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Mendeliome v1.308 TMEM163 Zornitza Stark Marked gene: TMEM163 as ready
Mendeliome v1.308 TMEM163 Zornitza Stark Gene: tmem163 has been classified as Green List (High Evidence).
Mendeliome v1.308 TMEM163 Zornitza Stark Phenotypes for gene: TMEM163 were changed from Hypomyelinating leukodystrophy to Hypomyelinating leukodystrophy, MONDO:0019046
Mendeliome v1.307 TMEM163 Zornitza Stark Classified gene: TMEM163 as Green List (high evidence)
Mendeliome v1.307 TMEM163 Zornitza Stark Gene: tmem163 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1654 TMEM163 Zornitza Stark Marked gene: TMEM163 as ready
Genetic Epilepsy v0.1654 TMEM163 Zornitza Stark Gene: tmem163 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1654 TMEM163 Zornitza Stark Phenotypes for gene: TMEM163 were changed from Hypomyelinating leukodystrophy, MONDO:0019046 to Hypomyelinating leukodystrophy, MONDO:0019046
Genetic Epilepsy v0.1654 TMEM163 Zornitza Stark Phenotypes for gene: TMEM163 were changed from Hypomyelinating leukodystrophy to Hypomyelinating leukodystrophy, MONDO:0019046
Genetic Epilepsy v0.1653 TMEM163 Zornitza Stark Classified gene: TMEM163 as Green List (high evidence)
Genetic Epilepsy v0.1653 TMEM163 Zornitza Stark Gene: tmem163 has been classified as Green List (High Evidence).
Mendeliome v1.306 NBAS Zornitza Stark Phenotypes for gene: NBAS were changed from Short stature, optic nerve atrophy, and Pelger-Huet anomaly, MIM# 614800; Infantile liver failure syndrome 2, MIM# 616483 to Short stature, optic nerve atrophy, and Pelger-Huet anomaly, MIM# 614800; Infantile liver failure syndrome 2, MIM# 616483; Haemophagocytic lymphohistiocytosis (HLH), MONDO:0015541
Mendeliome v1.305 NBAS Zornitza Stark Publications for gene: NBAS were set to 31761904
Mendeliome v1.304 NBAS Zornitza Stark edited their review of gene: NBAS: Added comment: PMID 35902954 - Biallelic NBAS variants identifed in three HLH patients who harbored no pathogenic variants in any of the known HLH genes. Functionally, impaired NK-cell cytotoxicity and degranulation were revealed in both NBAS biallelic variant patients and in an NBAS-defcient NK-cell line. Knockdown of NBAS in an NK-cell line (IMC-1) using short hairpin RNA (shRNA) resulted in loss of lytic granule polarization and a decreased number of cytotoxic vesicles near the Golgi apparatus.; Changed publications: 31761904, 35902954; Changed phenotypes: Short stature, optic nerve atrophy, and Pelger-Huet anomaly, MIM# 614800, Infantile liver failure syndrome 2, MIM# 616483, Haemophagocytic lymphohistiocytosis (HLH), MONDO:0015541
Disorders of immune dysregulation v0.155 NBAS Zornitza Stark Marked gene: NBAS as ready
Disorders of immune dysregulation v0.155 NBAS Zornitza Stark Gene: nbas has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.155 NBAS Zornitza Stark Phenotypes for gene: NBAS were changed from Hemophagocytic lymphohistiocytosis (HLH) to Haemophagocytic lymphohistiocytosis (HLH), MONDO:0015541
Disorders of immune dysregulation v0.154 NBAS Zornitza Stark Classified gene: NBAS as Green List (high evidence)
Disorders of immune dysregulation v0.154 NBAS Zornitza Stark Gene: nbas has been classified as Green List (High Evidence).
Bone Marrow Failure v1.19 TYMS Zornitza Stark Marked gene: TYMS as ready
Bone Marrow Failure v1.19 TYMS Zornitza Stark Gene: tyms has been classified as Amber List (Moderate Evidence).
Bone Marrow Failure v1.19 TYMS Zornitza Stark Classified gene: TYMS as Amber List (moderate evidence)
Bone Marrow Failure v1.19 TYMS Zornitza Stark Gene: tyms has been classified as Amber List (Moderate Evidence).
Mendeliome v1.304 TYMS Zornitza Stark Marked gene: TYMS as ready
Mendeliome v1.304 TYMS Zornitza Stark Gene: tyms has been classified as Amber List (Moderate Evidence).
Bone Marrow Failure v1.18 TYMS Zornitza Stark reviewed gene: TYMS: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Dyskeratosis congenita MONDO:0015780; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.304 TYMS Zornitza Stark Classified gene: TYMS as Amber List (moderate evidence)
Mendeliome v1.304 TYMS Zornitza Stark Gene: tyms has been classified as Amber List (Moderate Evidence).
Mendeliome v1.303 TYMS Zornitza Stark reviewed gene: TYMS: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Dyskeratosis congenita MONDO:0015780; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.1652 COX11 Zornitza Stark Marked gene: COX11 as ready
Genetic Epilepsy v0.1652 COX11 Zornitza Stark Gene: cox11 has been classified as Green List (High Evidence).
Mitochondrial disease v0.836 COX11 Zornitza Stark Marked gene: COX11 as ready
Mitochondrial disease v0.836 COX11 Zornitza Stark Gene: cox11 has been classified as Green List (High Evidence).
Mitochondrial disease v0.836 COX11 Zornitza Stark Classified gene: COX11 as Green List (high evidence)
Mitochondrial disease v0.836 COX11 Zornitza Stark Gene: cox11 has been classified as Green List (High Evidence).
Mitochondrial disease v0.835 COX11 Zornitza Stark gene: COX11 was added
gene: COX11 was added to Mitochondrial disease. Sources: Literature
Mode of inheritance for gene: COX11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COX11 were set to 36030551
Phenotypes for gene: COX11 were set to Mitochondrial disease (MONDO:0044970), COX11-related
Review for gene: COX11 was set to GREEN
Added comment: PMID: 36030551
- Biallelic variants in COX11 associated with infantile-onset mitochondrial encephalopathies in two unrelated consanguineous families, one with homozygous missense variant, another with homozygous frameshift variant.
- Functional studies supported pathogenicity of the missense variant, and showed that mutant COX11 fibroblasts had decreased ATP levels which could be rescued by CoQ10.
- RNA studies suggested the mutant transcript with p.(Val12Glyfs*21) is not degraded by nonsense mediated decay.
Sources: Literature
Mendeliome v1.303 COX11 Zornitza Stark Marked gene: COX11 as ready
Mendeliome v1.303 COX11 Zornitza Stark Gene: cox11 has been classified as Green List (High Evidence).
Mendeliome v1.303 COX11 Zornitza Stark Classified gene: COX11 as Green List (high evidence)
Mendeliome v1.303 COX11 Zornitza Stark Gene: cox11 has been classified as Green List (High Evidence).
Mendeliome v1.302 COX11 Zornitza Stark gene: COX11 was added
gene: COX11 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: COX11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COX11 were set to 36030551
Phenotypes for gene: COX11 were set to Mitochondrial disease (MONDO:0044970), COX11-related
Review for gene: COX11 was set to GREEN
Added comment: PMID: 36030551
- Biallelic variants in COX11 associated with infantile-onset mitochondrial encephalopathies in two unrelated consanguineous families, one with homozygous missense variant, another with homozygous frameshift variant.
- Functional studies supported pathogenicity of the missense variant, and showed that mutant COX11 fibroblasts had decreased ATP levels which could be rescued by CoQ10.
- RNA studies suggested the mutant transcript with p.(Val12Glyfs*21) is not degraded by nonsense mediated decay.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4922 COX11 Zornitza Stark Marked gene: COX11 as ready
Intellectual disability syndromic and non-syndromic v0.4922 COX11 Zornitza Stark Gene: cox11 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1652 COX11 Zornitza Stark Classified gene: COX11 as Green List (high evidence)
Genetic Epilepsy v0.1652 COX11 Zornitza Stark Gene: cox11 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4922 COX11 Zornitza Stark Classified gene: COX11 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4922 COX11 Zornitza Stark Gene: cox11 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1651 COX11 Zornitza Stark Classified gene: COX11 as Green List (high evidence)
Genetic Epilepsy v0.1651 COX11 Zornitza Stark Gene: cox11 has been classified as Green List (High Evidence).
Mendeliome v1.301 SARS Zornitza Stark Publications for gene: SARS were set to 28236339; 34570399; 35790048
Intellectual disability syndromic and non-syndromic v0.4921 TMEM147 Zornitza Stark Marked gene: TMEM147 as ready
Intellectual disability syndromic and non-syndromic v0.4921 TMEM147 Zornitza Stark Gene: tmem147 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4921 TMEM147 Zornitza Stark Classified gene: TMEM147 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4921 TMEM147 Zornitza Stark Gene: tmem147 has been classified as Green List (High Evidence).
Mendeliome v1.300 TMEM147 Zornitza Stark Marked gene: TMEM147 as ready
Mendeliome v1.300 TMEM147 Zornitza Stark Gene: tmem147 has been classified as Green List (High Evidence).
Mendeliome v1.300 TMEM147 Zornitza Stark Classified gene: TMEM147 as Green List (high evidence)
Mendeliome v1.300 TMEM147 Zornitza Stark Gene: tmem147 has been classified as Green List (High Evidence).
Autoinflammatory Disorders v0.164 SAT1 Zornitza Stark Marked gene: SAT1 as ready
Autoinflammatory Disorders v0.164 SAT1 Zornitza Stark Gene: sat1 has been classified as Amber List (Moderate Evidence).
Autoinflammatory Disorders v0.164 SAT1 Zornitza Stark Marked gene: SAT1 as ready
Autoinflammatory Disorders v0.164 SAT1 Zornitza Stark Gene: sat1 has been classified as Amber List (Moderate Evidence).
Autoinflammatory Disorders v0.164 SAT1 Zornitza Stark Classified gene: SAT1 as Amber List (moderate evidence)
Autoinflammatory Disorders v0.164 SAT1 Zornitza Stark Gene: sat1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.299 SAT1 Zornitza Stark Phenotypes for gene: SAT1 were changed from to Systemic lupus erythematosus, MONDO:0007915, SAT1-related; Keratosis follicularis spinulosa decalvans
Mendeliome v1.298 SAT1 Zornitza Stark Publications for gene: SAT1 were set to
Mendeliome v1.297 SAT1 Zornitza Stark Mode of inheritance for gene: SAT1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.296 SAT1 Zornitza Stark Classified gene: SAT1 as Amber List (moderate evidence)
Mendeliome v1.296 SAT1 Zornitza Stark Gene: sat1 has been classified as Amber List (Moderate Evidence).
Hereditary Spastic Paraplegia v1.48 NOTCH1 Zornitza Stark Marked gene: NOTCH1 as ready
Hereditary Spastic Paraplegia v1.48 NOTCH1 Zornitza Stark Gene: notch1 has been classified as Green List (High Evidence).
Leukodystrophy v0.276 NOTCH1 Zornitza Stark Marked gene: NOTCH1 as ready
Leukodystrophy v0.276 NOTCH1 Zornitza Stark Gene: notch1 has been classified as Green List (High Evidence).
Leukodystrophy v0.276 NOTCH1 Zornitza Stark Classified gene: NOTCH1 as Green List (high evidence)
Leukodystrophy v0.276 NOTCH1 Zornitza Stark Gene: notch1 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v1.48 NOTCH1 Zornitza Stark Classified gene: NOTCH1 as Green List (high evidence)
Hereditary Spastic Paraplegia v1.48 NOTCH1 Zornitza Stark Gene: notch1 has been classified as Green List (High Evidence).
Mendeliome v1.295 CEP104 Zornitza Stark Phenotypes for gene: CEP104 were changed from Joubert syndrome 25, MIM# 616781; MONDO:0014770 to Joubert syndrome 25, MIM# 616781; MONDO:0014770; Neurodevelopmental disorder; MONDO:0014770, CEP104-related
Mendeliome v1.294 CEP104 Zornitza Stark Publications for gene: CEP104 were set to 26477546
Intellectual disability syndromic and non-syndromic v0.4920 CEP104 Zornitza Stark Phenotypes for gene: CEP104 were changed from Joubert syndrome 25, MIM# 616781; MONDO:0014770 to Joubert syndrome 25, MIM# 616781; MONDO:0014770; Neurodevelopmental disorder; MONDO:0014770, CEP104-related
Mendeliome v1.293 GATA1 Zornitza Stark Phenotypes for gene: GATA1 were changed from Thrombocytopaenia, X-linked, with or without dyserythropoietic anaemia, MIM# 300367; Haemolytic anaemia due to elevated adenosine deaminase, MIM# 301083; Anemia, X-linked, with/without neutropenia and/or platelet abnormalities, MIM# 300835 to Thrombocytopaenia, X-linked, with or without dyserythropoietic anaemia, MIM# 300367; Haemolytic anaemia due to elevated adenosine deaminase, MIM# 301083; Anemia, X-linked, with/without neutropenia and/or platelet abnormalities, MIM# 300835; Diamond-Blackfan anemia (MONDO:0015253)
Intellectual disability syndromic and non-syndromic v0.4919 CEP104 Zornitza Stark Publications for gene: CEP104 were set to 26477546
Intellectual disability syndromic and non-syndromic v0.4918 NOTCH1 Zornitza Stark Marked gene: NOTCH1 as ready
Intellectual disability syndromic and non-syndromic v0.4918 NOTCH1 Zornitza Stark Gene: notch1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4918 NOTCH1 Zornitza Stark Classified gene: NOTCH1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4918 NOTCH1 Zornitza Stark Gene: notch1 has been classified as Green List (High Evidence).
Diamond Blackfan anaemia v1.4 GATA1 Zornitza Stark Marked gene: GATA1 as ready
Diamond Blackfan anaemia v1.4 GATA1 Zornitza Stark Gene: gata1 has been classified as Green List (High Evidence).
Mendeliome v1.292 GATA1 Zornitza Stark Publications for gene: GATA1 were set to
Mendeliome v1.291 GATA1 Zornitza Stark edited their review of gene: GATA1: Added comment: PMID 36029112: De novo GATA1 initiation codon variant (c.3G>A) identified in a Diamond-Blackfan Anaemia patient. Functional evidence showed that the variant does not affect the GATA1 mRNA but brings about a shorter GATA1 isoform (GATA1s) and reduced full-length functional GATA1 protein (GATA1fl), thereby contributing to an erythropoietic defect. Four other GATA1 variants (c.2T>C, c.220G>C, c.220delG, c.220+2T>C) found in eight families have been described as DBA phenotype.; Changed publications: 36029112; Changed phenotypes: Thrombocytopaenia, X-linked, with or without dyserythropoietic anaemia, MIM# 300367, Haemolytic anaemia due to elevated adenosine deaminase, MIM# 301083, Anemia, X-linked, with/without neutropenia and/or platelet abnormalities, MIM# 300835, Diamond-Blackfan anemia (MONDO:0015253)
Diamond Blackfan anaemia v1.4 GATA1 Zornitza Stark Classified gene: GATA1 as Green List (high evidence)
Diamond Blackfan anaemia v1.4 GATA1 Zornitza Stark Gene: gata1 has been classified as Green List (High Evidence).
Mendeliome v1.291 LGI3 Zornitza Stark Marked gene: LGI3 as ready
Mendeliome v1.291 LGI3 Zornitza Stark Gene: lgi3 has been classified as Green List (High Evidence).
Mendeliome v1.291 LGI3 Zornitza Stark Phenotypes for gene: LGI3 were changed from Global developmental delay; Intellectual disability; Distal deformities; Diminished reflexes; Facial myokymia; Hyporeflexia/areflexi to Neurodevelopmental disorder, MONDO:0700092, LGI3-related; Global developmental delay; Intellectual disability; Distal deformities; Diminished reflexes; Facial myokymia; Hyporeflexia/areflexi
Mendeliome v1.290 LGI3 Zornitza Stark Classified gene: LGI3 as Green List (high evidence)
Mendeliome v1.290 LGI3 Zornitza Stark Gene: lgi3 has been classified as Green List (High Evidence).
Mendeliome v1.289 LGI3 Zornitza Stark reviewed gene: LGI3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, LGI3-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4917 LGI3 Zornitza Stark Marked gene: LGI3 as ready
Intellectual disability syndromic and non-syndromic v0.4917 LGI3 Zornitza Stark Gene: lgi3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4917 LGI3 Zornitza Stark Phenotypes for gene: LGI3 were changed from Global developmental delay; Intellectual disability; Distal deformities; Diminished reflexes; Facial myokymia; Hyporeflexia/areflexi to Neurodevelopmental disorder, MONDO:0700092, LGI3-related; Global developmental delay; Intellectual disability; Distal deformities; Diminished reflexes; Facial myokymia; Hyporeflexia/areflexi
Intellectual disability syndromic and non-syndromic v0.4916 LGI3 Zornitza Stark Classified gene: LGI3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4916 LGI3 Zornitza Stark Gene: lgi3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4915 LGI3 Zornitza Stark reviewed gene: LGI3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, LGI3-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.352 ADAMTS15 Zornitza Stark Marked gene: ADAMTS15 as ready
Arthrogryposis v0.352 ADAMTS15 Zornitza Stark Gene: adamts15 has been classified as Green List (High Evidence).
Fetal anomalies v1.65 ADAMTS15 Zornitza Stark Marked gene: ADAMTS15 as ready
Fetal anomalies v1.65 ADAMTS15 Zornitza Stark Gene: adamts15 has been classified as Green List (High Evidence).
Fetal anomalies v1.65 ADAMTS15 Zornitza Stark Classified gene: ADAMTS15 as Green List (high evidence)
Fetal anomalies v1.65 ADAMTS15 Zornitza Stark Gene: adamts15 has been classified as Green List (High Evidence).
Fetal anomalies v1.64 ADAMTS15 Zornitza Stark gene: ADAMTS15 was added
gene: ADAMTS15 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ADAMTS15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAMTS15 were set to 35962790
Phenotypes for gene: ADAMTS15 were set to Arthrogryposis (MONDO:0008779), ADMATS15-related
Review for gene: ADAMTS15 was set to GREEN
Added comment: PMID: 35962790; Four different homozygous variants identified in five affected individuals from four unrelated consanguineous families presenting with congenital flexion contractures of the interphalangeal joints and hypoplastic or absent palmar creases. All patients also had a mild appearance of fetal finger pads and clinodactyly of the fifth finger. Other reported phenotypes include: contractures of knee, Achilles tendon, and ankle (4/5), spine involvement (kyphoscoliosis and/or spinal stiffness) (4/5), and orthodontic features (small mouth, dental crowding, missing teeth, or arched palate) (4/5).
Sources: Literature
Mendeliome v1.289 TMEM147 Naomi Baker gene: TMEM147 was added
gene: TMEM147 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TMEM147 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM147 were set to PMID: 36044892
Phenotypes for gene: TMEM147 were set to Neurodevelopmental disorder (MONDO:0700092), TMEM147-related
Review for gene: TMEM147 was set to GREEN
Added comment: PMID: 36044892; Twelve different variants reported in 23 affected individuals from 15 unrelated families with biallelic variants. All individuals had global developmental delay and intellectual disability. Consistent facial dysmorphisms included coarse facies, prominent forehead, board depressed nasal root, tented mouth, long smooth philtrum, and low-set ears. In vitro studies of missense variants demonstrated accelerated protein degradation via the autophagy-lysosomal pathway, while analysis of primary fibroblasts and granulocytes provided functional evidence of ER and nuclear envelope dysfunction.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4915 TMEM147 Naomi Baker gene: TMEM147 was added
gene: TMEM147 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: TMEM147 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM147 were set to PMID: 36044892
Phenotypes for gene: TMEM147 were set to Neurodevelopmental disorder (MONDO:0700092), TMEM147-related
Review for gene: TMEM147 was set to GREEN
Added comment: PMID: 36044892; Twelve different variants reported in 23 affected individuals from 15 unrelated families with biallelic variants. All individuals had global developmental delay and intellectual disability. Consistent facial dysmorphisms included coarse facies, prominent forehead, board depressed nasal root, tented mouth, long smooth philtrum, and low-set ears. In vitro studies of missense variants demonstrated accelerated protein degradation via the autophagy-lysosomal pathway, while analysis of primary fibroblasts and granulocytes provided functional evidence of ER and nuclear envelope dysfunction.
Sources: Literature
Mendeliome v1.289 SARS Ee Ming Wong reviewed gene: SARS: Rating: RED; Mode of pathogenicity: Other; Publications: 36041817; Phenotypes: neurodevelopmental disorder, MONDO#070009, SARS1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Autoinflammatory Disorders v0.163 SAT1 Ee Ming Wong gene: SAT1 was added
gene: SAT1 was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Literature
Mode of inheritance for gene: SAT1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SAT1 were set to 25977808
Phenotypes for gene: SAT1 were set to Systemic lupus erythematosus, MONDO:0007915, SAT1-related
Penetrance for gene: SAT1 were set to unknown
Review for gene: SAT1 was set to AMBER
gene: SAT1 was marked as current diagnostic
Added comment: - Two SAT1 loss of function variants reported in four SLE males across two American-African families, inherited from their unaffected mothers
- Using a minigene assay, the p.(Asp40Tyr) variant was shown to result in aberrant splicing
- Hemizygous knock-in male mice and homozygous female mice carrying the p.(Glu92Leufs*6) variant spontaneously developed lupus-like autoimmune disease, including splenomegaly, glomerular infiltration of leukocytes, proteinuria and elevated type I interferon scores
Sources: Literature
Mendeliome v1.289 ADAMTS15 Zornitza Stark Marked gene: ADAMTS15 as ready
Mendeliome v1.289 ADAMTS15 Zornitza Stark Gene: adamts15 has been classified as Green List (High Evidence).
Mendeliome v1.289 ADAMTS15 Zornitza Stark Classified gene: ADAMTS15 as Green List (high evidence)
Mendeliome v1.289 ADAMTS15 Zornitza Stark Gene: adamts15 has been classified as Green List (High Evidence).
Arthrogryposis v0.352 ADAMTS15 Zornitza Stark Classified gene: ADAMTS15 as Green List (high evidence)
Arthrogryposis v0.352 ADAMTS15 Zornitza Stark Gene: adamts15 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1650 CAPRIN1 Zornitza Stark Marked gene: CAPRIN1 as ready
Genetic Epilepsy v0.1650 CAPRIN1 Zornitza Stark Gene: caprin1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1650 CAPRIN1 Zornitza Stark Classified gene: CAPRIN1 as Green List (high evidence)
Genetic Epilepsy v0.1650 CAPRIN1 Zornitza Stark Gene: caprin1 has been classified as Green List (High Evidence).
Incidentalome v0.217 UCHL1 Zornitza Stark Marked gene: UCHL1 as ready
Incidentalome v0.217 UCHL1 Zornitza Stark Gene: uchl1 has been classified as Green List (High Evidence).
Mendeliome v1.288 CAPRIN1 Zornitza Stark Marked gene: CAPRIN1 as ready
Mendeliome v1.288 CAPRIN1 Zornitza Stark Gene: caprin1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4915 SARS Ee Ming Wong reviewed gene: SARS: Rating: RED; Mode of pathogenicity: Other; Publications: 36041817; Phenotypes: neurodevelopmental disorder MONDO#070009, SARS1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v1.288 CAPRIN1 Zornitza Stark Classified gene: CAPRIN1 as Green List (high evidence)
Mendeliome v1.288 CAPRIN1 Zornitza Stark Gene: caprin1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1649 COX11 Chern Lim gene: COX11 was added
gene: COX11 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: COX11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COX11 were set to 36030551
Phenotypes for gene: COX11 were set to Mitochondrial disease (MONDO:0044970), COX11-related
Review for gene: COX11 was set to GREEN
gene: COX11 was marked as current diagnostic
Added comment: PMID: 36030551
- Biallelic variants in COX11 associated with infantile-onset mitochondrial encephalopathies in two unrelated consanguineous families, one with homozygous missense variant, another with homozygous frameshift variant.
- Functional studies supported pathogenicity of the missense variant, and showed that mutant COX11 fibroblasts had decreased ATP levels which could be rescued by CoQ10.
- RNA studies suggested the mutant transcript with p.(Val12Glyfs*21) is not degraded by nonsense mediated decay.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4915 COX11 Chern Lim gene: COX11 was added
gene: COX11 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: COX11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COX11 were set to 36030551
Phenotypes for gene: COX11 were set to Mitochondrial disease (MONDO:0044970), COX11-related
Review for gene: COX11 was set to GREEN
gene: COX11 was marked as current diagnostic
Added comment: PMID: 36030551
- Biallelic variants in COX11 associated with infantile-onset mitochondrial encephalopathies in two unrelated consanguineous families, one with homozygous missense variant, another with homozygous frameshift variant.
- Functional studies supported pathogenicity of the missense variant, and showed that mutant COX11 fibroblasts had decreased ATP levels which could be rescued by CoQ10.
- RNA studies suggested the mutant transcript with p.(Val12Glyfs*21) is not degraded by nonsense mediated decay.
Sources: Literature
Mendeliome v1.287 CBLB Alison Yeung Marked gene: CBLB as ready
Mendeliome v1.287 CBLB Alison Yeung Gene: cblb has been classified as Green List (High Evidence).
Mendeliome v1.287 CBLB Alison Yeung Classified gene: CBLB as Green List (high evidence)
Mendeliome v1.287 CBLB Alison Yeung Gene: cblb has been classified as Green List (High Evidence).
Mendeliome v1.286 CBLB Alison Yeung gene: CBLB was added
gene: CBLB was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CBLB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CBLB were set to 36006710
Phenotypes for gene: CBLB were set to Autoimmune disease, MONDO:0007179
Review for gene: CBLB was set to GREEN
Added comment: Distinct homozygous mutations in CBLB were identified in three unrelated children with early onset autoimmunity. Mice homozygous for the CBL-B p.H257L mutation, which corresponds to the patient's p.H285L mutation, had T and B cell hyper-proliferation in response to antigen receptor cross-linking.
Sources: Literature
Mendeliome v1.285 TYMS Lucy Spencer gene: TYMS was added
gene: TYMS was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TYMS was set to Other
Publications for gene: TYMS were set to 35931051
Phenotypes for gene: TYMS were set to Dyskeratosis congenita MONDO:0015780
Review for gene: TYMS was set to RED
Added comment: 8 families with dyskeratosis congenita and heterozygous variants in TYMS. 4 PTCs, 2 missense and 1 splice (2 families had the same frameshift). However in all families 1 unaffected parent was also heterozygous for the same TYSM variant.

The other parent in 3 of these families was then shown to carry a heterozygous variant in ENOSF1 which each affected child was also heterozygous for. ENOSF1 has been shown to modify TYMS expression at the RNA level by acting as an antisense molecule to TYMS. ENOSF1 partially overlaps TYMS on chromosome 18 and is transcribed in the opposite direction to TYMS. This paper is suggesting digenic inheritance.

The TYMS wild type parent from another family was seen to have a TYMSOS variant which was also observed along with the TYMS variant in their 2 affected children.

Immunoblotting showed a stark reduction in TYMS protein level in the cells of affected probands when compared to the parent carrier, wild-type parent, and the controls.

Lymphoblastoid cells from affected probands have severe TYMS deficiency, altered cellular deoxyribonucleotide triphosphate pools, and hypersensitivity to the TYMS-specific inhibitor 5-fluorouracil. These defects in the nucleotide metabolism pathway resulted in genotoxic stress, defective transcription, and abnormal telomere maintenance. Gene-rescue studies in cells from affected probands revealed that post-transcriptional epistatic silencing of TYMS is occurring via elevated ENOSF1.
Sources: Literature
Disorders of immune dysregulation v0.153 CBLB Alison Yeung Marked gene: CBLB as ready
Disorders of immune dysregulation v0.153 CBLB Alison Yeung Gene: cblb has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.153 CBLB Alison Yeung Classified gene: CBLB as Green List (high evidence)
Disorders of immune dysregulation v0.153 CBLB Alison Yeung Gene: cblb has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.152 CBLB Alison Yeung gene: CBLB was added
gene: CBLB was added to Disorders of immune dysregulation. Sources: Literature
Mode of inheritance for gene: CBLB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CBLB were set to 36006710
Phenotypes for gene: CBLB were set to Autoimmune disease, MONDO:0007179
Review for gene: CBLB was set to GREEN
Added comment: Distinct homozygous mutations in CBLB were identified in three unrelated children with early onset autoimmunity. Mice homozygous for the CBL-B p.H257L mutation, which corresponds to the patient's p.H285L mutation, had T and B cell hyper-proliferation in response to antigen receptor cross-linking.
Sources: Literature
Mendeliome v1.285 CEP104 Belinda Chong reviewed gene: CEP104: Rating: GREEN; Mode of pathogenicity: None; Publications: 34196201, 35359234; Phenotypes: CEP104 Neurodevelopmental disorder, MONDO:0014770; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Disorders of immune dysregulation v0.151 NBAS Belinda Chong gene: NBAS was added
gene: NBAS was added to Disorders of immune dysregulation. Sources: Literature
Mode of inheritance for gene: NBAS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NBAS were set to 35902954
Phenotypes for gene: NBAS were set to Hemophagocytic lymphohistiocytosis (HLH)
Review for gene: NBAS was set to GREEN
gene: NBAS was marked as current diagnostic
Added comment: 35902954 - Biallelic NBAS variants identifed in three HLH patients who harbored no pathogenic variants in any of the known HLH genes. Functionally, impaired NK-cell cytotoxicity and degranulation were revealed in both NBAS biallelic variant patients and in an NBAS-defcient NK-cell line. Knockdown of NBAS in an NK-cell line (IMC-1) using short hairpin RNA (shRNA) resulted in loss of lytic granule polarization and a decreased number of cytotoxic vesicles near the Golgi apparatus.
Sources: Literature
Genetic Epilepsy v0.1649 TMEM163 Teresa Zhao gene: TMEM163 was added
gene: TMEM163 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TMEM163 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TMEM163 were set to PMID: 35953447
Phenotypes for gene: TMEM163 were set to Hypomyelinating leukodystrophy
Review for gene: TMEM163 was set to GREEN
Added comment: Four unrelated families with a hypomyelinating leukodystrophy phenotype. Genomic testing identified three distinct heterozygous missense variants in TMEM163 with two unrelated individuals sharing the same de novo variant.

All have global developmental delay, three of them have seizures.
Sources: Literature
Mendeliome v1.285 LGI3 Melanie Marty edited their review of gene: LGI3: Changed phenotypes: Global developmental delay, Intellectual disability, Distal deformities, Diminished reflexes, Facial myokymia, Hyporeflexia/areflexia
Mendeliome v1.285 HNRNPH1 Hazel Phillimore changed review comment from: PMID: 35989590; Ouyang, J. et al. (2022): Two loss of function variants c.2dup, p.(M1?) and c.121dup, p.(Q41Pfs*20), were found in two individuals with early onset high myopia. They were in cohort of 928 probands with early onset high myopia. The pedigrees for these probands indicate that no other relatives were affected. However, it does not appear that any relatives were tested for these variants. These variants were reported to be absent in gnomAD. Note: there is actually 1 heterozygote for an alternative variant that is predicted to cause p.(Met1?) in gnomADv2).
In gnomAD, there are very few LOF variants. (LOF shows pLI = 1).
The group also studied knockdown of this gene in zebrafish, which resulted in ocular coloboma.; to: PMID: 35989590; Ouyang, J. et al. (2022): Two loss of function variants c.2dup, p.(M1?) and c.121dup, p.(Q41Pfs*20), were found in two individuals with early onset high myopia. They were in cohort of 928 probands with early onset high myopia. The pedigrees for these probands indicate that no other relatives were affected. However, it does not appear that any relatives were tested for these variants. These variants were reported to be absent in gnomAD. Note: there is actually 1 heterozygote for an alternative variant that is predicted to cause p.(Met1?) in gnomADv2.
In gnomAD, there are very few LOF variants. (LOF shows pLI = 1).
The group also studied knockdown of this gene in zebrafish, which resulted in ocular coloboma.
Intellectual disability syndromic and non-syndromic v0.4915 LGI3 Melanie Marty edited their review of gene: LGI3: Changed phenotypes: Global developmental delay, Intellectual disability, Distal deformities, Diminished reflexes, Facial myokymia, Hyporeflexia/areflexia
Mendeliome v1.285 HNRNPH1 Hazel Phillimore reviewed gene: HNRNPH1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 35989590; Phenotypes: early onset high myopia, blindness; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Bone Marrow Failure v1.18 TYMS Lucy Spencer gene: TYMS was added
gene: TYMS was added to Bone Marrow Failure. Sources: Literature
Mode of inheritance for gene: TYMS was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TYMS were set to 35931051
Phenotypes for gene: TYMS were set to Dyskeratosis congenita MONDO:0015780
Review for gene: TYMS was set to RED
Added comment: 8 families with dyskeratosis congenita and heterozygous variants in TYMS. 4 PTCs, 2 missense and 1 splice (2 families had the same frameshift). However in all families 1 unaffected parent was also heterozygous for the same TYSM variant.

The other parent in 3 of these families was then shown to carry a heterozygous variant in ENOSF1 which each affected child was also heterozygous for. ENOSF1 has been shown to modify TYMS expression at the RNA level by acting as an antisense molecule to TYMS. ENOSF1 partially overlaps TYMS on chromosome 18 and is transcribed in the opposite direction to TYMS. This paper is suggesting digenic inheritance.

The TYMS wild type parent from another family was seen to have a TYMSOS variant which was also observed along with the TYMS variant in their 2 affected children.

Immunoblotting showed a stark reduction in TYMS protein level in the cells of affected probands when compared to the parent carrier, wild-type parent, and the controls.

Lymphoblastoid cells from affected probands have severe TYMS deficiency, altered cellular deoxyribonucleotide triphosphate pools, and hypersensitivity to the TYMS-specific inhibitor 5-fluorouracil. These defects in the nucleotide metabolism pathway resulted in genotoxic stress, defective transcription, and abnormal telomere maintenance. Gene-rescue studies in cells from affected probands revealed that post-transcriptional epistatic silencing of TYMS is occurring via elevated ENOSF1.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4915 CAPRIN1 Zornitza Stark Marked gene: CAPRIN1 as ready
Intellectual disability syndromic and non-syndromic v0.4915 CAPRIN1 Zornitza Stark Gene: caprin1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4915 TMEM163 Teresa Zhao gene: TMEM163 was added
gene: TMEM163 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: TMEM163 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TMEM163 were set to PMID: 35953447
Phenotypes for gene: TMEM163 were set to Hypomyelinating leukodystrophy
Review for gene: TMEM163 was set to GREEN
Added comment: Four unrelated families with a hypomyelinating leukodystrophy phenotype. Genomic testing identified three distinct heterozygous missense variants in TMEM163 with two unrelated individuals sharing the same de novo variant.

All have global developmental delay, three of them have seizures.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4915 CAPRIN1 Zornitza Stark Classified gene: CAPRIN1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4915 CAPRIN1 Zornitza Stark Gene: caprin1 has been classified as Green List (High Evidence).
Mendeliome v1.285 TMEM163 Teresa Zhao changed review comment from: Four unrelated families with a hypomyelinating leukodystrophy phenotype. Genomic testing identified three distinct heterozygous missense variants in TMEM163 with two unrelated individuals sharing the same de novo variant.

All have global developmental delay, three of them have seizures and two have ID.
Sources: Literature; to: Four unrelated families with a hypomyelinating leukodystrophy phenotype. Genomic testing identified three distinct heterozygous missense variants in TMEM163 with two unrelated individuals sharing the same de novo variant.

All have global developmental delay, three of them have seizures.
Sources: Literature
Leukodystrophy v0.275 TMEM163 Teresa Zhao changed review comment from: Four unrelated families with a hypomyelinating leukodystrophy phenotype. Genomic testing identified three distinct heterozygous missense variants in TMEM163 with two unrelated individuals sharing the same de novo variant.

All have global developmental delay, three of them have seizures and two have ID.

Sources: Literature; to: Four unrelated families with a hypomyelinating leukodystrophy phenotype. Genomic testing identified three distinct heterozygous missense variants in TMEM163 with two unrelated individuals sharing the same de novo variant.

All have global developmental delay, three of them have seizures.

Sources: Literature
Arthrogryposis v0.351 MET Zornitza Stark Marked gene: MET as ready
Arthrogryposis v0.351 MET Zornitza Stark Gene: met has been classified as Amber List (Moderate Evidence).
Mendeliome v1.285 MET Zornitza Stark Phenotypes for gene: MET were changed from Renal cell carcinoma, papillary, 1, familial and somatic, MIM# 605074; Papillary renal cell carcinoma MONDO:0017884 to Arthrogryposis, distal, type 11 (MIM#620019), AD; Renal cell carcinoma, papillary, 1, familial and somatic, MIM# 605074; Papillary renal cell carcinoma MONDO:0017884
Arthrogryposis v0.351 MET Zornitza Stark Classified gene: MET as Amber List (moderate evidence)
Arthrogryposis v0.351 MET Zornitza Stark Gene: met has been classified as Amber List (Moderate Evidence).
Mendeliome v1.284 MET Zornitza Stark Publications for gene: MET were set to
Arthrogryposis v0.351 MET Zornitza Stark Classified gene: MET as Amber List (moderate evidence)
Arthrogryposis v0.351 MET Zornitza Stark Gene: met has been classified as Amber List (Moderate Evidence).
Mendeliome v1.283 MET Zornitza Stark changed review comment from: PMID 30777867:
Four-generation Chinese arthrogryposis pedigree with only upper limb involvement. MET c.3701A>G p.Y1234C segregated as heterozygous in 11 affected family members and was absent from 12 unaffected family members. Variant is absent from gnomad. Functional studies showed this variant caused failure of phosphorylation and loss of tyrosine kinase activity of MET receptor. A mouse model was also created with this variant, mutated mice were found to be smaller than WT mice and had reduced myofibres. These mouse models also had defective migration of muscle progenitor cells and impaired proliferation of secondary myoblasts. Phenotypes in this family included camptodactyly, absent flexion crease, and limited forearm supination.; to: PMID 30777867:
Four-generation Chinese arthrogryposis pedigree with only upper limb involvement. MET c.3701A>G p.Y1234C segregated as heterozygous in 11 affected family members and was absent from 12 unaffected family members. Variant is absent from gnomad. Functional studies showed this variant caused failure of phosphorylation and loss of tyrosine kinase activity of MET receptor. A mouse model was also created with this variant, mutated mice were found to be smaller than WT mice and had reduced myofibres. These mouse models also had defective migration of muscle progenitor cells and impaired proliferation of secondary myoblasts. Phenotypes in this family included camptodactyly, absent flexion crease, and limited forearm supination.

AMBER for this association
Mendeliome v1.283 MET Zornitza Stark edited their review of gene: MET: Added comment: PMID 30777867:
Four-generation Chinese arthrogryposis pedigree with only upper limb involvement. MET c.3701A>G p.Y1234C segregated as heterozygous in 11 affected family members and was absent from 12 unaffected family members. Variant is absent from gnomad. Functional studies showed this variant caused failure of phosphorylation and loss of tyrosine kinase activity of MET receptor. A mouse model was also created with this variant, mutated mice were found to be smaller than WT mice and had reduced myofibres. These mouse models also had defective migration of muscle progenitor cells and impaired proliferation of secondary myoblasts. Phenotypes in this family included camptodactyly, absent flexion crease, and limited forearm supination.; Changed publications: 30777867
Intellectual disability syndromic and non-syndromic v0.4914 GRIN2A Zornitza Stark Publications for gene: GRIN2A were set to 30544257
Incidentalome v0.217 UCHL1 Zornitza Stark Phenotypes for gene: UCHL1 were changed from to Spastic paraplegia 79, autosomal recessive, MIM# 615491; MONDO:0014209; Neurodegenerative disease, MONDO:0005559, UCHL1-related
Mendeliome v1.283 TMEM163 Teresa Zhao gene: TMEM163 was added
gene: TMEM163 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TMEM163 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TMEM163 were set to PMID: 35953447
Phenotypes for gene: TMEM163 were set to Hypomyelinating leukodystrophy
Review for gene: TMEM163 was set to GREEN
Added comment: Four unrelated families with a hypomyelinating leukodystrophy phenotype. Genomic testing identified three distinct heterozygous missense variants in TMEM163 with two unrelated individuals sharing the same de novo variant.

All have global developmental delay, three of them have seizures and two have ID.
Sources: Literature
Mendeliome v1.283 LGI3 Melanie Marty gene: LGI3 was added
gene: LGI3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LGI3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LGI3 were set to PMID: 35948005
Phenotypes for gene: LGI3 were set to Global developmental delay; Intellectual disability; Distal deformities; Diminished reflexes; Facial myokymia; Hyporeflexia/areflexi
Review for gene: LGI3 was set to GREEN
Added comment: Sixteen individuals from eight unrelated families with loss-of-function (LoF) bi-allelic variants in LGI3.
Lgi3-null mice showed reduced and mis-local-ized Kv1 channel complexes in myelinated peripheral axons.
Sources: Literature
Genetic Epilepsy v0.1649 CAPRIN1 Paul De Fazio gene: CAPRIN1 was added
gene: CAPRIN1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: CAPRIN1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CAPRIN1 were set to 35979925
Phenotypes for gene: CAPRIN1 were set to Neurodevelopmental disorder, CAPRIN1-related MONDO:0700092
Review for gene: CAPRIN1 was set to GREEN
gene: CAPRIN1 was marked as current diagnostic
Added comment: 12 individuals reported with ID and language impairment. Other features included seizures (4 individuals), hands and feet malformations (5 individuals), breathing problems (6 individuals), ocular problems (4 individuals) and hearing problems (3 individuals).

All of the variants were nonsense (NMD-predicted) or splicing variants. 10 were de novo, 1 was inherited from an affected father. Functional studies supported pathogenicity.
Sources: Literature
Mendeliome v1.283 NOTCH1 Zornitza Stark Phenotypes for gene: NOTCH1 were changed from Adams-Oliver syndrome 5 (MIM#616028) to Adams-Oliver syndrome 5 (MIM#616028); Genetic cerebral small vessel disease (MONDO:0018787), NOTCH1-related
Leukodystrophy v0.275 TMEM163 Teresa Zhao changed review comment from: Four unrelated families with a hypomyelinating leukodystrophy phenotype. Genomic testing identified three distinct heterozygous missense variants in TMEM163 with two unrelated individuals sharing the same de novo variant.
Sources: Literature; to: Four unrelated families with a hypomyelinating leukodystrophy phenotype. Genomic testing identified three distinct heterozygous missense variants in TMEM163 with two unrelated individuals sharing the same de novo variant.

All have global developmental delay, three of them have seizures and two have ID.

Sources: Literature
Mendeliome v1.282 NOTCH1 Zornitza Stark Publications for gene: NOTCH1 were set to 25963545; 25132448
Pituitary hormone deficiency v0.26 SIX3 Paul De Fazio reviewed gene: SIX3: Rating: RED; Mode of pathogenicity: None; Publications: 35951005; Phenotypes: Non-acquired combined pituitary hormone deficiency MONDO:0018762; Mode of inheritance: Other; Current diagnostic: yes
Genetic Epilepsy v0.1649 GRIN2A Zornitza Stark Publications for gene: GRIN2A were set to 30544257
Mendeliome v1.281 NOTCH1 Zornitza Stark Mode of pathogenicity for gene: NOTCH1 was changed from to Other
Mendeliome v1.280 BUD13 Alison Yeung Marked gene: BUD13 as ready
Mendeliome v1.280 BUD13 Alison Yeung Gene: bud13 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.280 BUD13 Alison Yeung Classified gene: BUD13 as Amber List (moderate evidence)
Mendeliome v1.280 BUD13 Alison Yeung Gene: bud13 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1648 GRIN2A Zornitza Stark Mode of inheritance for gene: GRIN2A was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Lipodystrophy_Lipoatrophy v1.7 BUD13 Alison Yeung changed review comment from: 5 unrelated individuals with a lipodystrophy phenotype with a typical facial appearance, corneal clouding, achalasia, progressive hearing loss, and variable severity. Although 3 individuals showed stunted growth, intellectual disability, and died within the first decade of life, 2 are adults with normal intellectual development. All individuals harbored an identical homozygous nonsense variant affecting the retention and splicing complex component BUD13.

Individuals from two Algerian families.
Sources: Literature; to: 5 individuals with a lipodystrophy phenotype with a typical facial appearance, corneal clouding, achalasia, progressive hearing loss, and variable severity. Although 3 individuals showed stunted growth, intellectual disability, and died within the first decade of life, 2 are adults with normal intellectual development. All individuals harbored an identical homozygous nonsense variant affecting the retention and splicing complex component BUD13.

Individuals from only two Algerian families.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4913 GRIN2A Zornitza Stark Mode of inheritance for gene: GRIN2A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.279 BUD13 Alison Yeung gene: BUD13 was added
gene: BUD13 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BUD13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BUD13 were set to 35670808
Phenotypes for gene: BUD13 were set to Lipodystrophy, MONDO:0006573
Review for gene: BUD13 was set to AMBER
Added comment: 5 individuals with a lipodystrophy phenotype with a typical facial appearance, corneal clouding, achalasia, progressive hearing loss, and variable severity. Although 3 individuals showed stunted growth, intellectual disability, and died within the first decade of life, 2 are adults with normal intellectual development. All individuals harbored an identical homozygous nonsense variant affecting the retention and splicing complex component BUD13. Individuals from only two Algerian families.
Sources: Literature
Genetic Epilepsy v0.1647 GRIN2A Zornitza Stark Mode of inheritance for gene: GRIN2A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.278 GRIN2A Zornitza Stark Publications for gene: GRIN2A were set to 30544257
Leukodystrophy v0.275 TMEM163 Teresa Zhao changed review comment from: Four unrelated with a hypomyelinating leukodystrophy phenotype. Genomic testing identified three distinct heterozygous missense variants in TMEM163 with two unrelated individuals sharing the same de novo variant.
Sources: Literature; to: Four unrelated families with a hypomyelinating leukodystrophy phenotype. Genomic testing identified three distinct heterozygous missense variants in TMEM163 with two unrelated individuals sharing the same de novo variant.
Sources: Literature
Regression v0.499 UCHL1 Zornitza Stark Phenotypes for gene: UCHL1 were changed from Spastic paraplegia 79, autosomal recessive, MIM# 615491; MONDO:0014209; Neurodegenerative disease, MONDO:0005559, UCHL1-related to Spastic paraplegia 79, autosomal recessive, MIM# 615491; MONDO:0014209; Neurodegenerative disease, MONDO:0005559, UCHL1-related
Leukodystrophy v0.275 TMEM163 Teresa Zhao gene: TMEM163 was added
gene: TMEM163 was added to Leukodystrophy - paediatric. Sources: Literature
Mode of inheritance for gene: TMEM163 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TMEM163 were set to PMID: 35953447
Phenotypes for gene: TMEM163 were set to Hypomyelinating leukodystrophy
Review for gene: TMEM163 was set to GREEN
Added comment: Four unrelated with a hypomyelinating leukodystrophy phenotype. Genomic testing identified three distinct heterozygous missense variants in TMEM163 with two unrelated individuals sharing the same de novo variant.
Sources: Literature
Mendeliome v1.277 GRIN2A Zornitza Stark Mode of inheritance for gene: GRIN2A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Lipodystrophy_Lipoatrophy v1.7 BUD13 Alison Yeung Classified gene: BUD13 as Amber List (moderate evidence)
Lipodystrophy_Lipoatrophy v1.7 BUD13 Alison Yeung Gene: bud13 has been classified as Amber List (Moderate Evidence).
Incidentalome v0.216 UCHL1 Zornitza Stark Publications for gene: UCHL1 were set to 23359680; 3340629; 28007905; 32656641; 29735986; 28007905; 35986737
Lipodystrophy_Lipoatrophy v1.7 BUD13 Alison Yeung Marked gene: BUD13 as ready
Lipodystrophy_Lipoatrophy v1.7 BUD13 Alison Yeung Gene: bud13 has been classified as Amber List (Moderate Evidence).
Incidentalome v0.216 UCHL1 Zornitza Stark Publications for gene: UCHL1 were set to
Lipodystrophy_Lipoatrophy v1.7 BUD13 Alison Yeung Classified gene: BUD13 as Amber List (moderate evidence)
Lipodystrophy_Lipoatrophy v1.7 BUD13 Alison Yeung Gene: bud13 has been classified as Amber List (Moderate Evidence).
Incidentalome v0.216 UCHL1 Zornitza Stark Mode of inheritance for gene: UCHL1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Regression v0.498 UCHL1 Zornitza Stark Phenotypes for gene: UCHL1 were changed from Spastic paraplegia 79, autosomal recessive, MIM# 615491; MONDO:0014209 to Spastic paraplegia 79, autosomal recessive, MIM# 615491; MONDO:0014209; Neurodegenerative disease, MONDO:0005559, UCHL1-related
Leukodystrophy v0.275 NOTCH1 Chern Lim gene: NOTCH1 was added
gene: NOTCH1 was added to Leukodystrophy - paediatric. Sources: Literature
Mode of inheritance for gene: NOTCH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NOTCH1 were set to 35947102
Phenotypes for gene: NOTCH1 were set to Genetic cerebral small vessel disease (MONDO:0018787), NOTCH1-related
Mode of pathogenicity for gene: NOTCH1 was set to Other
Review for gene: NOTCH1 was set to GREEN
gene: NOTCH1 was marked as current diagnostic
Added comment: PMID: 35947102:
- Seven unrelated patients with leukoencephalopathy and calcifications, germline heterozygous de novo gain-of-function variants in NOTCH1.
- Other clinical features include intellectual disability, spasticity and etc. Childhood onset in most individuals however 15y and 40y reported in two individuals.
- Missense and small inframe insertion variants in the negative regulatory region.
Sources: Literature
Mendeliome v1.276 SAT1 Ee Ming Wong reviewed gene: SAT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 35977808; Phenotypes: Systemic lupus erythematosus, MONDO:0007915, SAT1-related; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Incidentalome v0.215 UCHL1 Zornitza Stark reviewed gene: UCHL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23359680, 3340629, 28007905, 32656641, 29735986, 28007905, 35986737; Phenotypes: Spastic paraplegia 79, autosomal recessive, MIM# 615491, MONDO:0014209, Neurodegenerative disease, MONDO:0005559, UCHL1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Lipodystrophy_Lipoatrophy v1.6 BUD13 Alison Yeung gene: BUD13 was added
gene: BUD13 was added to Lipodystrophy_Lipoatrophy. Sources: Literature
Mode of inheritance for gene: BUD13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BUD13 were set to 35670808
Phenotypes for gene: BUD13 were set to Lipodystrophy, MONDO:0006573
Review for gene: BUD13 was set to AMBER
Added comment: 5 unrelated individuals with a lipodystrophy phenotype with a typical facial appearance, corneal clouding, achalasia, progressive hearing loss, and variable severity. Although 3 individuals showed stunted growth, intellectual disability, and died within the first decade of life, 2 are adults with normal intellectual development. All individuals harbored an identical homozygous nonsense variant affecting the retention and splicing complex component BUD13.

Individuals from two Algerian families.
Sources: Literature
Regression v0.497 UCHL1 Zornitza Stark Publications for gene: UCHL1 were set to 23359680; 3340629; 28007905; 32656641; 29735986; 28007905
Regression v0.496 UCHL1 Zornitza Stark Mode of inheritance for gene: UCHL1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Regression v0.495 UCHL1 Zornitza Stark edited their review of gene: UCHL1: Added comment: PMID 35986737: 34 individuals from 18 unrelated families, carrying 13 heterozygous loss-of-function variants (15 families) and an inframe insertion (3 families). Affected individuals mainly presented with spasticity (24/31), ataxia (28/31), neuropathy (11/21), and optic atrophy (9/17).; Changed publications: 23359680, 3340629, 28007905, 32656641, 29735986, 28007905, 35986737; Changed phenotypes: Spastic paraplegia 79, autosomal recessive, MIM# 615491, MONDO:0014209, Neurodegenerative disease, MONDO:0005559, UCHL1-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary Neuropathy v0.134 UCHL1 Zornitza Stark Marked gene: UCHL1 as ready
Hereditary Neuropathy v0.134 UCHL1 Zornitza Stark Gene: uchl1 has been classified as Green List (High Evidence).
Hereditary Neuropathy v0.134 UCHL1 Zornitza Stark Classified gene: UCHL1 as Green List (high evidence)
Hereditary Neuropathy v0.134 UCHL1 Zornitza Stark Gene: uchl1 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v1.47 NOTCH1 Chern Lim gene: NOTCH1 was added
gene: NOTCH1 was added to Hereditary Spastic Paraplegia - paediatric. Sources: Literature
Mode of inheritance for gene: NOTCH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NOTCH1 were set to 35947102
Phenotypes for gene: NOTCH1 were set to Genetic cerebral small vessel disease (MONDO:0018787), NOTCH1-related
Mode of pathogenicity for gene: NOTCH1 was set to Other
Review for gene: NOTCH1 was set to GREEN
gene: NOTCH1 was marked as current diagnostic
Added comment: PMID: 35947102:
- Seven unrelated patients with leukoencephalopathy and calcifications, germline heterozygous de novo gain-of-function variants in NOTCH1.
- Other clinical features include intellectual disability, spasticity and etc. Childhood onset in most individuals however 15y and 40y reported in two individuals.
- Missense and small inframe insertion variants in the negative regulatory region.
Sources: Literature
Hereditary Neuropathy v0.133 UCHL1 Zornitza Stark gene: UCHL1 was added
gene: UCHL1 was added to Hereditary Neuropathy - complex. Sources: Literature
Mode of inheritance for gene: UCHL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: UCHL1 were set to 35986737
Phenotypes for gene: UCHL1 were set to Neurodegenerative disease, MONDO:0005559, UCHL1-related
Review for gene: UCHL1 was set to GREEN
Added comment: PMID 35986737: 34 individuals from 18 unrelated families, carrying 13 heterozygous loss-of-function variants (15 families) and an inframe insertion (3 families). Affected individuals mainly presented with spasticity (24/31), ataxia (28/31), neuropathy (11/21), and optic atrophy (9/17).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4912 NOTCH1 Chern Lim changed review comment from: PMID: 35947102:
- Seven unrelated patients with leukoencephalopathy and calcifications, germline heterozygous de novo gain-of-function variants in NOTCH1.
- Missense and small inframe insertion variants in the negative regulatory region.
Sources: Literature; to: PMID: 35947102:
- Seven unrelated patients with leukoencephalopathy and calcifications, germline heterozygous de novo gain-of-function variants in NOTCH1.
- Other clinical features include intellectual disability, spasticity and etc. Childhood onset in most individuals however 15y and 40y reported in two individuals.
- Missense and small inframe insertion variants in the negative regulatory region.
Mendeliome v1.276 NOTCH1 Chern Lim changed review comment from: PMID: 35947102:
- Seven unrelated patients with leukoencephalopathy and calcifications, germline heterozygous de novo gain-of-function variants in NOTCH1.
- Missense and small inframe insertion variants in the negative regulatory region.; to: PMID: 35947102:
- Seven unrelated patients with leukoencephalopathy and calcifications, germline heterozygous de novo gain-of-function variants in NOTCH1.
- Other clinical features include intellectual disability, spasticity and etc. Childhood onset in most individuals however 15y and 40y reported in two individuals.
- Missense and small inframe insertion variants in the negative regulatory region.
Hereditary Spastic Paraplegia v1.47 UCHL1 Zornitza Stark Phenotypes for gene: UCHL1 were changed from Spastic paraplegia 79, autosomal recessive, 615491; MONDO:0014209 to Spastic paraplegia 79, autosomal recessive, 615491; MONDO:0014209; Neurodegenerative disease, MONDO:0005559, UCHL1-related
Hereditary Spastic Paraplegia v1.46 UCHL1 Zornitza Stark Publications for gene: UCHL1 were set to 23359680; 3340629; 28007905; 32656641; 29735986; 28007905
Hereditary Spastic Paraplegia v1.45 UCHL1 Zornitza Stark Mode of inheritance for gene: UCHL1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary Spastic Paraplegia v1.44 UCHL1 Zornitza Stark edited their review of gene: UCHL1: Added comment: PMID 35986737: 34 individuals from 18 unrelated families, carrying 13 heterozygous loss-of-function variants (15 families) and an inframe insertion (3 families). Affected individuals mainly presented with spasticity (24/31), ataxia (28/31), neuropathy (11/21), and optic atrophy (9/17).; Changed publications: 23359680, 3340629, 28007905, 32656641, 29735986, 28007905, 35986737; Changed phenotypes: Spastic paraplegia 79, autosomal recessive, MIM#615491, Neurodegenerative disease, MONDO:0005559, UCHL1-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Optic Atrophy v1.9 UCHL1 Zornitza Stark Publications for gene: UCHL1 were set to 29735986; 23359680; 28007905
Intellectual disability syndromic and non-syndromic v0.4912 CEP104 Belinda Chong reviewed gene: CEP104: Rating: GREEN; Mode of pathogenicity: None; Publications: 34196201, 35359234; Phenotypes: CEP104 Neurodevelopmental disorder, MONDO:0014770; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Optic Atrophy v1.8 UCHL1 Zornitza Stark Mode of inheritance for gene: UCHL1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Optic Atrophy v1.7 UCHL1 Zornitza Stark reviewed gene: UCHL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28007905, 23359680, 11555633, 35986737; Phenotypes: Spastic paraplegia 79, autosomal recessive, MIM#615491, Neurodegenerative disease, MONDO:0005559, UCHL1-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ataxia v0.343 UCHL1 Zornitza Stark Phenotypes for gene: UCHL1 were changed from Early onset ataxia and optic neuropathy; Autosomal recessive spastic paraplegia 79, 615491 to Spastic paraplegia 79, autosomal recessive, MIM#615491; Neurodegenerative disease, MONDO:0005559, UCHL1-related
Ataxia v0.342 UCHL1 Zornitza Stark Publications for gene: UCHL1 were set to
Arthrogryposis v0.350 ADAMTS15 Naomi Baker changed review comment from: PMID: 35962790; Four different homozygous variants identified in five affected individuals from four unrelated consanguineous families presenting with congenital flexion contractures of the interphalangeal joints and hypoplastic or absent palmar creases. All patients also had a mild appearance of fetal finger pads and clinodactyly of the fifth finger. Other reported phenotypes include: ontractures of knee, Achilles tendon, and ankle (4/5), spine involvement (kyphoscoliosis and/or spinal stiffness) (4/5), and orthodontic features (small mouth, dental crowding,
missing teeth, or arched palate) (4/5).
Sources: Literature; to: PMID: 35962790; Four different homozygous variants identified in five affected individuals from four unrelated consanguineous families presenting with congenital flexion contractures of the interphalangeal joints and hypoplastic or absent palmar creases. All patients also had a mild appearance of fetal finger pads and clinodactyly of the fifth finger. Other reported phenotypes include: contractures of knee, Achilles tendon, and ankle (4/5), spine involvement (kyphoscoliosis and/or spinal stiffness) (4/5), and orthodontic features (small mouth, dental crowding,
missing teeth, or arched palate) (4/5).
Sources: Literature
Ataxia v0.341 UCHL1 Zornitza Stark Mode of inheritance for gene: UCHL1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ataxia v0.340 UCHL1 Zornitza Stark edited their review of gene: UCHL1: Added comment: PMID 35986737: 34 individuals from 18 unrelated families, carrying 13 heterozygous loss-of-function variants (15 families) and an inframe insertion (3 families). Affected individuals mainly presented with spasticity (24/31), ataxia (28/31), neuropathy (11/21), and optic atrophy (9/17).; Changed publications: 28007905, 23359680, 11555633, 35986737; Changed phenotypes: Spastic paraplegia 79, autosomal recessive, MIM#615491, Neurodegenerative disease, MONDO:0005559, UCHL1-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.276 ADAMTS15 Naomi Baker changed review comment from: PMID: 35962790; Four different homozygous variants identified in five affected individuals from four unrelated consanguineous families presenting with congenital flexion contractures of the interphalangeal joints and hypoplastic or absent palmar creases. All patients also had a mild appearance of fetal finger pads and clinodactyly of the fifth finger. Other reported phenotypes include: ontractures of knee, Achilles tendon, and ankle (4/5), spine involvement (kyphoscoliosis and/or spinal stiffness) (4/5), and orthodontic features (small mouth, dental crowding, missing teeth, or arched palate) (4/5).
Sources: Literature; to: PMID: 35962790; Four different homozygous variants identified in five affected individuals from four unrelated consanguineous families presenting with congenital flexion contractures of the interphalangeal joints and hypoplastic or absent palmar creases. All patients also had a mild appearance of fetal finger pads and clinodactyly of the fifth finger. Other reported phenotypes include: contractures of knee, Achilles tendon, and ankle (4/5), spine involvement (kyphoscoliosis and/or spinal stiffness) (4/5), and orthodontic features (small mouth, dental crowding, missing teeth, or arched palate) (4/5).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4912 NOTCH1 Chern Lim gene: NOTCH1 was added
gene: NOTCH1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: NOTCH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NOTCH1 were set to 35947102
Phenotypes for gene: NOTCH1 were set to Genetic cerebral small vessel disease (MONDO:0018787), NOTCH1-related
Mode of pathogenicity for gene: NOTCH1 was set to Other
Review for gene: NOTCH1 was set to GREEN
gene: NOTCH1 was marked as current diagnostic
Added comment: PMID: 35947102:
- Seven unrelated patients with leukoencephalopathy and calcifications, germline heterozygous de novo gain-of-function variants in NOTCH1.
- Missense and small inframe insertion variants in the negative regulatory region.
Sources: Literature
Diamond Blackfan anaemia v1.3 GATA1 Daniel Flanagan gene: GATA1 was added
gene: GATA1 was added to Diamond Blackfan anaemia. Sources: Expert list
Mode of inheritance for gene: GATA1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: GATA1 were set to PMID: 36029112
Phenotypes for gene: GATA1 were set to Diamond-Blackfan anemia (MONDO:0015253)
Review for gene: GATA1 was set to GREEN
Added comment: De novo GATA1 initiation codon variant (c.3G>A) identified in a Diamond-Blackfan Anaemia patient. Functional evidence showed that the variant does not affect the GATA1 mRNA but brings about a shorter GATA1 isoform (GATA1s) and reduced full-length functional GATA1 protein (GATA1fl), thereby contributing to an erythropoietic defect. Four other GATA1 variants (c.2T>C, c.220G>C, c.220delG, c.220+2T>C) found in eight families have been described as DBA phenotype.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.4912 LGI3 Melanie Marty changed review comment from: Six individuals from eight unrelated families with loss-of-function (LoF) bi-allelic variants in LGI3.
Lgi3-null mice showed reduced and mis-local-ized Kv1 channel complexes in myelinated peripheral axons.
Sources: Literature; to: Sixteen individuals from eight unrelated families with loss-of-function (LoF) bi-allelic variants in LGI3.
Lgi3-null mice showed reduced and mis-local-ized Kv1 channel complexes in myelinated peripheral axons.
Sources: Literature
Mendeliome v1.276 ADAMTS15 Naomi Baker gene: ADAMTS15 was added
gene: ADAMTS15 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ADAMTS15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAMTS15 were set to PMID: 35962790
Phenotypes for gene: ADAMTS15 were set to Arthrogryposis (MONDO:0008779), ADMATS15-related
Review for gene: ADAMTS15 was set to GREEN
Added comment: PMID: 35962790; Four different homozygous variants identified in five affected individuals from four unrelated consanguineous families presenting with congenital flexion contractures of the interphalangeal joints and hypoplastic or absent palmar creases. All patients also had a mild appearance of fetal finger pads and clinodactyly of the fifth finger. Other reported phenotypes include: ontractures of knee, Achilles tendon, and ankle (4/5), spine involvement (kyphoscoliosis and/or spinal stiffness) (4/5), and orthodontic features (small mouth, dental crowding, missing teeth, or arched palate) (4/5).
Sources: Literature
Mendeliome v1.276 NOTCH1 Chern Lim edited their review of gene: NOTCH1: Changed phenotypes: Genetic cerebral small vessel disease (MONDO:0018787), NOTCH1-related
Intellectual disability syndromic and non-syndromic v0.4912 LGI3 Melanie Marty gene: LGI3 was added
gene: LGI3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: LGI3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LGI3 were set to PMID: 35948005
Phenotypes for gene: LGI3 were set to Global developmental delay; Intellectual disability; Distal deformities; Diminished reflexes; Facial myokymia; Hyporeflexia/areflexi
Review for gene: LGI3 was set to GREEN
Added comment: Six individuals from eight unrelated families with loss-of-function (LoF) bi-allelic variants in LGI3.
Lgi3-null mice showed reduced and mis-local-ized Kv1 channel complexes in myelinated peripheral axons.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4912 GRIN2A Teresa Zhao reviewed gene: GRIN2A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35983985; Phenotypes: Epilepsy, focal, with speech disorder and with or without mental retardation (MIM#245570); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.1646 GRIN2A Teresa Zhao reviewed gene: GRIN2A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35983985; Phenotypes: Epilepsy, focal, with speech disorder and with or without impaired intellectual development (MIM#245570); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.350 ADAMTS15 Naomi Baker gene: ADAMTS15 was added
gene: ADAMTS15 was added to Arthrogryposis. Sources: Literature
Mode of inheritance for gene: ADAMTS15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAMTS15 were set to PMID: 35962790
Phenotypes for gene: ADAMTS15 were set to Arthrogryposis (MONDO:0008779), ADMATS15-related
Review for gene: ADAMTS15 was set to GREEN
Added comment: PMID: 35962790; Four different homozygous variants identified in five affected individuals from four unrelated consanguineous families presenting with congenital flexion contractures of the interphalangeal joints and hypoplastic or absent palmar creases. All patients also had a mild appearance of fetal finger pads and clinodactyly of the fifth finger. Other reported phenotypes include: ontractures of knee, Achilles tendon, and ankle (4/5), spine involvement (kyphoscoliosis and/or spinal stiffness) (4/5), and orthodontic features (small mouth, dental crowding,
missing teeth, or arched palate) (4/5).
Sources: Literature
Mendeliome v1.276 CAPRIN1 Paul De Fazio gene: CAPRIN1 was added
gene: CAPRIN1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CAPRIN1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CAPRIN1 were set to 35979925
Phenotypes for gene: CAPRIN1 were set to Neurodevelopmental disorder, CAPRIN1-related MONDO:0700092
Review for gene: CAPRIN1 was set to GREEN
gene: CAPRIN1 was marked as current diagnostic
Added comment: 12 individuals reported with ID and language impairment. Other features included seizures (4 individuals), hands and feet malformations (5 individuals), breathing problems (6 individuals), ocular problems (4 individuals) and hearing problems (3 individuals).

All of the variants were nonsense (NMD-predicted) or splicing variants. 10 were de novo, 1 was inherited from an affected father. Functional studies supported pathogenicity.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4912 CAPRIN1 Paul De Fazio gene: CAPRIN1 was added
gene: CAPRIN1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CAPRIN1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CAPRIN1 were set to 35979925
Phenotypes for gene: CAPRIN1 were set to Neurodevelopmental disorder, CAPRIN1-related MONDO:0700092
Review for gene: CAPRIN1 was set to GREEN
gene: CAPRIN1 was marked as current diagnostic
Added comment: 12 individuals reported with ID and language impairment. Other features included seizures (4 individuals), hands and feet malformations (5 individuals), breathing problems (6 individuals), ocular problems (4 individuals) and hearing problems (3 individuals).

All of the variants were nonsense (NMD-predicted) or splicing variants. 10 were de novo, 1 was inherited from an affected father. Functional studies supported pathogenicity.
Sources: Literature
Arthrogryposis v0.350 MET Lucy Spencer gene: MET was added
gene: MET was added to Arthrogryposis. Sources: Literature
Mode of inheritance for gene: MET was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MET were set to 30777867
Phenotypes for gene: MET were set to ?Arthrogryposis, distal, type 11 (MIM#620019), AD
Review for gene: MET was set to AMBER
Added comment: Four-generation Chinese arthrogryposis pedigree with only upper limb involvement. MET c.3701A>G p.Y1234C segregated as heterozygous in 11 affected family members and was absent from 12 unaffected family members. Variant is absent from gnomad.

Functional studies showed this variant caused failure of phosphorylation and loss of tyrosine kinase activity of MET receptor. A mouse model was also created with this variant, mutated mice were found to be smaller than WT mice and had reduced myofibres. These mouse models also had defective migration of muscle progenitor cells and impaired proliferation of secondary myoblasts.

