v1.535 ANKS6 Zornitza Stark Phenotypes for gene: ANKS6 were changed from Nephronophthisis 16, 615382 (3) to Nephronophthisis 16 MIM#615382
Prepair 1000+ v1.534 ANKS6 Zornitza Stark Publications for gene: ANKS6 were set to
Prepair 1000+ v1.533 BBS9 Zornitza Stark Marked gene: BBS9 as ready
Prepair 1000+ v1.533 BBS9 Zornitza Stark Gene: bbs9 has been classified as Green List (High Evidence).
Prepair 1000+ v1.533 BBS9 Zornitza Stark Phenotypes for gene: BBS9 were changed from Bardet-Biedl syndrome 9, 615986 (3) to Bardet-Biedl syndrome 9 MIM#615986
Prepair 1000+ v1.532 BBS9 Zornitza Stark Publications for gene: BBS9 were set to
Prepair 1000+ v1.531 BOLA3 Zornitza Stark Marked gene: BOLA3 as ready
Prepair 1000+ v1.531 BOLA3 Zornitza Stark Gene: bola3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.531 BOLA3 Zornitza Stark Phenotypes for gene: BOLA3 were changed from Multiple mitochondrial dysfunctions syndrome 2, 614299 (3) to Multiple mitochondrial dysfunctions syndrome 2 with hyperglycinemia MIM#614299
Prepair 1000+ v1.530 BOLA3 Zornitza Stark Publications for gene: BOLA3 were set to
Prepair 1000+ v1.529 CASR Zornitza Stark Marked gene: CASR as ready
Prepair 1000+ v1.529 CASR Zornitza Stark Gene: casr has been classified as Green List (High Evidence).
Prepair 1000+ v1.529 CASR Zornitza Stark Phenotypes for gene: CASR were changed from Hyperparathyroidism, neonatal, 239200 (3) to Hyperparathyroidism, neonatal MIM#239200
Prepair 1000+ v1.528 CASR Zornitza Stark Publications for gene: CASR were set to
Prepair 1000+ v1.527 CCBE1 Zornitza Stark Marked gene: CCBE1 as ready
Prepair 1000+ v1.527 CCBE1 Zornitza Stark Gene: ccbe1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.527 CCBE1 Zornitza Stark Publications for gene: CCBE1 were set to
Prepair 1000+ v1.526 CCDC39 Zornitza Stark Marked gene: CCDC39 as ready
Prepair 1000+ v1.526 CCDC39 Zornitza Stark Gene: ccdc39 has been classified as Green List (High Evidence).
Prepair 1000+ v1.526 CCDC39 Zornitza Stark Publications for gene: CCDC39 were set to
Prepair 1000+ v1.525 FYCO1 Zornitza Stark Tag review tag was added to gene: FYCO1.
Prepair 1000+ v1.525 SPG11 Lucy Spencer edited their review of gene: SPG11: Changed phenotypes: Hereditary spastic paraplegia 11 MONDO:0011445
Prepair 1000+ v1.525 SPG11 Lucy Spencer changed review comment from: OMIM:
Charcot-Marie-Tooth disease type 2X (CMT2X) is an autosomal recessive, slowly progressive, axonal peripheral sensorimotor neuropathy characterized by lower limb muscle weakness and atrophy associated with distal sensory impairment and gait difficulties. Some patients also have involvement of the upper limbs. Onset usually occurs in the first 2 decades of life, although later onset can also occur (summary by Montecchiani et al., 2016). Mean age of onset 11.4 years.

Hereditary spastic paraplegia (SPG or HSP) is characterized by progressive weakness and spasticity of the lower limbs due to degeneration of corticospinal axons. SPG11 is a form of complicated SPG, in that it has neurologic features in addition to spasticity.