Phenotypes in this family included camptodactyly, absent flexion crease, and limited forearm supination.
Sources: Literature
Mendeliome v1.276 LHX8 Alison Yeung gene: LHX8 was added
gene: LHX8 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LHX8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LHX8 were set to 36029299
Phenotypes for gene: LHX8 were set to Inherited premature ovarian failure, MONDO:0019852, LHX8-related
Review for gene: LHX8 was set to GREEN
Added comment: Heterozygous LOF variants identified in 6 families with premature ovarian failure due to oocyte maturation arrest.
Sources: Literature
Mendeliome v1.275 NOTCH1 Chern Lim reviewed gene: NOTCH1: Rating: GREEN; Mode of pathogenicity: Other; Publications: 35947102; Phenotypes: leukoencephalopathy and calcifications; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.306 LHX8 Alison Yeung Publications for gene: LHX8 were set to 34794894; 34095689; 29329412; 27603904
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.305 LHX8 Alison Yeung Classified gene: LHX8 as Green List (high evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.305 LHX8 Alison Yeung Gene: lhx8 has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.304 LHX8 Alison Yeung reviewed gene: LHX8: Rating: GREEN; Mode of pathogenicity: None; Publications: 36029299; Phenotypes: Inherited premature ovarian failure, MONDO:0019852, LHX8-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.275 GRIN2A Teresa Zhao reviewed gene: GRIN2A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35983985; Phenotypes: Epilepsy, focal, with speech disorder and with or without impaired intellectual development (MIM#245570); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.275 LEF1 Zornitza Stark Phenotypes for gene: LEF1 were changed from Ectodermal dysplasia, no OMIM# yet to Syndromic disease, MONDO:0002254, LEF1-related
Ectodermal Dysplasia v0.72 LEF1 Zornitza Stark Publications for gene: LEF1 were set to PMID: 32022899
Mendeliome v1.274 LEF1 Zornitza Stark Publications for gene: LEF1 were set to 32022899
Mendeliome v1.273 LEF1 Zornitza Stark Mode of inheritance for gene: LEF1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ectodermal Dysplasia v0.71 LEF1 Zornitza Stark Mode of inheritance for gene: LEF1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.272 LEF1 Zornitza Stark Classified gene: LEF1 as Green List (high evidence)
Mendeliome v1.272 LEF1 Zornitza Stark Gene: lef1 has been classified as Green List (High Evidence).
Mendeliome v1.271 LEF1 Zornitza Stark edited their review of gene: LEF1: Added comment: Monoallelic variants in LEF1 reported in 11 affected individuals from 4 unrelated families, and a biallelic variant reported in an affected individual from a consanguineous family. The phenotypic spectrum included various limb malformations, such as radial ray defects, polydactyly or split hand/foot, and ectodermal dysplasia. Haploinsufficiency or loss of DNA binding postulated to be responsible for a mild to moderate phenotype, whereas loss of β-catenin binding caused by biallelic variants postulated to be associated with a severe phenotype.; Changed rating: GREEN; Changed publications: 32022899, 35583550; Changed phenotypes: Syndromic disease, MONDO:0002254, LEF1-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ectodermal Dysplasia v0.70 LEF1 Zornitza Stark Deleted their comment
Ectodermal Dysplasia v0.70 LEF1 Zornitza Stark Phenotypes for gene: LEF1 were changed from Ectodermal dysplasia, no OMIM# yet to Syndromic disease, MONDO:0002254, LEF1-related
Ectodermal Dysplasia v0.69 LEF1 Zornitza Stark Classified gene: LEF1 as Green List (high evidence)
Ectodermal Dysplasia v0.69 LEF1 Zornitza Stark Gene: lef1 has been classified as Green List (High Evidence).
Polydactyly v0.260 LEF1 Zornitza Stark Classified gene: LEF1 as Green List (high evidence)
Polydactyly v0.260 LEF1 Zornitza Stark Gene: lef1 has been classified as Green List (High Evidence).
Ectodermal Dysplasia v0.68 LEF1 Zornitza Stark edited their review of gene: LEF1: Added comment: Monoallelic variants in LEF1 reported in 11 affected individuals from 4 unrelated families, and a biallelic variant reported in an affected individual from a consanguineous family. The phenotypic spectrum included various limb malformations, such as radial ray defects, polydactyly or split hand/foot, and ectodermal dysplasia. Haploinsufficiency or loss of DNA binding postulated to be responsible for a mild to moderate phenotype, whereas loss of β-catenin binding caused by biallelic variants postulated to be associated with a severe phenotype.; Changed rating: GREEN; Changed publications: 32022899, 35583550; Changed phenotypes: Syndromic disease, MONDO:0002254, LEF1-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Polydactyly v0.259 LEF1 Zornitza Stark Classified gene: LEF1 as Green List (high evidence)
Polydactyly v0.259 LEF1 Zornitza Stark Gene: lef1 has been classified as Green List (High Evidence).
Polydactyly v0.258 LEF1 Zornitza Stark Marked gene: LEF1 as ready
Polydactyly v0.258 LEF1 Zornitza Stark Gene: lef1 has been classified as Red List (Low Evidence).
Polydactyly v0.258 LEF1 Zornitza Stark gene: LEF1 was added
gene: LEF1 was added to Polydactyly. Sources: Literature
Mode of inheritance for gene: LEF1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: LEF1 were set to 35583550
Phenotypes for gene: LEF1 were set to Syndromic disease, MONDO:0002254, LEF1-related
Review for gene: LEF1 was set to GREEN
Added comment: Monoallelic variants in LEF1 reported in 11 affected individuals from 4 unrelated families, and a biallelic variant reported in an affected individual from a consanguineous family. The phenotypic spectrum included various limb malformations, such as radial ray defects, polydactyly or split hand/foot, and ectodermal dysplasia. Haploinsufficiency or loss of DNA binding postulated to be responsible for a mild to moderate phenotype, whereas loss of β-catenin binding caused by biallelic variants postulated to be associated with a severe phenotype.
Sources: Literature
Radial Ray Abnormalities v1.4 LEF1 Zornitza Stark Marked gene: LEF1 as ready
Radial Ray Abnormalities v1.4 LEF1 Zornitza Stark Gene: lef1 has been classified as Green List (High Evidence).
Radial Ray Abnormalities v1.4 LEF1 Zornitza Stark Classified gene: LEF1 as Green List (high evidence)
Radial Ray Abnormalities v1.4 LEF1 Zornitza Stark Gene: lef1 has been classified as Green List (High Evidence).
Radial Ray Abnormalities v1.3 LEF1 Zornitza Stark gene: LEF1 was added
gene: LEF1 was added to Radial Ray Abnormalities. Sources: Literature
Mode of inheritance for gene: LEF1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: LEF1 were set to 35583550
Phenotypes for gene: LEF1 were set to Syndromic disease, MONDO:0002254, LEF1-related
Review for gene: LEF1 was set to GREEN
Added comment: Monoallelic variants in LEF1 reported in 11 affected individuals from 4 unrelated families, and a biallelic variant reported in an affected individual from a consanguineous family. The phenotypic spectrum included various limb malformations, such as radial ray defects, polydactyly or split hand/foot, and ectodermal dysplasia. Haploinsufficiency or loss of DNA binding postulated to be responsible for a mild to moderate phenotype, whereas loss of β-catenin binding caused by biallelic variants postulated to be associated with a severe phenotype.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4911 Zornitza Stark List of related panels changed from to Intellectual disability; HP:0001249; Neurodevelopmental delay; HP:0012758
Mendeliome v1.271 REEP1 Zornitza Stark Phenotypes for gene: REEP1 were changed from Neuronopathy, distal hereditary motor, type VB MIM#614751; Spastic paraplegia 31, autosomal dominant MIM#610250; Charcot-Marie-Tooth; severe congenital distal SMA with diaphragmatic paralysis; congenital axonal neuropathy and diaphragmatic palsy to Spinal muscular atrophy, distal, autosomal recessive, 6, MIM#620011; Neuronopathy, distal hereditary motor, type VB MIM#614751; Spastic paraplegia 31, autosomal dominant MIM#610250
Mendeliome v1.270 REEP1 Zornitza Stark reviewed gene: REEP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinal muscular atrophy, distal, autosomal recessive, 6, MIM#620011; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia v0.340 Zornitza Stark HPO terms changed from to Ataxia, HP:0001251
Arthrogryposis v0.350 Zornitza Stark HPO terms changed from to Flexion contracture, HP:0001371
Aortopathy_Connective Tissue Disorders v1.69 Zornitza Stark HPO terms changed from to Aortic aneurysm, HP:0004942;Joint dislocation, HP:0001373;Cutis laxa, HP:0000973; Ectopia lentis, HP:0001083;Arachnodactyly, HP:0001166
Anophthalmia_Microphthalmia_Coloboma v1.29 Zornitza Stark HPO terms changed from to Anophthalmia, HP:0000528;Microphthalmia, HP:0000568;Coloboma, HP:0000589
Achromatopsia v1.4 Zornitza Stark HPO terms changed from to Achromatopsia, HP:0011516
Leukodystrophy v0.275 Zornitza Stark HPO terms changed from to Leukodystrophy, HP:0002415; Abnormal cerebral white matter morphology, HP:0002500
Genetic Epilepsy v0.1646 Zornitza Stark HPO terms changed from to Seizure, HP:0001250
Intellectual disability syndromic and non-syndromic v0.4910 Zornitza Stark HPO terms changed from to Intellectual disability, HP:0001249; Neurodevelopmental delay, HP:0012758
Ciliopathies v1.34 TMEM218 Zornitza Stark Marked gene: TMEM218 as ready
Ciliopathies v1.34 TMEM218 Zornitza Stark Gene: tmem218 has been classified as Green List (High Evidence).
Ciliopathies v1.34 TMEM218 Zornitza Stark Classified gene: TMEM218 as Green List (high evidence)
Ciliopathies v1.34 TMEM218 Zornitza Stark Gene: tmem218 has been classified as Green List (High Evidence).
Ciliopathies v1.33 TMEM218 Zornitza Stark gene: TMEM218 was added
gene: TMEM218 was added to Ciliopathies. Sources: Expert Review
Mode of inheritance for gene: TMEM218 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM218 were set to 35137054; 33791682
Phenotypes for gene: TMEM218 were set to Joubert syndrome 39, MIM#619562; retinal dystrophy; polycystic kidneys; occipital encephalocele
Review for gene: TMEM218 was set to GREEN
Added comment: More than 3 unrelated families reported, with a range of ciliopathy phenotypes, including Joubert syndrome, MKS and BBS.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.4909 LNPK Zornitza Stark Publications for gene: LNPK were set to 30032983
Hereditary Spastic Paraplegia v1.44 CCDC82 Zornitza Stark Marked gene: CCDC82 as ready
Hereditary Spastic Paraplegia v1.44 CCDC82 Zornitza Stark Gene: ccdc82 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v1.44 CCDC82 Zornitza Stark Phenotypes for gene: CCDC82 were changed from Intellectual disability and spastic paraparesis, no OMIM # to Neurodevelopmental disorder, MONDO:0700092, CCDC82-related
Hereditary Spastic Paraplegia v1.43 CCDC82 Zornitza Stark Publications for gene: CCDC82 were set to PMID: 35373332, 35118659, 27457812
Hereditary Spastic Paraplegia v1.42 CCDC82 Zornitza Stark reviewed gene: CCDC82: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, CCDC82-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4908 CCDC82 Zornitza Stark Marked gene: CCDC82 as ready
Intellectual disability syndromic and non-syndromic v0.4908 CCDC82 Zornitza Stark Gene: ccdc82 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4908 CCDC82 Zornitza Stark Phenotypes for gene: CCDC82 were changed from Intellectual disability and spastic paraparesis, no OMIM # to Neurodevelopmental disorder, MONDO:0700092, CCDC82-related
Intellectual disability syndromic and non-syndromic v0.4907 CCDC82 Zornitza Stark Publications for gene: CCDC82 were set to PMID: 35373332, 35118659, 27457812
Intellectual disability syndromic and non-syndromic v0.4906 CCDC82 Zornitza Stark reviewed gene: CCDC82: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, CCDC82-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.270 CCDC82 Zornitza Stark Marked gene: CCDC82 as ready
Mendeliome v1.270 CCDC82 Zornitza Stark Gene: ccdc82 has been classified as Green List (High Evidence).
Mendeliome v1.270 CCDC82 Zornitza Stark Phenotypes for gene: CCDC82 were changed from Intellectual disability and spastic paraparesis, no OMIM # to Neurodevelopmental disorder, MONDO:0700092, CCDC82-related
Mendeliome v1.269 CCDC82 Zornitza Stark Publications for gene: CCDC82 were set to PMID: 35373332, 35118659, 27457812
Mendeliome v1.268 CCDC82 Zornitza Stark reviewed gene: CCDC82: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, CCDC82-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.63 NPNT Zornitza Stark Marked gene: NPNT as ready
Fetal anomalies v1.63 NPNT Zornitza Stark Gene: npnt has been classified as Green List (High Evidence).
Fetal anomalies v1.63 NPNT Zornitza Stark Phenotypes for gene: NPNT were changed from Renal agenesis, no OMIM # to Renal agenesis, MONDO:0018470, NPNT-related
Fetal anomalies v1.62 NPNT Zornitza Stark Publications for gene: NPNT were set to PMID: 35246978, 34049960, 17537792
Fetal anomalies v1.61 NPNT Zornitza Stark reviewed gene: NPNT: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Renal agenesis, MONDO:0018470, NPNT-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.268 NPNT Zornitza Stark Marked gene: NPNT as ready
Mendeliome v1.268 NPNT Zornitza Stark Gene: npnt has been classified as Green List (High Evidence).
Mendeliome v1.268 NPNT Zornitza Stark Phenotypes for gene: NPNT were changed from Renal agenesis, no OMIM # to Renal agenesis, MONDO:0018470, NPNT-related
Mendeliome v1.267 NPNT Zornitza Stark Publications for gene: NPNT were set to PMID: 35246978, 34049960, 17537792
Mendeliome v1.266 NPNT Zornitza Stark reviewed gene: NPNT: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Renal agenesis, MONDO:0018470, NPNT-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v0.184 KIF5B Zornitza Stark Marked gene: KIF5B as ready
Skeletal dysplasia v0.184 KIF5B Zornitza Stark Gene: kif5b has been classified as Green List (High Evidence).
Skeletal dysplasia v0.184 KIF5B Zornitza Stark Phenotypes for gene: KIF5B were changed from Kyphomelic dysplasia, no OMIM # to Skeletal dysplasia, MONDO:0018230, KIF5B-related; Kyphomelic dysplasia
Skeletal dysplasia v0.183 KIF5B Zornitza Stark reviewed gene: KIF5B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Skeletal dysplasia, MONDO:0018230, KIF5B-related, Kyphomelic dysplasia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.266 KIF5B Zornitza Stark Phenotypes for gene: KIF5B were changed from Skeletal dysplasia, MONDO:0018230 to Skeletal dysplasia, MONDO:0018230, KIF5B-related; Kyphomelic dysplasia
Mendeliome v1.265 KIF5B Zornitza Stark Marked gene: KIF5B as ready
Mendeliome v1.265 KIF5B Zornitza Stark Gene: kif5b has been classified as Green List (High Evidence).
Mendeliome v1.265 KIF5B Zornitza Stark Phenotypes for gene: KIF5B were changed from Kyphomelic dysplasia, no OMIM # to Skeletal dysplasia, MONDO:0018230
Mendeliome v1.264 KIF5B Zornitza Stark reviewed gene: KIF5B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Skeletal dysplasia, MONDO:0018230; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Clefting disorders v0.184 COL9A3 Zornitza Stark Phenotypes for gene: COL9A3 were changed from Stickler syndrome; Cleft palate to Stickler syndrome, type VI, MIM# 620022
Clefting disorders v0.183 COL9A3 Zornitza Stark edited their review of gene: COL9A3: Changed phenotypes: Stickler syndrome, type VI, MIM# 620022
Stickler Syndrome v1.4 COL9A3 Zornitza Stark Phenotypes for gene: COL9A3 were changed from Stickler syndrome, AR; Deafness, AD; Peripheral vitreoretinal degeneration and retinal detachment, AD to Stickler syndrome, type VI, MIM# 620022; Deafness, AD; Peripheral vitreoretinal degeneration and retinal detachment, AD
Stickler Syndrome v1.3 COL9A3 Zornitza Stark edited their review of gene: COL9A3: Changed phenotypes: Stickler syndrome, type VI, MIM# 620022, Deafness, AD, Peripheral vitreoretinal degeneration and retinal detachment, AD
Deafness_IsolatedAndComplex v1.144 COL9A3 Zornitza Stark Phenotypes for gene: COL9A3 were changed from Stickler syndrome to Stickler syndrome, type VI, MIM# 620022
Deafness_IsolatedAndComplex v1.143 COL9A3 Zornitza Stark edited their review of gene: COL9A3: Changed phenotypes: Stickler syndrome, type VI, MIM# 620022
Mendeliome v1.264 COL9A3 Zornitza Stark Phenotypes for gene: COL9A3 were changed from Epiphyseal dysplasia, multiple, 3, with or without myopathy, MIM# 600969; Stickler syndrome AR; Deafness AD; Peripheral vitreoretinal degeneration and retinal detachment, AD to Epiphyseal dysplasia, multiple, 3, with or without myopathy, MIM# 600969; Stickler syndrome, type VI, MIM# 620022; Deafness AD; Peripheral vitreoretinal degeneration and retinal detachment, AD
Mendeliome v1.263 COL9A3 Zornitza Stark edited their review of gene: COL9A3: Changed phenotypes: Epiphyseal dysplasia, multiple, 3, with or without myopathy, MIM# 600969, Stickler syndrome, type VI, MIM# 620022, Deafness
Mendeliome v1.263 LNPK Chirag Patel Classified gene: LNPK as Green List (high evidence)
Mendeliome v1.263 LNPK Chirag Patel Gene: lnpk has been classified as Green List (High Evidence).
Callosome v0.462 LNPK Chirag Patel Classified gene: LNPK as Green List (high evidence)
Callosome v0.462 LNPK Chirag Patel Gene: lnpk has been classified as Green List (High Evidence).
Callosome v0.462 LNPK Chirag Patel Classified gene: LNPK as Green List (high evidence)
Callosome v0.462 LNPK Chirag Patel Gene: lnpk has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1645 LNPK Chirag Patel Classified gene: LNPK as Green List (high evidence)
Genetic Epilepsy v0.1645 LNPK Chirag Patel Gene: lnpk has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4906 LNPK Chirag Patel Classified gene: LNPK as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4906 LNPK Chirag Patel Gene: lnpk has been classified as Green List (High Evidence).
Callosome v0.461 LNPK Chirag Patel gene: LNPK was added
gene: LNPK was added to Callosome. Sources: Literature
Mode of inheritance for gene: LNPK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LNPK were set to PMID: 35599435, 30032983
Phenotypes for gene: LNPK were set to Neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum, MIM# 618090
Review for gene: LNPK was set to GREEN
Added comment: 3 unrelated consanguineous families with 4 affected individuals reported. WES revealed 3 novel homozygous frameshift variants in exon 10 of the LNPK gene (detected as a heterozygote in healthy parents). Some functional evidence with mRNA expression decreased in the fibroblast tissues of the affected individuals with homozygous variants and healthy heterozygous parents, with a greater rate in individuals with homozygous variants. There was no full-length protein in the affected individuals with homozygous variants detected using immunohistochemical studies. Common clinical manifestations in all cases included developmental delay, movement disorders, epilepsy, corpus callosum anomalies, and regression phenotype.
Sources: Literature
Mendeliome v1.262 LNPK Chirag Patel reviewed gene: LNPK: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35599435; Phenotypes: Neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum, MIM# 618090; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.1644 LNPK Chirag Patel reviewed gene: LNPK: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35599435; Phenotypes: Neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum, MIM# 618090; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4905 LNPK Chirag Patel reviewed gene: LNPK: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35599435; Phenotypes: Neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum, MIM# 618090; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4905 CCDC82 Chirag Patel Classified gene: CCDC82 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4905 CCDC82 Chirag Patel Gene: ccdc82 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4905 CCDC82 Chirag Patel Classified gene: CCDC82 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4905 CCDC82 Chirag Patel Gene: ccdc82 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v1.42 CCDC82 Chirag Patel Classified gene: CCDC82 as Green List (high evidence)
Hereditary Spastic Paraplegia v1.42 CCDC82 Chirag Patel Gene: ccdc82 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4904 CCDC82 Chirag Patel gene: CCDC82 was added
gene: CCDC82 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CCDC82 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC82 were set to PMID: 35373332, 35118659, 27457812
Phenotypes for gene: CCDC82 were set to Intellectual disability and spastic paraparesis, no OMIM #
Review for gene: CCDC82 was set to GREEN
Added comment: 4 consanguineous families with 9 affected individuals with developmental delay/intellectual disability, and 2 families had spasticity and 1 had epilepsy. WES identified 3 homozgyous truncating variants, segregating with disease and parents as carriers. No functional studies.
Sources: Literature
Mendeliome v1.262 CCDC82 Chirag Patel Classified gene: CCDC82 as Green List (high evidence)
Mendeliome v1.262 CCDC82 Chirag Patel Gene: ccdc82 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v1.41 CCDC82 Chirag Patel gene: CCDC82 was added
gene: CCDC82 was added to Hereditary Spastic Paraplegia - paediatric. Sources: Literature
Mode of inheritance for gene: CCDC82 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC82 were set to PMID: 35373332, 35118659, 27457812
Phenotypes for gene: CCDC82 were set to Intellectual disability and spastic paraparesis, no OMIM #
Review for gene: CCDC82 was set to GREEN
Added comment: 4 consanguineous families with 9 affected individuals with developmental delay/intellectual disability, and 2 families had spasticity and 1 had epilepsy. WES identified 3 homozgyous truncating variants, segregating with disease and parents as carriers. No functional studies.
Sources: Literature
Mendeliome v1.261 CCDC82 Chirag Patel gene: CCDC82 was added
gene: CCDC82 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CCDC82 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC82 were set to PMID: 35373332, 35118659, 27457812
Phenotypes for gene: CCDC82 were set to Intellectual disability and spastic paraparesis, no OMIM #
Review for gene: CCDC82 was set to GREEN
Added comment: 4 consanguineous families with 9 affected individuals with developmental delay/intellectual disability, and 2 families had spasticity and 1 had epilepsy. WES identified 3 homozgyous truncating variants, segregating with disease and parents as carriers. No functional studies.
Sources: Literature
Mendeliome v1.260 NPNT Chirag Patel Classified gene: NPNT as Green List (high evidence)
Mendeliome v1.260 NPNT Chirag Patel Gene: npnt has been classified as Green List (High Evidence).
Mendeliome v1.260 NPNT Chirag Patel Classified gene: NPNT as Green List (high evidence)
Mendeliome v1.260 NPNT Chirag Patel Gene: npnt has been classified as Green List (High Evidence).
Mendeliome v1.259 NPNT Chirag Patel gene: NPNT was added
gene: NPNT was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NPNT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NPNT were set to PMID: 35246978, 34049960, 17537792
Phenotypes for gene: NPNT were set to Renal agenesis, no OMIM #
Review for gene: NPNT was set to GREEN
Added comment: 3 consanguineous families with multiple affecteds with bilateral renal agenesis. Whole-exome sequencing (WES)-based homozygosity mapping identified 2 homozygous truncating variants. Reverse transcription polymerase chain reaction data showing complete nonsense-mediated decay of the NPNT transcript. Loss of nephronectin (NPNT) is known to lead to failure of metanephric kidney development with resulting renal agenesis in murine models.
Sources: Literature
Fetal anomalies v1.61 NPNT Chirag Patel Classified gene: NPNT as Green List (high evidence)
Fetal anomalies v1.61 NPNT Chirag Patel Gene: npnt has been classified as Green List (High Evidence).
Fetal anomalies v1.60 NPNT Chirag Patel gene: NPNT was added
gene: NPNT was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: NPNT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NPNT were set to PMID: 35246978, 34049960, 17537792
Phenotypes for gene: NPNT were set to Renal agenesis, no OMIM #
Review for gene: NPNT was set to GREEN
Added comment: 3 consanguineous families with multiple affecteds with bilateral renal agenesis. Whole-exome sequencing (WES)-based homozygosity mapping identified 2 homozygous truncating variants. Reverse transcription polymerase chain reaction data showing complete nonsense-mediated decay of the NPNT transcript. Loss of nephronectin (NPNT) is known to lead to failure of metanephric kidney development with resulting renal agenesis in murine models.
Sources: Literature
Mendeliome v1.258 KIF5B Chirag Patel Classified gene: KIF5B as Green List (high evidence)
Mendeliome v1.258 KIF5B Chirag Patel Gene: kif5b has been classified as Green List (High Evidence).
Mendeliome v1.258 KIF5B Chirag Patel Classified gene: KIF5B as Green List (high evidence)
Mendeliome v1.258 KIF5B Chirag Patel Gene: kif5b has been classified as Green List (High Evidence).
Mendeliome v1.257 KIF5B Chirag Patel gene: KIF5B was added
gene: KIF5B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KIF5B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF5B were set to PMID: 35342932
Phenotypes for gene: KIF5B were set to Kyphomelic dysplasia, no OMIM #
Review for gene: KIF5B was set to GREEN
Added comment: 4 individuals with Kyphomelic dysplasia (severe bowing of the limbs, sharp angulation of the femora and humeri, short stature, narrow thorax, distinctive facial features, and neonatal respiratory distress. WES found de novo heterozygous missense variants in KIF5B encoding kinesin-1 heavy chain. All variants involved conserved amino acids in or close to the ATPase activity-related motifs in the catalytic motor domain of the KIF5B protein. No functional studies of variants. Previously 2 animal model experiments showed that loss of function of KIF5B can cause kyphomelic dysplasia. First, chondrocyte-specific knockout of Kif5b in mice was shown to produce a disorganized growth plate, leading to bone deformity. Second, double mutants disrupting the two zebrafish kif5b caused abnormal skeletal morphogenesis and the curvature of Meckel's and ceratohyal cartilages.
Sources: Literature
Fetal anomalies v1.59 KIF5B Chirag Patel Classified gene: KIF5B as Green List (high evidence)
Fetal anomalies v1.59 KIF5B Chirag Patel Gene: kif5b has been classified as Green List (High Evidence).
Fetal anomalies v1.58 KIF5B Chirag Patel gene: KIF5B was added
gene: KIF5B was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: KIF5B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF5B were set to PMID: 35342932
Phenotypes for gene: KIF5B were set to Kyphomelic dysplasia, no OMIM #
Review for gene: KIF5B was set to GREEN
Added comment: 4 individuals with Kyphomelic dysplasia (severe bowing of the limbs, sharp angulation of the femora and humeri, short stature, narrow thorax, distinctive facial features, and neonatal respiratory distress. WES found de novo heterozygous missense variants in KIF5B encoding kinesin-1 heavy chain. All variants involved conserved amino acids in or close to the ATPase activity-related motifs in the catalytic motor domain of the KIF5B protein. No functional studies of variants.

Previously 2 animal model experiments showed that loss of function of KIF5B can cause kyphomelic dysplasia. First, chondrocyte-specific knockout of Kif5b in mice was shown to produce a disorganized growth plate, leading to bone deformity. Second, double mutants disrupting the two zebrafish kif5b caused abnormal skeletal morphogenesis and the curvature of Meckel's and ceratohyal cartilages.
Sources: Literature
Skeletal dysplasia v0.183 KIF5B Chirag Patel Classified gene: KIF5B as Green List (high evidence)
Skeletal dysplasia v0.183 KIF5B Chirag Patel Gene: kif5b has been classified as Green List (High Evidence).
Skeletal dysplasia v0.182 KIF5B Chirag Patel gene: KIF5B was added
gene: KIF5B was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: KIF5B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF5B were set to PMID: 35342932
Phenotypes for gene: KIF5B were set to Kyphomelic dysplasia, no OMIM #
Review for gene: KIF5B was set to GREEN
Added comment: 4 individuals with Kyphomelic dysplasia (severe bowing of the limbs, sharp angulation of the femora and humeri, short stature, narrow thorax, distinctive facial features, and neonatal respiratory distress. WES found de novo heterozygous missense variants in KIF5B encoding kinesin-1 heavy chain. All variants involved conserved amino acids in or close to the ATPase activity-related motifs in the catalytic motor domain of the KIF5B protein. No functional studies of variants.

Previously 2 animal model experiments showed that loss of function of KIF5B can cause kyphomelic dysplasia. First, chondrocyte-specific knockout of Kif5b in mice was shown to produce a disorganized growth plate, leading to bone deformity. Second, double mutants disrupting the two zebrafish kif5b caused abnormal skeletal morphogenesis and the curvature of Meckel's and ceratohyal cartilages.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4903 FBXW7 Zornitza Stark Phenotypes for gene: FBXW7 were changed from FBXW7-related neurodevelopmental syndrome to Developmental delay, hypotonia, and impaired language, MIM# 620012
Intellectual disability syndromic and non-syndromic v0.4902 FBXW7 Zornitza Stark edited their review of gene: FBXW7: Changed phenotypes: Developmental delay, hypotonia, and impaired language, MIM# 620012
Mendeliome v1.256 FBXW7 Zornitza Stark Phenotypes for gene: FBXW7 were changed from neurodevelopmental disorder MONDO:0700092; FBXW7-related neurodevelopmental syndrome; Wilms tumor MONDO:0006058 to Developmental delay, hypotonia, and impaired language, MIM# 620012; Wilms tumour predisposition
Mendeliome v1.255 FBXW7 Zornitza Stark edited their review of gene: FBXW7: Changed phenotypes: Developmental delay, hypotonia, and impaired language, MIM# 620012, Wilms tumour predisposition
Prepair 1000+ v0.167 VPS13A Zornitza Stark Marked gene: VPS13A as ready
Prepair 1000+ v0.167 VPS13A Zornitza Stark Gene: vps13a has been classified as Red List (Low Evidence).
Prepair 1000+ v0.167 VPS13A Zornitza Stark Publications for gene: VPS13A were set to
Prepair 1000+ v0.166 VPS13A Zornitza Stark Classified gene: VPS13A as Red List (low evidence)
Prepair 1000+ v0.166 VPS13A Zornitza Stark Gene: vps13a has been classified as Red List (Low Evidence).
Prepair 1000+ v0.165 VPS13A Zornitza Stark Tag for review was removed from gene: VPS13A.
Prepair 1000+ v0.165 VPS13A Zornitza Stark changed review comment from: Appears to be adult onset disorder. For further review.; to: Appears to be adult onset disorder.
Prepair 1000+ v0.165 VPS13A Zornitza Stark edited their review of gene: VPS13A: Changed rating: RED
Prepair 1000+ v0.165 RYR1 Zornitza Stark Publications for gene: RYR1 were set to
Prepair 1000+ v0.164 RYR1 Zornitza Stark Tag for review was removed from gene: RYR1.
Prepair 1000+ v0.164 RYR1 Zornitza Stark commented on gene: RYR1: Hard to predict outcome in a screening context. However, multiple reports of severe perinatal outcomes.
Prepair 1000+ v0.164 TFR2 Zornitza Stark Marked gene: TFR2 as ready
Prepair 1000+ v0.164 TFR2 Zornitza Stark Gene: tfr2 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.164 TFR2 Zornitza Stark Phenotypes for gene: TFR2 were changed from Hemochromatosis, type 3, MIM#604250 to Haemochromatosis, type 3, MIM#604250
Prepair 1000+ v0.163 TFR2 Zornitza Stark Classified gene: TFR2 as Red List (low evidence)
Prepair 1000+ v0.163 TFR2 Zornitza Stark Gene: tfr2 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.162 TFR2 Zornitza Stark Tag for review was removed from gene: TFR2.
Prepair 1000+ v0.162 TFR2 Zornitza Stark reviewed gene: TFR2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Haemochromatosis, type 3, MIM#604250; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.162 TAT Zornitza Stark reviewed gene: TAT: Rating: AMBER; Mode of pathogenicity: None; Publications: 28255985; Phenotypes: Tyrosinaemia, type II, MIM# 276600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.162 PYGM Zornitza Stark Marked gene: PYGM as ready
Prepair 1000+ v0.162 PYGM Zornitza Stark Gene: pygm has been classified as Red List (Low Evidence).
Prepair 1000+ v0.162 SLC12A3 Zornitza Stark Marked gene: SLC12A3 as ready
Prepair 1000+ v0.162 SLC12A3 Zornitza Stark Gene: slc12a3 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.162 PYGM Zornitza Stark Classified gene: PYGM as Red List (low evidence)
Prepair 1000+ v0.162 PYGM Zornitza Stark Gene: pygm has been classified as Red List (Low Evidence).
Prepair 1000+ v0.161 SLC4A11 Zornitza Stark Marked gene: SLC4A11 as ready
Prepair 1000+ v0.161 SLC4A11 Zornitza Stark Gene: slc4a11 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.161 PYGM Zornitza Stark Tag for review was removed from gene: PYGM.
Prepair 1000+ v0.161 SLC4A11 Zornitza Stark Classified gene: SLC4A11 as Red List (low evidence)
Prepair 1000+ v0.161 SLC4A11 Zornitza Stark Gene: slc4a11 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.160 SLC4A11 Zornitza Stark Tag for review was removed from gene: SLC4A11.
Prepair 1000+ v0.160 SLC4A11 Zornitza Stark reviewed gene: SLC4A11: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Corneal endothelial dystrophy and perceptive deafness, MIM# 217400, Corneal endothelial dystrophy, autosomal recessive, MIM# 217700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.160 OAT Zornitza Stark Marked gene: OAT as ready
Prepair 1000+ v0.160 OAT Zornitza Stark Gene: oat has been classified as Red List (Low Evidence).
Prepair 1000+ v0.160 SLC12A3 Zornitza Stark Classified gene: SLC12A3 as Red List (low evidence)
Prepair 1000+ v0.160 SLC12A3 Zornitza Stark Gene: slc12a3 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.159 SLC12A3 Zornitza Stark Tag for review was removed from gene: SLC12A3.
Prepair 1000+ v0.159 SLC12A3 Zornitza Stark reviewed gene: SLC12A3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Gitelman syndrome, MIM#263800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.159 RS1 Zornitza Stark Marked gene: RS1 as ready
Prepair 1000+ v0.159 RS1 Zornitza Stark Gene: rs1 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.159 OAT Zornitza Stark Classified gene: OAT as Red List (low evidence)
Prepair 1000+ v0.159 OAT Zornitza Stark Gene: oat has been classified as Red List (Low Evidence).
Prepair 1000+ v0.158 RS1 Zornitza Stark Classified gene: RS1 as Red List (low evidence)
Prepair 1000+ v0.158 RS1 Zornitza Stark Gene: rs1 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.157 RS1 Zornitza Stark reviewed gene: RS1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Retinoschisis (MIM#312700); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v0.157 NR2E3 Zornitza Stark Marked gene: NR2E3 as ready
Prepair 1000+ v0.157 NR2E3 Zornitza Stark Gene: nr2e3 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.157 PYGM Zornitza Stark reviewed gene: PYGM: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: McArdle disease (MIM#232600); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.157 OAT Zornitza Stark reviewed gene: OAT: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Gyrate atrophy of choroid and retina with or without ornithinemia, MIM# 258870; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.157 NR2E3 Zornitza Stark Classified gene: NR2E3 as Red List (low evidence)
Prepair 1000+ v0.157 NR2E3 Zornitza Stark Gene: nr2e3 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.156 NR2E3 Zornitza Stark reviewed gene: NR2E3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Prepair 1000+ v0.156 Zornitza Stark Panel name changed from Reproductive Carrier Screen_VCGS to Prepair 1000+
Regression v0.495 CC2D2A Zornitza Stark Marked gene: CC2D2A as ready
Regression v0.495 CC2D2A Zornitza Stark Gene: cc2d2a has been classified as Red List (Low Evidence).
Regression v0.495 CC2D2A Zornitza Stark Phenotypes for gene: CC2D2A were changed from to COACH syndrome 2, MIM# 619111; Joubert syndrome 9, 612285; Meckel syndrome 6, 612284
Regression v0.494 CC2D2A Zornitza Stark Mode of inheritance for gene: CC2D2A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Regression v0.493 CC2D2A Zornitza Stark Classified gene: CC2D2A as Red List (low evidence)
Regression v0.493 CC2D2A Zornitza Stark Gene: cc2d2a has been classified as Red List (Low Evidence).
Regression v0.492 CC2D2A Zornitza Stark reviewed gene: CC2D2A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: COACH syndrome 2, MIM# 619111, Joubert syndrome 9, 612285, Meckel syndrome 6, 612284; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.155 RPGR Zornitza Stark Tag for review tag was added to gene: RPGR.
Fetal anomalies v1.57 MDFIC Zornitza Stark Phenotypes for gene: MDFIC were changed from Hydrops fetalis MONDO:0015193 to Lymphatic malformation 12, MIM# 620014
Fetal anomalies v1.56 MDFIC Zornitza Stark reviewed gene: MDFIC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Lymphatic malformation 12, MIM# 620014; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.255 MDFIC Zornitza Stark Phenotypes for gene: MDFIC were changed from Hydrops fetalis MONDO:0015193 to Lymphatic malformation 12, MIM# 620014
Mendeliome v1.254 MDFIC Zornitza Stark reviewed gene: MDFIC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Lymphatic malformation 12, MIM# 620014; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hydrops fetalis v0.291 MDFIC Zornitza Stark Phenotypes for gene: MDFIC were changed from Hydrops fetalis MONDO:0015193 to Lymphatic malformation 12, MIM# 620014
Hydrops fetalis v0.290 MDFIC Zornitza Stark edited their review of gene: MDFIC: Changed phenotypes: Lymphatic malformation 12, MIM# 620014; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Additional findings_Paediatric v0.272 ACADS Zornitza Stark Phenotypes for gene: ACADS were changed from Acyl-CoA dehydrogenase, short-chain, deficiency of to Acyl-CoA dehydrogenase, short-chain, deficiency of 201470
Additional findings_Paediatric v0.271 ACADS Zornitza Stark Classified gene: ACADS as Red List (low evidence)
Additional findings_Paediatric v0.271 ACADS Zornitza Stark Gene: acads has been classified as Red List (Low Evidence).
Additional findings_Paediatric v0.270 ACADS Zornitza Stark changed review comment from: SCAD deficiency is an autosomal recessive metabolic disorder of fatty acid beta-oxidation. Clinical features are variable: a severe form of the disorder can cause infantile onset of acidosis and neurologic impairment, whereas some patients develop only myopathy. Definitive gene-disease association. Rated category 'C' by BabySeq, due to moderate penetrance and lack of actionability. Some mildly affected individuals are being identified as part of newborn screening programs. However, a diagnosis of this disorder has the potential for avoidance of unnecessary investigations, therefore promoted to Green.; to: SCAD deficiency is an autosomal recessive metabolic disorder of fatty acid beta-oxidation. Clinical features are variable: a severe form of the disorder can cause infantile onset of acidosis and neurologic impairment, whereas some patients develop only myopathy. Definitive gene-disease association. Rated category 'C' by BabySeq, due to moderate penetrance and lack of actionability.
Additional findings_Paediatric v0.270 ACADS Zornitza Stark edited their review of gene: ACADS: Added comment: Definitive by ClinGen. However, largely just causes a biochemical abnormality, and association with clinical disease is debated.; Changed rating: RED
Intellectual disability syndromic and non-syndromic v0.4902 ACADS Zornitza Stark Classified gene: ACADS as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.4902 ACADS Zornitza Stark Gene: acads has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.4901 ACADS Zornitza Stark changed review comment from: Definitive by ClinGen. Metabolic decompensation. DD/ID is a feature.; to: Definitive by ClinGen. However, largely just causes a biochemical abnormality, and association with clinical disease is debated. DD/ID reported.
Intellectual disability syndromic and non-syndromic v0.4901 ACADS Zornitza Stark edited their review of gene: ACADS: Changed rating: AMBER
Callosome v0.460 ACADS Zornitza Stark Marked gene: ACADS as ready
Callosome v0.460 ACADS Zornitza Stark Gene: acads has been classified as Red List (Low Evidence).
Callosome v0.460 ACADS Zornitza Stark Phenotypes for gene: ACADS were changed from to Acyl-CoA dehydrogenase, short-chain, deficiency of, MIM# 201470; MONDO:0008722
Callosome v0.459 ACADS Zornitza Stark Mode of inheritance for gene: ACADS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Callosome v0.458 ACADS Zornitza Stark Classified gene: ACADS as Red List (low evidence)
Callosome v0.458 ACADS Zornitza Stark Gene: acads has been classified as Red List (Low Evidence).
Callosome v0.457 ACADS Zornitza Stark reviewed gene: ACADS: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Acyl-CoA dehydrogenase, short-chain, deficiency of, MIM# 201470, MONDO:0008722; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.834 ACADS Zornitza Stark Phenotypes for gene: ACADS were changed from Acyl-CoA dehydrogenase, short-chain, deficiency of MIM#201470 to Acyl-CoA dehydrogenase, short-chain, deficiency of, MIM# 201470; MONDO:0008722
Mitochondrial disease v0.833 ACADS Zornitza Stark Classified gene: ACADS as Amber List (moderate evidence)
Mitochondrial disease v0.833 ACADS Zornitza Stark Gene: acads has been classified as Amber List (Moderate Evidence).
Mitochondrial disease v0.832 ACADS Zornitza Stark reviewed gene: ACADS: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Acyl-CoA dehydrogenase, short-chain, deficiency of, MIM# 201470, MONDO:0008722; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.254 ACADS Zornitza Stark Classified gene: ACADS as Amber List (moderate evidence)
Mendeliome v1.254 ACADS Zornitza Stark Gene: acads has been classified as Amber List (Moderate Evidence).
Mendeliome v1.253 ACADS Zornitza Stark changed review comment from: Definitive by ClinGen.; to: Definitive by ClinGen. However, largely just causes a biochemical abnormality, and association with clinical disease is debated.
Fatty Acid Oxidation Defects v1.8 ACADS Zornitza Stark Classified gene: ACADS as Amber List (moderate evidence)
Fatty Acid Oxidation Defects v1.8 ACADS Zornitza Stark Gene: acads has been classified as Amber List (Moderate Evidence).
Mendeliome v1.253 ACADS Zornitza Stark edited their review of gene: ACADS: Changed rating: AMBER
Fatty Acid Oxidation Defects v1.7 ACADS Zornitza Stark changed review comment from: Definitive by ClinGen.; to: Definitive by ClinGen. However, largely just causes a biochemical abnormality, and association with clinical disease is debated.
Fatty Acid Oxidation Defects v1.7 ACADS Zornitza Stark edited their review of gene: ACADS: Changed rating: AMBER
Cholestasis v0.234 FOCAD Zornitza Stark changed review comment from: Moreno Traspas et al 2022 reported 14 children from ten unrelated families with syndromic form of pediatric liver cirrhosis. Genome/exome sequencing analysis reveled biallelic variants in the FOCAD gene. Most of the mutations were nonsense, frameshift, or splice site alterations, predicted to result in a loss of function, but there were also 3 missense variants at highly conserved residues. Western blot analysis of dermal fibroblasts derived from 2 patients showed near absent FOCAD expression in cellular extracts. There were also decreased levels of the SKIC2 protein, suggesting that FOCAD may contribute to the stability of RNA helicase (OMIM: 619991).
Sources: Expert Review; to: Moreno Traspas et al 2022 reported 14 children from ten unrelated families with syndromic form of pediatric liver cirrhosis. Genome/exome sequencing analysis reveled biallelic variants in the FOCAD gene. Most of the mutations were nonsense, frameshift, or splice site alterations, predicted to result in a loss of function, but there were also 3 missense variants at highly conserved residues. Western blot analysis of dermal fibroblasts derived from 2 patients showed near absent FOCAD expression in cellular extracts. There were also decreased levels of the SKIC2 protein, suggesting that FOCAD may contribute to the stability of RNA helicase (OMIM: 619991).

Cholestasis is a feature.


Sources: Expert Review
Cholestasis v0.234 FOCAD Zornitza Stark Marked gene: FOCAD as ready
Cholestasis v0.234 FOCAD Zornitza Stark Gene: focad has been classified as Green List (High Evidence).
Cholestasis v0.234 FOCAD Zornitza Stark Classified gene: FOCAD as Green List (high evidence)
Cholestasis v0.234 FOCAD Zornitza Stark Gene: focad has been classified as Green List (High Evidence).
Cholestasis v0.233 FOCAD Zornitza Stark gene: FOCAD was added
gene: FOCAD was added to Cholestasis. Sources: Expert Review
Mode of inheritance for gene: FOCAD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FOCAD were set to 35864190
Phenotypes for gene: FOCAD were set to Liver disease, severe congenital, MIM# 619991
Review for gene: FOCAD was set to GREEN
Added comment: Moreno Traspas et al 2022 reported 14 children from ten unrelated families with syndromic form of pediatric liver cirrhosis. Genome/exome sequencing analysis reveled biallelic variants in the FOCAD gene. Most of the mutations were nonsense, frameshift, or splice site alterations, predicted to result in a loss of function, but there were also 3 missense variants at highly conserved residues. Western blot analysis of dermal fibroblasts derived from 2 patients showed near absent FOCAD expression in cellular extracts. There were also decreased levels of the SKIC2 protein, suggesting that FOCAD may contribute to the stability of RNA helicase (OMIM: 619991).
Sources: Expert Review
Mendeliome v1.253 FOCAD Zornitza Stark Marked gene: FOCAD as ready
Mendeliome v1.253 FOCAD Zornitza Stark Gene: focad has been classified as Green List (High Evidence).
Mendeliome v1.253 FOCAD Zornitza Stark Classified gene: FOCAD as Green List (high evidence)
Mendeliome v1.253 FOCAD Zornitza Stark Gene: focad has been classified as Green List (High Evidence).
Mendeliome v1.252 FOCAD Zornitza Stark gene: FOCAD was added
gene: FOCAD was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: FOCAD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FOCAD were set to 35864190
Phenotypes for gene: FOCAD were set to Liver disease, severe congenital, MIM# 619991
Review for gene: FOCAD was set to GREEN
Added comment: Moreno Traspas et al 2022 reported 14 children from ten unrelated families with syndromic form of pediatric liver cirrhosis. Genome/exome sequencing analysis reveled biallelic variants in the FOCAD gene. Most of the mutations were nonsense, frameshift, or splice site alterations, predicted to result in a loss of function, but there were also 3 missense variants at highly conserved residues. Western blot analysis of dermal fibroblasts derived from 2 patients showed near absent FOCAD expression in cellular extracts. There were also decreased levels of the SKIC2 protein, suggesting that FOCAD may contribute to the stability of RNA helicase (OMIM: 619991).
Sources: Expert Review
Liver Failure_Paediatric v1.19 FOCAD Zornitza Stark Phenotypes for gene: FOCAD were changed from Infantile liver failure, MONDO:0000023, FOCAD-related to Liver disease, severe congenital, MIM# 619991
Liver Failure_Paediatric v1.18 FOCAD Zornitza Stark edited their review of gene: FOCAD: Changed phenotypes: Liver disease, severe congenital, MIM# 619991
Liver Failure_Paediatric v1.18 FOCAD Zornitza Stark Marked gene: FOCAD as ready
Liver Failure_Paediatric v1.18 FOCAD Zornitza Stark Gene: focad has been classified as Green List (High Evidence).
Liver Failure_Paediatric v1.18 FOCAD Zornitza Stark Phenotypes for gene: FOCAD were changed from pediatric syndromic liver cirrhosis to Infantile liver failure, MONDO:0000023, FOCAD-related
Liver Failure_Paediatric v1.17 FOCAD Zornitza Stark Mode of pathogenicity for gene: FOCAD was changed from Other to None
Liver Failure_Paediatric v1.16 FOCAD Zornitza Stark Classified gene: FOCAD as Green List (high evidence)
Liver Failure_Paediatric v1.16 FOCAD Zornitza Stark Gene: focad has been classified as Green List (High Evidence).
Liver Failure_Paediatric v1.15 FOCAD Zornitza Stark reviewed gene: FOCAD: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Infantile liver failure, MONDO:0000023, FOCAD-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.56 SETD5 Zornitza Stark Mode of inheritance for gene: SETD5 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.55 SETD5 Zornitza Stark reviewed gene: SETD5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual disability, autosomal dominant 23 (MIM # 615761); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital diaphragmatic hernia v1.10 SETD5 Zornitza Stark Marked gene: SETD5 as ready
Congenital diaphragmatic hernia v1.10 SETD5 Zornitza Stark Gene: setd5 has been classified as Green List (High Evidence).
Congenital diaphragmatic hernia v1.10 SETD5 Zornitza Stark Classified gene: SETD5 as Green List (high evidence)
Congenital diaphragmatic hernia v1.10 SETD5 Zornitza Stark Gene: setd5 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v1.15 FOCAD Suliman Khan changed review comment from: Moreno Traspas et al 2022 reported 14 children from ten unrelated families with syndromic form of pediatric liver cirrhosis. Genome/exome sequencing analysis reveled biallelic variants in the FOCAD gene. Most of the mutations were nonsense, frameshift, or splice site alterations, predicted to result in a loss of function, but there were also 3 missense variants at highly conserved residues. Western blot analysis of dermal fibroblasts derived from 2 patients showed near absent FOCAD expression in cellular extracts. There were also decreased levels of the SKIC2 protein, suggesting that FOCAD may contribute to the stability of this RNA helicase (OMIM: 619991).
Sources: Literature; to: Moreno Traspas et al 2022 reported 14 children from ten unrelated families with syndromic form of pediatric liver cirrhosis. Genome/exome sequencing analysis reveled biallelic variants in the FOCAD gene. Most of the mutations were nonsense, frameshift, or splice site alterations, predicted to result in a loss of function, but there were also 3 missense variants at highly conserved residues. Western blot analysis of dermal fibroblasts derived from 2 patients showed near absent FOCAD expression in cellular extracts. There were also decreased levels of the SKIC2 protein, suggesting that FOCAD may contribute to the stability of RNA helicase (OMIM: 619991).
Sources: Literature, OMIM
Liver Failure_Paediatric v1.15 FOCAD Suliman Khan gene: FOCAD was added
gene: FOCAD was added to Liver Failure_Paediatric. Sources: Literature
Mode of inheritance for gene: FOCAD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FOCAD were set to PMID: 35864190
Phenotypes for gene: FOCAD were set to pediatric syndromic liver cirrhosis
Penetrance for gene: FOCAD were set to Complete
Mode of pathogenicity for gene: FOCAD was set to Other
Review for gene: FOCAD was set to GREEN
gene: FOCAD was marked as current diagnostic
Added comment: Moreno Traspas et al 2022 reported 14 children from ten unrelated families with syndromic form of pediatric liver cirrhosis. Genome/exome sequencing analysis reveled biallelic variants in the FOCAD gene. Most of the mutations were nonsense, frameshift, or splice site alterations, predicted to result in a loss of function, but there were also 3 missense variants at highly conserved residues. Western blot analysis of dermal fibroblasts derived from 2 patients showed near absent FOCAD expression in cellular extracts. There were also decreased levels of the SKIC2 protein, suggesting that FOCAD may contribute to the stability of this RNA helicase (OMIM: 619991).
Sources: Literature
Congenital diaphragmatic hernia v1.9 SETD5 Elena Savva gene: SETD5 was added
gene: SETD5 was added to Congenital diaphragmatic hernia. Sources: Literature
Mode of inheritance for gene: SETD5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SETD5 were set to PMID: 28263952; 24680889
Phenotypes for gene: SETD5 were set to Intellectual developmental disorder, autosomal dominant 23 MIM#615761
Review for gene: SETD5 was set to GREEN
Added comment: Internal VCGS patient with a de novo PTC, p.Lys766Glufs*35, and features including diaphragmatic hernia and ID.

PMID: 28263952 - describes an additional patient with a PTC, with diaphragmatic hernia and severe cerebral cortical dysplasia

PMID: 24680889 - 2 reported children with PTCs had inguinal hernia, 1 had paraumbilical hernia
Sources: Literature
Vascular Malformations SuperPanel v1.14 Zornitza Stark Panel types changed to Superpanel; Victorian Clinical Genetics Services; Royal Melbourne Hospital
Prepair 1000+ v0.155 RPGR Crystle Lee reviewed gene: RPGR: Rating: AMBER; Mode of pathogenicity: None; Publications: 12657579, 30193314; Phenotypes: Retinitis pigmentosa 3 (MIM#300029); 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+ v0.155 RYR1 Lilian Downie reviewed gene: RYR1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 16917943, PMID: 23919265, PMID: 30155738, PMID: 27855725; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.251 TAF4 Zornitza Stark Phenotypes for gene: TAF4 were changed from Neurodevelopmental disorder to Neurodevelopmental disorder, MONDO:0700092, TAF4-related
Mendeliome v1.250 TAF4 Zornitza Stark Publications for gene: TAF4 were set to 33875846; 28191890
Mendeliome v1.249 TAF4 Zornitza Stark Classified gene: TAF4 as Green List (high evidence)
Mendeliome v1.249 TAF4 Zornitza Stark Gene: taf4 has been classified as Green List (High Evidence).
Mendeliome v1.248 TAF4 Zornitza Stark edited their review of gene: TAF4: Changed rating: GREEN; Changed publications: 33875846, 28191890, 35904126; Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, TAF4-related
Intellectual disability syndromic and non-syndromic v0.4901 TAF4 Zornitza Stark Phenotypes for gene: TAF4 were changed from Neurodevelopmental disorder to Neurodevelopmental disorder, MONDO:0700092, TAF4-related
Intellectual disability syndromic and non-syndromic v0.4900 TAF4 Zornitza Stark Publications for gene: TAF4 were set to 33875846; 28191890
Intellectual disability syndromic and non-syndromic v0.4899 TAF4 Zornitza Stark Classified gene: TAF4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4899 TAF4 Zornitza Stark Gene: taf4 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1644 ZMYND8 Zornitza Stark Marked gene: ZMYND8 as ready
Genetic Epilepsy v0.1644 ZMYND8 Zornitza Stark Gene: zmynd8 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1644 ZMYND8 Zornitza Stark Classified gene: ZMYND8 as Green List (high evidence)
Genetic Epilepsy v0.1644 ZMYND8 Zornitza Stark Gene: zmynd8 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1643 ZMYND8 Zornitza Stark gene: ZMYND8 was added
gene: ZMYND8 was added to Genetic Epilepsy. Sources: Expert Review
Mode of inheritance for gene: ZMYND8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZMYND8 were set to 35916866; 32530565
Phenotypes for gene: ZMYND8 were set to Neurodevelopmental disorder, MONDO:0700092, ZMYND8-related; Delayed speech and language development; Motor delay; Intellectual disability; Abnormality of cardiovascular system morphology; Hearing abnormality; Abnormality of vision; Abnormality of the face; Seizures
Review for gene: ZMYND8 was set to GREEN
Added comment: Dias et al (2022 - PMID: 35916866) describe the phenotype of 11 unrelated individuals with monoallelic de novo (or suspected de novo) missense (N=9) or truncating (N=2) ZMYND8 variants. One of these subjects was previously reported by Suzuki et al (2020 - PMID: 32530565).

Features included speech delay/language difficulties (9/11), motor delay (9/11), ID (in 10/11 - profound in 1, moderate in 2), CHD (7/11 - PDA, VSD, ASD, pulmonary stenosis, etc), hearing or vision impairment (7/11). Seizures were reported in few (in text 5/11, table 2/11). Variable non-familial facial features were present in (9/11).

As the authors discuss, ZMYND8 encodes a multidomain protein playing a role in transcription regulation, chromatin remodeling, regulation of super enhancers, DNA damage response/tumor suppression.

The protein is broadly expressed in brain and shows highest expression in early development.

Molecular modeling and/or a yeast two-hybrid system were suggestive of disrupted interaction of ZMYND8 with Drebrin (missense variants in PWWP domain) or GATAD2A (variants in MYND domain).

Neuronal Zmynd8 knockdown in Drosophila resulted in deficits in habituation learning.
Sources: Expert Review
Fetal anomalies v1.55 ZMYND8 Zornitza Stark Marked gene: ZMYND8 as ready
Fetal anomalies v1.55 ZMYND8 Zornitza Stark Gene: zmynd8 has been classified as Green List (High Evidence).
Fetal anomalies v1.55 ZMYND8 Zornitza Stark Classified gene: ZMYND8 as Green List (high evidence)
Fetal anomalies v1.55 ZMYND8 Zornitza Stark Gene: zmynd8 has been classified as Green List (High Evidence).
Fetal anomalies v1.54 ZMYND8 Zornitza Stark gene: ZMYND8 was added
gene: ZMYND8 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: ZMYND8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZMYND8 were set to 35916866; 32530565
Phenotypes for gene: ZMYND8 were set to Neurodevelopmental disorder, MONDO:0700092, ZMYND8-related; Delayed speech and language development; Motor delay; Intellectual disability; Abnormality of cardiovascular system morphology; Hearing abnormality; Abnormality of vision; Abnormality of the face; Seizures
Review for gene: ZMYND8 was set to GREEN
Added comment: Dias et al (2022 - PMID: 35916866) describe the phenotype of 11 unrelated individuals with monoallelic de novo (or suspected de novo) missense (N=9) or truncating (N=2) ZMYND8 variants. One of these subjects was previously reported by Suzuki et al (2020 - PMID: 32530565).

Features included speech delay/language difficulties (9/11), motor delay (9/11), ID (in 10/11 - profound in 1, moderate in 2), CHD (7/11 - PDA, VSD, ASD, pulmonary stenosis, etc), hearing or vision impairment (7/11). Seizures were reported in few (in text 5/11, table 2/11). Variable non-familial facial features were present in (9/11).

As the authors discuss, ZMYND8 encodes a multidomain protein playing a role in transcription regulation, chromatin remodeling, regulation of super enhancers, DNA damage response/tumor suppression.

The protein is broadly expressed in brain and shows highest expression in early development.

Molecular modeling and/or a yeast two-hybrid system were suggestive of disrupted interaction of ZMYND8 with Drebrin (missense variants in PWWP domain) or GATAD2A (variants in MYND domain).

Neuronal Zmynd8 knockdown in Drosophila resulted in deficits in habituation learning.
Sources: Expert Review
Congenital Heart Defect v0.261 ZMYND8 Zornitza Stark Marked gene: ZMYND8 as ready
Congenital Heart Defect v0.261 ZMYND8 Zornitza Stark Gene: zmynd8 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.261 ZMYND8 Zornitza Stark Classified gene: ZMYND8 as Green List (high evidence)
Congenital Heart Defect v0.261 ZMYND8 Zornitza Stark Gene: zmynd8 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.260 ZMYND8 Zornitza Stark gene: ZMYND8 was added
gene: ZMYND8 was added to Congenital Heart Defect. Sources: Expert Review
Mode of inheritance for gene: ZMYND8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZMYND8 were set to 35916866; 32530565
Phenotypes for gene: ZMYND8 were set to Neurodevelopmental disorder, MONDO:0700092, ZMYND8-related; Delayed speech and language development; Motor delay; Intellectual disability; Abnormality of cardiovascular system morphology; Hearing abnormality; Abnormality of vision; Abnormality of the face; Seizures
Review for gene: ZMYND8 was set to GREEN
Added comment: Dias et al (2022 - PMID: 35916866) describe the phenotype of 11 unrelated individuals with monoallelic de novo (or suspected de novo) missense (N=9) or truncating (N=2) ZMYND8 variants. One of these subjects was previously reported by Suzuki et al (2020 - PMID: 32530565).

Features included speech delay/language difficulties (9/11), motor delay (9/11), ID (in 10/11 - profound in 1, moderate in 2), CHD (7/11 - PDA, VSD, ASD, pulmonary stenosis, etc), hearing or vision impairment (7/11). Seizures were reported in few (in text 5/11, table 2/11). Variable non-familial facial features were present in (9/11).

As the authors discuss, ZMYND8 encodes a multidomain protein playing a role in transcription regulation, chromatin remodeling, regulation of super enhancers, DNA damage response/tumor suppression.

The protein is broadly expressed in brain and shows highest expression in early development.

Molecular modeling and/or a yeast two-hybrid system were suggestive of disrupted interaction of ZMYND8 with Drebrin (missense variants in PWWP domain) or GATAD2A (variants in MYND domain).

Neuronal Zmynd8 knockdown in Drosophila resulted in deficits in habituation learning.
Sources: Expert Review
Mendeliome v1.248 ZMYND8 Zornitza Stark Marked gene: ZMYND8 as ready
Mendeliome v1.248 ZMYND8 Zornitza Stark Gene: zmynd8 has been classified as Green List (High Evidence).
Mendeliome v1.248 ZMYND8 Zornitza Stark Classified gene: ZMYND8 as Green List (high evidence)
Mendeliome v1.248 ZMYND8 Zornitza Stark Gene: zmynd8 has been classified as Green List (High Evidence).
Mendeliome v1.247 ZMYND8 Zornitza Stark gene: ZMYND8 was added
gene: ZMYND8 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: ZMYND8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZMYND8 were set to 35916866; 32530565
Phenotypes for gene: ZMYND8 were set to Neurodevelopmental disorder, MONDO:0700092, ZMYND8-related; Delayed speech and language development; Motor delay; Intellectual disability; Abnormality of cardiovascular system morphology; Hearing abnormality; Abnormality of vision; Abnormality of the face; Seizures
Review for gene: ZMYND8 was set to GREEN
Added comment: Dias et al (2022 - PMID: 35916866) describe the phenotype of 11 unrelated individuals with monoallelic de novo (or suspected de novo) missense (N=9) or truncating (N=2) ZMYND8 variants. One of these subjects was previously reported by Suzuki et al (2020 - PMID: 32530565).

Features included speech delay/language difficulties (9/11), motor delay (9/11), ID (in 10/11 - profound in 1, moderate in 2), CHD (7/11 - PDA, VSD, ASD, pulmonary stenosis, etc), hearing or vision impairment (7/11). Seizures were reported in few (in text 5/11, table 2/11). Variable non-familial facial features were present in (9/11).

As the authors discuss, ZMYND8 encodes a multidomain protein playing a role in transcription regulation, chromatin remodeling, regulation of super enhancers, DNA damage response/tumor suppression.

The protein is broadly expressed in brain and shows highest expression in early development.

Molecular modeling and/or a yeast two-hybrid system were suggestive of disrupted interaction of ZMYND8 with Drebrin (missense variants in PWWP domain) or GATAD2A (variants in MYND domain).

Neuronal Zmynd8 knockdown in Drosophila resulted in deficits in habituation learning.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.4898 ZMYND8 Zornitza Stark Marked gene: ZMYND8 as ready
Intellectual disability syndromic and non-syndromic v0.4898 ZMYND8 Zornitza Stark Gene: zmynd8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4898 ZMYND8 Zornitza Stark Phenotypes for gene: ZMYND8 were changed from Delayed speech and language development; Motor delay; Intellectual disability; Abnormality of cardiovascular system morphology; Hearing abnormality; Abnormality of vision; Abnormality of the face; Seizures to Neurodevelopmental disorder, MONDO:0700092, ZMYND8-related; Delayed speech and language development; Motor delay; Intellectual disability; Abnormality of cardiovascular system morphology; Hearing abnormality; Abnormality of vision; Abnormality of the face; Seizures
Intellectual disability syndromic and non-syndromic v0.4897 ZMYND8 Zornitza Stark Mode of inheritance for gene: ZMYND8 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.4896 ZMYND8 Zornitza Stark Classified gene: ZMYND8 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4896 ZMYND8 Zornitza Stark Gene: zmynd8 has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.26 TRAC Zornitza Stark Tag founder tag was added to gene: TRAC.
Mendeliome v1.246 TRAC Zornitza Stark Tag founder tag was added to gene: TRAC.
Intellectual disability syndromic and non-syndromic v0.4895 TAF4 Konstantinos Varvagiannis reviewed gene: TAF4: Rating: GREEN; Mode of pathogenicity: None; Publications: 35904126; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability syndromic and non-syndromic v0.4895 ZMYND8 Konstantinos Varvagiannis gene: ZMYND8 was added
gene: ZMYND8 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ZMYND8 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ZMYND8 were set to 35916866; 32530565
Phenotypes for gene: ZMYND8 were set to Delayed speech and language development; Motor delay; Intellectual disability; Abnormality of cardiovascular system morphology; Hearing abnormality; Abnormality of vision; Abnormality of the face; Seizures
Penetrance for gene: ZMYND8 were set to unknown
Review for gene: ZMYND8 was set to GREEN
Added comment: Dias et al (2022 - PMID: 35916866) describe the phenotype of 11 unrelated individuals with monoallelic de novo (or suspected de novo) missense (N=9) or truncating (N=2) ZMYND8 variants. One of these subjects was previously reported by Suzuki et al (2020 - PMID: 32530565).

Features included speech delay/language difficulties (9/11), motor delay (9/11), ID (in 10/11 - profound in 1, moderate in 2), CHD (7/11 - PDA, VSD, ASD, pulmonary stenosis, etc), hearing or vision impairment (7/11). Seizures were reported in few (in text 5/11, table 2/11). Variable non-familial facial features were present in (9/11).

As the authors discuss, ZMYND8 encodes a multidomain protein playing a role in transcription regulation, chromatin remodeling, regulation of super enhancers, DNA damage response/tumor suppression.

The protein is broadly expressed in brain and shows highest expression in early development.

Molecular modeling and/or a yeast two-hybrid system were suggestive of disrupted interaction of ZMYND8 with Drebrin (missense variants in PWWP domain) or GATAD2A (variants in MYND domain).

Neuronal Zmynd8 knockdown in Drosophila resulted in deficits in habituation learning.
Sources: Literature
Prepair 1000+ v0.155 MEFV Zornitza Stark Marked gene: MEFV as ready
Prepair 1000+ v0.155 MEFV Zornitza Stark Gene: mefv has been classified as Red List (Low Evidence).
Prepair 1000+ v0.155 MEFV Zornitza Stark Mode of inheritance for gene: MEFV was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.154 MEFV Zornitza Stark Classified gene: MEFV as Red List (low evidence)
Prepair 1000+ v0.154 MEFV Zornitza Stark Gene: mefv has been classified as Red List (Low Evidence).
Prepair 1000+ v0.153 MEFV Zornitza Stark Tag for review was removed from gene: MEFV.
Prepair 1000+ v0.153 MEFV Zornitza Stark reviewed gene: MEFV: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Familial Mediterranean fever, AR (MIM#249100); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.153 HOGA1 Zornitza Stark Marked gene: HOGA1 as ready
Prepair 1000+ v0.153 HOGA1 Zornitza Stark Gene: hoga1 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.153 HOGA1 Zornitza Stark Classified gene: HOGA1 as Red List (low evidence)
Prepair 1000+ v0.153 HOGA1 Zornitza Stark Gene: hoga1 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.152 HOGA1 Zornitza Stark Tag for review was removed from gene: HOGA1.
Prepair 1000+ v0.152 HOGA1 Zornitza Stark reviewed gene: HOGA1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hyperoxaluria, primary, type III (MIM#613616); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.152 GRHPR Zornitza Stark Marked gene: GRHPR as ready
Prepair 1000+ v0.152 GRHPR Zornitza Stark Gene: grhpr has been classified as Red List (Low Evidence).
Prepair 1000+ v0.152 GRHPR Zornitza Stark Classified gene: GRHPR as Red List (low evidence)
Prepair 1000+ v0.152 GRHPR Zornitza Stark Gene: grhpr has been classified as Red List (Low Evidence).
Prepair 1000+ v0.151 GRHPR Zornitza Stark reviewed gene: GRHPR: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hyperoxaluria, primary, type II (MIM#260000); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.151 GJB1 Zornitza Stark commented on gene: GJB1
Prepair 1000+ v0.151 GALK1 Zornitza Stark Marked gene: GALK1 as ready
Prepair 1000+ v0.151 GALK1 Zornitza Stark Gene: galk1 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.151 GALK1 Zornitza Stark Classified gene: GALK1 as Red List (low evidence)
Prepair 1000+ v0.151 GALK1 Zornitza Stark Gene: galk1 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.150 GALK1 Zornitza Stark Tag for review was removed from gene: GALK1.
Prepair 1000+ v0.150 GALK1 Zornitza Stark reviewed gene: GALK1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Galactokinase deficiency with cataracts (MIM#230200); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.150 G6PD Zornitza Stark Marked gene: G6PD as ready
Prepair 1000+ v0.150 G6PD Zornitza Stark Gene: g6pd has been classified as Red List (Low Evidence).
Prepair 1000+ v0.150 G6PD Zornitza Stark Phenotypes for gene: G6PD were changed from Hemolytic anemia, G6PD deficient (favism) (MIM#300908) to Haemolytic anaemia, G6PD deficient (favism) (MIM#300908)
Prepair 1000+ v0.149 G6PD Zornitza Stark Mode of inheritance for gene: G6PD was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v0.148 G6PD Zornitza Stark Classified gene: G6PD as Red List (low evidence)
Prepair 1000+ v0.148 G6PD Zornitza Stark Gene: g6pd has been classified as Red List (Low Evidence).
Prepair 1000+ v0.147 G6PD Zornitza Stark Tag for review was removed from gene: G6PD.
Prepair 1000+ v0.147 G6PD Zornitza Stark reviewed gene: G6PD: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Haemolytic anaemia, G6PD deficient (favism) (MIM#300908); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v0.147 EYS Zornitza Stark Marked gene: EYS as ready
Prepair 1000+ v0.147 EYS Zornitza Stark Gene: eys has been classified as Red List (Low Evidence).
Prepair 1000+ v0.147 EYS Zornitza Stark Classified gene: EYS as Red List (low evidence)
Prepair 1000+ v0.147 EYS Zornitza Stark Gene: eys has been classified as Red List (Low Evidence).
Prepair 1000+ v0.146 EYS Zornitza Stark Tag for review was removed from gene: EYS.
Prepair 1000+ v0.146 EYS Zornitza Stark reviewed gene: EYS: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Retinitis pigmentosa 25 (MIM#602772); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.146 CYP21A2 Zornitza Stark Marked gene: CYP21A2 as ready
Prepair 1000+ v0.146 CYP21A2 Zornitza Stark Gene: cyp21a2 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.146 CYP21A2 Zornitza Stark Classified gene: CYP21A2 as Red List (low evidence)
Prepair 1000+ v0.146 CYP21A2 Zornitza Stark Gene: cyp21a2 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.145 CYP21A2 Zornitza Stark Tag for review was removed from gene: CYP21A2.
Prepair 1000+ v0.145 CYP21A2 Zornitza Stark reviewed gene: CYP21A2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Adrenal hyperplasia, congenital, due to 21-hydroxylase deficiency (MIM#201910); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.145 CYP11B1 Zornitza Stark Marked gene: CYP11B1 as ready
Prepair 1000+ v0.145 CYP11B1 Zornitza Stark Gene: cyp11b1 has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v0.145 CYP11B1 Zornitza Stark Classified gene: CYP11B1 as Amber List (moderate evidence)
Prepair 1000+ v0.145 CYP11B1 Zornitza Stark Gene: cyp11b1 has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v0.144 CYP11B1 Zornitza Stark reviewed gene: CYP11B1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Adrenal hyperplasia, congenital, due to 11-beta-hydroxylase deficiency (MIM#202010); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.144 CERKL Zornitza Stark Marked gene: CERKL as ready
Prepair 1000+ v0.144 CERKL Zornitza Stark Gene: cerkl has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v0.144 CERKL Zornitza Stark Classified gene: CERKL as Amber List (moderate evidence)
Prepair 1000+ v0.144 CERKL Zornitza Stark Gene: cerkl has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v0.143 CERKL Zornitza Stark Tag for review was removed from gene: CERKL.
Prepair 1000+ v0.143 CERKL Zornitza Stark reviewed gene: CERKL: Rating: AMBER; Mode of pathogenicity: None; Publications: 33322828; Phenotypes: Retinitis pigmentosa 26 (MIM#608380); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.143 BTD Zornitza Stark Marked gene: BTD as ready
Prepair 1000+ v0.143 BTD Zornitza Stark Gene: btd has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v0.143 BTD Zornitza Stark Classified gene: BTD as Amber List (moderate evidence)
Prepair 1000+ v0.143 BTD Zornitza Stark Gene: btd has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v0.142 BTD Zornitza Stark reviewed gene: BTD: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Biotinidase deficiency (MIM#253260); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.246 TRAC Seb Lunke Classified gene: TRAC as Amber List (moderate evidence)
Mendeliome v1.246 TRAC Seb Lunke Added comment: Comment on list classification: Single variant reported to date in 6 patients; 2 unrelated children from consanguineous families of Pakistani descent (PMID: 21206088); 1 non-consanguineous family from North-west India (PMID: 33909184) and 1 consanguineous parents of East Indian (https://lymphosign.com/doi/10.14785/lymphosign-2022-0001) Also note annotation issues in certain variant curation and annotation tools.
Mendeliome v1.246 TRAC Seb Lunke Gene: trac has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v0.142 AIRE Zornitza Stark Marked gene: AIRE as ready
Prepair 1000+ v0.142 AIRE Zornitza Stark Gene: aire has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v0.142 AIRE Zornitza Stark Publications for gene: AIRE were set to 35521792; 28323927
Prepair 1000+ v0.141 AIRE Zornitza Stark Classified gene: AIRE as Amber List (moderate evidence)
Prepair 1000+ v0.141 AIRE Zornitza Stark Gene: aire has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v0.140 AIRE Zornitza Stark Tag for review was removed from gene: AIRE.
Combined Immunodeficiency v1.26 TRAC Seb Lunke Classified gene: TRAC as Amber List (moderate evidence)
Combined Immunodeficiency v1.26 TRAC Seb Lunke Gene: trac has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v0.140 AIRE Zornitza Stark reviewed gene: AIRE: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Autoimmune polyendocrinopathy syndrome , type I, with or without reversible metaphyseal dysplasia (MIM#240300); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v1.25 TRAC Seb Lunke reviewed gene: TRAC: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Prepair 1000+ v0.140 C8B Zornitza Stark Tag for review was removed from gene: C8B.
Prepair 1000+ v0.140 TRAC Zornitza Stark Marked gene: TRAC as ready
Prepair 1000+ v0.140 TRAC Zornitza Stark Gene: trac has been classified as Red List (Low Evidence).
Prepair 1000+ v0.140 TRAC Zornitza Stark Tag for review was removed from gene: TRAC.
Prepair 1000+ v0.140 RPL10 Zornitza Stark Tag for review was removed from gene: RPL10.
Prepair 1000+ v0.140 RPL10 Zornitza Stark Marked gene: RPL10 as ready
Prepair 1000+ v0.140 RPL10 Zornitza Stark Gene: rpl10 has been classified as Green List (High Evidence).
Prepair 1000+ v0.140 RPL10 Zornitza Stark Phenotypes for gene: RPL10 were changed from Mental retardation, X-linked, syndromic, 35 (MIM#300998) to Intellectual developmental disorder, X-linked, syndromic, 35, MIM300998
Prepair 1000+ v0.139 RPL10 Zornitza Stark Publications for gene: RPL10 were set to
Prepair 1000+ v0.138 TRAC Zornitza Stark Classified gene: TRAC as Red List (low evidence)
Prepair 1000+ v0.138 TRAC Zornitza Stark Gene: trac has been classified as Red List (Low Evidence).
Prepair 1000+ v0.137 TRAC Zornitza Stark reviewed gene: TRAC: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency 7, TCR-alpha/beta deficient (MIM#615387); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.137 RPL10 Zornitza Stark Classified gene: RPL10 as Green List (high evidence)
Prepair 1000+ v0.137 RPL10 Zornitza Stark Gene: rpl10 has been classified as Green List (High Evidence).
Prepair 1000+ v0.136 RPL10 Zornitza Stark reviewed gene: RPL10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, X-linked, syndromic, 35, MIM300998; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v0.136 AIRE Crystle Lee edited their review of gene: AIRE: Changed publications: 35521792, 28323927, 33352647
Prepair 1000+ v0.136 VPS13A Zornitza Stark reviewed gene: VPS13A: Rating: GREEN; Mode of pathogenicity: None; Publications: 29518281; Phenotypes: Choreoacanthocytosis (MIM#200150); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.136 RYR1 Zornitza Stark Marked gene: RYR1 as ready
Prepair 1000+ v0.136 RYR1 Zornitza Stark Gene: ryr1 has been classified as Green List (High Evidence).
Prepair 1000+ v0.136 RYR1 Zornitza Stark Phenotypes for gene: RYR1 were changed from Minicore myopathy with external ophthalmoplegia, 255320 (3) to Neuromuscular disease, congenital, with uniform type 1 fiber, MIM# 117000; Central core disease, MIM# 117000
Prepair 1000+ v0.135 RYR1 Zornitza Stark reviewed gene: RYR1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuromuscular disease, congenital, with uniform type 1 fiber, MIM# 117000, Central core disease, MIM# 117000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.135 PROC Zornitza Stark Marked gene: PROC as ready
Prepair 1000+ v0.135 PROC Zornitza Stark Gene: proc has been classified as Green List (High Evidence).
Prepair 1000+ v0.135 PROC Zornitza Stark Tag for review was removed from gene: PROC.
Prepair 1000+ v0.135 PROC Zornitza Stark reviewed gene: PROC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Thrombophilia 3 due to protein C deficiency, autosomal recessive (MIM#612304); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.135 PRKRA Zornitza Stark changed review comment from: Founder variant but multiple other families reported.

Pseudogene is a processed pseudogene and therefore false positives can be identified on manual inspection.; to: Founder variant but multiple other families reported.