ClinGen lumps all 3 conditions under spastic paraplegia 11

Autosomal recessive juvenile amyotrophic lateral sclerosis-5 (ALS5) is a neurodegenerative disorder characterized by onset of upper and lower motor neuron signs before age 25. Affected individuals have progressive spasticity of limb and facial muscles associated with distal amyotrophy. The disorder is slowly progressive, with cases of prolonged survival of more than 3 decades (summary by Orlacchio et al., 2010).; to: OMIM:
Charcot-Marie-Tooth disease type 2X (CMT2X) is an autosomal recessive, slowly progressive, axonal peripheral sensorimotor neuropathy characterized by lower limb muscle weakness and atrophy associated with distal sensory impairment and gait difficulties. Some patients also have involvement of the upper limbs. Onset usually occurs in the first 2 decades of life, although later onset can also occur (summary by Montecchiani et al., 2016). Mean age of onset 11.4 years.

Hereditary spastic paraplegia (SPG or HSP) is characterized by progressive weakness and spasticity of the lower limbs due to degeneration of corticospinal axons. SPG11 is a form of complicated SPG, in that it has neurologic features in addition to spasticity.

Autosomal recessive juvenile amyotrophic lateral sclerosis-5 (ALS5) is a neurodegenerative disorder characterized by onset of upper and lower motor neuron signs before age 25. Affected individuals have progressive spasticity of limb and facial muscles associated with distal amyotrophy. The disorder is slowly progressive, with cases of prolonged survival of more than 3 decades (summary by Orlacchio et al., 2010).

These 3 conditions represent a spectrum of disease and ClinGen lumps all 3 conditions under hereditary spastic paraplegia 11 MONDO:0011445
Prepair 1000+ v1.525 CTPS1 Zornitza Stark Tag founder tag was added to gene: CTPS1.
Prepair 1000+ v1.525 DMD Zornitza Stark Marked gene: DMD as ready
Prepair 1000+ v1.525 DMD Zornitza Stark Gene: dmd has been classified as Green List (High Evidence).
Prepair 1000+ v1.525 DMD Zornitza Stark Phenotypes for gene: DMD were changed from Duchenne muscular dystrophy, 310200 (3) to Becker muscular dystrophy MIM#300376; Duchenne muscular dystrophy MIM#310200
Prepair 1000+ v1.524 DMD Zornitza Stark Publications for gene: DMD were set to
Prepair 1000+ v1.523 DMD Zornitza Stark Tag SV/CNV tag was added to gene: DMD.
Prepair 1000+ v1.523 CTNS Zornitza Stark Marked gene: CTNS as ready
Prepair 1000+ v1.523 CTNS Zornitza Stark Gene: ctns has been classified as Green List (High Evidence).
Prepair 1000+ v1.523 CTNS Zornitza Stark Phenotypes for gene: CTNS were changed from Cystinosis, nephropathic, 219800 (3) to Cystinosis, nephropathic MIM#219800; Cystinosis, late-onset juvenile or adolescent nephropathic MIM#219900; Cystinosis, atypical nephropathic MIM#219800
Prepair 1000+ v1.522 CTNS Zornitza Stark Publications for gene: CTNS were set to
Prepair 1000+ v1.521 CTNS Zornitza Stark Tag SV/CNV tag was added to gene: CTNS.
Prepair 1000+ v1.521 TSPYL1 Zornitza Stark Tag review tag was added to gene: TSPYL1.
Prepair 1000+ v1.521 GOSR2 Andrew Coventry reviewed gene: GOSR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29855340 33639315 1549339 23449775 24458321 30838261 32105965; Phenotypes: Epilepsy, progressive myoclonic 6 MIM#614018, Muscular dystrophy, congenital, with or without seizures MIM#620166; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.521 GLB1 Andrew Coventry reviewed gene: GLB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34539759 24156116 16941474 17309651 25936995 32219518 1928092 33558080 10841810; Phenotypes: GM1-gangliosidosis, type I MIM#230500, GM1-gangliosidosis, type II MIM#230600, GM1-gangliosidosis, type III MIM#230650, Mucopolysaccharidosis type IVB (Morquio) MIM#253010; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2073 TOMM7 Eleanor Williams commented on gene: TOMM7
Prepair 1000+ v1.521 CCDC40 Zornitza Stark Marked gene: CCDC40 as ready
Prepair 1000+ v1.521 CCDC40 Zornitza Stark Gene: ccdc40 has been classified as Green List (High Evidence).
Prepair 1000+ v1.521 CCDC40 Zornitza Stark Phenotypes for gene: CCDC40 were changed from Ciliary dyskinesia, primary, 15, 613808 (3) to Ciliary dyskinesia, primary, 15 MIM#613808
Prepair 1000+ v1.520 CCDC40 Zornitza Stark Publications for gene: CCDC40 were set to
Prepair 1000+ v1.519 RAPSN Zornitza Stark Marked gene: RAPSN as ready
Prepair 1000+ v1.519 RAPSN Zornitza Stark Gene: rapsn has been classified as Green List (High Evidence).
Prepair 1000+ v1.519 RAPSN Zornitza Stark Phenotypes for gene: RAPSN were changed from Fetal akinesia deformation sequence, 208150 (3) to Myasthenic syndrome, congenital, 11, associated with acetylcholine receptor deficiency MIM#616326; Fetal akinesia deformation sequence 2 MIM#618388
Prepair 1000+ v1.518 RAPSN Zornitza Stark Publications for gene: RAPSN were set to
Prepair 1000+ v1.517 REEP6 Zornitza Stark Marked gene: REEP6 as ready
Prepair 1000+ v1.517 REEP6 Zornitza Stark Gene: reep6 has been classified as Green List (High Evidence).
Prepair 1000+ v1.517 REEP6 Zornitza Stark Phenotypes for gene: REEP6 were changed from Retinitis pigmentosa 77, 617304 (3), Autosomal recessive to Retinitis pigmentosa 77 MIM#617304
Prepair 1000+ v1.516 REN Zornitza Stark Marked gene: REN as ready
Prepair 1000+ v1.516 REN Zornitza Stark Gene: ren has been classified as Green List (High Evidence).
Prepair 1000+ v1.516 REN Zornitza Stark Phenotypes for gene: REN were changed from Renal tubular dysgenesis, 267430 (3) to Renal tubular dysgenesis MIM#267430
Prepair 1000+ v1.515 RLIM Zornitza Stark Marked gene: RLIM as ready
Prepair 1000+ v1.515 RLIM Zornitza Stark Gene: rlim has been classified as Green List (High Evidence).
Prepair 1000+ v1.515 RLIM Zornitza Stark Phenotypes for gene: RLIM were changed from Mental retardation, X-linked 61, 300978 (3), X-linked recessive to Tonne-Kalscheuer syndrome MIM#300978
Prepair 1000+ v1.514 RTN4IP1 Zornitza Stark Marked gene: RTN4IP1 as ready
Prepair 1000+ v1.514 RTN4IP1 Zornitza Stark Gene: rtn4ip1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.514 RTN4IP1 Zornitza Stark Phenotypes for gene: RTN4IP1 were changed from Optic atrophy 10 with or without ataxia, mental retardation, and seizures, 616732 (3), Autosomal recessive to Optic atrophy 10 with or without ataxia, impaired intellectual development and seizures MIM#616732
Prepair 1000+ v1.513 SCYL1 Zornitza Stark Marked gene: SCYL1 as ready
Prepair 1000+ v1.513 SCYL1 Zornitza Stark Gene: scyl1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.513 SCYL1 Zornitza Stark Phenotypes for gene: SCYL1 were changed from Spinocerebellar ataxia, autosomal recessive 21, 616719 (3) to Spinocerebellar ataxia, autosomal recessive 21, MIM#616719
Prepair 1000+ v1.512 SH3TC2 Zornitza Stark Marked gene: SH3TC2 as ready
Prepair 1000+ v1.512 SH3TC2 Zornitza Stark Gene: sh3tc2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.512 SH3TC2 Zornitza Stark Phenotypes for gene: SH3TC2 were changed from Charcot-Marie-Tooth disease, type 4C, 601596 (3) to Charcot-Marie-Tooth disease, type 4C, MIM#601596
Prepair 1000+ v1.511 SPINK5 Zornitza Stark Marked gene: SPINK5 as ready
Prepair 1000+ v1.511 SPINK5 Zornitza Stark Gene: spink5 has been classified as Green List (High Evidence).