Pseudogene is a processed pseudogene and therefore false positives can be identified on manual inspection. Risk of false negatives is low.
Prepair 1000+ v0.135 PRKRA Zornitza Stark Marked gene: PRKRA as ready
Prepair 1000+ v0.135 PRKRA Zornitza Stark Gene: prkra has been classified as Green List (High Evidence).
Prepair 1000+ v0.135 PRKRA Zornitza Stark Tag for review was removed from gene: PRKRA.
Prepair 1000+ v0.135 PRKRA Zornitza Stark reviewed gene: PRKRA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Dystonia 16 (MIM#612067); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.135 PGK1 Zornitza Stark Marked gene: PGK1 as ready
Prepair 1000+ v0.135 PGK1 Zornitza Stark Gene: pgk1 has been classified as Green List (High Evidence).
Prepair 1000+ v0.135 PLG Zornitza Stark Marked gene: PLG as ready
Prepair 1000+ v0.135 PLG Zornitza Stark Gene: plg has been classified as Green List (High Evidence).
Prepair 1000+ v0.135 PLG Zornitza Stark Publications for gene: PLG were set to
Prepair 1000+ v0.134 PLG Zornitza Stark Tag for review was removed from gene: PLG.
Prepair 1000+ v0.134 PLG Zornitza Stark reviewed gene: PLG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Plasminogen deficiency, type I, MIM# 217090; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.134 PDHA1 Zornitza Stark Marked gene: PDHA1 as ready
Prepair 1000+ v0.134 PDHA1 Zornitza Stark Gene: pdha1 has been classified as Green List (High Evidence).
Prepair 1000+ v0.134 PGK1 Zornitza Stark Publications for gene: PGK1 were set to
Prepair 1000+ v0.133 PGK1 Zornitza Stark Tag for review was removed from gene: PGK1.
Prepair 1000+ v0.133 PGK1 Zornitza Stark reviewed gene: PGK1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Phosphoglycerate kinase 1 deficiency (MIM#300653); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v0.133 PDHA1 Zornitza Stark Phenotypes for gene: PDHA1 were changed from Pyruvate dehydrogenase E1-alpha deficiency to Pyruvate dehydrogenase E1-alpha deficiency (MIM#312170)
Prepair 1000+ v0.132 PDHA1 Zornitza Stark Publications for gene: PDHA1 were set to
Prepair 1000+ v0.131 PDHA1 Zornitza Stark Tag for review was removed from gene: PDHA1.
Prepair 1000+ v0.131 PDHA1 Zornitza Stark reviewed gene: PDHA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pyruvate dehydrogenase E1-alpha deficiency (MIM#312170); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v0.131 KCNQ1 Zornitza Stark Tag for review was removed from gene: KCNQ1.
Prepair 1000+ v0.131 OCA2 Zornitza Stark Marked gene: OCA2 as ready
Prepair 1000+ v0.131 OCA2 Zornitza Stark Gene: oca2 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.131 OCA2 Zornitza Stark Phenotypes for gene: OCA2 were changed from Albinism, brown oculocutaneous, 203200 (3) to Albinism, oculocutaneous, type II (MIM#203200)
Prepair 1000+ v0.130 OCA2 Zornitza Stark Classified gene: OCA2 as Red List (low evidence)
Prepair 1000+ v0.130 OCA2 Zornitza Stark Gene: oca2 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.129 OCA2 Zornitza Stark Tag for review was removed from gene: OCA2.
Prepair 1000+ v0.129 OCA2 Zornitza Stark reviewed gene: OCA2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Albinism, oculocutaneous, type II (MIM#203200); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.129 NEB Zornitza Stark Marked gene: NEB as ready
Prepair 1000+ v0.129 NEB Zornitza Stark Gene: neb has been classified as Green List (High Evidence).
Prepair 1000+ v0.129 NEB Zornitza Stark Phenotypes for gene: NEB were changed from Nemaline myopathy 2, autosomal recessive, 256030 (3) to Arthrogryposis multiplex congenita 6 (MIM#619334); Nemaline myopathy 2, autosomal recessive (MIM#256030)
Prepair 1000+ v0.128 NEB Zornitza Stark Publications for gene: NEB were set to
Prepair 1000+ v0.127 MPZ Zornitza Stark Marked gene: MPZ as ready
Prepair 1000+ v0.127 MPZ Zornitza Stark Gene: mpz has been classified as Green List (High Evidence).
Prepair 1000+ v0.127 MPZ Zornitza Stark Publications for gene: MPZ were set to
Prepair 1000+ v0.126 MPZ Zornitza Stark Tag for review was removed from gene: MPZ.
Prepair 1000+ v0.126 NEB Zornitza Stark Tag for review was removed from gene: NEB.
Prepair 1000+ v0.126 NEB Zornitza Stark reviewed gene: NEB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Arthrogryposis multiplex congenita 6 (MIM#619334), Nemaline myopathy 2, autosomal recessive (MIM#256030); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.126 LDLR Zornitza Stark Marked gene: LDLR as ready
Prepair 1000+ v0.126 LDLR Zornitza Stark Gene: ldlr has been classified as Green List (High Evidence).
Prepair 1000+ v0.126 MPZ Zornitza Stark changed review comment from: More than 3 families reported with biallelic variants.; to: More than 3 families reported with biallelic variants. Childhood/congenital onset.
Prepair 1000+ v0.126 MPZ Zornitza Stark reviewed gene: MPZ: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Dejerine-Sottas disease, MIM#145900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.126 LDLR Zornitza Stark Tag for review was removed from gene: LDLR.
Prepair 1000+ v0.126 LDLR Zornitza Stark reviewed gene: LDLR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypercholesterolaemia, familial, 1 143890; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.126 IGHM Zornitza Stark Marked gene: IGHM as ready
Prepair 1000+ v0.126 IGHM Zornitza Stark Gene: ighm has been classified as Green List (High Evidence).
Prepair 1000+ v0.126 KCNQ1 Zornitza Stark Marked gene: KCNQ1 as ready
Prepair 1000+ v0.126 KCNQ1 Zornitza Stark Gene: kcnq1 has been classified as Green List (High Evidence).
Prepair 1000+ v0.126 IGHM Zornitza Stark Phenotypes for gene: IGHM were changed from Agammaglobulinemia 1, 601495 (3) to Agammaglobulinaemia 1, 601495 (3)
Prepair 1000+ v0.125 IGHM Zornitza Stark Publications for gene: IGHM were set to
Prepair 1000+ v0.124 KCNQ1 Zornitza Stark Publications for gene: KCNQ1 were set to
Prepair 1000+ v0.123 KCNQ1 Zornitza Stark reviewed gene: KCNQ1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Jervell and Lange-Nielsen syndrome (MIM#220400); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.123 IGHM Zornitza Stark reviewed gene: IGHM: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Agammaglobulinaemia 1 (MIM#601495); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4895 ADAR Zornitza Stark Marked gene: ADAR as ready
Intellectual disability syndromic and non-syndromic v0.4895 ADAR Zornitza Stark Gene: adar has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4895 ADAR Zornitza Stark Phenotypes for gene: ADAR were changed from to Aicardi-Goutieres syndrome 6, MIM# 615010
Intellectual disability syndromic and non-syndromic v0.4894 ADAR Zornitza Stark Mode of inheritance for gene: ADAR was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4893 ADAR Zornitza Stark reviewed gene: ADAR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Aicardi-Goutieres syndrome 6, MIM# 615010; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4893 ACTG1 Zornitza Stark Marked gene: ACTG1 as ready
Intellectual disability syndromic and non-syndromic v0.4893 ACTG1 Zornitza Stark Gene: actg1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4893 ACTG1 Zornitza Stark Phenotypes for gene: ACTG1 were changed from to Baraitser-Winter syndrome 2, MIM#614583
Intellectual disability syndromic and non-syndromic v0.4892 ACTG1 Zornitza Stark Mode of inheritance for gene: ACTG1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.4891 ACTG1 Zornitza Stark reviewed gene: ACTG1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Baraitser-Winter syndrome 2, MIM#614583; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.4891 ACTB Zornitza Stark Marked gene: ACTB as ready
Intellectual disability syndromic and non-syndromic v0.4891 ACTB Zornitza Stark Gene: actb has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4891 ACTB Zornitza Stark Phenotypes for gene: ACTB were changed from to Baraitser-Winter syndrome 1, MIM# 243310; ACTB-related neurodevelopment disorder
Intellectual disability syndromic and non-syndromic v0.4890 ACTB Zornitza Stark Publications for gene: ACTB were set to
Intellectual disability syndromic and non-syndromic v0.4889 ACTB Zornitza Stark Mode of inheritance for gene: ACTB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.4888 ACTB Zornitza Stark reviewed gene: ACTB: Rating: GREEN; Mode of pathogenicity: None; Publications: 29220674; Phenotypes: Baraitser-Winter syndrome 1 243310, ACTB-related neurodevelopment disorder; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Regression v0.492 ACO2 Zornitza Stark Marked gene: ACO2 as ready
Regression v0.492 ACO2 Zornitza Stark Gene: aco2 has been classified as Green List (High Evidence).
Regression v0.492 ACO2 Zornitza Stark Phenotypes for gene: ACO2 were changed from to Infantile cerebellar-retinal degeneration, MIM#614559
Regression v0.491 ACO2 Zornitza Stark Publications for gene: ACO2 were set to
Regression v0.490 ACO2 Zornitza Stark Mode of inheritance for gene: ACO2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Regression v0.489 ACO2 Zornitza Stark reviewed gene: ACO2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22405087, 25351951, 30689204, 32519519, 25351951; Phenotypes: Infantile cerebellar-retinal degeneration, MIM#614559; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4888 ACO2 Zornitza Stark Marked gene: ACO2 as ready
Intellectual disability syndromic and non-syndromic v0.4888 ACO2 Zornitza Stark Gene: aco2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4888 ACO2 Zornitza Stark Phenotypes for gene: ACO2 were changed from to Infantile cerebellar-retinal degeneration, MIM#614559
Intellectual disability syndromic and non-syndromic v0.4887 ACO2 Zornitza Stark Publications for gene: ACO2 were set to
Intellectual disability syndromic and non-syndromic v0.4886 ACO2 Zornitza Stark Mode of inheritance for gene: ACO2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4885 ACO2 Zornitza Stark reviewed gene: ACO2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22405087, 25351951, 30689204, 32519519, 25351951; Phenotypes: Infantile cerebellar-retinal degeneration, MIM#614559; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4885 ABCD1 Zornitza Stark Marked gene: ABCD1 as ready
Intellectual disability syndromic and non-syndromic v0.4885 ABCD1 Zornitza Stark Gene: abcd1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4885 ABCD1 Zornitza Stark Phenotypes for gene: ABCD1 were changed from to Adrenoleukodystrophy, MIM# 300100
Intellectual disability syndromic and non-syndromic v0.4884 ABCD1 Zornitza Stark Mode of inheritance for gene: ABCD1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.4883 ABCD1 Zornitza Stark reviewed gene: ABCD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Adrenoleukodystrophy, MIM# 300100; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.4883 ACADS Zornitza Stark Marked gene: ACADS as ready
Intellectual disability syndromic and non-syndromic v0.4883 ACADS Zornitza Stark Gene: acads has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4883 ACADS Zornitza Stark Phenotypes for gene: ACADS were changed from to Acyl-CoA dehydrogenase, short-chain, deficiency of, MIM# 201470
Intellectual disability syndromic and non-syndromic v0.4882 ACADS Zornitza Stark Mode of inheritance for gene: ACADS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4881 ACADS Zornitza Stark reviewed gene: ACADS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Acyl-CoA dehydrogenase, short-chain, deficiency of, MIM# 201470; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4881 ACADM Zornitza Stark Marked gene: ACADM as ready
Intellectual disability syndromic and non-syndromic v0.4881 ACADM Zornitza Stark Gene: acadm has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4881 ACADM Zornitza Stark Phenotypes for gene: ACADM were changed from to Acyl-CoA dehydrogenase, medium chain, deficiency of, MIM# 201450
Intellectual disability syndromic and non-syndromic v0.4880 ACADM Zornitza Stark Mode of inheritance for gene: ACADM was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4879 ACADM Zornitza Stark reviewed gene: ACADM: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Acyl-CoA dehydrogenase, medium chain, deficiency of, MIM# 201450; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4879 PAX5 Zornitza Stark Phenotypes for gene: PAX5 were changed from neurodevelopmental disorder MONDO:0700092 to Neurodevelopmental disorder MONDO:0700092, PAX5-related; Hypogammaglobulinaemia
Intellectual disability syndromic and non-syndromic v0.4878 PAX5 Zornitza Stark Publications for gene: PAX5 were set to 35094443; 31452935; 28263302; 25418537; 8001127; 27626380
Intellectual disability syndromic and non-syndromic v0.4877 PAX5 Zornitza Stark Mode of inheritance for gene: PAX5 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4876 PAX5 Zornitza Stark reviewed gene: PAX5: Rating: AMBER; Mode of pathogenicity: None; Publications: 35947077; Phenotypes: Neurodevelopmental disorder MONDO:0700092, PAX5-related, Hypogammaglobulinaemia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.245 PAX5 Zornitza Stark Phenotypes for gene: PAX5 were changed from Neurodevelopmental disorder MONDO:0700092, PAX5-related to Neurodevelopmental disorder MONDO:0700092, PAX5-related; Hypogammaglobulinaemia
Mendeliome v1.244 PAX5 Zornitza Stark Publications for gene: PAX5 were set to 35094443; 31452935; 28263302; 25418537; 8001127; 27626380
Mendeliome v1.243 PAX5 Zornitza Stark Mode of inheritance for gene: PAX5 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.242 PAX5 Zornitza Stark reviewed gene: PAX5: Rating: AMBER; Mode of pathogenicity: None; Publications: 35947077; Phenotypes: Neurodevelopmental disorder MONDO:0700092, PAX5-related, Hypogammaglobulinaemia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Predominantly Antibody Deficiency v0.119 PAX5 Zornitza Stark Marked gene: PAX5 as ready
Predominantly Antibody Deficiency v0.119 PAX5 Zornitza Stark Gene: pax5 has been classified as Amber List (Moderate Evidence).
Predominantly Antibody Deficiency v0.119 PAX5 Zornitza Stark Phenotypes for gene: PAX5 were changed from Hypogammaglobulinaemia to Neurodevelopmental disorder MONDO:0700092, PAX5-related; Hypogammaglobulinaemia
Predominantly Antibody Deficiency v0.118 PAX5 Zornitza Stark Mode of inheritance for gene: PAX5 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Predominantly Antibody Deficiency v0.117 PAX5 Zornitza Stark Classified gene: PAX5 as Amber List (moderate evidence)
Predominantly Antibody Deficiency v0.117 PAX5 Zornitza Stark Gene: pax5 has been classified as Amber List (Moderate Evidence).
Renal Macrocystic Disease v0.52 IFT140 Chirag Patel reviewed gene: IFT140: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Lipodystrophy_Lipoatrophy v1.5 PRIM1 Zornitza Stark Marked gene: PRIM1 as ready
Lipodystrophy_Lipoatrophy v1.5 PRIM1 Zornitza Stark Gene: prim1 has been classified as Amber List (Moderate Evidence).
Lipodystrophy_Lipoatrophy v1.5 PRIM1 Zornitza Stark Classified gene: PRIM1 as Amber List (moderate evidence)
Lipodystrophy_Lipoatrophy v1.5 PRIM1 Zornitza Stark Gene: prim1 has been classified as Amber List (Moderate Evidence).
Lipodystrophy_Lipoatrophy v1.4 PRIM1 Zornitza Stark gene: PRIM1 was added
gene: PRIM1 was added to Lipodystrophy_Lipoatrophy. Sources: Literature
Mode of inheritance for gene: PRIM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRIM1 were set to 33060134
Phenotypes for gene: PRIM1 were set to Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, MIM# 620005
Review for gene: PRIM1 was set to AMBER
Added comment: - PMID: 33060134 (2020) - From a cohort of 220 families with microcephalic dwarfism spectrum disorders (OFC ≤−4 SD; height ≤−2 SD), three families (4 individuals) were identified with the same homozygous intronic variant (c.638+36C>G) in PRIM1. This variant was present in gnomAD in 2 individuals across all populations, but only in a heterozygous state. Haplotype analysis indicated that all three families share a distant common ancestor - i.e. confirmed founder variant.
Authors subsequently identified a single individual with compound heterozygous PRIM1 variants (c.103+1G>T, c.901T>C) from the DDD study, who also presented microcephaly and short stature (OFC ≤−3 SD; height ≤−3 SD).

Clinical overlap was evident in all 5 individuals, presenting extreme pre- and postnatal growth restriction, severe microcephaly (OFC −6.0 ± 1.5 SD) with simplified gyri appearance, hypothyroidism, hypo/agammaglobulinaemia, and lymphopaenia accompanied by intermittent anaemia/thrombocytopaenia. All had chronic respiratory symptoms, and four died in early childhood from respiratory or GI infections.

Lipodystrophy was part of the phenotype.

Functional studies demonstrated reduced PRIM1 protein levels, replication fork defects and prolonged S-phase duration in PRIM1-deficient cells. The resulting delay to the cell cycle and inability to sustain sufficient cell proliferation provides a likely mechanism for the presenting phenotype.
Sources: Literature
Fetal anomalies v1.53 PRIM1 Zornitza Stark Phenotypes for gene: PRIM1 were changed from Microcephalic primordial dwarfism, MONDO:0017950 to Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, MIM# 620005
Fetal anomalies v1.52 PRIM1 Zornitza Stark Tag deep intronic tag was added to gene: PRIM1.
Tag founder tag was added to gene: PRIM1.
Fetal anomalies v1.52 PRIM1 Zornitza Stark reviewed gene: PRIM1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, MIM# 620005; Mode of inheritance: None
Microcephaly v1.149 PRIM1 Zornitza Stark Phenotypes for gene: PRIM1 were changed from Microcephalic primordial dwarfism, MONDO:0017950 to Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, MIM# 620005
Microcephaly v1.148 PRIM1 Zornitza Stark edited their review of gene: PRIM1: Changed phenotypes: Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, MIM# 620005
Mendeliome v1.242 PRIM1 Zornitza Stark Phenotypes for gene: PRIM1 were changed from Microcephalic primordial dwarfism, MONDO:0017950 to Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, MIM# 620005
Mendeliome v1.241 PRIM1 Zornitza Stark edited their review of gene: PRIM1: Changed phenotypes: Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, MIM# 620005
Intellectual disability syndromic and non-syndromic v0.4876 SMG9 Zornitza Stark Phenotypes for gene: SMG9 were changed from Heart and brain malformation syndrome, MIM# 616920 to Heart and brain malformation syndrome, MIM# 616920; Neurodevelopmental disorder with intention tremor, pyramidal signs, dyspraxia, and ocular anomalies, MIM# 619995
Intellectual disability syndromic and non-syndromic v0.4875 SMG9 Zornitza Stark Publications for gene: SMG9 were set to 27018474; 31390136
Intellectual disability syndromic and non-syndromic v0.4874 SMG9 Zornitza Stark edited their review of gene: SMG9: Added comment: PMID 35087184: 5 individuals from 3 unrelated Finnish families reported with same homozygous missense variant (founder effect) and predominantly neurological phenotype. Uncertain if this is a distinct disorder or part of a spectrum with the previously reported cases.; Changed publications: 27018474, 31390136, 35087184; Changed phenotypes: Heart and brain malformation syndrome, MIM# 616920, Neurodevelopmental disorder with intention tremor, pyramidal signs, dyspraxia, and ocular anomalies, MIM# 619995
Mendeliome v1.241 SMG9 Zornitza Stark Phenotypes for gene: SMG9 were changed from Heart and brain malformation syndrome, MIM# 616920 to Heart and brain malformation syndrome, MIM# 616920; Neurodevelopmental disorder with intention tremor, pyramidal signs, dyspraxia, and ocular anomalies, MIM# 619995
Mendeliome v1.240 SMG9 Zornitza Stark Publications for gene: SMG9 were set to 27018474; 31390136
Mendeliome v1.239 SMG9 Zornitza Stark edited their review of gene: SMG9: Added comment: PMID 35087184: 5 individuals from 3 unrelated Finnish families reported with same homozygous missense variant (founder effect) and predominantly neurological phenotype. Uncertain if this is a distinct disorder or part of a spectrum with the previously reported cases.; Changed publications: 27018474, 31390136, 35087184; Changed phenotypes: Heart and brain malformation syndrome, MIM# 616920, Neurodevelopmental disorder with intention tremor, pyramidal signs, dyspraxia, and ocular anomalies, MIM# 619995
Predominantly Antibody Deficiency v0.116 PAX5 Peter McNaughton gene: PAX5 was added
gene: PAX5 was added to Predominantly Antibody Deficiency. Sources: Literature
Mode of inheritance for gene: PAX5 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: PAX5 were set to PMID: 35947077
Phenotypes for gene: PAX5 were set to Hypogammaglobulinaemia
Review for gene: PAX5 was set to AMBER
Added comment: 2.5yo male with recurrent infections and hypogammaglobulinaemia, later also ASD, sensorimotor and cognitive defects. Functional studies showing reduced B cells. Mouse model replicating partial B cell developmental arrest.
Sources: Literature
Hereditary Neuropathy v0.132 MYH14 Zornitza Stark Marked gene: MYH14 as ready
Hereditary Neuropathy v0.132 MYH14 Zornitza Stark Gene: myh14 has been classified as Green List (High Evidence).
Hereditary Neuropathy v0.132 MYH14 Zornitza Stark Phenotypes for gene: MYH14 were changed from ?Peripheral neuropathy, myopathy, hoarseness, and hearing loss, 614369; HMSN to Peripheral neuropathy, myopathy, hoarseness, and hearing loss MIM#614369
Hereditary Neuropathy v0.131 MYH14 Zornitza Stark Publications for gene: MYH14 were set to
Hereditary Neuropathy v0.130 MYH14 Zornitza Stark reviewed gene: MYH14: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peripheral neuropathy, myopathy, hoarseness, and hearing loss MIM#614369; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.215 ANXA11 Zornitza Stark Tag adult onset neurodegenerative tag was added to gene: ANXA11.
Hereditary Neuropathy v0.130 MYH14 Elena Savva edited their review of gene: MYH14: Added comment: PMID: 21480433 - 1 large Korean fam with peripheral neuropathy, myopathy, hoarseness, and hearing loss. Missense variant (p.R941L) found to segregate in all affecteds, but not all presented with hearing loss.

PMID: 35274842 - same authors as PMID: 21480433, report a second Korean family with a similar presentation to the first and the missense p.R941L.
- Reviews literature reporting an additional 2 families (American, Canadian) with this same p.R941L variant, who presented with distal HMN and hearing loss or CMT with hearing loss (PMID:31231018;27875632). These multigenerational families were Caucasian or not described, with no de novo evidence shown. Authors speculate recurrence due to the broad geographical location where families have been described.


Single recurring missense appears to be responsible for this phenotype; Changed rating: GREEN; Changed publications: PMID: 21480433, 35274842, 31231018, 27875632
Incidentalome v0.215 APC Zornitza Stark Marked gene: APC as ready
Incidentalome v0.215 APC Zornitza Stark Gene: apc has been classified as Green List (High Evidence).
Incidentalome v0.215 APC Zornitza Stark Phenotypes for gene: APC were changed from to Adenomatous polyposis coli, MIM# 175100
Incidentalome v0.214 APC Zornitza Stark Mode of inheritance for gene: APC was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.213 APC Zornitza Stark Tag cancer tag was added to gene: APC.
Incidentalome v0.213 APC Zornitza Stark reviewed gene: APC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Adenomatous polyposis coli, MIM# 175100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.213 A2M Zornitza Stark Marked gene: A2M as ready
Incidentalome v0.213 A2M Zornitza Stark Gene: a2m has been classified as Red List (Low Evidence).
Incidentalome v0.213 A2M Zornitza Stark Phenotypes for gene: A2M were changed from to Alzheimer disease, MONDO:0004975
Incidentalome v0.212 A2M Zornitza Stark Mode of inheritance for gene: A2M was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.211 A2M Zornitza Stark Classified gene: A2M as Red List (low evidence)
Incidentalome v0.211 A2M Zornitza Stark Gene: a2m has been classified as Red List (Low Evidence).
Incidentalome v0.210 A2M Zornitza Stark Tag adult onset neurodegenerative tag was added to gene: A2M.
Incidentalome v0.210 A2M Zornitza Stark reviewed gene: A2M: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Alzheimer disease, MONDO:0004975; Mode of inheritance: None
Incidentalome v0.210 GPD1L Zornitza Stark edited their review of gene: GPD1L: Changed rating: RED
Incidentalome v0.210 GPD1L Zornitza Stark Tag cardiac tag was added to gene: GPD1L.
Incidentalome v0.210 ANK2 Zornitza Stark Tag cardiac tag was added to gene: ANK2.
Incidentalome v0.210 TNNT2 Zornitza Stark Tag cardiac tag was added to gene: TNNT2.
Incidentalome v0.210 KCNE1 Zornitza Stark Tag cardiac tag was added to gene: KCNE1.
Incidentalome v0.210 CACNA1C Zornitza Stark Tag review tag was added to gene: CACNA1C.
Incidentalome v0.210 CASQ2 Zornitza Stark Tag cardiac tag was added to gene: CASQ2.
Incidentalome v0.210 CASQ2 Zornitza Stark Marked gene: CASQ2 as ready
Incidentalome v0.210 CASQ2 Zornitza Stark Gene: casq2 has been classified as Green List (High Evidence).
Incidentalome v0.210 CASQ2 Zornitza Stark Phenotypes for gene: CASQ2 were changed from to Ventricular tachycardia, catecholaminergic polymorphic, 2, MIM# 611938
Incidentalome v0.209 CASQ2 Zornitza Stark Publications for gene: CASQ2 were set to
Incidentalome v0.208 CASQ2 Zornitza Stark Mode of inheritance for gene: CASQ2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.207 CASQ2 Zornitza Stark reviewed gene: CASQ2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ventricular tachycardia, catecholaminergic polymorphic, 2, MIM# 611938; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.206 SNTA1 Zornitza Stark Marked gene: SNTA1 as ready
Incidentalome v0.206 SNTA1 Zornitza Stark Gene: snta1 has been classified as Red List (Low Evidence).
Incidentalome v0.206 SNTA1 Zornitza Stark Phenotypes for gene: SNTA1 were changed from to Long QT syndrome 12, MIM# 612955
Incidentalome v0.205 SNTA1 Zornitza Stark Publications for gene: SNTA1 were set to
Incidentalome v0.204 SNTA1 Zornitza Stark Mode of inheritance for gene: SNTA1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.203 SNTA1 Zornitza Stark Classified gene: SNTA1 as Red List (low evidence)
Incidentalome v0.203 SNTA1 Zornitza Stark Gene: snta1 has been classified as Red List (Low Evidence).
Incidentalome v0.202 SNTA1 Zornitza Stark Tag disputed tag was added to gene: SNTA1.
Tag cardiac tag was added to gene: SNTA1.
Incidentalome v0.202 SNTA1 Zornitza Stark reviewed gene: SNTA1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Long QT syndrome 12, MIM# 612955; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.202 SCN4B Zornitza Stark Tag disputed tag was added to gene: SCN4B.
Incidentalome v0.202 SCN4B Zornitza Stark Marked gene: SCN4B as ready
Incidentalome v0.202 SCN4B Zornitza Stark Gene: scn4b has been classified as Red List (Low Evidence).
Incidentalome v0.202 SCN4B Zornitza Stark Phenotypes for gene: SCN4B were changed from to Long QT syndrome 10, MIM# 611819
Incidentalome v0.201 SCN4B Zornitza Stark Publications for gene: SCN4B were set to
Incidentalome v0.200 SCN4B Zornitza Stark Mode of inheritance for gene: SCN4B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.199 SCN4B Zornitza Stark Classified gene: SCN4B as Red List (low evidence)
Incidentalome v0.199 SCN4B Zornitza Stark Gene: scn4b has been classified as Red List (Low Evidence).
Incidentalome v0.198 SCN4B Zornitza Stark Tag cardiac tag was added to gene: SCN4B.
Incidentalome v0.198 KCNE2 Zornitza Stark Marked gene: KCNE2 as ready
Incidentalome v0.198 KCNE2 Zornitza Stark Gene: kcne2 has been classified as Amber List (Moderate Evidence).
Incidentalome v0.198 KCNE2 Zornitza Stark Phenotypes for gene: KCNE2 were changed from to Long QT syndrome 6, MIM# 613693
Incidentalome v0.197 KCNE2 Zornitza Stark Publications for gene: KCNE2 were set to
Incidentalome v0.196 KCNE2 Zornitza Stark Mode of inheritance for gene: KCNE2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.195 KCNE2 Zornitza Stark Classified gene: KCNE2 as Amber List (moderate evidence)
Incidentalome v0.195 KCNE2 Zornitza Stark Gene: kcne2 has been classified as Amber List (Moderate Evidence).
Incidentalome v0.194 KCNE2 Zornitza Stark Tag cardiac tag was added to gene: KCNE2.
Incidentalome v0.194 KCNE2 Zornitza Stark reviewed gene: KCNE2: Rating: AMBER; Mode of pathogenicity: None; Publications: 31983240; Phenotypes: Long QT syndrome 6, MIM# 613693; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.194 KCNE1 Zornitza Stark Marked gene: KCNE1 as ready
Incidentalome v0.194 KCNE1 Zornitza Stark Gene: kcne1 has been classified as Green List (High Evidence).
Incidentalome v0.194 KCNE1 Zornitza Stark Phenotypes for gene: KCNE1 were changed from to Jervell and Lange-Nielsen syndrome 2, MIM# 612347; Long QT syndrome 5, MIM# 613695
Incidentalome v0.193 KCNE1 Zornitza Stark Mode of inheritance for gene: KCNE1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.192 KCNE1 Zornitza Stark edited their review of gene: KCNE1: Changed rating: GREEN; Changed phenotypes: Jervell and Lange-Nielsen syndrome 2, MIM# 612347, Long QT syndrome 5, MIM# 613695; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.191 KCNQ1 Zornitza Stark Tag cardiac tag was added to gene: KCNQ1.
Incidentalome v0.191 KCNQ1 Zornitza Stark Marked gene: KCNQ1 as ready
Incidentalome v0.191 KCNQ1 Zornitza Stark Gene: kcnq1 has been classified as Green List (High Evidence).
Incidentalome v0.191 KCNQ1 Zornitza Stark Phenotypes for gene: KCNQ1 were changed from to Long QT syndrome 1, MIM# 192500; Short QT syndrome 2, MIM# 609621; Jervell and Lange-Nielsen syndrome, MIM# 220400; Atrial fibrillation, familial, 3, MIM# 607554
Incidentalome v0.190 KCNQ1 Zornitza Stark Mode of inheritance for gene: KCNQ1 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Incidentalome v0.189 KCNQ1 Zornitza Stark reviewed gene: KCNQ1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Long QT syndrome 1, MIM# 192500, Short QT syndrome 2, MIM# 609621, Jervell and Lange-Nielsen syndrome, MIM# 220400, Atrial fibrillation, familial, 3, MIM# 607554; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Incidentalome v0.189 KCNH2 Zornitza Stark Tag cardiac tag was added to gene: KCNH2.
Incidentalome v0.189 KCNH2 Zornitza Stark Marked gene: KCNH2 as ready
Incidentalome v0.189 KCNH2 Zornitza Stark Gene: kcnh2 has been classified as Green List (High Evidence).
Incidentalome v0.189 KCNH2 Zornitza Stark Phenotypes for gene: KCNH2 were changed from to Long QT syndrome 2, MIM# 613688; Short QT syndrome , MIM#1 609620
Incidentalome v0.188 KCNH2 Zornitza Stark Publications for gene: KCNH2 were set to
Incidentalome v0.187 KCNH2 Zornitza Stark Mode of inheritance for gene: KCNH2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.186 KCNH2 Zornitza Stark reviewed gene: KCNH2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31983240; Phenotypes: Long QT syndrome 2, MIM# 613688, Short QT syndrome , MIM#1 609620; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.186 CACNB2 Zornitza Stark Tag cardiac tag was added to gene: CACNB2.
Incidentalome v0.186 CACNB2 Zornitza Stark Marked gene: CACNB2 as ready
Incidentalome v0.186 CACNB2 Zornitza Stark Gene: cacnb2 has been classified as Red List (Low Evidence).
Incidentalome v0.186 CACNB2 Zornitza Stark Phenotypes for gene: CACNB2 were changed from to Brugada syndrome 4, MIM# 611876
Incidentalome v0.185 CACNB2 Zornitza Stark Publications for gene: CACNB2 were set to
Incidentalome v0.184 CACNB2 Zornitza Stark Mode of inheritance for gene: CACNB2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.183 CACNB2 Zornitza Stark Classified gene: CACNB2 as Red List (low evidence)
Incidentalome v0.183 CACNB2 Zornitza Stark Gene: cacnb2 has been classified as Red List (Low Evidence).
Incidentalome v0.182 CACNB2 Zornitza Stark reviewed gene: CACNB2: Rating: RED; Mode of pathogenicity: None; Publications: 29959160; Phenotypes: Brugada syndrome 4, MIM# 611876; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.182 PRKAG2 Zornitza Stark Tag cardiac tag was added to gene: PRKAG2.
Incidentalome v0.182 PRKAG2 Zornitza Stark Marked gene: PRKAG2 as ready
Incidentalome v0.182 PRKAG2 Zornitza Stark Gene: prkag2 has been classified as Green List (High Evidence).
Incidentalome v0.182 PRKAG2 Zornitza Stark Phenotypes for gene: PRKAG2 were changed from to Cardiomyopathy, hypertrophic 6, MIM# 600858; Glycogen storage disease of heart, lethal congenital, MIM# 261740
Incidentalome v0.181 PRKAG2 Zornitza Stark Publications for gene: PRKAG2 were set to
Incidentalome v0.180 PRKAG2 Zornitza Stark Mode of inheritance for gene: PRKAG2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.179 PRKAG2 Zornitza Stark Deleted their comment
Incidentalome v0.179 PRKAG2 Zornitza Stark edited their review of gene: PRKAG2: Added comment: Variants associated with cardiomyopathy, conduction disease, and ventricular pre-excitation. More than 50 unrelated individuals reported. Can present with isolated HCM.; Changed publications: 15877279, 17667862, 32646569; Changed phenotypes: Cardiomyopathy, hypertrophic 6, MIM# 600858, Glycogen storage disease of heart, lethal congenital, MIM# 261740
Incidentalome v0.179 MYL3 Zornitza Stark Tag cardiac tag was added to gene: MYL3.
Incidentalome v0.179 MYL3 Zornitza Stark Marked gene: MYL3 as ready
Incidentalome v0.179 MYL3 Zornitza Stark Gene: myl3 has been classified as Green List (High Evidence).
Incidentalome v0.179 MYL3 Zornitza Stark Phenotypes for gene: MYL3 were changed from to Cardiomyopathy, hypertrophic, 8, MIM# 608751
Incidentalome v0.178 MYL3 Zornitza Stark Publications for gene: MYL3 were set to
Incidentalome v0.177 MYL3 Zornitza Stark Mode of inheritance for gene: MYL3 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.176 MYL3 Zornitza Stark reviewed gene: MYL3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cardiomyopathy, hypertrophic, 8, MIM# 608751; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.176 MYL2 Zornitza Stark Marked gene: MYL2 as ready
Incidentalome v0.176 MYL2 Zornitza Stark Gene: myl2 has been classified as Green List (High Evidence).
Incidentalome v0.176 MYL2 Zornitza Stark Tag cardiac tag was added to gene: MYL2.
Incidentalome v0.176 MYL2 Zornitza Stark Phenotypes for gene: MYL2 were changed from to Myopathy, myofibrillar, 12, infantile-onset, with cardiomyopathy, MIM# 619424; Cardiomyopathy, hypertrophic, 10, MIM# 608758
Incidentalome v0.175 MYL2 Zornitza Stark Publications for gene: MYL2 were set to
Incidentalome v0.174 MYL2 Zornitza Stark Mode of inheritance for gene: MYL2 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Incidentalome v0.173 MYL2 Zornitza Stark reviewed gene: MYL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23365102, 32453731; Phenotypes: Myopathy, myofibrillar, 12, infantile-onset, with cardiomyopathy, MIM# 619424, Cardiomyopathy, hypertrophic, 10, MIM# 608758; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Incidentalome v0.173 GLA Zornitza Stark Publications for gene: GLA were set to 8878432; 31613176
Incidentalome v0.172 GLA Zornitza Stark Tag cardiac tag was added to gene: GLA.
Incidentalome v0.172 CACNA1C Zornitza Stark Marked gene: CACNA1C as ready
Incidentalome v0.172 CACNA1C Zornitza Stark Gene: cacna1c has been classified as Green List (High Evidence).
Incidentalome v0.172 CACNA1C Zornitza Stark Phenotypes for gene: CACNA1C were changed from to Hypertrophic cardiomyopathy; congenital heart defects; conduction abnormalities; Timothy syndrome, MIM# 601005; Long QT syndrome 8, MIM# 618447
Incidentalome v0.171 CACNA1C Zornitza Stark Publications for gene: CACNA1C were set to
Incidentalome v0.170 CACNA1C Zornitza Stark Mode of inheritance for gene: CACNA1C was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.169 CACNA1C Zornitza Stark changed review comment from: Association with HCM: Recurrent missense at position p.Arg518Cys/His observed in three families with complex cardiac phenotype including HCM. Digenic/trigenic inheritance postulated in other families.

Arrhythmia: definitive evidence for causality in Timothy syndrome but only moderate or limited evidence for isolated LQTS as reported in Circulation. 2020 Feb 11;141(6):418-428 PMID: 31983240, by the International, Multicentered LQTS ClinGen Working Group
Sources: Expert list; to: Association with HCM: Recurrent missense at position p.Arg518Cys/His observed in three families with complex cardiac phenotype including HCM. Digenic/trigenic inheritance postulated in other families.

Arrhythmia: definitive evidence for causality in Timothy syndrome but only moderate or limited evidence for isolated LQTS as reported in Circulation. 2020 Feb 11;141(6):418-428 PMID: 31983240, by the International, Multicentered LQTS ClinGen Working Group

DISPUTED for Brugada.

Sources: Expert list
Incidentalome v0.169 CACNA1C Zornitza Stark edited their review of gene: CACNA1C: Changed phenotypes: Hypertrophic cardiomyopathy, congenital heart defects, conduction abnormalities, Timothy syndrome, MIM# 601005, Long QT syndrome 8, MIM# 618447
Incidentalome v0.169 CACNA1C Zornitza Stark edited their review of gene: CACNA1C: Changed rating: GREEN
Incidentalome v0.169 CACNA1C Zornitza Stark changed review comment from: Association with HCM: Recurrent missense at position p.Arg518Cys/His observed in three families with complex cardiac phenotype including HCM. Digenic/trigenic inheritance postulated in other families.
Sources: Expert list; to: Association with HCM: Recurrent missense at position p.Arg518Cys/His observed in three families with complex cardiac phenotype including HCM. Digenic/trigenic inheritance postulated in other families.

Arrhythmia: definitive evidence for causality in Timothy syndrome but only moderate or limited evidence for isolated LQTS as reported in Circulation. 2020 Feb 11;141(6):418-428 PMID: 31983240, by the International, Multicentered LQTS ClinGen Working Group
Sources: Expert list
Incidentalome v0.169 CACNA1C Zornitza Stark changed review comment from: Recurrent missense at position p.Arg518Cys/His observed in three families with complex cardiac phenotype including HCM. Digenic/trigenic inheritance postulated in other families.
Sources: Expert list; to: Association with HCM: Recurrent missense at position p.Arg518Cys/His observed in three families with complex cardiac phenotype including HCM. Digenic/trigenic inheritance postulated in other families.
Sources: Expert list
Incidentalome v0.168 TTN Zornitza Stark Marked gene: TTN as ready
Incidentalome v0.168 TTN Zornitza Stark Gene: ttn has been classified as Green List (High Evidence).
Incidentalome v0.168 TTN Zornitza Stark Publications for gene: TTN were set to
Incidentalome v0.167 TTN Zornitza Stark Mode of inheritance for gene: TTN was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.166 TTN Zornitza Stark Tag cardiac tag was added to gene: TTN.
Incidentalome v0.166 TTN Zornitza Stark changed review comment from: DEFINITIVE by ClinGen.; to: DEFINITIVE by ClinGen for DCM and myopathy.

MODERATE for tibial muscular dystrophy and myofibrillar myopathy.

LIMITED for HCM and ARVC.
Incidentalome v0.166 TTN Zornitza Stark edited their review of gene: TTN: Changed phenotypes: Cardiomyopathy, dilated, 1G, MIM#604145, Cardiomyopathy, familial hypertrophic, 9, MIM# 613765, Tibial muscular dystrophy, tardive, MIM#600334, Salih myopathy (MIM#611705), Muscular dystrophy, limb-girdle, type 2J, 608807; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.166 TPM1 Zornitza Stark Marked gene: TPM1 as ready
Incidentalome v0.166 TPM1 Zornitza Stark Gene: tpm1 has been classified as Green List (High Evidence).
Incidentalome v0.166 TPM1 Zornitza Stark Tag cardiac tag was added to gene: TPM1.
Incidentalome v0.166 TPM1 Zornitza Stark Phenotypes for gene: TPM1 were changed from to Cardiomyopathy, dilated, 1Y, MIM# 611878; Cardiomyopathy, hypertrophic, 3, MIM# 115196
Incidentalome v0.165 TPM1 Zornitza Stark Publications for gene: TPM1 were set to
Incidentalome v0.164 TPM1 Zornitza Stark Mode of inheritance for gene: TPM1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.163 TPM1 Zornitza Stark changed review comment from: Several families reported, including ones with extensive segregation evidence; functional data, including animal model.

MODERATE by ClinGen.; to: Several families reported, including ones with extensive segregation evidence; functional data, including animal model.

MODERATE by ClinGen for DCM.
DEFINITIVE for HCM.
Incidentalome v0.163 TPM1 Zornitza Stark edited their review of gene: TPM1: Changed phenotypes: Cardiomyopathy, dilated, 1Y, MIM# 611878, Cardiomyopathy, hypertrophic, 3, MIM# 115196; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.163 TNNT2 Zornitza Stark Marked gene: TNNT2 as ready
Incidentalome v0.163 TNNT2 Zornitza Stark Gene: tnnt2 has been classified as Green List (High Evidence).
Incidentalome v0.163 TNNT2 Zornitza Stark Phenotypes for gene: TNNT2 were changed from to Cardiomyopathy, dilated, 1D, MIM# 601494; Cardiomyopathy, hypertrophic, 2, MIM# 115195; Cardiomyopathy, familial restrictive, 3, MIM# 612422; Left ventricular noncompaction 6, MIM# 601494
Incidentalome v0.162 TNNT2 Zornitza Stark Publications for gene: TNNT2 were set to
Incidentalome v0.161 TNNT2 Zornitza Stark Mode of inheritance for gene: TNNT2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.160 TNNT2 Zornitza Stark changed review comment from: DEFINITIVE by ClinGen, multiple families, functional data. The p.Lys210del variant is a recurrent pathogenic variant.; to: DEFINITIVE by ClinGen for DCM and HCM, multiple families, functional data. The p.Lys210del variant is a recurrent pathogenic variant.
Incidentalome v0.160 TNNT2 Zornitza Stark edited their review of gene: TNNT2: Changed publications: 33947203, 11106718, 20978592, 20031601, 15542288, 17556660, 30681346; Changed phenotypes: Cardiomyopathy, dilated, 1D, MIM# 601494, Cardiomyopathy, hypertrophic, 2, MIM# 115195, Cardiomyopathy, familial restrictive, 3, MIM# 612422, Left ventricular noncompaction 6, MIM# 601494
Incidentalome v0.160 TNNI3 Zornitza Stark Tag cardiac tag was added to gene: TNNI3.
Incidentalome v0.160 TNNI3 Zornitza Stark Marked gene: TNNI3 as ready
Incidentalome v0.160 TNNI3 Zornitza Stark Gene: tnni3 has been classified as Green List (High Evidence).
Incidentalome v0.160 TNNI3 Zornitza Stark Phenotypes for gene: TNNI3 were changed from to Cardiomyopathy, dilated, 1FF, MIM#613286; Cardiomyopathy, hypertrophic, 7, MIM# 613690; Cardiomyopathy, familial restrictive, MIM#1115210
Incidentalome v0.159 TNNI3 Zornitza Stark Publications for gene: TNNI3 were set to
Incidentalome v0.158 TNNI3 Zornitza Stark Mode of inheritance for gene: TNNI3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.157 TNNI3 Zornitza Stark edited their review of gene: TNNI3: Changed publications: 22464770, 31568572, 19590045, 20215591, 21846512, 2226790, 30681346; Changed phenotypes: Cardiomyopathy, dilated, 1FF, MIM#613286, Cardiomyopathy, hypertrophic, 7, MIM# 613690
Incidentalome v0.157 SCN5A Zornitza Stark Marked gene: SCN5A as ready
Incidentalome v0.157 SCN5A Zornitza Stark Gene: scn5a has been classified as Green List (High Evidence).
Incidentalome v0.157 SCN5A Zornitza Stark Tag cardiac tag was added to gene: SCN5A.
Incidentalome v0.157 SCN5A Zornitza Stark Phenotypes for gene: SCN5A were changed from to Long QT syndrome 3 (MIM#603830); Sick sinus syndrome 1, MIM# 608567; Ventricular fibrillation, familial, 1, MIM# 603829; Brugada syndrome 1, MIM# 601144; Heart block, progressive, type IA, MIM# 113900; Cardiomyopathy, dilated, 1E, MIM# 601154
Incidentalome v0.156 SCN5A Zornitza Stark Publications for gene: SCN5A were set to
Incidentalome v0.155 SCN5A Zornitza Stark edited their review of gene: SCN5A: Added comment: Variants in this gene are also associated with a range of arrhythmia disorders.; Changed phenotypes: Long QT syndrome 3 (MIM#603830), Sick sinus syndrome 1, MIM# 608567, Ventricular fibrillation, familial, 1, MIM# 603829, Brugada syndrome 1, MIM# 601144, Heart block, progressive, type IA, MIM# 113900
Incidentalome v0.155 SCN5A Zornitza Stark Mode of inheritance for gene: SCN5A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.154 MYH7 Zornitza Stark Marked gene: MYH7 as ready
Incidentalome v0.154 MYH7 Zornitza Stark Gene: myh7 has been classified as Green List (High Evidence).
Incidentalome v0.154 MYH7 Zornitza Stark Phenotypes for gene: MYH7 were changed from to Cardiomyopathy, dilated, 1S, MIM# 613426; MONDO:0013262; Cardiomyopathy, hypertrophic, 1, MIM# 192600; Laing distal myopathy, MIM# 160500; Myopathy, myosin storage, autosomal dominant, MIM# 608358; Myopathy, myosin storage, autosomal recessive, MIM# 255160
Incidentalome v0.153 MYH7 Zornitza Stark Publications for gene: MYH7 were set to
Incidentalome v0.152 MYH7 Zornitza Stark Mode of inheritance for gene: MYH7 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.151 MYH7 Zornitza Stark Tag cardiac tag was added to gene: MYH7.
Incidentalome v0.151 MYH7 Zornitza Stark edited their review of gene: MYH7: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.151 MYH7 Zornitza Stark changed review comment from: DEFINITIVE by ClinGen, multiple families with segregation evidence and functional data.; to: DEFINITIVE by ClinGen for HCM and DCM, multiple families with segregation evidence and functional data.

Also multiple families reported with skeletal myopathies.
Incidentalome v0.151 MYH7 Zornitza Stark edited their review of gene: MYH7: Changed publications: 21483645, 30874888, 21846512, 30384889, 25935763, 24558114, 27000522, 31179125, 24119082, 27965028, 33947203, 30681346, 15322983; Changed phenotypes: Cardiomyopathy, dilated, 1S, MIM# 613426, MONDO:0013262, Cardiomyopathy, hypertrophic, 1, MIM# 192600, Laing distal myopathy, MIM# 160500, Myopathy, myosin storage, autosomal dominant, MIM# 608358, Myopathy, myosin storage, autosomal recessive, MIM# 255160
Incidentalome v0.151 MYBPC3 Zornitza Stark Marked gene: MYBPC3 as ready
Incidentalome v0.151 MYBPC3 Zornitza Stark Gene: mybpc3 has been classified as Green List (High Evidence).
Incidentalome v0.151 MYBPC3 Zornitza Stark Tag cardiac tag was added to gene: MYBPC3.
Incidentalome v0.151 MYBPC3 Zornitza Stark Phenotypes for gene: MYBPC3 were changed from to Cardiomyopathy, dilated, 1MM, MIM#615396; Cardiomyopathy, hypertrophic, 4, MIM# 115197
Incidentalome v0.150 MYBPC3 Zornitza Stark Mode of inheritance for gene: MYBPC3 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.149 MYBPC3 Zornitza Stark changed review comment from: Association with HCM is definitive.

No segregation or experimental data to support association with DCM. VOUS only in large cohorts.; to: Association with HCM is DEFINITIVE.

No segregation or experimental data to support association with DCM. VOUS only in large cohorts.
Incidentalome v0.149 MYBPC3 Zornitza Stark edited their review of gene: MYBPC3: Changed rating: GREEN; Changed phenotypes: Cardiomyopathy, dilated, 1MM, MIM#615396, Cardiomyopathy, hypertrophic, 4, MIM# 115197; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.149 ACTC1 Zornitza Stark Tag cardiac tag was added to gene: ACTC1.
Incidentalome v0.149 ACTC1 Zornitza Stark Marked gene: ACTC1 as ready
Incidentalome v0.149 ACTC1 Zornitza Stark Gene: actc1 has been classified as Green List (High Evidence).
Incidentalome v0.149 ACTC1 Zornitza Stark Phenotypes for gene: ACTC1 were changed from to Cardiomyopathy, dilated, 1R, MIM# 613424; Cardiomyopathy, hypertrophic, 11, MIM# 612098; Atrial septal defect 5, MIM# 612794
Incidentalome v0.148 ACTC1 Zornitza Stark Publications for gene: ACTC1 were set to
Incidentalome v0.147 ACTC1 Zornitza Stark Mode of inheritance for gene: ACTC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.146 ACTC1 Zornitza Stark edited their review of gene: ACTC1: Added comment: LIMITED to MODERATE association with congenital heart disease.; Changed publications: 31430208, 30384889, 9563954, 14605248, 20600154, 26432839, 17947298, 31430208; Changed phenotypes: Cardiomyopathy, dilated, 1R, MIM# 613424, Cardiomyopathy, hypertrophic, 11, MIM# 612098, Atrial septal defect 5, MIM# 612794
Incidentalome v0.145 TMEM43 Zornitza Stark Marked gene: TMEM43 as ready
Incidentalome v0.145 TMEM43 Zornitza Stark Gene: tmem43 has been classified as Green List (High Evidence).
Incidentalome v0.145 TMEM43 Zornitza Stark Phenotypes for gene: TMEM43 were changed from to Arrhythmogenic right ventricular dysplasia 5, MIM# 604400; Auditory neuropathy, autosomal dominant 3, MIM# 619832; Emery-Dreifuss muscular dystrophy 7 (MIM#614302)
Incidentalome v0.144 TMEM43 Zornitza Stark Publications for gene: TMEM43 were set to
Incidentalome v0.143 TMEM43 Zornitza Stark Mode of inheritance for gene: TMEM43 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.142 TMEM43 Zornitza Stark Tag cardiac tag was added to gene: TMEM43.
Incidentalome v0.142 TMEM43 Zornitza Stark changed review comment from: DEFINITIVE by ClinGen, multiple families reported, functional data. Common founder variant p.Ser358Leu.; to: DEFINITIVE by ClinGen for ARVC, multiple families reported, functional data. Common founder variant p.Ser358Leu.
Incidentalome v0.142 TMEM43 Zornitza Stark edited their review of gene: TMEM43: Added comment: Association with deafness: MODERATE, two multiplex families with missense variants.

Association with muscular dystrophy LIMITED to MODERATE:
PMID: 21391237 (2011): Different variants reported in 2 adults with EDMD-related myopathy. Ile91Val present in gnomad, 20 hets. Other variant, Glu85Lys, presented in gnomad (1 het)

PMID: 30311943 (2019): 1 EDMD family reported with the same Glu85Lys variant. Muscle disease suspected at age of 17 in one family member.; Changed publications: 18313022, 21214875, 23812740, 22725725, 24598986, 29980933, 34050020, 21391237, 30311943; Changed phenotypes: Arrhythmogenic right ventricular dysplasia 5, MIM# 604400, Auditory neuropathy, autosomal dominant 3, MIM# 619832, Emery-Dreifuss muscular dystrophy 7 (MIM#614302)
Deafness_IsolatedAndComplex v1.143 TMEM43 Zornitza Stark Marked gene: TMEM43 as ready
Deafness_IsolatedAndComplex v1.143 TMEM43 Zornitza Stark Gene: tmem43 has been classified as Amber List (Moderate Evidence).
Deafness_IsolatedAndComplex v1.143 TMEM43 Zornitza Stark Classified gene: TMEM43 as Amber List (moderate evidence)
Deafness_IsolatedAndComplex v1.143 TMEM43 Zornitza Stark Gene: tmem43 has been classified as Amber List (Moderate Evidence).
Deafness_IsolatedAndComplex v1.142 TMEM43 Zornitza Stark gene: TMEM43 was added
gene: TMEM43 was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: TMEM43 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TMEM43 were set to 34050020
Phenotypes for gene: TMEM43 were set to Auditory neuropathy, autosomal dominant 3, MIM# 619832
Review for gene: TMEM43 was set to AMBER
Added comment: 15 individuals reported from two families with missense variants and deafness.
Sources: Literature
Hereditary Neuropathy v0.130 MYH14 Elena Savva reviewed gene: MYH14: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 21480433, 35274842; Phenotypes: ?Peripheral neuropathy, myopathy, hoarseness, and hearing loss MIM#614369; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Incidentalome v0.142 RYR2 Zornitza Stark Marked gene: RYR2 as ready
Incidentalome v0.142 RYR2 Zornitza Stark Gene: ryr2 has been classified as Green List (High Evidence).
Incidentalome v0.142 RYR2 Zornitza Stark Phenotypes for gene: RYR2 were changed from to Ventricular tachycardia, catecholaminergic polymorphic, 1, MIM# 604772; Arrhythmogenic right ventricular dysplasia 2, MIM# 600996; Hypertrophic cardiomyopathy
Incidentalome v0.141 RYR2 Zornitza Stark Publications for gene: RYR2 were set to
Incidentalome v0.140 RYR2 Zornitza Stark Mode of inheritance for gene: RYR2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.139 RYR2 Zornitza Stark Tag cardiac tag was added to gene: RYR2.
Incidentalome v0.139 RYR2 Zornitza Stark changed review comment from: Gene-disease association assessed as REFUTED by ClinGen: 57 papers reviewed in the process. Some of the original variants were relatively often present in reference alleles from the gnomAD database, clear ARVD diagnosis was not provided, segregation information was not informative and/or CPVT was also present in the family. In a recent review it was also recognized that the observed phenotype in the original three publications that reported RYR2 variants in ARVD for the first time should be catecholamine-induced ventricular tachycardia rather than ARVD, and this gene is no longer considered as ARVD causing (29543670).; to: ARVC: gene-disease association assessed as REFUTED by ClinGen: 57 papers reviewed in the process. Some of the original variants were relatively often present in reference alleles from the gnomAD database, clear ARVD diagnosis was not provided, segregation information was not informative and/or CPVT was also present in the family. In a recent review it was also recognized that the observed phenotype in the original three publications that reported RYR2 variants in ARVD for the first time should be catecholamine-induced ventricular tachycardia rather than ARVD, and this gene is no longer considered as ARVD causing (29543670).
Incidentalome v0.139 RYR2 Zornitza Stark edited their review of gene: RYR2: Added comment: DEFINITVE for CPVT.

REFUTED for ARVC.

LIMITED for HCM.; Changed rating: GREEN; Changed publications: 11159936, 25041964, 29543670, 11208676, 12093772; Changed phenotypes: Ventricular tachycardia, catecholaminergic polymorphic, 1, MIM# 604772, Arrhythmogenic right ventricular dysplasia 2, MIM# 600996, Hypertrophic cardiomyopathy
Incidentalome v0.139 PKP2 Zornitza Stark Tag cardiac tag was added to gene: PKP2.
Incidentalome v0.139 LMNA Zornitza Stark Tag cardiac tag was added to gene: LMNA.
Incidentalome v0.139 DSP Zornitza Stark Tag cardiac tag was added to gene: DSP.
Incidentalome v0.139 DSG2 Zornitza Stark Tag cardiac tag was added to gene: DSG2.
Incidentalome v0.139 DSC2 Zornitza Stark Tag cardiac tag was added to gene: DSC2.
Incidentalome v0.139 PKP2 Zornitza Stark Marked gene: PKP2 as ready
Incidentalome v0.139 PKP2 Zornitza Stark Gene: pkp2 has been classified as Green List (High Evidence).
Incidentalome v0.139 PKP2 Zornitza Stark Phenotypes for gene: PKP2 were changed from to Arrhythmogenic right ventricular dysplasia 9, MIM# 609040
Incidentalome v0.138 PKP2 Zornitza Stark Publications for gene: PKP2 were set to
Incidentalome v0.137 PKP2 Zornitza Stark Mode of inheritance for gene: PKP2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.136 LMNA Zornitza Stark Marked gene: LMNA as ready
Incidentalome v0.136 LMNA Zornitza Stark Gene: lmna has been classified as Green List (High Evidence).
Incidentalome v0.136 LMNA Zornitza Stark Phenotypes for gene: LMNA were changed from to Cardiomyopathy, dilated, 1A, MIM# 115200; Arrhythmogenic right ventricular cardiomyopathy; Lipodystrophy, familial partial, type 2, MIM# 151660; Emery-Dreifuss muscular dystrophy 2, MIM#181350; Mandibuloacral dysplasia 248370; Restrictive dermopathy, lethal 275210; Hutchinson-Gilford progeria 176670; Muscular dystrophy, congenital 613205
Incidentalome v0.135 LMNA Zornitza Stark Publications for gene: LMNA were set to
Incidentalome v0.134 LMNA Zornitza Stark Mode of inheritance for gene: LMNA was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.133 LMNA Zornitza Stark edited their review of gene: LMNA: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.133 LMNA Zornitza Stark Mode of inheritance for gene: LMNA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.132 LMNA Zornitza Stark changed review comment from: Association between LMNA and ARVC has been rated as LIMITED by ClinGen: small number of families reported where only some of the individuals with the variants had convincing ARVC phenotype. Rated Amber on this panel more due to phenotypic overlap with DCM and arrhythmias arising in this context.
Sources: Expert list; to: Established association with multiple phenotypes.
Incidentalome v0.132 LMNA Zornitza Stark edited their review of gene: LMNA: Changed rating: GREEN; Changed phenotypes: Cardiomyopathy, dilated, 1A, MIM# 115200, Arrhythmogenic right ventricular cardiomyopathy, Lipodystrophy, familial partial, type 2, MIM# 151660, Emery-Dreifuss muscular dystrophy 2, MIM#181350, Mandibuloacral dysplasia 248370, Restrictive dermopathy, lethal 275210, Hutchinson-Gilford progeria 176670, Muscular dystrophy, congenital 613205
Incidentalome v0.132 DSP Zornitza Stark Marked gene: DSP as ready
Incidentalome v0.132 DSP Zornitza Stark Gene: dsp has been classified as Green List (High Evidence).
Incidentalome v0.132 DSP Zornitza Stark Phenotypes for gene: DSP were changed from to Arrhythmogenic right ventricular dysplasia 8, MIM# 607450; Dilated cardiomyopathy with woolly hair, keratoderma, and tooth agenesis, MIM# 615821; Cardiomyopathy, dilated, with woolly hair and keratoderma, MIM# 605676; Epidermolysis bullosa, lethal acantholytic, MIM# 609638
Incidentalome v0.131 DSP Zornitza Stark Publications for gene: DSP were set to
Incidentalome v0.130 DSP Zornitza Stark Mode of inheritance for gene: DSP was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.129 DSP Zornitza Stark edited their review of gene: DSP: Added comment: Established gene-disease associations.; Changed phenotypes: Arrhythmogenic right ventricular dysplasia 8, MIM# 607450, Dilated cardiomyopathy with woolly hair, keratoderma, and tooth agenesis, MIM# 615821, Cardiomyopathy, dilated, with woolly hair and keratoderma, MIM# 605676, Epidermolysis bullosa, lethal acantholytic, MIM# 609638
Incidentalome v0.129 DSG2 Zornitza Stark Marked gene: DSG2 as ready
Incidentalome v0.129 DSG2 Zornitza Stark Gene: dsg2 has been classified as Green List (High Evidence).
Incidentalome v0.129 DSG2 Zornitza Stark Phenotypes for gene: DSG2 were changed from to Arrhythmogenic right ventricular dysplasia 10, MIM# 610193; Cardiomyopathy, dilated, 1BB, MIM# 612877
Incidentalome v0.128 DSG2 Zornitza Stark Publications for gene: DSG2 were set to
Incidentalome v0.127 DSG2 Zornitza Stark Mode of inheritance for gene: DSG2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.126 DSG2 Zornitza Stark Deleted their comment
Incidentalome v0.126 DSG2 Zornitza Stark edited their review of gene: DSG2: Added comment: Assessed as LIMITED by ClinGen for mono-allelic variants and DCM:

Human genetic evidence supporting this gene-disease relationship includes one published definitive DCM case with truncating variant in DSG2 published by Garcia-Pavia et al (2011, PMID: 21859740). Of note, this person had limited ECG/arrhythmia phenotyping. Multiple other published variants have population frequencies which exclude them from scoring, as they are observed at a frequency higher than would be expected to have a pathogenic effect. In addition, this gene-disease association is supported by experimental evidence from postnatal DCM hearts showing reduced DSG2 signal in myocardium and other intercalated disc proteins were normal(Kessler et al, 2017, PMID: 28764973). In summary, there is limited evidence to support this gene-disease relationship.

Bi-allelic variants and DCM: three families reported, two with missense variants.

DEFINITIVE for ARVC.; Changed phenotypes: Arrhythmogenic right ventricular dysplasia 10, MIM# 610193, Cardiomyopathy, dilated, 1BB, MIM# 612877; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Dilated Cardiomyopathy v1.12 DSG2 Zornitza Stark Publications for gene: DSG2 were set to 23071725
Dilated Cardiomyopathy v1.11 DSG2 Zornitza Stark Mode of inheritance for gene: DSG2 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Dilated Cardiomyopathy v1.10 DSG2 Zornitza Stark Classified gene: DSG2 as Amber List (moderate evidence)
Dilated Cardiomyopathy v1.10 DSG2 Zornitza Stark Gene: dsg2 has been classified as Amber List (Moderate Evidence).
Dilated Cardiomyopathy v1.9 DSG2 Zornitza Stark changed review comment from: Assessed as LIMITED by ClinGen for mono-allelic variants:

Human genetic evidence supporting this gene-disease relationship includes one published definitive DCM case with truncating variant in DSG2 published by Garcia-Pavia et al (2011, PMID: 21859740). Of note, this person had limited ECG/arrhythmia phenotyping. Multiple other published variants have population frequencies which exclude them from scoring, as they are observed at a frequency higher than would be expected to have a pathogenic effect. In addition, this gene-disease association is supported by experimental evidence from postnatal DCM hearts showing reduced DSG2 signal in myocardium and other intercalated disc proteins were normal(Kessler et al, 2017, PMID: 28764973). In summary, there is limited evidence to support this gene-disease relationship.

Bi-allelic variants: three families reported.; to: Assessed as LIMITED by ClinGen for mono-allelic variants:

Human genetic evidence supporting this gene-disease relationship includes one published definitive DCM case with truncating variant in DSG2 published by Garcia-Pavia et al (2011, PMID: 21859740). Of note, this person had limited ECG/arrhythmia phenotyping. Multiple other published variants have population frequencies which exclude them from scoring, as they are observed at a frequency higher than would be expected to have a pathogenic effect. In addition, this gene-disease association is supported by experimental evidence from postnatal DCM hearts showing reduced DSG2 signal in myocardium and other intercalated disc proteins were normal(Kessler et al, 2017, PMID: 28764973). In summary, there is limited evidence to support this gene-disease relationship.

Bi-allelic variants: three families reported, two with missense variants.

DEFINITIVE for ARVC.
Dilated Cardiomyopathy v1.9 DSG2 Zornitza Stark changed review comment from: Assessed as LIMITED by ClinGen for mono-allelic variants:

Human genetic evidence supporting this gene-disease relationship includes one published definitive DCM case with truncating variant in DSG2 published by Garcia-Pavia et al (2011, PMID: 21859740). Of note, this person had limited ECG/arrhythmia phenotyping. Multiple other published variants have population frequencies which exclude them from scoring, as they are observed at a frequency higher than would be expected to have a pathogenic effect. In addition, this gene-disease association is supported by experimental evidence from postnatal DCM hearts showing reduced DSG2 signal in myocardium and other intercalated disc proteins were normal(Kessler et al, 2017, PMID: 28764973). In summary, there is limited evidence to support this gene-disease relationship.

Bi-allelic variants: two families reported.; to: Assessed as LIMITED by ClinGen for mono-allelic variants:

Human genetic evidence supporting this gene-disease relationship includes one published definitive DCM case with truncating variant in DSG2 published by Garcia-Pavia et al (2011, PMID: 21859740). Of note, this person had limited ECG/arrhythmia phenotyping. Multiple other published variants have population frequencies which exclude them from scoring, as they are observed at a frequency higher than would be expected to have a pathogenic effect. In addition, this gene-disease association is supported by experimental evidence from postnatal DCM hearts showing reduced DSG2 signal in myocardium and other intercalated disc proteins were normal(Kessler et al, 2017, PMID: 28764973). In summary, there is limited evidence to support this gene-disease relationship.

Bi-allelic variants: three families reported.
Dilated Cardiomyopathy v1.9 DSG2 Zornitza Stark edited their review of gene: DSG2: Changed publications: 33949662, 18678517, 21859740, 28764973, 35941102
Dilated Cardiomyopathy v1.9 DSG2 Zornitza Stark reviewed gene: DSG2: Rating: AMBER; Mode of pathogenicity: None; Publications: 33949662, 18678517, 21859740, 28764973; Phenotypes: Cardiomyopathy, dilated, 1BB, MIM# 612877; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.126 DSC2 Zornitza Stark Marked gene: DSC2 as ready
Incidentalome v0.126 DSC2 Zornitza Stark Gene: dsc2 has been classified as Green List (High Evidence).
Incidentalome v0.126 DSC2 Zornitza Stark Phenotypes for gene: DSC2 were changed from to Arrhythmogenic right ventricular dysplasia 11, MIM# 610476; Arrhythmogenic right ventricular dysplasia 11 with mild palmoplantar keratoderma and woolly hair, MIM# 610476
Incidentalome v0.125 DSC2 Zornitza Stark Publications for gene: DSC2 were set to
Incidentalome v0.124 DSC2 Zornitza Stark Mode of inheritance for gene: DSC2 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 v0.4874 THUMPD1 Zornitza Stark edited their review of gene: THUMPD1: Changed phenotypes: Neurodevelopmental disorder with speech delay and variable ocular anomalies, MIM# 619989; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.141 THUMPD1 Zornitza Stark Phenotypes for gene: THUMPD1 were changed from Syndromic disease, MONDO:0002254, THUMPD1-related to Neurodevelopmental disorder with speech delay and variable ocular anomalies, MIM# 619989
Deafness_IsolatedAndComplex v1.140 THUMPD1 Zornitza Stark reviewed gene: THUMPD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with speech delay and variable ocular anomalies, MIM# 619989; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.148 THUMPD1 Zornitza Stark Phenotypes for gene: THUMPD1 were changed from Syndromic disease, MONDO:0002254, THUMPD1-related to Neurodevelopmental disorder with speech delay and variable ocular anomalies, MIM# 619989
Microcephaly v1.147 THUMPD1 Zornitza Stark reviewed gene: THUMPD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with speech delay and variable ocular anomalies, MIM# 619989; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.239 THUMPD1 Zornitza Stark Phenotypes for gene: THUMPD1 were changed from Syndromic disease, MONDO:0002254, THUMPD1-related to Neurodevelopmental disorder with speech delay and variable ocular anomalies, MIM# 619989
Mendeliome v1.238 THUMPD1 Zornitza Stark reviewed gene: THUMPD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with speech delay and variable ocular anomalies, MIM# 619989; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Phagocyte Defects v1.9 OTULIN Zornitza Stark Phenotypes for gene: OTULIN were changed from Susceptibility to infection with Staphylococcus aureus; Hereditary predisposition to infections, MONDO:0015979, OTULIN-related to Immunodeficiency 107, susceptibility to invasive staphylococcus aureus infection, MIM# 619986
Phagocyte Defects v1.8 OTULIN Zornitza Stark edited their review of gene: OTULIN: Changed phenotypes: Immunodeficiency 107, susceptibility to invasive staphylococcus aureus infection, MIM# 619986
Mendeliome v1.238 OTULIN Zornitza Stark Phenotypes for gene: OTULIN were changed from Autoinflammation, panniculitis, and dermatosis syndrome, MIM# 617099; Susceptibility to infection with Staphylococcus aureus; Hereditary predisposition to infections, MONDO:0015979, OTULIN-related to Autoinflammation, panniculitis, and dermatosis syndrome, MIM# 617099; Immunodeficiency 107, susceptibility to invasive staphylococcus aureus infection, MIM# 619986
Mendeliome v1.237 OTULIN Zornitza Stark edited their review of gene: OTULIN: Changed phenotypes: Autoinflammation, panniculitis, and dermatosis syndrome, MIM# 617099, Immunodeficiency 107, susceptibility to invasive staphylococcus aureus infection, MIM# 619986
Prepair 1000+ v0.123 GYS2 Zornitza Stark Marked gene: GYS2 as ready
Prepair 1000+ v0.123 GYS2 Zornitza Stark Gene: gys2 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.123 GYS2 Zornitza Stark Publications for gene: GYS2 were set to
Prepair 1000+ v0.122 GYS2 Zornitza Stark Classified gene: GYS2 as Red List (low evidence)
Prepair 1000+ v0.122 GYS2 Zornitza Stark Gene: gys2 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.121 GYS2 Zornitza Stark Tag for review was removed from gene: GYS2.
Prepair 1000+ v0.121 GYS2 Zornitza Stark reviewed gene: GYS2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Glycogen storage disease 0, liver (MIM#240600); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.121 GK Zornitza Stark edited their review of gene: GK: Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v0.121 GK Zornitza Stark Marked gene: GK as ready
Prepair 1000+ v0.121 GK Zornitza Stark Gene: gk has been classified as Red List (Low Evidence).
Prepair 1000+ v0.121 GK Zornitza Stark Publications for gene: GK were set to
Prepair 1000+ v0.120 GK Zornitza Stark Classified gene: GK as Red List (low evidence)
Prepair 1000+ v0.120 GK Zornitza Stark Gene: gk has been classified as Red List (Low Evidence).
Prepair 1000+ v0.119 GK Zornitza Stark Tag for review was removed from gene: GK.
Prepair 1000+ v0.119 GK Zornitza Stark edited their review of gene: GK: Changed rating: RED; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.119 GK Zornitza Stark reviewed gene: GK: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Glycerol kinase deficiency (MIM#307030); Mode of inheritance: None
Prepair 1000+ v0.119 PCDH19 Crystle Lee gene: PCDH19 was added
gene: PCDH19 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: PCDH19 was set to Other
Publications for gene: PCDH19 were set to 18469813; 30287595
Phenotypes for gene: PCDH19 were set to Developmental and epileptic encephalopathy 9 (MIM#300088)
Review for gene: PCDH19 was set to AMBER
Added comment: XLD. Affects heterozygous females, hemizygous males are mainly unaffected
> 3 unrelated families with phenotype, > 3 de novo mutation carriers with phenotype
Evidence of mosaicism and incomplete penetrance
Sources: Literature
Prepair 1000+ v0.119 FTCD Zornitza Stark Marked gene: FTCD as ready
Prepair 1000+ v0.119 FTCD Zornitza Stark Gene: ftcd has been classified as Red List (Low Evidence).
Prepair 1000+ v0.119 FTCD Zornitza Stark Phenotypes for gene: FTCD were changed from Glutamate formiminotransferase deficiency, 229100 (3) to Glutamate formiminotransferase deficiency (MIM#229100)
Prepair 1000+ v0.118 FTCD Zornitza Stark Classified gene: FTCD as Red List (low evidence)
Prepair 1000+ v0.118 FTCD Zornitza Stark Gene: ftcd has been classified as Red List (Low Evidence).
Prepair 1000+ v0.117 FTCD Zornitza Stark Tag for review was removed from gene: FTCD.
Prepair 1000+ v0.117 FTCD Zornitza Stark reviewed gene: FTCD: Rating: RED; Mode of pathogenicity: None; Publications: 29178637, 30740726; Phenotypes: Glutamate formiminotransferase deficiency (MIM#229100); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.117 EFNB1 Zornitza Stark Marked gene: EFNB1 as ready
Prepair 1000+ v0.117 EFNB1 Zornitza Stark Gene: efnb1 has been classified as Green List (High Evidence).
Prepair 1000+ v0.117 EFNB1 Zornitza Stark Phenotypes for gene: EFNB1 were changed from Craniofrontonasal dysplasia, 304110 (3) to Craniofrontonasal dysplasia (MIM#304110)
Prepair 1000+ v0.116 EFNB1 Zornitza Stark Tag for review was removed from gene: EFNB1.
Prepair 1000+ v0.116 EFNB1 Zornitza Stark reviewed gene: EFNB1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Craniofrontonasal dysplasia (MIM#304110); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v0.116 CNGA3 Zornitza Stark Marked gene: CNGA3 as ready
Prepair 1000+ v0.116 CNGA3 Zornitza Stark Gene: cnga3 has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v0.116 CNGA3 Zornitza Stark Publications for gene: CNGA3 were set to
Prepair 1000+ v0.115 CNGA3 Zornitza Stark Classified gene: CNGA3 as Amber List (moderate evidence)
Prepair 1000+ v0.115 CNGA3 Zornitza Stark Gene: cnga3 has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v0.114 CNGA3 Zornitza Stark Tag for review was removed from gene: CNGA3.
Prepair 1000+ v0.114 CNGA3 Zornitza Stark reviewed gene: CNGA3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Achromatopsia 2 (MIM#216900); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.237 TAF4 Ee Ming Wong reviewed gene: TAF4: Rating: GREEN; Mode of pathogenicity: None; Publications: 33875846, 28191890, 35904126; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, TAF4-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Prepair 1000+ v0.114 CHM Zornitza Stark Marked gene: CHM as ready
Prepair 1000+ v0.114 CHM Zornitza Stark Gene: chm has been classified as Red List (Low Evidence).
Prepair 1000+ v0.114 CHM Zornitza Stark Phenotypes for gene: CHM were changed from Choroideremia to Choroideremia (MIM#303100)
Prepair 1000+ v0.113 CHM Zornitza Stark Phenotypes for gene: CHM were changed from Choroideremia to Choroideremia
Prepair 1000+ v0.112 CHM Zornitza Stark Publications for gene: CHM were set to 33110609; 27820636
Prepair 1000+ v0.112 CHM Zornitza Stark Publications for gene: CHM were set to
Prepair 1000+ v0.111 CHM Zornitza Stark Classified gene: CHM as Red List (low evidence)
Prepair 1000+ v0.111 CHM Zornitza Stark Gene: chm has been classified as Red List (Low Evidence).
Prepair 1000+ v0.110 CHM Zornitza Stark Tag for review was removed from gene: CHM.
Prepair 1000+ v0.110 CHM Zornitza Stark reviewed gene: CHM: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Choroideremia (MIM#303100); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v0.110 CASQ2 Zornitza Stark Marked gene: CASQ2 as ready
Prepair 1000+ v0.110 CASQ2 Zornitza Stark Gene: casq2 has been classified as Green List (High Evidence).
Prepair 1000+ v0.110 CASQ2 Zornitza Stark Publications for gene: CASQ2 were set to
Prepair 1000+ v0.109 CASQ2 Zornitza Stark Tag for review was removed from gene: CASQ2.
Prepair 1000+ v0.109 CASQ2 Zornitza Stark reviewed gene: CASQ2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ventricular tachycardia, catecholaminergic polymorphic, 2 (MIM#611938); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.109 CARD9 Zornitza Stark Marked gene: CARD9 as ready
Prepair 1000+ v0.109 CARD9 Zornitza Stark Gene: card9 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.109 CARD9 Zornitza Stark Phenotypes for gene: CARD9 were changed from Candidiasis, familial, 2, autosomal recessive, 212050 (3) to Immunodeficiency 103, susceptibility to fungal infection, MIM# 212050
Prepair 1000+ v0.108 CARD9 Zornitza Stark Publications for gene: CARD9 were set to
Prepair 1000+ v0.107 CARD9 Zornitza Stark Classified gene: CARD9 as Red List (low evidence)
Prepair 1000+ v0.107 CARD9 Zornitza Stark Gene: card9 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.106 CARD9 Zornitza Stark Tag for review was removed from gene: CARD9.
Prepair 1000+ v0.106 CARD9 Zornitza Stark reviewed gene: CARD9: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency 103, susceptibility to fungal infection, MIM# 212050; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4874 TAF4 Ee Ming Wong reviewed gene: TAF4: Rating: GREEN; Mode of pathogenicity: None; Publications: 33875846, 28191890, 35904126; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, TAF4-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Prepair 1000+ v0.106 C8B Alison Yeung Marked gene: C8B as ready
Prepair 1000+ v0.106 C8B Alison Yeung Gene: c8b has been classified as Red List (Low Evidence).
Prepair 1000+ v0.106 C8B Alison Yeung Classified gene: C8B as Red List (low evidence)
Prepair 1000+ v0.106 C8B Alison Yeung Added comment: Comment on list classification: susceptibility to infection - not suitable for reproductive screening panel
Prepair 1000+ v0.106 C8B Alison Yeung Gene: c8b has been classified as Red List (Low Evidence).
Prepair 1000+ v0.105 C8B Alison Yeung Phenotypes for gene: C8B were changed from C8 deficiency, type II, 613789 (3) to C8 deficiency, type II (MIM#613789)
Prepair 1000+ v0.104 C8B Alison Yeung Publications for gene: C8B were set to
Prepair 1000+ v0.103 C7 Zornitza Stark Marked gene: C7 as ready
Prepair 1000+ v0.103 C7 Zornitza Stark Gene: c7 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.103 C7 Zornitza Stark Publications for gene: C7 were set to
Prepair 1000+ v0.102 C7 Zornitza Stark Classified gene: C7 as Red List (low evidence)
Prepair 1000+ v0.102 C7 Zornitza Stark Gene: c7 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.101 C6 Zornitza Stark Marked gene: C6 as ready
Prepair 1000+ v0.101 C6 Zornitza Stark Gene: c6 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.101 C6 Zornitza Stark Publications for gene: C6 were set to
Prepair 1000+ v0.100 C6 Zornitza Stark Classified gene: C6 as Red List (low evidence)
Prepair 1000+ v0.100 C6 Zornitza Stark Gene: c6 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.99 C6 Zornitza Stark Tag for review was removed from gene: C6.
Prepair 1000+ v0.99 C6 Zornitza Stark reviewed gene: C6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: C6 deficiency (MIM#612446); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.99 C7 Zornitza Stark Tag for review was removed from gene: C7.
Prepair 1000+ v0.99 C7 Zornitza Stark reviewed gene: C7: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: C7 deficiency (MIM#610102); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.99 BGN Zornitza Stark Tag for review was removed from gene: BGN.
Prepair 1000+ v0.99 BGN Zornitza Stark Marked gene: BGN as ready
Prepair 1000+ v0.99 BGN Zornitza Stark Gene: bgn has been classified as Green List (High Evidence).
Prepair 1000+ v0.99 BGN Zornitza Stark Phenotypes for gene: BGN were changed from Meester-Loeys syndrome, 300989 (3), X-linked to Meester-Loeys syndrome (MIM#300989); Spondyloepimetaphyseal dysplasia, X-linked (MIM#300106)
Prepair 1000+ v0.98 BGN Zornitza Stark Publications for gene: BGN were set to
Prepair 1000+ v0.97 BGN Zornitza Stark reviewed gene: BGN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Meester-Loeys syndrome (MIM#300989), Spondyloepimetaphyseal dysplasia, X-linked (MIM#300106); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v0.97 ATP13A2 Zornitza Stark Marked gene: ATP13A2 as ready
Prepair 1000+ v0.97 ATP13A2 Zornitza Stark Gene: atp13a2 has been classified as Green List (High Evidence).
Prepair 1000+ v0.97 ATP13A2 Zornitza Stark Publications for gene: ATP13A2 were set to
Prepair 1000+ v0.96 ATP13A2 Zornitza Stark Phenotypes for gene: ATP13A2 were changed from Spastic paraplegia 78, autosomal recessive, 617225 (3) to Kufor-Rakeb syndrome (MIM#606693)
Prepair 1000+ v0.95 ATP13A2 Zornitza Stark Tag for review was removed from gene: ATP13A2.
Prepair 1000+ v0.95 ATP13A2 Zornitza Stark reviewed gene: ATP13A2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Kufor-Rakeb syndrome (MIM#606693); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.237 SPTBN5 Zornitza Stark Phenotypes for gene: SPTBN5 were changed from Sacral agenesis; congenital anomalies to Neurodevelopmental disorder, MONDO:0700092, SPTBN5-related; Sacral agenesis; congenital anomalies
Mendeliome v1.236 SPTBN5 Zornitza Stark Publications for gene: SPTBN5 were set to 32732226; 28007035
Mendeliome v1.235 SPTBN5 Zornitza Stark Mode of inheritance for gene: SPTBN5 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.234 SPTBN5 Zornitza Stark Classified gene: SPTBN5 as Green List (high evidence)
Mendeliome v1.234 SPTBN5 Zornitza Stark Gene: sptbn5 has been classified as Green List (High Evidence).
Mendeliome v1.233 SPTBN5 Zornitza Stark changed review comment from: Identified as a candidate gene in a sacral agenesis cohort.

PMID 32732226: compound het variants identified in a fetus with multicystic kidney and oligohydramnios detected by fetal ultrasound. Autopsy showed multiple congenital abnormalities including hygroma coli, spina bifida, polycystic kidneys, facial dysmorphism, common mesenterin, rachischisis, sacral vertebral agenesis.
Sources: Literature; to: Bi-allelic variants: Identified as a candidate gene in a sacral agenesis cohort.

PMID 32732226: compound het variants identified in a fetus with multicystic kidney and oligohydramnios detected by fetal ultrasound. Autopsy showed multiple congenital abnormalities including hygroma coli, spina bifida, polycystic kidneys, facial dysmorphism, common mesenterin, rachischisis, sacral vertebral agenesis.
Sources: Literature
Mendeliome v1.233 SPTBN5 Zornitza Stark edited their review of gene: SPTBN5: Added comment: Monoallelic variants:
- Four probands from unrelated families (1x Pakistani and 3x Italian) with de novo heterozygous SPTBN5 variants
- 3x missense variants and 1x LoF variant were reported
- Phenotypes include intellectual disability (mild to severe), aggressive tendencies and variable features such as craniofacial and physical dysmorphisms, autistic behavior, and gastroesophageal reflux; Changed rating: GREEN; Changed publications: 35782384, 32732226, 28007035; Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, SPTBN5-related, Sacral agenesis, congenital anomalies; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.4874 SPTBN5 Zornitza Stark Marked gene: SPTBN5 as ready
Intellectual disability syndromic and non-syndromic v0.4874 SPTBN5 Zornitza Stark Gene: sptbn5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4874 SPTBN5 Zornitza Stark Classified gene: SPTBN5 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4874 SPTBN5 Zornitza Stark Gene: sptbn5 has been classified as Green List (High Evidence).
Incidentalome v0.122 THSD4 Zornitza Stark Tag cardiac tag was added to gene: THSD4.
Incidentalome v0.122 THSD4 Zornitza Stark Deleted their review
Incidentalome v0.122 TGFBR2 Zornitza Stark Marked gene: TGFBR2 as ready
Incidentalome v0.122 TGFBR2 Zornitza Stark Gene: tgfbr2 has been classified as Green List (High Evidence).
Incidentalome v0.122 TGFBR2 Zornitza Stark Phenotypes for gene: TGFBR2 were changed from to Loeys-Dietz syndrome 2 , MIM#610168
Incidentalome v0.121 TGFBR2 Zornitza Stark Publications for gene: TGFBR2 were set to
Incidentalome v0.120 TGFBR2 Zornitza Stark Mode of inheritance for gene: TGFBR2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.119 TGFBR2 Zornitza Stark Tag cardiac tag was added to gene: TGFBR2.
Incidentalome v0.119 TGFBR2 Zornitza Stark reviewed gene: TGFBR2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Loeys-Dietz syndrome 2 , MIM#610168; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.119 TGFBR1 Zornitza Stark Marked gene: TGFBR1 as ready
Incidentalome v0.119 TGFBR1 Zornitza Stark Gene: tgfbr1 has been classified as Green List (High Evidence).
Incidentalome v0.119 TGFBR1 Zornitza Stark Phenotypes for gene: TGFBR1 were changed from to Loeys-Dietz syndrome 1, MIM# 609192
Incidentalome v0.118 TGFBR1 Zornitza Stark Publications for gene: TGFBR1 were set to
Incidentalome v0.117 TGFBR1 Zornitza Stark Mode of inheritance for gene: TGFBR1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.116 TGFBR1 Zornitza Stark Tag cardiac tag was added to gene: TGFBR1.
Incidentalome v0.116 TGFBR1 Zornitza Stark reviewed gene: TGFBR1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Loeys-Dietz syndrome 1, MIM# 609192; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.116 SMAD3 Zornitza Stark Publications for gene: SMAD3 were set to 21217753; 30661052
Incidentalome v0.115 SMAD3 Zornitza Stark Tag cardiac tag was added to gene: SMAD3.
Incidentalome v0.115 MYLK Zornitza Stark Marked gene: MYLK as ready
Incidentalome v0.115 MYLK Zornitza Stark Gene: mylk has been classified as Green List (High Evidence).
Incidentalome v0.115 MYLK Zornitza Stark Phenotypes for gene: MYLK were changed from to Aortic aneurysm, familial thoracic 7, MIM#613780; Megacystis-microcolon-intestinal hypoperistalsis syndrome, MIM#249210
Incidentalome v0.114 MYLK Zornitza Stark Publications for gene: MYLK were set to
Incidentalome v0.113 MYLK Zornitza Stark Mode of inheritance for gene: MYLK was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.112 MYLK Zornitza Stark Tag cardiac tag was added to gene: MYLK.
Incidentalome v0.112 MYLK Zornitza Stark edited their review of gene: MYLK: Changed publications: 28602422
Incidentalome v0.112 MYLK Zornitza Stark edited their review of gene: MYLK: Added comment: Amber for bi-allelic variants and gastrointestinal neuromuscular disease:
PMID: 28602422;
- 3 affecteds from 2 consanguineous families. each family is homozygous for 1x fs and 1x splice (abnormal splicing proven).
- IHC of 1 affected showed no protein expression in intestine and bladder
- For both families, no cardiac problems were reported for the carrier parents.; Changed phenotypes: Aortic aneurysm, familial thoracic 7, MIM#613780, Megacystis-microcolon-intestinal hypoperistalsis syndrome, MIM#249210; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.112 MYH11 Zornitza Stark Marked gene: MYH11 as ready
Incidentalome v0.112 MYH11 Zornitza Stark Gene: myh11 has been classified as Green List (High Evidence).
Incidentalome v0.112 MYH11 Zornitza Stark Tag cardiac tag was added to gene: MYH11.
Incidentalome v0.112 MYH11 Zornitza Stark Phenotypes for gene: MYH11 were changed from to Visceral myopathy 2, MIM# 619350; Megacystis microcolon intestinal hypoperistalsis syndrome, autosomal recessive, MIM#619351; Aortic aneurysm, familial thoracic 4, MIM# 132900
Incidentalome v0.111 MYH11 Zornitza Stark Publications for gene: MYH11 were set to
Incidentalome v0.110 MYH11 Zornitza Stark Mode of inheritance for gene: MYH11 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.109 MYH11 Zornitza Stark reviewed gene: MYH11: Rating: GREEN; Mode of pathogenicity: None; Publications: 31944481; Phenotypes: Visceral myopathy 2, MIM# 619350, Megacystis microcolon intestinal hypoperistalsis syndrome, autosomal recessive, MIM#619351, Aortic aneurysm, familial thoracic 4, MIM# 132900; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.109 HCN4 Zornitza Stark Tag cardiac tag was added to gene: HCN4.
Incidentalome v0.109 HCN4 Zornitza Stark Marked gene: HCN4 as ready
Incidentalome v0.109 HCN4 Zornitza Stark Gene: hcn4 has been classified as Green List (High Evidence).
Incidentalome v0.109 HCN4 Zornitza Stark Phenotypes for gene: HCN4 were changed from to Sick sinus syndrome 2, MIM# 163800; Aortopathy
Incidentalome v0.108 HCN4 Zornitza Stark Publications for gene: HCN4 were set to
Incidentalome v0.107 HCN4 Zornitza Stark Mode of inheritance for gene: HCN4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.106 HCN4 Zornitza Stark reviewed gene: HCN4: Rating: GREEN; Mode of pathogenicity: None; Publications: 12750403, 15123648, 16407510, 17646576, 25145518; Phenotypes: Sick sinus syndrome 2, MIM# 163800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.106 FBN1 Zornitza Stark Marked gene: FBN1 as ready
Incidentalome v0.106 FBN1 Zornitza Stark Gene: fbn1 has been classified as Green List (High Evidence).
Incidentalome v0.106 FBN1 Zornitza Stark Phenotypes for gene: FBN1 were changed from to Acromicric dysplasia (102370); Ectopia lentis, familial (129600); Geleophysic dysplasia 2 (614185); Marfan lipodystrophy syndrome (616914); Marfan syndrome (154700); MASS syndrome (604308); Stiff skin syndrome (184900); Weill-Marchesani syndrome 2, dominant (608328)
Incidentalome v0.105 FBN1 Zornitza Stark Publications for gene: FBN1 were set to
Incidentalome v0.104 FBN1 Zornitza Stark Mode of inheritance for gene: FBN1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.103 FBN1 Zornitza Stark Tag cardiac tag was added to gene: FBN1.
Incidentalome v0.103 COL3A1 Zornitza Stark Marked gene: COL3A1 as ready
Incidentalome v0.103 COL3A1 Zornitza Stark Gene: col3a1 has been classified as Green List (High Evidence).
Incidentalome v0.103 COL3A1 Zornitza Stark Phenotypes for gene: COL3A1 were changed from to Ehlers-Danlos syndrome, vascular type, MIM# 130050; Polymicrogyria with or without vascular-type EDS, MIM# 618343
Incidentalome v0.102 COL3A1 Zornitza Stark Publications for gene: COL3A1 were set to
Incidentalome v0.101 COL3A1 Zornitza Stark Mode of inheritance for gene: COL3A1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.100 COL3A1 Zornitza Stark Tag cardiac tag was added to gene: COL3A1.
Incidentalome v0.100 COL3A1 Zornitza Stark reviewed gene: COL3A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28742248, 19455184, 25205403; Phenotypes: Ehlers-Danlos syndrome, vascular type, MIM# 130050, Polymicrogyria with or without vascular-type EDS, MIM# 618343; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.100 BGN Zornitza Stark Tag cardiac tag was added to gene: BGN.
Incidentalome v0.100 BGN Zornitza Stark Marked gene: BGN as ready
Incidentalome v0.100 BGN Zornitza Stark Gene: bgn has been classified as Green List (High Evidence).
Incidentalome v0.100 BGN Zornitza Stark Phenotypes for gene: BGN were changed from to Meester-Loeys syndrome, MIM# 300989; Spondyloepimetaphyseal dysplasia, X-linked, MIM# 300106
Incidentalome v0.99 BGN Zornitza Stark Publications for gene: BGN were set to
Incidentalome v0.98 BGN Zornitza Stark Mode of inheritance for gene: BGN was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Incidentalome v0.97 BGN Zornitza Stark edited their review of gene: BGN: Changed rating: GREEN; Changed phenotypes: Meester-Loeys syndrome, MIM# 300989, Spondyloepimetaphyseal dysplasia, X-linked, MIM# 300106; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Incidentalome v0.96 ACTA2 Zornitza Stark Marked gene: ACTA2 as ready
Incidentalome v0.96 ACTA2 Zornitza Stark Gene: acta2 has been classified as Green List (High Evidence).
Incidentalome v0.96 ACTA2 Zornitza Stark Tag cardiac tag was added to gene: ACTA2.
Incidentalome v0.96 ACTA2 Zornitza Stark Phenotypes for gene: ACTA2 were changed from to Aortic aneurysm, familial thoracic 6, MIM# 611788; Multisystemic smooth muscle dysfunction syndrome, MIM# 613834
Incidentalome v0.95 ACTA2 Zornitza Stark Publications for gene: ACTA2 were set to
Incidentalome v0.94 ACTA2 Zornitza Stark Mode of inheritance for gene: ACTA2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.93 ACTA2 Zornitza Stark reviewed gene: ACTA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30724374; Phenotypes: Aortic aneurysm, familial thoracic 6, MIM# 611788, Multisystemic smooth muscle dysfunction syndrome, MIM# 613834; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Vascular Malformations SuperPanel v1.13 Zornitza Stark Panel types changed to Superpanel; Royal Melbourne Hospital
Movement Disorders Superpanel v1.204 Zornitza Stark Panel types changed to Superpanel; Royal Melbourne Hospital
Malformations of cortical development_Superpanel v4.31 Zornitza Stark Panel types changed to Superpanel; Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Retinal Disorders Superpanel v6.130 Zornitza Stark Panel types changed to Superpanel; Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Myopathy Superpanel v1.119 Zornitza Stark Panel types changed to Royal Melbourne Hospital; Rare Disease; Victorian Clinical Genetics Services; Superpanel
Intellectual disability syndromic and non-syndromic v0.4873 SPTBN5 Ee Ming Wong gene: SPTBN5 was added
gene: SPTBN5 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SPTBN5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPTBN5 were set to 35782384
Phenotypes for gene: SPTBN5 were set to Neurodevelopmental disorder, MONDO:0700092, SPTBN5-related
Review for gene: SPTBN5 was set to GREEN
gene: SPTBN5 was marked as current diagnostic
Added comment: - Four probands from unrelated families (1x Pakistani and 3x Italian) with de novo heterozygous SPTBN5 variants
- 3x missense variants and 1x LoF variant were reported
- Phenotypes include intellectual disability (mild to severe), aggressive tendencies and variable features such as craniofacial and physical dysmorphisms, autistic behavior, and
gastroesophageal reflux
Sources: Literature
Progressive Neurological Conditions v7.1361 Zornitza Stark Panel types changed to Superpanel; Royal Melbourne Hospital; Rare Disease
Mendeliome v1.233 CPS1 Zornitza Stark Phenotypes for gene: CPS1 were changed from to Carbamoylphosphate synthetase I deficiency MIM#237300
Mendeliome v1.232 CPS1 Zornitza Stark Mode of inheritance for gene: CPS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.231 CPS1 Zornitza Stark reviewed gene: CPS1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Pulmonary hypertension, neonatal, susceptibility to} 615371; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.231 OTULIN Zornitza Stark Phenotypes for gene: OTULIN were changed from Autoinflammation, panniculitis, and dermatosis syndrome, MIM# 617099 to Autoinflammation, panniculitis, and dermatosis syndrome, MIM# 617099; Susceptibility to infection with Staphylococcus aureus; Hereditary predisposition to infections, MONDO:0015979, OTULIN-related
Mendeliome v1.230 OTULIN Zornitza Stark Publications for gene: OTULIN were set to 27523608; 27559085
Mendeliome v1.229 OTULIN Zornitza Stark Mode of inheritance for gene: OTULIN was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.228 OTULIN Zornitza Stark changed review comment from: Autoinflammatory disorder presenting in the newborn period with recurrent fever, erythematous rash with painful nodules, painful joints, diarrhoea and lipodystrophy.; to: Bi-allelic variants: Autoinflammatory disorder presenting in the newborn period with recurrent fever, erythematous rash with painful nodules, painful joints, diarrhoea and lipodystrophy.
Mendeliome v1.228 OTULIN Zornitza Stark edited their review of gene: OTULIN: Added comment: PMID 35587511: Multiple individuals reported with haploinsufficiency of OTULIN and severe staphylococcal disease, with life-threatening skin or pulmonary necrosis. Functional data.; Changed publications: 27523608, 27559085, 35587511; Changed phenotypes: Autoinflammation, panniculitis, and dermatosis syndrome, MIM# 617099, Susceptibility to infection with Staphylococcus aureus, Hereditary predisposition to infections, MONDO:0015979, OTULIN-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phagocyte Defects v1.8 OTULIN Zornitza Stark Marked gene: OTULIN as ready
Phagocyte Defects v1.8 OTULIN Zornitza Stark Gene: otulin has been classified as Green List (High Evidence).
Phagocyte Defects v1.8 OTULIN Zornitza Stark Classified gene: OTULIN as Green List (high evidence)
Phagocyte Defects v1.8 OTULIN Zornitza Stark Gene: otulin has been classified as Green List (High Evidence).
Phagocyte Defects v1.7 OTULIN Zornitza Stark gene: OTULIN was added
gene: OTULIN was added to Phagocyte Defects. Sources: Literature
Mode of inheritance for gene: OTULIN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: OTULIN were set to 35587511
Phenotypes for gene: OTULIN were set to Susceptibility to infection with Staphylococcus aureus; Hereditary predisposition to infections, MONDO:0015979, OTULIN-related
Review for gene: OTULIN was set to GREEN
Added comment: Multiple individuals reported with haploinsufficiency of OTULIN and severe staphylococcal disease, with life-threatening skin or pulmonary necrosis. Functional data.

Note bi-allelic variants case early-onset autoinflammatory condition called OTULIN-related autoinflammatory syndrome (ORAS).
Sources: Literature
Mendeliome v1.228 NOX1 Zornitza Stark gene: NOX1 was added
gene: NOX1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NOX1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: NOX1 were set to 29091079; 32064493
Phenotypes for gene: NOX1 were set to Inflammatory bowel disease, MONDO:0005265, NOX1-related
Review for gene: NOX1 was set to AMBER
Added comment: 8 IBD patients with early onset of IBD with progressive and severe colonic disease, refractory to conventional therapy and functional studies suggesting variant-dependent loss of NOX1-mediated superoxide generation. However, high frequency of nonsynonymous mutations in NOX1 suggests that NOX1 is not a highly penetrant Mendelian disorder and that other genetic modifiers or environmental factors may contribute to disease pathogenesis.

The variant reported in PMID 32064493 is present in 6 hets in gnomad.
Sources: Literature
Inflammatory bowel disease v0.84 NOX1 Zornitza Stark Marked gene: NOX1 as ready
Inflammatory bowel disease v0.84 NOX1 Zornitza Stark Gene: nox1 has been classified as Amber List (Moderate Evidence).
Inflammatory bowel disease v0.84 NOX1 Zornitza Stark Phenotypes for gene: NOX1 were changed from Inflammatory bowel disease to Inflammatory bowel disease, MONDO:0005265, NOX1-related
Inflammatory bowel disease v0.83 NOX1 Zornitza Stark edited their review of gene: NOX1: Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Inflammatory bowel disease v0.83 NOX1 Zornitza Stark Classified gene: NOX1 as Amber List (moderate evidence)
Inflammatory bowel disease v0.83 NOX1 Zornitza Stark Gene: nox1 has been classified as Amber List (Moderate Evidence).
Inflammatory bowel disease v0.83 NOX1 Zornitza Stark Classified gene: NOX1 as Amber List (moderate evidence)
Inflammatory bowel disease v0.83 NOX1 Zornitza Stark Gene: nox1 has been classified as Amber List (Moderate Evidence).
Inflammatory bowel disease v0.82 NOX1 Zornitza Stark reviewed gene: NOX1: Rating: AMBER; Mode of pathogenicity: None; Publications: 32064493; Phenotypes: Inflammatory bowel disease, MONDO:0005265, NOX1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.227 BICD2 Zornitza Stark Phenotypes for gene: BICD2 were changed from Spinal muscular atrophy, lower extremity-predominant, 2A, autosomal dominant, MIM# 615290; MONDO:0014121; Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, MIM# 618291 to Neurodevelopmental disorder (MONDO#0700092), BICD2-related; Spinal muscular atrophy, lower extremity-predominant, 2A, autosomal dominant, MIM# 615290; MONDO:0014121; Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, MIM# 618291
Mendeliome v1.226 BICD2 Zornitza Stark Publications for gene: BICD2 were set to 23664116; 23664119; 23664120; 27751653; 28635954; 30054298; 29528393
Mendeliome v1.225 BICD2 Zornitza Stark Mode of inheritance for gene: BICD2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4873 PSMC1 Zornitza Stark Marked gene: PSMC1 as ready
Intellectual disability syndromic and non-syndromic v0.4873 PSMC1 Zornitza Stark Gene: psmc1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.4873 PSMC1 Zornitza Stark Classified gene: PSMC1 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.4873 PSMC1 Zornitza Stark Gene: psmc1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.4872 PSMC1 Hazel Phillimore gene: PSMC1 was added
gene: PSMC1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PSMC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMC1 were set to PMID: 35861243
Phenotypes for gene: PSMC1 were set to spastic paraplegia; severe developmental delay; severe intellectual disability; hearing loss; micropenis; undescended testes; Syndromic disease MONDO:0002254, PSMC1-related
Review for gene: PSMC1 was set to RED
Added comment: Homozygosity mapping on one large consanguineous Bedouin kindred showed three affected children (out of the ten) to be homozygous for NM_002802.3:c.983T>C; p.(Ile328Thr).

Drosophila rescue experiments were carried out. Transgenic studies using drosophila with the silenced ortholog Rpt2 gene were rescued by the human wild-type PSMC1.

Three of the ten offspring of healthy consanguineous parents of Bedouin Israeli ancestry were affected with a similar phenotype of failure to thrive, developmental delay and severe intellectual disability, spastic tetraplegia with central hypotonia, chorea, as well as hearing loss. None of the three achieved verbal communication or ambulation (sitting / standing) at any age. They had mild dysmorphism of borderline dolichocephaly and microcephaly, prominent bushy eyebrows, flat midface, long nasal bridge and micrognathia. All three had micropenis with undescended testes. One of the affected (as a toddler) underwent thorough endocrinological analysis: testosterone and gonadotropin levels were low.
Sources: Literature
Anophthalmia_Microphthalmia_Coloboma v1.28 KIF15 Alison Yeung Marked gene: KIF15 as ready
Anophthalmia_Microphthalmia_Coloboma v1.28 KIF15 Alison Yeung Gene: kif15 has been classified as Red List (Low Evidence).
Anophthalmia_Microphthalmia_Coloboma v1.28 KIF15 Alison Yeung Phenotypes for gene: KIF15 were changed from ?Braddock-Carey syndrome 2 - MIM#619981 to Braddock-Carey syndrome 2 - MIM#619981
Anophthalmia_Microphthalmia_Coloboma v1.27 KIF15 Alison Yeung Classified gene: KIF15 as Red List (low evidence)
Anophthalmia_Microphthalmia_Coloboma v1.27 KIF15 Alison Yeung Gene: kif15 has been classified as Red List (Low Evidence).
Bleeding and Platelet Disorders v1.15 KIF15 Alison Yeung Marked gene: KIF15 as ready
Bleeding and Platelet Disorders v1.15 KIF15 Alison Yeung Gene: kif15 has been classified as Red List (Low Evidence).
Bleeding and Platelet Disorders v1.15 KIF15 Alison Yeung Phenotypes for gene: KIF15 were changed from ?Braddock-Carey syndrome 2 - MIM#619981 to Braddock-Carey syndrome 2 - MIM#619981
Bleeding and Platelet Disorders v1.14 KIF15 Alison Yeung Classified gene: KIF15 as Red List (low evidence)
Bleeding and Platelet Disorders v1.14 KIF15 Alison Yeung Gene: kif15 has been classified as Red List (Low Evidence).
Microcephaly v1.147 SARS Zornitza Stark Classified gene: SARS as Green List (high evidence)
Microcephaly v1.147 SARS Zornitza Stark Gene: sars has been classified as Green List (High Evidence).
Microcephaly v1.146 KIF15 Alison Yeung Marked gene: KIF15 as ready
Microcephaly v1.146 KIF15 Alison Yeung Gene: kif15 has been classified as Red List (Low Evidence).
Microcephaly v1.146 KIF15 Alison Yeung Phenotypes for gene: KIF15 were changed from ?Braddock-Carey syndrome 2 - MIM#619981 to Braddock-Carey syndrome 2 - MIM#619981
Microcephaly v1.145 KIF15 Alison Yeung Classified gene: KIF15 as Red List (low evidence)
Microcephaly v1.145 KIF15 Alison Yeung Gene: kif15 has been classified as Red List (Low Evidence).
Pierre Robin Sequence v0.43 KIF15 Alison Yeung Marked gene: KIF15 as ready
Pierre Robin Sequence v0.43 KIF15 Alison Yeung Gene: kif15 has been classified as Red List (Low Evidence).
Pierre Robin Sequence v0.43 KIF15 Alison Yeung Phenotypes for gene: KIF15 were changed from ?Braddock-Carey syndrome 2 - MIM#619981 to Braddock-Carey syndrome 2 - MIM#619981
Pierre Robin Sequence v0.42 KIF15 Alison Yeung Classified gene: KIF15 as Red List (low evidence)
Pierre Robin Sequence v0.42 KIF15 Alison Yeung Gene: kif15 has been classified as Red List (Low Evidence).
Mendeliome v1.224 KIF15 Alison Yeung Phenotypes for gene: KIF15 were changed from ?Braddock-Carey syndrome 2 - MIM#619981 to Braddock-Carey syndrome 2 - MIM#619981
Mendeliome v1.223 KIF15 Alison Yeung Marked gene: KIF15 as ready
Mendeliome v1.223 KIF15 Alison Yeung Gene: kif15 has been classified as Red List (Low Evidence).
Mendeliome v1.223 KIF15 Alison Yeung Classified gene: KIF15 as Red List (low evidence)
Mendeliome v1.223 KIF15 Alison Yeung Gene: kif15 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.4872 SARS Ain Roesley Phenotypes for gene: SARS were changed from Intellectual disability to neurodevelopmental disorder MONDO#070009, SARS1-related
Intellectual disability syndromic and non-syndromic v0.4872 SARS Ain Roesley Publications for gene: SARS were set to 28236339; 34570399
Microcephaly v1.142 SARS Ain Roesley gene: SARS was added
gene: SARS was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: SARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SARS were set to 35790048; 28236339; 34570399
Phenotypes for gene: SARS were set to neurodevelopmental disorder MONDO#070009, SARS1-related
Review for gene: SARS was set to GREEN
gene: SARS was marked as current diagnostic
Added comment: Total of 3 families
Sources: Literature
Microcephaly v1.142 SARS Ain Roesley Marked gene: SARS as ready
Microcephaly v1.142 SARS Ain Roesley Gene: sars has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.4872 SARS Ain Roesley Classified gene: SARS as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4872 SARS Ain Roesley Gene: sars has been classified as Green List (High Evidence).
Microcephaly v1.142 SARS Ain Roesley gene: SARS was added
gene: SARS was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: SARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SARS were set to 35790048; 28236339; 34570399
Phenotypes for gene: SARS were set to neurodevelopmental disorder MONDO#070009, SARS1-related
Review for gene: SARS was set to GREEN
gene: SARS was marked as current diagnostic
Added comment: Total of 3 families
Sources: Literature
Mendeliome v1.222 SARS Ain Roesley Publications for gene: SARS were set to 28236339; 34570399
Mendeliome v1.222 SARS Ain Roesley Classified gene: SARS as Green List (high evidence)
Mendeliome v1.222 SARS Ain Roesley Gene: sars has been classified as Green List (High Evidence).
Mendeliome v1.222 SARS Ain Roesley Phenotypes for gene: SARS were changed from Intellectual disability to neurodevelopmental disorder MONDO#070009, SARS1-related
Leukodystrophy v0.274 WARS Seb Lunke Marked gene: WARS as ready
Leukodystrophy v0.274 WARS Seb Lunke Gene: wars has been classified as Green List (High Evidence).
Leukodystrophy v0.274 WARS Seb Lunke Classified gene: WARS as Green List (high evidence)
Leukodystrophy v0.274 WARS Seb Lunke Gene: wars has been classified as Green List (High Evidence).
Mendeliome v1.221 PSMC1 Zornitza Stark Marked gene: PSMC1 as ready
Mendeliome v1.221 PSMC1 Zornitza Stark Gene: psmc1 has been classified as Red List (Low Evidence).
Mendeliome v1.221 PSMC1 Zornitza Stark Phenotypes for gene: PSMC1 were changed from spastic paraplegia; severe developmental delay; severe intellectual disability; hearing loss; micropenis; undescended testes to 35861243; spastic paraplegia; severe developmental delay; severe intellectual disability; hearing loss; micropenis; undescended testes
Mendeliome v1.220 SARS Ain Roesley reviewed gene: SARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 35790048; Phenotypes: neurodevelopmental disorder MONDO#070009, SARS1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.4871 SARS Ain Roesley reviewed gene: SARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 35790048; Phenotypes: neurodevelopmental disorder MONDO#070009, SARS1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v1.220 PSMC1 Zornitza Stark Mode of pathogenicity for gene: PSMC1 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 None
Mendeliome v1.219 PSMC1 Zornitza Stark Classified gene: PSMC1 as Red List (low evidence)
Mendeliome v1.219 PSMC1 Zornitza Stark Gene: psmc1 has been classified as Red List (Low Evidence).
Mendeliome v1.218 PSMC1 Zornitza Stark edited their review of gene: PSMC1: Changed phenotypes: Syndromic disease MONDO:0002254, PSMC1-related
Mendeliome v1.218 PSMC1 Zornitza Stark commented on gene: PSMC1: Single family only, homozygous missense variant.
Mendeliome v1.218 PSMC1 Zornitza Stark reviewed gene: PSMC1: Rating: RED; Mode of pathogenicity: None; Publications: 35861243; Phenotypes: Syndromic disease MONDO:0002254, PSMC1; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Lissencephaly and Band Heterotopia v1.10 BICD2 Zornitza Stark Marked gene: BICD2 as ready
Lissencephaly and Band Heterotopia v1.10 BICD2 Zornitza Stark Gene: bicd2 has been classified as Red List (Low Evidence).
Lissencephaly and Band Heterotopia v1.10 BICD2 Zornitza Stark Classified gene: BICD2 as Red List (low evidence)
Lissencephaly and Band Heterotopia v1.10 BICD2 Zornitza Stark Gene: bicd2 has been classified as Red List (Low Evidence).
Mendeliome v1.218 WARS Seb Lunke Publications for gene: WARS were set to PMID: 28369220; 31321409; 31069783.
Mendeliome v1.217 DOHH Zornitza Stark Marked gene: DOHH as ready
Mendeliome v1.217 DOHH Zornitza Stark Gene: dohh has been classified as Green List (High Evidence).
Mendeliome v1.217 WARS Seb Lunke Phenotypes for gene: WARS were changed from Neuronopathy, distal hereditary motor, type IX (OMIM:617721); juvenile to adult onset (15-23 years); distal wasting; distal weakness; length-dependent motor axonal degeneration to Neuronopathy, distal hereditary motor, type IX (OMIM:617721); juvenile to adult onset (15-23 years); Neurodevelopmental disorder (MONDO:0700092), WARS-related
Leukodystrophy v0.273 WARS Anna Ritchie gene: WARS was added
gene: WARS was added to Leukodystrophy - paediatric. Sources: Literature
Mode of inheritance for gene: WARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WARS were set to PMID: 35815345 PMID: 35790048
Phenotypes for gene: WARS were set to Neurodevelopmental disorder (MONDO:0700092), WARS-related
Review for gene: WARS was set to GREEN
Added comment: Seven affected individuals from four families with biallelic variants, showing varying severities of developmental delay, intellectual disability and microcephaly. Hearing impairment and, as well as brain anomalies, skeletal system, movement/gait, and behaviour were variable features.
Sources: Literature
Anophthalmia_Microphthalmia_Coloboma v1.26 KIF15 Krithika Murali gene: KIF15 was added
gene: KIF15 was added to Anophthalmia_Microphthalmia_Coloboma. Sources: Literature
Mode of inheritance for gene: KIF15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF15 were set to 28150392
Phenotypes for gene: KIF15 were set to ?Braddock-Carey syndrome 2 - MIM#619981
Review for gene: KIF15 was set to AMBER
Added comment: PMID 28150392 Sleiman et al 2017 report one individual with homozygous R501* variant (NMD-predicted) from a consanguineous family. The child had thrombocytopenia, PRS, microcephaly -3SD by age 6, dysmorphic facies, bilateral external auditory canal atresia and deafness, microphthalmia, clinodactyly, short stature. Variant absent from gnomAD. Parents confirmed to be carriers and unaffected siblings were carriers/homozygous wild-type.

No other SNVs reported in ClinVar. Variant is absent from gnomAD. Authors note phenotypic similarities with Braddock-Carey syndrome (21q22 contiguous deletion also involving RUNX1).
Sources: Literature
Mendeliome v1.216 DOHH Zornitza Stark Classified gene: DOHH as Green List (high evidence)
Mendeliome v1.216 DOHH Zornitza Stark Gene: dohh has been classified as Green List (High Evidence).
Mendeliome v1.215 WARS Seb Lunke Mode of inheritance for gene: WARS was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.214 PPFIBP1 Zornitza Stark Publications for gene: PPFIBP1 were set to https://www.medrxiv.org/content/10.1101/2022.04.04.22273309v1
Intellectual disability syndromic and non-syndromic v0.4871 WARS Seb Lunke Marked gene: WARS as ready
Intellectual disability syndromic and non-syndromic v0.4871 WARS Seb Lunke Gene: wars has been classified as Green List (High Evidence).
Microcephaly v1.141 KIF15 Krithika Murali gene: KIF15 was added
gene: KIF15 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: KIF15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF15 were set to 28150392
Phenotypes for gene: KIF15 were set to ?Braddock-Carey syndrome 2 - MIM#619981
Review for gene: KIF15 was set to AMBER
Added comment: PMID 28150392 Sleiman et al 2017 report one individual with homozygous R501* variant (NMD-predicted) from a consanguineous family. The child had thrombocytopenia, PRS, microcephaly -3SD by age 6, dysmorphic facies, bilateral external auditory canal atresia and deafness, microphthalmia, clinodactyly, short stature. Variant absent from gnomAD. Parents confirmed to be carriers and unaffected siblings were carriers/homozygous wild-type.

No other SNVs reported in ClinVar. Variant is absent from gnomAD. Authors note phenotypic similarities with Braddock-Carey syndrome (21q22 contiguous deletion also involving RUNX1).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4871 WARS Seb Lunke Classified gene: WARS as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4871 WARS Seb Lunke Gene: wars has been classified as Green List (High Evidence).
Motor Neurone Disease v0.138 RNF13 Alison Yeung Marked gene: RNF13 as ready
Motor Neurone Disease v0.138 RNF13 Alison Yeung Gene: rnf13 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.213 SLITRK2 Zornitza Stark Marked gene: SLITRK2 as ready
Mendeliome v1.213 SLITRK2 Zornitza Stark Gene: slitrk2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1642 SLITRK2 Zornitza Stark Marked gene: SLITRK2 as ready
Genetic Epilepsy v0.1642 SLITRK2 Zornitza Stark Gene: slitrk2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1642 SLITRK2 Zornitza Stark Classified gene: SLITRK2 as Green List (high evidence)
Genetic Epilepsy v0.1642 SLITRK2 Zornitza Stark Gene: slitrk2 has been classified as Green List (High Evidence).
Mendeliome v1.213 BICD2 Lucy Spencer reviewed gene: BICD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 35896821; Phenotypes: Neurodevelopmental disorder (MONDO#0700092), BICD2-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Motor Neurone Disease v0.138 RNF13 Alison Yeung Classified gene: RNF13 as Amber List (moderate evidence)
Motor Neurone Disease v0.138 RNF13 Alison Yeung Gene: rnf13 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.213 KIF15 Krithika Murali reviewed gene: KIF15: Rating: AMBER; Mode of pathogenicity: None; Publications: 28150392; Phenotypes: ?Braddock-Carey syndrome 2 - MIM#619981; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.213 WARS Anna Ritchie reviewed gene: WARS: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35815345, PMID: 35790048; Phenotypes: Neurodevelopmental disorder (MONDO:0700092), WARS-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Motor Neurone Disease v0.138 RNF13 Alison Yeung Classified gene: RNF13 as Amber List (moderate evidence)
Motor Neurone Disease v0.138 RNF13 Alison Yeung Gene: rnf13 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.213 SLITRK2 Zornitza Stark Classified gene: SLITRK2 as Green List (high evidence)
Mendeliome v1.213 SLITRK2 Zornitza Stark Gene: slitrk2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1641 RAC3 Zornitza Stark Marked gene: RAC3 as ready
Genetic Epilepsy v0.1641 RAC3 Zornitza Stark Gene: rac3 has been classified as Green List (High Evidence).
Mendeliome v1.212 KIF15 Krithika Murali Deleted their review
Congenital Heart Defect v0.259 DOHH Zornitza Stark Marked gene: DOHH as ready
Congenital Heart Defect v0.259 DOHH Zornitza Stark Gene: dohh has been classified as Green List (High Evidence).
Congenital Heart Defect v0.259 DOHH Zornitza Stark Classified gene: DOHH as Green List (high evidence)
Congenital Heart Defect v0.259 DOHH Zornitza Stark Gene: dohh has been classified as Green List (High Evidence).
Microcephaly v1.141 WARS Seb Lunke Marked gene: WARS as ready
Microcephaly v1.141 WARS Seb Lunke Gene: wars has been classified as Green List (High Evidence).
Mendeliome v1.212 PSMC1 Hazel Phillimore gene: PSMC1 was added
gene: PSMC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PSMC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMC1 were set to PMID: 35861243
Phenotypes for gene: PSMC1 were set to spastic paraplegia; severe developmental delay; severe intellectual disability; hearing loss; micropenis; undescended testes
Mode of pathogenicity for gene: PSMC1 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: PSMC1 was set to AMBER
Added comment: Homozygosity mapping on one large consanguineous Bedouin kindred showed three affected children (out of the ten) to be homozygous for NM_002802.3:c.983T>C; p.(Ile328Thr).

Drosophila rescue experiments were carried out. Transgenic studies using drosophila with the silenced ortholog Rpt2 gene were rescued by the human wild-type PSMC1.

Three of the ten offspring of healthy consanguineous parents of Bedouin Israeli ancestry were affected with a similar phenotype of failure to thrive, developmental delay and severe intellectual disability, spastic tetraplegia with central hypotonia, chorea, as well as hearing loss. None of the three achieved verbal communication or ambulation (sitting / standing) at any age. They had mild dysmorphism of borderline dolichocephaly and microcephaly, prominent bushy eyebrows, flat midface, long nasal bridge and micrognathia. All three had micropenis with undescended testes. One of the affected (as a toddler) underwent thorough endocrinological analysis: testosterone and gonadotropin levels were low.
Sources: Literature
Mendeliome v1.212 KIF15 Krithika Murali gene: KIF15 was added
gene: KIF15 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KIF15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF15 were set to 28150392
Phenotypes for gene: KIF15 were set to ?Braddock-Carey syndrome 2 - MIM#619981
Review for gene: KIF15 was set to GREEN
Added comment: PMID 28150392 Sleiman et al 2017 report one individual with homozygous R501* variant (NMD-predicted) from a consanguineous family. The child had thrombocytopenia, PRS, microcephaly -3SD by age 6, dysmorphic facies, bilateral external auditory canal atresia and deafness, microphthalmia, clinodactyly, short stature. Variant absent from gnomAD. Parents confirmed to be carriers and unaffected siblings were carriers/homozygous wild-type.

No other SNVs reported in ClinVar. Variant is absent from gnomAD. Authors note phenotypic similarities with Braddock-Carey syndrome (21q22 contiguous deletion also involving RUNX1).
Sources: Literature
Microcephaly v1.141 PPFIBP1 Zornitza Stark Publications for gene: PPFIBP1 were set to https://www.medrxiv.org/content/10.1101/2022.04.04.22273309v1
Intellectual disability syndromic and non-syndromic v0.4870 BICD2 Lucy Spencer reviewed gene: BICD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 35896821; Phenotypes: Neurodevelopmental disorder (MONDO#0700092), BICD2-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Pierre Robin Sequence v0.41 KIF15 Krithika Murali gene: KIF15 was added
gene: KIF15 was added to Pierre Robin Sequence. Sources: Literature
Mode of inheritance for gene: KIF15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF15 were set to 28150392
Phenotypes for gene: KIF15 were set to ?Braddock-Carey syndrome 2 - MIM#619981
Review for gene: KIF15 was set to AMBER
Added comment: PMID 28150392 Sleiman et al 2017 report one individual with homozygous R501* variant (NMD-predicted) from a consanguineous family. The child had thrombocytopenia, PRS, microcephaly -3SD by age 6, dysmorphic facies, bilateral external auditory canal atresia and deafness, microphthalmia, clinodactyly, short stature. Variant absent from gnomAD. Parents confirmed to be carriers and unaffected siblings were carriers/homozygous wild-type.

No other SNVs reported in ClinVar. Variant is absent from gnomAD. Authors note phenotypic similarities with Braddock-Carey syndrome (21q22 contiguous deletion also involving RUNX1).
Sources: Literature
Microcephaly v1.140 DOHH Zornitza Stark Marked gene: DOHH as ready
Microcephaly v1.140 DOHH Zornitza Stark Gene: dohh has been classified as Green List (High Evidence).
Microcephaly v1.140 DOHH Zornitza Stark Classified gene: DOHH as Green List (high evidence)
Microcephaly v1.140 DOHH Zornitza Stark Gene: dohh has been classified as Green List (High Evidence).
Motor Neurone Disease v0.137 RNF13 Melanie Marty changed review comment from: 3 x affected siblings with hom canonical splice variant. 2 x unaffected siblings het for the variant. RT-PCR showed expression of two mis-spliced forms of RNF13 mRNA (1 with a PTC and the other with an inframe del). Functional studies on patients cells showed an absence of protein.
Sources: Literature; to: 3 x affected siblings with hom canonical splice variant. 2 x unaffected siblings het for the variant. RT-PCR showed expression of two mis-spliced forms of RNF13 mRNA (1 with a PTC and the other with an inframe del). Functional studies showed an absence of protein.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4870 PPFIBP1 Zornitza Stark Publications for gene: PPFIBP1 were set to https://www.medrxiv.org/content/10.1101/2022.04.04.22273309v1
Bleeding and Platelet Disorders v1.13 KIF15 Krithika Murali gene: KIF15 was added
gene: KIF15 was added to Bleeding and Platelet Disorders. Sources: Literature
Mode of inheritance for gene: KIF15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF15 were set to 28150392
Phenotypes for gene: KIF15 were set to ?Braddock-Carey syndrome 2 - MIM#619981
Review for gene: KIF15 was set to AMBER
Added comment: PMID 28150392 Sleiman et al 2017 report one individual with homozygous R501* variant (NMD-predicted) from a consanguineous family. The child had thrombocytopenia, PRS, microcephaly <3 SD by age 6, dysmorphic facies, bilateral external auditory canal atresia and deafness, microphthalmia, clinodactyly, short stature. Variant absent from gnomAD. Parents confirmed to be carriers and unaffected siblings were carriers/homozygous wild-type.

No other SNVs reported in ClinVar. Variant is absent from gnomAD. Authors note phenotypic similarities with Braddock-Carey syndrome (21q22 contiguous deletion also involving RUNX1).
Sources: Literature
Microcephaly v1.139 WARS Seb Lunke Classified gene: WARS as Green List (high evidence)
Microcephaly v1.139 WARS Seb Lunke Gene: wars has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4869 C18orf32 Alison Yeung Marked gene: C18orf32 as ready
Intellectual disability syndromic and non-syndromic v0.4869 C18orf32 Alison Yeung Gene: c18orf32 has been classified as Red List (Low Evidence).
Congenital nystagmus v1.12 DOHH Zornitza Stark Marked gene: DOHH as ready
Congenital nystagmus v1.12 DOHH Zornitza Stark Gene: dohh has been classified as Green List (High Evidence).
Congenital nystagmus v1.12 DOHH Zornitza Stark Classified gene: DOHH as Green List (high evidence)
Congenital nystagmus v1.12 DOHH Zornitza Stark Gene: dohh has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4869 C18orf32 Alison Yeung Classified gene: C18orf32 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.4869 C18orf32 Alison Yeung Gene: c18orf32 has been classified as Red List (Low Evidence).
Mendeliome v1.212 BMP3 Seb Lunke Marked gene: BMP3 as ready
Mendeliome v1.212 BMP3 Seb Lunke Gene: bmp3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.212 BMP3 Seb Lunke Classified gene: BMP3 as Amber List (moderate evidence)
Mendeliome v1.212 BMP3 Seb Lunke Gene: bmp3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.211 BMP3 Seb Lunke gene: BMP3 was added
gene: BMP3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BMP3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BMP3 were set to 35089417
Phenotypes for gene: BMP3 were set to coloboma, MONDO:0001476; microphthalmia, MONDO:0021129
Review for gene: BMP3 was set to AMBER
Added comment: Single missense variant identified segregating with disease following WES screen in a family with coloboma and/or microphthalmia in BMP3. Two additional unrelated patients identified with different missense in BMP3. Pathogenicity however largely on in-silicos, with one of the 3 missense having 29 hets in gnomAD. Additional functional work in bmp3 -/- zebra fish and some supporting evidence but not conclusive
Sources: Literature
Cerebellar and Pontocerebellar Hypoplasia v1.56 BICD2 Zornitza Stark Marked gene: BICD2 as ready
Cerebellar and Pontocerebellar Hypoplasia v1.56 BICD2 Zornitza Stark Gene: bicd2 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v1.56 BICD2 Zornitza Stark Classified gene: BICD2 as Green List (high evidence)
Cerebellar and Pontocerebellar Hypoplasia v1.56 BICD2 Zornitza Stark Gene: bicd2 has been classified as Green List (High Evidence).
Mendeliome v1.210 C18orf32 Alison Yeung Marked gene: C18orf32 as ready
Mendeliome v1.210 C18orf32 Alison Yeung Gene: c18orf32 has been classified as Red List (Low Evidence).
Mendeliome v1.210 C18orf32 Alison Yeung Classified gene: C18orf32 as Red List (low evidence)
Mendeliome v1.210 C18orf32 Alison Yeung Gene: c18orf32 has been classified as Red List (Low Evidence).
Fetal anomalies v1.52 BMP3 Seb Lunke Marked gene: BMP3 as ready
Fetal anomalies v1.52 BMP3 Seb Lunke Gene: bmp3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.52 BMP3 Seb Lunke Classified gene: BMP3 as Amber List (moderate evidence)
Fetal anomalies v1.52 BMP3 Seb Lunke Gene: bmp3 has been classified as Amber List (Moderate Evidence).
Renal Macrocystic Disease v0.52 ALG5 Zornitza Stark Marked gene: ALG5 as ready
Renal Macrocystic Disease v0.52 ALG5 Zornitza Stark Gene: alg5 has been classified as Green List (High Evidence).
Mendeliome v1.209 ALG5 Zornitza Stark Marked gene: ALG5 as ready
Mendeliome v1.209 ALG5 Zornitza Stark Gene: alg5 has been classified as Green List (High Evidence).
Motor Neurone Disease v0.137 RNF13 Melanie Marty gene: RNF13 was added
gene: RNF13 was added to Motor Neurone Disease. Sources: Literature
Mode of inheritance for gene: RNF13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNF13 were set to PMID: 35879052
Phenotypes for gene: RNF13 were set to Amyotrophic lateral sclerosis
Review for gene: RNF13 was set to AMBER
Added comment: 3 x affected siblings with hom canonical splice variant. 2 x unaffected siblings het for the variant. RT-PCR showed expression of two mis-spliced forms of RNF13 mRNA (1 with a PTC and the other with an inframe del). Functional studies on patients cells showed an absence of protein.
Sources: Literature
Fetal anomalies v1.51 BMP3 Seb Lunke gene: BMP3 was added
gene: BMP3 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: BMP3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BMP3 were set to 35089417
Phenotypes for gene: BMP3 were set to coloboma, MONDO:0001476; microphthalmia, MONDO:0021129
Added comment: Single missense variant identified segregating with disease following WES screen in a family with coloboma and/or microphthalmia in BMP3. Two additional unrelated patients identified with different missense in BMP3. Pathogenicity however largely on in-silicos, with one of the 3 missense having 29 hets in gnomAD. Additional functional work in bmp3 -/- zebra fish and some supporting evidence but not conclusive.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4868 C18orf32 Naomi Baker gene: C18orf32 was added
gene: C18orf32 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: C18orf32 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C18orf32 were set to PMID:35107634
Phenotypes for gene: C18orf32 were set to Neurodevelopmental disorder (MONDO:0700092), C18orf32-related
Review for gene: C18orf32 was set to RED
Added comment: Two siblings reported as affected, although sequencing only performed in one sibling, with homozygous loss-of-function variant identified. Clinical presentation included developmental delay, recurrent lower respiratory tract infections, sparse rough hair, roving eye movements, hypotonia, bilateral ankle contractures and inverted nipples.
Sources: Literature
Mendeliome v1.209 ALG5 Zornitza Stark Classified gene: ALG5 as Green List (high evidence)
Mendeliome v1.209 ALG5 Zornitza Stark Gene: alg5 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.52 ALG5 Zornitza Stark Phenotypes for gene: ALG5 were changed from Multiple small kidney cysts, progressive interstitial fibrosis, and kidney function decline to Cystic renal disease MONDO:0002473, ALG5-related; Multiple small kidney cysts, progressive interstitial fibrosis, and kidney function decline
Mendeliome v1.208 ALG5 Chern Lim edited their review of gene: ALG5: Changed phenotypes: Cystic renal disease MONDO:0002473, ALG5-related, Multiple small kidney cysts, progressive interstitial fibrosis, and kidney function decline, few or no liver cysts.
Anophthalmia_Microphthalmia_Coloboma v1.26 BMP3 Zornitza Stark Marked gene: BMP3 as ready
Anophthalmia_Microphthalmia_Coloboma v1.26 BMP3 Zornitza Stark Gene: bmp3 has been classified as Amber List (Moderate Evidence).
Anophthalmia_Microphthalmia_Coloboma v1.26 BMP3 Seb Lunke Marked gene: BMP3 as ready
Anophthalmia_Microphthalmia_Coloboma v1.26 BMP3 Seb Lunke Gene: bmp3 has been classified as Amber List (Moderate Evidence).
Anophthalmia_Microphthalmia_Coloboma v1.26 BMP3 Zornitza Stark Classified gene: BMP3 as Amber List (moderate evidence)
Anophthalmia_Microphthalmia_Coloboma v1.26 BMP3 Zornitza Stark Gene: bmp3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.208 ALG5 Chern Lim gene: ALG5 was added
gene: ALG5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ALG5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ALG5 were set to 35896117
Phenotypes for gene: ALG5 were set to Cystic renal disease MONDO:0002473, ALG5-related
Review for gene: ALG5 was set to GREEN
gene: ALG5 was marked as current diagnostic
Added comment: PMID:35896117:
- Five unrelated families, including 23 affected individuals with non-enlarged cystic kidneys and few or no liver cysts, 8 of them reached end-stage kidney disease from 62 to 91 years of age. Variant confirmed in all but one individual.
- Various variant types: frameshift, nonsense, two missense, splice.
- Functional studies showed haploinsufficiency is the disease mechanism.
Sources: Literature
Genetic Epilepsy v0.1641 RAC3 Zornitza Stark Classified gene: RAC3 as Green List (high evidence)
Genetic Epilepsy v0.1641 RAC3 Zornitza Stark Gene: rac3 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v1.55 BICD2 Lucy Spencer changed review comment from: Child with developmental delay, microcephaly, dysmorphic facial features, optic atrophy, lissencephaly, hypogenesis of the corpus callosum and cerebellar hypoplasia. Also short stature and underweight. Found to have a homozygous NMD predicted stop gain variant (consanguineous parents). This study reviewed previous patients and cerebellar hypoplasia seen in 3 other patients, and hypogenesis of the corpus callosum seen in 5 others but these individuals all had only 1 heterozygous variant, mostly missense.
Sources: Literature; to: Child with developmental delay, microcephaly, dysmorphic facial features, optic atrophy, lissencephaly, hypogenesis of the corpus callosum and cerebellar hypoplasia. Also short stature and underweight. Found to have a homozygous NMD predicted stop gain variant (consanguineous parents). This study reviewed previous patients and cerebellar hypoplasia seen in 3 other patients, and hypogenesis of the corpus callosum seen in 5 others but these individuals all had only 1 heterozygous variant, mostly missense. The patient in this paper appears to be a new mode of inheritance and mechanism associated with AR LOF variants (most previous variants are single heterozygous missense). This patient also appears to be the first report of lissencephaly.
Sources: Literature
Microcephaly v1.138 WARS Anna Ritchie gene: WARS was added
gene: WARS was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: WARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WARS were set to PMID: 35815345; 35790048
Phenotypes for gene: WARS were set to Neurodevelopmental disorder (MONDO:0700092), WARS-related
Review for gene: WARS was set to GREEN
Added comment: Seven affected individuals from four families with biallelic variants, showing varying
severities of developmental delay, intellectual disability and microcephaly. Hearing impairment and, as well as brain anomalies, skeletal system, movement/gait, and behaviour were variable features.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4868 SLITRK2 Zornitza Stark Marked gene: SLITRK2 as ready
Intellectual disability syndromic and non-syndromic v0.4868 SLITRK2 Zornitza Stark Gene: slitrk2 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.51 ALG5 Zornitza Stark Classified gene: ALG5 as Green List (high evidence)
Renal Macrocystic Disease v0.51 ALG5 Zornitza Stark Gene: alg5 has been classified as Green List (High Evidence).
Lissencephaly and Band Heterotopia v1.9 BICD2 Lucy Spencer gene: BICD2 was added
gene: BICD2 was added to Lissencephaly and Band Heterotopia. Sources: Literature
Mode of inheritance for gene: BICD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BICD2 were set to 35896821
Phenotypes for gene: BICD2 were set to Neurodevelopmental disorder (MONDO#0700092), BICD2-related
Review for gene: BICD2 was set to RED
Added comment: Child with developmental delay, microcephaly, dysmorphic facial features, optic atrophy, lissencephaly, hypogenesis of the corpus callosum and cerebellar hypoplasia. Also short stature and underweight. Found to have a homozygous NMD predicted stop gain variant (consanguineous parents). This paper reviews previous patients and found others with brain abnormalities including cerebellar hypoplasia but it looks like lissencephaly is a new phenotype in this individual associated with AR LOF variants (most previous variants are single heterozygous missense).
Sources: Literature
Genetic Epilepsy v0.1640 SLITRK2 Paul De Fazio edited their review of gene: SLITRK2: Changed rating: GREEN
Polycystic liver disease v1.3 ALG5 Zornitza Stark Marked gene: ALG5 as ready
Polycystic liver disease v1.3 ALG5 Zornitza Stark Gene: alg5 has been classified as Green List (High Evidence).
Mendeliome v1.208 DOHH Daniel Flanagan gene: DOHH was added
gene: DOHH was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: DOHH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DOHH were set to PMID: 35858628
Phenotypes for gene: DOHH were set to Neurodevelopmental disorder, DOHH-related (MONDO#0700092)
Review for gene: DOHH was set to GREEN
Added comment: Bi-allelic missense and truncating DOHH variants segregating with disease in five affected individuals from four unrelated families. Clinical features were developmental delay and/or intellectual disability (5/5), microcephaly (5/5), visual impairment (nystagmus (3/5), strabismus (3/5), and cortical visual impairment (1/5)) and congenital heart malformations (3/5 individuals).
Sources: Expert list
Polycystic liver disease v1.3 ALG5 Zornitza Stark Phenotypes for gene: ALG5 were changed from Multiple small kidney cysts, progressive interstitial fibrosis, and kidney function decline to Cystic renal disease MONDO:0002473, ALG5-related; Multiple small kidney cysts, progressive interstitial fibrosis, and kidney function decline
Genetic Epilepsy v0.1640 SLITRK2 Paul De Fazio gene: SLITRK2 was added
gene: SLITRK2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SLITRK2 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: SLITRK2 were set to 35840571
Phenotypes for gene: SLITRK2 were set to Neurodevelopmental disorder, SLITRK2-related MONDO:0700092
gene: SLITRK2 was marked as current diagnostic
Added comment: 6 missense variants and 1 nonsense variant (NOT NMD-predicted, single-exon gene) reported in 7 males and 1 female with neurodevelopmental disorders. Phenotypes included dev delay, mild to severe ID, delayed or absent speech, seizures and brain MRI anomalies (in some patients).

The nonsense variant was identified in two affected brothers but not in the mother, suggesting it was de novo in the maternal germline. The variant in the one affected female was de novo. All other variants in hemizygous males were inherited from an unaffected mother. In one case, the variant was also identified in the unaffected grandmother.

Functional studies showed some but not all variants displayed impaired membrane transport and impaired excitatory synapse-promoting effects. Conditional knockout mice exhibited impaired long-term memory and abnormal gait.
Sources: Literature
Polycystic liver disease v1.2 ALG5 Zornitza Stark Mode of pathogenicity for gene: ALG5 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 None
Mendeliome v1.208 PPFIBP1 Ee Ming Wong reviewed gene: PPFIBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35830857; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, PPFIBP1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Polycystic liver disease v1.1 ALG5 Zornitza Stark Classified gene: ALG5 as Green List (high evidence)
Polycystic liver disease v1.1 ALG5 Zornitza Stark Gene: alg5 has been classified as Green List (High Evidence).
Mendeliome v1.208 SLITRK2 Paul De Fazio gene: SLITRK2 was added
gene: SLITRK2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLITRK2 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: SLITRK2 were set to 35840571
Phenotypes for gene: SLITRK2 were set to Neurodevelopmental disorder, SLITRK2-related MONDO:0700092
Review for gene: SLITRK2 was set to GREEN
gene: SLITRK2 was marked as current diagnostic
Added comment: 6 missense variants and 1 nonsense variant (NOT NMD-predicted, single-exon gene) reported in 7 males and 1 female with neurodevelopmental disorders. Phenotypes included dev delay, mild to severe ID, delayed or absent speech, seizures and brain MRI anomalies (in some patients).

The nonsense variant was identified in two affected brothers but not in the mother, suggesting it was de novo in the maternal germline. The variant in the one affected female was de novo. All other variants in hemizygous males were inherited from an unaffected mother. In one case, the variant was also identified in the unaffected grandmother.

Functional studies showed some but not all variants displayed impaired membrane transport and impaired excitatory synapse-promoting effects. Conditional knockout mice exhibited impaired long-term memory and abnormal gait.
Sources: Literature
Congenital Heart Defect v0.258 DOHH Daniel Flanagan gene: DOHH was added
gene: DOHH was added to Congenital Heart Defect. Sources: Expert list
Mode of inheritance for gene: DOHH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DOHH were set to PMID: 35858628
Phenotypes for gene: DOHH were set to Neurodevelopmental disorder, DOHH-related (MONDO#0700092)
Review for gene: DOHH was set to GREEN
Added comment: Bi-allelic missense and truncating DOHH variants segregating with disease in five affected individuals from four unrelated families. Clinical features were developmental delay and/or intellectual disability (5/5), microcephaly (5/5), visual impairment (nystagmus (3/5), strabismus (3/5), and cortical visual impairment (1/5)) and congenital heart malformations (3/5 individuals).
Sources: Expert list
Genetic Epilepsy v0.1640 RAC3 Alison Yeung gene: RAC3 was added
gene: RAC3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: RAC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAC3 were set to 35851598
Phenotypes for gene: RAC3 were set to Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies, MIM#618577
Review for gene: RAC3 was set to GREEN
Added comment: Sources: Literature
Anophthalmia_Microphthalmia_Coloboma v1.25 BMP3 Seb Lunke gene: BMP3 was added
gene: BMP3 was added to Anophthalmia_Microphthalmia_Coloboma. Sources: Literature
Mode of inheritance for gene: BMP3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BMP3 were set to 35089417
Phenotypes for gene: BMP3 were set to coloboma, MONDO:0001476; microphthalmia, MONDO:0021129
Review for gene: BMP3 was set to AMBER
Added comment: Single missense variant identified segregating with disease following WES screen in a family with coloboma and/or microphthalmia in BMP3. Two additional unrelated patients identified with different missense in BMP3. Pathogenicity however largely on in-silicos, with one of the 3 missense having 29 hets in gnomAD.

Additional functional work in bmp3 -/- zebra fish and some supporting evidence but not conclusive.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4868 SLITRK2 Zornitza Stark Classified gene: SLITRK2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4868 SLITRK2 Zornitza Stark Gene: slitrk2 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.50 ALG5 Chern Lim edited their review of gene: ALG5: Changed phenotypes: Multiple small kidney cysts, progressive interstitial fibrosis, and kidney function decline, few or no liver cysts.
Microcephaly v1.138 PPFIBP1 Ee Ming Wong reviewed gene: PPFIBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35830857; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, PPFIBP1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v1.208 RFC1 Ain Roesley Publications for gene: RFC1 were set to 30926972
Mendeliome v1.208 RFC1 Ain Roesley Phenotypes for gene: RFC1 were changed from Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome OMIM 614575 to Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome MIM#614575
Polycystic liver disease v1.0 ALG5 Chern Lim edited their review of gene: ALG5: Changed phenotypes: Multiple small kidney cysts, progressive interstitial fibrosis, and kidney function decline, few or no liver cysts.
Mendeliome v1.207 RFC1 Ain Roesley Classified gene: RFC1 as Amber List (moderate evidence)
Mendeliome v1.207 RFC1 Ain Roesley Gene: rfc1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1640 RAC3 Alison Yeung gene: RAC3 was added
gene: RAC3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: RAC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAC3 were set to 35851598
Phenotypes for gene: RAC3 were set to Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies, MIM#618577
Review for gene: RAC3 was set to GREEN
Added comment: Sources: Literature
Microcephaly v1.138 DOHH Daniel Flanagan gene: DOHH was added
gene: DOHH was added to Microcephaly. Sources: Expert list
Mode of inheritance for gene: DOHH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DOHH were set to PMID: 35858628
Phenotypes for gene: DOHH were set to Neurodevelopmental disorder, DOHH-related (MONDO#0700092)
Review for gene: DOHH was set to GREEN
Added comment: Bi-allelic missense and truncating DOHH variants segregating with disease in five affected individuals from four unrelated families. Clinical features were developmental delay and/or intellectual disability (5/5), microcephaly (5/5), visual impairment (nystagmus (3/5), strabismus (3/5), and cortical visual impairment (1/5)) and congenital heart malformations (3/5 individuals).
Sources: Expert list
Mendeliome v1.206 C18orf32 Naomi Baker gene: C18orf32 was added
gene: C18orf32 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: C18orf32 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C18orf32 were set to PMID:35107634
Phenotypes for gene: C18orf32 were set to Neurodevelopmental disorder (MONDO:0700092), C18orf32-related
Review for gene: C18orf32 was set to RED
Added comment: Two siblings reported as affected, although sequencing only performed in one sibling, with homozygous loss-of-function variant identified. Clinical presentation included developmental delay, recurrent lower respiratory tract infections, sparse rough hair, roving eye movements, hypotonia, bilateral ankle contractures and inverted nipples.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4867 WARS Anna Ritchie gene: WARS was added
gene: WARS was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: WARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WARS were set to PMID: 35815345; 35790048
Phenotypes for gene: WARS were set to Neurodevelopmental disorder (MONDO:0700092), WARS-related
Review for gene: WARS was set to GREEN
Added comment: At least seven affected individuals from four families with biallelic variants, showing varying
severities of developmental delay, intellectual disability and microcephaly. Hearing impairment and, as well as brain anomalies, skeletal system, movement/gait, and behaviour were variable features.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4867 PPFIBP1 Ee Ming Wong reviewed gene: PPFIBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35830857; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, PPFIBP1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Hereditary Neuropathy v0.130 RFC1 Zornitza Stark Mode of pathogenicity for gene: RFC1 was changed from None to Other
Hereditary Neuropathy v0.129 RFC1 Zornitza Stark Classified gene: RFC1 as Amber List (moderate evidence)
Hereditary Neuropathy v0.129 RFC1 Zornitza Stark Gene: rfc1 has been classified as Amber List (Moderate Evidence).
Renal Macrocystic Disease v0.50 ALG5 Chern Lim gene: ALG5 was added
gene: ALG5 was added to Renal Macrocystic Disease. Sources: Literature
Mode of inheritance for gene: ALG5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ALG5 were set to 35896117
Phenotypes for gene: ALG5 were set to Multiple small kidney cysts, progressive interstitial fibrosis, and kidney function decline
Review for gene: ALG5 was set to GREEN
gene: ALG5 was marked as current diagnostic
Added comment: PMID:35896117:
- Five unrelated families, including 23 affected individuals with non-enlarged cystic kidneys and few or no liver cysts, 8 of them reached end-stage kidney disease from 62 to 91 years of age. Variant confirmed in all but one individual.
- Various variant types: frameshift, nonsense, two missense, splice.
- Functional studies showed haploinsufficiency is the disease mechanism.
Sources: Literature
Congenital nystagmus v1.11 DOHH Daniel Flanagan gene: DOHH was added
gene: DOHH was added to Congenital nystagmus. Sources: Expert list
Mode of inheritance for gene: DOHH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DOHH were set to PMID: 35858628
Phenotypes for gene: DOHH were set to Neurodevelopmental disorder, DOHH-related (MONDO#0700092)
Review for gene: DOHH was set to GREEN
Added comment: Bi-allelic missense and truncating DOHH variants segregating with disease in five affected individuals from four unrelated families. Clinical features were developmental delay and/or intellectual disability (5/5), microcephaly (5/5), visual impairment (nystagmus (3/5), strabismus (3/5), and cortical visual impairment (1/5)) and congenital heart malformations (3/5 individuals).
Sources: Expert list
Genetic Epilepsy v0.1639 PPFIBP1 Zornitza Stark Publications for gene: PPFIBP1 were set to https://www.medrxiv.org/content/10.1101/2022.04.04.22273309v1
Cerebellar and Pontocerebellar Hypoplasia v1.55 BICD2 Lucy Spencer gene: BICD2 was added
gene: BICD2 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Literature
Mode of inheritance for gene: BICD2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: BICD2 were set to 35896821
Phenotypes for gene: BICD2 were set to Neurodevelopmental disorder, BICD2-related (MONDO#0700092)
Review for gene: BICD2 was set to GREEN
Added comment: Child with developmental delay, microcephaly, dysmorphic facial features, optic atrophy, lissencephaly, hypogenesis of the corpus callosum and cerebellar hypoplasia. Also short stature and underweight. Found to have a homozygous NMD predicted stop gain variant (consanguineous parents). This study reviewed previous patients and cerebellar hypoplasia seen in 3 other patients, and hypogenesis of the corpus callosum seen in 5 others but these individuals all had only 1 heterozygous variant, mostly missense.
Sources: Literature
Polycystic liver disease v1.0 ALG5 Chern Lim gene: ALG5 was added
gene: ALG5 was added to Polycystic liver disease. Sources: Literature
Mode of inheritance for gene: ALG5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ALG5 were set to 35896117
Phenotypes for gene: ALG5 were set to Multiple small kidney cysts, progressive interstitial fibrosis, and kidney function decline
Mode of pathogenicity for gene: ALG5 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: ALG5 was set to GREEN
gene: ALG5 was marked as current diagnostic
Added comment: PMID:35896117:
- Five unrelated families, including 23 affected individuals with non-enlarged cystic kidneys and few or no liver cysts, 8 of them reached end-stage kidney disease from 62 to 91 years of age. Variant confirmed in all but one individual.
- Various variant types: frameshift, nonsense, two missense, splice.
- Functional studies showed haploinsufficiency is the disease mechanism.
Sources: Literature
Genetic Epilepsy v0.1638 ADGRL1 Elena Savva Classified gene: ADGRL1 as Amber List (moderate evidence)
Genetic Epilepsy v0.1638 ADGRL1 Elena Savva Gene: adgrl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.206 ADGRL1 Elena Savva Classified gene: ADGRL1 as Green List (high evidence)
Mendeliome v1.206 ADGRL1 Elena Savva Gene: adgrl1 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.178 RAC3 Alison Yeung Marked gene: RAC3 as ready
Polymicrogyria and Schizencephaly v0.178 RAC3 Alison Yeung Gene: rac3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4867 DOHH Zornitza Stark Marked gene: DOHH as ready
Intellectual disability syndromic and non-syndromic v0.4867 DOHH Zornitza Stark Gene: dohh has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4867 ADGRL1 Zornitza Stark Marked gene: ADGRL1 as ready
Intellectual disability syndromic and non-syndromic v0.4867 ADGRL1 Zornitza Stark Gene: adgrl1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4867 DOHH Zornitza Stark Classified gene: DOHH as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4867 DOHH Zornitza Stark Gene: dohh has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.178 RAC3 Alison Yeung Classified gene: RAC3 as Green List (high evidence)
Polymicrogyria and Schizencephaly v0.178 RAC3 Alison Yeung Gene: rac3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4867 SLITRK2 Paul De Fazio gene: SLITRK2 was added
gene: SLITRK2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SLITRK2 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: SLITRK2 were set to 35840571
Phenotypes for gene: SLITRK2 were set to Neurodevelopmental disorder, SLITRK2-related MONDO:0700092
Review for gene: SLITRK2 was set to GREEN
gene: SLITRK2 was marked as current diagnostic
Added comment: 6 missense variants and 1 nonsense variant (NOT NMD-predicted, single-exon gene) reported in 7 males and 1 female with neurodevelopmental disorders. Phenotypes included dev delay, mild to severe ID, delayed or absent speech, seizures and brain MRI anomalies (in some patients).

The nonsense variant was identified in two affected brothers but not in the mother, suggesting it was de novo in the maternal germline. The variant in the one affected female was de novo. All other variants in hemizygous males were inherited from an unaffected mother. In one case, the variant was also identified in the unaffected grandmother.

Functional studies showed some but not all variants displayed impaired membrane transport and impaired excitatory synapse-promoting effects. Conditional knockout mice exhibited impaired long-term memory and abnormal gait.
Sources: Literature
Polymicrogyria and Schizencephaly v0.178 RAC3 Alison Yeung Classified gene: RAC3 as Green List (high evidence)
Polymicrogyria and Schizencephaly v0.178 RAC3 Alison Yeung Gene: rac3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4867 ADGRL1 Zornitza Stark Classified gene: ADGRL1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4867 ADGRL1 Zornitza Stark Gene: adgrl1 has been classified as Green List (High Evidence).
Mendeliome v1.205 RFC1 Ain Roesley reviewed gene: RFC1: Rating: AMBER; Mode of pathogenicity: None; Publications: 35883251; Phenotypes: Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome MIM#614575; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Genetic Epilepsy v0.1637 ADGRL1 Elena Savva Classified gene: ADGRL1 as Amber List (moderate evidence)
Genetic Epilepsy v0.1637 ADGRL1 Elena Savva Gene: adgrl1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1637 ADGRL1 Elena Savva Classified gene: ADGRL1 as Amber List (moderate evidence)
Genetic Epilepsy v0.1637 ADGRL1 Elena Savva Gene: adgrl1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.4866 ADGRL1 Elena Savva Marked gene: ADGRL1 as ready
Intellectual disability syndromic and non-syndromic v0.4866 ADGRL1 Elena Savva Gene: adgrl1 has been classified as Green List (High Evidence).
Mendeliome v1.205 ADGRL1 Elena Savva Classified gene: ADGRL1 as Green List (high evidence)
Mendeliome v1.205 ADGRL1 Elena Savva Gene: adgrl1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4866 ADGRL1 Zornitza Stark Classified gene: ADGRL1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4866 ADGRL1 Zornitza Stark Gene: adgrl1 has been classified as Green List (High Evidence).
Mendeliome v1.204 ADGRL1 Elena Savva Marked gene: ADGRL1 as ready
Mendeliome v1.204 ADGRL1 Elena Savva Gene: adgrl1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.1636 ADGRL1 Elena Savva Marked gene: ADGRL1 as ready
Genetic Epilepsy v0.1636 ADGRL1 Elena Savva Gene: adgrl1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.4866 ADGRL1 Elena Savva Classified gene: ADGRL1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4866 ADGRL1 Elena Savva Gene: adgrl1 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.177 RAC3 Alison Yeung gene: RAC3 was added
gene: RAC3 was added to Polymicrogyria and Schizencephaly. Sources: Literature
Mode of inheritance for gene: RAC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAC3 were set to 35851598
Phenotypes for gene: RAC3 were set to Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies, MIM#618577
Review for gene: RAC3 was set to GREEN
Added comment: Polymicrogyria commonly reported in cohort of 10 patients
Sources: Literature
Hereditary Neuropathy v0.128 RFC1 Ain Roesley reviewed gene: RFC1: Rating: AMBER; Mode of pathogenicity: None; Publications: 35883251; Phenotypes: Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome MIM#614575; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Genetic Epilepsy v0.1636 PPFIBP1 Ee Ming Wong reviewed gene: PPFIBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35830857; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, PPFIBP1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Genetic Epilepsy v0.1636 ADGRL1 Elena Savva gene: ADGRL1 was added
gene: ADGRL1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: ADGRL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ADGRL1 were set to PMID: 35907405
Phenotypes for gene: ADGRL1 were set to Neurodevelopmental disorder, ADGRL1-related (MONDO#0700092)
Review for gene: ADGRL1 was set to AMBER
Added comment: PMID: 35907405 - 9 patients, only had epilepsy (2/9).

Het null mouse model shows neurological and developmental abnormalities, with hom null mice non-viable.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4865 DOHH Daniel Flanagan gene: DOHH was added
gene: DOHH was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: DOHH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DOHH were set to PMID: 35858628
Phenotypes for gene: DOHH were set to Neurodevelopmental disorder, DOHH-related (MONDO#0700092)
Review for gene: DOHH was set to GREEN
Added comment: Bi-allelic missense and truncating DOHH variants segregating with disease in five affected individuals from four unrelated families. Clinical features were developmental delay and/or intellectual disability (5/5), microcephaly (5/5), visual impairment (nystagmus (3/5), strabismus (3/5), and cortical visual impairment (1/5)) and congenital heart malformations (3/5 individuals).
Sources: Expert list
Mendeliome v1.204 ADGRL1 Elena Savva gene: ADGRL1 was added
gene: ADGRL1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ADGRL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ADGRL1 were set to PMID: 35907405
Phenotypes for gene: ADGRL1 were set to Neurodevelopmental disorder, ADGRL1-related (MONDO#0700092)
Review for gene: ADGRL1 was set to GREEN
Added comment: PMID: 35907405 - 9 patients w/ ADHD (3/9), autism (4/9), mild-moderate ID (5/9) and epilepsy (2/9) and facial dysmorphism (7/9). Variants include missense (4) and PTCs (5), and were either de novo (7/9) or inherited from parents with learning difficulties/ID (2/9).

Functional studies on both PTCs and missense variants show significant reductions in calcium signalling and surface protein.

Het null mouse model shows neurological and developmental abnormalities, with hom null mice non-viable.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4865 ADGRL1 Elena Savva gene: ADGRL1 was added
gene: ADGRL1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ADGRL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ADGRL1 were set to PMID: 35907405
Phenotypes for gene: ADGRL1 were set to Neurodevelopmental disorder, ADGRL1-related (MONDO#0700092)
Review for gene: ADGRL1 was set to GREEN
Added comment: PMID: 35907405 - 9 patients w/ ADHD (3/9), autism (4/9), mild-moderate ID (5/9) and epilepsy (2/9) and facial dysmorphism (7/9). Variants include missense (4) and PTCs (5), and were either de novo (7/9) or inherited from parents with learning difficulties/ID (2/9).

Functional studies on both PTCs and missense variants show significant reductions in calcium signalling and surface protein.