Prepair 1000+ v1.511 SPINK5 Zornitza Stark Phenotypes for gene: SPINK5 were changed from Netherton syndrome, 256500 (3) to Netherton syndrome MIM#256500
Prepair 1000+ v1.510 SUCLA2 Zornitza Stark Marked gene: SUCLA2 as ready
Prepair 1000+ v1.510 SUCLA2 Zornitza Stark Gene: sucla2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.510 SUCLA2 Zornitza Stark Phenotypes for gene: SUCLA2 were changed from Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), 612073 (3) to Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), MIM#612073
Prepair 1000+ v1.509 TANGO2 Zornitza Stark Marked gene: TANGO2 as ready
Prepair 1000+ v1.509 TANGO2 Zornitza Stark Gene: tango2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.509 TANGO2 Zornitza Stark Tag SV/CNV tag was added to gene: TANGO2.
Prepair 1000+ v1.509 DNAAF3 Zornitza Stark Marked gene: DNAAF3 as ready
Prepair 1000+ v1.509 DNAAF3 Zornitza Stark Gene: dnaaf3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.509 DNAAF3 Zornitza Stark Phenotypes for gene: DNAAF3 were changed from Ciliary dyskinesia, primary, 2, 606763 (3) to Ciliary dyskinesia, primary, 2, MIM#606763
Prepair 1000+ v1.508 DNAAF3 Zornitza Stark Publications for gene: DNAAF3 were set to
Prepair 1000+ v1.507 EXTL3 Zornitza Stark Marked gene: EXTL3 as ready
Prepair 1000+ v1.507 EXTL3 Zornitza Stark Gene: extl3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.507 EXTL3 Zornitza Stark Phenotypes for gene: EXTL3 were changed from Immunoskeletal dysplasia with neurodevelopmental abnormalities, 617425 (3), Autosomal recessive to Immunoskeletal dysplasia with neurodevelopmental abnormalities, MIM#617425
Prepair 1000+ v1.506 EXTL3 Zornitza Stark Publications for gene: EXTL3 were set to
Prepair 1000+ v1.505 FANCF Zornitza Stark Marked gene: FANCF as ready
Prepair 1000+ v1.505 FANCF Zornitza Stark Gene: fancf has been classified as Green List (High Evidence).
Prepair 1000+ v1.505 FANCF Zornitza Stark Phenotypes for gene: FANCF were changed from Fanconi anemia, complementation group F, 603467 (3) to Fanconi anaemia, complementation group F, MIM#603467
Prepair 1000+ v1.504 FANCF Zornitza Stark Publications for gene: FANCF were set to
Prepair 1000+ v1.503 FOLR1 Zornitza Stark Marked gene: FOLR1 as ready
Prepair 1000+ v1.503 FOLR1 Zornitza Stark Gene: folr1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.503 FOLR1 Zornitza Stark Phenotypes for gene: FOLR1 were changed from Neurodegeneration due to cerebral folate transport deficiency, 613068 (3) to Neurodegeneration due to cerebral folate transport deficiency, MIM#613068
Prepair 1000+ v1.502 FOLR1 Zornitza Stark Publications for gene: FOLR1 were set to
Prepair 1000+ v1.501 GFPT1 Zornitza Stark Marked gene: GFPT1 as ready
Prepair 1000+ v1.501 GFPT1 Zornitza Stark Gene: gfpt1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.501 GFPT1 Zornitza Stark Phenotypes for gene: GFPT1 were changed from Myasthenia, congenital, 12, with tubular aggregates, 610542 (3) to Myasthenia, congenital, 12, with tubular aggregates, MIM#610542
Prepair 1000+ v1.500 GFPT1 Zornitza Stark Publications for gene: GFPT1 were set to
Skeletal dysplasia v0.289 DDX41 Zornitza Stark Marked gene: DDX41 as ready
Skeletal dysplasia v0.289 DDX41 Zornitza Stark Gene: ddx41 has been classified as Red List (Low Evidence).
Prepair 1000+ v1.499 CLRN1 Zornitza Stark Marked gene: CLRN1 as ready
Prepair 1000+ v1.499 CLRN1 Zornitza Stark Gene: clrn1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.499 CLRN1 Zornitza Stark Phenotypes for gene: CLRN1 were changed from Usher syndrome, type 3A, 276902 (3) to Usher syndrome, type 3A (MIM#276902)
Prepair 1000+ v1.498 CLRN1 Zornitza Stark Publications for gene: CLRN1 were set to
Prepair 1000+ v1.497 COL27A1 Zornitza Stark Marked gene: COL27A1 as ready
Prepair 1000+ v1.497 COL27A1 Zornitza Stark Gene: col27a1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.497 COL27A1 Zornitza Stark Phenotypes for gene: COL27A1 were changed from Steel Syndrome to Steel Syndrome, MIM#615155
Prepair 1000+ v1.496 COL27A1 Zornitza Stark Publications for gene: COL27A1 were set to
Prepair 1000+ v1.495 DARS2 Zornitza Stark Marked gene: DARS2 as ready
Prepair 1000+ v1.495 DARS2 Zornitza Stark Gene: dars2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.495 DARS2 Zornitza Stark Publications for gene: DARS2 were set to
Prepair 1000+ v1.494 DDC Zornitza Stark Marked gene: DDC as ready
Prepair 1000+ v1.494 DDC Zornitza Stark Gene: ddc has been classified as Green List (High Evidence).
Prepair 1000+ v1.494 DDC Zornitza Stark Phenotypes for gene: DDC were changed from Aromatic L-amino acid decarboxylase deficiency, 608643 (3) to Aromatic L-amino acid decarboxylase deficiency 608643; Aromatic L-amino acid decarboxylase deficiency (MIM#608643)
Prepair 1000+ v1.493 DLD Zornitza Stark Marked gene: DLD as ready
Prepair 1000+ v1.493 DLD Zornitza Stark Gene: dld has been classified as Green List (High Evidence).
Prepair 1000+ v1.493 DLD Zornitza Stark Publications for gene: DLD were set to
Prepair 1000+ v1.492 DNAJC19 Zornitza Stark Marked gene: DNAJC19 as ready
Prepair 1000+ v1.492 DNAJC19 Zornitza Stark Gene: dnajc19 has been classified as Green List (High Evidence).
Prepair 1000+ v1.492 DNAJC19 Zornitza Stark Publications for gene: DNAJC19 were set to
Prepair 1000+ v1.491 DNMT3B Zornitza Stark Marked gene: DNMT3B as ready
Prepair 1000+ v1.491 DNMT3B Zornitza Stark Gene: dnmt3b has been classified as Green List (High Evidence).
Prepair 1000+ v1.491 DONSON Zornitza Stark Marked gene: DONSON as ready
Prepair 1000+ v1.491 DONSON Zornitza Stark Gene: donson has been classified as Green List (High Evidence).
Prepair 1000+ v1.491 DONSON Zornitza Stark Phenotypes for gene: DONSON were changed from Microcephaly, short stature, and limb abnormalities, 617604 (3), Autosomal recessive to Microcephaly-micromelia syndrome (MIM#251230); Microcephaly, short stature, and limb abnormalities (MIM#617604)
Prepair 1000+ v1.490 DONSON Zornitza Stark Publications for gene: DONSON were set to
Prepair 1000+ v1.489 COX15 Zornitza Stark Marked gene: COX15 as ready
Prepair 1000+ v1.489 COX15 Zornitza Stark Gene: cox15 has been classified as Green List (High Evidence).