Het null mouse model shows neurological and developmental abnormalities, with hom null mice non-viable.
Sources: Literature
Callosome v0.457 RAC3 Alison Yeung Marked gene: RAC3 as ready
Callosome v0.457 RAC3 Alison Yeung Gene: rac3 has been classified as Green List (High Evidence).
Callosome v0.457 RAC3 Alison Yeung Classified gene: RAC3 as Green List (high evidence)
Callosome v0.457 RAC3 Alison Yeung Gene: rac3 has been classified as Green List (High Evidence).
Callosome v0.456 RAC3 Alison Yeung gene: RAC3 was added
gene: RAC3 was added to Callosome. Sources: Literature
Mode of inheritance for gene: RAC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAC3 were set to 35851598
Phenotypes for gene: RAC3 were set to Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies, MIM#618577
Review for gene: RAC3 was set to GREEN
Added comment: Corpus callosal abnormalities reported in 100% of cohort of 10 patients
Sources: Literature
Congenital Heart Defect v0.258 DNAH9 Zornitza Stark Marked gene: DNAH9 as ready
Congenital Heart Defect v0.258 DNAH9 Zornitza Stark Gene: dnah9 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.258 DNAH9 Zornitza Stark Classified gene: DNAH9 as Green List (high evidence)
Congenital Heart Defect v0.258 DNAH9 Zornitza Stark Gene: dnah9 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.257 DNAH9 Zornitza Stark gene: DNAH9 was added
gene: DNAH9 was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: DNAH9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAH9 were set to 35116053; 35050399; 30471717; 30471718
Phenotypes for gene: DNAH9 were set to Ciliary dyskinesia, primary, 40 618300; Heterotaxy
Review for gene: DNAH9 was set to GREEN
Added comment: Multiple families reported including with significant CHD.
Sources: Literature
Heterotaxy v1.20 DNAH9 Zornitza Stark reviewed gene: DNAH9: Rating: GREEN; Mode of pathogenicity: None; Publications: 35116053, 35050399; Phenotypes: Ciliary dyskinesia, primary, 40 618300, Heterotaxy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.203 EHHADH Zornitza Stark Classified gene: EHHADH as Amber List (moderate evidence)
Mendeliome v1.203 EHHADH Zornitza Stark Gene: ehhadh has been classified as Amber List (Moderate Evidence).
Mendeliome v1.202 EHHADH Zornitza Stark edited their review of gene: EHHADH: Added comment: https://clinmedjournals.org/articles/jcnrc/journal-of-clinical-nephrology-and-renal-care-jcnrc-3-027.pdf

Second case report, same variant, de novo. Also, experimental evidence. Assessed as MODERATE by ClinGen.; Changed rating: AMBER
Inflammatory bowel disease v0.82 NOX1 Peter McNaughton gene: NOX1 was added
gene: NOX1 was added to Inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: NOX1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: NOX1 were set to PMID: 29091079; 32064493
Phenotypes for gene: NOX1 were set to Inflammatory bowel disease
Review for gene: NOX1 was set to AMBER
Added comment: 8 IBD patients with early onset of IBD with progressive and severe colonic disease, refractory to conventional therapy and functional studies suggesting variant-dependent loss of NOX1-mediated superoxide generation. However, high frequency of nonsynonymous mutations in NOX1 suggests that NOX1 is not a highly penetrant Mendelian disorder and that other genetic modifiers or environmental factors may contribute to disease pathogenesis
Sources: Literature
Pulmonary Arterial Hypertension v1.13 SARS2 Zornitza Stark Marked gene: SARS2 as ready
Pulmonary Arterial Hypertension v1.13 SARS2 Zornitza Stark Gene: sars2 has been classified as Green List (High Evidence).
Mendeliome v1.202 DUOX2 Zornitza Stark Phenotypes for gene: DUOX2 were changed from Thyroid dyshormonogenesis 6 - MIM#607200 to Thyroid dyshormonogenesis 6 - MIM#607200; Inflammatory bowel disease, MONDO:0005265, DUOX2-related
Mendeliome v1.201 DUOX2 Zornitza Stark Publications for gene: DUOX2 were set to
Mendeliome v1.200 DUOX2 Zornitza Stark Mode of inheritance for gene: DUOX2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.199 DUOX2 Zornitza Stark Classified gene: DUOX2 as Amber List (moderate evidence)
Mendeliome v1.199 DUOX2 Zornitza Stark Gene: duox2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.198 DUOX2 Zornitza Stark reviewed gene: DUOX2: Rating: AMBER; Mode of pathogenicity: None; Publications: 35429653, 27373512, 26301257, 28683258; Phenotypes: Inflammatory bowel disease, MONDO:0005265, DUOX2-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Inflammatory bowel disease v0.82 DUOX2 Zornitza Stark Marked gene: DUOX2 as ready
Inflammatory bowel disease v0.82 DUOX2 Zornitza Stark Gene: duox2 has been classified as Amber List (Moderate Evidence).
Inflammatory bowel disease v0.82 DUOX2 Zornitza Stark Phenotypes for gene: DUOX2 were changed from Colitis to Inflammatory bowel disease, MONDO:0005265, DUOX2-related
Inflammatory bowel disease v0.81 DUOX2 Zornitza Stark Classified gene: DUOX2 as Amber List (moderate evidence)
Inflammatory bowel disease v0.81 DUOX2 Zornitza Stark Gene: duox2 has been classified as Amber List (Moderate Evidence).
Inflammatory bowel disease v0.80 DUOX2 Zornitza Stark reviewed gene: DUOX2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hydrocephalus_Ventriculomegaly v0.118 CWH43 Zornitza Stark Marked gene: CWH43 as ready
Hydrocephalus_Ventriculomegaly v0.118 CWH43 Zornitza Stark Gene: cwh43 has been classified as Red List (Low Evidence).
Hydrocephalus_Ventriculomegaly v0.118 CWH43 Zornitza Stark gene: CWH43 was added
gene: CWH43 was added to Hydrocephalus_Ventriculomegaly. Sources: Expert Review
cnv tags were added to gene: CWH43.
Mode of inheritance for gene: CWH43 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CWH43 were set to 33459505; 34380733
Phenotypes for gene: CWH43 were set to Hydrocephalus MONDO:0001150, CWH43-related
Review for gene: CWH43 was set to RED
Added comment: Two individuals with recurrent deletion reported.
Sources: Expert Review
Mendeliome v1.198 CWH43 Zornitza Stark Marked gene: CWH43 as ready
Mendeliome v1.198 CWH43 Zornitza Stark Gene: cwh43 has been classified as Red List (Low Evidence).
Mendeliome v1.198 CWH43 Zornitza Stark Phenotypes for gene: CWH43 were changed from normal pressure hydrocephalus to Hydrocephalus MONDO:0001150, CWH43-related
Mendeliome v1.197 CWH43 Zornitza Stark Classified gene: CWH43 as Red List (low evidence)
Mendeliome v1.197 CWH43 Zornitza Stark Gene: cwh43 has been classified as Red List (Low Evidence).
Mendeliome v1.196 CWH43 Zornitza Stark Tag cnv tag was added to gene: CWH43.
Mendeliome v1.196 CWH43 Zornitza Stark reviewed gene: CWH43: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hydrocephalus MONDO:0001150, CWH43-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pulmonary Arterial Hypertension v1.13 SARS2 Chirag Patel Classified gene: SARS2 as Green List (high evidence)
Pulmonary Arterial Hypertension v1.13 SARS2 Chirag Patel Gene: sars2 has been classified as Green List (High Evidence).
Pulmonary Arterial Hypertension v1.12 SARS2 Chirag Patel gene: SARS2 was added
gene: SARS2 was added to Pulmonary Arterial Hypertension. Sources: Literature
Mode of inheritance for gene: SARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SARS2 were set to 24034276; 21255763; 33751860
Phenotypes for gene: SARS2 were set to Hyperuricemia, pulmonary hypertension, renal failure, and alkalosis, MIM#613845
Review for gene: SARS2 was set to GREEN
Added comment: HUPRA syndrome is a severe autosomal recessive multisystem disorder characterized by onset in infancy of progressive renal failure leading to electrolyte imbalances, metabolic alkalosis, pulmonary hypertension, hypotonia, and delayed development. Six patients from 4 unrelated families reported - only 1 patient did not have PAH.
Sources: Literature
Limb and Digital Malformations SuperPanel v0.28 Zornitza Stark Panel types changed to Superpanel; Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Inflammatory bowel disease v0.80 DUOX2 Peter McNaughton gene: DUOX2 was added
gene: DUOX2 was added to Inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: DUOX2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: DUOX2 were set to PMID: 35429653; 27373512; 26301257; 28683258
Phenotypes for gene: DUOX2 were set to Colitis
Review for gene: DUOX2 was set to AMBER
Added comment: 4 case reports of early onset colitis (1-4y) associated with monoallelic or biallelic variants in NOX2. Also reported in 15 members of the same Ashkenazi Jewish family with a high incidence of adult-onset CD.
Sources: Literature
Mendeliome v1.196 CWH43 Anna Le Fevre gene: CWH43 was added
gene: CWH43 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CWH43 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CWH43 were set to PMID: 33459505; 34380733
Phenotypes for gene: CWH43 were set to normal pressure hydrocephalus
Penetrance for gene: CWH43 were set to Incomplete
Review for gene: CWH43 was set to AMBER
Added comment: Sources: Literature
Retinitis pigmentosa v0.128 ADGRA3 Zornitza Stark Marked gene: ADGRA3 as ready
Retinitis pigmentosa v0.128 ADGRA3 Zornitza Stark Gene: adgra3 has been classified as Red List (Low Evidence).
Retinitis pigmentosa v0.128 ADGRA3 Zornitza Stark Phenotypes for gene: ADGRA3 were changed from retinal dystrophy to Retinitis pigmentosa, MONDO:0019200, ADGRA3-related
Mendeliome v1.196 ADGRA3 Zornitza Stark Marked gene: ADGRA3 as ready
Mendeliome v1.196 ADGRA3 Zornitza Stark Gene: adgra3 has been classified as Red List (Low Evidence).
Mendeliome v1.196 ADGRA3 Zornitza Stark gene: ADGRA3 was added
gene: ADGRA3 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: ADGRA3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADGRA3 were set to 23105016
Phenotypes for gene: ADGRA3 were set to Retinitis pigmentosa, MONDO:0019200, ADGRA3-related
Review for gene: ADGRA3 was set to RED
Added comment: Only one report of a missense that is a VUS identified as a candidate through autozygome analysis (PMID: 23105016)
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.4864 TAF8 Zornitza Stark Phenotypes for gene: TAF8 were changed from Neurodevelopmental disorder, MONDO:0700092, TAF8-related to Neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophy, MIM# 619972
Intellectual disability syndromic and non-syndromic v0.4863 TAF8 Zornitza Stark edited their review of gene: TAF8: Changed phenotypes: Neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophy, MIM# 619972
Genetic Epilepsy v0.1635 TAF8 Zornitza Stark Phenotypes for gene: TAF8 were changed from Neurodevelopmental disorder, MONDO:0700092, TAF8-related to Neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophy, MIM# 619972
Microcephaly v1.138 TAF8 Zornitza Stark Phenotypes for gene: TAF8 were changed from Neurodevelopmental disorder, MONDO:0700092, TAF8-related to Neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophy, MIM# 619972
Genetic Epilepsy v0.1634 TAF8 Zornitza Stark edited their review of gene: TAF8: Changed phenotypes: Neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophy, MIM# 619972
Microcephaly v1.137 TAF8 Zornitza Stark edited their review of gene: TAF8: Changed phenotypes: Neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophy, MIM# 619972
Mendeliome v1.195 TAF8 Zornitza Stark Phenotypes for gene: TAF8 were changed from Neurodevelopmental disorder, MONDO:0700092, TAF8-related to Neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophy, MIM# 619972
Mendeliome v1.194 TAF8 Zornitza Stark edited their review of gene: TAF8: Changed phenotypes: Neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophy, MIM# 619972
Holoprosencephaly and septo-optic dysplasia v1.6 ARID1A Zornitza Stark Marked gene: ARID1A as ready
Holoprosencephaly and septo-optic dysplasia v1.6 ARID1A Zornitza Stark Gene: arid1a has been classified as Amber List (Moderate Evidence).
Holoprosencephaly and septo-optic dysplasia v1.6 ARID1A Zornitza Stark Classified gene: ARID1A as Amber List (moderate evidence)
Holoprosencephaly and septo-optic dysplasia v1.6 ARID1A Zornitza Stark Gene: arid1a has been classified as Amber List (Moderate Evidence).
Holoprosencephaly and septo-optic dysplasia v1.5 ARID1A Zornitza Stark reviewed gene: ARID1A: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Coffin-Siris syndrome 2 #614607; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Holoprosencephaly and septo-optic dysplasia v1.5 SOX2 Zornitza Stark Marked gene: SOX2 as ready
Holoprosencephaly and septo-optic dysplasia v1.5 SOX2 Zornitza Stark Gene: sox2 has been classified as Amber List (Moderate Evidence).
Holoprosencephaly and septo-optic dysplasia v1.5 SOX2 Zornitza Stark Classified gene: SOX2 as Amber List (moderate evidence)
Holoprosencephaly and septo-optic dysplasia v1.5 SOX2 Zornitza Stark Gene: sox2 has been classified as Amber List (Moderate Evidence).
Holoprosencephaly and septo-optic dysplasia v1.4 SOX2 Zornitza Stark reviewed gene: SOX2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Optic nerve hypoplasia and abnormalities of the central nervous system #206900, Microphthalmia, syndromic 3 #206900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Holoprosencephaly and septo-optic dysplasia v1.4 ARID1A Di Milnes gene: ARID1A was added
gene: ARID1A was added to Holoprosencephaly and septo-optic dysplasia. Sources: Literature
Mode of inheritance for gene: ARID1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARID1A were set to 35885948
Phenotypes for gene: ARID1A were set to Coffin-Siris syndrome 2 #614607
Review for gene: ARID1A was set to AMBER
Added comment: single case SOD (absent septum pellucidum, absent corpus callosum, ventriculomegaly, aqueductal stenosis ONH), a ventricular septal defect and a patent foramen ovale, 13 pairs of ribs, bilateral clinodactyly, single palmar crease, broad large toe with hypoplastic nail, cleft palate, choanal atresia, seizures, apnoea, and dysmorphic facial features, including down-slanting palpebral fissures, long columella, low-set and posteriorly rotated ears, depressed nasal bridge, scant hair due to premature birth; he died at 6 weeks of age.
Mosaic truncating variant confirmed de novo Sanger sequencing (33% exome reads, lower peak on Sanger)
Sources: Literature
Holoprosencephaly and septo-optic dysplasia v1.4 SOX2 Di Milnes gene: SOX2 was added
gene: SOX2 was added to Holoprosencephaly and septo-optic dysplasia. Sources: Literature
Mode of inheritance for gene: SOX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOX2 were set to 35885948
Phenotypes for gene: SOX2 were set to Optic nerve hypoplasia and abnormalities of the central nervous system #206900; Microphthalmia, syndromic 3 #206900
Review for gene: SOX2 was set to AMBER
Added comment: single case SOD (mild ONH, absent septum pellucidum, hypoplasia corpus callosum, dilated lateral ventricles de novo trio WES confirmed Sanger sequencing
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4863 POU3F3 Zornitza Stark Phenotypes for gene: POU3F3 were changed from Snijders Blok-Fisher syndrome MIM#618604 to Snijders Blok-Fisher syndrome MIM#618604
Intellectual disability syndromic and non-syndromic v0.4862 POU3F3 Zornitza Stark Phenotypes for gene: POU3F3 were changed from no OMIM number yet. to Snijders Blok-Fisher syndrome MIM#618604
Intellectual disability syndromic and non-syndromic v0.4861 POU3F3 Zornitza Stark reviewed gene: POU3F3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Snijders Blok-Fisher syndrome MIM#618604; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.194 POU3F3 Zornitza Stark Phenotypes for gene: POU3F3 were changed from Intellectual disability to Snijders Blok-Fisher syndrome MIM#618604
Mendeliome v1.193 POU3F3 Zornitza Stark edited their review of gene: POU3F3: Changed phenotypes: Snijders Blok-Fisher syndrome MIM#618604
Congenital Heart Defect v0.256 ROBO4 Zornitza Stark Phenotypes for gene: ROBO4 were changed from bicuspid aortic valve; ascending aortic aneurysm; ascending aorta dilatation to Aortic valve disease 8, MIM# 618496; bicuspid aortic valve; ascending aortic aneurysm; ascending aorta dilatation
Congenital Heart Defect v0.255 ROBO4 Zornitza Stark Classified gene: ROBO4 as Amber List (moderate evidence)
Congenital Heart Defect v0.255 ROBO4 Zornitza Stark Gene: robo4 has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v0.254 ROBO4 Zornitza Stark Deleted their comment
Congenital Heart Defect v0.254 ROBO4 Zornitza Stark edited their review of gene: ROBO4: Added comment: LoF variants in this gene have high frequency in gnomad. Only two families reported. Functional data is not entirely convincing. May be a susceptibility factor to a relatively common phenotype (bicuspid aortic valve).; Changed rating: AMBER; Changed publications: 30455415; Changed phenotypes: Aortic valve disease 8, MIM# 618496, bicuspid aortic valve, ascending aortic aneurysm, ascending aorta dilatation; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v1.68 ROBO4 Zornitza Stark Classified gene: ROBO4 as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v1.68 ROBO4 Zornitza Stark Gene: robo4 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v1.67 ROBO4 Zornitza Stark Deleted their comment
Aortopathy_Connective Tissue Disorders v1.67 ROBO4 Zornitza Stark edited their review of gene: ROBO4: Added comment: LoF variants in this gene have high frequency in gnomad.

Only two families reported. Functional data is not entirely convincing. May be a susceptibility factor to a relatively common phenotype (bicuspid aortic valve).; Changed rating: AMBER
Mendeliome v1.193 ROBO4 Zornitza Stark Phenotypes for gene: ROBO4 were changed from bicuspid aortic valve; ascending aortic aneurysm; ascending aorta dilatation to Aortic valve disease 8, MIM#618496; bicuspid aortic valve; ascending aortic aneurysm; ascending aorta dilatation
Mendeliome v1.192 ROBO4 Zornitza Stark Publications for gene: ROBO4 were set to 30455415
Mendeliome v1.191 ROBO4 Zornitza Stark Classified gene: ROBO4 as Amber List (moderate evidence)
Mendeliome v1.191 ROBO4 Zornitza Stark Gene: robo4 has been classified as Amber List (Moderate Evidence).
Monogenic Diabetes v0.30 EIF2B1 Zornitza Stark Marked gene: EIF2B1 as ready
Monogenic Diabetes v0.30 EIF2B1 Zornitza Stark Gene: eif2b1 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.30 EIF2B1 Zornitza Stark Classified gene: EIF2B1 as Green List (high evidence)
Monogenic Diabetes v0.30 EIF2B1 Zornitza Stark Gene: eif2b1 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.29 EIF2B1 Zornitza Stark gene: EIF2B1 was added
gene: EIF2B1 was added to Monogenic Diabetes. Sources: Expert Review
Mode of inheritance for gene: EIF2B1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EIF2B1 were set to 31882561
Phenotypes for gene: EIF2B1 were set to Neonatal diabetes mellitus, MONDO:0016391, EIF2B1-related
Review for gene: EIF2B1 was set to GREEN
Added comment: PMID: 31882561: heterozygous de novo variants in 5 patients with permanent neonatal/early onset diabetes and transient liver dysfunction (4 missense, 1 stop-loss). No functional studies performed, missense clustered within a small region (p.Leu34-Ser77).
Sources: Expert Review
Mendeliome v1.190 EIF2B1 Zornitza Stark Phenotypes for gene: EIF2B1 were changed from leukoencephalopathy with vanishing white matter MONDO:0011380; ataxia; spasticity; optic atrophy to leukoencephalopathy with vanishing white matter MONDO:0011380; ataxia; spasticity; optic atrophy; Neonatal diabetes mellitus, MONDO:0016391, EIF2B1-related
Mendeliome v1.189 EIF2B1 Zornitza Stark Publications for gene: EIF2B1 were set to 11835386; 26285592; 15776425; 18263758; 25843247; 25761052; 30014503
Mendeliome v1.188 EIF2B1 Zornitza Stark Mode of inheritance for gene: EIF2B1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.187 EIF2B1 Zornitza Stark reviewed gene: EIF2B1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neonatal diabetes mellitus, MONDO:0016391, EIF2B1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v0.133 MCM10 Zornitza Stark Classified gene: MCM10 as Amber List (moderate evidence)
Cardiomyopathy_Paediatric v0.133 MCM10 Zornitza Stark Gene: mcm10 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v0.132 MCM10 Zornitza Stark edited their review of gene: MCM10: Added comment: Upgraded due to functional evidence.; Changed rating: AMBER
Mendeliome v1.187 MCM10 Zornitza Stark Publications for gene: MCM10 were set to 32865517; 33712616
Mendeliome v1.186 MCM10 Zornitza Stark Classified gene: MCM10 as Amber List (moderate evidence)
Mendeliome v1.186 MCM10 Zornitza Stark Gene: mcm10 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.185 MCM10 Zornitza Stark edited their review of gene: MCM10: Added comment: PMID 33712616: further functional validation.; Changed rating: AMBER; Changed publications: 32865517, 33712616, 33712616
Susceptibility to Viral Infections v0.93 MCM10 Zornitza Stark Publications for gene: MCM10 were set to 32865517
Susceptibility to Viral Infections v0.92 MCM10 Zornitza Stark Classified gene: MCM10 as Amber List (moderate evidence)
Susceptibility to Viral Infections v0.92 MCM10 Zornitza Stark Gene: mcm10 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.35 ASXL3 Zornitza Stark Publications for gene: ASXL3 were set to
Cerebral Palsy v1.34 ASXL3 Zornitza Stark Classified gene: ASXL3 as Green List (high evidence)
Cerebral Palsy v1.34 ASXL3 Zornitza Stark Gene: asxl3 has been classified as Green List (High Evidence).
Autoinflammatory Disorders v0.163 CEBPE Zornitza Stark Marked gene: CEBPE as ready
Autoinflammatory Disorders v0.163 CEBPE Zornitza Stark Gene: cebpe has been classified as Amber List (Moderate Evidence).
Autoinflammatory Disorders v0.163 CEBPE Zornitza Stark Phenotypes for gene: CEBPE were changed from Autoinflammation to Autoinflammatory syndrome MONDO:0019751, CEBPE-related
Autoinflammatory Disorders v0.162 CEBPE Zornitza Stark Classified gene: CEBPE as Amber List (moderate evidence)
Autoinflammatory Disorders v0.162 CEBPE Zornitza Stark Gene: cebpe has been classified as Amber List (Moderate Evidence).
Autoinflammatory Disorders v0.161 CEBPE Zornitza Stark changed review comment from: Three individuals from a single family homozygous for a missense variant. Extensive functional data presented.; to: Three individuals from a single family homozygous for a missense variant. Extensive functional data presented. Gene already has an established role in immunological disorders.
Autoinflammatory Disorders v0.161 CEBPE Zornitza Stark reviewed gene: CEBPE: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.185 IKZF1 Zornitza Stark Phenotypes for gene: IKZF1 were changed from Immunodeficiency, common variable, 13 MIM# 616873; recurrent bacterial respiratory infections; Thrombocytopaenia; immunodeficiency; Hypogammaglobulinaemia; decrease B-cells; decrease B-cell differentiation; decrease memory B/T cells; Low Ig; pneumocystis early CID onset to Immunodeficiency, common variable, 13 MIM# 616873; recurrent bacterial respiratory infections; Thrombocytopaenia; immunodeficiency; Hypogammaglobulinaemia; decrease B-cells; decrease B-cell differentiation; decrease memory B/T cells; Low Ig; pneumocystis early CID onset; Immune dysregulation
Mendeliome v1.184 IKZF1 Zornitza Stark Publications for gene: IKZF1 were set to 21548011; 26981933; 29889099; 31057532; 7923373; 11805317
Mendeliome v1.183 IKZF1 Zornitza Stark edited their review of gene: IKZF1: Added comment: PMID 35333544: Eight individuals harboring heterozygous IKZF1R183H or IKZF1R183C variants associated with GOF effects reported. The clinical phenotypes and pathophysiology associated with IKZF1R183H/C differ from those of previously reported patients with IKZF1HI, IKZF1DN, and IKZF1DD and should therefore be considered as a novel IKAROS-associated disease entity. This condition is characterized by immune dysregulation manifestations including inflammation, autoimmunity, atopy, and polyclonal PC proliferation.; Changed publications: 21548011, 26981933, 29889099, 31057532, 7923373, 11805317, 35333544; Changed phenotypes: Immunodeficiency, common variable, 13 MIM# 616873, recurrent bacterial respiratory infections, Thrombocytopaenia, immunodeficiency, Hypogammaglobulinaemia, decrease B-cells, decrease B-cell differentiation, decrease memory B/T cells, Low Ig, pneumocystis early CID onset, Immune dysregulation
Autoinflammatory Disorders v0.161 TBK1 Zornitza Stark Phenotypes for gene: TBK1 were changed from Autoinflammation to Immunodeficiency, MONDO:0021094, TBK1-related, AR; Autoinflammation
Mendeliome v1.183 IKZF2 Zornitza Stark Phenotypes for gene: IKZF2 were changed from Immune dysregulation to Immunodeficiency, MONDO:0021094, IKZF2-related; Immune dysregulation
Mendeliome v1.182 IKZF2 Zornitza Stark Publications for gene: IKZF2 were set to 34920454
Mendeliome v1.181 IKZF2 Zornitza Stark Mode of inheritance for gene: IKZF2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.180 IKZF2 Zornitza Stark edited their review of gene: IKZF2: Added comment: Iranian male with homozygous missense variant with recurrent infection, hypogammaglobulinaemia. Extends inheritance to AR. Supportive functional data.; Changed publications: 34920454, 34826259; Changed phenotypes: Immunodeficiency, MONDO:0021094, IKZF2-related, Immune dysregulation; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Disorders of immune dysregulation v0.151 IKZF2 Zornitza Stark Phenotypes for gene: IKZF2 were changed from Immune dysregulation to Immunodeficiency, MONDO:0021094, IKZF2-related; Immune dysregulation
Disorders of immune dysregulation v0.150 IKZF2 Zornitza Stark Publications for gene: IKZF2 were set to 34920454
Disorders of immune dysregulation v0.149 IKZF2 Zornitza Stark Mode of inheritance for gene: IKZF2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary Spastic Paraplegia v1.40 TMEM63C Zornitza Stark Phenotypes for gene: TMEM63C were changed from Hereditary spastic paraplegia, MONDO:0019064, TMEM63C-related to Spastic paraplegia 87, autosomal recessive, MIM# 619966
Hereditary Spastic Paraplegia v1.39 TMEM63C Zornitza Stark reviewed gene: TMEM63C: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 87, autosomal recessive, MIM# 619966; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4861 TMEM63C Zornitza Stark Phenotypes for gene: TMEM63C were changed from Hereditary spastic paraplegia, MONDO:0019064, TMEM63C-related to Spastic paraplegia 87, autosomal recessive, MIM# 619966
Intellectual disability syndromic and non-syndromic v0.4860 TMEM63C Zornitza Stark reviewed gene: TMEM63C: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 87, autosomal recessive, MIM# 619966; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.180 TMEM63C Zornitza Stark Marked gene: TMEM63C as ready
Mendeliome v1.180 TMEM63C Zornitza Stark Gene: tmem63c has been classified as Green List (High Evidence).
Mendeliome v1.180 TMEM63C Zornitza Stark Phenotypes for gene: TMEM63C were changed from Hereditary spastic paraplegia, MONDO:0019064, TMEM63C-related to Spastic paraplegia 87, autosomal recessive, MIM# 619966
Mendeliome v1.179 TMEM63C Zornitza Stark reviewed gene: TMEM63C: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 87, autosomal recessive, MIM# 619966; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.95 WNT10A Zornitza Stark Marked gene: WNT10A as ready
Prepair 1000+ v0.95 WNT10A Zornitza Stark Gene: wnt10a has been classified as Red List (Low Evidence).
Prepair 1000+ v0.95 WNT10A Zornitza Stark Classified gene: WNT10A as Red List (low evidence)
Prepair 1000+ v0.95 WNT10A Zornitza Stark Gene: wnt10a has been classified as Red List (Low Evidence).
Prepair 1000+ v0.94 TFR2 Zornitza Stark Tag for review tag was added to gene: TFR2.
Prepair 1000+ v0.94 TECPR2 Zornitza Stark Marked gene: TECPR2 as ready
Prepair 1000+ v0.94 TECPR2 Zornitza Stark Gene: tecpr2 has been classified as Green List (High Evidence).
Prepair 1000+ v0.94 TECPR2 Zornitza Stark Classified gene: TECPR2 as Green List (high evidence)
Prepair 1000+ v0.94 TECPR2 Zornitza Stark Gene: tecpr2 has been classified as Green List (High Evidence).
Prepair 1000+ v0.93 TECPR2 Zornitza Stark reviewed gene: TECPR2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuropathy, hereditary sensory and autonomic, type IX, with developmental delay, MIM#615031; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.93 TAT Zornitza Stark Tag for review tag was added to gene: TAT.
Prepair 1000+ v0.93 SLC4A11 Zornitza Stark Tag for review tag was added to gene: SLC4A11.
Prepair 1000+ v0.93 SLC26A4 Zornitza Stark Marked gene: SLC26A4 as ready
Prepair 1000+ v0.93 SLC26A4 Zornitza Stark Gene: slc26a4 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.93 SLC26A4 Zornitza Stark Classified gene: SLC26A4 as Red List (low evidence)
Prepair 1000+ v0.93 SLC26A4 Zornitza Stark Gene: slc26a4 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.92 SLC26A4 Zornitza Stark reviewed gene: SLC26A4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal recessive 4, with enlarged vestibular aqueduct (MIM#600791), Pendred syndrome (MIM#274600); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.92 SLC12A3 Zornitza Stark Tag for review tag was added to gene: SLC12A3.
Prepair 1000+ v0.92 RS1 Zornitza Stark Tag for review tag was added to gene: RS1.
Prepair 1000+ v0.92 PYGM Zornitza Stark Tag for review tag was added to gene: PYGM.
Prepair 1000+ v0.92 OAT Zornitza Stark Tag for review tag was added to gene: OAT.
Prepair 1000+ v0.92 NR2E3 Zornitza Stark Tag for review tag was added to gene: NR2E3.
Prepair 1000+ v0.92 MEFV Zornitza Stark Tag for review tag was added to gene: MEFV.
Prepair 1000+ v0.92 MCCC2 Zornitza Stark Marked gene: MCCC2 as ready
Prepair 1000+ v0.92 MCCC2 Zornitza Stark Gene: mccc2 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.92 MCCC2 Zornitza Stark Classified gene: MCCC2 as Red List (low evidence)
Prepair 1000+ v0.92 MCCC2 Zornitza Stark Gene: mccc2 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.91 MCCC1 Zornitza Stark reviewed gene: MCCC1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: 3-Methylcrotonyl-CoA carboxylase 1 deficiency (MIM#210200); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.91 MCCC1 Zornitza Stark Marked gene: MCCC1 as ready
Prepair 1000+ v0.91 MCCC1 Zornitza Stark Gene: mccc1 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.91 MCCC1 Zornitza Stark Classified gene: MCCC1 as Red List (low evidence)
Prepair 1000+ v0.91 MCCC1 Zornitza Stark Gene: mccc1 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.90 LOXHD1 Zornitza Stark Marked gene: LOXHD1 as ready
Prepair 1000+ v0.90 LOXHD1 Zornitza Stark Gene: loxhd1 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.90 LOXHD1 Zornitza Stark Classified gene: LOXHD1 as Red List (low evidence)
Prepair 1000+ v0.90 LOXHD1 Zornitza Stark Gene: loxhd1 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.89 LOXHD1 Zornitza Stark reviewed gene: LOXHD1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal recessive 77 (MIM#613079); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Autoinflammatory Disorders v0.160 ALPK1 Zornitza Stark Publications for gene: ALPK1 were set to 31053777
Autoinflammatory Disorders v0.159 ALPK1 Zornitza Stark Phenotypes for gene: ALPK1 were changed from Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome to Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache (ROSAH) syndrome, MIM#614979; Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome
Autoinflammatory Disorders v0.158 ALPK1 Zornitza Stark Classified gene: ALPK1 as Green List (high evidence)
Autoinflammatory Disorders v0.158 ALPK1 Zornitza Stark Gene: alpk1 has been classified as Green List (High Evidence).
Mendeliome v1.179 ROBO4 Elena Savva reviewed gene: ROBO4: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID:30455415, 32748548; Phenotypes: Aortic valve disease 8 MIM#618496; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.179 EIF2B1 Elena Savva reviewed gene: EIF2B1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31882561; Phenotypes: Leukoencephalopathy with vanishing white matter MIM#603896, permanent neonatal/early onset diabetes and transient liver dysfunction; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Disorders of immune dysregulation v0.148 IKZF1 Bryony Thompson Marked gene: IKZF1 as ready
Disorders of immune dysregulation v0.148 IKZF1 Bryony Thompson Gene: ikzf1 has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.148 IKZF1 Bryony Thompson Classified gene: IKZF1 as Green List (high evidence)
Disorders of immune dysregulation v0.148 IKZF1 Bryony Thompson Gene: ikzf1 has been classified as Green List (High Evidence).
Autoinflammatory Disorders v0.157 TBK1 Bryony Thompson Marked gene: TBK1 as ready
Autoinflammatory Disorders v0.157 TBK1 Bryony Thompson Gene: tbk1 has been classified as Green List (High Evidence).
Autoinflammatory Disorders v0.157 TBK1 Bryony Thompson Classified gene: TBK1 as Green List (high evidence)
Autoinflammatory Disorders v0.157 TBK1 Bryony Thompson Gene: tbk1 has been classified as Green List (High Evidence).
Photosensitivity Syndromes v1.2 RECQL Bryony Thompson Marked gene: RECQL as ready
Photosensitivity Syndromes v1.2 RECQL Bryony Thompson Gene: recql has been classified as Amber List (Moderate Evidence).
Photosensitivity Syndromes v1.2 RECQL Bryony Thompson Classified gene: RECQL as Amber List (moderate evidence)
Photosensitivity Syndromes v1.2 RECQL Bryony Thompson Gene: recql has been classified as Amber List (Moderate Evidence).
Photosensitivity Syndromes v1.1 Bryony Thompson Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Susceptibility to Viral Infections v0.91 MCM10 Peter McNaughton reviewed gene: MCM10: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 33712616; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.33 ASXL3 Clare van Eyk reviewed gene: ASXL3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35863334, 33528536; Phenotypes: Bainbridge-Ropers syndrome (MIM #615485); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.4860 ARFGEF1 Zornitza Stark Phenotypes for gene: ARFGEF1 were changed from Intellectual disability; Epilepsy to Developmental delay, impaired speech, and behavioral abnormalities, MIM# 619964
Intellectual disability syndromic and non-syndromic v0.4859 ARFGEF1 Zornitza Stark edited their review of gene: ARFGEF1: Changed phenotypes: Developmental delay, impaired speech, and behavioral abnormalities, MIM# 619964
Autoinflammatory Disorders v0.156 CEBPE Peter McNaughton gene: CEBPE was added
gene: CEBPE was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Literature
Mode of inheritance for gene: CEBPE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEBPE were set to PMID: 31201888
Phenotypes for gene: CEBPE were set to Autoinflammation
Mode of pathogenicity for gene: CEBPE was set to Other
Review for gene: CEBPE was set to AMBER
Added comment: Single family presenting with autoinflammatory syndrome - recurrent attacks of abdominal pain, aseptic fever, and systemic inflammation lasting 4 to 5 days. These were accompanied by an acute-phase response and occasionally by nailbed, tongue, submandibular and gluteal abscesses; intra-abdominal granulomas; pyoderma gangrenosum; and buccal ulcerations
Sources: Literature
Genetic Epilepsy v0.1634 ARFGEF1 Zornitza Stark Phenotypes for gene: ARFGEF1 were changed from Intellectual disability; Epilepsy to Developmental delay, impaired speech, and behavioral abnormalities, MIM# 619964
Genetic Epilepsy v0.1633 ARFGEF1 Zornitza Stark edited their review of gene: ARFGEF1: Changed phenotypes: Developmental delay, impaired speech, and behavioral abnormalities, MIM# 619964
Mendeliome v1.179 ARFGEF1 Zornitza Stark Phenotypes for gene: ARFGEF1 were changed from Intellectual disability; Epilepsy to Developmental delay, impaired speech, and behavioral abnormalities, MIM# 619964
Mendeliome v1.178 ARFGEF1 Zornitza Stark edited their review of gene: ARFGEF1: Changed phenotypes: Developmental delay, impaired speech, and behavioral abnormalities, MIM# 619964
Mendeliome v1.178 PAK2 Zornitza Stark Phenotypes for gene: PAK2 were changed from Knobloch 2 syndrome to Knobloch 2 syndrome, MIM#618458
Mendeliome v1.177 INPP5E Zornitza Stark Publications for gene: INPP5E were set to 19668216; 32139166; 29230161; 29052317; 27998989; 27401686; 19668215
Mendeliome v1.176 INPP5E Zornitza Stark edited their review of gene: INPP5E: Added comment: Additional MORM family reported in PMID 34211432, hmz LoF.; Changed publications: 19668216, 32139166, 29230161, 29052317, 27998989, 27401686, 19668215, 34211432
Disorders of immune dysregulation v0.147 IKZF1 Peter McNaughton gene: IKZF1 was added
gene: IKZF1 was added to Disorders of immune dysregulation. Sources: Literature
Mode of inheritance for gene: IKZF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IKZF1 were set to PMID: 35333544
Phenotypes for gene: IKZF1 were set to Immune dysregulation
Mode of pathogenicity for gene: IKZF1 was set to Other
Review for gene: IKZF1 was set to GREEN
Added comment: Eight individuals harboring heterozygous IKZF1R183H or IKZF1R183C variants associated with GOF effects. The clinical phenotypes and pathophysiology associated with IKZF1R183H/C differ from those of previously reported patients with IKZF1HI, IKZF1DN, and IKZF1DD and should therefore be considered as a novel IKAROS-associated disease entity. This condition is characterized by immune dysregulation manifestations including inflammation, autoimmunity, atopy, and polyclonal PC proliferation.
Sources: Literature
Autoinflammatory Disorders v0.156 TBK1 Peter McNaughton gene: TBK1 was added
gene: TBK1 was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Literature
Mode of inheritance for gene: TBK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBK1 were set to PMID: 34363755
Phenotypes for gene: TBK1 were set to Autoinflammation
Review for gene: TBK1 was set to GREEN
Added comment: 4 individuals from 3 unrelated families with biallelic LOF mutations with early onset autoinflammatory syndrome without susceptibility to viral infection.
Sources: Literature
Disorders of immune dysregulation v0.147 IKZF2 Peter McNaughton reviewed gene: IKZF2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34826259; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Prepair 1000+ v0.89 HYAL1 Zornitza Stark Marked gene: HYAL1 as ready
Prepair 1000+ v0.89 HYAL1 Zornitza Stark Gene: hyal1 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.89 HYAL1 Zornitza Stark Classified gene: HYAL1 as Red List (low evidence)
Prepair 1000+ v0.89 HYAL1 Zornitza Stark Gene: hyal1 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.88 HOGA1 Zornitza Stark Tag for review tag was added to gene: HOGA1.
Prepair 1000+ v0.88 HGD Zornitza Stark Marked gene: HGD as ready
Prepair 1000+ v0.88 HGD Zornitza Stark Gene: hgd has been classified as Red List (Low Evidence).
Prepair 1000+ v0.88 HGD Zornitza Stark Classified gene: HGD as Red List (low evidence)
Prepair 1000+ v0.88 HGD Zornitza Stark Gene: hgd has been classified as Red List (Low Evidence).
Prepair 1000+ v0.87 HFE Zornitza Stark Marked gene: HFE as ready
Prepair 1000+ v0.87 HFE Zornitza Stark Gene: hfe has been classified as Red List (Low Evidence).
Prepair 1000+ v0.87 HFE Zornitza Stark Classified gene: HFE as Red List (low evidence)
Prepair 1000+ v0.87 HFE Zornitza Stark Gene: hfe has been classified as Red List (Low Evidence).
Prepair 1000+ v0.86 HBA2 Zornitza Stark Tag for review tag was added to gene: HBA2.
Prepair 1000+ v0.86 HBA1 Zornitza Stark Tag for review tag was added to gene: HBA1.
Prepair 1000+ v0.86 GRHPR Zornitza Stark Tag for review tag was added to gene: GRHPR.
Prepair 1000+ v0.86 GP9 Zornitza Stark Tag for review tag was added to gene: GP9.
Prepair 1000+ v0.86 GP1BA Zornitza Stark Tag for review tag was added to gene: GP1BA.
Prepair 1000+ v0.86 GJB2 Zornitza Stark Marked gene: GJB2 as ready
Prepair 1000+ v0.86 GJB2 Zornitza Stark Gene: gjb2 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.86 GJB2 Zornitza Stark Classified gene: GJB2 as Red List (low evidence)
Prepair 1000+ v0.86 GJB2 Zornitza Stark Gene: gjb2 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.85 GJB2 Zornitza Stark reviewed gene: GJB2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Prepair 1000+ v0.85 GJB1 Zornitza Stark Tag for review tag was added to gene: GJB1.
Prepair 1000+ v0.85 GALK1 Zornitza Stark Tag for review tag was added to gene: GALK1.
Prepair 1000+ v0.85 G6PD Zornitza Stark Tag for review tag was added to gene: G6PD.
Prepair 1000+ v0.85 F11 Zornitza Stark Tag for review tag was added to gene: F11.
Hydrops fetalis v0.290 SPTA1 Zornitza Stark Marked gene: SPTA1 as ready
Hydrops fetalis v0.290 SPTA1 Zornitza Stark Gene: spta1 has been classified as Green List (High Evidence).
Hydrops fetalis v0.290 SPTA1 Zornitza Stark Publications for gene: SPTA1 were set to 34132406; 35483216; 31333484; 29594000
Fetal anomalies v1.50 SPTA1 Zornitza Stark Marked gene: SPTA1 as ready
Fetal anomalies v1.50 SPTA1 Zornitza Stark Gene: spta1 has been classified as Green List (High Evidence).
Fetal anomalies v1.50 SPTA1 Zornitza Stark Classified gene: SPTA1 as Green List (high evidence)
Fetal anomalies v1.50 SPTA1 Zornitza Stark Gene: spta1 has been classified as Green List (High Evidence).
Hydrops fetalis v0.289 SPTA1 Zornitza Stark Publications for gene: SPTA1 were set to 34132406
Fetal anomalies v1.49 SPTA1 Zornitza Stark gene: SPTA1 was added
gene: SPTA1 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: SPTA1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SPTA1 were set to 34132406; 35483216; 31333484; 29594000
Phenotypes for gene: SPTA1 were set to Spherocytosis type 3 #270970; Elliptocytosis-2 #130600; pyropoikilocytosis #266140
Review for gene: SPTA1 was set to GREEN
Added comment: Severe presentations with hydrops reported.
Sources: Expert Review
Hydrops fetalis v0.289 SPTA1 Zornitza Stark Mode of inheritance for gene: SPTA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hydrops fetalis v0.288 SPTA1 Zornitza Stark Classified gene: SPTA1 as Green List (high evidence)
Hydrops fetalis v0.288 SPTA1 Zornitza Stark Gene: spta1 has been classified as Green List (High Evidence).
Hydrops fetalis v0.287 SPTA1 Zornitza Stark reviewed gene: SPTA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35483216, 31333484, 29594000; Phenotypes: Spherocytosis type 3 #270970, Elliptocytosis-2 #130600, Pyropoikilocytosis #266140; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hydrops fetalis v0.287 GLDN Zornitza Stark Marked gene: GLDN as ready
Hydrops fetalis v0.287 GLDN Zornitza Stark Gene: gldn has been classified as Amber List (Moderate Evidence).
Hydrops fetalis v0.287 GLDN Zornitza Stark Classified gene: GLDN as Amber List (moderate evidence)
Hydrops fetalis v0.287 GLDN Zornitza Stark Gene: gldn has been classified as Amber List (Moderate Evidence).
Hydrops fetalis v0.286 GLDN Zornitza Stark reviewed gene: GLDN: Rating: AMBER; Mode of pathogenicity: None; Publications: 35806855; Phenotypes: Lethal congenital contracture syndrome 11, MIM# 617194; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.85 EYS Zornitza Stark Tag for review tag was added to gene: EYS.
Hydrops fetalis v0.286 DOK7 Zornitza Stark Publications for gene: DOK7 were set to 31880392; 19261599
Hydrops fetalis v0.285 DOK7 Zornitza Stark Classified gene: DOK7 as Green List (high evidence)
Hydrops fetalis v0.285 DOK7 Zornitza Stark Gene: dok7 has been classified as Green List (High Evidence).
Hydrops fetalis v0.284 DOK7 Zornitza Stark edited their review of gene: DOK7: Added comment: Upgrade to Green with additional families published (founder variant).; Changed rating: GREEN; Changed publications: 31880392, 19261599, 34132406
Prepair 1000+ v0.85 CYP21A2 Zornitza Stark Tag for review tag was added to gene: CYP21A2.
Early-onset Parkinson disease v0.230 ATXN1_CAG Zornitza Stark Marked STR: ATXN1_CAG as ready
Early-onset Parkinson disease v0.230 ATXN1_CAG Zornitza Stark Str: atxn1_cag has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.230 ATXN1_CAG Zornitza Stark Classified STR: ATXN1_CAG as Green List (high evidence)
Early-onset Parkinson disease v0.230 ATXN1_CAG Zornitza Stark Str: atxn1_cag has been classified as Green List (High Evidence).
Congenital Heart Defect v0.254 KYNU Zornitza Stark Marked gene: KYNU as ready
Congenital Heart Defect v0.254 KYNU Zornitza Stark Gene: kynu has been classified as Green List (High Evidence).
Congenital Heart Defect v0.254 KYNU Zornitza Stark Phenotypes for gene: KYNU were changed from MIM# 617661 Vertebral, cardiac, renal, and limb defects syndrome 2 to Vertebral, cardiac, renal, and limb defects syndrome 2, MIM# 617661
Congenital Heart Defect v0.253 KYNU Zornitza Stark Classified gene: KYNU as Green List (high evidence)
Congenital Heart Defect v0.253 KYNU Zornitza Stark Gene: kynu has been classified as Green List (High Evidence).
Congenital Heart Defect v0.252 KDR Zornitza Stark Marked gene: KDR as ready
Congenital Heart Defect v0.252 KDR Zornitza Stark Gene: kdr has been classified as Red List (Low Evidence).
Congenital Heart Defect v0.252 KDR Zornitza Stark Phenotypes for gene: KDR were changed from Tetralogy of Fallot to Tetralogy of Fallot, MONDO:0008542
Congenital Heart Defect v0.251 KDR Zornitza Stark Mode of inheritance for gene: KDR was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.250 KDR Zornitza Stark Classified gene: KDR as Red List (low evidence)
Congenital Heart Defect v0.250 KDR Zornitza Stark Gene: kdr has been classified as Red List (Low Evidence).
Congenital Heart Defect v0.249 KDR Zornitza Stark reviewed gene: KDR: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Tetralogy of Fallot, MONDO:0008542; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.249 HDAC8 Zornitza Stark Marked gene: HDAC8 as ready
Congenital Heart Defect v0.249 HDAC8 Zornitza Stark Gene: hdac8 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.249 HDAC8 Zornitza Stark Phenotypes for gene: HDAC8 were changed from MIM# 300882 Cornelia de Lange syndrome 5 to Cornelia de Lange syndrome 5, MIM# 300882
Congenital Heart Defect v0.248 HDAC8 Zornitza Stark Mode of inheritance for gene: HDAC8 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Congenital Heart Defect v0.247 HDAC8 Zornitza Stark reviewed gene: HDAC8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cornelia de Lange syndrome 5, MIM# 300882; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Congenital Heart Defect v0.247 HDAC8 Zornitza Stark Classified gene: HDAC8 as Green List (high evidence)
Congenital Heart Defect v0.247 HDAC8 Zornitza Stark Gene: hdac8 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.246 HAAO Zornitza Stark Marked gene: HAAO as ready
Congenital Heart Defect v0.246 HAAO Zornitza Stark Gene: haao has been classified as Green List (High Evidence).
Congenital Heart Defect v0.246 HAAO Zornitza Stark Phenotypes for gene: HAAO were changed from Atrial septal defect; Hypoplastic left heart syndrome; Aortic stenosis; Mitral stenosis; Tetralogy of fallot with complete atriventricular canal and pulmonary stenosis; Lsvc and left pulmonary artery arising from the ductus arteriosus; Shone syndrome with aortic coarctation to Vertebral, cardiac, renal, and limb defects syndrome 1, MIM# 617660; Atrial septal defect; Hypoplastic left heart syndrome; Aortic stenosis; Mitral stenosis; Tetralogy of fallot with complete atriventricular canal and pulmonary stenosis; Lsvc and left pulmonary artery arising from the ductus arteriosus; Shone syndrome with aortic coarctation
Congenital Heart Defect v0.245 HAAO Zornitza Stark Classified gene: HAAO as Green List (high evidence)
Congenital Heart Defect v0.245 HAAO Zornitza Stark Gene: haao has been classified as Green List (High Evidence).
Congenital Heart Defect v0.244 GLI3 Zornitza Stark Marked gene: GLI3 as ready
Congenital Heart Defect v0.244 GLI3 Zornitza Stark Gene: gli3 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.244 GLI3 Zornitza Stark Phenotypes for gene: GLI3 were changed from ASD, VSD, AVSD, aortic arch anomaly, PDA to Pallister-Hall syndrome, MIM# 146510; ASD, VSD, AVSD, aortic arch anomaly, PDA
Congenital Heart Defect v0.243 GLI3 Zornitza Stark Mode of pathogenicity for gene: GLI3 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 Other
Congenital Heart Defect v0.242 GLI3 Zornitza Stark Classified gene: GLI3 as Green List (high evidence)
Congenital Heart Defect v0.242 GLI3 Zornitza Stark Gene: gli3 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.241 GLI3 Zornitza Stark reviewed gene: GLI3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pallister-Hall syndrome, MIM# 146510; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.241 FOXP1 Zornitza Stark Marked gene: FOXP1 as ready
Congenital Heart Defect v0.241 FOXP1 Zornitza Stark Gene: foxp1 has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v0.241 FOXP1 Zornitza Stark Phenotypes for gene: FOXP1 were changed from Atrial septal defect; Atrioventricular septal defect; Patent ductus arteriosus; Pulmonic stenosis; Hypoplastic left heart syndrome to Intellectual developmental disorder with language impairment with or without autistic features, MIM# 613670; Atrial septal defect; Atrioventricular septal defect; Patent ductus arteriosus; Pulmonic stenosis; Hypoplastic left heart syndrome
Congenital Heart Defect v0.240 FOXP1 Zornitza Stark Classified gene: FOXP1 as Amber List (moderate evidence)
Congenital Heart Defect v0.240 FOXP1 Zornitza Stark Gene: foxp1 has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v0.239 FOXP1 Zornitza Stark reviewed gene: FOXP1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder with language impairment with or without autistic features, MIM# 613670; Mode of inheritance: None
Prepair 1000+ v0.85 CYP19A1 Zornitza Stark Tag for review tag was added to gene: CYP19A1.
Early-onset Parkinson disease v0.229 MT-ND6 Zornitza Stark Tag mtDNA tag was added to gene: MT-ND6.
Prepair 1000+ v0.85 WNT10A Crystle Lee gene: WNT10A was added
gene: WNT10A was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: WNT10A was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: WNT10A were set to 19559398; 30426266
Phenotypes for gene: WNT10A were set to Odontoonychodermal dysplasia 257980 AR; Schopf-Schulz-Passarge syndrome 224750 AR; Tooth agenesis, selective, 4 150400 AR, AD
Penetrance for gene: WNT10A were set to Incomplete
Review for gene: WNT10A was set to RED
Added comment: Well established gene disease association.

Genotype-phenotype correlation is unclear. The same variant has been associated with all 3 phenotypes and both AR and AD inheritance. Variable expressivity, however milder phenotypes seem to be associated with AD (PMID: 19559398; 30426266)
Sources: Literature
Prepair 1000+ v0.85 TFR2 Crystle Lee gene: TFR2 was added
gene: TFR2 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: TFR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TFR2 were set to 29743178
Phenotypes for gene: TFR2 were set to Hemochromatosis, type 3, MIM#604250
Review for gene: TFR2 was set to AMBER
Added comment: Age of onset in individuals with TFR2-HHC is earlier than in individuals with HFE-associated hereditary hemochromatosis (Gene Reviews)

PMID: 29743178: Mean age at diagnosis for TFR2 HH (32 years) was significantly higher than for HJV HH
Sources: Literature
Early-onset Parkinson disease v0.229 WASL Zornitza Stark Marked gene: WASL as ready
Early-onset Parkinson disease v0.229 WASL Zornitza Stark Gene: wasl has been classified as Red List (Low Evidence).
Prepair 1000+ v0.85 TECPR2 Crystle Lee gene: TECPR2 was added
gene: TECPR2 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: TECPR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TECPR2 were set to 23176824; 26542466; 35130874
Phenotypes for gene: TECPR2 were set to Neuropathy, hereditary sensory and autonomic, type IX, with developmental delay, MIM#615031
Review for gene: TECPR2 was set to GREEN
Added comment: SPG49 is an autosomal recessive complicated form of spastic paraplegia. PMID 23176824 reported 4 Jewish Bukharian individuals homozygous for same founder variant and delayed psychomotor development, intellectual disability, and onset of spastic paraplegia in the first decade. Affected individuals also had dysmorphic features, thin corpus callosum on brain imaging, and episodes of central apnea, some of which were fatal. Three additional patients from unrelated non-Bukharian families reported in PMID 26542466, harboring two novel variants (c.1319delT, c.C566T) in this gene. In addition to intellectual disability and evolving spasticity, autonomic-sensory neuropathy accompanied by chronic respiratory disease and paroxysmal autonomic events were prominent
Sources: Literature
Prepair 1000+ v0.85 TAT Crystle Lee gene: TAT was added
gene: TAT was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: TAT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TAT were set to 16574453
Phenotypes for gene: TAT were set to Tyrosinemia, type II (MIM#276600)
Review for gene: TAT was set to AMBER
Added comment: Well established gene-disease association. Also known as Richner-Hanhart syndrome, the clinical hallmarks consist of a triad of painful palmoplantar keratoderma, keratitis with photophobia and variable mental impairment.

RHS shows inter and intrafamilial phenotypic variability. Phenotype variability observed even among individuals sharing the same pathogenic variant.
Sources: Literature
Mendeliome v1.176 WASL Zornitza Stark Marked gene: WASL as ready
Mendeliome v1.176 WASL Zornitza Stark Gene: wasl has been classified as Red List (Low Evidence).
Early-onset Parkinson disease v0.229 WASL Zornitza Stark Phenotypes for gene: WASL were changed from Early onset parkinsonism to Parkinson's disease, MONDO:0005180, WASL-related
Mendeliome v1.176 WASL Zornitza Stark gene: WASL was added
gene: WASL was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: WASL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WASL were set to 33571872
Phenotypes for gene: WASL were set to Parkinson's disease, MONDO:0005180, WASL-related
Review for gene: WASL was set to RED
Added comment: Single family reported, where bi-allelic variants segregated with PD in three affected individuals.
Sources: Literature
Early-onset Parkinson disease v0.228 WASL Zornitza Stark Classified gene: WASL as Red List (low evidence)
Early-onset Parkinson disease v0.228 WASL Zornitza Stark Gene: wasl has been classified as Red List (Low Evidence).
Prepair 1000+ v0.85 SLC4A11 Crystle Lee gene: SLC4A11 was added
gene: SLC4A11 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: SLC4A11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC4A11 were set to 26451371; 20118786; 21203343
Phenotypes for gene: SLC4A11 were set to Corneal dystrophy, Fuchs endothelial, 4, MIM# 613268; Corneal endothelial dystrophy and perceptive deafness, MIM# 217400; Corneal endothelial dystrophy, autosomal recessive, MIM# 217700
Review for gene: SLC4A11 was set to AMBER
Added comment: Well established gene-disease association. Inter- and intra-familial variability and no genotype-phenotype correlation
Sources: Literature
Early-onset Parkinson disease v0.227 WASL Zornitza Stark reviewed gene: WASL: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Parkinson's disease, MONDO:0005180, WASL-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.227 KMT2B Zornitza Stark Marked gene: KMT2B as ready
Early-onset Parkinson disease v0.227 KMT2B Zornitza Stark Gene: kmt2b has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.227 KMT2B Zornitza Stark Phenotypes for gene: KMT2B were changed from DYT28; Childhood‐onset and progressive dystonia; Dysarthria; Dysphagia; Developmental delay; Dysmorphic features; Parkinsonism; OMIM 617284 to Dystonia 28, childhood-onset , MIM#617284
Early-onset Parkinson disease v0.226 KMT2B Zornitza Stark Mode of inheritance for gene: KMT2B was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.225 KMT2B Zornitza Stark Classified gene: KMT2B as Green List (high evidence)
Early-onset Parkinson disease v0.225 KMT2B Zornitza Stark Gene: kmt2b has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.224 KMT2B Zornitza Stark reviewed gene: KMT2B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Dystonia 28, childhood-onset , MIM#617284; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.224 GBA Zornitza Stark Marked gene: GBA as ready
Early-onset Parkinson disease v0.224 GBA Zornitza Stark Gene: gba has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.224 GBA Zornitza Stark Phenotypes for gene: GBA were changed from Gaucher Disease Type 1; Early onset parkinsonism; Bone lesions; Hepatosplenomegaly; Hematologic disorders; OMIM 230800 to Parkinson's disease, MONDO:0005180, GBA-related
Prepair 1000+ v0.85 SLC26A4 Crystle Lee gene: SLC26A4 was added
gene: SLC26A4 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: SLC26A4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC26A4 were set to 24599119
Phenotypes for gene: SLC26A4 were set to Deafness, autosomal recessive 4, with enlarged vestibular aqueduct (MIM#600791); Pendred syndrome (MIM#274600)
Review for gene: SLC26A4 was set to AMBER
Added comment: PDS and NSEVA are considered a disease spectrum and are distinguishable based on the presence of thyroid dysfunction in PDS (GeneReviews).

In relation to severity of hearing, there's no correlation between missense vs PTCs. There was great variation in hearing loss severity with the same mutations. Phenotype cannot be predicted from the genotype (PMID: 24599119)
Sources: Literature
Early-onset Parkinson disease v0.223 GBA Zornitza Stark Publications for gene: GBA were set to PMID: 12809640
Early-onset Parkinson disease v0.222 GBA Zornitza Stark Mode of inheritance for gene: GBA was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.221 GBA Zornitza Stark Classified gene: GBA as Green List (high evidence)
Early-onset Parkinson disease v0.221 GBA Zornitza Stark Gene: gba has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.220 GBA Zornitza Stark reviewed gene: GBA: Rating: GREEN; Mode of pathogenicity: None; Publications: 35639160; Phenotypes: Parkinson's disease, MONDO:0005180, GBA-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.220 FRRS1L Zornitza Stark Marked gene: FRRS1L as ready
Early-onset Parkinson disease v0.220 FRRS1L Zornitza Stark Gene: frrs1l has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.220 FRRS1L Zornitza Stark Phenotypes for gene: FRRS1L were changed from Developmental and epileptic dyskinetic encephalopathy; Seizures; Chorea; Parkinsonism; Developmental delay; OMIM 616981 to Developmental and epileptic encephalopathy 37, MIM# 616981; Seizures; Chorea; Parkinsonism; Developmental delay
Early-onset Parkinson disease v0.219 FRRS1L Zornitza Stark Classified gene: FRRS1L as Green List (high evidence)
Early-onset Parkinson disease v0.219 FRRS1L Zornitza Stark Gene: frrs1l has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.218 FRRS1L Zornitza Stark reviewed gene: FRRS1L: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 37, MIM# 616981; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.85 SLC12A3 Crystle Lee gene: SLC12A3 was added
gene: SLC12A3 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: SLC12A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC12A3 were set to 8528245; 11102542
Phenotypes for gene: SLC12A3 were set to Gitelman syndrome (MIM#263800)
Review for gene: SLC12A3 was set to AMBER
Added comment: Gitelman syndrome is an autosomal recessive renal tubular salt-wasting disorder characterized by hypokalemic metabolic alkalosis with hypomagnesemia and hypocalciuria. It is the most common renal tubular disorder among Caucasians (prevalence of 1 in 40,000). Most individuals have onset of symptoms as adults, but some can present in childhood. Clinical features include transient periods of muscle weakness and tetany, abdominal pains, and chondrocalcinosis.

Well established gene-disease association.
Sources: Literature
Prepair 1000+ v0.85 CYP11B1 Zornitza Stark Tag for review tag was added to gene: CYP11B1.
Prepair 1000+ v0.85 RS1 Crystle Lee gene: RS1 was added
gene: RS1 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: RS1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: RS1 were set to 15932525; 23453514; 23847049
Phenotypes for gene: RS1 were set to Retinoschisis (MIM#312700)
Review for gene: RS1 was set to AMBER
Added comment: - This gene is known to be associated with X-linked recessive disease, however, some affected females have been reported (OMIM).
- May not clinically manifest until middle life (OMIM)
- Many PTCs and missense reported. All result in same XLRS phenotype (although expression can be variable). Also a knockout mouse with similar phenotype.
- PTCs and missense involving cysteines tend to result in a more severe phenotype, whereas other missense can vary widely in severity (PMID: 23847049).
Sources: Literature
Prepair 1000+ v0.85 PYGM Crystle Lee gene: PYGM was added
gene: PYGM was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: PYGM was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PYGM were set to McArdle disease (MIM#232600)
Review for gene: PYGM was set to AMBER
Added comment: Gene-disease association for bi-allelic variants is well established.

McCardle disease: glycogen storage disease type V (GSD5), characterized by onset of exercise intolerance and muscle cramps in childhood or adolescence. Transient myoglobinuria may occur after exercise, due to rhabdomyolysis. Severe myoglobinuria may lead to acute renal failure. Patients may report muscle weakness, myalgia, and lack of endurance since childhood or adolescence. Later in adult life, there is persistent and progressive muscle weakness and atrophy with fatty replacement. McArdle disease is a relatively benign disorder, except for possible renal failure as a complication of myoglobinuria

Clinical heterogeneity exists; about 10% of all affected individuals have mild manifestations (e.g., fatigue or poor stamina without contractures) and remain virtually asymptomatic during daily activities of living(Gene Reviews)
Sources: Literature
Prepair 1000+ v0.85 OAT Crystle Lee gene: OAT was added
gene: OAT was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: OAT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OAT were set to 33463379; 34340878
Phenotypes for gene: OAT were set to Gyrate atrophy of choroid and retina with or without ornithinemia (MIM#258870)
Review for gene: OAT was set to AMBER
Added comment: Biallelic variants associated with deficiency of mitochondrial enzyme ornithine aminotransferase and elevation of plasma ornithine levels without elevation of ammonia. Characterized by ocular anomalies; however, neurological and muscular features may also be present.

There is evidence of intra-familial variability.
Sources: Literature
Prepair 1000+ v0.85 NR2E3 Crystle Lee gene: NR2E3 was added
gene: NR2E3 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: NR2E3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: NR2E3 were set to 32679203; 33138239; 19139342; 26910043
Phenotypes for gene: NR2E3 were set to Enhanced S-cone syndrome (MIM#268100); Retinitis pigmentosa 37 (MIM#611131)
Review for gene: NR2E3 was set to AMBER
Added comment: Both biallelic and monoallelic variants associated with a range of phenotypes including retinitis pigments (NR2E3-related retinal dystrophy). Highly variable phenotype.

PMID: 26910043: Single variant associated with a wide range of phenotypic characteristics
Sources: Literature
Prepair 1000+ v0.85 MEFV Crystle Lee gene: MEFV was added
gene: MEFV was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: MEFV was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for gene: MEFV were set to Familial Mediterranean fever, AR (MIM#249100)
Penetrance for gene: MEFV were set to Incomplete
Review for gene: MEFV was set to AMBER
Added comment: Well established association. Predominantly bi-allelic, though a limited range of heterozygous variants have been associated with disease.
Sources: Literature
Prepair 1000+ v0.85 MCCC2 Crystle Lee gene: MCCC2 was added
gene: MCCC2 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: MCCC2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MCCC2 were set to 3-Methylcrotonyl-CoA carboxylase 2 deficiency (MIM#210210)
Review for gene: MCCC2 was set to RED
Added comment: Variants in this gene cause a biochemical defect. Relationship to clinical features is less certain.

Variants in this gene have been reported in multiple individuals with ID/regression/neurological phenotypes. However, ascertainment through NBS programs indicates most individuals remain asymptomatic and therefore caution should be applied in interpreting the clinical significance of variants in this gene (though they undoubtedly cause a biochemical phenotype).
Sources: Literature
Early-onset Parkinson disease v0.218 ALPL Zornitza Stark Marked gene: ALPL as ready
Early-onset Parkinson disease v0.218 ALPL Zornitza Stark Gene: alpl has been classified as Red List (Low Evidence).
Early-onset Parkinson disease v0.218 ALPL Zornitza Stark Phenotypes for gene: ALPL were changed from Hypophosphatasia; Osteomalacia; Parkinsonism; OMIM 146300 to Hypophosphatasia, adult, MIM# 146300; Osteomalacia; Parkinsonism
Early-onset Parkinson disease v0.217 ALPL Zornitza Stark Classified gene: ALPL as Red List (low evidence)
Early-onset Parkinson disease v0.217 ALPL Zornitza Stark Gene: alpl has been classified as Red List (Low Evidence).
Early-onset Parkinson disease v0.216 ALPL Zornitza Stark reviewed gene: ALPL: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypophosphatasia, adult, MIM# 146300; Mode of inheritance: None
Prepair 1000+ v0.85 CERKL Zornitza Stark Tag for review tag was added to gene: CERKL.
Early-onset Parkinson disease v0.216 ADAR Zornitza Stark Marked gene: ADAR as ready
Early-onset Parkinson disease v0.216 ADAR Zornitza Stark Gene: adar has been classified as Green List (High Evidence).
Prepair 1000+ v0.85 MCCC1 Crystle Lee gene: MCCC1 was added
gene: MCCC1 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: MCCC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCCC1 were set to 31730530
Phenotypes for gene: MCCC1 were set to 3-Methylcrotonyl-CoA carboxylase 1 deficiency (MIM#210200)
Review for gene: MCCC1 was set to RED
Added comment: Highly variable phenotype. May present in infancy but also be present in asymptomatic adults (OMIM)

Variants in this gene cause a biochemical defect. The relationship to clinical phenotype has been questioned by NBS programs, PMID 31730530.
Sources: Literature
Early-onset Parkinson disease v0.216 ADAR Zornitza Stark Classified gene: ADAR as Green List (high evidence)
Early-onset Parkinson disease v0.216 ADAR Zornitza Stark Gene: adar has been classified as Green List (High Evidence).
Prepair 1000+ v0.85 BTD Zornitza Stark Tag for review tag was added to gene: BTD.
Prepair 1000+ v0.85 AIRE Zornitza Stark Tag for review tag was added to gene: AIRE.
Prepair 1000+ v0.85 KCNE1 Zornitza Stark Marked gene: KCNE1 as ready
Prepair 1000+ v0.85 KCNE1 Zornitza Stark Gene: kcne1 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.85 KCNE1 Zornitza Stark Phenotypes for gene: KCNE1 were changed from Jervell and Lange-Nielsen syndrome 2, 612347 (3) to Jervell and Lange-Nielsen syndrome 2, MIM# 612347
Prepair 1000+ v0.84 KCNE1 Zornitza Stark Classified gene: KCNE1 as Red List (low evidence)
Prepair 1000+ v0.84 KCNE1 Zornitza Stark Gene: kcne1 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.83 KCNE1 Zornitza Stark reviewed gene: KCNE1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Prepair 1000+ v0.83 VPS13A Zornitza Stark Tag for review tag was added to gene: VPS13A.
Prepair 1000+ v0.83 TH Zornitza Stark Marked gene: TH as ready
Prepair 1000+ v0.83 TH Zornitza Stark Gene: th has been classified as Green List (High Evidence).
Prepair 1000+ v0.83 TH Zornitza Stark Phenotypes for gene: TH were changed from Segawa syndrome, recessive, 605407 (3) to Segawa syndrome, recessive, MIM# 605407
Prepair 1000+ v0.82 SPG11 Zornitza Stark Marked gene: SPG11 as ready
Prepair 1000+ v0.82 SPG11 Zornitza Stark Gene: spg11 has been classified as Green List (High Evidence).
Prepair 1000+ v0.82 SPG11 Zornitza Stark Phenotypes for gene: SPG11 were changed from Spastic paraplegia 11, autosomal recessive, 604360 (3) to Spastic paraplegia 11, autosomal recessive, MIM# 604360
Prepair 1000+ v0.81 SPG11 Zornitza Stark Publications for gene: SPG11 were set to
Prepair 1000+ v0.80 SPART Zornitza Stark Marked gene: SPART as ready
Prepair 1000+ v0.80 SPART Zornitza Stark Gene: spart has been classified as Green List (High Evidence).
Prepair 1000+ v0.80 SPART Zornitza Stark Phenotypes for gene: SPART were changed from Troyer syndrome, 275900 (3) to Troyer syndrome (MIM#275900); SPG20; MONDO:0010156
Prepair 1000+ v0.79 SPART Zornitza Stark Publications for gene: SPART were set to
Prepair 1000+ v0.78 SETX Zornitza Stark Marked gene: SETX as ready
Prepair 1000+ v0.78 SETX Zornitza Stark Gene: setx has been classified as Green List (High Evidence).
Prepair 1000+ v0.78 SETX Zornitza Stark Phenotypes for gene: SETX were changed from Spinocerebellar ataxia, autosomal recessive 1, 606002 (3) to Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 (MIM#606002)
Prepair 1000+ v0.77 SETX Zornitza Stark Publications for gene: SETX were set to
Prepair 1000+ v0.76 PLA2G6 Zornitza Stark Marked gene: PLA2G6 as ready
Prepair 1000+ v0.76 PLA2G6 Zornitza Stark Gene: pla2g6 has been classified as Green List (High Evidence).
Prepair 1000+ v0.76 PLA2G6 Zornitza Stark Phenotypes for gene: PLA2G6 were changed from Neurodegeneration with brain iron accumulation 2B, 610217 (3) to Infantile neuroaxonal dystrophy 1 MIM#256600; Neurodegeneration with brain iron accumulation 2B MIM#610217
Prepair 1000+ v0.75 PLA2G6 Zornitza Stark Publications for gene: PLA2G6 were set to
Prepair 1000+ v0.74 PANK2 Zornitza Stark Marked gene: PANK2 as ready
Prepair 1000+ v0.74 PANK2 Zornitza Stark Gene: pank2 has been classified as Green List (High Evidence).
Prepair 1000+ v0.74 PANK2 Zornitza Stark Phenotypes for gene: PANK2 were changed from Neurodegeneration with brain iron accumulation 1, 234200 (3) to Neurodegeneration with brain iron accumulation 1, MIM#234200
Prepair 1000+ v0.73 PANK2 Zornitza Stark Publications for gene: PANK2 were set to
Prepair 1000+ v0.72 NPC2 Zornitza Stark Marked gene: NPC2 as ready
Prepair 1000+ v0.72 NPC2 Zornitza Stark Gene: npc2 has been classified as Green List (High Evidence).
Prepair 1000+ v0.72 NPC2 Zornitza Stark Phenotypes for gene: NPC2 were changed from Niemann-pick disease, type C2, 607625 (3) to Niemann-pick disease, type C2, MIM#607625
Prepair 1000+ v0.71 NPC2 Zornitza Stark Publications for gene: NPC2 were set to
Prepair 1000+ v0.70 NPC1 Zornitza Stark Marked gene: NPC1 as ready
Prepair 1000+ v0.70 NPC1 Zornitza Stark Gene: npc1 has been classified as Green List (High Evidence).
Prepair 1000+ v0.70 NPC1 Zornitza Stark Phenotypes for gene: NPC1 were changed from Niemann-Pick disease, type C1, 257220 (3) to Niemann-Pick disease, type C1, MIM#257220
Prepair 1000+ v0.69 NPC1 Zornitza Stark Publications for gene: NPC1 were set to
Prepair 1000+ v0.68 LMNA Zornitza Stark reviewed gene: LMNA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Restrictive dermopathy, lethal, MIM#275210; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.68 LMNA Zornitza Stark Marked gene: LMNA as ready
Prepair 1000+ v0.68 LMNA Zornitza Stark Gene: lmna has been classified as Green List (High Evidence).
Prepair 1000+ v0.68 LMNA Zornitza Stark Publications for gene: LMNA were set to
Prepair 1000+ v0.67 LDLR Zornitza Stark Tag for review tag was added to gene: LDLR.
Prepair 1000+ v0.67 FIG4 Zornitza Stark Marked gene: FIG4 as ready
Prepair 1000+ v0.67 FIG4 Zornitza Stark Gene: fig4 has been classified as Green List (High Evidence).
Prepair 1000+ v0.67 FIG4 Zornitza Stark Phenotypes for gene: FIG4 were changed from Yunis-Varon syndrome, 216340 (3) to Yunis-Varon syndrome, MIM#216340
Prepair 1000+ v0.66 FIG4 Zornitza Stark Publications for gene: FIG4 were set to
Hyperinsulinism v0.32 PMM2 Zornitza Stark edited their review of gene: PMM2: Added comment: Cabezas et al (2017) reported co-occurrence of hyperinsulinaemic hypoglycaemia and polycystic kidney disease (HIPKD in 17 children from 11 unrelated families. Patients presented with hyperinsulinaemic hypoglycaemia in infancy and enlarged kidneys with multiple kidney cysts. Some progressed to ESKD and some had liver cysts. Whole-genome linkage analysis in 5 informative families identified a single significant locus on chromosome 16p13.2. Sequencing of the coding regions of all linked genes failed to identify biallelic mutations. Instead, they found in all patients a promoter mutation (c.-167G>T) in PMM2, either homozygous or in trans with PMM2 coding mutations. They found deglycosylation in cultured pancreatic β cells altered insulin secretion. In vitro, the PMM2 promoter mutation associated with decreased transcriptional activity in patient kidney cells and impaired binding of the transcription factor ZNF143. In silico analysis suggested an important role of ZNF143 for the formation of a chromatin loop including PMM2. They proposed that the PMM2 promoter mutation alters tissue-specific chromatin loop formation, with consequent organ-specific deficiency of PMM2 leading to the restricted phenotype of HIPKD.

None of the patients exhibited the typical clinical or diagnostic features of CDG1A. Serum transferrin glycosylation was normal in 11 patients who had assessment.; Changed phenotypes: Hyperinsulinaemic Hypoglycaemia and Polycystic Kidney Disease (HIPKD), MONDO:0020642, PMM2-related; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal Macrocystic Disease v0.50 PMM2 Zornitza Stark Marked gene: PMM2 as ready
Renal Macrocystic Disease v0.50 PMM2 Zornitza Stark Gene: pmm2 has been classified as Green List (High Evidence).
Hyperinsulinism v0.32 PMM2 Zornitza Stark reviewed gene: PMM2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v1.175 PMM2 Zornitza Stark Phenotypes for gene: PMM2 were changed from Congenital disorder of glycosylation, type Ia (MIM#212065) to Congenital disorder of glycosylation, type Ia (MIM#212065); Hyperinsulinaemic Hypoglycaemia and Polycystic Kidney Disease (HIPKD), MONDO:0020642, PMM2-related
Mendeliome v1.174 PMM2 Zornitza Stark Publications for gene: PMM2 were set to 28108845
Mendeliome v1.173 PMM2 Zornitza Stark changed review comment from: Well established gene-disease association.; to: CDG: Well established gene-disease association.
Mendeliome v1.173 PMM2 Zornitza Stark edited their review of gene: PMM2: Added comment: Association with HIPKD:
Cabezas et al (2017) reported co-occurrence of hyperinsulinaemic hypoglycaemia and polycystic kidney disease (HIPKD in 17 children from 11 unrelated families. Patients presented with hyperinsulinaemic hypoglycaemia in infancy and enlarged kidneys with multiple kidney cysts. Some progressed to ESKD and some had liver cysts. Whole-genome linkage analysis in 5 informative families identified a single significant locus on chromosome 16p13.2. Sequencing of the coding regions of all linked genes failed to identify biallelic mutations. Instead, they found in all patients a promoter mutation (c.-167G>T) in PMM2, either homozygous or in trans with PMM2 coding mutations. They found deglycosylation in cultured pancreatic β cells altered insulin secretion. In vitro, the PMM2 promoter mutation associated with decreased transcriptional activity in patient kidney cells and impaired binding of the transcription factor ZNF143. In silico analysis suggested an important role of ZNF143 for the formation of a chromatin loop including PMM2. They proposed that the PMM2 promoter mutation alters tissue-specific chromatin loop formation, with consequent organ-specific deficiency of PMM2 leading to the restricted phenotype of HIPKD. None of the patients exhibited the typical clinical or diagnostic features of CDG1A. Serum transferrin glycosylation was normal in 11 patients who had assessment.; Changed publications: 28108845, 28373276, 32595772; Changed phenotypes: Congenital disorder of glycosylation, type Ia (MIM#212065), Hyperinsulinaemic Hypoglycaemia and Polycystic Kidney Disease (HIPKD), MONDO:0020642, PMM2-related
Renal Macrocystic Disease v0.50 PMM2 Zornitza Stark Publications for gene: PMM2 were set to PMID: 28373276, 32595772
Renal Macrocystic Disease v0.49 PMM2 Zornitza Stark Phenotypes for gene: PMM2 were changed from Hyperinsulinaemic Hypoglycaemia and Polycystic Kidney Disease (HIPKD) to Hyperinsulinaemic Hypoglycaemia and Polycystic Kidney Disease (HIPKD), MONDO:0020642, PMM2-related
Prepair 1000+ v0.65 LOXHD1 Crystle Lee gene: LOXHD1 was added
gene: LOXHD1 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: LOXHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LOXHD1 were set to 31547530
Phenotypes for gene: LOXHD1 were set to Deafness, autosomal recessive 77 (MIM#613079)
Review for gene: LOXHD1 was set to AMBER
Added comment: Well established gene disease association with non-syndromic hearing loss.
Sources: Literature
Renal Macrocystic Disease v0.48 PMM2 Zornitza Stark Tag 5'UTR tag was added to gene: PMM2.
Prepair 1000+ v0.65 IGHM Zornitza Stark Tag for review tag was added to gene: IGHM.
Prepair 1000+ v0.65 DOCK2 Zornitza Stark Marked gene: DOCK2 as ready
Prepair 1000+ v0.65 DOCK2 Zornitza Stark Gene: dock2 has been classified as Green List (High Evidence).
Prepair 1000+ v0.65 DOCK2 Zornitza Stark Publications for gene: DOCK2 were set to
Prepair 1000+ v0.64 PRKRA Zornitza Stark Tag for review tag was added to gene: PRKRA.
Mendeliome v1.173 SLCO2A1 Zornitza Stark Phenotypes for gene: SLCO2A1 were changed from Hypertrophic osteoarthropathy, primary, autosomal dominant, MIM# 167100; Hypertrophic osteoarthropathy, primary, autosomal recessive 2, MIM# 614441 to Hypertrophic osteoarthropathy, primary, autosomal dominant, MIM# 167100; Hypertrophic osteoarthropathy, primary, autosomal recessive 2, MIM# 614441; Inflammatory bowel disease, MONDO:0005265, SLCO2A1-related
Mendeliome v1.172 SLCO2A1 Zornitza Stark Publications for gene: SLCO2A1 were set to 23509104; 27134495; 33852188; 22331663; 27134495
Mendeliome v1.171 SLCO2A1 Zornitza Stark edited their review of gene: SLCO2A1: Added comment: PMID 29313109: Over 40 Japanese individuals reported with bi-allelic variants in this gene and multiple small intestinal ulcers of nonspecific histology. Some overlap with the hypertrophic osteoarthropathy also associated with bi-allelic variants in this gene. Mild digital clubbing or periostosis was found in 13 patients (28%), with five male patients fulfilling the major diagnostic criteria of PHO.; Changed publications: 23509104, 27134495, 33852188, 22331663, 27134495, 29313109; Changed phenotypes: Hypertrophic osteoarthropathy, primary, autosomal dominant, MIM# 167100, Hypertrophic osteoarthropathy, primary, autosomal recessive 2, MIM# 614441, Inflammatory bowel disease, MONDO:0005265, SLCO2A1-related
Autoinflammatory Disorders v0.156 ALPK1 Peter McNaughton reviewed gene: ALPK1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35868845; Phenotypes: retinal dystrophy, optic nerve oedema, splenomegaly, anhidrosis, headache; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Inflammatory bowel disease v0.80 SLCO2A1 Zornitza Stark Marked gene: SLCO2A1 as ready
Inflammatory bowel disease v0.80 SLCO2A1 Zornitza Stark Gene: slco2a1 has been classified as Green List (High Evidence).
Inflammatory bowel disease v0.80 SLCO2A1 Zornitza Stark Phenotypes for gene: SLCO2A1 were changed from Enteropathy to Inflammatory bowel disease, MONDO:0005265, SLCO2A1-related; Enteropathy
Inflammatory bowel disease v0.79 SLCO2A1 Zornitza Stark Classified gene: SLCO2A1 as Green List (high evidence)
Inflammatory bowel disease v0.79 SLCO2A1 Zornitza Stark Gene: slco2a1 has been classified as Green List (High Evidence).
Inflammatory bowel disease v0.78 SLCO2A1 Zornitza Stark changed review comment from: Over 40 Japanese individuals reported with bi-allelic variants in this gene and multiple small intestinal ulcers of nonspecific histology.

This is distinct from the hypertrophic osteoarthropathy also associated with bi-allelic variants in this gene.; to: Over 40 Japanese individuals reported with bi-allelic variants in this gene and multiple small intestinal ulcers of nonspecific histology.

Some overlap with the hypertrophic osteoarthropathy also associated with bi-allelic variants in this gene. Mild digital clubbing or periostosis was found in 13 patients (28%), with five male patients fulfilling the major diagnostic criteria of PHO.
Inflammatory bowel disease v0.78 SLCO2A1 Zornitza Stark changed review comment from: Over 40 Japanese individuals reported with bi-allelic variants in this gene and multiple small intestinal ulcers of nonspecific histology.

This distinct from the hypertrophic osteoarthropathy also associated with bi-allelic variants in this gene.; to: Over 40 Japanese individuals reported with bi-allelic variants in this gene and multiple small intestinal ulcers of nonspecific histology.

This is distinct from the hypertrophic osteoarthropathy also associated with bi-allelic variants in this gene.
Inflammatory bowel disease v0.78 SLCO2A1 Zornitza Stark reviewed gene: SLCO2A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Inflammatory bowel disease, MONDO:0005265, SLCO2A1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.64 KCNQ1 Zornitza Stark Tag for review tag was added to gene: KCNQ1.
Prepair 1000+ v0.64 GLA Zornitza Stark Marked gene: GLA as ready
Prepair 1000+ v0.64 GLA Zornitza Stark Gene: gla has been classified as Green List (High Evidence).
Prepair 1000+ v0.64 GLA Zornitza Stark Phenotypes for gene: GLA were changed from Fabry disease, 301500 (3) to Fabry disease, MIM#301500
Prepair 1000+ v0.63 GLA Zornitza Stark Publications for gene: GLA were set to
Prepair 1000+ v0.62 FA2H Zornitza Stark Marked gene: FA2H as ready
Prepair 1000+ v0.62 FA2H Zornitza Stark Gene: fa2h has been classified as Green List (High Evidence).
Prepair 1000+ v0.62 FA2H Zornitza Stark Publications for gene: FA2H were set to
Prepair 1000+ v0.61 HYAL1 Crystle Lee gene: HYAL1 was added
gene: HYAL1 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: HYAL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HYAL1 were set to 10339581; 18344557; 21559944
Phenotypes for gene: HYAL1 were set to Mucopolysaccharidosis type IX (MIM#601492)
Review for gene: HYAL1 was set to RED
Added comment: Two families reported: in one, multiple soft tissue masses were the predominant clinical manifestation, and in the second, juvenile arthritis. Mouse model.

>15 pLoF variants reported as pathogenic in ClinVar. All submitted by a single lab and evidence suggests that the variant has not been previously reported.

Insufficient gene disease association. Not suitable for inclusion in a carrier screening panel
Sources: Literature
Prepair 1000+ v0.61 HOGA1 Crystle Lee gene: HOGA1 was added
gene: HOGA1 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: HOGA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HOGA1 were set to 31123811
Phenotypes for gene: HOGA1 were set to Hyperoxaluria, primary, type III (MIM#613616)
Review for gene: HOGA1 was set to AMBER
Added comment: Well-established association with primary hyperoxaluria type III (PH3). Variable phenotype

Three distinct genetic forms of PH have been defined: PH1–3. PH3 might be the least severe form with a milder phenotype with good preservation of kidney function in most patients. It does not develop ESRD generally
Sources: Literature
Prepair 1000+ v0.61 HGD Crystle Lee gene: HGD was added
gene: HGD was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: HGD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HGD were set to 25804398
Phenotypes for gene: HGD were set to Alkaptonuria (MIM#203500)
Review for gene: HGD was set to RED
Added comment: Well established gene disease association. Symptoms occur in adulthood.

Ochronosis generally occurs after age 30 years; arthritis often begins in the third decade. (Gene Reviews)
Sources: Literature
Hydrops fetalis v0.284 SPTA1 Di Milnes Deleted their comment
Hydrops fetalis v0.284 SPTA1 Di Milnes edited their review of gene: SPTA1: Added comment: single case fetus consanguineous parents
severe anaemia with NIHF
homozygous variant NM_003126.4:c.83G>A; Changed phenotypes: Spherocytosis type 3 #270970, Elliptocytosis-2 #130600, Pyropoikilocytosis #266140
Cancer Predisposition_Paediatric v0.126 TRIM37 Zornitza Stark Marked gene: TRIM37 as ready
Cancer Predisposition_Paediatric v0.126 TRIM37 Zornitza Stark Gene: trim37 has been classified as Green List (High Evidence).
Cancer Predisposition_Paediatric v0.126 TRIM37 Zornitza Stark Classified gene: TRIM37 as Green List (high evidence)
Cancer Predisposition_Paediatric v0.126 TRIM37 Zornitza Stark Gene: trim37 has been classified as Green List (High Evidence).
Cancer Predisposition_Paediatric v0.125 TRIM37 Zornitza Stark gene: TRIM37 was added
gene: TRIM37 was added to Cancer Predisposition_Paediatric. Sources: Expert Review
Mode of inheritance for gene: TRIM37 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRIM37 were set to 34309235; 19334051; 17100991
Phenotypes for gene: TRIM37 were set to Mulibrey nanism, MIM# 253250
Review for gene: TRIM37 was set to GREEN
Added comment: Multiple reports of WT with mulibrey nanism.
Sources: Expert Review
Hydrops fetalis v0.284 SPTA1 Di Milnes reviewed gene: SPTA1: Rating: AMBER; Mode of pathogenicity: None; Publications: 34132406; Phenotypes: Spherocytosis type 3 #270970, Elliptocytosis-2 #130600, pyropoikilocytosis #266140; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hydrops fetalis v0.284 SPTA1 Di Milnes Deleted their review
Hydrops fetalis v0.284 DOK7 Di Milnes reviewed gene: DOK7: Rating: AMBER; Mode of pathogenicity: None; Publications: 34132406; Phenotypes: Fetal akinesia deformation sequence 3, MIM# 618389; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hydrops fetalis v0.284 DOK7 Di Milnes Deleted their review
Prepair 1000+ v0.61 HFE Crystle Lee gene: HFE was added
gene: HFE was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: HFE was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: HFE were set to Hemochromatosis (MIM#235200)
Penetrance for gene: HFE were set to Incomplete
Review for gene: HFE was set to RED
Added comment: Well established gene disease association. HFE hemochromatosis is an adult-onset, treatable disorder with low clinical penetrance (Gene Reviews).

Not suitable for population carrier screening.
Sources: Literature
Cancer Predisposition_Paediatric v0.124 TRIM28 Zornitza Stark Marked gene: TRIM28 as ready
Cancer Predisposition_Paediatric v0.124 TRIM28 Zornitza Stark Gene: trim28 has been classified as Green List (High Evidence).
Cancer Predisposition_Paediatric v0.124 TRIM28 Zornitza Stark Classified gene: TRIM28 as Green List (high evidence)
Cancer Predisposition_Paediatric v0.124 TRIM28 Zornitza Stark Gene: trim28 has been classified as Green List (High Evidence).
Cancer Predisposition_Paediatric v0.123 TRIM28 Zornitza Stark gene: TRIM28 was added
gene: TRIM28 was added to Cancer Predisposition_Paediatric. Sources: Expert Review
Mode of inheritance for gene: TRIM28 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRIM28 were set to 30694527
Phenotypes for gene: TRIM28 were set to Wilms tumour, MONDO:0006058, TRIM28-related
Review for gene: TRIM28 was set to GREEN
Added comment: Eleven individuals with germline variants identified; plus one somatic. Exome sequencing on eight tumor DNA samples from six individuals showed loss-of-heterozygosity (LOH) of the TRIM28-locus by mitotic recombination in seven tumors, suggesting that TRIM28 functions as a tumor suppressor gene in Wilms tumor development.
Sources: Expert Review
Prepair 1000+ v0.61 HBA2 Crystle Lee gene: HBA2 was added
gene: HBA2 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: HBA2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: HBA2 were set to Erythrocytosis 7, MIM# 617981; Heinz body anaemia, MIM# 140700; Haemoglobin H disease, deletional and nondeletional, MIM# 613978; Thalassaemia, alpha-, MIM# 604131
Review for gene: HBA2 was set to RED
Added comment: Haemoglobinopathies of alpha-globin can result from variants at either of the 2 alpha-globin loci, HBA1 or HBA2.

Note deletions are common.
Sources: Literature
Prepair 1000+ v0.61 HBA1 Crystle Lee gene: HBA1 was added
gene: HBA1 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: HBA1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: HBA1 were set to Erythrocytosis 7, MIM# 617981; Heinz body anemias, alpha-, MIM# 140700; Methemoglobinemia, alpha type , MIM#617973; Thalassemias, alpha-, MIM# 604131; Hemoglobin H disease, nondeletional, MIM# 613978
Review for gene: HBA1 was set to RED
Added comment: Well established gene-disease associations. Haemoglobinopathies of alpha-globin can result from variants at either of the 2 alpha-globin loci, HBA1 or HBA2.

Note deletions are common.
Sources: Literature
Prepair 1000+ v0.61 GRHPR Crystle Lee gene: GRHPR was added
gene: GRHPR was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: GRHPR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GRHPR were set to 28569194; 10484776; 10484776; 24116921
Phenotypes for gene: GRHPR were set to Hyperoxaluria, primary, type II (MIM#260000)
Review for gene: GRHPR was set to AMBER
Added comment: Well established gene-disease association, more than 10 families reported.
Onset usually in infancy or early childhood, variable severity and some patients may be asymptomatic (OMIM; Gene Reviews)
Sources: Literature
Prepair 1000+ v0.61 GP9 Crystle Lee gene: GP9 was added
gene: GP9 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: GP9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GP9 were set to 8049428; 33553065; 32030720; 31484196
Phenotypes for gene: GP9 were set to Bernard-Soulier syndrome, type C (MIM#231200)
Review for gene: GP9 was set to AMBER
Added comment: Bernard-Soulier syndrome is a bleeding disorder caused by a defect in or deficiency of the platelet membrane von Willebrand factor receptor complex, glycoprotein Ib (GP Ib). GP Ib is composed of 4 subunits encoded by 4 separate genes: GP1BA, GP1BB, GP9, and GP5.

At least 3 unrelated families reported, animal model.
Sources: Literature
Cancer Predisposition_Paediatric v0.122 REST Zornitza Stark Marked gene: REST as ready
Cancer Predisposition_Paediatric v0.122 REST Zornitza Stark Gene: rest has been classified as Green List (High Evidence).
Cancer Predisposition_Paediatric v0.122 REST Zornitza Stark Classified gene: REST as Green List (high evidence)
Cancer Predisposition_Paediatric v0.122 REST Zornitza Stark Gene: rest has been classified as Green List (High Evidence).
Cancer Predisposition_Paediatric v0.121 REST Zornitza Stark gene: REST was added
gene: REST was added to Cancer Predisposition_Paediatric. Sources: Expert Review
Mode of inheritance for gene: REST was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: REST were set to 26551668; 34308104
Phenotypes for gene: REST were set to {Wilms tumor 6, susceptibility to}, MIM# 616806
Review for gene: REST was set to GREEN
Added comment: More than 10 families reported.
Sources: Expert Review
Prepair 1000+ v0.61 GP1BA Crystle Lee gene: GP1BA was added
gene: GP1BA was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: GP1BA was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: GP1BA were set to 21173099; 24934643; 18081445
Phenotypes for gene: GP1BA were set to Bernard-Soulier syndrome, type A1 (recessive), (MIM#231200), AR (AR BSS); von Willebrand disease, platelet-type, (MIM#177820), AD (VWD); MONDO:0008332; Bernard-Soulier syndrome, type A2 (dominant), (MIM#153670) (AD BSS); MONDO:0007930
Review for gene: GP1BA was set to AMBER
Added comment: Bernard-Soulier syndrome is usually transmitted as a recessive trait with giant platelets and severe bleeding tendency.
Sources: Literature
Cancer Predisposition_Paediatric v0.120 PIK3CA Zornitza Stark Marked gene: PIK3CA as ready
Cancer Predisposition_Paediatric v0.120 PIK3CA Zornitza Stark Gene: pik3ca has been classified as Green List (High Evidence).
Cancer Predisposition_Paediatric v0.120 PIK3CA Zornitza Stark Classified gene: PIK3CA as Green List (high evidence)
Cancer Predisposition_Paediatric v0.120 PIK3CA Zornitza Stark Gene: pik3ca has been classified as Green List (High Evidence).
Cancer Predisposition_Paediatric v0.119 PIK3CA Zornitza Stark gene: PIK3CA was added
gene: PIK3CA was added to Cancer Predisposition_Paediatric. Sources: Expert Review
somatic tags were added to gene: PIK3CA.
Mode of inheritance for gene: PIK3CA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PIK3CA were set to Megalencephaly-capillary malformation-polymicrogyria syndrome, somatic, MIM# 602501
Review for gene: PIK3CA was set to GREEN
Added comment: MCAP syndrome is associated with increased risk of Wilm's tumour, and other neoplasms (leukaemia, meningioma).
Sources: Expert Review
Cancer Predisposition_Paediatric v0.118 GPC3 Zornitza Stark Marked gene: GPC3 as ready
Cancer Predisposition_Paediatric v0.118 GPC3 Zornitza Stark Gene: gpc3 has been classified as Green List (High Evidence).
Prepair 1000+ v0.61 GJB2 Crystle Lee gene: GJB2 was added
gene: GJB2 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: GJB2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for gene: GJB2 were set to Bart-Pumphrey syndrome, MIM#149200; Deafness, autosomal dominant 3A, MIM#601544; Deafness, autosomal recessive 1A, MIM#220290; Hystrix-like ichthyosis with deafness, MIM#602540; Keratitis-ichthyosis-deafness syndrome, MIM#148210; Keratoderma, palmoplantar, with deafness, MIM#148350; Vohwinkel syndrome, MIM# 124500
Review for gene: GJB2 was set to AMBER
Added comment: Well established gene disease association. AR deafness MIM#220290 is associated with biallelic variants or digenic dominant with large deletion in GJB6
Sources: Literature
Prepair 1000+ v0.61 GJB1 Crystle Lee gene: GJB1 was added
gene: GJB1 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: GJB1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: GJB1 were set to Charcot-Marie-Tooth neuropathy, X-linked dominant, 1 (MIM#302800)
Review for gene: GJB1 was set to AMBER
Added comment: CMTX has both demyelinating and axonal features. Well established gene-disease association, over 100 families reported. Variable phenotype with incomplete penetrance (OMIM)

PMID 31842800: Three unrelated males with GJB1 variants and recurrent episodes of reversible posterior leukoencephalopathy reported.
Sources: Literature
Prepair 1000+ v0.61 GALK1 Crystle Lee gene: GALK1 was added
gene: GALK1 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: GALK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GALK1 were set to 32807972
Phenotypes for gene: GALK1 were set to Galactokinase deficiency with cataracts (MIM#230200)
Review for gene: GALK1 was set to AMBER
Added comment: Well established gene disease association. Galactokinase (GALK1) deficiency is a rare hereditary galactose metabolism disorder. Beyond cataract, the phenotypic spectrum is questionable
Sources: Literature
Prepair 1000+ v0.61 G6PD Crystle Lee gene: G6PD was added
gene: G6PD was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: G6PD was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: G6PD were set to Hemolytic anemia, G6PD deficient (favism) (MIM#300908)
Review for gene: G6PD was set to AMBER
Added comment: Well established gene disease association. Most G6PD-deficient patients are asymptomatic throughout their life, but G6PD deficiency can be life-threatening

Note: OMIM states this is XLD, however it is males that a repeatedly reported affected and just carrier females; females are affected when HOMOZYGOUS, meaning this is primarily an XLR condition
Sources: Literature
Prepair 1000+ v0.61 F11 Crystle Lee gene: F11 was added
gene: F11 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: F11 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: F11 were set to 18446632; 15026311; 27723456
Phenotypes for gene: F11 were set to Factor XI deficiency, autosomal dominant (MIM#612416); Factor XI deficiency, autosomal recessive, (MIM#612416)
Review for gene: F11 was set to AMBER
Added comment: Recessive cases are more severe than heterozygous carriers, who may be asymptomatic despite having FXI deficiency (PMID:18446632). Dominant negative missense tend to have dominant inheritance patterns (PMID:15026311), while PTCs are generally recessive, though symptomatic carriers have been reported (OMIM).

PMID: 27723456 - "Bleeding due to FXI deficiency is variable and does not correlate with the plasma FXI level or FXI coagulant activity1"
Sources: Literature
Hydrops fetalis v0.284 SPTA1 Di Milnes gene: SPTA1 was added
gene: SPTA1 was added to Hydrops fetalis. Sources: Literature
Mode of inheritance for gene: SPTA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPTA1 were set to 34132406
Phenotypes for gene: SPTA1 were set to Spherocytosis type 3 #270970; Elliptocytosis-2 #130600; pyropoikilocytosis #266140
Review for gene: SPTA1 was set to AMBER
Added comment: single case fetus consanguineous parents
severe anaemia with NIHF
homozygous variant NM_003126.4:c.83G>A
Sources: Literature
Hydrops fetalis v0.284 DOK7 Di Milnes changed review comment from: Homozygous pathogenic variant NM_173660.5:c.439delG
recurrent NIHF in four consanguineous families
NIHF as part of the presentation of FADS; to: Homozygous pathogenic variant NM_173660.5:c.439delG
recurrent NIHF in four consanguineous families
NIHF as part of the presentation of FADS
PMID didn't save the last digit - 34132406
Hydrops fetalis v0.284 GLDN Di Milnes gene: GLDN was added
gene: GLDN was added to Hydrops fetalis. Sources: Literature
Mode of inheritance for gene: GLDN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GLDN were set to 34132406
Phenotypes for gene: GLDN were set to Lethal congenital contracture syndrome 11, MIM# 617194
Review for gene: GLDN was set to AMBER
Added comment: Homozygous pathogenic variant in two of three recurrent NIHF in consanguineous couple (no DNA from the 3rd fetus available - two prior pregnancies and current pregnancy NIHF), segregated in parents
NM_181789.4:c.385_392delTGCAACAG
Sources: Literature
Prepair 1000+ v0.61 EYS Crystle Lee gene: EYS was added
gene: EYS was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: EYS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EYS were set to 31074760
Phenotypes for gene: EYS were set to Retinitis pigmentosa 25 (MIM#602772)
Review for gene: EYS was set to AMBER
Added comment: Well established gene disease association. Highly variable age of onset of retinal disease
Sources: Literature
Hydrops fetalis v0.284 DOK7 Di Milnes reviewed gene: DOK7: Rating: AMBER; Mode of pathogenicity: None; Publications: 3413240; Phenotypes: Fetal akinesia deformation sequence 3, MIM# 618389; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.61 CYP21A2 Crystle Lee gene: CYP21A2 was added
gene: CYP21A2 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: CYP21A2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CYP21A2 were set to Adrenal hyperplasia, congenital, due to 21-hydroxylase deficiency (MIM#201910)
Review for gene: CYP21A2 was set to RED
Added comment: Well established gene-disease association.

Pseudogene and structural variants make NGS data difficult to interpret. Not suitable for inclusion in a carrier screening panel due to technical reasons
Sources: Literature
Early-onset Parkinson disease v0.215 ATXN1_CAG SHEKEEB MOHAMMAD STR: ATXN1_CAG was added
STR: ATXN1_CAG was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for STR: ATXN1_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: ATXN1_CAG were set to • PMID: 24602359
Phenotypes for STR: ATXN1_CAG were set to Spinocerebellar Ataxia type 1; Parkinsonism; OMIM 164400
Review for STR: ATXN1_CAG was set to GREEN
Added comment: Sources: Literature
Congenital Heart Defect v0.239 KYNU Chloe Stutterd gene: KYNU was added
gene: KYNU was added to Congenital Heart Defect. Sources: Literature,Expert list
Mode of inheritance for gene: KYNU was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KYNU were set to 28792876; 33942433
Phenotypes for gene: KYNU were set to MIM# 617661 Vertebral, cardiac, renal, and limb defects syndrome 2
Review for gene: KYNU was set to GREEN
gene: KYNU was marked as current diagnostic
Added comment: Biallelic, inactivating variants in three genes encoding enzymes of the NAD biosynthesis pathway (KYNU, HAAO, and NADSYN1) disrupt NAD synthesis and have been identified in patients with multiple malformations of the heart, kidney, vertebrae, and limbs; these patients have Congenital NAD Deficiency Disorder (PMID: 33942433)
Sources: Literature, Expert list
Congenital Heart Defect v0.239 KDR Chloe Stutterd gene: KDR was added
gene: KDR was added to Congenital Heart Defect. Sources: Literature,Expert list
Mode of inheritance for gene: KDR was set to Unknown
Publications for gene: KDR were set to 34113005; 34328347; 30232381
Phenotypes for gene: KDR were set to Tetralogy of Fallot
Review for gene: KDR was set to RED
gene: KDR was marked as current diagnostic
Added comment: Rare variants associated with ToF but lacking evidence for causality and pathogenesis.

PMID 34113005 (2021): Exome sequencing in a family with two siblings affected by TOF revealed biallelic missense variants in KDR. Studies in knock-in mice and in HEK 293T cells identified embryonic lethality for one variant when occurring in the homozygous state, and a significantly reduced VEGFR2 phosphorylation for both variants. Rare variant burden analysis conducted in a set of 1,569 patients of European descent with TOF identified a 46-fold enrichment of protein-truncating variants (PTVs) in TOF cases compared to controls (P = 7 × 10-11).

PMID 34328347 (2021): exome sequencing data from 811 probands with ToF, four patients had novel LoF variants in KDR demonstrating enrichment in ToF compared with controls. Segregation data not available.

PMID: 30232381 (2019): KDR variants identified in four patients (two stopgain and two nonsynonymous variants) with other VUS identified in one patient. Segregation data not available.
Sources: Literature, Expert list
Congenital Heart Defect v0.239 HDAC8 Chloe Stutterd gene: HDAC8 was added
gene: HDAC8 was added to Congenital Heart Defect. Sources: Literature,Expert list
Mode of inheritance for gene: HDAC8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HDAC8 were set to 24403048
Phenotypes for gene: HDAC8 were set to MIM# 300882 Cornelia de Lange syndrome 5
Review for gene: HDAC8 was set to GREEN
gene: HDAC8 was marked as current diagnostic
Added comment: PMID:24403048: 11/30 individuals with HDAC8-related CdLS identified with CHD (ASD, VSD, ToF, valve dysplasia, PDA)(Supp table).
Sources: Literature, Expert list
Cancer Predisposition_Paediatric v0.118 GPC3 Zornitza Stark Classified gene: GPC3 as Green List (high evidence)
Cancer Predisposition_Paediatric v0.118 GPC3 Zornitza Stark Gene: gpc3 has been classified as Green List (High Evidence).
Cancer Predisposition_Paediatric v0.117 GPC3 Zornitza Stark gene: GPC3 was added
gene: GPC3 was added to Cancer Predisposition_Paediatric. Sources: Expert Review
Mode of inheritance for gene: GPC3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: GPC3 were set to Simpson-Golabi-Behmel syndrome, type 1, MIM# 312870
Review for gene: GPC3 was set to GREEN
Added comment: Increased risk of Wilms tumour and embryonal tumours is a feature of Simpson-Golabi-Behmel syndrome.
Sources: Expert Review
Congenital Heart Defect v0.239 HAAO Chloe Stutterd edited their review of gene: HAAO: Added comment: CHD reported: Atrial septal defect; Hypoplastic left heart syndrome; Aortic stenosis; Mitral stenosis; Tetralogy of fallot with complete atriventricular canal and pulmonary stenosis; Lsvc and left pulmonary artery arising from the ductus arteriosus; Shone syndrome with aortic coarctation; Changed phenotypes: MIM#617660 Vertebral, cardiac, renal, and limb defects syndrome 1
Congenital Heart Defect v0.239 HAAO Chloe Stutterd gene: HAAO was added
gene: HAAO was added to Congenital Heart Defect. Sources: Literature,Expert list
Mode of inheritance for gene: HAAO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HAAO were set to 28792876; 33942433
Phenotypes for gene: HAAO were set to Atrial septal defect; Hypoplastic left heart syndrome; Aortic stenosis; Mitral stenosis; Tetralogy of fallot with complete atriventricular canal and pulmonary stenosis; Lsvc and left pulmonary artery arising from the ductus arteriosus; Shone syndrome with aortic coarctation
Review for gene: HAAO was set to GREEN
gene: HAAO was marked as current diagnostic
Added comment: MIM#617660 phenotype is called 'Vertebral, cardiac, renal, and limb defects syndrome type 1' and is a form of Congenital NAD Deficiency Disorder.

Biallelic, inactivating variants in three genes encoding enzymes of the NAD biosynthesis pathway (KYNU, HAAO, and NADSYN1) disrupt NAD synthesis and have been identified in patients with multiple malformations of the heart, kidney, vertebrae, and limbs; these patients have Congenital NAD Deficiency Disorder (PMID: 33942433).
Sources: Literature, Expert list
Congenital Heart Defect v0.239 GLI3 Chloe Stutterd gene: GLI3 was added
gene: GLI3 was added to Congenital Heart Defect. Sources: Literature,Expert list
Mode of inheritance for gene: GLI3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GLI3 were set to 24736735; 7211952
Phenotypes for gene: GLI3 were set to ASD, VSD, AVSD, aortic arch anomaly, PDA
Mode of pathogenicity for gene: GLI3 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: GLI3 was set to GREEN
gene: GLI3 was marked as current diagnostic
Added comment: Syndromic CHD associated with the Pallister-Hall syndrome (PHS) phenotype which is caused by truncating mutations in the middle third of the gene that produce a truncated functional repressor protein.

OMIM #146510 (Pallister-Hall syndrome; PHS) phenotype includes ventricular septal defect, aortic coarctation and patent ductus arteriosus based on original clinical description of syndrome in 1980 in patients without molecular confirmation of diagnosis (PubMed 7211952)

PMID 24736735 (2015): French cohort of 76 individuals from 55 families carrying a GLI3 molecular defect. CHD identified in 5/21 unrelated patients with PHS (septal defects, aortic arch anomaly).
Sources: Literature, Expert list
Congenital Heart Defect v0.239 FOXP1 Chloe Stutterd gene: FOXP1 was added
gene: FOXP1 was added to Congenital Heart Defect. Sources: Literature,Expert list
Mode of inheritance for gene: FOXP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOXP1 were set to 29090079; 23766104
Phenotypes for gene: FOXP1 were set to Atrial septal defect; Atrioventricular septal defect; Patent ductus arteriosus; Pulmonic stenosis; Hypoplastic left heart syndrome
Review for gene: FOXP1 was set to AMBER
gene: FOXP1 was marked as current diagnostic
Added comment: Best evidence of association with CHD comes from PMID:29090079 but only for two patients and one with very mild CHD only. Study is a prospective investigation of nine children with FOXP1 syndrome using a battery of standardized clinical assessments, two had CHD (one with pulmonary stenosis, the other with self-resolving PDA). Authors recommend cardiac screening for patients with FOXP1 neurodevelopmental syndrome.

PMID:23766104: Single patient with CHD (AVSD, hypoplastic left ventricle and aortic arch, left atrioventricular valve stenosis, bilateral superior vena cavae, transposed great vessels) and cryptorchidism and a novel 3p14 microdeletion involving first 4 exons of FOXP1, inherited from an unaffected mother. FOXP1 sequenced in 82 patients with AVSD or HLHS: 2/82 patients had FOXP1 variant c.1702C>T;p.(Pro568Ser), inheritance unknown, variant present gnomAD in 153 hets, benign/likely benign in ClinVar .

PMID: 25908055; 22290856: CHD associated with 3p14 contiguous gene deletion syndrome involving FOXP1 and up to 30 other genes.

Homozygous null mice have CHD (MGI ID:1914004; PMID: 15342473).
Sources: Literature, Expert list
Mendeliome v1.171 CTR9 Zornitza Stark Phenotypes for gene: CTR9 were changed from Neurodevelopmental disorder (MONDO:0700092), CTR9 related to Neurodevelopmental disorder (MONDO:0700092), CTR9 related; Familial Wilms tumour, MONDO:0006058, CTR9-related
Mendeliome v1.170 CTR9 Zornitza Stark Publications for gene: CTR9 were set to PMID: 35499524
Mendeliome v1.169 CTR9 Zornitza Stark reviewed gene: CTR9: Rating: GREEN; Mode of pathogenicity: None; Publications: 25099282, 29292210; Phenotypes: Familial Wilms tumour, MONDO:0006058, CTR9-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cancer Predisposition_Paediatric v0.116 CTR9 Zornitza Stark Marked gene: CTR9 as ready
Cancer Predisposition_Paediatric v0.116 CTR9 Zornitza Stark Gene: ctr9 has been classified as Green List (High Evidence).
Cancer Predisposition_Paediatric v0.116 CTR9 Zornitza Stark Classified gene: CTR9 as Green List (high evidence)
Cancer Predisposition_Paediatric v0.116 CTR9 Zornitza Stark Gene: ctr9 has been classified as Green List (High Evidence).
Cancer Predisposition_Paediatric v0.115 CTR9 Zornitza Stark gene: CTR9 was added
gene: CTR9 was added to Cancer Predisposition_Paediatric. Sources: Expert Review
Mode of inheritance for gene: CTR9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CTR9 were set to 25099282; 29292210
Phenotypes for gene: CTR9 were set to Familial Wilms tumour, MONDO:0006058, CTR9-related
Review for gene: CTR9 was set to GREEN
Added comment: Four unrelated families reported, where germline variants segregated with disease. Postulated to be a tumour suppressor gene.

Note variants in this gene have also been associated with a neurodevelopmental disorder.
Sources: Expert Review
Prepair 1000+ v0.61 CERKL Crystle Lee edited their review of gene: CERKL: Changed rating: AMBER
Prepair 1000+ v0.61 CYP19A1 Crystle Lee gene: CYP19A1 was added
gene: CYP19A1 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: CYP19A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYP19A1 were set to 29553041; 17164303; 25264451
Phenotypes for gene: CYP19A1 were set to Aromatase deficiency (MIM#613546)
Review for gene: CYP19A1 was set to AMBER
Added comment: Aromatase deficiency is a rare disease characterized by a decrease in estrogen synthesis. Clinical characteristics of patients with aromatase deficiency vary depending on gender, age and enzymatic activity

CYP19A1 loss-of-function because of biallelic mutations leads to aromatase deficiency, whereas CYP19A1 overexpression because of genomic rearrangements results in aromatase excess syndrome (https://doi.org/10.1016/j.coemr.2020.03.002)
Sources: Literature
Early-onset Parkinson disease v0.215 MT-ND6 SHEKEEB MOHAMMAD gene: MT-ND6 was added
gene: MT-ND6 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene gene: MT-ND6 was set to MITOCHONDRIAL
Publications for gene: MT-ND6 were set to PMID: 33109474
Phenotypes for gene: MT-ND6 were set to Leber Optic Atrophy; Parkinsonism; OMIM 516006
Review for gene: MT-ND6 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.215 WASL SHEKEEB MOHAMMAD gene: WASL was added
gene: WASL was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: WASL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WASL were set to PMID: 33571872
Phenotypes for gene: WASL were set to Early onset parkinsonism
Review for gene: WASL was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.215 KMT2B SHEKEEB MOHAMMAD gene: KMT2B was added
gene: KMT2B was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: KMT2B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KMT2B were set to PMID: 33816656
Phenotypes for gene: KMT2B were set to DYT28; Childhood‐onset and progressive dystonia; Dysarthria; Dysphagia; Developmental delay; Dysmorphic features; Parkinsonism; OMIM 617284
Review for gene: KMT2B was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.215 GBA SHEKEEB MOHAMMAD gene: GBA was added
gene: GBA was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: GBA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GBA were set to PMID: 12809640
Phenotypes for gene: GBA were set to Gaucher Disease Type 1; Early onset parkinsonism; Bone lesions; Hepatosplenomegaly; Hematologic disorders; OMIM 230800
Review for gene: GBA was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.215 FRRS1L SHEKEEB MOHAMMAD gene: FRRS1L was added
gene: FRRS1L was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: FRRS1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FRRS1L were set to PMID: 29086067
Phenotypes for gene: FRRS1L were set to Developmental and epileptic dyskinetic encephalopathy; Seizures; Chorea; Parkinsonism; Developmental delay; OMIM 616981
Review for gene: FRRS1L was set to GREEN
Added comment: Sources: Literature
Prepair 1000+ v0.61 CYP11B1 Crystle Lee gene: CYP11B1 was added
gene: CYP11B1 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: CYP11B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYP11B1 were set to 8768848
Phenotypes for gene: CYP11B1 were set to Adrenal hyperplasia, congenital, due to 11-beta-hydroxylase deficiency (MIM#202010)
Review for gene: CYP11B1 was set to AMBER
Added comment: CAH due to 11-beta-hydroxylase deficiency is an autosomal recessive disorder of corticosteroid biosynthesis resulting in androgen excess, virilization, and hypertension.

Well established gene-disease association.
Sources: Literature
Early-onset Parkinson disease v0.215 ALPL SHEKEEB MOHAMMAD gene: ALPL was added
gene: ALPL was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: ALPL was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: ALPL were set to PMID: 32956941
Phenotypes for gene: ALPL were set to Hypophosphatasia; Osteomalacia; Parkinsonism; OMIM 146300
Review for gene: ALPL was set to GREEN
Added comment: Sources: Literature
Prepair 1000+ v0.61 CERKL Crystle Lee edited their review of gene: CERKL: Changed publications: 33322828, 32036094
Prepair 1000+ v0.61 CERKL Crystle Lee changed review comment from: More than 20 families reported, though some variants are recurrent (founder). This gene causes nonsyndromic retinal disease. Highly variable age of onset (7-45 years) and severity. There is also evidence of phenotypic intra- and inter-familial variability between patients with the same genotype.
Sources: Literature; to: More than 20 families reported, though some variants are recurrent (founder). This gene causes nonsyndromic retinal disease. Highly variable age of onset (7-45 years) and severity. There is also evidence of phenotypic intra- and inter-familial variability between patients with the same genotype.
Sources: Literature
Prepair 1000+ v0.61 CERKL Crystle Lee gene: CERKL was added
gene: CERKL was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: CERKL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CERKL were set to 33322828
Phenotypes for gene: CERKL were set to Retinitis pigmentosa 26 (MIM#608380)
Review for gene: CERKL was set to RED
Added comment: More than 20 families reported, though some variants are recurrent (founder). This gene causes nonsyndromic retinal disease. Highly variable age of onset (7-45 years) and severity. There is also evidence of phenotypic intra- and inter-familial variability between patients with the same genotype.
Sources: Literature
Early-onset Parkinson disease v0.215 ADAR SHEKEEB MOHAMMAD gene: ADAR was added
gene: ADAR was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: ADAR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAR were set to PMID: 32911246
Phenotypes for gene: ADAR were set to Aicardi-Goutieres syndrome 6; neuroinflammatory disorder with cerebral calcification; progressive loss of cognition; spasticity; dystonia; parkinsonism; OMIM 615010
Review for gene: ADAR was set to GREEN
Added comment: Sources: Literature
Prepair 1000+ v0.61 BTD Crystle Lee gene: BTD was added
gene: BTD was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: BTD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BTD were set to 16435182; 20301497; 32440248
Phenotypes for gene: BTD were set to Biotinidase deficiency (MIM#253260)
Review for gene: BTD was set to RED
Added comment: Well-established gene disease association. Genotype/phenotype correlations in biotinidase deficiency are not well established, decisions regarding treatment should be based on the results of enzyme activity rather than molecular genetic testing.

May be challenging to predict phenotypic outcome in a carrier screening context.
Sources: Literature
Prepair 1000+ v0.61 AIRE Crystle Lee gene: AIRE was added
gene: AIRE was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: AIRE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AIRE were set to 35521792; 28323927
Phenotypes for gene: AIRE were set to Autoimmune polyendocrinopathy syndrome , type I, with or without reversible metaphyseal dysplasia (MIM#240300)
Review for gene: AIRE was set to AMBER
Added comment: Well established gene disease association. Onset in childhood however phenotype can vary even between siblings with the same genotype. Therefore, it may be difficult (?impossible) to predict the severity/age of onset from the genotype

Most reported individuals have bi-allelic variants. AD inheritance has been reported in a single family (OMIM) p.G228W has been shown to have a dominant-negative effect by binding to WT AIRE (OMIM)
Sources: Literature
Prepair 1000+ v0.61 KCNE1 Crystle Lee reviewed gene: KCNE1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Long QT syndrome 5, MIM# 613695, Jervell and Lange-Nielsen syndrome 2, MIM# 612347, Acquired LQTS; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.61 VPS13A Crystle Lee reviewed gene: VPS13A: Rating: AMBER; Mode of pathogenicity: None; Publications: 28446873; Phenotypes: Choreoacanthocytosis (MIM#200150); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.61 TH Crystle Lee reviewed gene: TH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Segawa syndrome, recessive (MIM#605407); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.61 SPG11 Crystle Lee reviewed gene: SPG11: Rating: GREEN; Mode of pathogenicity: None; Publications: 33581793; Phenotypes: Spastic paraplegia 11, autosomal recessive (MIM#604360); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.61 SPART Crystle Lee reviewed gene: SPART: Rating: GREEN; Mode of pathogenicity: None; Publications: 31535723, 28875386, 28679690; Phenotypes: Troyer syndrome (MIM#275900), SPG20, MONDO:0010156; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.61 SETX Crystle Lee reviewed gene: SETX: Rating: GREEN; Mode of pathogenicity: None; Publications: 23129421; Phenotypes: Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 (MIM#606002); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.61 PLA2G6 Crystle Lee reviewed gene: PLA2G6: Rating: GREEN; Mode of pathogenicity: None; Publications: 35803092; Phenotypes: Infantile neuroaxonal dystrophy 1 MIM#256600, Neurodegeneration with brain iron accumulation 2B MIM#610217; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.61 PANK2 Crystle Lee reviewed gene: PANK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 15911822; Phenotypes: HARP syndrome (MIM#607236), Neurodegeneration with brain iron accumulation 1 (MIM#234200); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.61 NPC2 Crystle Lee reviewed gene: NPC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29625568, 17470133; Phenotypes: Niemann-pick disease, type C2 (MIM#607625); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.61 NPC1 Crystle Lee reviewed gene: NPC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11333381, 26910362; Phenotypes: Niemann-Pick disease, type C1 (MIM#257220); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.61 LMNA Crystle Lee reviewed gene: LMNA: Rating: GREEN; Mode of pathogenicity: None; Publications: 18551513, 15148145, 17377071; Phenotypes: Emery-Dreifuss muscular dystrophy 3, autosomal recessive (MIM#616516), Mandibuloacral dysplasia (MIM#248370); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Prepair 1000+ v0.61 LDLR Crystle Lee reviewed gene: LDLR: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: LDL cholesterol level QTL2/Hypercholesterolemia, familial, 1 (MIM#143890); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Prepair 1000+ v0.61 FIG4 Crystle Lee reviewed gene: FIG4: Rating: GREEN; Mode of pathogenicity: None; Publications: 30740813, 23623387, 17572665, 24878229; Phenotypes: Yunis-Varon syndrome (MIM#216340); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal Macrocystic Disease v0.48 PMM2 Chirag Patel Classified gene: PMM2 as Green List (high evidence)
Renal Macrocystic Disease v0.48 PMM2 Chirag Patel Gene: pmm2 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.47 PMM2 Chirag Patel gene: PMM2 was added
gene: PMM2 was added to Renal Macrocystic Disease. Sources: Literature
Mode of inheritance for gene: PMM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PMM2 were set to PMID: 28373276, 32595772
Phenotypes for gene: PMM2 were set to Hyperinsulinaemic Hypoglycaemia and Polycystic Kidney Disease (HIPKD)
Review for gene: PMM2 was set to GREEN
gene: PMM2 was marked as current diagnostic
Added comment: Cabezas et al (2017) reported co-occurrence of hyperinsulinaemic hypoglycaemia and polycystic kidney disease (HIPKD in 17 children from 11 unrelated families. Patients presented with hyperinsulinaemic hypoglycaemia in infancy and enlarged kidneys with multiple kidney cysts. Some progressed to ESKD and some had liver cysts.

Whole-genome linkage analysis in 5 informative families identified a single significant locus on chromosome 16p13.2. Sequencing of the coding regions of all linked genes failed to identify biallelic mutations. Instead, they found in all patients a promoter mutation (c.-167G>T) in PMM2, either homozygous or in trans with PMM2 coding mutations. They found deglycosylation in cultured pancreatic β cells altered insulin secretion. In vitro, the PMM2 promoter mutation associated with decreased transcriptional activity in patient kidney cells and impaired binding of the transcription factor ZNF143. In silico analysis suggested an important role of ZNF143 for the formation of a chromatin loop including PMM2. They proposed that the PMM2 promoter mutation alters tissue-specific chromatin loop formation, with consequent organ-specific deficiency of PMM2 leading to the restricted phenotype of HIPKD.

None of the patients exhibited the typical clinical or diagnostic features of CDG1A. Serum transferrin glycosylation was normal in 11 patients who had assessment.
Sources: Literature
Prepair 1000+ v0.61 IGHM Crystle Lee reviewed gene: IGHM: Rating: AMBER; Mode of pathogenicity: None; Publications: 12370281, 8890099; Phenotypes: Agammaglobulinemia 1 (MIM#601495); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.61 DOCK2 Crystle Lee reviewed gene: DOCK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26083206, 29204803, 33928462, 30826364; Phenotypes: Immunodeficiency 40 (MIM#616433); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.61 PRKRA Crystle Lee reviewed gene: PRKRA: Rating: AMBER; Mode of pathogenicity: None; Publications: 35844281, 18243799, 25142429, 35844287; Phenotypes: Dystonia 16 (MIM#612067); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Inflammatory bowel disease v0.78 SLCO2A1 Peter McNaughton gene: SLCO2A1 was added
gene: SLCO2A1 was added to Inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: SLCO2A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLCO2A1 were set to PMID: 29313109
Phenotypes for gene: SLCO2A1 were set to Enteropathy
Review for gene: SLCO2A1 was set to GREEN
Added comment: Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4859 C20orf24 Zornitza Stark Marked gene: C20orf24 as ready
Intellectual disability syndromic and non-syndromic v0.4859 C20orf24 Zornitza Stark Gene: c20orf24 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.4859 C20orf24 Zornitza Stark gene: C20orf24 was added
gene: C20orf24 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
new gene name tags were added to gene: C20orf24.
Mode of inheritance for gene: C20orf24 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C20orf24 were set to 35614220; 24194475
Phenotypes for gene: C20orf24 were set to Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome 2, MIM# 616994
Review for gene: C20orf24 was set to RED
Added comment: Bi-allelic LoF variant identified in patient originally reported in PMID 24194475. HGNC approved name is RAB5IF.
Sources: Literature
Mendeliome v1.169 C20orf24 Zornitza Stark Tag new gene name tag was added to gene: C20orf24.
Mendeliome v1.169 C20orf24 Zornitza Stark Marked gene: C20orf24 as ready
Mendeliome v1.169 C20orf24 Zornitza Stark Gene: c20orf24 has been classified as Red List (Low Evidence).
Mendeliome v1.169 C20orf24 Zornitza Stark gene: C20orf24 was added
gene: C20orf24 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: C20orf24 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C20orf24 were set to 35614220; 24194475
Phenotypes for gene: C20orf24 were set to Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome 2, MIM# 616994
Review for gene: C20orf24 was set to RED
Added comment: Bi-allelic LoF variant identified in patient originally reported in PMID 24194475.

HGNC approved name is RAB5IF.
Sources: Literature
Prepair 1000+ v0.61 KCNQ1 Crystle Lee reviewed gene: KCNQ1: Rating: AMBER; Mode of pathogenicity: None; Publications: 29033053, 28438721; Phenotypes: Jervell and Lange-Nielsen syndrome (MIM#220400); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.61 GLA Crystle Lee reviewed gene: GLA: Rating: GREEN; Mode of pathogenicity: None; Publications: 29649853, 20301469; Phenotypes: Fabry disease (MIM#301500); 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+ v0.61 DSP Zornitza Stark Marked gene: DSP as ready
Prepair 1000+ v0.61 DSP Zornitza Stark Gene: dsp has been classified as Green List (High Evidence).
Prepair 1000+ v0.61 DSP Zornitza Stark Phenotypes for gene: DSP were changed from Cardiomyopathy, dilated, with woolly hair and keratoderma, 605676 (3) to Cardiomyopathy, dilated, with woolly hair and keratoderma (MIM#605676); Epidermolysis bullosa, lethal acantholytic (MIM#609638)
Prepair 1000+ v0.60 DSP Zornitza Stark Publications for gene: DSP were set to
Prepair 1000+ v0.59 CASQ2 Zornitza Stark Tag for review tag was added to gene: CASQ2.
Prepair 1000+ v0.59 ATP7B Zornitza Stark Marked gene: ATP7B as ready
Prepair 1000+ v0.59 ATP7B Zornitza Stark Gene: atp7b has been classified as Green List (High Evidence).
Prepair 1000+ v0.59 ATP7B Zornitza Stark Publications for gene: ATP7B were set to
Prepair 1000+ v0.58 ATP13A2 Zornitza Stark Tag for review tag was added to gene: ATP13A2.
Prepair 1000+ v0.58 BGN Zornitza Stark Tag for review tag was added to gene: BGN.
Prepair 1000+ v0.58 C8B Zornitza Stark Tag for review tag was added to gene: C8B.
Prepair 1000+ v0.58 C7 Zornitza Stark Tag for review tag was added to gene: C7.
Prepair 1000+ v0.58 C6 Zornitza Stark Tag for review tag was added to gene: C6.
Mendeliome v1.168 IL23R Zornitza Stark edited their review of gene: IL23R: Changed phenotypes: Immunodeficiency disease, MONDO:0021094, Susceptibility to mycobacteria and Salmonella Edit
Mendeliome v1.168 IL23R Zornitza Stark edited their review of gene: IL23R: Changed phenotypes: Immunodeficiency disease, MONDO:0021094
Mendeliome v1.168 IL23R Zornitza Stark Phenotypes for gene: IL23R were changed from Susceptibility to mycobacteria and Salmonella to Immunodeficiency disease, MONDO:0021094; Susceptibility to mycobacteria and Salmonella
Mendeliome v1.167 IL23R Zornitza Stark Publications for gene: IL23R were set to 30578351
Mendeliome v1.166 IL23R Zornitza Stark Classified gene: IL23R as Amber List (moderate evidence)
Mendeliome v1.166 IL23R Zornitza Stark Gene: il23r has been classified as Amber List (Moderate Evidence).
Mendeliome v1.165 IL23R Zornitza Stark edited their review of gene: IL23R: Added comment: PMID 35829840: 48yo male with disseminated NTM homozygous (p.R381X) with supportive functional data.; Changed rating: AMBER; Changed publications: 30578351, 35829840
Defects of intrinsic and innate immunity v0.117 IL23R Zornitza Stark Phenotypes for gene: IL23R were changed from Susceptibility to mycobacteria and Salmonella to Immunodeficiency disease, MONDO:0021094; Susceptibility to mycobacteria and Salmonella
Defects of intrinsic and innate immunity v0.116 IL23R Zornitza Stark Publications for gene: IL23R were set to 30578351
Defects of intrinsic and innate immunity v0.115 IL23R Zornitza Stark Classified gene: IL23R as Green List (high evidence)
Defects of intrinsic and innate immunity v0.115 IL23R Zornitza Stark Gene: il23r has been classified as Green List (High Evidence).
Prepair 1000+ v0.58 FA2H Crystle Lee reviewed gene: FA2H: Rating: GREEN; Mode of pathogenicity: None; Publications: 31135052, 31837835, 22146942, 19068277; Phenotypes: Spastic paraplegia 35, autosomal recessive (MIM#612319); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Phagocyte Defects v1.6 HYOU1 Zornitza Stark edited their review of gene: HYOU1: Changed rating: AMBER; Changed phenotypes: Immunodeficiency 59 and hypoglycemia, MIM# 233600
Prepair 1000+ v0.58 DSP Crystle Lee reviewed gene: DSP: Rating: GREEN; Mode of pathogenicity: None; Publications: 22795705, 16175511, 20302578, 20613772, 16467215; Phenotypes: Cardiomyopathy, dilated, with woolly hair and keratoderma (MIM#605676), Epidermolysis bullosa, lethal acantholytic (MIM#609638); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.165 HYOU1 Zornitza Stark Classified gene: HYOU1 as Amber List (moderate evidence)
Mendeliome v1.165 HYOU1 Zornitza Stark Gene: hyou1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.164 HYOU1 Zornitza Stark edited their review of gene: HYOU1: Added comment: Second individual reported in PMID: 35822684 with severe neutropenia.; Changed rating: AMBER; Changed publications: 27913302, 35822684; Changed phenotypes: Immunodeficiency 59 and hypoglycemia, MIM# 233600
Phagocyte Defects v1.6 HYOU1 Zornitza Stark Marked gene: HYOU1 as ready
Phagocyte Defects v1.6 HYOU1 Zornitza Stark Added comment: Comment when marking as ready: Promoted to Amber as two individuals now reported.
Phagocyte Defects v1.6 HYOU1 Zornitza Stark Gene: hyou1 has been classified as Amber List (Moderate Evidence).
Phagocyte Defects v1.6 HYOU1 Zornitza Stark Publications for gene: HYOU1 were set to 27913302
Phagocyte Defects v1.5 HYOU1 Zornitza Stark Classified gene: HYOU1 as Amber List (moderate evidence)
Phagocyte Defects v1.5 HYOU1 Zornitza Stark Gene: hyou1 has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v0.58 PGK1 Zornitza Stark Tag for review tag was added to gene: PGK1.
Prepair 1000+ v0.58 GK Zornitza Stark Tag for review tag was added to gene: GK.
Prepair 1000+ v0.58 CASQ2 Crystle Lee reviewed gene: CASQ2: Rating: AMBER; Mode of pathogenicity: None; Publications: 34012068; Phenotypes: Ventricular tachycardia, catecholaminergic polymorphic, 2 (MIM#611938); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.58 ATP7B Crystle Lee reviewed gene: ATP7B: Rating: GREEN; Mode of pathogenicity: None; Publications: 28433102; Phenotypes: Wilson disease (MIM#277900); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.58 ATP13A2 Crystle Lee reviewed gene: ATP13A2: Rating: RED; Mode of pathogenicity: None; Publications: 28137957, 30746398; Phenotypes: Kufor-Rakeb syndrome (MIM#606693), Spastic paraplegia 78, autosomal recessive (MIM#617225); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.58 BGN Crystle Lee reviewed gene: BGN: Rating: AMBER; Mode of pathogenicity: None; Publications: 27632686, 17502576, 27236923; Phenotypes: Meester-Loeys syndrome (MIM#300989), Spondyloepimetaphyseal dysplasia, X-linked (MIM#300106); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v0.58 C8B Crystle Lee reviewed gene: C8B: Rating: AMBER; Mode of pathogenicity: None; Publications: 8098723, 33563058, 27183977, 9476133, 19434484, 31440263; Phenotypes: C8 deficiency, type II (MIM#613789); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.58 C7 Crystle Lee reviewed gene: C7: Rating: AMBER; Mode of pathogenicity: None; Publications: 22206826, 20591074, 17407100, 16771861; Phenotypes: C7 deficiency (MIM#610102); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.58 C6 Crystle Lee reviewed gene: C6: Rating: AMBER; Mode of pathogenicity: None; Publications: 31440263, 23537992, 17257682, 22668955, 32670577; Phenotypes: C6 deficiency (MIM#612446); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Complement Deficiencies v0.72 C5 Crystle Lee reviewed gene: C5: Rating: AMBER; Mode of pathogenicity: None; Publications: 31440263, 23743184, 15488949, 15778377, 23371790; Phenotypes: C5 deficiency (MIM#609536); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Defects of intrinsic and innate immunity v0.114 IL23R Peter McNaughton reviewed gene: IL23R: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35829840; Phenotypes: Susceptibility to mycobacterial disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Phagocyte Defects v1.4 HYOU1 Peter McNaughton reviewed gene: HYOU1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 35822684; Phenotypes: Severe congenital neutropaenia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.58 PGK1 Crystle Lee reviewed gene: PGK1: Rating: ; Mode of pathogenicity: None; Publications: 16567715, 30887539, 22348148, 28580215; Phenotypes: Phosphoglycerate kinase 1 deficiency (MIM#300653); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v0.58 GK Crystle Lee reviewed gene: GK: Rating: AMBER; Mode of pathogenicity: None; Publications: 33212314, 16549535, 10851254, 9719371, 8651297; Phenotypes: Glycerol kinase deficiency (MIM#307030); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hydrops fetalis v0.284 UROS Zornitza Stark Publications for gene: UROS were set to 24027798
Hydrops fetalis v0.283 UROS Zornitza Stark Classified gene: UROS as Green List (high evidence)
Hydrops fetalis v0.283 UROS Zornitza Stark Gene: uros has been classified as Green List (High Evidence).
Hydrops fetalis v0.282 UROS Chern Lim reviewed gene: UROS: Rating: GREEN; Mode of pathogenicity: None; Publications: 30685241, 34828434, 15065102, 11254675; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v0.58 HERC2 Zornitza Stark Tag for review tag was added to gene: HERC2.
Prepair 1000+ v0.58 GBA Zornitza Stark Tag for review tag was added to gene: GBA.
Prepair 1000+ v0.58 SAMD9 Zornitza Stark Marked gene: SAMD9 as ready
Prepair 1000+ v0.58 SAMD9 Zornitza Stark Gene: samd9 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.58 SAMD9 Zornitza Stark Publications for gene: SAMD9 were set to
Prepair 1000+ v0.57 SAMD9 Zornitza Stark Classified gene: SAMD9 as Red List (low evidence)
Prepair 1000+ v0.57 SAMD9 Zornitza Stark Gene: samd9 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.56 FTCD Zornitza Stark Tag for review tag was added to gene: FTCD.
Prepair 1000+ v0.56 KRT85 Zornitza Stark Marked gene: KRT85 as ready
Prepair 1000+ v0.56 KRT85 Zornitza Stark Gene: krt85 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.56 KRT85 Zornitza Stark Classified gene: KRT85 as Red List (low evidence)
Prepair 1000+ v0.56 KRT85 Zornitza Stark Gene: krt85 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.55 KRT85 Zornitza Stark reviewed gene: KRT85: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ectodermal dysplasia 4, hair/nail type (MIM#602032); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.55 RAG2 Zornitza Stark Marked gene: RAG2 as ready
Prepair 1000+ v0.55 RAG2 Zornitza Stark Gene: rag2 has been classified as Green List (High Evidence).
Prepair 1000+ v0.55 RAG2 Zornitza Stark Publications for gene: RAG2 were set to
Cardiomyopathy_Paediatric v0.132 PPP1R13L Zornitza Stark Phenotypes for gene: PPP1R13L were changed from Dilated cardiomyopathy, onset in infancy to Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042 - PPP1R13L-related; Dilated cardiomyopathy, onset in infancy
Mendeliome v1.164 PPP1R13L Zornitza Stark Phenotypes for gene: PPP1R13L were changed from Dilated cardiomyopathy, onset in infancy to Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042 - PPP1R13L-related; Dilated cardiomyopathy, onset in infancy
Clefting disorders v0.183 PPP1R13L Zornitza Stark Phenotypes for gene: PPP1R13L were changed from Dilated cardiomyopathy, onset in infancy; Cleft lip and palate to Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042 - PPP1R13L-related; Dilated cardiomyopathy, onset in infancy; Cleft lip and palate
Fetal anomalies v1.48 PPP1R13L Zornitza Stark Phenotypes for gene: PPP1R13L were changed from Dilated cardiomyopathy, onset in infancy; Cleft lip and palate to Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042 - PPP1R13L-related; Dilated cardiomyopathy, onset in infancy; Cleft lip and palate
Prepair 1000+ v0.54 CARD9 Zornitza Stark Tag for review tag was added to gene: CARD9.
Prepair 1000+ v0.54 PLG Zornitza Stark Tag for review tag was added to gene: PLG.
Prepair 1000+ v0.54 GYS2 Zornitza Stark Tag for review tag was added to gene: GYS2.
Prepair 1000+ v0.54 MPZ Zornitza Stark Tag for review tag was added to gene: MPZ.
Early-onset Parkinson disease v0.215 KIAA1161 Zornitza Stark Tag new gene name tag was added to gene: KIAA1161.
Prepair 1000+ v0.54 HERC2 Crystle Lee reviewed gene: HERC2: Rating: AMBER; Mode of pathogenicity: None; Publications: 31124564, 11896453; Phenotypes: Intellectual developmental disorder, autosomal recessive 38 (MIM#615516); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.54 GBA Crystle Lee reviewed gene: GBA: Rating: AMBER; Mode of pathogenicity: None; Publications: 28727984; Phenotypes: Gaucher disease, perinatal lethal (MIM#608013); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.215 KIAA1161 Zornitza Stark Marked gene: KIAA1161 as ready
Early-onset Parkinson disease v0.215 KIAA1161 Zornitza Stark Gene: kiaa1161 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.215 KIAA1161 Zornitza Stark Phenotypes for gene: KIAA1161 were changed from Primary familial brain calcification; Atypical parkinsonism; Supranuclear gaze palsy; OMIM 618317 to Basal ganglia calcification, idiopathic, 7, autosomal recessive, OMIM #618317; Primary familial brain calcification; Atypical parkinsonism; Supranuclear gaze palsy
Early-onset Parkinson disease v0.214 KIAA1161 Zornitza Stark Publications for gene: KIAA1161 were set to PMID: 32211515
Early-onset Parkinson disease v0.213 KIAA1161 Zornitza Stark Classified gene: KIAA1161 as Green List (high evidence)
Early-onset Parkinson disease v0.213 KIAA1161 Zornitza Stark Gene: kiaa1161 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.212 KIAA1161 Zornitza Stark reviewed gene: KIAA1161: Rating: GREEN; Mode of pathogenicity: None; Publications: 30656188, 30649222, 30460687, 29910000, 31951047; Phenotypes: Basal ganglia calcification, idiopathic, 7, autosomal recessive, OMIM #618317; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.212 NHLRC1 Zornitza Stark Marked gene: NHLRC1 as ready
Early-onset Parkinson disease v0.212 NHLRC1 Zornitza Stark Gene: nhlrc1 has been classified as Amber List (Moderate Evidence).
Early-onset Parkinson disease v0.212 NHLRC1 Zornitza Stark Phenotypes for gene: NHLRC1 were changed from Lafora disease; Progressive Myoclonic Epilepsy; Parkinsonism; OMIM 254780 to Epilepsy, progressive myoclonic 2B (Lafora), MIM# 254780; Lafora disease; Progressive Myoclonic Epilepsy; Parkinsonism
Early-onset Parkinson disease v0.211 NHLRC1 Zornitza Stark Classified gene: NHLRC1 as Amber List (moderate evidence)
Early-onset Parkinson disease v0.211 NHLRC1 Zornitza Stark Gene: nhlrc1 has been classified as Amber List (Moderate Evidence).
Early-onset Parkinson disease v0.210 NHLRC1 Zornitza Stark reviewed gene: NHLRC1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Epilepsy, progressive myoclonic 2B (Lafora), MIM# 254780; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.210 C9orf3 Zornitza Stark Tag new gene name tag was added to gene: C9orf3.
Early-onset Parkinson disease v0.210 C9orf3 Zornitza Stark Marked gene: C9orf3 as ready
Early-onset Parkinson disease v0.210 C9orf3 Zornitza Stark Gene: c9orf3 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.210 C9orf3 Zornitza Stark Phenotypes for gene: C9orf3 were changed from Dystonia-31; Childhood/Adolescence onset generalised dystonia; Dystonia parkinsonism; Zech-Boesch Syndrome; OMIM 619565 to Dystonia 31, MIM# 619565; Childhood/Adolescence onset generalised dystonia; Dystonia parkinsonism; Zech-Boesch Syndrome
Early-onset Parkinson disease v0.209 C9orf3 Zornitza Stark Classified gene: C9orf3 as Green List (high evidence)
Early-onset Parkinson disease v0.209 C9orf3 Zornitza Stark Gene: c9orf3 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.208 C9orf3 Zornitza Stark reviewed gene: C9orf3: Rating: GREEN; Mode of pathogenicity: None; Publications: 35306330; Phenotypes: Dystonia 31, MIM# 619565; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.54 NCF1 Zornitza Stark Tag for review tag was added to gene: NCF1.
Prepair 1000+ v0.54 NEB Zornitza Stark Tag for review tag was added to gene: NEB.
Prepair 1000+ v0.54 HYDIN Zornitza Stark Tag for review tag was added to gene: HYDIN.
Prepair 1000+ v0.54 SNORD118 Zornitza Stark Marked gene: SNORD118 as ready
Prepair 1000+ v0.54 SNORD118 Zornitza Stark Gene: snord118 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.54 SNORD118 Zornitza Stark Publications for gene: SNORD118 were set to
Prepair 1000+ v0.53 SNORD118 Zornitza Stark Classified gene: SNORD118 as Red List (low evidence)
Prepair 1000+ v0.53 SNORD118 Zornitza Stark Gene: snord118 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.52 SNORD118 Zornitza Stark reviewed gene: SNORD118: Rating: RED; Mode of pathogenicity: None; Publications: 32361877, 33029936; Phenotypes: Leukoencephalopathy, brain calcifications, and cysts, MIM#614561; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.52 UBA1 Zornitza Stark Marked gene: UBA1 as ready
Prepair 1000+ v0.52 UBA1 Zornitza Stark Gene: uba1 has been classified as Green List (High Evidence).
Prepair 1000+ v0.52 UBA1 Zornitza Stark Publications for gene: UBA1 were set to
Prepair 1000+ v0.51 CHM Zornitza Stark Tag for review tag was added to gene: CHM.
Prepair 1000+ v0.51 PROC Zornitza Stark Tag for review tag was added to gene: PROC.
Prepair 1000+ v0.51 IKBKG Zornitza Stark Marked gene: IKBKG as ready
Prepair 1000+ v0.51 IKBKG Zornitza Stark Gene: ikbkg has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v0.51 IKBKG Zornitza Stark Classified gene: IKBKG as Amber List (moderate evidence)
Prepair 1000+ v0.51 IKBKG Zornitza Stark Gene: ikbkg has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v0.50 IKBKG Zornitza Stark reviewed gene: IKBKG: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Early-onset Parkinson disease v0.208 ATXN10 Zornitza Stark Marked gene: ATXN10 as ready
Early-onset Parkinson disease v0.208 ATXN10 Zornitza Stark Gene: atxn10 has been removed from the panel.
Early-onset Parkinson disease v0.208 ATXN10 Zornitza Stark Tag STR tag was added to gene: ATXN10.
Early-onset Parkinson disease v0.208 ATXN10 Zornitza Stark commented on gene: ATXN10
Early-onset Parkinson disease v0.208 ATXN2 Zornitza Stark Marked gene: ATXN2 as ready
Early-onset Parkinson disease v0.208 ATXN2 Zornitza Stark Gene: atxn2 has been removed from the panel.
Early-onset Parkinson disease v0.208 ATXN2 Zornitza Stark Publications for gene: ATXN2 were set to PMID: 11761482, 17923635
Early-onset Parkinson disease v0.207 ATXN2 Zornitza Stark Tag STR tag was added to gene: ATXN2.
Early-onset Parkinson disease v0.207 ATXN2 Zornitza Stark commented on gene: ATXN2
Early-onset Parkinson disease v0.207 ATXN3 Zornitza Stark Tag STR tag was added to gene: ATXN3.
Early-onset Parkinson disease v0.207 ATXN3 Zornitza Stark Marked gene: ATXN3 as ready
Early-onset Parkinson disease v0.207 ATXN3 Zornitza Stark Gene: atxn3 has been removed from the panel.
Early-onset Parkinson disease v0.207 ATXN3 Zornitza Stark commented on gene: ATXN3
Early-onset Parkinson disease v0.207 ATXN8 Zornitza Stark Marked gene: ATXN8 as ready
Early-onset Parkinson disease v0.207 ATXN8 Zornitza Stark Gene: atxn8 has been removed from the panel.
Early-onset Parkinson disease v0.207 ATXN8 Zornitza Stark Tag STR tag was added to gene: ATXN8.
Early-onset Parkinson disease v0.207 ATXN8 Zornitza Stark commented on gene: ATXN8
Early-onset Parkinson disease v0.207 TPP1 Zornitza Stark Marked gene: TPP1 as ready
Early-onset Parkinson disease v0.207 TPP1 Zornitza Stark Gene: tpp1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.207 TPP1 Zornitza Stark Phenotypes for gene: TPP1 were changed from Late Infantile NCL; Parkinsonism; OMIM 204500 to Ceroid lipofuscinosis, neuronal, 2, MIM# 204500; Parkinsonism
Early-onset Parkinson disease v0.206 TPP1 Zornitza Stark Classified gene: TPP1 as Green List (high evidence)
Early-onset Parkinson disease v0.206 TPP1 Zornitza Stark Gene: tpp1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.205 TPP1 Zornitza Stark reviewed gene: TPP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ceroid lipofuscinosis, neuronal, 2, MIM# 204500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.205 CYP27A1 Zornitza Stark Marked gene: CYP27A1 as ready
Early-onset Parkinson disease v0.205 CYP27A1 Zornitza Stark Gene: cyp27a1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.205 CYP27A1 Zornitza Stark Phenotypes for gene: CYP27A1 were changed from Cerebrotendinous xanthomatosis, infantile-onset diarrhoea, juvenile-onset cataract, young adult-onset tendon xanthomas; Epilepsy; Parkinsonism; Ataxia; Peripheral neuropathy; OMIM 213700 to Cerebrotendinous xanthomatosis, MIM# 213700; Cerebrotendinous xanthomatosis, infantile-onset diarrhoea, juvenile-onset cataract, young adult-onset tendon xanthomas; Epilepsy; Parkinsonism; Ataxia; Peripheral neuropathy
Early-onset Parkinson disease v0.204 CYP27A1 Zornitza Stark Classified gene: CYP27A1 as Green List (high evidence)
Early-onset Parkinson disease v0.204 CYP27A1 Zornitza Stark Gene: cyp27a1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.203 DDC Zornitza Stark Marked gene: DDC as ready
Early-onset Parkinson disease v0.203 DDC Zornitza Stark Gene: ddc has been classified as Amber List (Moderate Evidence).
Early-onset Parkinson disease v0.203 DDC Zornitza Stark Phenotypes for gene: DDC were changed from Aromatic L-amino acid decarboxylase deficiency (DYT-DDC); Infantile-onset parkinsonism & dystonia; Bulbar dysfunction; Oculogyric crisis; Autonomic dysfunction; Intellectual disability; OMIM 608603 to Aromatic L-amino acid decarboxylase deficiency, MIM# 608643; Infantile-onset parkinsonism & dystonia; Bulbar dysfunction; Oculogyric crisis; Autonomic dysfunction; Intellectual disability
Early-onset Parkinson disease v0.202 DDC Zornitza Stark Classified gene: DDC as Amber List (moderate evidence)
Early-onset Parkinson disease v0.202 DDC Zornitza Stark Gene: ddc has been classified as Amber List (Moderate Evidence).
Early-onset Parkinson disease v0.201 DDC Zornitza Stark reviewed gene: DDC: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Aromatic L-amino acid decarboxylase deficiency, MIM# 608643; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.50 SAMD9 Crystle Lee reviewed gene: SAMD9: Rating: RED; Mode of pathogenicity: None; Publications: 16960814, 18094730; Phenotypes: MIRAGE syndrome (MIM#617053), Monosomy 7 myelodysplasia and leukemia syndrome 2 (MIM#619041), Tumoral calcinosis, familial, normophosphatemic (MIM#610455); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Prepair 1000+ v0.50 FTCD Crystle Lee reviewed gene: FTCD: Rating: AMBER; Mode of pathogenicity: None; Publications: 29178637, 30740726, 12815595; Phenotypes: Glutamate formiminotransferase deficiency (MIM#229100); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.50 KRT85 Crystle Lee reviewed gene: KRT85: Rating: AMBER; Mode of pathogenicity: None; Publications: 16525032, 19865094, 31273852; Phenotypes: Ectodermal dysplasia 4, hair/nail type (MIM#602032); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.163 CHD5 Elena Savva Phenotypes for gene: CHD5 were changed from Intellectual disability; Epilepsy to Parenti-Mignot neurodevelopmental syndrome MIM#619873
Mendeliome v1.162 CHD5 Elena Savva reviewed gene: CHD5: Rating: GREEN; Mode of pathogenicity: None; Publications: 33944996; Phenotypes: Parenti-Mignot neurodevelopmental syndrome MIM#619873; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Prepair 1000+ v0.50 RAG2 Crystle Lee reviewed gene: RAG2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26996199, 30046960; Phenotypes: Combined cellular and humoral immune defects with granulomas (MIM#233650), Omenn syndrome (MIM#603554), Severe combined immunodeficiency, B cell-negative (MIM#601457); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.162 PPP1R13L Krithika Murali reviewed gene: PPP1R13L: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042 - PPP1R13L-related disorder; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Clefting disorders v0.182 PPP1R13L Krithika Murali reviewed gene: PPP1R13L: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042 - PPP1R13L-related disorder; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v0.131 PPP1R13L Krithika Murali reviewed gene: PPP1R13L: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042 - PPP1R13L-related disorder; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.47 PPP1R13L Krithika Murali edited their review of gene: PPP1R13L: Changed phenotypes: Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042 - PPP1R13L-related disorder, Dilated cardiomyopathy, onset in infancy, Cleft lip and palate
Early-onset Parkinson disease v0.201 DHDDS Zornitza Stark Marked gene: DHDDS as ready
Early-onset Parkinson disease v0.201 DHDDS Zornitza Stark Gene: dhdds has been classified as Amber List (Moderate Evidence).
Early-onset Parkinson disease v0.201 DHDDS Zornitza Stark Phenotypes for gene: DHDDS were changed from Myoclonic Epilepsy; Parkinsonism; Ataxia; Intellectual disability; OMIM 617836 to Developmental delay and seizures with or without movement abnormalities, MIM# 617836; Myoclonic Epilepsy; Parkinsonism; Ataxia; Intellectual disability
Early-onset Parkinson disease v0.200 DHDDS Zornitza Stark Publications for gene: DHDDS were set to PMID: 34837344, 29100083
Early-onset Parkinson disease v0.199 DHDDS Zornitza Stark Classified gene: DHDDS as Amber List (moderate evidence)
Early-onset Parkinson disease v0.199 DHDDS Zornitza Stark Gene: dhdds has been classified as Amber List (Moderate Evidence).
Early-onset Parkinson disease v0.198 DHDDS Zornitza Stark reviewed gene: DHDDS: Rating: AMBER; Mode of pathogenicity: None; Publications: 34837344; Phenotypes: Developmental delay and seizures with or without movement abnormalities, MIM# 617836; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.198 EIF2AK2 Zornitza Stark Marked gene: EIF2AK2 as ready
Early-onset Parkinson disease v0.198 EIF2AK2 Zornitza Stark Gene: eif2ak2 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.198 EIF2AK2 Zornitza Stark Phenotypes for gene: EIF2AK2 were changed from Neurodevelopmental Syndrome; Developmental delays; Ataxia; Parkinsonism; White matter alterations; OMIM 618877 to Leukoencephalopathy, developmental delay, and episodic neurologic regression syndrome, MIM# 618877; Neurodevelopmental Syndrome; Developmental delays; Ataxia; Parkinsonism; White matter alterations
Early-onset Parkinson disease v0.197 EIF2AK2 Zornitza Stark Mode of inheritance for gene: EIF2AK2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.196 EIF2AK2 Zornitza Stark Classified gene: EIF2AK2 as Green List (high evidence)
Early-onset Parkinson disease v0.196 EIF2AK2 Zornitza Stark Gene: eif2ak2 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.195 EIF2AK2 Zornitza Stark reviewed gene: EIF2AK2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Leukoencephalopathy, developmental delay, and episodic neurologic regression syndrome, MIM# 618877; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.195 EPM2A Zornitza Stark Marked gene: EPM2A as ready
Early-onset Parkinson disease v0.195 EPM2A Zornitza Stark Gene: epm2a has been classified as Amber List (Moderate Evidence).
Early-onset Parkinson disease v0.195 EPM2A Zornitza Stark Phenotypes for gene: EPM2A were changed from Lafora disease; Progressive Myoclonic Epilepsy; Parkinsonism; OMIM 254780 to Epilepsy, progressive myoclonic 2A (Lafora), MIM# 254780; Progressive Myoclonic Epilepsy; Parkinsonism
Early-onset Parkinson disease v0.194 EPM2A Zornitza Stark Classified gene: EPM2A as Amber List (moderate evidence)
Early-onset Parkinson disease v0.194 EPM2A Zornitza Stark Gene: epm2a has been classified as Amber List (Moderate Evidence).
Early-onset Parkinson disease v0.193 EPM2A Zornitza Stark reviewed gene: EPM2A: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Epilepsy, progressive myoclonic 2A (Lafora), MIM# 254780; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.193 FOXG1 Zornitza Stark Classified gene: FOXG1 as Green List (high evidence)
Early-onset Parkinson disease v0.193 FOXG1 Zornitza Stark Gene: foxg1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.192 FOXG1 Zornitza Stark Marked gene: FOXG1 as ready
Early-onset Parkinson disease v0.192 FOXG1 Zornitza Stark Gene: foxg1 has been removed from the panel.
Early-onset Parkinson disease v0.192 FOXG1 Zornitza Stark Phenotypes for gene: FOXG1 were changed from Developmental and Epileptic Encephalopathy; Dystonia,; Athetosis; Parkinsonism; Stereotypies; OMIM 613454 to Rett syndrome, congenital variant, MIM# 613454; Developmental and Epileptic Encephalopathy; Dystonia,; Athetosis; Parkinsonism; Stereotypies
Early-onset Parkinson disease v0.191 GLB1 Zornitza Stark changed review comment from: Reported in Type 3.; to: Parkinsonism reported in Type 3.
Early-onset Parkinson disease v0.191 GLB1 Zornitza Stark Marked gene: GLB1 as ready
Early-onset Parkinson disease v0.191 GLB1 Zornitza Stark Gene: glb1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.191 GLB1 Zornitza Stark Phenotypes for gene: GLB1 were changed from GM1 Gangliosidosis; Parkinsonism; OMIM 230650 to GM1-gangliosidosis, type III , MIM#230650; Parkinsonism
Early-onset Parkinson disease v0.190 GLB1 Zornitza Stark Classified gene: GLB1 as Green List (high evidence)
Early-onset Parkinson disease v0.190 GLB1 Zornitza Stark Gene: glb1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.189 GLB1 Zornitza Stark reviewed gene: GLB1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: GM1-gangliosidosis, type III , MIM#230650; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v0.181 GINS3 Zornitza Stark Marked gene: GINS3 as ready
Skeletal dysplasia v0.181 GINS3 Zornitza Stark Gene: gins3 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.181 GINS3 Zornitza Stark Classified gene: GINS3 as Green List (high evidence)
Skeletal dysplasia v0.181 GINS3 Zornitza Stark Gene: gins3 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.180 GINS3 Zornitza Stark gene: GINS3 was added
gene: GINS3 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: GINS3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GINS3 were set to 35603789
Phenotypes for gene: GINS3 were set to Meier-Gorlin syndrome, MONDO:0016817, GINS3-related
Review for gene: GINS3 was set to GREEN
Added comment: 7 individuals from 5 families reported, presenting with prenatal and postnatal growth deficiency as well as other features. Three unique missense variants identified, two affecting p.Asp24. These variants are thought to be hypomorphic. Supportive mouse model.
Sources: Literature
Prepair 1000+ v0.50 CARD9 Crystle Lee reviewed gene: CARD9: Rating: AMBER; Mode of pathogenicity: None; Publications: 30136218; Phenotypes: Immunodeficiency 103, susceptibility to fungal infection (MIM#212050); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.137 GINS3 Zornitza Stark Marked gene: GINS3 as ready
Microcephaly v1.137 GINS3 Zornitza Stark Gene: gins3 has been classified as Green List (High Evidence).
Microcephaly v1.137 GINS3 Zornitza Stark Classified gene: GINS3 as Green List (high evidence)
Microcephaly v1.137 GINS3 Zornitza Stark Gene: gins3 has been classified as Green List (High Evidence).
Microcephaly v1.136 GINS3 Zornitza Stark gene: GINS3 was added
gene: GINS3 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: GINS3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GINS3 were set to 35603789
Phenotypes for gene: GINS3 were set to Meier-Gorlin syndrome, MONDO:0016817, GINS3-related
Review for gene: GINS3 was set to GREEN
Added comment: 7 individuals from 5 families reported, presenting with prenatal and postnatal growth deficiency as well as other features. Three unique missense variants identified, two affecting p.Asp24. These variants are thought to be hypomorphic. Supportive mouse model.
Sources: Literature
Fetal anomalies v1.47 GINS3 Zornitza Stark gene: GINS3 was added
gene: GINS3 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: GINS3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GINS3 were set to 35603789
Phenotypes for gene: GINS3 were set to Meier-Gorlin syndrome, MONDO:0016817, GINS3-related
Review for gene: GINS3 was set to GREEN
Added comment: 7 individuals from 5 families reported, presenting with prenatal and postnatal growth deficiency as well as other features. Three unique missense variants identified, two affecting p.Asp24. These variants are thought to be hypomorphic. Supportive mouse model.
Sources: Literature
Growth failure v1.44 GINS3 Zornitza Stark Marked gene: GINS3 as ready
Growth failure v1.44 GINS3 Zornitza Stark Gene: gins3 has been classified as Green List (High Evidence).
Growth failure v1.44 GINS3 Zornitza Stark Classified gene: GINS3 as Green List (high evidence)
Growth failure v1.44 GINS3 Zornitza Stark Gene: gins3 has been classified as Green List (High Evidence).
Growth failure v1.43 GINS3 Zornitza Stark gene: GINS3 was added
gene: GINS3 was added to Growth failure. Sources: Literature
Mode of inheritance for gene: GINS3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GINS3 were set to 35603789
Phenotypes for gene: GINS3 were set to Meier-Gorlin syndrome, MONDO:0016817, GINS3-related
Review for gene: GINS3 was set to GREEN
Added comment: 7 individuals from 5 families reported, presenting with prenatal and postnatal growth deficiency as well as other features. Three unique missense variants identified, two affecting p.Asp24. These variants are thought to be hypomorphic. Supportive mouse model.
Sources: Literature
Mendeliome v1.162 GINS3 Zornitza Stark Marked gene: GINS3 as ready
Mendeliome v1.162 GINS3 Zornitza Stark Gene: gins3 has been classified as Green List (High Evidence).
Mendeliome v1.162 GINS3 Zornitza Stark Classified gene: GINS3 as Green List (high evidence)
Mendeliome v1.162 GINS3 Zornitza Stark Gene: gins3 has been classified as Green List (High Evidence).
Mendeliome v1.161 GINS3 Zornitza Stark gene: GINS3 was added
gene: GINS3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GINS3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GINS3 were set to 35603789
Phenotypes for gene: GINS3 were set to Meier-Gorlin syndrome, MONDO:0016817, GINS3-related
Review for gene: GINS3 was set to GREEN
Added comment: 7 individuals from 5 families reported, presenting with prenatal and postnatal growth deficiency as well as other features. Three unique missense variants identified, two affecting p.Asp24. These variants are thought to be hypomorphic. Supportive mouse model.
Sources: Literature
Prepair 1000+ v0.50 PLG Crystle Lee changed review comment from: 2 AR conditions associated with PLG; Type I plasminogen deficiency and type II plasminogen deficiency, also known as 'dysplasminogenemia'. Patients with type II deficiency are usually asymptomatic (OMIM). The most common clinical manifestation is ligneous conjunctivitis. Other neurological manifestations such as hydrocephalus and Dandy Walker malformation can also be present in some patients

PMID: 21174000: Phenotype shows inter- and intra- familial variability. Residual PLG activity does not always correlate with clinical severity

AR condition can be associated with severe, early onset presentation; to: 2 AR conditions associated with PLG; Type I plasminogen deficiency and type II plasminogen deficiency, also known as 'dysplasminogenemia'. Patients with type II deficiency are usually asymptomatic (OMIM). The most common clinical manifestation is ligneous conjunctivitis. Other neurological manifestations such as hydrocephalus and Dandy Walker malformation can also be present in some patients

PMID: 21174000: Phenotype shows inter- and intra- familial variability. Residual PLG activity does not always correlate with clinical severity

AR condition can be associated with severe, early onset presentation
Prepair 1000+ v0.50 PLG Crystle Lee reviewed gene: PLG: Rating: AMBER; Mode of pathogenicity: None; Publications: 9242524, 35244080; Phenotypes: Angioedema, hereditary, 4 (MIM#619360), Dysplasminogenemia (MIM#217090), Plasminogen deficiency, type I (MIM#217090); Mode of inheritance: None
Prepair 1000+ v0.50 GYS2 Crystle Lee reviewed gene: GYS2: Rating: AMBER; Mode of pathogenicity: None; Publications: 18341095, 32395408; Phenotypes: Glycogen storage disease 0, liver (MIM#240600); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.50 MPZ Crystle Lee reviewed gene: MPZ: Rating: AMBER; Mode of pathogenicity: None; Publications: 30239779, 8816708, 12845552, 16488608, 26310628, 8630052; Phenotypes: Charcot-Marie-Tooth disease, dominant intermediate D (MIM#607791), Charcot-Marie-Tooth disease, type 1B (MIM#118200), Charcot-Marie-Tooth disease, type 2I (MIM#607677), Charcot-Marie-Tooth disease, type 2J (MIM#607736), Dejerine-Sottas disease (MIM#145900), Hypomyelinating neuropathy, congenital, 2 (MIM#618184), Roussy-Levy syndrome (MIM#180800); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Early-onset Parkinson disease v0.189 KIAA1161 SHEKEEB MOHAMMAD gene: KIAA1161 was added
gene: KIAA1161 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: KIAA1161 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA1161 were set to PMID: 32211515
Phenotypes for gene: KIAA1161 were set to Primary familial brain calcification; Atypical parkinsonism; Supranuclear gaze palsy; OMIM 618317
Review for gene: KIAA1161 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.189 C9orf3 SHEKEEB MOHAMMAD reviewed gene: C9orf3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Early-onset Parkinson disease v0.189 NHLRC1 SHEKEEB MOHAMMAD gene: NHLRC1 was added
gene: NHLRC1 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: NHLRC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NHLRC1 were set to PMID: 22425593
Phenotypes for gene: NHLRC1 were set to Lafora disease; Progressive Myoclonic Epilepsy; Parkinsonism; OMIM 254780
Review for gene: NHLRC1 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.189 C9orf3 SHEKEEB MOHAMMAD gene: C9orf3 was added
gene: C9orf3 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: C9orf3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C9orf3 were set to PMID: 35306330
Phenotypes for gene: C9orf3 were set to Dystonia-31; Childhood/Adolescence onset generalised dystonia; Dystonia parkinsonism; Zech-Boesch Syndrome; OMIM 619565
Early-onset Parkinson disease v0.189 HEXA Zornitza Stark edited their review of gene: HEXA: Changed rating: RED; Changed phenotypes: Tay-Sachs disease, MIM# 272800; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.189 HEXA Zornitza Stark Marked gene: HEXA as ready
Early-onset Parkinson disease v0.189 HEXA Zornitza Stark Gene: hexa has been classified as Red List (Low Evidence).
Early-onset Parkinson disease v0.189 HEXA Zornitza Stark Classified gene: HEXA as Red List (low evidence)
Early-onset Parkinson disease v0.189 HEXA Zornitza Stark Gene: hexa has been classified as Red List (Low Evidence).
Early-onset Parkinson disease v0.188 HEXA Zornitza Stark Classified gene: HEXA as Amber List (moderate evidence)
Early-onset Parkinson disease v0.188 HEXA Zornitza Stark Gene: hexa has been classified as Amber List (Moderate Evidence).
Early-onset Parkinson disease v0.187 HEXA Zornitza Stark reviewed gene: HEXA: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Early-onset Parkinson disease v0.187 JPH3 Zornitza Stark Marked gene: JPH3 as ready
Early-onset Parkinson disease v0.187 JPH3 Zornitza Stark Gene: jph3 has been removed from the panel.
Early-onset Parkinson disease v0.187 JPH3 Zornitza Stark Tag STR tag was added to gene: JPH3.
Early-onset Parkinson disease v0.187 JPH3 Zornitza Stark commented on gene: JPH3
Early-onset Parkinson disease v0.187 NPC2 Zornitza Stark Marked gene: NPC2 as ready
Early-onset Parkinson disease v0.187 NPC2 Zornitza Stark Gene: npc2 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.187 NPC2 Zornitza Stark Phenotypes for gene: NPC2 were changed from Niemann Pick C2; Parkinsonism; OMIM 607625 to Niemann Pick C2, OMIM 607625; Parkinsonism
Early-onset Parkinson disease v0.186 NPC2 Zornitza Stark Classified gene: NPC2 as Green List (high evidence)
Early-onset Parkinson disease v0.186 NPC2 Zornitza Stark Gene: npc2 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.185 NPC1 Zornitza Stark Marked gene: NPC1 as ready
Early-onset Parkinson disease v0.185 NPC1 Zornitza Stark Gene: npc1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.185 NPC1 Zornitza Stark Phenotypes for gene: NPC1 were changed from Niemann Pick C1; Parkinsonism; OMIM 257220 to Niemann-Pick disease, MIM# 257220; Parkinsonism
Early-onset Parkinson disease v0.184 NPC1 Zornitza Stark Publications for gene: NPC1 were set to PMID: 24035292
Early-onset Parkinson disease v0.183 NPC1 Zornitza Stark Mode of inheritance for gene: NPC1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.182 NPC1 Zornitza Stark Classified gene: NPC1 as Green List (high evidence)
Early-onset Parkinson disease v0.182 NPC1 Zornitza Stark Gene: npc1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.181 NPC1 Zornitza Stark reviewed gene: NPC1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Niemann-Pick disease, MIM# 257220; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.181 NUS1 Zornitza Stark Marked gene: NUS1 as ready
Early-onset Parkinson disease v0.181 NUS1 Zornitza Stark Gene: nus1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.181 NUS1 Zornitza Stark Phenotypes for gene: NUS1 were changed from Mental retardation 55 with seizures (MRD55); Parkinsonism; Developmental delay; Intellectual disability; Ataxia; Myoclonus; OMIM 617831 to Intellectual developmental disorder, autosomal dominant 55, with seizures, MIM# 617831; Parkinsonism; Developmental delay; Intellectual disability; Ataxia; Myoclonus
Early-onset Parkinson disease v0.180 NUS1 Zornitza Stark Mode of inheritance for gene: NUS1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.179 NUS1 Zornitza Stark Classified gene: NUS1 as Green List (high evidence)
Early-onset Parkinson disease v0.179 NUS1 Zornitza Stark Gene: nus1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.178 PGK1 Zornitza Stark Marked gene: PGK1 as ready
Early-onset Parkinson disease v0.178 PGK1 Zornitza Stark Gene: pgk1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.178 PGK1 Zornitza Stark Phenotypes for gene: PGK1 were changed from Haemolytic anaemia; Rhabdomyolysis; Myopathy; Juvenile Parkinsonism; OMIM 300653 to Phosphoglycerate kinase 1 deficiency, MIM# 300653; Haemolytic anaemia; Rhabdomyolysis; Myopathy; Juvenile Parkinsonism; OMIM 300653
Early-onset Parkinson disease v0.177 PGK1 Zornitza Stark Classified gene: PGK1 as Green List (high evidence)
Early-onset Parkinson disease v0.177 PGK1 Zornitza Stark Gene: pgk1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.176 PGK1 Zornitza Stark reviewed gene: PGK1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Phosphoglycerate kinase 1 deficiency, MIM# 300653; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Early-onset Parkinson disease v0.176 POLR3A Zornitza Stark Marked gene: POLR3A as ready
Early-onset Parkinson disease v0.176 POLR3A Zornitza Stark Gene: polr3a has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.176 POLR3A Zornitza Stark Phenotypes for gene: POLR3A were changed from POLR3A Leukoencephalopathy; Parkinsonism; Ocular and dental abnormality; Hypogonadism, OMIM 607694 to Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism, MIM# 607694; POLR3A Leukoencephalopathy; Parkinsonism; Ocular and dental abnormality; Hypogonadism
Early-onset Parkinson disease v0.175 POLR3A Zornitza Stark Classified gene: POLR3A as Green List (high evidence)
Early-onset Parkinson disease v0.175 POLR3A Zornitza Stark Gene: polr3a has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.174 POLR3A Zornitza Stark reviewed gene: POLR3A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism, MIM# 607694; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.174 PPP2R2B Zornitza Stark Marked gene: PPP2R2B as ready
Early-onset Parkinson disease v0.174 PPP2R2B Zornitza Stark Gene: ppp2r2b has been removed from the panel.
Early-onset Parkinson disease v0.174 PPP2R2B Zornitza Stark Tag STR tag was added to gene: PPP2R2B.
Early-onset Parkinson disease v0.174 PPP2R2B Zornitza Stark commented on gene: PPP2R2B
Early-onset Parkinson disease v0.174 PRKCG Zornitza Stark Marked gene: PRKCG as ready
Early-onset Parkinson disease v0.174 PRKCG Zornitza Stark Gene: prkcg has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.174 PRKCG Zornitza Stark Phenotypes for gene: PRKCG were changed from Spinocerebellar ataxia 14; Myoclonus; Parkinsonism; OMIM 605361 to Spinocerebellar ataxia 14, MIM# 605361; Myoclonus; Parkinsonism
Early-onset Parkinson disease v0.173 PRKCG Zornitza Stark Mode of inheritance for gene: PRKCG was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.172 PRKCG Zornitza Stark Classified gene: PRKCG as Green List (high evidence)
Early-onset Parkinson disease v0.172 PRKCG Zornitza Stark Gene: prkcg has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.171 PRKCG Zornitza Stark reviewed gene: PRKCG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinocerebellar ataxia 14, MIM# 605361; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.171 QDPR Zornitza Stark Marked gene: QDPR as ready
Early-onset Parkinson disease v0.171 QDPR Zornitza Stark Gene: qdpr has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.171 QDPR Zornitza Stark Phenotypes for gene: QDPR were changed from Dehydropteridin reductase deficiency, Infantile-onset dystonia; Parkinsonism; Epilepsy; Autonomic dysfunction; Hyperphenylalaninemia; OMIM 261360 to Hyperphenylalaninemia, BH4-deficient, C, MIM#261630; Dehydropteridin reductase deficiency, Infantile-onset dystonia; Parkinsonism; Epilepsy; Autonomic dysfunction; Hyperphenylalaninemia
Early-onset Parkinson disease v0.170 QDPR Zornitza Stark Classified gene: QDPR as Green List (high evidence)
Early-onset Parkinson disease v0.170 QDPR Zornitza Stark Gene: qdpr has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.169 QDPR Zornitza Stark reviewed gene: QDPR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hyperphenylalaninemia, BH4-deficient, C, MIM#261630; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.169 SCN1A Zornitza Stark Marked gene: SCN1A as ready
Early-onset Parkinson disease v0.169 SCN1A Zornitza Stark Gene: scn1a has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.169 SCN1A Zornitza Stark Phenotypes for gene: SCN1A were changed from Dravet syndrome; Epilepsy, Paekinsonism; OMIM 607208 to Dravet syndrome, MIM# 607208; Epilepsy, Paekinsonism
Early-onset Parkinson disease v0.168 SCN1A Zornitza Stark Mode of inheritance for gene: SCN1A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.167 SCN1A Zornitza Stark Classified gene: SCN1A as Green List (high evidence)
Early-onset Parkinson disease v0.167 SCN1A Zornitza Stark Gene: scn1a has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.166 SCN1A Zornitza Stark reviewed gene: SCN1A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Dravet syndrome, MIM# 607208; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.166 SERAC1 Zornitza Stark Marked gene: SERAC1 as ready
Early-onset Parkinson disease v0.166 SERAC1 Zornitza Stark Gene: serac1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.166 SERAC1 Zornitza Stark Phenotypes for gene: SERAC1 were changed from MEGDEL Syndrome; Parkinsonism to 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, MIM# 614739; Parkinsonism
Early-onset Parkinson disease v0.165 SERAC1 Zornitza Stark Classified gene: SERAC1 as Green List (high evidence)
Early-onset Parkinson disease v0.165 SERAC1 Zornitza Stark Gene: serac1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.164 SERAC1 Zornitza Stark reviewed gene: SERAC1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, MIM# 614739; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.164 SLC19A3 Zornitza Stark Marked gene: SLC19A3 as ready
Early-onset Parkinson disease v0.164 SLC19A3 Zornitza Stark Gene: slc19a3 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.164 SLC19A3 Zornitza Stark Phenotypes for gene: SLC19A3 were changed from Biotin-Thiamine Responsive Basal Ganglia disease; Childhood onset Dystonia and Parkinsonism; OMIM 607483 to Thiamine metabolism dysfunction syndrome 2 (biotin- or thiamine-responsive encephalopathy type 2), MIM# 607483; Childhood onset Dystonia and Parkinsonism
Early-onset Parkinson disease v0.163 SLC19A3 Zornitza Stark Classified gene: SLC19A3 as Green List (high evidence)
Early-onset Parkinson disease v0.163 SLC19A3 Zornitza Stark Gene: slc19a3 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.162 SLC19A3 Zornitza Stark reviewed gene: SLC19A3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Thiamine metabolism dysfunction syndrome 2 (biotin- or thiamine-responsive encephalopathy type 2), MIM# 607483; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.162 SLC18A2 Zornitza Stark Marked gene: SLC18A2 as ready
Early-onset Parkinson disease v0.162 SLC18A2 Zornitza Stark Gene: slc18a2 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.162 SLC18A2 Zornitza Stark Phenotypes for gene: SLC18A2 were changed from Brain dopamine-serotonin transport disease, Childhood-onset parkinsonism, OMIM 618049 to Parkinsonism-dystonia, infantile, 2 , MIM# 618049; Brain dopamine-serotonin transport disease, Childhood-onset parkinsonism
Early-onset Parkinson disease v0.161 SLC18A2 Zornitza Stark Publications for gene: SLC18A2 were set to PMID: 23363473, 33983693
Early-onset Parkinson disease v0.160 SLC18A2 Zornitza Stark Classified gene: SLC18A2 as Green List (high evidence)
Early-onset Parkinson disease v0.160 SLC18A2 Zornitza Stark Gene: slc18a2 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.159 SLC18A2 Zornitza Stark reviewed gene: SLC18A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23363473, 31240161, 26497564; Phenotypes: Parkinsonism-dystonia, infantile, 2 , MIM# 618049; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.159 SOX6 Zornitza Stark Marked gene: SOX6 as ready
Early-onset Parkinson disease v0.159 SOX6 Zornitza Stark Gene: sox6 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.159 SOX6 Zornitza Stark Publications for gene: SOX6 were set to PMID: 24453155, 25127144
Early-onset Parkinson disease v0.158 SOX6 Zornitza Stark Phenotypes for gene: SOX6 were changed from Tolchin-Le Caignec syndrome; Developmental delay; ID; ASD; ADHD; Parkinsonism; Syringomyelia, OMIM 618971 to Tolchin-Le Caignec syndrome, MIM# 618971; Developmental delay; ID; ASD; ADHD; Parkinsonism; Syringomyelia
Early-onset Parkinson disease v0.157 SOX6 Zornitza Stark Mode of inheritance for gene: SOX6 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.156 SOX6 Zornitza Stark Classified gene: SOX6 as Green List (high evidence)
Early-onset Parkinson disease v0.156 SOX6 Zornitza Stark Gene: sox6 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.155 SPG7 Zornitza Stark Marked gene: SPG7 as ready
Early-onset Parkinson disease v0.155 SPG7 Zornitza Stark Gene: spg7 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.155 SPG7 Zornitza Stark Phenotypes for gene: SPG7 were changed from Hereditary Spastic Paraplegia 7; Ataxia; Progressive external opthalmoplegia; Parkinsonism; OMIM 607259 to Spastic paraplegia 7, autosomal recessive, MIM# 607259; Ataxia; Progressive external opthalmoplegia; Parkinsonism
Early-onset Parkinson disease v0.154 SPG7 Zornitza Stark Classified gene: SPG7 as Green List (high evidence)
Early-onset Parkinson disease v0.154 SPG7 Zornitza Stark Gene: spg7 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.153 STUB1 Zornitza Stark Marked gene: STUB1 as ready
Early-onset Parkinson disease v0.153 STUB1 Zornitza Stark Gene: stub1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.153 STUB1 Zornitza Stark Phenotypes for gene: STUB1 were changed from Spinocerebellar Ataxia 48; Parkinsonism, OMIM 618093 to Spinocerebellar Ataxia 48, OMIM 618093; Parkinsonism
Early-onset Parkinson disease v0.152 STUB1 Zornitza Stark Publications for gene: STUB1 were set to PubMed: 30381368; 32285148, 32337344
Early-onset Parkinson disease v0.152 STUB1 Zornitza Stark Mode of inheritance for gene: STUB1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.151 STUB1 Zornitza Stark Mode of inheritance for gene: STUB1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.151 STUB1 Zornitza Stark Classified gene: STUB1 as Green List (high evidence)
Early-onset Parkinson disease v0.151 STUB1 Zornitza Stark Gene: stub1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.150 STXBP1 Zornitza Stark Marked gene: STXBP1 as ready
Early-onset Parkinson disease v0.150 STXBP1 Zornitza Stark Gene: stxbp1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.150 STXBP1 Zornitza Stark Phenotypes for gene: STXBP1 were changed from Developmental and epileptic encephalopathy 4; Juvenile onset Parkinsonism; OMIM 612164 to Developmental and epileptic encephalopathy 4, MIM# 612164; Juvenile onset Parkinsonism
Early-onset Parkinson disease v0.149 STXBP1 Zornitza Stark Publications for gene: STXBP1 were set to PMID: 25418441, 32643187, 29929108
Early-onset Parkinson disease v0.148 STXBP1 Zornitza Stark Mode of inheritance for gene: STXBP1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.147 STXBP1 Zornitza Stark Classified gene: STXBP1 as Green List (high evidence)
Early-onset Parkinson disease v0.147 STXBP1 Zornitza Stark Gene: stxbp1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.146 STXBP1 Zornitza Stark reviewed gene: STXBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 4, MIM# 612164; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.146 TBC1D24 Zornitza Stark Marked gene: TBC1D24 as ready
Early-onset Parkinson disease v0.146 TBC1D24 Zornitza Stark Gene: tbc1d24 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.146 TBC1D24 Zornitza Stark Phenotypes for gene: TBC1D24 were changed from Developmental and epileptic encephalopathy 16; Intellectual disability; Parkinsonism; Seizures; Psychosis; OMIM 615338 to Developmental and epileptic encephalopathy 16, MIM# 615338; Intellectual disability; Parkinsonism; Seizures; Psychosis
Early-onset Parkinson disease v0.145 TBC1D24 Zornitza Stark Classified gene: TBC1D24 as Green List (high evidence)
Early-onset Parkinson disease v0.145 TBC1D24 Zornitza Stark Gene: tbc1d24 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.144 TBC1D24 Zornitza Stark reviewed gene: TBC1D24: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 16, MIM# 615338; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.144 TBP Zornitza Stark Marked gene: TBP as ready
Early-onset Parkinson disease v0.144 TBP Zornitza Stark Gene: tbp has been removed from the panel.
Early-onset Parkinson disease v0.144 TBP Zornitza Stark Tag STR tag was added to gene: TBP.
Early-onset Parkinson disease v0.144 TBP Zornitza Stark commented on gene: TBP
Early-onset Parkinson disease v0.144 UBTF Zornitza Stark Marked gene: UBTF as ready
Early-onset Parkinson disease v0.144 UBTF Zornitza Stark Gene: ubtf has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.144 UBTF Zornitza Stark Phenotypes for gene: UBTF were changed from Neurodegeneration, childhood-onset; Parkinsonism; Dystonia; Chorea; Brain atrophy to Neurodegeneration, childhood-onset, with brain atrophy, MIM# 617672; Parkinsonism; Dystonia; Chorea; Brain atrophy
Early-onset Parkinson disease v0.143 UBTF Zornitza Stark Mode of inheritance for gene: UBTF was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.142 UBTF Zornitza Stark Classified gene: UBTF as Green List (high evidence)
Early-onset Parkinson disease v0.142 UBTF Zornitza Stark Gene: ubtf has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.141 UBTF Zornitza Stark reviewed gene: UBTF: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodegeneration, childhood-onset, with brain atrophy, MIM# 617672; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.141 VAC14 Zornitza Stark Marked gene: VAC14 as ready
Early-onset Parkinson disease v0.141 VAC14 Zornitza Stark Gene: vac14 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.141 VAC14 Zornitza Stark Phenotypes for gene: VAC14 were changed from Childhood onset Striatonigral degeneration; Dystonia; Parkinsonism; OMIM 617054 to Striatonigral degeneration, childhood-onset, MIM# 617054; Dystonia; Parkinsonism
Early-onset Parkinson disease v0.140 VAC14 Zornitza Stark Classified gene: VAC14 as Green List (high evidence)
Early-onset Parkinson disease v0.140 VAC14 Zornitza Stark Gene: vac14 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.139 VAC14 Zornitza Stark reviewed gene: VAC14: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Striatonigral degeneration, childhood-onset, MIM# 617054; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.50 NCF1 Crystle Lee reviewed gene: NCF1: Rating: AMBER; Mode of pathogenicity: None; Publications: 30651282, 23688784; Phenotypes: Chronic granulomatous disease 1, autosomal recessive (MIM#233700); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.50 NEB Crystle Lee reviewed gene: NEB: Rating: AMBER; Mode of pathogenicity: None; Publications: 27228465; Phenotypes: Arthrogryposis multiplex congenita 6 (MIM#619334), Nemaline myopathy 2, autosomal recessive (MIM#256030); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.50 HYDIN Crystle Lee reviewed gene: HYDIN: Rating: AMBER; Mode of pathogenicity: None; Publications: 23022101, 28441829, 31116566; Phenotypes: Ciliary dyskinesia, primary, 5 (MIM#608647); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.50 SNORD118 Crystle Lee reviewed gene: SNORD118: Rating: AMBER; Mode of pathogenicity: None; Publications: 33029936; Phenotypes: Leukoencephalopathy, brain calcifications, and cysts (MIM#614561); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.50 UBA1 Crystle Lee reviewed gene: UBA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18179898, 32181232, 31932168, 29034082, 23518311, 26028276; Phenotypes: Spinal muscular atrophy, X-linked 2, infantile (MIM#301830); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Familial hypoparathyroidism v1.1 Bryony Thompson Panel status changed from internal to public
Familial hypoparathyroidism v1.0 Bryony Thompson promoted panel to version 1.0
Familial hypoparathyroidism v0.26 TBCE Bryony Thompson Marked gene: TBCE as ready
Familial hypoparathyroidism v0.26 TBCE Bryony Thompson Gene: tbce has been classified as Green List (High Evidence).
Familial hypoparathyroidism v0.26 TBCE Bryony Thompson Publications for gene: TBCE were set to
Familial hypoparathyroidism v0.25 TBCE Bryony Thompson Classified gene: TBCE as Green List (high evidence)
Familial hypoparathyroidism v0.25 TBCE Bryony Thompson Gene: tbce has been classified as Green List (High Evidence).
Familial hypoparathyroidism v0.24 TBCE Bryony Thompson Deleted their review
Familial hypoparathyroidism v0.24 PTH Bryony Thompson Marked gene: PTH as ready
Familial hypoparathyroidism v0.24 PTH Bryony Thompson Gene: pth has been classified as Green List (High Evidence).
Familial hypoparathyroidism v0.24 PTH Bryony Thompson Publications for gene: PTH were set to
Familial hypoparathyroidism v0.23 PTH Bryony Thompson Classified gene: PTH as Green List (high evidence)
Familial hypoparathyroidism v0.23 PTH Bryony Thompson Gene: pth has been classified as Green List (High Evidence).
Familial hypoparathyroidism v0.22 PTH Bryony Thompson Deleted their review
Familial hypoparathyroidism v0.22 PTH Bryony Thompson Deleted their comment
Familial hypoparathyroidism v0.22 GNA11 Bryony Thompson Marked gene: GNA11 as ready
Familial hypoparathyroidism v0.22 GNA11 Bryony Thompson Gene: gna11 has been classified as Green List (High Evidence).
Familial hypoparathyroidism v0.22 GNA11 Bryony Thompson Publications for gene: GNA11 were set to
Familial hypoparathyroidism v0.21 GNA11 Bryony Thompson Mode of pathogenicity for gene: GNA11 was changed from None to Other
Familial hypoparathyroidism v0.20 GNA11 Bryony Thompson Classified gene: GNA11 as Green List (high evidence)
Familial hypoparathyroidism v0.20 GNA11 Bryony Thompson Gene: gna11 has been classified as Green List (High Evidence).
Familial hypoparathyroidism v0.19 GNA11 Bryony Thompson Deleted their review
Familial hypoparathyroidism v0.19 GCM2 Bryony Thompson Marked gene: GCM2 as ready
Familial hypoparathyroidism v0.19 GCM2 Bryony Thompson Gene: gcm2 has been classified as Green List (High Evidence).
Familial hypoparathyroidism v0.19 GCM2 Bryony Thompson Publications for gene: GCM2 were set to
Familial hypoparathyroidism v0.18 GCM2 Bryony Thompson Mode of pathogenicity for gene: GCM2 was changed from None to Other
Familial hypoparathyroidism v0.17 GCM2 Bryony Thompson Mode of inheritance for gene: GCM2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Familial hypoparathyroidism v0.16 GCM2 Bryony Thompson Classified gene: GCM2 as Green List (high evidence)
Familial hypoparathyroidism v0.16 GCM2 Bryony Thompson Gene: gcm2 has been classified as Green List (High Evidence).
Familial hypoparathyroidism v0.15 GCM2 Bryony Thompson Deleted their review
Familial hypoparathyroidism v0.15 GCM2 Bryony Thompson Deleted their comment
Familial hypoparathyroidism v0.15 GATA3 Bryony Thompson Marked gene: GATA3 as ready
Familial hypoparathyroidism v0.15 GATA3 Bryony Thompson Gene: gata3 has been classified as Green List (High Evidence).
Familial hypoparathyroidism v0.15 GATA3 Bryony Thompson Publications for gene: GATA3 were set to
Familial hypoparathyroidism v0.14 GATA3 Bryony Thompson Classified gene: GATA3 as Green List (high evidence)
Familial hypoparathyroidism v0.14 GATA3 Bryony Thompson Gene: gata3 has been classified as Green List (High Evidence).
Familial hypoparathyroidism v0.13 GATA3 Bryony Thompson Deleted their review
Familial hypoparathyroidism v0.13 CASR Bryony Thompson Marked gene: CASR as ready
Familial hypoparathyroidism v0.13 CASR Bryony Thompson Gene: casr has been classified as Green List (High Evidence).
Familial hypoparathyroidism v0.13 CASR Bryony Thompson Publications for gene: CASR were set to
Familial hypoparathyroidism v0.12 CASR Bryony Thompson Mode of inheritance for gene: CASR was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Familial hypoparathyroidism v0.11 CASR Bryony Thompson Classified gene: CASR as Green List (high evidence)
Familial hypoparathyroidism v0.11 CASR Bryony Thompson Gene: casr has been classified as Green List (High Evidence).
Familial hypoparathyroidism v0.10 CASR Bryony Thompson Deleted their review
Familial hypoparathyroidism v0.10 CASR Bryony Thompson Deleted their comment
Familial hypoparathyroidism v0.10 AIRE Bryony Thompson Marked gene: AIRE as ready
Familial hypoparathyroidism v0.10 AIRE Bryony Thompson Gene: aire has been classified as Green List (High Evidence).
Familial hypoparathyroidism v0.10 AIRE Bryony Thompson Mode of inheritance for gene: AIRE was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Familial hypoparathyroidism v0.9 AIRE Bryony Thompson Classified gene: AIRE as Green List (high evidence)
Familial hypoparathyroidism v0.9 AIRE Bryony Thompson Gene: aire has been classified as Green List (High Evidence).
Familial hypoparathyroidism v0.8 AIRE Bryony Thompson Deleted their review
Familial hypoparathyroidism v0.8 AIRE Bryony Thompson Deleted their comment
Clefting disorders v0.182 RYR1 Zornitza Stark Marked gene: RYR1 as ready
Clefting disorders v0.182 RYR1 Zornitza Stark Gene: ryr1 has been classified as Red List (Low Evidence).
Clefting disorders v0.182 RYR1 Zornitza Stark Phenotypes for gene: RYR1 were changed from CCD; CENTRAL CORE DISEASE OF MUSCLE to RYR1-related myopathy - MONDO:0100150
Clefting disorders v0.181 RYR1 Zornitza Stark Classified gene: RYR1 as Red List (low evidence)
Clefting disorders v0.181 RYR1 Zornitza Stark Gene: ryr1 has been classified as Red List (Low Evidence).
Familial hypoparathyroidism v0.7 TBCE Bryony Thompson gene: TBCE was added
gene: TBCE was added to Familial hypoparathyroidism. Sources: NHS GMS
Mode of inheritance for gene: TBCE was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TBCE were set to hypoparathyroidism-retardation-dysmorphism syndrome MONDO:0009426
Review for gene: TBCE was set to GREEN
Added comment: Sources: NHS GMS
Familial hypoparathyroidism v0.6 PTH Bryony Thompson gene: PTH was added
gene: PTH was added to Familial hypoparathyroidism. Sources: NHS GMS
Mode of inheritance for gene: PTH was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: PTH were set to familial isolated hypoparathyroidism due to impaired PTH secretion MONDO:0016000
Review for gene: PTH was set to GREEN
Added comment: Sources: NHS GMS
Familial hypoparathyroidism v0.5 GNA11 Bryony Thompson gene: GNA11 was added
gene: GNA11 was added to Familial hypoparathyroidism. Sources: NHS GMS
Mode of inheritance for gene: GNA11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: GNA11 were set to autosomal dominant hypocalcemia MONDO:0018543
Review for gene: GNA11 was set to GREEN
Added comment: Sources: NHS GMS
Familial hypoparathyroidism v0.4 GCM2 Bryony Thompson gene: GCM2 was added
gene: GCM2 was added to Familial hypoparathyroidism. Sources: NHS GMS
Mode of inheritance for gene: GCM2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: GCM2 were set to Familial isolated hyperparathyroidism MONDO:0015027
Review for gene: GCM2 was set to GREEN
Added comment: Sources: NHS GMS
Familial hypoparathyroidism v0.3 GATA3 Bryony Thompson gene: GATA3 was added
gene: GATA3 was added to Familial hypoparathyroidism. Sources: NHS GMS
Mode of inheritance for gene: GATA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: GATA3 were set to Hypoparathyroidism-deafness-renal disease syndrome MONDO:0007797
Review for gene: GATA3 was set to GREEN
Added comment: Sources: NHS GMS
Familial hypoparathyroidism v0.2 CASR Bryony Thompson gene: CASR was added
gene: CASR was added to Familial hypoparathyroidism. Sources: NHS GMS
Mode of inheritance for gene: CASR was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: CASR were set to autosomal dominant hypocalcemia 1 MONDO:0011013
Review for gene: CASR was set to GREEN
Added comment: Sources: NHS GMS
Familial hypoparathyroidism v0.1 AIRE Bryony Thompson gene: AIRE was added
gene: AIRE was added to Familial hypoparathyroidism. Sources: NHS GMS
Mode of inheritance for gene: AIRE was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: AIRE were set to Autoimmune polyendocrine syndrome type 1 MONDO:0009411
Review for gene: AIRE was set to GREEN
Added comment: Sources: NHS GMS
Familial hypoparathyroidism v0.0 Bryony Thompson Added Panel Familial hypoparathyroidism
Set panel types to: Royal Melbourne Hospital; Rare Disease
Clefting disorders v0.180 RYR1 Krithika Murali reviewed gene: RYR1: Rating: RED; Mode of pathogenicity: None; Publications: 23553484; Phenotypes: RYR1-related myopathy - MONDO:0100150; Mode of inheritance: None
Prepair 1000+ v0.50 CHM Crystle Lee reviewed gene: CHM: Rating: AMBER; Mode of pathogenicity: None; Publications: 33110609, 27820636; Phenotypes: Choroideremia (MIM#303100); 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+ v0.50 PROC Crystle Lee reviewed gene: PROC: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Thrombophilia 3 due to protein C deficiency, autosomal recessive (MIM#612304), Thrombophilia 3 due to protein C deficiency, autosomal dominant (MIM#176860); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Prepair 1000+ v0.50 PROC Crystle Lee Deleted their review
Prepair 1000+ v0.50 PROC Crystle Lee changed review comment from: Gene is associated AD and AR thrombophilia 3 due to protein C deficiency

AR form of condition is associated with variable severity and occasional late-onset of symptoms with homozygosity

Heterozygous 'carriers' of pathogenic variants in the PROC gene are said to have mild protein C deficiency which is often asymptomatic, but may involve recurrent venous thrombosis.

Difficult to define penetrance as represents risk factor for thrombophilia.

Challenge in interpretation and reporting in a carrier screening context; to: Gene is associated AD and AR thrombophilia 3 due to protein C deficiency

AR form of condition is associated with variable severity and occasional late-onset of symptoms with homozygosity

Heterozygous 'carriers' of pathogenic variants in the PROC gene are said to have mild protein C deficiency which is often asymptomatic, but may involve recurrent venous thrombosis.

Difficult to define penetrance as represents risk factor for thrombophilia.

Challenge in interpretation and reporting in a carrier screening context
Prepair 1000+ v0.50 PROC Crystle Lee reviewed gene: PROC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Thrombophilia 3 due to protein C deficiency, autosomal recessive (MIM#612304), Thrombophilia 3 due to protein C deficiency, autosomal dominant (MIM#176860); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Prepair 1000+ v0.50 IKBKG Crystle Lee reviewed gene: IKBKG: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Ectodermal dysplasia and immunodeficiency 1, MIM# 300291, Immunodeficiency 33 , MIM#300636, Incontinentia pigmenti, MIM# 308300, Autoinflammatory disease, systemic, X-linked, MIM# 301081; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Early-onset Parkinson disease v0.139 WARS2 Zornitza Stark Marked gene: WARS2 as ready
Early-onset Parkinson disease v0.139 WARS2 Zornitza Stark Gene: wars2 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.139 WARS2 Zornitza Stark Phenotypes for gene: WARS2 were changed from Parkinsonism-dystonia 3, childhood-onset, MIM# 619738 to Parkinsonism-dystonia 3, childhood-onset, MIM# 619738
Early-onset Parkinson disease v0.139 WARS2 Zornitza Stark Phenotypes for gene: WARS2 were changed from Childhood onset parkinsonism dystonia-3; Myoclonus ataxia; OMIM 619738 to Parkinsonism-dystonia 3, childhood-onset, MIM# 619738
Early-onset Parkinson disease v0.138 WARS2 Zornitza Stark Publications for gene: WARS2 were set to PMID: 29120065; 34890876
Early-onset Parkinson disease v0.137 WARS2 Zornitza Stark Classified gene: WARS2 as Green List (high evidence)
Early-onset Parkinson disease v0.137 WARS2 Zornitza Stark Gene: wars2 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.136 WARS2 Zornitza Stark reviewed gene: WARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34890876, 31970218, 29120065; Phenotypes: Parkinsonism-dystonia 3, childhood-onset, MIM# 619738; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.136 ZFYVE26 Zornitza Stark Marked gene: ZFYVE26 as ready
Early-onset Parkinson disease v0.136 ZFYVE26 Zornitza Stark Gene: zfyve26 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.136 ZFYVE26 Zornitza Stark Phenotypes for gene: ZFYVE26 were changed from Spastic paraplegia and retinal degeneration; Kjellin syndrome; Parkinsonism; OMIM 270700 to Spastic paraplegia 15, autosomal recessive, MIM# 270700; Spastic paraplegia and retinal degeneration; Kjellin syndrome; Parkinsonism
Early-onset Parkinson disease v0.135 ZFYVE26 Zornitza Stark Classified gene: ZFYVE26 as Green List (high evidence)
Early-onset Parkinson disease v0.135 ZFYVE26 Zornitza Stark Gene: zfyve26 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v1.67 COL11A1 Zornitza Stark Marked gene: COL11A1 as ready
Aortopathy_Connective Tissue Disorders v1.67 COL11A1 Zornitza Stark Gene: col11a1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.134 ATXN10 SHEKEEB MOHAMMAD gene: ATXN10 was added
gene: ATXN10 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: ATXN10 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ATXN10 were set to PMID: 28890930
Phenotypes for gene: ATXN10 were set to Spinocerebellar Ataxia 10; Parkinsonism; OMIM 603516
Review for gene: ATXN10 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 ATXN2 SHEKEEB MOHAMMAD gene: ATXN2 was added
gene: ATXN2 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: ATXN2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ATXN2 were set to PMID: 11761482, 17923635
Phenotypes for gene: ATXN2 were set to Spinocerebellar Ataxia 2; Parkinsonism; Myoclonus; OMIM 183090
Review for gene: ATXN2 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 ATXN3 SHEKEEB MOHAMMAD gene: ATXN3 was added
gene: ATXN3 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: ATXN3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ATXN3 were set to PMID: 11176969; 7574470
Phenotypes for gene: ATXN3 were set to Spinocerebellar 3; Machado Joseph disease; Ataxia; Parkinsonism; OMIM 109150
Review for gene: ATXN3 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 ATXN8 SHEKEEB MOHAMMAD gene: ATXN8 was added
gene: ATXN8 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: ATXN8 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ATXN8 were set to PMID: 24285970
Phenotypes for gene: ATXN8 were set to Spinocerebellar 8; Parkinsonism; OMIM 608768
Review for gene: ATXN8 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 TPP1 SHEKEEB MOHAMMAD gene: TPP1 was added
gene: TPP1 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: TPP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TPP1 were set to PMID: 21940688
Phenotypes for gene: TPP1 were set to Late Infantile NCL; Parkinsonism; OMIM 204500
Review for gene: TPP1 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 CYP27A1 SHEKEEB MOHAMMAD gene: CYP27A1 was added
gene: CYP27A1 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: CYP27A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYP27A1 were set to PMID: 30054180
Phenotypes for gene: CYP27A1 were set to Cerebrotendinous xanthomatosis, infantile-onset diarrhoea, juvenile-onset cataract, young adult-onset tendon xanthomas; Epilepsy; Parkinsonism; Ataxia; Peripheral neuropathy; OMIM 213700
Review for gene: CYP27A1 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 DDC SHEKEEB MOHAMMAD gene: DDC was added
gene: DDC was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: DDC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DDC were set to PMID: 33983693
Phenotypes for gene: DDC were set to Aromatic L-amino acid decarboxylase deficiency (DYT-DDC); Infantile-onset parkinsonism & dystonia; Bulbar dysfunction; Oculogyric crisis; Autonomic dysfunction; Intellectual disability; OMIM 608603
Review for gene: DDC was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 DHDDS SHEKEEB MOHAMMAD gene: DHDDS was added
gene: DHDDS was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: DHDDS was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DHDDS were set to PMID: 34837344, 29100083
Phenotypes for gene: DHDDS were set to Myoclonic Epilepsy; Parkinsonism; Ataxia; Intellectual disability; OMIM 617836
Review for gene: DHDDS was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 EIF2AK2 SHEKEEB MOHAMMAD gene: EIF2AK2 was added
gene: EIF2AK2 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: EIF2AK2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: EIF2AK2 were set to PMID: 32197074
Phenotypes for gene: EIF2AK2 were set to Neurodevelopmental Syndrome; Developmental delays; Ataxia; Parkinsonism; White matter alterations; OMIM 618877
Review for gene: EIF2AK2 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 EPM2A SHEKEEB MOHAMMAD gene: EPM2A was added
gene: EPM2A was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: EPM2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EPM2A were set to PMID: 27574708
Phenotypes for gene: EPM2A were set to Lafora disease; Progressive Myoclonic Epilepsy; Parkinsonism; OMIM 254780
Review for gene: EPM2A was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 FOXG1 SHEKEEB MOHAMMAD gene: FOXG1 was added
gene: FOXG1 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: FOXG1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FOXG1 were set to PMID: 21953941
Phenotypes for gene: FOXG1 were set to Developmental and Epileptic Encephalopathy; Dystonia,; Athetosis; Parkinsonism; Stereotypies; OMIM 613454
Review for gene: FOXG1 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 GLB1 SHEKEEB MOHAMMAD gene: GLB1 was added
gene: GLB1 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: GLB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GLB1 were set to PMID: 34514040
Phenotypes for gene: GLB1 were set to GM1 Gangliosidosis; Parkinsonism; OMIM 230650
Review for gene: GLB1 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 HEXA SHEKEEB MOHAMMAD gene: HEXA was added
gene: HEXA was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: HEXA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HEXA were set to PMID: 33069254
Phenotypes for gene: HEXA were set to GM2 Gangliosidosis; Tay-Sachs disease; Parkinsonism; OMIM 272800
Review for gene: HEXA was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 JPH3 SHEKEEB MOHAMMAD gene: JPH3 was added
gene: JPH3 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: JPH3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: JPH3 were set to PMID: 28131164
Phenotypes for gene: JPH3 were set to Huntington Disease Like 2 (HDL2); Parkinsonism; Severe Dementia; OMIM 606438
Review for gene: JPH3 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 NPC2 SHEKEEB MOHAMMAD gene: NPC2 was added
gene: NPC2 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: NPC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NPC2 were set to PMID: 35695805
Phenotypes for gene: NPC2 were set to Niemann Pick C2; Parkinsonism; OMIM 607625
Review for gene: NPC2 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 NPC1 SHEKEEB MOHAMMAD edited their review of gene: NPC1: Changed publications: PMID: 24035292, 30369906
Early-onset Parkinson disease v0.134 NPC1 SHEKEEB MOHAMMAD gene: NPC1 was added
gene: NPC1 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: NPC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NPC1 were set to PMID: 24035292
Phenotypes for gene: NPC1 were set to Niemann Pick C1; Parkinsonism; OMIM 257220
Review for gene: NPC1 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 NUS1 SHEKEEB MOHAMMAD gene: NUS1 was added
gene: NUS1 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: NUS1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NUS1 were set to PMID: 32485575; 30348779
Phenotypes for gene: NUS1 were set to Mental retardation 55 with seizures (MRD55); Parkinsonism; Developmental delay; Intellectual disability; Ataxia; Myoclonus; OMIM 617831
Review for gene: NUS1 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 PGK1 SHEKEEB MOHAMMAD gene: PGK1 was added
gene: PGK1 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: PGK1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PGK1 were set to PMID: 30975619
Phenotypes for gene: PGK1 were set to Haemolytic anaemia; Rhabdomyolysis; Myopathy; Juvenile Parkinsonism; OMIM 300653
Review for gene: PGK1 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 POLR3A SHEKEEB MOHAMMAD gene: POLR3A was added
gene: POLR3A was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: POLR3A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR3A were set to PMID: 33652360
Phenotypes for gene: POLR3A were set to POLR3A Leukoencephalopathy; Parkinsonism; Ocular and dental abnormality; Hypogonadism, OMIM 607694
Review for gene: POLR3A was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 PPP2R2B SHEKEEB MOHAMMAD gene: PPP2R2B was added
gene: PPP2R2B was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: PPP2R2B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PPP2R2B were set to PMID: 31286011
Phenotypes for gene: PPP2R2B were set to Spinocerebellar ataxia 12; Parkinsonism; OMIM 604326
Review for gene: PPP2R2B was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 PRKCG SHEKEEB MOHAMMAD gene: PRKCG was added
gene: PRKCG was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: PRKCG was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PRKCG were set to PMID: 29603387
Phenotypes for gene: PRKCG were set to Spinocerebellar ataxia 14; Myoclonus; Parkinsonism; OMIM 605361
Review for gene: PRKCG was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 QDPR SHEKEEB MOHAMMAD gene: QDPR was added
gene: QDPR was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: QDPR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: QDPR were set to PMID: 28413401
Phenotypes for gene: QDPR were set to Dehydropteridin reductase deficiency, Infantile-onset dystonia; Parkinsonism; Epilepsy; Autonomic dysfunction; Hyperphenylalaninemia; OMIM 261360
Review for gene: QDPR was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 SCN1A SHEKEEB MOHAMMAD gene: SCN1A was added
gene: SCN1A was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: SCN1A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SCN1A were set to PMID: 28186331; 24850485
Phenotypes for gene: SCN1A were set to Dravet syndrome; Epilepsy, Paekinsonism; OMIM 607208
Review for gene: SCN1A was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 SERAC1 SHEKEEB MOHAMMAD gene: SERAC1 was added
gene: SERAC1 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: SERAC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SERAC1 were set to PMID: 29332177; 16527507
Phenotypes for gene: SERAC1 were set to MEGDEL Syndrome; Parkinsonism
Review for gene: SERAC1 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 SLC19A3 SHEKEEB MOHAMMAD gene: SLC19A3 was added
gene: SLC19A3 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: SLC19A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC19A3 were set to PMID: 24260777
Phenotypes for gene: SLC19A3 were set to Biotin-Thiamine Responsive Basal Ganglia disease; Childhood onset Dystonia and Parkinsonism; OMIM 607483
Review for gene: SLC19A3 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 SLC18A2 SHEKEEB MOHAMMAD gene: SLC18A2 was added
gene: SLC18A2 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: SLC18A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC18A2 were set to PMID: 23363473, 33983693
Phenotypes for gene: SLC18A2 were set to Brain dopamine-serotonin transport disease, Childhood-onset parkinsonism, OMIM 618049
Review for gene: SLC18A2 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 SOX6 SHEKEEB MOHAMMAD gene: SOX6 was added
gene: SOX6 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: SOX6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SOX6 were set to PMID: 24453155, 25127144
Phenotypes for gene: SOX6 were set to Tolchin-Le Caignec syndrome; Developmental delay; ID; ASD; ADHD; Parkinsonism; Syringomyelia, OMIM 618971
Review for gene: SOX6 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 SPG7 SHEKEEB MOHAMMAD gene: SPG7 was added
gene: SPG7 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: SPG7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPG7 were set to PMID: 31433872
Phenotypes for gene: SPG7 were set to Hereditary Spastic Paraplegia 7; Ataxia; Progressive external opthalmoplegia; Parkinsonism; OMIM 607259
Review for gene: SPG7 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 STUB1 SHEKEEB MOHAMMAD gene: STUB1 was added
gene: STUB1 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: STUB1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: STUB1 were set to PubMed: 30381368; 32285148, 32337344
Phenotypes for gene: STUB1 were set to Spinocerebellar Ataxia 48; Parkinsonism, OMIM 618093
Review for gene: STUB1 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 STXBP1 SHEKEEB MOHAMMAD gene: STXBP1 was added
gene: STXBP1 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: STXBP1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: STXBP1 were set to PMID: 25418441, 32643187, 29929108
Phenotypes for gene: STXBP1 were set to Developmental and epileptic encephalopathy 4; Juvenile onset Parkinsonism; OMIM 612164
Review for gene: STXBP1 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 TBC1D24 SHEKEEB MOHAMMAD gene: TBC1D24 was added
gene: TBC1D24 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: TBC1D24 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBC1D24 were set to PMID: 28663785; 21087195
Phenotypes for gene: TBC1D24 were set to Developmental and epileptic encephalopathy 16; Intellectual disability; Parkinsonism; Seizures; Psychosis; OMIM 615338
Review for gene: TBC1D24 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 TBP SHEKEEB MOHAMMAD gene: TBP was added
gene: TBP was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: TBP was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TBP were set to PMID: 27172828; 14638975; 11313753; 11914409
Phenotypes for gene: TBP were set to Spinocerebellar Ataxia 17; Parkinsonism; Chorea; Seizures; Psychosis; Dementia; OMIM 607136
Review for gene: TBP was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 UBTF SHEKEEB MOHAMMAD gene: UBTF was added
gene: UBTF was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: UBTF was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: UBTF were set to PubMed: 28777933; 29300972
Phenotypes for gene: UBTF were set to Neurodegeneration, childhood-onset; Parkinsonism; Dystonia; Chorea; Brain atrophy
Review for gene: UBTF was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 VAC14 SHEKEEB MOHAMMAD gene: VAC14 was added
gene: VAC14 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: VAC14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VAC14 were set to PMID: 31392254; 28502045
Phenotypes for gene: VAC14 were set to Childhood onset Striatonigral degeneration; Dystonia; Parkinsonism; OMIM 617054
Review for gene: VAC14 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 WARS2 SHEKEEB MOHAMMAD reviewed gene: WARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Early-onset Parkinson disease v0.134 WARS2 SHEKEEB MOHAMMAD gene: WARS2 was added
gene: WARS2 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: WARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WARS2 were set to PMID: 29120065; 34890876
Phenotypes for gene: WARS2 were set to Childhood onset parkinsonism dystonia-3; Myoclonus ataxia; OMIM 619738
Early-onset Parkinson disease v0.134 ZFYVE26 SHEKEEB MOHAMMAD gene: ZFYVE26 was added
gene: ZFYVE26 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: ZFYVE26 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZFYVE26 were set to PMID: 33033739; 21462267
Phenotypes for gene: ZFYVE26 were set to Spastic paraplegia and retinal degeneration; Kjellin syndrome; Parkinsonism; OMIM 270700
Review for gene: ZFYVE26 was set to GREEN
Added comment: Sources: Literature
Hand and foot malformations v0.58 UBA2 Zornitza Stark Marked gene: UBA2 as ready
Hand and foot malformations v0.58 UBA2 Zornitza Stark Gene: uba2 has been classified as Green List (High Evidence).
Hand and foot malformations v0.58 UBA2 Zornitza Stark Classified gene: UBA2 as Green List (high evidence)
Hand and foot malformations v0.58 UBA2 Zornitza Stark Gene: uba2 has been classified as Green List (High Evidence).
Hand and foot malformations v0.57 UBA2 Zornitza Stark gene: UBA2 was added
gene: UBA2 was added to Hand and foot malformations. Sources: Expert Review
Mode of inheritance for gene: UBA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: UBA2 were set to 31332306; 31587267; 34159400
Phenotypes for gene: UBA2 were set to ACCES syndrome, MIM# 619959; Split-Hand/Foot Malformation; Aplasia Cutis Congenita; Ectrodactyly
Review for gene: UBA2 was set to GREEN
Added comment: 2x unrelated probands with isolated split hand malformation. fs variants - 1x de novo and 1x inherited from apparent unaffected mother (no radiographs of her hand available)

1x proband with unilateral split-hand malformation (missense). Her daughter and grandson reported to have ectrofactyly but were unavailable for testing
Sources: Expert Review
Skeletal dysplasia v0.179 UBA2 Zornitza Stark Publications for gene: UBA2 were set to 31332306; 31587267
Fetal anomalies v1.46 UBA2 Zornitza Stark Phenotypes for gene: UBA2 were changed from Split-Hand/Foot Malformation; Aplasia Cutis Congenita; Ectrodactyly to ACCES syndrome, MIM# 619959; Split-Hand/Foot Malformation; Aplasia Cutis Congenita; Ectrodactyly
Fetal anomalies v1.45 UBA2 Zornitza Stark Publications for gene: UBA2 were set to PMID: 31332306; 31587267
Skeletal dysplasia v0.178 UBA2 Zornitza Stark Phenotypes for gene: UBA2 were changed from Split-Hand/Foot Malformation; Aplasia Cutis Congenita; Ectrodactyly to ACCES syndrome, MIM# 619959; Split-Hand/Foot Malformation; Aplasia Cutis Congenita; Ectrodactyly
Mendeliome v1.160 UBA2 Zornitza Stark Phenotypes for gene: UBA2 were changed from Split-Hand/Foot Malformation; Aplasia Cutis Congenita; Ectrodactyly to ACCES syndrome, MIM# 619959; Split-Hand/Foot Malformation; Aplasia Cutis Congenita; Ectrodactyly
Mendeliome v1.159 UBA2 Zornitza Stark reviewed gene: UBA2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ACCES syndrome, MIM# 619959; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.239 ANKRD11 Zornitza Stark Marked gene: ANKRD11 as ready
Congenital Heart Defect v0.239 ANKRD11 Zornitza Stark Gene: ankrd11 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.239 ANKRD11 Zornitza Stark Phenotypes for gene: ANKRD11 were changed from to KBG syndrome, MIM# 148050
Congenital Heart Defect v0.238 ANKRD11 Zornitza Stark Publications for gene: ANKRD11 were set to
Congenital Heart Defect v0.237 ANKRD11 Zornitza Stark Mode of inheritance for gene: ANKRD11 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.236 ANKRD11 Zornitza Stark reviewed gene: ANKRD11: Rating: GREEN; Mode of pathogenicity: None; Publications: 27605097; Phenotypes: KBG syndrome 148050; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.236 ADAMTS10 Zornitza Stark Marked gene: ADAMTS10 as ready
Congenital Heart Defect v0.236 ADAMTS10 Zornitza Stark Gene: adamts10 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.236 ADAMTS10 Zornitza Stark Phenotypes for gene: ADAMTS10 were changed from to Weill-Marchesani syndrome 1, recessive, MIM# 277600
Congenital Heart Defect v0.235 ADAMTS10 Zornitza Stark Publications for gene: ADAMTS10 were set to
Congenital Heart Defect v0.234 ADAMTS10 Zornitza Stark Mode of inheritance for gene: ADAMTS10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.233 ADAMTS10 Zornitza Stark reviewed gene: ADAMTS10: Rating: GREEN; Mode of pathogenicity: None; Publications: 15368195, 18567016, 19836009; Phenotypes: Weill-Marchesani syndrome 1, recessive, MIM# 277600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.233 ACVR1 Zornitza Stark Marked gene: ACVR1 as ready
Congenital Heart Defect v0.233 ACVR1 Zornitza Stark Gene: acvr1 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.233 ACVR1 Zornitza Stark Phenotypes for gene: ACVR1 were changed from to Congenital heart disease, MONDO:0005453
Congenital Heart Defect v0.232 ACVR1 Zornitza Stark Publications for gene: ACVR1 were set to
Congenital Heart Defect v0.231 ACVR1 Zornitza Stark Mode of inheritance for gene: ACVR1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.230 ACVR1 Zornitza Stark reviewed gene: ACVR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29089047, 19506109, 21248739; Phenotypes: Congenital heart disease, MONDO:0005453; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.33 ASXL1 Zornitza Stark Marked gene: ASXL1 as ready
Cerebral Palsy v1.33 ASXL1 Zornitza Stark Gene: asxl1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.33 ASXL1 Zornitza Stark Classified gene: ASXL1 as Green List (high evidence)
Cerebral Palsy v1.33 ASXL1 Zornitza Stark Gene: asxl1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.32 ASXL1 Clare van Eyk gene: ASXL1 was added
gene: ASXL1 was added to Cerebral Palsy. Sources: Literature,Expert Review
Mode of inheritance for gene: ASXL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ASXL1 were set to 33528536; 30542205
Phenotypes for gene: ASXL1 were set to Bohring-Opitz syndrome (MIM 605039)
Review for gene: ASXL1 was set to GREEN
Added comment: 3 individuals with de novo loss of function variants identified in a retrospective CP cohort analysis (PMID 33528536) . One additional individual reported in PMID 30542205 with "atypical cerebral palsy".

Truncal hypotonia with spasticity of the extremities are sometimes reported in BOS (but are not characteristic of the disorder), along with multiple developmental abnormalities of varying severity.
Sources: Literature, Expert Review
Cerebral Palsy v1.32 ATP1A3 Zornitza Stark Classified gene: ATP1A3 as Green List (high evidence)
Cerebral Palsy v1.32 ATP1A3 Zornitza Stark Gene: atp1a3 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.230 ESCO2 Zornitza Stark Marked gene: ESCO2 as ready
Congenital Heart Defect v0.230 ESCO2 Zornitza Stark Gene: esco2 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.230 ESCO2 Zornitza Stark Phenotypes for gene: ESCO2 were changed from Atrial septal defect; Ventricular septal defect; Pulmonic stenosis; tricuspid regurgitation to Roberts-SC phocomelia syndrome, MIM# 268300; Atrial septal defect; Ventricular septal defect; Pulmonic stenosis; tricuspid regurgitation
Congenital Heart Defect v0.229 ESCO2 Zornitza Stark Classified gene: ESCO2 as Green List (high evidence)
Congenital Heart Defect v0.229 ESCO2 Zornitza Stark Gene: esco2 has been classified as Green List (High Evidence).
Prepair 1000+ v0.50 RYR1 Zornitza Stark Tag for review tag was added to gene: RYR1.
Congenital Heart Defect v0.228 EP300 Zornitza Stark Marked gene: EP300 as ready
Congenital Heart Defect v0.228 EP300 Zornitza Stark Gene: ep300 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.228 EP300 Zornitza Stark Marked gene: EP300 as ready
Congenital Heart Defect v0.228 EP300 Zornitza Stark Gene: ep300 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.228 EP300 Zornitza Stark Phenotypes for gene: EP300 were changed from Ventricular septal defect; Patent foramen ovale; Patent ductus arteriosus; mild valve dysplasia to Rubinstein-Taybi syndrome 2, MIM# 613684
Congenital Heart Defect v0.227 EP300 Zornitza Stark Classified gene: EP300 as Green List (high evidence)
Congenital Heart Defect v0.227 EP300 Zornitza Stark Gene: ep300 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.226 EP300 Zornitza Stark reviewed gene: EP300: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Rubinstein-Taybi syndrome 2, MIM# 613684; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.226 DNAH5 Zornitza Stark Marked gene: DNAH5 as ready
Congenital Heart Defect v0.226 DNAH5 Zornitza Stark Gene: dnah5 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.226 DNAH5 Zornitza Stark Phenotypes for gene: DNAH5 were changed from Atrial septal defect; Ventricular septal defect; Atrioventricular septal defect; Transposition of the great arteries to Ciliary dyskinesia, primary, 3, with or without situs inversus, MIM# 608644
Congenital Heart Defect v0.225 DNAH5 Zornitza Stark Classified gene: DNAH5 as Green List (high evidence)
Congenital Heart Defect v0.225 DNAH5 Zornitza Stark Gene: dnah5 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.224 DNAH5 Zornitza Stark reviewed gene: DNAH5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 3, with or without situs inversus, MIM# 608644; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.224 CHST14 Zornitza Stark Marked gene: CHST14 as ready
Congenital Heart Defect v0.224 CHST14 Zornitza Stark Gene: chst14 has been classified as Red List (Low Evidence).
Congenital Heart Defect v0.224 CHST14 Zornitza Stark Phenotypes for gene: CHST14 were changed from Atrial septal defect; Coarctation of the aorta to Ehlers-Danlos syndrome, musculocontractural type 1, MIM# 601776
Congenital Heart Defect v0.223 CHST14 Zornitza Stark Classified gene: CHST14 as Red List (low evidence)
Congenital Heart Defect v0.223 CHST14 Zornitza Stark Gene: chst14 has been classified as Red List (Low Evidence).
Congenital Heart Defect v0.222 CHST14 Zornitza Stark reviewed gene: CHST14: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ehlers-Danlos syndrome, musculocontractural type 1, MIM# 601776; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.222 CFC1 Zornitza Stark Marked gene: CFC1 as ready
Congenital Heart Defect v0.222 CFC1 Zornitza Stark Gene: cfc1 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.222 CFC1 Zornitza Stark Phenotypes for gene: CFC1 were changed from Atrioventricular septal defect; Interrupted aortic arch; Tetralogy of fallot; Transposition of the great arteries; Truncus arteriosus; Double outlet right ventricle; Heterotaxy to Heterotaxy, visceral, 2, MIM# 605376
Congenital Heart Defect v0.221 CFC1 Zornitza Stark Publications for gene: CFC1 were set to
Congenital Heart Defect v0.220 CFC1 Zornitza Stark Classified gene: CFC1 as Green List (high evidence)
Congenital Heart Defect v0.220 CFC1 Zornitza Stark Gene: cfc1 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.219 CFC1 Zornitza Stark reviewed gene: CFC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31633655, 18162845, 25423076, 11062482; Phenotypes: Heterotaxy, visceral, 2, MIM# 605376; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Prepair 1000+ v0.50 CNGA3 Zornitza Stark Tag for review tag was added to gene: CNGA3.
Prepair 1000+ v0.50 F2 Zornitza Stark Tag for review tag was added to gene: F2.
Prepair 1000+ v0.50 F5 Zornitza Stark Tag for review tag was added to gene: F5.
Prepair 1000+ v0.50 F9 Zornitza Stark Tag for review tag was added to gene: F9.
Prepair 1000+ v0.50 ITGA6 Zornitza Stark Marked gene: ITGA6 as ready
Prepair 1000+ v0.50 ITGA6 Zornitza Stark Gene: itga6 has been classified as Green List (High Evidence).
Prepair 1000+ v0.50 ITGA6 Zornitza Stark Publications for gene: ITGA6 were set to
Prepair 1000+ v0.49 PDHA1 Zornitza Stark Tag for review tag was added to gene: PDHA1.
Cerebral Palsy v1.31 ATP1A3 Clare van Eyk reviewed gene: ATP1A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 33528536, 30542205; Phenotypes: Developmental and epileptic encephalopathy 99 (MIM# 619606); Mode of inheritance: None
Congenital Heart Defect v0.219 ESCO2 Chloe Stutterd gene: ESCO2 was added
gene: ESCO2 was added to Congenital Heart Defect. Sources: Expert list,Literature
Mode of inheritance for gene: ESCO2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ESCO2 were set to 19574259; 31976146
Phenotypes for gene: ESCO2 were set to Atrial septal defect; Ventricular septal defect; Pulmonic stenosis; tricuspid regurgitation
Penetrance for gene: ESCO2 were set to Complete
Review for gene: ESCO2 was set to GREEN
gene: ESCO2 was marked as current diagnostic
Added comment: CHD reported in 8/31 patients with molecularly-confirmed Roberts syndrome (PMID 19574259). Septal defect and tricuspid regurgitation reported in one patient with molecularly-confirmed Roberts syndrome (PMID:31976146).
Sources: Expert list, Literature
Prepair 1000+ v0.49 RYR1 Crystle Lee reviewed gene: RYR1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Central core disease (MIM#117000), Minicore myopathy with external ophthalmoplegia (MIM#255320), Neuromuscular disease, congenital, with uniform type 1 fiber (MIM#117000); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Congenital Heart Defect v0.219 EP300 Chloe Stutterd gene: EP300 was added
gene: EP300 was added to Congenital Heart Defect. Sources: Expert list,Literature
Mode of inheritance for gene: EP300 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EP300 were set to 24352918; 24476420
Phenotypes for gene: EP300 were set to Ventricular septal defect; Patent foramen ovale; Patent ductus arteriosus; mild valve dysplasia
Penetrance for gene: EP300 were set to unknown
Review for gene: EP300 was set to AMBER
gene: EP300 was marked as current diagnostic
Added comment: Included in Victor Chang CHD gene list. Mice homozygotes for targeted null mutations have CHD (MGI ID: 1276116). Five patients reported with with CHD (VSD, PFO, PDA, valve dysplasia), all with extra-cardiac features of Rubinstein–Taybi syndrome (24352918; 24476420).
Sources: Expert list, Literature
Congenital Heart Defect v0.219 DNAH5 Chloe Stutterd gene: DNAH5 was added
gene: DNAH5 was added to Congenital Heart Defect. Sources: Expert list,Literature
Mode of inheritance for gene: DNAH5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAH5 were set to 31638833
Phenotypes for gene: DNAH5 were set to Atrial septal defect; Ventricular septal defect; Atrioventricular septal defect; Transposition of the great arteries
Penetrance for gene: DNAH5 were set to unknown
Review for gene: DNAH5 was set to AMBER
gene: DNAH5 was marked as current diagnostic
Added comment: Gene included in Victor Chang CHD gene list but all references to CHD are in association with heterotaxy. PMID 31638833: 8/132 (6.1%) patients with DNAH5-associated primary ciliary dyskinesia presented with CHD (septal defects with or without valve and vessel defects) and all had heterotaxy (three with situs solitus and five had situs inversus).
Sources: Expert list, Literature
Congenital Heart Defect v0.219 CHST14 Chloe Stutterd gene: CHST14 was added
gene: CHST14 was added to Congenital Heart Defect. Sources: Expert list,Literature
Mode of inheritance for gene: CHST14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHST14 were set to 20503305
Phenotypes for gene: CHST14 were set to Atrial septal defect; Coarctation of the aorta
Penetrance for gene: CHST14 were set to unknown
Review for gene: CHST14 was set to RED
Added comment: Gene included in Victor Chang CHD gene list however evidence does not exist for causality of significant or isolated CHD and only reported in association with the EDS phenotype. PMID 20503305 reports one patient with EDS and moderate tricuspid valve regurgitation, prolapse of the tricuspid and mitral valves, and left-to-right shunt via a small atrial septal defect, and two patients with valvular regurgitation diagnosed in adulthood in association with the EDS phenotype.
Sources: Expert list, Literature
Congenital Heart Defect v0.219 CFC1 Chloe Stutterd gene: CFC1 was added
gene: CFC1 was added to Congenital Heart Defect. Sources: Expert list,Literature
Mode of inheritance for gene: CFC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CFC1 were set to Atrioventricular septal defect; Interrupted aortic arch; Tetralogy of fallot; Transposition of the great arteries; Truncus arteriosus; Double outlet right ventricle; Heterotaxy
Penetrance for gene: CFC1 were set to unknown
Review for gene: CFC1 was set to RED
Added comment: Strong evidence for causality of heterotaxy syndromes with congenital cardiac malformations (11062482), however investigation of CFC1 as a cause of isolated CHD identified only the polymorphism R78W or the A145T variant which was also present in controls (11799476; 17072672).
Sources: Expert list, Literature
Prepair 1000+ v0.49 CNGA3 Crystle Lee reviewed gene: CNGA3: Rating: RED; Mode of pathogenicity: None; Publications: 11536077, 35332618; Phenotypes: Achromatopsia 2 (MIM#216900); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.49 F2 Crystle Lee reviewed gene: F2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Dysprothrombinemia (MIM#613679), Hypoprothrombinemia (MIM#613679); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.49 F5 Crystle Lee reviewed gene: F5: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Factor V deficiency (MIM#227400); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v0.49 F9 Crystle Lee reviewed gene: F9: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hemophilia B (MIM#306900); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.159 C9orf84 Zornitza Stark Marked gene: C9orf84 as ready
Mendeliome v1.159 C9orf84 Zornitza Stark Gene: c9orf84 has been classified as Green List (High Evidence).
Mendeliome v1.159 C9orf84 Zornitza Stark Classified gene: C9orf84 as Green List (high evidence)
Mendeliome v1.159 C9orf84 Zornitza Stark Gene: c9orf84 has been classified as Green List (High Evidence).
Mendeliome v1.158 C9orf84 Zornitza Stark Tag new gene name tag was added to gene: C9orf84.
Mendeliome v1.158 C9orf84 Zornitza Stark changed review comment from: 8 families reported with bi-allelic variants in this gene and spermatogenic failure.
Sources: Literature; to: 8 families reported with bi-allelic variants in this gene and spermatogenic failure. A male germ cell-specific Shoc1 knockout mouse model recapitulates the phenotype (germline knockout: early lethality).

HGNC approved name is SHOC1.

Sources: Literature
Mendeliome v1.158 C9orf84 Zornitza Stark gene: C9orf84 was added
gene: C9orf84 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: C9orf84 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C9orf84 were set to 32741963; 32900840; 35485979
Phenotypes for gene: C9orf84 were set to Spermatogenic failure 75, MIM# 619949
Review for gene: C9orf84 was set to GREEN
Added comment: 8 families reported with bi-allelic variants in this gene and spermatogenic failure.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4858 HIST1H4E Zornitza Stark Phenotypes for gene: HIST1H4E were changed from Neurodevelopmental disorder, HIST1H4E-related MONDO:0700092 to Tessadori-van Haaften neurodevelopmental syndrome 3, MIM# 619950
Intellectual disability syndromic and non-syndromic v0.4857 HIST1H4E Zornitza Stark Mode of inheritance for gene: HIST1H4E was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.4856 HIST1H4E Zornitza Stark reviewed gene: HIST1H4E: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Tessadori-van Haaften neurodevelopmental syndrome 3, MIM# 619950; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v1.135 HIST1H4E Zornitza Stark Marked gene: HIST1H4E as ready
Microcephaly v1.135 HIST1H4E Zornitza Stark Gene: hist1h4e has been classified as Green List (High Evidence).
Microcephaly v1.135 HIST1H4E Zornitza Stark Phenotypes for gene: HIST1H4E were changed from Neurodevelopmental disorder, HIST1H4E-related MONDO:0700092 to Tessadori-van Haaften neurodevelopmental syndrome 3, MIM# 619950
Microcephaly v1.134 HIST1H4E Zornitza Stark Mode of inheritance for gene: HIST1H4E was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v1.133 HIST1H4E Zornitza Stark Classified gene: HIST1H4E as Green List (high evidence)
Microcephaly v1.133 HIST1H4E Zornitza Stark Gene: hist1h4e has been classified as Green List (High Evidence).
Microcephaly v1.132 HIST1H4E Zornitza Stark Tag new gene name tag was added to gene: HIST1H4E.
Microcephaly v1.132 HIST1H4E Zornitza Stark reviewed gene: HIST1H4E: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Tessadori-van Haaften neurodevelopmental syndrome 3, MIM# 619950; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.157 HIST1H4E Zornitza Stark Phenotypes for gene: HIST1H4E were changed from Neurodevelopmental disorder, HIST1H4E-related MONDO:0700092 to Tessadori-van Haaften neurodevelopmental syndrome 3, MIM# 619950
Mendeliome v1.156 HIST1H4E Zornitza Stark Tag new gene name tag was added to gene: HIST1H4E.
Mendeliome v1.156 HIST1H4E Zornitza Stark reviewed gene: HIST1H4E: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Tessadori-van Haaften neurodevelopmental syndrome 3, MIM# 619950; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.4856 KMT2B Zornitza Stark Phenotypes for gene: KMT2B were changed from Dystonia 28, childhood-onset, MIM#617284 to Dystonia 28, childhood-onset 617284; MONDO:0015004; Intellectual developmental disorder, autosomal dominant 68, MIM# 619934
Intellectual disability syndromic and non-syndromic v0.4855 KMT2B Zornitza Stark Publications for gene: KMT2B were set to
Intellectual disability syndromic and non-syndromic v0.4854 KMT2B Zornitza Stark changed review comment from: ID described as part of the phenotype in some patients.; to: Childhood-onset dystonia: ID described as part of the phenotype in some patients.
Intellectual disability syndromic and non-syndromic v0.4854 KMT2B Zornitza Stark edited their review of gene: KMT2B: Added comment: Nine individuals reported in PMID 33150406 with heterozygous variants in this gene and intellectual disability, speech delay, microcephaly, growth delay, feeding problems, and dysmorphic features, including epicanthic folds, posteriorly rotated ears, syndactyly/clinodactyly of toes, and fifth finger clinodactyly, normal MRIs and NO dystonia.; Changed publications: 33150406; Changed phenotypes: Dystonia 28, childhood-onset 617284, MONDO:0015004, Intellectual developmental disorder, autosomal dominant 68, MIM# 619934
Mendeliome v1.156 KMT2B Zornitza Stark Publications for gene: KMT2B were set to 27839873; 27992417
Mendeliome v1.155 KMT2B Zornitza Stark edited their review of gene: KMT2B: Added comment: Nine individuals reported in PMID 33150406 with heterozygous variants in this gene and intellectual disability, speech delay, microcephaly, growth delay, feeding problems, and dysmorphic features, including epicanthic folds, posteriorly rotated ears, syndactyly/clinodactyly of toes, and fifth finger clinodactyly, normal MRIs and NO dystonia.; Changed publications: 27839873, 27992417, 33150406; Changed phenotypes: Dystonia 28, childhood-onset 617284, MONDO:0015004, Intellectual developmental disorder, autosomal dominant 68, MIM# 619934
Intellectual disability syndromic and non-syndromic v0.4854 LMAN2L Zornitza Stark Phenotypes for gene: LMAN2L were changed from ?Mental retardation, autosomal recessive, 52; OMIM #616887 to Mental retardation, autosomal recessive, 52 OMIM #616887; Intellectual developmental disorder, autosomal dominant 69 , MIM# 617863
Intellectual disability syndromic and non-syndromic v0.4853 LMAN2L Zornitza Stark reviewed gene: LMAN2L: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Mental retardation, autosomal recessive, 52 OMIM #616887, Intellectual developmental disorder, autosomal dominant 69 , MIM# 617863; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.155 LMAN2L Zornitza Stark Phenotypes for gene: LMAN2L were changed from Mental retardation, autosomal recessive, 52; OMIM #616887 to Mental retardation, autosomal recessive, 52 OMIM #616887; Intellectual developmental disorder, autosomal dominant 69 , MIM# 617863
Mendeliome v1.154 LMAN2L Zornitza Stark edited their review of gene: LMAN2L: Changed phenotypes: Mental retardation, autosomal recessive, 52 OMIM #616887, Intellectual developmental disorder, autosomal dominant 69 , MIM# 617863
Mendeliome v1.154 CDH2 Zornitza Stark edited their review of gene: CDH2: Changed phenotypes: Intellectual disability, corpus callosum abnormalities, congenital abnormalities, Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, MIM# 618929, Attention deficit-hyperactivity disorder 8 , MIM# 619957
Mendeliome v1.154 CDH2 Zornitza Stark Phenotypes for gene: CDH2 were changed from Intellectual disability; corpus callosum abnormalities; congenital abnormalities; Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, MIM# 618929 to Intellectual disability; corpus callosum abnormalities; congenital abnormalities; Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, MIM# 618929; Attention deficit-hyperactivity disorder 8 , MIM# 619957
Mendeliome v1.153 CDH2 Zornitza Stark Mode of inheritance for gene: CDH2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.152 CDH2 Zornitza Stark edited their review of gene: CDH2: Added comment: PMID 34702855: three sibs with homozygous missense and strikingly severe ADHD. Mouse model of same variant recapitulated the phenotype. AMBER for bi-allelic association (segregation and functional data).; Changed publications: 31585109, 34702855; Changed phenotypes: Intellectual disability, corpus callosum abnormalities, congenital abnormalities, Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, MIM# 618929:Attention deficit-hyperactivity disorder 8 , MIM# 619957; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4853 PLXNA1 Zornitza Stark reviewed gene: PLXNA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Dworschak-Punetha neurodevelopmental syndrome, MIM# 619955; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4853 PLXNA1 Zornitza Stark Phenotypes for gene: PLXNA1 were changed from Neurodevelopmental disorder with cerebral and eye anomalies to Dworschak-Punetha neurodevelopmental syndrome, MIM# 619955
Genetic Epilepsy v0.1633 PLXNA1 Zornitza Stark Phenotypes for gene: PLXNA1 were changed from Neurodevelopmental disorder with cerebral and eye anomalies to Dworschak-Punetha neurodevelopmental syndrome, MIM# 619955
Genetic Epilepsy v0.1632 PLXNA1 Zornitza Stark edited their review of gene: PLXNA1: Changed phenotypes: Dworschak-Punetha neurodevelopmental syndrome, MIM# 619955
Mendeliome v1.152 PLXNA1 Zornitza Stark Phenotypes for gene: PLXNA1 were changed from Neurodevelopmental disorder with cerebral and eye anomalies to Dworschak-Punetha neurodevelopmental syndrome, MIM# 619955
Mendeliome v1.151 PLXNA1 Zornitza Stark edited their review of gene: PLXNA1: Changed phenotypes: Dworschak-Punetha neurodevelopmental syndrome, MIM# 619955
Mendeliome v1.151 TBP Zornitza Stark Tag STR tag was added to gene: TBP.
Prepair 1000+ v0.49 ITGA6 Crystle Lee reviewed gene: ITGA6: Rating: GREEN; Mode of pathogenicity: None; Publications: 31502654, 27607025, 9158140, 34525201, 20301336; Phenotypes: Epidermolysis bullosa, junctional 6, with pyloric atresia (MIM#619817); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.49 PDHA1 Crystle Lee reviewed gene: PDHA1: Rating: AMBER; Mode of pathogenicity: None; Publications: 28584645, 22142326; Phenotypes: Pyruvate dehydrogenase E1-alpha deficiency (MIM#312170); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral Palsy v1.31 ADAT3 Zornitza Stark Marked gene: ADAT3 as ready
Cerebral Palsy v1.31 ADAT3 Zornitza Stark Gene: adat3 has been classified as Green List (High Evidence).
Cerebral Palsy v1.31 ADAT3 Zornitza Stark Phenotypes for gene: ADAT3 were changed from MIM #615286 to Neurodevelopmental disorder with brain abnormalities, poor growth, and dysmorphic facies, MIM# 615286
Cerebral Palsy v1.30 ADAT3 Zornitza Stark Classified gene: ADAT3 as Green List (high evidence)
Cerebral Palsy v1.30 ADAT3 Zornitza Stark Gene: adat3 has been classified as Green List (High Evidence).
Prepair 1000+ v0.49 TTN Zornitza Stark Marked gene: TTN as ready
Prepair 1000+ v0.49 TTN Zornitza Stark Gene: ttn has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v0.49 TTN Zornitza Stark Classified gene: TTN as Amber List (moderate evidence)
Prepair 1000+ v0.49 TTN Zornitza Stark Gene: ttn has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v0.48 VWF Zornitza Stark Marked gene: VWF as ready
Prepair 1000+ v0.48 VWF Zornitza Stark Gene: vwf has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v0.48 VWF Zornitza Stark Classified gene: VWF as Amber List (moderate evidence)
Prepair 1000+ v0.48 VWF Zornitza Stark Gene: vwf has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v0.47 SHOX Zornitza Stark Marked gene: SHOX as ready
Prepair 1000+ v0.47 SHOX Zornitza Stark Gene: shox has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v0.47 SHOX Zornitza Stark Mode of inheritance for gene: SHOX was changed from BIALLELIC, autosomal or pseudoautosomal to Other
Prepair 1000+ v0.46 SHOX Zornitza Stark Classified gene: SHOX as Amber List (moderate evidence)
Prepair 1000+ v0.46 SHOX Zornitza Stark Gene: shox has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v0.45 SHOX Zornitza Stark Tag SV/CNV tag was added to gene: SHOX.
Prepair 1000+ v0.45 EFNB1 Zornitza Stark Tag for review tag was added to gene: EFNB1.
Prepair 1000+ v0.45 VPS11 Zornitza Stark Marked gene: VPS11 as ready
Prepair 1000+ v0.45 VPS11 Zornitza Stark Gene: vps11 has been classified as Green List (High Evidence).
Prepair 1000+ v0.45 VPS11 Zornitza Stark Publications for gene: VPS11 were set to
Prepair 1000+ v0.44 TNFRSF13B Zornitza Stark Marked gene: TNFRSF13B as ready
Prepair 1000+ v0.44 TNFRSF13B Zornitza Stark Gene: tnfrsf13b has been classified as Red List (Low Evidence).
Prepair 1000+ v0.44 TNFRSF13B Zornitza Stark Publications for gene: TNFRSF13B were set to
Prepair 1000+ v0.43 TNFRSF13B Zornitza Stark Classified gene: TNFRSF13B as Red List (low evidence)
Prepair 1000+ v0.43 TNFRSF13B Zornitza Stark Gene: tnfrsf13b has been classified as Red List (Low Evidence).
Prepair 1000+ v0.42 RPL10 Zornitza Stark Tag for review tag was added to gene: RPL10.
Prepair 1000+ v0.42 SERPINA1 Zornitza Stark Marked gene: SERPINA1 as ready
Prepair 1000+ v0.42 SERPINA1 Zornitza Stark Gene: serpina1 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.42 SERPINA1 Zornitza Stark Classified gene: SERPINA1 as Red List (low evidence)
Prepair 1000+ v0.42 SERPINA1 Zornitza Stark Gene: serpina1 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.41 TRAC Zornitza Stark Tag for review tag was added to gene: TRAC.
Prepair 1000+ v0.41 OCA2 Zornitza Stark Tag for review tag was added to gene: OCA2.
Prepair 1000+ v0.41 F8 Zornitza Stark Marked gene: F8 as ready
Prepair 1000+ v0.41 F8 Zornitza Stark Gene: f8 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.41 F8 Zornitza Stark Tag SV/CNV tag was added to gene: F8.
Prepair 1000+ v0.41 F8 Zornitza Stark Classified gene: F8 as Red List (low evidence)
Prepair 1000+ v0.41 F8 Zornitza Stark Gene: f8 has been classified as Red List (Low Evidence).
Mendeliome v1.151 KITLG Zornitza Stark Phenotypes for gene: KITLG were changed from Deafness, autosomal dominant 69, unilateral or asymmetric, MIM# 616697 to Deafness, autosomal dominant 69, unilateral or asymmetric, MIM# 616697; deafness; heterochromia iridis; hypopigmentation of the skin; hyperpigmentation of the skin; Waardenburg syndrome,MONDO:0018094, KITLG-related
Mendeliome v1.150 KITLG Zornitza Stark Publications for gene: KITLG were set to 26522471
Mendeliome v1.149 KITLG Zornitza Stark Classified gene: KITLG as Green List (high evidence)
Mendeliome v1.149 KITLG Zornitza Stark Gene: kitlg has been classified as Green List (High Evidence).
Brain Calcification v1.14 CLDN5 Zornitza Stark Marked gene: CLDN5 as ready
Brain Calcification v1.14 CLDN5 Zornitza Stark Gene: cldn5 has been classified as Amber List (Moderate Evidence).
Brain Calcification v1.14 CLDN5 Zornitza Stark Classified gene: CLDN5 as Amber List (moderate evidence)
Brain Calcification v1.14 CLDN5 Zornitza Stark Gene: cldn5 has been classified as Amber List (Moderate Evidence).
Brain Calcification v1.13 CLDN5 Zornitza Stark gene: CLDN5 was added
gene: CLDN5 was added to Brain Calcification. Sources: Literature
Mode of inheritance for gene: CLDN5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CLDN5 were set to 35714222
Phenotypes for gene: CLDN5 were set to alternating hemiplegia, MONDO:0016210, CLDN5-related
Mode of pathogenicity for gene: CLDN5 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: CLDN5 was set to AMBER
Added comment: PMID: 35714222; Hashimoto, Y. et al. (2022): Two unrelated cases (early-onset) with alternating hemiplegia with microcephaly were shown to have the same de novo variant, NM_001363066.2:c.178G>A, p.(Gly60Arg).

One with Jewish / Tunisian ancestry: Onset was at 8 months, three episodes of febrile tonic-clonic 1 seizures of the four limbs, with eye rolling, loss of consciousness, transient left and right post-2 ictal hemiparesis and vomiting. The other with Asian / European ancestry: Onset was at 30 months with three iterative episodes of febrile and non-febrile hemiplegia and loss of 18 consciousness. The recurrent episodes alternatively involved the left-and 19 right-hand side, then generalised and were followed by post ictal hemiparesis.

CT scans of both showed brain calcifications and aberrant blood flow patterns. Transfected cell lines with this variant, c178G>A, showed higher chloride ion permeability and lower sodium ion permeability when compared to wildtype.
Sources: Literature
Mendeliome v1.148 CLDN5 Zornitza Stark Marked gene: CLDN5 as ready
Mendeliome v1.148 CLDN5 Zornitza Stark Gene: cldn5 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.148 CLDN5 Zornitza Stark Classified gene: CLDN5 as Amber List (moderate evidence)
Mendeliome v1.148 CLDN5 Zornitza Stark Gene: cldn5 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.147 CLDN5 Zornitza Stark gene: CLDN5 was added
gene: CLDN5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CLDN5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CLDN5 were set to 35714222
Phenotypes for gene: CLDN5 were set to alternating hemiplegia, MONDO:0016210, CLDN5-related
Mode of pathogenicity for gene: CLDN5 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: CLDN5 was set to AMBER
Added comment: PMID: 35714222; Hashimoto, Y. et al. (2022): Two unrelated cases (early-onset) with alternating hemiplegia with microcephaly were shown to have the same de novo variant, NM_001363066.2:c.178G>A, p.(Gly60Arg).

One with Jewish / Tunisian ancestry: Onset was at 8 months, three episodes of febrile tonic-clonic 1 seizures of the four limbs, with eye rolling, loss of consciousness, transient left and right post-2 ictal hemiparesis and vomiting. The other with Asian / European ancestry: Onset was at 30 months with three iterative episodes of febrile and non-febrile hemiplegia and loss of 18 consciousness. The recurrent episodes alternatively involved the left-and 19 right-hand side, then generalised and were followed by post ictal hemiparesis.

CT scans of both showed brain calcifications and aberrant blood flow patterns. Transfected cell lines with this variant, c178G>A, showed higher chloride ion permeability and lower sodium ion permeability when compared to wildtype.
Sources: Literature
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.304 CCDC155 Zornitza Stark Marked gene: CCDC155 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.304 CCDC155 Zornitza Stark Gene: ccdc155 has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.304 CCDC155 Zornitza Stark Phenotypes for gene: CCDC155 were changed from Non-obstructive azoospermia; Premature ovarian insufficiency; Infertility disorder, MONDO:0005047, CCDC155-related to Premature ovarian insufficiency; Infertility disorder, MONDO:0005047, CCDC155-related
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.303 CCDC155 Zornitza Stark Classified gene: CCDC155 as Green List (high evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.303 CCDC155 Zornitza Stark Gene: ccdc155 has been classified as Green List (High Evidence).
Leukodystrophy v0.273 Zornitza Stark removed gene:MAK from the panel
Mendeliome v1.146 PSMB9 Zornitza Stark Publications for gene: PSMB9 were set to 26524591
Mendeliome v1.145 PSMB9 Zornitza Stark Mode of inheritance for gene: PSMB9 was changed from Other to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.144 PSMB9 Zornitza Stark Classified gene: PSMB9 as Green List (high evidence)
Mendeliome v1.144 PSMB9 Zornitza Stark Gene: psmb9 has been classified as Green List (High Evidence).
Mendeliome v1.143 PSMB9 Zornitza Stark edited their review of gene: PSMB9: Added comment: Two additional individuals with neonatal onset autoinflammatory syndrome and a mouse model. De novo recurrent missense G156D.; Changed rating: GREEN; Changed publications: 26524591, 34819510; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Autoinflammatory Disorders v0.156 PSMB9 Zornitza Stark Publications for gene: PSMB9 were set to 26524591
Autoinflammatory Disorders v0.155 PSMB9 Zornitza Stark Mode of pathogenicity for gene: PSMB9 was changed from to Other
Autoinflammatory Disorders v0.154 PSMB9 Zornitza Stark Mode of inheritance for gene: PSMB9 was changed from Other to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Autoinflammatory Disorders v0.153 PSMB9 Zornitza Stark Classified gene: PSMB9 as Green List (high evidence)
Autoinflammatory Disorders v0.153 PSMB9 Zornitza Stark Gene: psmb9 has been classified as Green List (High Evidence).
Mendeliome v1.143 HCK Zornitza Stark Marked gene: HCK as ready
Mendeliome v1.143 HCK Zornitza Stark Gene: hck has been classified as Amber List (Moderate Evidence).
Mendeliome v1.143 HCK Zornitza Stark Classified gene: HCK as Amber List (moderate evidence)
Mendeliome v1.143 HCK Zornitza Stark Gene: hck has been classified as Amber List (Moderate Evidence).
Mendeliome v1.142 HCK Zornitza Stark gene: HCK was added
gene: HCK was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HCK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HCK were set to 34536415
Phenotypes for gene: HCK were set to Autoinflammatory syndrome, MONDO:0019751, HCK-related
Mode of pathogenicity for gene: HCK was set to Other
Review for gene: HCK was set to AMBER
Added comment: Single patient with supportive functional data.
Sources: Literature
Autoinflammatory Disorders v0.152 HCK Zornitza Stark Marked gene: HCK as ready
Autoinflammatory Disorders v0.152 HCK Zornitza Stark Gene: hck has been classified as Amber List (Moderate Evidence).
Autoinflammatory Disorders v0.152 HCK Zornitza Stark Phenotypes for gene: HCK were changed from Autoinflammation to Autoinflammatory syndrome, MONDO:0019751, HCK-related
Autoinflammatory Disorders v0.151 HCK Zornitza Stark Classified gene: HCK as Amber List (moderate evidence)
Autoinflammatory Disorders v0.151 HCK Zornitza Stark Gene: hck has been classified as Amber List (Moderate Evidence).
Mendeliome v1.141 TBX21 Zornitza Stark Classified gene: TBX21 as Amber List (moderate evidence)
Mendeliome v1.141 TBX21 Zornitza Stark Gene: tbx21 has been classified as Amber List (Moderate Evidence).
Defects of intrinsic and innate immunity v0.114 TBX21 Zornitza Stark Marked gene: TBX21 as ready
Defects of intrinsic and innate immunity v0.114 TBX21 Zornitza Stark Gene: tbx21 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.140 TBX21 Zornitza Stark changed review comment from: Single individual reported with disseminated disease following BCG vaccination, who subsequently developed severe persistent reactive airway disease and eosinophilia that responded to steroid treatment. Homozygous variant identified.

Association with asthma and nasal polyps pertains to promoter SNPs.; to: Single individual reported with disseminated disease following BCG vaccination, who subsequently developed severe persistent reactive airway disease and eosinophilia that responded to steroid treatment. Homozygous variant identified. Functional data.

Association with asthma and nasal polyps pertains to promoter SNPs.
Mendeliome v1.140 TBX21 Zornitza Stark edited their review of gene: TBX21: Changed rating: AMBER
Defects of intrinsic and innate immunity v0.114 TBX21 Zornitza Stark Classified gene: TBX21 as Amber List (moderate evidence)
Defects of intrinsic and innate immunity v0.114 TBX21 Zornitza Stark Gene: tbx21 has been classified as Amber List (Moderate Evidence).
Defects of intrinsic and innate immunity v0.113 TBX21 Zornitza Stark Phenotypes for gene: TBX21 were changed from Susceptibility to mycobacterial disease to Immunodeficiency 88, MIM# 619630; Susceptibility to mycobacterial disease
Fetal anomalies v1.44 TTC25 Zornitza Stark Publications for gene: TTC25 were set to 27486780
Fetal anomalies v1.43 TTC25 Zornitza Stark Classified gene: TTC25 as Green List (high evidence)
Fetal anomalies v1.43 TTC25 Zornitza Stark Gene: ttc25 has been classified as Green List (High Evidence).
Fetal anomalies v1.42 TTC25 Zornitza Stark edited their review of gene: TTC25: Added comment: At least 7 families reported now.; Changed rating: GREEN; Changed publications: 27486780, 31765523, 33715250, 33746037, 34215651
Heterotaxy v1.20 TTC25 Zornitza Stark Publications for gene: TTC25 were set to 27486780
Heterotaxy v1.19 TTC25 Zornitza Stark Classified gene: TTC25 as Green List (high evidence)
Heterotaxy v1.19 TTC25 Zornitza Stark Gene: ttc25 has been classified as Green List (High Evidence).
Heterotaxy v1.18 TTC25 Zornitza Stark edited their review of gene: TTC25: Added comment: At least 7 families reported now.; Changed rating: GREEN; Changed publications: 27486780, 31765523, 33715250, 33746037, 34215651
Ciliary Dyskinesia v1.20 TTC25 Zornitza Stark Publications for gene: TTC25 were set to 27486780
Ciliary Dyskinesia v1.19 TTC25 Zornitza Stark Classified gene: TTC25 as Green List (high evidence)
Ciliary Dyskinesia v1.19 TTC25 Zornitza Stark Gene: ttc25 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v1.18 TTC25 Zornitza Stark reviewed gene: TTC25: Rating: GREEN; Mode of pathogenicity: None; Publications: 27486780, 31765523, 33715250, 33746037, 34215651; Phenotypes: Ciliary dyskinesia, primary, 35, OMIM:617092; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.140 TTC25 Zornitza Stark Publications for gene: TTC25 were set to 27486780
Mendeliome v1.139 TTC25 Zornitza Stark Classified gene: TTC25 as Green List (high evidence)
Mendeliome v1.139 TTC25 Zornitza Stark Gene: ttc25 has been classified as Green List (High Evidence).
Cerebral Palsy v1.29 ADAT3 Clare van Eyk changed review comment from: Homozygous founder variant in ADAT3 (p.V144M) reported in two cohort studies of children diagnosed with cerebral palsy (PMIDs 35076175; 34321325).

Tone abnormalities, including spasticity and hypotonia, are frequently reported in individuals from additional families with the same variant (PMID 26842963, 11 families, variant also called V128M) and are variable within families. Intellectual disability/developmental delay are always present and the majority with strabismus and growth failure.
Sources: Literature; to: Homozygous founder variant in ADAT3 (p.V144M) reported in two cohort studies of children diagnosed with cerebral palsy (PMIDs 35076175; 34321325).

Tone abnormalities, including spasticity and hypotonia, are frequently reported in individuals from additional families with the same variant (PMID 26842963, 11 families, variant also called V128M) and are variable within families. Intellectual disability/developmental delay are always present and the majority with strabismus and growth failure.
Sources: Literature
Cerebral Palsy v1.29 ADAT3 Clare van Eyk gene: ADAT3 was added
gene: ADAT3 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ADAT3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAT3 were set to 35076175; 34321325
Phenotypes for gene: ADAT3 were set to MIM #615286
Review for gene: ADAT3 was set to GREEN
Added comment: Homozygous founder variant in ADAT3 (p.V144M) reported in two cohort studies of children diagnosed with cerebral palsy (PMIDs 35076175; 34321325).

Tone abnormalities, including spasticity and hypotonia, are frequently reported in individuals from additional families with the same variant (PMID 26842963, 11 families, variant also called V128M) and are variable within families. Intellectual disability/developmental delay are always present and the majority with strabismus and growth failure.
Sources: Literature
Prepair 1000+ v0.40 TTN Crystle Lee reviewed gene: TTN: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Cardiomyopathy, dilated, 1G (MIM#604145), Cardiomyopathy, familial hypertrophic, 9 (MIM#613765), Muscular dystrophy, limb-girdle, autosomal recessive 10 (MIM#608807), Myopathy, myofibrillar, 9, with early respiratory failure (MIM#603689), Salih myopathy (MIM#611705), Tibial muscular dystrophy, tardive (MIM#600334); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Prepair 1000+ v0.40 VWF Crystle Lee reviewed gene: VWF: Rating: AMBER; Mode of pathogenicity: Other; Publications: ; Phenotypes: von Willebrand disease, type 1 (MIM#193400), von Willebrand disease, type 3 (MIM#277480), von Willebrand disease, types 2A, 2B, 2M, and 2N (MIM#613554); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Prepair 1000+ v0.40 SHOX Crystle Lee reviewed gene: SHOX: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Langer mesomelic dysplasia (MIM#249700), Leri-Weill dyschondrosteosis (MIM#127300), Short stature, idiopathic familial (MIM#300582); Mode of inheritance: Other
Prepair 1000+ v0.40 EFNB1 Crystle Lee reviewed gene: EFNB1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Craniofrontonasal dysplasia (MIM#304110); 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+ v0.40 VPS11 Crystle Lee reviewed gene: VPS11: Rating: GREEN; Mode of pathogenicity: None; Publications: 27120463, 26307567, 27473128; Phenotypes: Leukodystrophy, hypomyelinating, 12 (MIM#616683); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.40 TNFRSF13B Crystle Lee reviewed gene: TNFRSF13B: Rating: RED; Mode of pathogenicity: None; Publications: 31681265; Phenotypes: Immunodeficiency, common variable, 2 (MIM#240500); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Prepair 1000+ v0.40 RPL10 Crystle Lee reviewed gene: RPL10: Rating: AMBER; Mode of pathogenicity: None; Publications: 25316788, 26290468, 25846674, 29066376; Phenotypes: Intellectual developmental disorder, X-linked, syndromic, 35, MIM300998; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v0.40 SERPINA1 Crystle Lee reviewed gene: SERPINA1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Emphysema due to AAT deficiency (MIM#613490), Emphysema-cirrhosis, due to AAT deficiency (MIM#613490), Hemorrhagic diathesis due to antithrombin Pittsburgh (MIM#613490); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.40 TRAC Crystle Lee reviewed gene: TRAC: Rating: RED; Mode of pathogenicity: None; Publications: 33909184, 21206088; Phenotypes: Immunodeficiency 7, TCR-alpha/beta deficient (MIM#615387); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.40 OCA2 Crystle Lee reviewed gene: OCA2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Albinism, brown oculocutaneous (MIM#203200), Albinism, oculocutaneous, type II (MIM#203200); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.40 F8 Crystle Lee reviewed gene: F8: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hemophilia A (MIM#306700); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Alternating Hemiplegia and Hemiplegic Migraine v0.53 CLDN5 Hazel Phillimore changed review comment from: PMID: 35714222; Hashimoto, Y. et al. (2022): Two unrelated cases (early-onset) with alternating hemiplegia with microcephaly were shown to have the same de novo variant, NM_001363066.2:c.178G>A, p.(Gly60Arg).
One with Jewish / Tunisian ancestry: Onset was at 8 months, three episodes of febrile tonic-clonic 1 seizures of the four limbs, with eye rolling, loss of consciousness, transient left and right post-2 ictal hemiparesis and vomiting.
The other with Asian / European ancestry: Onset was at 30 months with three iterative episodes of febrile and non-febrile hemiplegia and loss of 18 consciousness. The recurrent episodes alternatively involved the left-and 19 right-hand side, then generalised and were followed by post ictal hemiparesis.
CT scans of both showed brain calcifications and aberrant blood flow patterns.
Transfected HEK cell lines with this variant, c178G>A, showed higher chloride ion permeability and lower sodium ion permeability of the blood brain barrier when compared to wildtype.
Sources: Literature; to: PMID: 35714222; Hashimoto, Y. et al. (2022): Two unrelated cases (early-onset) with alternating hemiplegia with microcephaly were shown to have the same de novo variant, NM_001363066.2:c.178G>A, p.(Gly60Arg).
One with Jewish / Tunisian ancestry: Onset was at 8 months, three episodes of febrile tonic-clonic 1 seizures of the four limbs, with eye rolling, loss of consciousness, transient left and right post-2 ictal hemiparesis and vomiting.
The other with Asian / European ancestry: Onset was at 30 months with three iterative episodes of febrile and non-febrile hemiplegia and loss of 18 consciousness. The recurrent episodes alternatively involved the left-and 19 right-hand side, then generalised and were followed by post ictal hemiparesis.
CT scans of both showed brain calcifications and aberrant blood flow patterns.
Transfected cell lines with this variant, c178G>A, showed higher chloride ion permeability and lower sodium ion permeability when compared to wildtype.
Sources: Literature
Alternating Hemiplegia and Hemiplegic Migraine v0.53 CLDN5 Hazel Phillimore changed review comment from: PMID: 35714222; Hashimoto, Y et al (2022): Two unrelated cases (early-onset) with alternating hemiplegia with microcephaly were shown to have the same de novo variant, c.178G>A, p.(Gly60Arg).
One with Jewish / Tunisian ancestry: Onset was at 8 months, three episodes of febrile tonic-clonic 1 seizures of the four limbs, with eye rolling, loss of consciousness, transient left and right post-2 ictal hemiparesis and vomiting.
The other with Asian / European ancestry: Onset was at 30 months with three iterative episodes of febrile and non-febrile hemiplegia and loss of 18 consciousness. The recurrent episodes alternatively involved the left-and 19 right-hand side, then generalised and were followed by post ictal hemiparesis.
CT scans of both showed brain calcifications and aberrant blood flow patterns.
Transfected HEK cell lines with this variant, c178G>A, showed higher chloride ion permeability and lower sodium ion permeability of the blood brain barrier when compared to wildtype.
Sources: Literature; to: PMID: 35714222; Hashimoto, Y. et al. (2022): Two unrelated cases (early-onset) with alternating hemiplegia with microcephaly were shown to have the same de novo variant, NM_001363066.2:c.178G>A, p.(Gly60Arg).
One with Jewish / Tunisian ancestry: Onset was at 8 months, three episodes of febrile tonic-clonic 1 seizures of the four limbs, with eye rolling, loss of consciousness, transient left and right post-2 ictal hemiparesis and vomiting.
The other with Asian / European ancestry: Onset was at 30 months with three iterative episodes of febrile and non-febrile hemiplegia and loss of 18 consciousness. The recurrent episodes alternatively involved the left-and 19 right-hand side, then generalised and were followed by post ictal hemiparesis.
CT scans of both showed brain calcifications and aberrant blood flow patterns.
Transfected HEK cell lines with this variant, c178G>A, showed higher chloride ion permeability and lower sodium ion permeability of the blood brain barrier when compared to wildtype.
Sources: Literature
Mendeliome v1.138 KITLG Dean Phelan reviewed gene: KITLG: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 35543077, 28504826, 19375057, 21368769; Phenotypes: deafness, heterochromia iridis, hypopigmentation of the skin, hyperpigmentation of the skin, Waardenburg syndrome,MONDO:0018094, KITLG-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v1.42 WNT7B Zornitza Stark Marked gene: WNT7B as ready
Fetal anomalies v1.42 WNT7B Zornitza Stark Gene: wnt7b has been classified as Green List (High Evidence).
Microcephaly v1.132 AUTS2 Elena Savva Marked gene: AUTS2 as ready
Microcephaly v1.132 AUTS2 Elena Savva Gene: auts2 has been classified as Green List (High Evidence).
Microcephaly v1.132 AUTS2 Elena Savva Classified gene: AUTS2 as Green List (high evidence)
Microcephaly v1.132 AUTS2 Elena Savva Gene: auts2 has been classified as Green List (High Evidence).
Microcephaly v1.131 AUTS2 Elena Savva gene: AUTS2 was added
gene: AUTS2 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: AUTS2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: AUTS2 were set to PMID: 35802027; 34573342
Phenotypes for gene: AUTS2 were set to Intellectual developmental disorder, autosomal dominant 26 MIM#615834
Review for gene: AUTS2 was set to GREEN
Added comment: PMID: 35802027 - human cerebral organoid model used to illustrate functionality of de novo missense variants.
Describes rat model who lacked a microcephaly presentation.
Proband has profound ID, microcephaly, epilepsy, cerebellar hypoplasia and dysmorphic features.

PMID: 34573342 - microcephaly as a feature in 3/5 patients in an internal cohort. Review of the literature found 65% freq of microcephaly (34/52 patients)
Sources: Literature
Skeletal dysplasia v0.177 NFATC2 Zornitza Stark Marked gene: NFATC2 as ready
Skeletal dysplasia v0.177 NFATC2 Zornitza Stark Gene: nfatc2 has been classified as Red List (Low Evidence).
Skeletal dysplasia v0.177 NFATC2 Zornitza Stark Classified gene: NFATC2 as Red List (low evidence)
Skeletal dysplasia v0.177 NFATC2 Zornitza Stark Gene: nfatc2 has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v1.140 KITLG Zornitza Stark Phenotypes for gene: KITLG were changed from Deafness, autosomal dominant 69, unilateral or asymmetric, MIM# 616697 to Waardenburg syndrome, MONDO:0018094, KITLG-related; Deafness, autosomal dominant 69, unilateral or asymmetric, MIM# 616697
Mendeliome v1.138 NFATC2 Zornitza Stark Marked gene: NFATC2 as ready
Mendeliome v1.138 NFATC2 Zornitza Stark Gene: nfatc2 has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v1.139 KITLG Zornitza Stark Mode of inheritance for gene: KITLG was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.138 KITLG Zornitza Stark Classified gene: KITLG as Green List (high evidence)
Deafness_IsolatedAndComplex v1.138 KITLG Zornitza Stark Gene: kitlg has been classified as Green List (High Evidence).
Mendeliome v1.138 NFATC2 Zornitza Stark Classified gene: NFATC2 as Red List (low evidence)
Mendeliome v1.138 NFATC2 Zornitza Stark Gene: nfatc2 has been classified as Red List (Low Evidence).
Arthrogryposis v0.349 NFATC2 Zornitza Stark Marked gene: NFATC2 as ready
Arthrogryposis v0.349 NFATC2 Zornitza Stark Gene: nfatc2 has been classified as Red List (Low Evidence).
Arthrogryposis v0.349 NFATC2 Zornitza Stark Classified gene: NFATC2 as Red List (low evidence)
Arthrogryposis v0.349 NFATC2 Zornitza Stark Gene: nfatc2 has been classified as Red List (Low Evidence).
Skeletal dysplasia v0.176 NFATC2 Paul De Fazio gene: NFATC2 was added
gene: NFATC2 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: NFATC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NFATC2 were set to 35789258
Phenotypes for gene: NFATC2 were set to Skeletal system disorder MONDO:0005172
Review for gene: NFATC2 was set to RED
gene: NFATC2 was marked as current diagnostic
Added comment: Patient born to consanguineous parents homozygous for a frameshift variant. No other (unaffected) members of the family were homozygous. Family history of recurrent childhood deaths.

After a healthy birth the patient developed painless decreased range of motion at 1.5yrs leading to difficulty with ambulation at 3yrs. Formal orthopedic assessment at age 15 years
demonstrated a neurodevelopmentally normal young man with marked bilateral fixed flexion contractures of knees, hips, and ankles. The main musculoskeletal findings were painless contractures of the large and small joints of the upper and lower limbs, osteochondromas, and osteopenia. Patient was diagnosed with B-cell lymphoma at age 18.

Patient CD8+ T-cells show impaired polyfunctionality, and the patient had an accumulation of non-functional memory CD4+ T-cells. TFH cell function was also impaired.
Sources: Literature
Alternating Hemiplegia and Hemiplegic Migraine v0.53 CLDN5 Zornitza Stark Marked gene: CLDN5 as ready
Alternating Hemiplegia and Hemiplegic Migraine v0.53 CLDN5 Zornitza Stark Gene: cldn5 has been classified as Amber List (Moderate Evidence).
Alternating Hemiplegia and Hemiplegic Migraine v0.53 CLDN5 Zornitza Stark Phenotypes for gene: CLDN5 were changed from alternating hemiplegia with microcephaly to alternating hemiplegia, MONDO:0016210, CLDN5-related
Arthrogryposis v0.348 NFATC2 Paul De Fazio gene: NFATC2 was added
gene: NFATC2 was added to Arthrogryposis. Sources: Literature
Mode of inheritance for gene: NFATC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NFATC2 were set to 35789258
Phenotypes for gene: NFATC2 were set to Skeletal system disorder MONDO:0005172
Review for gene: NFATC2 was set to RED
gene: NFATC2 was marked as current diagnostic
Added comment: Patient born to consanguineous parents homozygous for a frameshift variant. No other (unaffected) members of the family were homozygous. Family history of recurrent childhood deaths.

After a healthy birth the patient developed painless decreased range of motion at 1.5yrs leading to difficulty with ambulation at 3yrs. Formal orthopedic assessment at age 15 years
demonstrated a neurodevelopmentally normal young man with marked bilateral fixed flexion contractures of knees, hips, and ankles. The main musculoskeletal findings were painless contractures of the large and small joints of the upper and lower limbs, osteochondromas, and osteopenia. Patient was diagnosed with B-cell lymphoma at age 18.

Patient CD8+ T-cells show impaired polyfunctionality, and the patient had an accumulation of non-functional memory CD4+ T-cells. TFH cell function was also impaired.
Sources: Literature
Deafness_IsolatedAndComplex v1.137 KITLG Dean Phelan reviewed gene: KITLG: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 35543077, 28504826, 19375057, 21368769; Phenotypes: deafness, heterochromia iridis, hypopigmentation of the skin, hyperpigmentation of the skin, Waardenburg syndrome; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Alternating Hemiplegia and Hemiplegic Migraine v0.52 CLDN5 Zornitza Stark Classified gene: CLDN5 as Amber List (moderate evidence)
Alternating Hemiplegia and Hemiplegic Migraine v0.52 CLDN5 Zornitza Stark Gene: cldn5 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.137 NFATC2 Paul De Fazio gene: NFATC2 was added
gene: NFATC2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NFATC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NFATC2 were set to 35789258
Phenotypes for gene: NFATC2 were set to Skeletal system disorder MONDO:0005172
Review for gene: NFATC2 was set to RED
gene: NFATC2 was marked as current diagnostic
Added comment: Patient born to consanguineous parents homozygous for a frameshift variant. No other (unaffected) members of the family were homozygous. Family history of recurrent childhood deaths.

After a healthy birth the patient developed painless decreased range of motion at 1.5yrs leading to difficulty with ambulation at 3yrs. Formal orthopedic assessment at age 15 years
demonstrated a neurodevelopmentally normal young man with marked bilateral fixed flexion contractures of knees, hips, and ankles. The main musculoskeletal findings were painless contractures of the large and small joints of the upper and lower limbs, osteochondromas, and osteopenia. Patient was diagnosed with B-cell lymphoma at age 18.

Patient CD8+ T-cells show impaired polyfunctionality, and the patient had an accumulation of non-functional memory CD4+ T-cells. TFH cell function was also impaired.
Sources: Literature
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.302 CCDC155 Melanie Marty gene: CCDC155 was added
gene: CCDC155 was added to Primary Ovarian Insufficiency_Premature Ovarian Failure. Sources: Literature
Mode of inheritance for gene: CCDC155 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC155 were set to 35674372; 35708642; 29790874; 35587281
Phenotypes for gene: CCDC155 were set to Non-obstructive azoospermia; Premature ovarian insufficiency; Infertility disorder, MONDO:0005047, CCDC155-related
Review for gene: CCDC155 was set to GREEN
Added comment: Current HGNC name is KASH5

Summary: 4 families reported with non-obstructive azoospermia or premature ovarian insufficiency. Functional studies have been performed and mouse models recapitulate the phenotype.

PMID: 35674372 CNV and frameshift variants in KASH5 were identified in a non-obstructive azoospermia affected patient and in his infertile sister by whole-exome sequencing and CNV array. Kash5 knockout mouse displayed similar phenotypes, including a meiotic arrest at a zygotene-like stage and impaired pairing and synapsis.

PMID: 35708642 Hom splice identified in KASH5 in 2 sisters with premature ovarian insufficiency. In vitro studies found the variant disturbed the nuclear membrane localization of KASH5 and its binding with SUN1. Moreover, the Kash5 C-terminal deleted mice revealed defective meiotic homolog pairing and accelerated depletion of oocytes.

PMID: 29790874 2 brothers with non-obstructive azoospermia with hom missense in CCDC155

PMID: 35587281 2 siblings with hom missense in CCDC155 non-obstructive azoospermia and premature ovarian insufficiency.
Sources: Literature
Alternating Hemiplegia and Hemiplegic Migraine v0.51 CLDN5 Hazel Phillimore gene: CLDN5 was added
gene: CLDN5 was added to Alternating Hemiplegia and Hemiplegic Migraine. Sources: Literature
Mode of inheritance for gene: CLDN5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CLDN5 were set to PMID: 35714222
Phenotypes for gene: CLDN5 were set to alternating hemiplegia with microcephaly
Mode of pathogenicity for gene: CLDN5 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: CLDN5 was set to AMBER
Added comment: PMID: 35714222; Hashimoto, Y et al (2022): Two unrelated cases (early-onset) with alternating hemiplegia with microcephaly were shown to have the same de novo variant, c.178G>A, p.(Gly60Arg).
One with Jewish / Tunisian ancestry: Onset was at 8 months, three episodes of febrile tonic-clonic 1 seizures of the four limbs, with eye rolling, loss of consciousness, transient left and right post-2 ictal hemiparesis and vomiting.
The other with Asian / European ancestry: Onset was at 30 months with three iterative episodes of febrile and non-febrile hemiplegia and loss of 18 consciousness. The recurrent episodes alternatively involved the left-and 19 right-hand side, then generalised and were followed by post ictal hemiparesis.
CT scans of both showed brain calcifications and aberrant blood flow patterns.
Transfected HEK cell lines with this variant, c178G>A, showed higher chloride ion permeability and lower sodium ion permeability of the blood brain barrier when compared to wildtype.
Sources: Literature
Mendeliome v1.137 PIK3C2B Zornitza Stark Marked gene: PIK3C2B as ready
Mendeliome v1.137 PIK3C2B Zornitza Stark Gene: pik3c2b has been classified as Amber List (Moderate Evidence).
Mendeliome v1.137 PIK3C2B Zornitza Stark Classified gene: PIK3C2B as Amber List (moderate evidence)
Mendeliome v1.137 PIK3C2B Zornitza Stark Gene: pik3c2b has been classified as Amber List (Moderate Evidence).
Mendeliome v1.136 CCDC155 Zornitza Stark Marked gene: CCDC155 as ready
Mendeliome v1.136 CCDC155 Zornitza Stark Gene: ccdc155 has been classified as Green List (High Evidence).
Mendeliome v1.136 CCDC155 Zornitza Stark Phenotypes for gene: CCDC155 were changed from Non-obstructive azoospermia; Premature ovarian insufficiency to Non-obstructive azoospermia; Premature ovarian insufficiency; Infertility disorder, MONDO:0005047, CCDC155-related
Mendeliome v1.135 CCDC155 Zornitza Stark Classified gene: CCDC155 as Green List (high evidence)
Mendeliome v1.135 CCDC155 Zornitza Stark Gene: ccdc155 has been classified as Green List (High Evidence).
Mendeliome v1.134 PIK3C2B Krithika Murali gene: PIK3C2B was added
gene: PIK3C2B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PIK3C2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PIK3C2B were set to PMID:35786744
Phenotypes for gene: PIK3C2B were set to familial partial epilepsy - MONDO#0017704
Review for gene: PIK3C2B was set to AMBER
Added comment: No OMIM gene disease association.

Gozzelino et al.(2022) Brain - report enrichment of ultra-rare PIK3C2B variants in focal epilepsy cohorts, including one variant shown to be de novo (G1294Q). Segregation data not provided for all cases. The p.G1345S variant was inherited from an affected father. The p.K584* variant was inherited from an unaffected father suggesting incomplete penetrance. Functional studies supported a LoF mechanism and mouse model studies suggestive of mTORC1 pathway hyperactivation.
Sources: Literature
Mendeliome v1.134 CCDC155 Zornitza Stark Tag new gene name tag was added to gene: CCDC155.
Mendeliome v1.134 CCDC155 Melanie Marty gene: CCDC155 was added
gene: CCDC155 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CCDC155 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC155 were set to 35674372; 35708642; 29790874; 35587281
Phenotypes for gene: CCDC155 were set to Non-obstructive azoospermia; Premature ovarian insufficiency
Review for gene: CCDC155 was set to GREEN
Added comment: Current HGNC name is KASH5

Summary: 4 families reported with non-obstructive azoospermia or premature ovarian insufficiency. Functional studies have been performed and mouse models recapitulate the phenotype.

PMID: 35674372 CNV and frameshift variants in KASH5 were identified in a non-obstructive azoospermia affected patient and in his infertile sister by whole-exome sequencing and CNV array. Kash5 knockout mouse displayed similar phenotypes, including a meiotic arrest at a zygotene-like stage and impaired pairing and synapsis.

PMID: 35708642 Hom splice identified in KASH5 in 2 sisters with premature ovarian insufficiency. In vitro studies found the variant disturbed the nuclear membrane localization of KASH5 and its binding with SUN1. Moreover, the Kash5 C-terminal deleted mice revealed defective meiotic homolog pairing and accelerated depletion of oocytes.

PMID: 29790874 2 brothers with non-obstructive azoospermia with hom missense in CCDC155

35587281 2 siblings with hom missense in CCDC155 non-obstructive azoospermia and premature ovarian insufficiency.
Sources: Literature
Polydactyly v0.257 SLC30A7 Alison Yeung Classified gene: SLC30A7 as Amber List (moderate evidence)
Polydactyly v0.257 SLC30A7 Alison Yeung Gene: slc30a7 has been classified as Amber List (Moderate Evidence).
Polydactyly v0.257 SLC30A7 Alison Yeung Marked gene: SLC30A7 as ready
Polydactyly v0.257 SLC30A7 Alison Yeung Gene: slc30a7 has been classified as Amber List (Moderate Evidence).
Polydactyly v0.257 SLC30A7 Alison Yeung Classified gene: SLC30A7 as Amber List (moderate evidence)
Polydactyly v0.257 SLC30A7 Alison Yeung Gene: slc30a7 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.134 SLC30A7 Alison Yeung Marked gene: SLC30A7 as ready
Mendeliome v1.134 SLC30A7 Alison Yeung Gene: slc30a7 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.134 SLC30A7 Alison Yeung Classified gene: SLC30A7 as Amber List (moderate evidence)
Mendeliome v1.134 SLC30A7 Alison Yeung Gene: slc30a7 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1632 PIK3C2B Zornitza Stark Marked gene: PIK3C2B as ready
Genetic Epilepsy v0.1632 PIK3C2B Zornitza Stark Gene: pik3c2b has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1632 PIK3C2B Zornitza Stark Classified gene: PIK3C2B as Amber List (moderate evidence)
Genetic Epilepsy v0.1632 PIK3C2B Zornitza Stark Gene: pik3c2b has been classified as Amber List (Moderate Evidence).
Ciliopathies v1.32 SLC30A7 Alison Yeung Marked gene: SLC30A7 as ready
Ciliopathies v1.32 SLC30A7 Alison Yeung Gene: slc30a7 has been classified as Amber List (Moderate Evidence).
Ciliopathies v1.32 SLC30A7 Alison Yeung Classified gene: SLC30A7 as Amber List (moderate evidence)
Ciliopathies v1.32 SLC30A7 Alison Yeung Gene: slc30a7 has been classified as Amber List (Moderate Evidence).
Polydactyly v0.256 SLC30A7 Naomi Baker gene: SLC30A7 was added
gene: SLC30A7 was added to Polydactyly. Sources: Literature
Mode of inheritance for gene: SLC30A7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC30A7 were set to PMID: 35751429
Phenotypes for gene: SLC30A7 were set to Joubert syndrome (MONDO:0018772), SLC30A7-related
Review for gene: SLC30A7 was set to AMBER
Added comment: PMID: 35751429: Two individuals reported with de novo variants, one missense and one delins resulting in missense. The first individual is a female with history of unilateral postaxial polydactyly, classic molar tooth sign on MRI, macrocephaly, ataxia, ocular motor apraxia, neurodevelopmental delay, and precocious puberty. The second individual had bilateral postaxial polydactyly, molar tooth sign, macrocephaly, developmental delay, and an extra oral frenulum. No functional studies reported.
Sources: Literature
Joubert syndrome and other neurological ciliopathies v1.23 SLC30A7 Alison Yeung Marked gene: SLC30A7 as ready
Joubert syndrome and other neurological ciliopathies v1.23 SLC30A7 Alison Yeung Gene: slc30a7 has been classified as Amber List (Moderate Evidence).
Joubert syndrome and other neurological ciliopathies v1.23 SLC30A7 Alison Yeung Classified gene: SLC30A7 as Amber List (moderate evidence)
Joubert syndrome and other neurological ciliopathies v1.23 SLC30A7 Alison Yeung Gene: slc30a7 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.130 WNK3 Zornitza Stark Marked gene: WNK3 as ready
Microcephaly v1.130 WNK3 Zornitza Stark Gene: wnk3 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.130 WNK3 Zornitza Stark Classified gene: WNK3 as Amber List (moderate evidence)
Microcephaly v1.130 WNK3 Zornitza Stark Gene: wnk3 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1631 PIK3C2B Krithika Murali gene: PIK3C2B was added
gene: PIK3C2B was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PIK3C2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PIK3C2B were set to PMID: 35786744
Phenotypes for gene: PIK3C2B were set to familial partial epilepsy - MONDO#0017704
Review for gene: PIK3C2B was set to AMBER
Added comment: No OMIM gene disease association.

Gozzelino et al.(2022) Brain - report enrichment of ultra-rare PIK3C2B variants in focal epilepsy cohorts, including one variant shown to be de novo (G1294Q). Segregation data not provided for all cases. The p.G1345S variant was inherited from an affected father. The p.K584* variant was inherited from an unaffected father suggesting incomplete penetrance. Functional studies supported a LoF mechanism and mouse model studies suggestive of mTORC1 pathway hyperactivation.
Sources: Literature
Genetic Epilepsy v0.1631 WNK3 Zornitza Stark Marked gene: WNK3 as ready
Genetic Epilepsy v0.1631 WNK3 Zornitza Stark Gene: wnk3 has been classified as Green List (High Evidence).
Macrocephaly_Megalencephaly v0.116 Zornitza Stark removed gene:SLC30A7 from the panel
Genetic Epilepsy v0.1631 WNK3 Zornitza Stark Classified gene: WNK3 as Green List (high evidence)
Genetic Epilepsy v0.1631 WNK3 Zornitza Stark Gene: wnk3 has been classified as Green List (High Evidence).
Malignant Hyperthermia Susceptibility v1.6 ASPH Zornitza Stark Phenotypes for gene: ASPH were changed from Exertional heat illness; malignant hyperthermia susceptibility HP:0002047, ASPH-related to Exertional heat illness; malignant hyperthermia susceptibility, MONDO:0018493, ASPH-related
Mendeliome v1.133 ASPH Zornitza Stark Phenotypes for gene: ASPH were changed from Traboulsi syndrome , MIM#601552 to Traboulsi syndrome , MIM#601552; Exertional heat illness; malignant hyperthermia susceptibility, MONDO:0018493, ASPH-related
Rhabdomyolysis and Metabolic Myopathy v0.90 ASPH Zornitza Stark Marked gene: ASPH as ready
Rhabdomyolysis and Metabolic Myopathy v0.90 ASPH Zornitza Stark Gene: asph has been classified as Amber List (Moderate Evidence).
Mendeliome v1.132 ASPH Zornitza Stark Publications for gene: ASPH were set to 24768550; 30194805; 34018898
Mendeliome v1.131 ASPH Zornitza Stark Mode of inheritance for gene: ASPH was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rhabdomyolysis and Metabolic Myopathy v0.90 ASPH Zornitza Stark Phenotypes for gene: ASPH were changed from Exertional heat illness; malignant hyperthermia susceptibility to Exertional heat illness; malignant hyperthermia susceptibility, MONDO:0018493, ASPH-related
Peroxisomal Disorders v0.42 ACOX1 Alison Yeung Phenotypes for gene: ACOX1 were changed from Peroxisomal acyl-CoA oxidase deficiency, MIM# 264470 to Peroxisomal acyl-CoA oxidase deficiency, MIM# 264470
Rhabdomyolysis and Metabolic Myopathy v0.89 ASPH Zornitza Stark Classified gene: ASPH as Amber List (moderate evidence)
Rhabdomyolysis and Metabolic Myopathy v0.89 ASPH Zornitza Stark Gene: asph has been classified as Amber List (Moderate Evidence).
Peroxisomal Disorders v0.42 ACOX1 Alison Yeung Marked gene: ACOX1 as ready
Peroxisomal Disorders v0.42 ACOX1 Alison Yeung Gene: acox1 has been classified as Green List (High Evidence).
Peroxisomal Disorders v0.42 ACOX1 Alison Yeung Phenotypes for gene: ACOX1 were changed from Peroxisomal acyl-CoA oxidase deficiency, MIM# 264470 to Peroxisomal acyl-CoA oxidase deficiency, MIM# 264470
Peroxisomal Disorders v0.41 ACOX1 Alison Yeung Phenotypes for gene: ACOX1 were changed from Peroxisomal acyl-CoA oxidase deficiency, MIM# 264470; Mitchell syndrome, MIM# 618960 to Peroxisomal acyl-CoA oxidase deficiency, MIM# 264470
Malignant Hyperthermia Susceptibility v1.5 ASPH Zornitza Stark Marked gene: ASPH as ready
Malignant Hyperthermia Susceptibility v1.5 ASPH Zornitza Stark Gene: asph has been classified as Amber List (Moderate Evidence).
Malignant Hyperthermia Susceptibility v1.5 ASPH Zornitza Stark Phenotypes for gene: ASPH were changed from Exertional heat illness; malignant hyperthermia susceptibility to Exertional heat illness; malignant hyperthermia susceptibility HP:0002047, ASPH-related
Peroxisomal Disorders v0.41 ACOX1 Alison Yeung Phenotypes for gene: ACOX1 were changed from to Peroxisomal acyl-CoA oxidase deficiency, MIM# 264470; Mitchell syndrome, MIM# 618960
Malignant Hyperthermia Susceptibility v1.4 ASPH Zornitza Stark Classified gene: ASPH as Amber List (moderate evidence)
Malignant Hyperthermia Susceptibility v1.4 ASPH Zornitza Stark Gene: asph has been classified as Amber List (Moderate Evidence).
Peroxisomal Disorders v0.40 ACOX1 Alison Yeung Mode of inheritance for gene: ACOX1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Peroxisomal Disorders v0.40 ACOX1 Alison Yeung Mode of inheritance for gene: ACOX1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.130 SLC30A7 Naomi Baker gene: SLC30A7 was added
gene: SLC30A7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC30A7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC30A7 were set to PMID: 35751429
Phenotypes for gene: SLC30A7 were set to Joubert syndrome (MONDO:0018772), SLC30A7-related
Review for gene: SLC30A7 was set to AMBER
Added comment: PMID: 35751429: Two individuals reported with de novo variants, one missense and one delins resulting in missense. The first individual is a female with history of unilateral postaxial polydactyly, classic molar tooth sign on MRI, macrocephaly, ataxia, ocular motor apraxia, neurodevelopmental delay, and precocious puberty. The second individual had bilateral postaxial polydactyly, molar tooth sign, macrocephaly, developmental delay, and an extra oral frenulum. No functional studies reported.
Sources: Literature
Regression v0.489 ACOX1 Alison Yeung Marked gene: ACOX1 as ready
Regression v0.489 ACOX1 Alison Yeung Gene: acox1 has been classified as Green List (High Evidence).
Regression v0.489 ACOX1 Alison Yeung Classified gene: ACOX1 as Green List (high evidence)
Regression v0.489 ACOX1 Alison Yeung Gene: acox1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4852 CHMP3 Zornitza Stark Marked gene: CHMP3 as ready
Intellectual disability syndromic and non-syndromic v0.4852 CHMP3 Zornitza Stark Gene: chmp3 has been classified as Amber List (Moderate Evidence).
Regression v0.488 ACOX1 Alison Yeung gene: ACOX1 was added
gene: ACOX1 was added to Regression. Sources: Literature
Mode of inheritance for gene: ACOX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ACOX1 were set to 32169171; 35715200
Phenotypes for gene: ACOX1 were set to Mitchell syndrome, MIM# 618960
Review for gene: ACOX1 was set to GREEN
Added comment: Mono-allelic variants (recurrent de novo missense, N237S) associated with Mitchell syndrome (MITCH): a progressive disorder characterised by episodic demyelination, sensorimotor polyneuropathy, and hearing loss. Bi-allelic variants cause a peroxisomal disorder characterised by neonatal hypotonia, seizures, apneic spells, delayed psychomotor development, and neurologic regression.
Sources: Literature
Macrocephaly_Megalencephaly v0.115 SLC30A7 Naomi Baker gene: SLC30A7 was added
gene: SLC30A7 was added to Macrocephaly_Megalencephaly. Sources: Literature
Mode of inheritance for gene: SLC30A7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC30A7 were set to PMID: 35751429
Phenotypes for gene: SLC30A7 were set to Joubert syndrome (MONDO:0018772), SLC30A7-related
Review for gene: SLC30A7 was set to AMBER
Added comment: PMID: 35751429: Two individuals reported with de novo variants, one missense and one delins resulting in missense. The first individual is a female with history of unilateral postaxial polydactyly, classic molar tooth sign on MRI, macrocephaly, ataxia, ocular motor apraxia, neurodevelopmental delay, and precocious puberty. The second individual had bilateral postaxial polydactyly, molar tooth sign, macrocephaly, developmental delay, and an extra oral frenulum. No functional studies reported.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4852 CHMP3 Zornitza Stark Classified gene: CHMP3 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.4852 CHMP3 Zornitza Stark Gene: chmp3 has been classified as Amber List (Moderate Evidence).
Regression v0.487 CHMP3 Zornitza Stark Marked gene: CHMP3 as ready
Regression v0.487 CHMP3 Zornitza Stark Gene: chmp3 has been classified as Amber List (Moderate Evidence).
Regression v0.487 CHMP3 Zornitza Stark Classified gene: CHMP3 as Amber List (moderate evidence)
Regression v0.487 CHMP3 Zornitza Stark Gene: chmp3 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.4851 PABPC1 Elena Savva Classified gene: PABPC1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4851 PABPC1 Elena Savva Gene: pabpc1 has been classified as Green List (High Evidence).
Mendeliome v1.130 ASPH Paul De Fazio reviewed gene: ASPH: Rating: AMBER; Mode of pathogenicity: None; Publications: 35697689; Phenotypes: Exertional heat illness, malignant hyperthermia susceptibility; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Genetic Epilepsy v0.1630 WNK3 Lucy Spencer gene: WNK3 was added
gene: WNK3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: WNK3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: WNK3 were set to 35678782
Phenotypes for gene: WNK3 were set to Neurodevelopmental disorder, WNK3-related (MONDO#0700092)
Review for gene: WNK3 was set to GREEN
Added comment: 6 maternally inherited hemizygous variants, 3 missense and 3 LOF. Seen in 14 individuals from 6 families. The variants cosegregated with disease in 3 families with multiple affected individuals. Phenotype described as intellectual disability, with the variable presence of seizures and structural brain defects. One family previously had a clinical diagnosis of X-linked Prieto syndrome.
Sources: Literature
Mendeliome v1.130 CHMP3 Zornitza Stark Marked gene: CHMP3 as ready
Mendeliome v1.130 CHMP3 Zornitza Stark Gene: chmp3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.130 CHMP3 Zornitza Stark Classified gene: CHMP3 as Amber List (moderate evidence)
Mendeliome v1.130 CHMP3 Zornitza Stark Gene: chmp3 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.4850 PABPC1 Elena Savva Classified gene: PABPC1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4850 PABPC1 Elena Savva Gene: pabpc1 has been classified as Green List (High Evidence).
Ciliopathies v1.31 SLC30A7 Naomi Baker gene: SLC30A7 was added
gene: SLC30A7 was added to Ciliopathies. Sources: Literature
Mode of inheritance for gene: SLC30A7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC30A7 were set to PMID: 35751429
Phenotypes for gene: SLC30A7 were set to Joubert syndrome (MONDO:0018772), SLC30A7-related
Review for gene: SLC30A7 was set to AMBER
Added comment: PMID: 35751429: Two individuals reported with de novo variants, one missense and one delins resulting in missense. The first individual is a female with history of unilateral postaxial polydactyly, classic molar tooth sign on MRI, macrocephaly, ataxia, ocular motor apraxia, neurodevelopmental delay, and precocious puberty. The second individual had bilateral postaxial polydactyly, molar tooth sign, macrocephaly, developmental delay, and an extra oral frenulum. No functional studies reported.
Sources: Literature
Hereditary Spastic Paraplegia v1.39 CHMP3 Zornitza Stark Marked gene: CHMP3 as ready
Hereditary Spastic Paraplegia v1.39 CHMP3 Zornitza Stark Gene: chmp3 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.4850 PABPC1 Elena Savva Classified gene: PABPC1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4850 PABPC1 Elena Savva Gene: pabpc1 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v1.39 CHMP3 Zornitza Stark Classified gene: CHMP3 as Amber List (moderate evidence)
Hereditary Spastic Paraplegia v1.39 CHMP3 Zornitza Stark Gene: chmp3 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.4849 PABPC1 Elena Savva Marked gene: PABPC1 as ready
Intellectual disability syndromic and non-syndromic v0.4849 PABPC1 Elena Savva Gene: pabpc1 has been classified as Red List (Low Evidence).
Mendeliome v1.129 PABPC1 Elena Savva Marked gene: PABPC1 as ready
Mendeliome v1.129 PABPC1 Elena Savva Gene: pabpc1 has been classified as Green List (High Evidence).
Mendeliome v1.129 PABPC1 Elena Savva Classified gene: PABPC1 as Green List (high evidence)
Mendeliome v1.129 PABPC1 Elena Savva Gene: pabpc1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4849 PABPC1 Elena Savva gene: PABPC1 was added
gene: PABPC1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PABPC1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PABPC1 were set to PMID: 35511136
Phenotypes for gene: PABPC1 were set to Neurodevelopmental disorder, PABPC1-related (MONDO#0700092)
Review for gene: PABPC1 was set to GREEN
Added comment: PMID: 35511136 - 4 probands with an overlapping phenotype of DD, expressive speech delay, and autistic features and heterozygous de novo variants that cluster in the PABP domain of PABPC1.
Electroporation of mouse embryo brains showed that Pabpc1 knockdown decreases the proliferation of neural progenitor cells. Wild-type Pabpc1 could rescue this disturbance, whereas 3 of the 4 variants did not.
Sources: Literature
Microcephaly v1.129 WNK3 Lucy Spencer gene: WNK3 was added
gene: WNK3 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: WNK3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: WNK3 were set to 35678782
Phenotypes for gene: WNK3 were set to Neurodevelopmental disorder, WNK3-related (MONDO#0700092)
Added comment: 6 individuals with microcephaly all at -2 to -2.4SD so leaving as amber for now. Individuals also had ID and other features
Sources: Literature
Mendeliome v1.128 PABPC1 Elena Savva gene: PABPC1 was added
gene: PABPC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PABPC1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PABPC1 were set to PMID: 35511136
Phenotypes for gene: PABPC1 were set to Neurodevelopmental disorder, PABPC1-related (MONDO#0700092)
Review for gene: PABPC1 was set to GREEN
Added comment: PMID: 35511136 - 4 probands with an overlapping phenotype of DD, expressive speech delay, and autistic features and heterozygous de novo variants that cluster in the PABP domain of PABPC1.
Electroporation of mouse embryo brains showed that Pabpc1 knockdown decreases the proliferation of neural progenitor cells. Wild-type Pabpc1 could rescue this disturbance, whereas 3 of the 4 variants did not.
Sources: Literature
Joubert syndrome and other neurological ciliopathies v1.22 SLC30A7 Naomi Baker gene: SLC30A7 was added
gene: SLC30A7 was added to Joubert syndrome and other neurological ciliopathies. Sources: Literature
Mode of inheritance for gene: SLC30A7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC30A7 were set to PMID: 35751429
Phenotypes for gene: SLC30A7 were set to Joubert syndrome (MONDO:0018772), SLC30A7-related
Review for gene: SLC30A7 was set to AMBER
Added comment: PMID: 35751429: Two individuals reported with de novo variants, one missense and one delins resulting in missense. The first individual is a female with history of unilateral postaxial polydactyly, classic molar tooth sign on MRI, macrocephaly, ataxia, ocular motor apraxia, neurodevelopmental delay, and precocious puberty. The second individual had bilateral postaxial polydactyly, molar tooth sign, macrocephaly, developmental delay, and an extra oral frenulum. No functional studies reported.
Sources: Literature
Leukodystrophy v0.272 ACOX1 Alison Yeung Marked gene: ACOX1 as ready
Leukodystrophy v0.272 ACOX1 Alison Yeung Gene: acox1 has been classified as Green List (High Evidence).
Leukodystrophy v0.272 ACOX1 Alison Yeung Added comment: Comment on phenotypes: Mono-allelic variants (recurrent de novo missense, N237S) associated with Mitchell syndrome (MITCH): a progressive disorder characterised by episodic demyelination, sensorimotor polyneuropathy, and hearing loss. Bi-allelic variants cause a peroxisomal disorder characterised by neonatal hypotonia, seizures, apneic spells, delayed psychomotor development, and neurologic regression.
Leukodystrophy v0.272 ACOX1 Alison Yeung Phenotypes for gene: ACOX1 were changed from Peroxisomal acyl-CoA oxidase deficiency 264470; General Leukodystrophy & Mitochondrial Leukoencephalopathy to Peroxisomal acyl-CoA oxidase deficiency, MIM# 264470; Mitchell syndrome, MIM# 618960
Mendeliome v1.127 WNK3 Zornitza Stark Marked gene: WNK3 as ready
Mendeliome v1.127 WNK3 Zornitza Stark Gene: wnk3 has been classified as Green List (High Evidence).
Mendeliome v1.127 WNK3 Zornitza Stark reviewed gene: WNK3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.127 WNK3 Zornitza Stark Classified gene: WNK3 as Green List (high evidence)
Mendeliome v1.127 WNK3 Zornitza Stark Gene: wnk3 has been classified as Green List (High Evidence).
Mendeliome v1.126 CHMP3 Chern Lim gene: CHMP3 was added
gene: CHMP3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CHMP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHMP3 were set to PMID: 35710109
Phenotypes for gene: CHMP3 were set to Hereditary spastic paraplegia (MONDO:0019064), CHMP3-related
Review for gene: CHMP3 was set to AMBER
gene: CHMP3 was marked as current diagnostic
Added comment: PMID: 35710109
- Single large family with consanguinity, homozygous missense variant in 5 affected individuals with intellectual and progressive motor disabilities, seizures and spastic quadriplegia.
- Functional studies showed reduced CHMP3 protein in patient's fibroblasts, lenti-rescue study showed improved cellular phenotypes associated with impaired autophagy.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4848 WNK3 Zornitza Stark Marked gene: WNK3 as ready
Intellectual disability syndromic and non-syndromic v0.4848 WNK3 Zornitza Stark Gene: wnk3 has been classified as Green List (High Evidence).
Leukodystrophy v0.271 ACOX1 Alison Yeung Mode of inheritance for gene: ACOX1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rhabdomyolysis and Metabolic Myopathy v0.88 ASPH Paul De Fazio gene: ASPH was added
gene: ASPH was added to Rhabdomyolysis. Sources: Literature
Mode of inheritance for gene: ASPH was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ASPH were set to 35697689
Phenotypes for gene: ASPH were set to Exertional heat illness; malignant hyperthermia susceptibility
Review for gene: ASPH was set to AMBER
gene: ASPH was marked as current diagnostic
Added comment: In a study of 103 individuals (63 affected from 34 families, plus 40 sporadic cases) who had either a sentinel event of EHI or MH, or else a positive CHCT and a first degree releative with EHI/MH, and where RYR1 and CACNA1S Sanger sequencing was negative, the following variants in ASPH were identified in unrelated individuals:

- c.161T > C in 2 members of a family with myalgias exacerbated by heat/exercise. One had elevated CK. Both had positive CHCT. An unaffected sibling did not have the variant. 27 hets in gnomad v2 / 17 hets in gnomad v3.
- c.445G>C in a patient with MH, myalgias and muscle cramps worsened by heat and exercise. 4 hets in gnomad v2 / 3 hets in gnomad v3. Non-coding in the MANE transcript.
- c.263A > C in a patient with EHI, diagnosed as MHN by in vitro contracture test. Absent from gnomad but non-coding in the MANE transcript.
- c.605A > G in a patient with EHI, diagnosed as MHN by in vitro contracture test. 223 hets in gnomad v2 / 120 hets in gnomad v3; no homs. Non-coding in the MANE transcript.

A zebrafish model and cell line functional studies supported pathogenicity of the c.161T > C and c.263A > C variants.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4848 WNK3 Zornitza Stark Classified gene: WNK3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4848 WNK3 Zornitza Stark Gene: wnk3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4847 ACOX1 Alison Yeung Phenotypes for gene: ACOX1 were changed from Peroxisomal acyl-CoA oxidase deficiency, MIM# 264470; Mitchell syndrome, MIM# 618960 to Peroxisomal acyl-CoA oxidase deficiency, MIM# 264470; Mitchell syndrome, MIM# 618960
Regression v0.486 CHMP3 Chern Lim gene: CHMP3 was added
gene: CHMP3 was added to Regression. Sources: Literature
Mode of inheritance for gene: CHMP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHMP3 were set to PMID: 35710109
Phenotypes for gene: CHMP3 were set to Hereditary spastic paraplegia (MONDO:0019064), CHMP3-related
Review for gene: CHMP3 was set to AMBER
gene: CHMP3 was marked as current diagnostic
Added comment: PMID: 35710109
- Single large family with consanguinity, homozygous missense variant in 5 affected individuals with intellectual and progressive motor disabilities, seizures and spastic quadriplegia.
- Functional studies showed reduced CHMP3 protein in patient's fibroblasts, lenti-rescue study showed improved cellular phenotypes associated with impaired autophagy.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4847 ACOX1 Alison Yeung Phenotypes for gene: ACOX1 were changed from Peroxisomal acyl-CoA oxidase deficiency, MIM# 264470; Mitchell syndrome, MIM# 618960 to Peroxisomal acyl-CoA oxidase deficiency, MIM# 264470; Mitchell syndrome, MIM# 618960
Intellectual disability syndromic and non-syndromic v0.4846 ACOX1 Alison Yeung Phenotypes for gene: ACOX1 were changed from Peroxisomal acyl-CoA oxidase deficiency, MIM# 264470; Mitchell syndrome, MIM# 618960 to Peroxisomal acyl-CoA oxidase deficiency, MIM# 264470; Mitchell syndrome, MIM# 618960
Intellectual disability syndromic and non-syndromic v0.4846 CHMP3 Chern Lim gene: CHMP3 was added
gene: CHMP3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CHMP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHMP3 were set to PMID: 35710109
Phenotypes for gene: CHMP3 were set to Hereditary spastic paraplegia (MONDO:0019064), CHMP3-related
Review for gene: CHMP3 was set to AMBER
gene: CHMP3 was marked as current diagnostic
Added comment: PMID: 35710109
- Single large family with consanguinity, homozygous missense variant in 5 affected individuals with intellectual and progressive motor disabilities, seizures and spastic quadriplegia.
- Functional studies showed reduced CHMP3 protein in patient's fibroblasts, lenti-rescue study showed improved cellular phenotypes associated with impaired autophagy.
Sources: Literature
Mendeliome v1.126 WNK3 Lucy Spencer gene: WNK3 was added
gene: WNK3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: WNK3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: WNK3 were set to 35678782
Phenotypes for gene: WNK3 were set to Neurodevelopmental disorder, WNK3-related (MONDO#0700092)
Added comment: 6 maternally inherited hemizygous variants, 3 missense, 2 canonical splice, and a nonsense. Seen in 14 individuals from 6 families, all 14 are male who inherited hemizygous variants from their unaffected heterozygous mothers. The variants cosegregated with disease in 3 families with multiple affected individuals. All 14 patients have ID, 11 have speech delay, 10 have facial abnormalities, 5 have seizures, 6 with microcephaly and 7 with anomalies in brain imaging.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4846 ACOX1 Alison Yeung Publications for gene: ACOX1 were set to 32169171; 17458872
Malignant Hyperthermia Susceptibility v1.3 ASPH Paul De Fazio gene: ASPH was added
gene: ASPH was added to Malignant Hyperthermia Susceptibility. Sources: Literature
Mode of inheritance for gene: ASPH was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ASPH were set to 35697689
Phenotypes for gene: ASPH were set to Exertional heat illness; malignant hyperthermia susceptibility
Review for gene: ASPH was set to AMBER
gene: ASPH was marked as current diagnostic
Added comment: In a study of 103 individuals (63 affected from 34 families, plus 40 sporadic cases) who had either a sentinel event of EHI or MH, or else a positive CHCT and a first degree releative with EHI/MH, and where RYR1 and CACNA1S Sanger sequencing was negative, the following variants in ASPH were identified in unrelated individuals:

- c.161T > C in 2 members of a family with myalgias exacerbated by heat/exercise. One had elevated CK. Both had positive CHCT. An unaffected sibling did not have the variant. 27 hets in gnomad v2 / 17 hets in gnomad v3.
- c.445G>C in a patient with MH, myalgias and muscle cramps worsened by heat and exercise. 4 hets in gnomad v2 / 3 hets in gnomad v3. Non-coding in the MANE transcript.
- c.263A > C in a patient with EHI, diagnosed as MHN by in vitro contracture test. Absent from gnomad but non-coding in the MANE transcript.
- c.605A > G in a patient with EHI, diagnosed as MHN by in vitro contracture test. 223 hets in gnomad v2 / 120 hets in gnomad v3; no homs. Non-coding in the MANE transcript.

A zebrafish model and cell line functional studies supported pathogenicity of the c.161T > C and c.263A > C variants.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4845 ACOX1 Alison Yeung Phenotypes for gene: ACOX1 were changed from to Peroxisomal acyl-CoA oxidase deficiency, MIM# 264470; Mitchell syndrome, MIM# 618960
Intellectual disability syndromic and non-syndromic v0.4845 ACOX1 Alison Yeung Marked gene: ACOX1 as ready
Intellectual disability syndromic and non-syndromic v0.4845 ACOX1 Alison Yeung Gene: acox1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4845 ACOX1 Alison Yeung Publications for gene: ACOX1 were set to
Hereditary Spastic Paraplegia v1.38 CHMP3 Chern Lim gene: CHMP3 was added
gene: CHMP3 was added to Hereditary Spastic Paraplegia - paediatric. Sources: Literature
Mode of inheritance for gene: CHMP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHMP3 were set to PMID: 35710109
Phenotypes for gene: CHMP3 were set to Hereditary spastic paraplegia (MONDO:0019064), CHMP3-related
Review for gene: CHMP3 was set to AMBER
gene: CHMP3 was marked as current diagnostic
Added comment: PMID: 35710109
- Single large family with consanguinity, homozygous missense variant in 5 affected individuals with intellectual and progressive motor disabilities, seizures and spastic quadriplegia.
- Functional studies showed reduced CHMP3 protein in patient's fibroblasts, lenti-rescue study showed improved cellular phenotypes associated with impaired autophagy.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4844 ACOX1 Alison Yeung Mode of inheritance for gene: ACOX1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.126 WNT7B Zornitza Stark Marked gene: WNT7B as ready
Mendeliome v1.126 WNT7B Zornitza Stark Gene: wnt7b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4843 ACOX1 Alison Yeung reviewed gene: ACOX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32169171, 17458872; Phenotypes: Peroxisomal acyl-CoA oxidase deficiency, MIM# 264470, Mitchell syndrome, MIM# 618960; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.126 WNT7B Zornitza Stark Classified gene: WNT7B as Green List (high evidence)
Mendeliome v1.126 WNT7B Zornitza Stark Gene: wnt7b has been classified as Green List (High Evidence).
Mendeliome v1.125 WNT7B Zornitza Stark gene: WNT7B was added
gene: WNT7B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: WNT7B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WNT7B were set to 35790350
Phenotypes for gene: WNT7B were set to Pulmonary hypoplasia, Diaphragmatic anomalies, Anophthalmia/microphthalmia and Cardiac defects syndrome; Multiple congenital anomalies/dysmorphic features syndrome MONDO:0043005, WNT7B-related
Review for gene: WNT7B was set to GREEN
Added comment: Three families reported with fetuses with multiple congenital anomalies and bi-allelic LoF variants. Two of the families had at the same variant. Supportive zebrafish model.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4843 WNK3 Lucy Spencer gene: WNK3 was added
gene: WNK3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: WNK3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: WNK3 were set to 35678782
Phenotypes for gene: WNK3 were set to Neurodevelopmental disorder, WNK3-related (MONDO#0700092)
Review for gene: WNK3 was set to GREEN
Added comment: 6 maternally inherited hemizygous variants, 3 missense, 2 canonical splice, and a nonsense. Seen in 14 individuals from 6 families, all 14 are male who inherited hemizygous variants from their unaffected heterozygous mothers. The variants cosegregated with disease in 3 families with multiple affected individuals. All 14 patients have ID, 11 have speech delay, 10 have facial abnormalities, 5 have seizures, 6 with microcephaly and 7 with anomalies in brain imaging.
Sources: Literature
Anophthalmia_Microphthalmia_Coloboma v1.24 WNT7B Zornitza Stark Marked gene: WNT7B as ready
Anophthalmia_Microphthalmia_Coloboma v1.24 WNT7B Zornitza Stark Gene: wnt7b has been classified as Amber List (Moderate Evidence).
Anophthalmia_Microphthalmia_Coloboma v1.24 WNT7B Zornitza Stark Classified gene: WNT7B as Amber List (moderate evidence)
Anophthalmia_Microphthalmia_Coloboma v1.24 WNT7B Zornitza Stark Gene: wnt7b has been classified as Amber List (Moderate Evidence).
Anophthalmia_Microphthalmia_Coloboma v1.23 WNT7B Zornitza Stark gene: WNT7B was added
gene: WNT7B was added to Anophthalmia_Microphthalmia_Coloboma. Sources: Literature
Mode of inheritance for gene: WNT7B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WNT7B were set to 35790350
Phenotypes for gene: WNT7B were set to Pulmonary hypoplasia, Diaphragmatic anomalies, Anophthalmia/microphthalmia and Cardiac defects syndrome; Multiple congenital anomalies/dysmorphic features syndrome MONDO:0043005, WNT7B-related
Review for gene: WNT7B was set to AMBER
Added comment: Three families reported with fetuses with multiple congenital anomalies and bi-allelic LoF variants. Two of the families had at the same variant. Supportive zebrafish model. Uncertain if all had anophthalmia/microphthalmia.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4843 MAL Zornitza Stark Marked gene: MAL as ready
Intellectual disability syndromic and non-syndromic v0.4843 MAL Zornitza Stark Gene: mal has been classified as Amber List (Moderate Evidence).
Mendeliome v1.124 TMEM63C Elena Savva Classified gene: TMEM63C as Green List (high evidence)
Mendeliome v1.124 TMEM63C Elena Savva Gene: tmem63c has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4843 TMEM63C Elena Savva Classified gene: TMEM63C as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4843 TMEM63C Elena Savva Gene: tmem63c has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4843 MAL Zornitza Stark Classified gene: MAL as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.4843 MAL Zornitza Stark Gene: mal has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.4842 TMEM63C Elena Savva Classified gene: TMEM63C as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4842 TMEM63C Elena Savva Gene: tmem63c has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4842 TMEM63C Elena Savva Classified gene: TMEM63C as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4842 TMEM63C Elena Savva Gene: tmem63c has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v1.38 TMEM63C Elena Savva Classified gene: TMEM63C as Green List (high evidence)
Hereditary Spastic Paraplegia v1.38 TMEM63C Elena Savva Gene: tmem63c has been classified as Green List (High Evidence).
Congenital diaphragmatic hernia v1.8 WNT7B Zornitza Stark Marked gene: WNT7B as ready
Congenital diaphragmatic hernia v1.8 WNT7B Zornitza Stark Gene: wnt7b has been classified as Green List (High Evidence).
Congenital diaphragmatic hernia v1.8 WNT7B Zornitza Stark Classified gene: WNT7B as Green List (high evidence)
Congenital diaphragmatic hernia v1.8 WNT7B Zornitza Stark Gene: wnt7b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4841 TMEM63C Elena Savva Marked gene: TMEM63C as ready
Intellectual disability syndromic and non-syndromic v0.4841 TMEM63C Elena Savva Gene: tmem63c has been classified as Red List (Low Evidence).
Hereditary Spastic Paraplegia v1.37 TMEM63C Elena Savva Classified gene: TMEM63C as Green List (high evidence)