Prepair 1000+ v1.489 COX15 Zornitza Stark Phenotypes for gene: COX15 were changed from Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 2, 615119 (3) to Mitochondrial complex IV deficiency, nuclear type 6, MIM #615119
Prepair 1000+ v1.488 COX15 Zornitza Stark Publications for gene: COX15 were set to
Prepair 1000+ v1.487 CTPS1 Zornitza Stark Marked gene: CTPS1 as ready
Prepair 1000+ v1.487 CTPS1 Zornitza Stark Gene: ctps1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.487 CTPS1 Zornitza Stark Publications for gene: CTPS1 were set to
Intellectual disability syndromic and non-syndromic v0.6620 KCNJ11 Zornitza Stark Phenotypes for gene: KCNJ11 were changed from to {Diabetes mellitus, type 2, susceptibility to} 125853; Diabetes mellitus, transient neonatal, 3 610582; Diabetes, permanent neonatal, with or without neurologic features 606176; Hyperinsulinemic hypoglycemia, familial, 2 601820; Maturity-onset diabetes of the young, type 13 616329 AD
Intellectual disability syndromic and non-syndromic v0.6619 KCNJ11 Zornitza Stark Mode of inheritance for gene: KCNJ11 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6618 KCNJ11 Zornitza Stark Marked gene: KCNJ11 as ready
Intellectual disability syndromic and non-syndromic v0.6618 KCNJ11 Zornitza Stark Gene: kcnj11 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.6618 YAP1 Zornitza Stark Marked gene: YAP1 as ready
Intellectual disability syndromic and non-syndromic v0.6618 YAP1 Zornitza Stark Gene: yap1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6618 YAP1 Zornitza Stark Phenotypes for gene: YAP1 were changed from to Coloboma, ocular, with or without hearing impairment, cleft lip/palate, and/or mental retardation OMIM #120433
Intellectual disability syndromic and non-syndromic v0.6617 YAP1 Zornitza Stark Publications for gene: YAP1 were set to
Intellectual disability syndromic and non-syndromic v0.6616 YAP1 Zornitza Stark Mode of inheritance for gene: YAP1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6615 TGFB1 Zornitza Stark Marked gene: TGFB1 as ready
Intellectual disability syndromic and non-syndromic v0.6615 TGFB1 Zornitza Stark Gene: tgfb1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6615 RSPRY1 Zornitza Stark Marked gene: RSPRY1 as ready
Intellectual disability syndromic and non-syndromic v0.6615 RSPRY1 Zornitza Stark Gene: rspry1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6615 RAB1A Zornitza Stark Marked gene: RAB1A as ready
Intellectual disability syndromic and non-syndromic v0.6615 RAB1A Zornitza Stark Gene: rab1a has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6615 NUP85 Zornitza Stark Marked gene: NUP85 as ready
Intellectual disability syndromic and non-syndromic v0.6615 NUP85 Zornitza Stark Gene: nup85 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6615 CACNB4 Zornitza Stark Marked gene: CACNB4 as ready
Intellectual disability syndromic and non-syndromic v0.6615 CACNB4 Zornitza Stark Gene: cacnb4 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6615 AASS Zornitza Stark Marked gene: AASS as ready
Intellectual disability syndromic and non-syndromic v0.6615 AASS Zornitza Stark Gene: aass has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6615 SUOX Zornitza Stark Marked gene: SUOX as ready
Intellectual disability syndromic and non-syndromic v0.6615 SUOX Zornitza Stark Gene: suox has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6615 SUOX Zornitza Stark Phenotypes for gene: SUOX were changed from to isolated sulfite oxidase deficiency MONDO:0010089
Intellectual disability syndromic and non-syndromic v0.6614 SUOX Zornitza Stark Publications for gene: SUOX were set to
Intellectual disability syndromic and non-syndromic v0.6613 SUOX Zornitza Stark Mode of inheritance for gene: SUOX was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6612 SPTBN2 Zornitza Stark Marked gene: SPTBN2 as ready
Intellectual disability syndromic and non-syndromic v0.6612 SPTBN2 Zornitza Stark Gene: sptbn2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6612 SPTBN2 Zornitza Stark Phenotypes for gene: SPTBN2 were changed from to Spinocerebellar ataxia, autosomal recessive 14, MIM# 615386; Spinocerebellar ataxia 5, MIM# 600224
Intellectual disability syndromic and non-syndromic v0.6611 SPTBN2 Zornitza Stark Publications for gene: SPTBN2 were set to
Intellectual disability syndromic and non-syndromic v0.6610 SLC6A19 Zornitza Stark Marked gene: SLC6A19 as ready
Intellectual disability syndromic and non-syndromic v0.6610 SLC6A19 Zornitza Stark Gene: slc6a19 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6610 SLC6A19 Zornitza Stark Phenotypes for gene: SLC6A19 were changed from to Hartnup disorder, MIM# 234500
Intellectual disability syndromic and non-syndromic v0.6609 SLC6A19 Zornitza Stark Mode of inheritance for gene: SLC6A19 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal