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Inherited pancreatic cancer v3.0 Sarah Leigh promoted panel to version 3.0
Vascular skin disorders v2.0 Achchuthan Shanmugasundram promoted panel to version 2.0
Mosaic skin disorders - deep sequencing v3.1 Eleanor Williams Panel version 3.0 has been signed off on 2025-04-30
Mosaic skin disorders - deep sequencing v3.0 Eleanor Williams promoted panel to version 3.0
Ichthyosis and erythrokeratoderma v4.1 Sarah Leigh Panel version 4.0 has been signed off on 2025-04-30
Thoracic aortic aneurysm or dissection (GMS) v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2025-04-30
Ichthyosis and erythrokeratoderma v4.0 Sarah Leigh promoted panel to version 4.0
Monogenic hearing loss v5.1 Eleanor Williams Panel version 5.0 has been signed off on 2025-04-30
Thoracic aortic aneurysm or dissection (GMS) v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
Monogenic hearing loss v5.0 Eleanor Williams promoted panel to version 5.0
Hypophosphataemia or rickets v4.1 Sarah Leigh Panel version 4.0 has been signed off on 2025-04-30
Hypophosphataemia or rickets v4.0 Sarah Leigh promoted panel to version 4.0
Skeletal dysplasia v8.1 Achchuthan Shanmugasundram Panel version 8.0 has been signed off on 2025-04-30
Skeletal dysplasia v8.0 Achchuthan Shanmugasundram promoted panel to version 8.0
Monogenic diabetes v3.1 Eleanor Williams Panel version 3.0 has been signed off on 2025-04-30
Monogenic diabetes v3.0 Eleanor Williams promoted panel to version 3.0
Hypogonadotropic hypogonadism (GMS) v4.1 Sarah Leigh Panel version 4.0 has been signed off on 2025-04-30
Hypogonadotropic hypogonadism (GMS) v4.0 Sarah Leigh promoted panel to version 4.0
Clefting v6.6 Arina Puzriakova Panel version 6.5 has been signed off on 2025-04-30
Skeletal ciliopathies v6.1 Achchuthan Shanmugasundram Panel version 6.0 has been signed off on 2025-04-30
Mitochondrial disorders v9.1 Eleanor Williams Panel version 9.0 has been signed off on 2025-04-30
Catecholaminergic polymorphic VT v5.2 Arina Puzriakova Panel version 5.1 has been signed off on 2025-04-30
Skeletal ciliopathies v6.0 Achchuthan Shanmugasundram promoted panel to version 6.0
Hypertrophic cardiomyopathy v5.1 Sarah Leigh Panel version 5.0 has been signed off on 2025-04-30
Mitochondrial disorders v9.0 Eleanor Williams promoted panel to version 9.0
Brugada syndrome and cardiac sodium channel disease v3.13 Arina Puzriakova Panel version 3.12 has been signed off on 2025-04-30
Hypertrophic cardiomyopathy v5.0 Sarah Leigh promoted panel to version 5.0
Severe microcephaly v8.1 Achchuthan Shanmugasundram Panel version 8.0 has been signed off on 2025-04-30
Atypical haemolytic uraemic syndrome v3.7 Arina Puzriakova Panel version 3.6 has been signed off on 2025-04-30
Severe microcephaly v8.0 Achchuthan Shanmugasundram promoted panel to version 8.0
Mitochondrial disorder with complex V deficiency v3.1 Eleanor Williams Panel version 3.0 has been signed off on 2025-04-30
Hereditary neuropathy or pain disorder v7.1 Sarah Leigh Panel version 7.0 has been signed off on 2025-04-30
Mitochondrial disorder with complex V deficiency v3.0 Eleanor Williams promoted panel to version 3.0
Hereditary neuropathy or pain disorder v7.0 Sarah Leigh promoted panel to version 7.0
Arrhythmogenic right ventricular cardiomyopathy v3.14 Arina Puzriakova Panel version 3.13 has been signed off on 2025-04-30
Severe early-onset obesity v5.1 Achchuthan Shanmugasundram Panel version 5.0 has been signed off on 2025-04-30
Mitochondrial disorder with complex IV deficiency v4.1 Eleanor Williams Panel version 4.0 has been signed off on 2025-04-30
Severe early-onset obesity v5.0 Achchuthan Shanmugasundram promoted panel to version 5.0
Mitochondrial disorder with complex IV deficiency v4.0 Eleanor Williams promoted panel to version 4.0
Congenital muscular dystrophy v6.1 Arina Puzriakova Panel version 6.0 has been signed off on 2025-04-30
Hereditary ataxia with onset in adulthood v8.1 Sarah Leigh Panel version 8.0 has been signed off on 2025-04-30
Congenital muscular dystrophy v6.0 Arina Puzriakova promoted panel to version 6.0
Hereditary ataxia with onset in adulthood v8.0 Sarah Leigh promoted panel to version 8.0
Segmental overgrowth disorders - Deep sequencing v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2025-04-30
Segmental overgrowth disorders - Deep sequencing v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v5.1 Eleanor Williams Panel version 5.0 has been signed off on 2025-04-30
Congenital hypothyroidism v3.1 Arina Puzriakova Panel version 3.0 has been signed off on 2025-04-30
Congenital hypothyroidism v3.0 Arina Puzriakova promoted panel to version 3.0
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v5.0 Eleanor Williams promoted panel to version 5.0
Fetal anomalies v6.1 Sarah Leigh Panel version 6.0 has been signed off on 2025-04-30
Congenital fibrosis of the extraocular muscles v2.1 Arina Puzriakova Panel version 2.0 has been signed off on 2025-04-30
Congenital fibrosis of the extraocular muscles v2.0 Arina Puzriakova promoted panel to version 2.0
Fetal anomalies v6.0 Sarah Leigh promoted panel to version 6.0
Retinal disorders v8.1 Achchuthan Shanmugasundram Panel version 8.0 has been signed off on 2025-04-30
Congenital disorders of glycosylation v7.1 Arina Puzriakova Panel version 7.0 has been signed off on 2025-04-30
Retinal disorders v8.0 Achchuthan Shanmugasundram promoted panel to version 8.0
Congenital disorders of glycosylation v7.0 Arina Puzriakova promoted panel to version 7.0
Congenital adrenal hypoplasia v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2025-04-30
Congenital adrenal hypoplasia v4.0 Arina Puzriakova promoted panel to version 4.0
Respiratory ciliopathies including non-CF bronchiectasis v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2025-04-30
Limb disorders v7.1 Eleanor Williams Panel version 7.0 has been signed off on 2025-04-30
Respiratory ciliopathies including non-CF bronchiectasis v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
Familial hypoparathyroidism v3.1 Sarah Leigh Panel version 3.0 has been signed off on 2025-04-30
Limb disorders v7.0 Eleanor Williams promoted panel to version 7.0
Familial hypoparathyroidism v3.0 Sarah Leigh promoted panel to version 3.0
Childhood solid tumours v5.1 Arina Puzriakova Panel version 5.0 has been signed off on 2025-04-30
Childhood solid tumours v5.0 Arina Puzriakova promoted panel to version 5.0
Renal tubulopathies v5.1 Achchuthan Shanmugasundram Panel version 5.0 has been signed off on 2025-04-30
Childhood onset hereditary spastic paraplegia v8.1 Arina Puzriakova Panel version 8.0 has been signed off on 2025-04-30
Childhood onset hereditary spastic paraplegia v8.0 Arina Puzriakova promoted panel to version 8.0
Renal tubulopathies v5.0 Achchuthan Shanmugasundram promoted panel to version 5.0
Ehlers Danlos syndrome with a likely monogenic cause v4.1 Sarah Leigh Panel version 4.0 has been signed off on 2025-04-30
Ehlers Danlos syndrome with a likely monogenic cause v4.0 Sarah Leigh promoted panel to version 4.0
Childhood onset dystonia, chorea or related movement disorder v7.1 Arina Puzriakova Panel version 7.0 has been signed off on 2025-04-30
Childhood onset dystonia, chorea or related movement disorder v7.0 Arina Puzriakova promoted panel to version 7.0
Renal ciliopathies v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2025-04-30
Renal ciliopathies v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
Cerebral vascular malformations v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2025-04-30
Ectodermal dysplasia v4.1 Sarah Leigh Panel version 4.0 has been signed off on 2025-04-30
Cerebral vascular malformations v4.0 Arina Puzriakova promoted panel to version 4.0
Likely inborn error of metabolism v8.1 Eleanor Williams Panel version 8.0 has been signed off on 2025-04-30
Ectodermal dysplasia v4.0 Sarah Leigh promoted panel to version 4.0
Bleeding and platelet disorders v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2025-04-30
Rare syndromic craniosynostosis or isolated multisuture synostosis v6.1 Achchuthan Shanmugasundram Panel version 6.0 has been signed off on 2025-04-30
Bleeding and platelet disorders v4.0 Arina Puzriakova promoted panel to version 4.0
Rare syndromic craniosynostosis or isolated multisuture synostosis v6.0 Achchuthan Shanmugasundram promoted panel to version 6.0
Early onset or syndromic epilepsy v8.1 Sarah Leigh Panel version 8.0 has been signed off on 2025-04-30
Bilateral congenital or childhood onset cataracts v7.1 Arina Puzriakova Panel version 7.0 has been signed off on 2025-04-30
Bilateral congenital or childhood onset cataracts v7.0 Arina Puzriakova promoted panel to version 7.0
Likely inborn error of metabolism v8.0 Eleanor Williams promoted panel to version 8.0
Early onset or syndromic epilepsy v8.0 Sarah Leigh promoted panel to version 8.0
Ataxia and cerebellar anomalies - narrow panel v8.1 Arina Puzriakova Panel version 8.0 has been signed off on 2025-04-30
Rare genetic inflammatory skin disorders v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2025-04-30
Ataxia and cerebellar anomalies - narrow panel v8.0 Arina Puzriakova promoted panel to version 8.0
Rare genetic inflammatory skin disorders v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
Arthrogryposis v9.1 Arina Puzriakova Panel version 9.0 has been signed off on 2025-04-30
Arthrogryposis v9.0 Arina Puzriakova promoted panel to version 9.0
Dilated and arrhythmogenic cardiomyopathy v3.1 Sarah Leigh Panel version 3.0 has been signed off on 2025-04-30
Pulmonary arterial hypertension v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2025-04-30
Laterality disorders and isomerism v4.1 Eleanor Williams Panel version 4.0 has been signed off on 2025-04-30
Dilated and arrhythmogenic cardiomyopathy v3.0 Sarah Leigh promoted panel to version 3.0
Pulmonary arterial hypertension v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
Amelogenesis imperfecta v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2025-04-30
Laterality disorders and isomerism v4.0 Eleanor Williams promoted panel to version 4.0
Amelogenesis imperfecta v4.0 Arina Puzriakova promoted panel to version 4.0
Albinism or congenital nystagmus v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2025-04-30
Albinism or congenital nystagmus v4.0 Arina Puzriakova promoted panel to version 4.0
DDG2P v6.1 Sarah Leigh Panel version 6.0 has been signed off on 2025-04-30
Proteinuric renal disease v5.1 Achchuthan Shanmugasundram Panel version 5.0 has been signed off on 2025-04-30
Proteinuric renal disease v5.0 Achchuthan Shanmugasundram promoted panel to version 5.0
Adult onset neurodegenerative disorder v8.1 Arina Puzriakova Panel version 8.0 has been signed off on 2025-04-30
DDG2P v6.0 Sarah Leigh promoted panel to version 6.0
Adult onset neurodegenerative disorder v8.0 Arina Puzriakova promoted panel to version 8.0
Adult onset leukodystrophy v6.1 Arina Puzriakova Panel version 6.0 has been signed off on 2025-04-30
Adult onset leukodystrophy v6.0 Arina Puzriakova promoted panel to version 6.0
Cytopenia - NOT Fanconi anaemia v4.1 Sarah Leigh Panel version 4.0 has been signed off on 2025-04-30
Adult onset hereditary spastic paraplegia v6.1 Arina Puzriakova Panel version 6.0 has been signed off on 2025-04-30
Adult onset hereditary spastic paraplegia v6.0 Arina Puzriakova promoted panel to version 6.0
Cytopenia - NOT Fanconi anaemia v4.0 Sarah Leigh promoted panel to version 4.0
Primary lymphoedema v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2025-04-30
Primary lymphoedema v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
Cystic kidney disease v8.1 Sarah Leigh Panel version 8.0 has been signed off on 2025-04-30
Adult onset dystonia, chorea or related movement disorder v5.1 Arina Puzriakova Panel version 5.0 has been signed off on 2025-04-30
Cystic kidney disease v8.0 Sarah Leigh promoted panel to version 8.0
Adult onset dystonia, chorea or related movement disorder v5.0 Arina Puzriakova promoted panel to version 5.0
Acute rhabdomyolysis v2.1 Arina Puzriakova Panel version 2.0 has been signed off on 2025-04-30
Primary immunodeficiency or monogenic inflammatory bowel disease v8.1 Achchuthan Shanmugasundram Panel version 8.0 has been signed off on 2025-04-30
Acute rhabdomyolysis v2.0 Arina Puzriakova promoted panel to version 2.0
Primary immunodeficiency or monogenic inflammatory bowel disease v8.0 Achchuthan Shanmugasundram promoted panel to version 8.0
Corneal dystrophy v4.1 Sarah Leigh Panel version 4.0 has been signed off on 2025-04-30
Corneal dystrophy v4.0 Sarah Leigh promoted panel to version 4.0
Congenital myopathy v6.1 Sarah Leigh Panel version 6.0 has been signed off on 2025-04-30
Possible mitochondrial disorder - nuclear genes v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2025-04-30
Possible mitochondrial disorder - nuclear genes v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
Congenital myopathy v6.0 Sarah Leigh promoted panel to version 6.0
Pituitary hormone deficiency v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2025-04-30
Pituitary hormone deficiency v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
Congenital myaesthenic syndrome v5.1 Sarah Leigh Panel version 5.0 has been signed off on 2025-04-30
Pigmentary skin disorders v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2025-04-30
Congenital myaesthenic syndrome v5.0 Sarah Leigh promoted panel to version 5.0
Pigmentary skin disorders v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
PTEN Hamartoma Tumour Syndrome v1.2 Achchuthan Shanmugasundram Panel name changed from PTEN Hamartoma Tumor Syndrome to PTEN Hamartoma Tumour Syndrome
List of related panels changed from R213 to R213; PTEN Hamartoma Tumor Syndrome
Sickle cell, thalassaemia and other haemoglobinopathies v2.2 Achchuthan Shanmugasundram Panel name changed from Thalassaemia and other haemoglobinopathies to Sickle cell, thalassaemia and other haemoglobinopathies
List of related panels changed from R93 to R93; Thalassaemia and other haemoglobinopathies
Sickle cell, thalassaemia and other haemoglobinopathies trait or carrier testing v2.2 Achchuthan Shanmugasundram Panel name changed from Haemoglobinopathy trait or carrier testing to Sickle cell, thalassaemia and other haemoglobinopathies trait or carrier testing
List of related panels changed from R361 to R361; Haemoglobinopathy trait or carrier testing
Intellectual disability v8.243 PRMT9 Shahryar Alavi reviewed gene: PRMT9: Rating: AMBER; Mode of pathogenicity: Other; Publications: PMID: 38561334; Phenotypes: intellectual disability, failure to thrive; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Thrombocythaemia v1.5 SH2B3 Terri McVeigh reviewed gene: SH2B3: Rating: GREEN; Mode of pathogenicity: None; Publications: https://doi.org/10.1182/blood-2024-210339; Phenotypes: thrombocytosis, myeloproliferative disease, ALL; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital myopathy v5.16 ZC4H2 Achchuthan Shanmugasundram Tag currently-not-available-via-GLH-non-WGS-testing was removed from gene: ZC4H2.
Congenital myopathy v5.16 UNC45B Achchuthan Shanmugasundram Tag currently-not-available-via-GLH-non-WGS-testing was removed from gene: UNC45B.
Congenital myopathy v5.16 TRDN Achchuthan Shanmugasundram Tag currently-not-available-via-GLH-non-WGS-testing was removed from gene: TRDN.
Congenital myopathy v5.16 SPTBN4 Achchuthan Shanmugasundram Tag currently-not-available-via-GLH-non-WGS-testing was removed from gene: SPTBN4.
Congenital myopathy v5.16 MLIP Achchuthan Shanmugasundram Tag currently-not-available-via-GLH-non-WGS-testing was removed from gene: MLIP.
Congenital myopathy v5.16 LETM1 Achchuthan Shanmugasundram Tag currently-not-available-via-GLH-non-WGS-testing was removed from gene: LETM1.
Congenital myopathy v5.16 KY Achchuthan Shanmugasundram Tag currently-not-available-via-GLH-non-WGS-testing was removed from gene: KY.
Congenital myopathy v5.16 GBE1 Achchuthan Shanmugasundram Tag currently-not-available-via-GLH-non-WGS-testing was removed from gene: GBE1.
Congenital myopathy v5.16 DNAJB4 Achchuthan Shanmugasundram Tag currently-not-available-via-GLH-non-WGS-testing was removed from gene: DNAJB4.
Congenital myopathy v5.16 COL25A1 Achchuthan Shanmugasundram Tag currently-not-available-via-GLH-non-WGS-testing was removed from gene: COL25A1.
Congenital myopathy v5.16 COL13A1 Achchuthan Shanmugasundram Tag currently-not-available-via-GLH-non-WGS-testing was removed from gene: COL13A1.
Congenital myopathy v5.16 ASCC1 Achchuthan Shanmugasundram Tag currently-not-available-via-GLH-non-WGS-testing was removed from gene: ASCC1.
Congenital muscular dystrophy v5.3 POGLUT1 Achchuthan Shanmugasundram Tag currently-not-available-via-GLH-non-WGS-testing was removed from gene: POGLUT1.
Congenital muscular dystrophy v5.3 GOSR2 Achchuthan Shanmugasundram Tag currently-not-available-via-GLH-non-WGS-testing was removed from gene: GOSR2.
Congenital muscular dystrophy v5.3 GOLGA2 Achchuthan Shanmugasundram Tag currently-not-available-via-GLH-non-WGS-testing was removed from gene: GOLGA2.
Congenital muscular dystrophy v5.3 EMD Achchuthan Shanmugasundram Tag currently-not-available-via-GLH-non-WGS-testing was removed from gene: EMD.
Congenital muscular dystrophy v5.3 DTNA Achchuthan Shanmugasundram Tag currently-not-available-via-GLH-non-WGS-testing was removed from gene: DTNA.
Congenital muscular dystrophy v5.3 DPM3 Achchuthan Shanmugasundram Tag currently-not-available-via-GLH-non-WGS-testing was removed from gene: DPM3.
Congenital muscular dystrophy v5.3 BET1 Achchuthan Shanmugasundram Tag currently-not-available-via-GLH-non-WGS-testing was removed from gene: BET1.
Skeletal dysplasia v7.42 NEPRO Achchuthan Shanmugasundram commented on gene: NEPRO: The 'new-gene-name' tag has been added to this gene as the official HGNC gene symbol for NEPRO is RMP64.
Skeletal dysplasia v7.42 NEPRO Achchuthan Shanmugasundram Tag new-gene-name tag was added to gene: NEPRO.
Intellectual disability v8.243 GAS8 Achchuthan Shanmugasundram Tag new-gene-name tag was added to gene: GAS8.
DDG2P v5.48 GAS8 Achchuthan Shanmugasundram Tag new-gene-name tag was added to gene: GAS8.
DDG2P v5.48 GAS8 Achchuthan Shanmugasundram commented on gene: GAS8: The 'new-gene-name' tag has been added as the official HGNC gene symbol for GAS8 is DRC4.
Fetal anomalies v5.98 GAS8 Achchuthan Shanmugasundram Tag new-gene-name tag was added to gene: GAS8.
Fetal anomalies v5.98 GAS8 Achchuthan Shanmugasundram commented on gene: GAS8
Respiratory ciliopathies including non-CF bronchiectasis v3.37 GAS8 Achchuthan Shanmugasundram Tag new-gene-name tag was added to gene: GAS8.
Respiratory ciliopathies including non-CF bronchiectasis v3.37 GAS8 Achchuthan Shanmugasundram commented on gene: GAS8
Laterality disorders and isomerism v3.22 GAS8 Achchuthan Shanmugasundram commented on gene: GAS8
Laterality disorders and isomerism v3.22 GAS8 Achchuthan Shanmugasundram Tag new-gene-name tag was added to gene: GAS8.
Intellectual disability v8.243 CCDC65 Achchuthan Shanmugasundram Tag new-gene-name tag was added to gene: CCDC65.
Intellectual disability v8.243 CCDC65 Achchuthan Shanmugasundram commented on gene: CCDC65
DDG2P v5.48 CCDC65 Achchuthan Shanmugasundram Tag new-gene-name tag was added to gene: CCDC65.
DDG2P v5.48 CCDC65 Achchuthan Shanmugasundram commented on gene: CCDC65: The 'new-gene-name' tag has been added as the approved HGNC gene symbol for CCDC65 is DRC2.
Fetal anomalies v5.98 CCDC65 Achchuthan Shanmugasundram Tag new-gene-name tag was added to gene: CCDC65.
Fetal anomalies v5.98 CCDC65 Achchuthan Shanmugasundram commented on gene: CCDC65
Laterality disorders and isomerism v3.22 CCDC65 Achchuthan Shanmugasundram Tag new-gene-name tag was added to gene: CCDC65.
Laterality disorders and isomerism v3.22 CCDC65 Achchuthan Shanmugasundram commented on gene: CCDC65
Respiratory ciliopathies including non-CF bronchiectasis v3.37 CCDC65 Achchuthan Shanmugasundram commented on gene: CCDC65
Respiratory ciliopathies including non-CF bronchiectasis v3.37 CCDC65 Achchuthan Shanmugasundram Tag new-gene-name tag was added to gene: CCDC65.
Fetal anomalies v5.98 ZSCAN10 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: ZSCAN10.
DDG2P v5.48 ZBTB47 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: ZBTB47.
DDG2P v5.48 PPFIA3 Achchuthan Shanmugasundram Tag gene-checked was removed from gene: PPFIA3.
DDG2P v5.48 PPFIA3 Achchuthan Shanmugasundram edited their review of gene: PPFIA3: Changed phenotypes to: PPFIA3-related neurodevelopmental disorder, Paul-Chao neurodevelopmental syndrome, OMIM:621122
Fetal anomalies v5.98 DISP1 Achchuthan Shanmugasundram Tag gene-checked was removed from gene: DISP1.
Holoprosencephaly v5.3 DISP1 Achchuthan Shanmugasundram Tag gene-checked was removed from gene: DISP1.
Fetal anomalies v5.98 DISP1 Achchuthan Shanmugasundram Phenotypes for gene: DISP1 were changed from Holoprosencephaly 10, OMIM:62114 to Holoprosencephaly 10, OMIM:621143
Fetal anomalies v5.97 DISP1 Achchuthan Shanmugasundram Tag watchlist was removed from gene: DISP1.
Fetal anomalies v5.97 DISP1 Achchuthan Shanmugasundram Phenotypes for gene: DISP1 were changed from Holoprosencephaly to Holoprosencephaly 10, OMIM:62114
Holoprosencephaly v5.3 DISP1 Achchuthan Shanmugasundram Phenotypes for gene: DISP1 were changed from holoprosencephaly MONDO:0016296 to Holoprosencephaly 10, OMIM:621143
Intellectual disability v8.243 EPB41L3 Julia Baptista gene: EPB41L3 was added
gene: EPB41L3 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: EPB41L3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EPB41L3 were set to 39292993
Phenotypes for gene: EPB41L3 were set to developmental delay; intellectual disability; seizures; hypotonia; neuroregression
Review for gene: EPB41L3 was set to GREEN
Added comment: Six individuals from five unrelated families with global developmental delay, intellectual disability, seizures, hypotonia, neuroregression and delayed myelination. Exome sequencing identified biallelic variants in EPB41L3 in all affected individuals: two nonsense [c.466C>T, p.(R156*); c.2776C>T, p.(R926*)] and three frameshift [c.666delT, p.(F222Lfs*46); c.2289dupC, p.(V764Rfs*19); c.948_949delTG, p.(A317Kfs*33)].
Sources: Literature
Intellectual disability v8.243 EEF1D Julia Baptista gene: EEF1D was added
gene: EEF1D was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: EEF1D was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EEF1D were set to 36576126; 30787422; 38083972; 28097321
Phenotypes for gene: EEF1D were set to Neurodevelopmental disorder; OMIM#621150
Review for gene: EEF1D was set to GREEN
Added comment: Biallelic variants described in at least 5 families from different areas (Syria, Turkey, Oman and China).
Sources: Literature
Intellectual disability v8.243 FBXO22 Julia Baptista gene: FBXO22 was added
gene: FBXO22 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: FBXO22 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FBXO22 were set to 40215970
Phenotypes for gene: FBXO22 were set to neurodevelopmental delay; malformations; OMIM# 621184
Review for gene: FBXO22 was set to GREEN
Added comment: 15 affected children (nine females and six males) and one fetus (16 cases in total) presenting a common core symptomatology of early-onset growth restriction, neurodevelopmental delay, craniofacial abnormalities, and additional poly-malformations (cardiovascular, gastrointestinal, urinal, and endocrinal) (Figure 1A). All individuals belonged to 14 families from four countries of the Greater Middle East region (UAE, KSA, Oman, and Lebanon), of which 12 were identified as consanguineous. Of the 16 cases, three passed away (F7-II:1, F9-II:1, and F13-II:4), and one was a second-trimester termination of pregnancy (TOP) of unknown sex.
Sources: Literature
Fetal anomalies v5.96 C1orf127 Julia Baptista gene: C1orf127 was added
gene: C1orf127 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: C1orf127 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C1orf127 were set to 39753129
Phenotypes for gene: C1orf127 were set to Heterotaxy
Review for gene: C1orf127 was set to GREEN
Added comment: OMIM entry now available for this gene and condition.
The HGNC approved gene name is CIROZ

Sixteen individuals from 10 independently ascertained families with Left-right anomalies with or without Congenital Heart Defects, consistent with Heterotaxy. Family 1 is of European ancestry, and families 9 and 10 are from Central America, while all remaining families were of Middle Eastern background and known to be consanguineous.

Of these 16 affected individuals, three were affected fetuses subjected to termination of pregnancy, and two died in the first year of life due to complex cardiac phenotypes.
Sources: Literature
Laterality disorders and isomerism v3.22 C1orf127 Julia Baptista gene: C1orf127 was added
gene: C1orf127 was added to Laterality disorders and isomerism. Sources: Literature
Mode of inheritance for gene: C1orf127 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C1orf127 were set to 39753129
Phenotypes for gene: C1orf127 were set to Heterotaxy
Review for gene: C1orf127 was set to GREEN
Added comment: OMIM entry now available for this gene and condition.
The HGNC approved gene name is CIROZ

Sixteen individuals from 10 independently ascertained families with Left-right anomalies with or without Congenital Heart Defects, consistent with Heterotaxy. Family 1 is of European ancestry, and families 9 and 10 are from Central America, while all remaining families were of Middle Eastern background and known to be consanguineous.

Of these 16 affected individuals, three were affected fetuses subjected to termination of pregnancy, and two died in the first year of life due to complex cardiac phenotypes.
Sources: Literature
Retinal disorders v7.26 THRB Achchuthan Shanmugasundram Tag Q2_25_ promote_green tag was added to gene: THRB.
Tag Q2_25_ NHS_review tag was added to gene: THRB.
Retinal disorders v7.26 THRB Achchuthan Shanmugasundram Classified gene: THRB as Amber List (moderate evidence)
Retinal disorders v7.26 THRB Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Romana Izakovicova, a new variant (c.283G>C p.(Gly95Arg)) was reported in five probands from her clinical practice and 100k diagnostic discovery patients. Hence, there is sufficient evidence available now for the promotion of this gene to green rating in the next GMS update.
Retinal disorders v7.26 THRB Achchuthan Shanmugasundram Gene: thrb has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.243 SEL1L Julia Baptista gene: SEL1L was added
gene: SEL1L was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: SEL1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SEL1L were set to 37943610, 37943617
Phenotypes for gene: SEL1L were set to Neurodevelopmental disorder
Review for gene: SEL1L was set to GREEN
Added comment: Biallelic missense variants of SEL1L and HRD1 (or SYVN1) in 6 children from 3 independent families presenting with developmental delay, intellectual disability, microcephaly, facial dysmorphisms, hypotonia, and/or ataxia (Wang et al 2024). Hypomorphic variants.

A biallelic SEL1L variant (p. Cys141Tyr) in 5 patients from a consanguineous Slovakian family reported by Weis et al 2024.

A gene-disease association is now described in OMIM.
Sources: Literature
Likely inborn error of metabolism v7.27 MAN2B2 Julia Baptista reviewed gene: MAN2B2: Rating: GREEN; Mode of pathogenicity: None; Publications: 38622837, 31775018, 35637269; Phenotypes: congenital disorders of glycosylation; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital disorders of glycosylation v6.11 MAN2B2 Julia Baptista reviewed gene: MAN2B2: Rating: GREEN; Mode of pathogenicity: None; Publications: 38622837, 31775018, 35637269; Phenotypes: congenital disorder of glycosylation; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v7.25 THRB Achchuthan Shanmugasundram edited their review of gene: THRB: Changed rating: GREEN
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.45 SNUPN Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Dmitrijs Rots, there is sufficient evidence available for the promotion of this gene to green rating in the next nGMS update.; to: Comment on list classification: As reviewed by Dmitrijs Rots, there is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.45 SNUPN Achchuthan Shanmugasundram Classified gene: SNUPN as Amber List (moderate evidence)
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.45 SNUPN Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Dmitrijs Rots, there is sufficient evidence available for the promotion of this gene to green rating in the next nGMS update.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.45 SNUPN Achchuthan Shanmugasundram Gene: snupn has been classified as Amber List (Moderate Evidence).
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.44 SNUPN Achchuthan Shanmugasundram Phenotypes for gene: SNUPN were changed from muscular dystrophy to Muscular dystrophy, limb-girdle, autosomal recessive 29, OMIM:620793
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.43 SNUPN Achchuthan Shanmugasundram Publications for gene: SNUPN were set to 38413582
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.42 SNUPN Achchuthan Shanmugasundram Tag Q2_25_ promote_green tag was added to gene: SNUPN.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.42 SNUPN Achchuthan Shanmugasundram reviewed gene: SNUPN: Rating: GREEN; Mode of pathogenicity: None; Publications: 38366623, 38413582; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 29, OMIM:620793; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary ataxia with onset in adulthood v7.23 NPTX1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Jenna Ridley, there are eight unrelated families identified with four different heterozygous missense variants in NPTX1 gene. Seven families were reported with late-onset ataxia, whereas it is early-onset in the six-year-old girl reported in PMID:35560436. There is also functional evidence available for the two variants reported in PMID:34788392.

This gene has been associated with relevant phenotype in OMIM (MIM #620158).

Hence, this gene should be promoted to green rating in the next GMS update.; to: Comment on list classification: As reviewed by Jenna Ridley, there are eight unrelated families identified with four different heterozygous missense variants in NPTX1 gene. Seven families were reported with late-onset ataxia, whereas it is early-onset in the six-year-old girl reported in PMID:35560436. There is also functional evidence available for the two variants reported in PMID:34788392.

This gene has been associated with relevant phenotype in OMIM (MIM #620158).

Hence, this gene should be promoted to green rating in the next GMS update.
Hereditary ataxia with onset in adulthood v7.23 NPTX1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Jenna Ridley, there are eight unrelated families identified with four different missense heterozygous NPTX1 variants. Seven families were reported with late-onset ataxia, whereas it is early onset in the six-year-old girl reported in PMID:35560436. There is also functional evidence available.

This gene has been associated with relevant phenotype in OMIM (MIM #620158).

Hence, this gene should be promoted to green rating in the next GMS update.; to: Comment on list classification: As reviewed by Jenna Ridley, there are eight unrelated families identified with four different heterozygous missense variants in NPTX1 gene. Seven families were reported with late-onset ataxia, whereas it is early-onset in the six-year-old girl reported in PMID:35560436. There is also functional evidence available for the two variants reported in PMID:34788392.

This gene has been associated with relevant phenotype in OMIM (MIM #620158).

Hence, this gene should be promoted to green rating in the next GMS update.
Hereditary ataxia with onset in adulthood v7.23 NPTX1 Achchuthan Shanmugasundram Classified gene: NPTX1 as Amber List (moderate evidence)
Hereditary ataxia with onset in adulthood v7.23 NPTX1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Jenna Ridley, there are eight unrelated families identified with four different missense heterozygous NPTX1 variants. Seven families were reported with late-onset ataxia, whereas it is early onset in the six-year-old girl reported in PMID:35560436. There is also functional evidence available.

This gene has been associated with relevant phenotype in OMIM (MIM #620158).

Hence, this gene should be promoted to green rating in the next GMS update.
Hereditary ataxia with onset in adulthood v7.23 NPTX1 Achchuthan Shanmugasundram Gene: nptx1 has been classified as Amber List (Moderate Evidence).
Hereditary ataxia with onset in adulthood v7.22 NPTX1 Achchuthan Shanmugasundram Tag Q2_25_ promote_green tag was added to gene: NPTX1.
Tag Q2_25_ NHS_review tag was added to gene: NPTX1.
Hereditary ataxia with onset in adulthood v7.22 NPTX1 Achchuthan Shanmugasundram edited their review of gene: NPTX1: Changed publications to: 34788392, 35285082, 35288776, 35560436
Hereditary ataxia with onset in adulthood v7.22 NPTX1 Achchuthan Shanmugasundram reviewed gene: NPTX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34788392, 35285082, 35288776, PMID:35560436; Phenotypes: Spinocerebellar ataxia 50, OMIM:620158; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia with onset in adulthood v7.22 FAT2 Achchuthan Shanmugasundram Classified gene: FAT2 as Amber List (moderate evidence)
Hereditary ataxia with onset in adulthood v7.22 FAT2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Jenna Ridley, there are four unrelated cases/ families identified with four different heterozygous missense variants in FAT2 gene and reported with late-onset spinocerebellar ataxia. There is some functional work available.

This gene has been associated with relevant phenotype in OMIM (MIM #617769).

This gene should therefore be promoted to green rating in the next GMS update.
Hereditary ataxia with onset in adulthood v7.22 FAT2 Achchuthan Shanmugasundram Gene: fat2 has been classified as Amber List (Moderate Evidence).
Hereditary ataxia with onset in adulthood v7.21 FAT2 Achchuthan Shanmugasundram Publications for gene: FAT2 were set to 29053796; 36339299; 33884300
Hereditary ataxia with onset in adulthood v7.20 FAT2 Achchuthan Shanmugasundram Tag Q2_25_ promote_green tag was added to gene: FAT2.
Tag Q2_25_ NHS_review tag was added to gene: FAT2.
Hereditary ataxia with onset in adulthood v7.20 FAT2 Achchuthan Shanmugasundram reviewed gene: FAT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29053796, 33884300, 36339299; Phenotypes: Spinocerebellar ataxia 45, OMIM:617769; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral vascular malformations v3.40 EVL Achchuthan Shanmugasundram Classified gene: EVL as Red List (low evidence)
Cerebral vascular malformations v3.40 EVL Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Alexandra Njegic and reported in PMID:34125151, there is one patient with Moyamoya disease identified with compound heterozygous variants in EVL gene. There are no other cases or functional work available.

This gene has not yet been reported with relevant phenotypes either in OMIM or in Gene2Phenotype.

Hence, this gene should be rated red with current evidence.
Cerebral vascular malformations v3.40 EVL Achchuthan Shanmugasundram Gene: evl has been classified as Red List (Low Evidence).
Cerebral vascular malformations v3.39 EVL Achchuthan Shanmugasundram Phenotypes for gene: EVL were changed from Moyamoya Disease to Moyamoya disease, MONDO:0016820
Cerebral vascular malformations v3.38 EVL Achchuthan Shanmugasundram reviewed gene: EVL: Rating: RED; Mode of pathogenicity: None; Publications: 34125151; Phenotypes: Moyamoya disease, MONDO:0016820; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.42 ACTN2 Achchuthan Shanmugasundram Publications for gene: ACTN2 were set to 30900782; 34170073; 34386585; 34471957; 36116040
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.41 ACTN2 Achchuthan Shanmugasundram Tag Q2_25_ MOI tag was added to gene: ACTN2.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.41 ACTN2 Achchuthan Shanmugasundram edited their review of gene: ACTN2: Changed publications to: 30900782, 34170073, 34386585, 34471957, 36116040, 3831179; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.41 ACTN2 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: As reviewed by Cassandra Smith, PMID:3831179 reported a different biallelic variant (p.Arg506Gly) in seven patients from five families of Palestinia decent, all presenting with a consistent phenotype of asymmetric, progressive, proximal, and distal lower extremity predominant muscle weakness. This variant is suggested to be a possible founder variant, which was confirmed through haplotype analysis in two families.

The MOI should be updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' as there is sufficient evidence available for the association of biallelic variants with the phenotype.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.41 ACTN2 Achchuthan Shanmugasundram Mode of inheritance for gene: ACTN2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral vascular malformations v3.38 KEL Achchuthan Shanmugasundram Classified gene: KEL as Amber List (moderate evidence)
Cerebral vascular malformations v3.38 KEL Achchuthan Shanmugasundram Gene: kel has been classified as Amber List (Moderate Evidence).
Cerebral vascular malformations v3.37 KEL Achchuthan Shanmugasundram Phenotypes for gene: KEL were changed from Vein of Galen Malformation to vein of Galen aneurysm, MONDO:0015196
Cerebral vascular malformations v3.36 KEL Achchuthan Shanmugasundram reviewed gene: KEL: Rating: AMBER; Mode of pathogenicity: None; Publications: 30578106, 37978175; Phenotypes: vein of Galen aneurysm, MONDO:0015196; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary neuropathy or pain disorder v6.168 HMBS Sarah Leigh Tag Q2_25_expert_review tag was added to gene: HMBS.
Non-acute porphyrias v1.26 HMBS Sarah Leigh Tag Q2_25_ demote_red tag was added to gene: HMBS.
Tag Q2_25_ MOI tag was added to gene: HMBS.
Tag Q2_25_expert_review tag was added to gene: HMBS.
Non-acute porphyrias v1.26 HMBS Sarah Leigh reviewed gene: HMBS: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Likely inborn error of metabolism v7.27 HMBS Sarah Leigh Tag Q2_25_ MOI tag was added to gene: HMBS.
Tag Q2_25_expert_review tag was added to gene: HMBS.
Likely inborn error of metabolism v7.27 HMBS Sarah Leigh reviewed gene: HMBS: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Likely inborn error of metabolism v7.27 HMBS Sarah Leigh Phenotypes for gene: HMBS were changed from Porphyria, acute intermittent, nonerythroid variant, 176000; Acute intermittent porphyria (Acute neuropathic porphyrias); Porphyria, acute intermittent, 176000 to Porphyria, acute intermittent OMIM:176000; acute intermittent porphyria MONDO:0008294; Leukoencephalopathy, porphyria-related OMIM:620711; leukoencephalopathy, porphyria-related, MONDO:0958226; Encephalopathy, porphyria-related, OMIM:620704; encephalopathy, porphyria-related, MONDO:0958224
Likely inborn error of metabolism v7.26 HMBS Sarah Leigh Publications for gene: HMBS were set to 27604308
Cutaneous photosensitivity with a likely genetic cause v3.9 HMBS Sarah Leigh commented on gene: HMBS: Based on review from Sharon Whatley (International Porphyria Network), changed MOI from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Cutaneous photosensitivity with a likely genetic cause v3.9 HMBS Sarah Leigh Deleted their comment
Cutaneous photosensitivity with a likely genetic cause v3.9 HMBS Sarah Leigh Phenotypes for gene: HMBS were changed from Porphyria, acute intermittent, 176000; Acute intermittent porphyria (Acute neuropathic porphyrias); Porphyria, acute intermittent, nonerythroid variant, 176000 to Porphyria, acute intermittent, OMIM:176000; Porphyria, acute intermittent, nonerythroid variant, OMIM:176000; Leukoencephalopathy, porphyria-related OMIM:620711; leukoencephalopathy, porphyria-related, MONDO:0958226; Encephalopathy, porphyria-related, OMIM:620704; encephalopathy, porphyria-related, MONDO:0958224
Cutaneous photosensitivity with a likely genetic cause v3.8 HMBS Sarah Leigh Added comment: Comment on phenotypes: Porphyria, acute intermittent, OMIM:176000;Porphyria, acute intermittent, nonerythroid variant, OMIM:176000;Leukoencephalopathy, porphyria-related OMIM:620711; leukoencephalopathy, porphyria-related, MONDO:0958226; Encephalopathy, porphyria-related, OMIM:620704; encephalopathy, porphyria-related, MONDO:0958224
Cutaneous photosensitivity with a likely genetic cause v3.8 HMBS Sarah Leigh Phenotypes for gene: HMBS were changed from Porphyria, acute intermittent, 176000; Acute intermittent porphyria (Acute neuropathic porphyrias); Porphyria, acute intermittent, nonerythroid variant, 176000 to Porphyria, acute intermittent, 176000; Acute intermittent porphyria (Acute neuropathic porphyrias); Porphyria, acute intermittent, nonerythroid variant, 176000
Cutaneous photosensitivity with a likely genetic cause v3.7 HMBS Sarah Leigh Publications for gene: HMBS were set to
Cutaneous photosensitivity with a likely genetic cause v3.6 HMBS Sarah Leigh Mode of inheritance for gene: HMBS was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.168 HMBS Sarah Leigh Tag Q2_25_ MOI tag was added to gene: HMBS.
Hereditary neuropathy or pain disorder v6.168 HMBS Sarah Leigh edited their review of gene: HMBS: Added comment: Based on review from Sharon Whatley (International Porphyria Network), the mode of inheritance of HMBS should be 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 on this panel - Hereditary neuropathy or pain disorder.; Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder v6.10 HMBS Sarah Leigh Mode of inheritance for gene: HMBS was changed from to BIALLELIC, autosomal or pseudoautosomal
Bilateral congenital or childhood onset cataracts v6.8 HMBS Sarah Leigh Tag Q2_25_ promote_green tag was added to gene: HMBS.
Bilateral congenital or childhood onset cataracts v6.8 HMBS Sarah Leigh reviewed gene: HMBS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Bilateral congenital or childhood onset cataracts v6.8 HMBS Sarah Leigh Phenotypes for gene: HMBS were changed from 620711; 620704 to Leukoencephalopathy, porphyria-related, OMIM: 620711; Encephalopathy, porphyria-related, OMIM: 620704
Bilateral congenital or childhood onset cataracts v6.7 HMBS Sarah Leigh Classified gene: HMBS as Amber List (moderate evidence)
Bilateral congenital or childhood onset cataracts v6.7 HMBS Sarah Leigh Gene: hmbs has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v7.31 HMBS Sarah Leigh Publications for gene: HMBS were set to 27558376; 34089223
Acute intermittent porphyria v1.3 HMBS Sarah Leigh reviewed gene: HMBS: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Acute intermittent porphyria v1.3 HMBS Sarah Leigh Tag Q2_25_ MOI tag was added to gene: HMBS.
Tag Q2_25_expert_review tag was added to gene: HMBS.
Acute intermittent porphyria v1.3 HMBS Sarah Leigh Phenotypes for gene: HMBS were changed from to Porphyria, acute intermittent, nonerythroid variant, OMIM:176000; Porphyria, acute intermittent, OMIM:176000; acute intermittent porphyria, MONDO:0008294; Encephalopathy, porphyria-related, OMIM:620704; encephalopathy, porphyria-related, MONDO:0958224; Leukoencephalopathy, porphyria-related, OMIM: 620711
White matter disorders and cerebral calcification - narrow panel v6.11 HMBS Sarah Leigh Publications for gene: HMBS were set to 27558376; 34089223
Non-acute porphyrias v1.26 HMBS Sarah Leigh Publications for gene: HMBS were set to 27604308; 2511016; 1714233
Non-acute porphyrias v1.25 HMBS Sarah Leigh Phenotypes for gene: HMBS were changed from Porphyria, acute intermittent, nonerythroid variant OMIM:176000; Porphyria, acute intermittent OMIM:176000; acute intermittent porphyria MONDO:0008294 to Porphyria, acute intermittent OMIM:176000; acute intermittent porphyria MONDO:0008294; Leukoencephalopathy, porphyria-related OMIM:620711; leukoencephalopathy, porphyria-related, MONDO:0958226; Encephalopathy, porphyria-related, OMIM:620704; encephalopathy, porphyria-related, MONDO:0958224
Hereditary neuropathy or pain disorder v6.168 HMBS Sarah Leigh Added comment: Comment on publications: Publications suggested by Sharon Whatley (International Porphyria Network): 27539938; 38940544; 35584894; 14262853; 1577472; 15534187; 31153822; 14970743; 34089223; 27558376
Hereditary neuropathy or pain disorder v6.168 HMBS Sarah Leigh Publications for gene: HMBS were set to 27558376; 34089223
Childhood onset hereditary spastic paraplegia v7.14 HMBS Sarah Leigh Phenotypes for gene: HMBS were changed from Leukoencephalopathy, porphyria-related, OMIM:620711; hereditary spastic paraplegia, MONDO:0019064 to Leukoencephalopathy, porphyria-related, OMIM:620711; Encephalopathy, porphyria-related, OMIM:620704
Childhood onset hereditary spastic paraplegia v7.13 HMBS Sarah Leigh Phenotypes for gene: HMBS were changed from Leukoencephalopathy, HP:0002352; hereditary spastic paraplegia, MONDO:0019064 to Leukoencephalopathy, porphyria-related, OMIM:620711; hereditary spastic paraplegia, MONDO:0019064
Childhood onset hereditary spastic paraplegia v7.12 HMBS Sarah Leigh Publications for gene: HMBS were set to 27558376; 34089223
Childhood onset dystonia, chorea or related movement disorder v6.9 HMBS Sarah Leigh Publications for gene: HMBS were set to
Acute intermittent porphyria v1.2 HMBS Sarah Leigh Publications for gene: HMBS were set to
Fetal anomalies v5.96 GPKOW Sarah Leigh reviewed gene: GPKOW: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Fetal anomalies v5.96 GPKOW Sarah Leigh Phenotypes for gene: GPKOW were changed from male-lethal microcephaly with intrauterine growth restriction to microcephaly with intrauterine growth restriction
Fetal anomalies v5.95 GPKOW Sarah Leigh Tag Q2_25_ promote_green tag was added to gene: GPKOW.
Fetal anomalies v5.95 GPKOW Sarah Leigh Mode of inheritance for gene: GPKOW was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Fetal anomalies v5.94 GPKOW Sarah Leigh Publications for gene: GPKOW were set to 28612833
Familial breast cancer v1.20 BARD1 Terri McVeigh reviewed gene: BARD1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33471991; Phenotypes: breast cancer; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
GI tract tumours v1.22 MBD4 Terri McVeigh reviewed gene: MBD4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35460607, PMID: 30049810, PMID: 35381620, PMID: 32421892, PMID: 32239153; Phenotypes: MBD4-Associated Neoplasia Syndrome: Colonic polyposis, colon cancer, uveal melanoma, acute myeloid leukaemia, schwannoma; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary ataxia v1.342 RAB3A Sarah Leigh Classified gene: RAB3A as Green List (high evidence)
Hereditary ataxia v1.342 RAB3A Sarah Leigh Gene: rab3a has been classified as Green List (High Evidence).
Hereditary ataxia v1.341 RAB3A Sarah Leigh edited their review of gene: RAB3A: Added comment: Hengel et al (PMID: 40166812) report six heterozygous RAB3A variants which appear to be associated with a condition that includes cerebellar ataxia; pyramidal features; neurodevelopmental delay. Five of the variants were only seen in one family each, while (NM_002866.5) c.247C>T (p.Arg83Trp) was seen in 14 members from nine families. The age of onset of phenotypic features ranged from 3 months to adulthood. The authors also present supportive functional studies.; Changed rating: GREEN
Ataxia and cerebellar anomalies - narrow panel v7.30 RAB3A Sarah Leigh Tag Q2_25_ promote_green tag was added to gene: RAB3A.
Tag Q2_25_ NHS_review tag was added to gene: RAB3A.
Ataxia and cerebellar anomalies - narrow panel v7.30 RAB3A Sarah Leigh edited their review of gene: RAB3A: Added comment: Hengel et al (PMID: 40166812) report six heterozygous RAB3A variants which appear to be associated with a condition that includes cerebellar ataxia; pyramidal features; neurodevelopmental delay. Five of the variants were only seen in one family each, while (NM_002866.5) c.247C>T (p.Arg83Trp) was seen in 14 members from nine families. The age of onset of phenotypic features ranged from 3 months to adulthood. The authors also present supportive functional studies.; Changed rating: GREEN
Ataxia and cerebellar anomalies - narrow panel v7.30 RAB3A Sarah Leigh Entity copied from Hereditary ataxia v1.341
Ataxia and cerebellar anomalies - narrow panel v7.30 RAB3A Sarah Leigh gene: RAB3A was added
gene: RAB3A was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Amber,Research
Mode of inheritance for gene: RAB3A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAB3A were set to 36928819; 40166812
Phenotypes for gene: RAB3A were set to RAB3A associated cerebellar ataxia; pyramidal features; neurodevelopmental delay
Penetrance for gene: RAB3A were set to Complete
Hereditary ataxia v1.341 RAB3A Sarah Leigh Classified gene: RAB3A as Amber List (moderate evidence)
Hereditary ataxia v1.341 RAB3A Sarah Leigh Gene: rab3a has been classified as Amber List (Moderate Evidence).
Hereditary ataxia v1.340 RAB3A Sarah Leigh Added comment: Comment on phenotypes: RAB3A variants have not yet been associated with a phenotype in OMIM
Hereditary ataxia v1.340 RAB3A Sarah Leigh Phenotypes for gene: RAB3A were changed from cerebellar ataxia; pyramidal features; neurodevelopmental delay to RAB3A associated cerebellar ataxia; pyramidal features; neurodevelopmental delay
Hereditary ataxia v1.339 RAB3A Sarah Leigh Publications for gene: RAB3A were set to PMID:36928819; 40166812
Adult onset neurodegenerative disorder v7.24 CACNA1A_CAG Sarah Leigh Tag watchlist was removed from STR: CACNA1A_CAG.
Tag Q2_25_ promote_green tag was added to STR: CACNA1A_CAG.
Childhood onset hereditary spastic paraplegia v7.11 CACNA1A_CAG Sarah Leigh reviewed STR: CACNA1A_CAG: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Adult onset neurodegenerative disorder v7.24 CACNA1A_CAG Sarah Leigh Phenotypes for STR: CACNA1A_CAG were changed from Spinocerebellar ataxia 6, OMIM:183086 to Spinocerebellar ataxia 6, OMIM:183086; spinocerebellar ataxia type 6, MONDO:0008457
Childhood onset hereditary spastic paraplegia v7.11 CACNA1A_CAG Sarah Leigh Publications for STR: CACNA1A_CAG were set to
Adult onset neurodegenerative disorder v7.23 CACNA1A_CAG Sarah Leigh Publications for STR: CACNA1A_CAG were set to
Adult onset neurodegenerative disorder v7.22 CACNA1A_CAG Sarah Leigh changed review comment from: There are numerous reports of CACNA1A_CAG repeat expansions in cases of Spinocerebellar ataxia 6 (OMIM: 183086)(PMID: 18285829;19817876;16595610;8988170). The age of onset of OMIM: 183086 is typically 20-65 years.; to: There are numerous reports of CACNA1A_CAG repeat expansions in cases of Spinocerebellar ataxia 6 (OMIM: 183086)(PMID: 18285829;19817876;16595610;8988170). The age of onset of OMIM: 183086 is typically 20-65 years (PMID: 9311738).
Adult onset neurodegenerative disorder v7.22 CACNA1A_CAG Sarah Leigh reviewed STR: CACNA1A_CAG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Ataxia and cerebellar anomalies - narrow panel v7.29 CACNA1A_CAG Sarah Leigh Tag watchlist was removed from STR: CACNA1A_CAG.
Tag Q2_25_ promote_green tag was added to STR: CACNA1A_CAG.
Ataxia and cerebellar anomalies - narrow panel v7.29 CACNA1A_CAG Sarah Leigh reviewed STR: CACNA1A_CAG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Ataxia and cerebellar anomalies - narrow panel v7.29 CACNA1A_CAG Sarah Leigh Phenotypes for STR: CACNA1A_CAG were changed from Spinocerebellar ataxia 6, OMIM:183086 to Spinocerebellar ataxia 6, OMIM:183086; spinocerebellar ataxia type 6, MONDO:0008457
Ataxia and cerebellar anomalies - narrow panel v7.28 CACNA1A_CAG Sarah Leigh Publications for STR: CACNA1A_CAG were set to
Early onset dystonia v1.149 ATXN10_ATTCT Sarah Leigh Tag curated_removed was removed from STR: ATXN10_ATTCT.
Thoracic dystrophies v1.21 ATXN10_ATTCT Sarah Leigh Tag curated_removed was removed from STR: ATXN10_ATTCT.
Thoracic dystrophies v1.21 ATXN10_ATTCT Sarah Leigh reviewed STR: ATXN10_ATTCT: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Thoracic dystrophies v1.21 ATXN10_ATTCT Sarah Leigh Classified STR: ATXN10_ATTCT as Red List (low evidence)
Thoracic dystrophies v1.21 ATXN10_ATTCT Sarah Leigh Str: atxn10_attct has been classified as Red List (Low Evidence).
Early onset dystonia v1.149 ATXN10_ATTCT Sarah Leigh Classified STR: ATXN10_ATTCT as Red List (low evidence)
Early onset dystonia v1.149 ATXN10_ATTCT Sarah Leigh Str: atxn10_attct has been classified as Red List (Low Evidence).
Early onset dystonia v1.148 ATXN10_ATTCT Sarah Leigh reviewed STR: ATXN10_ATTCT: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v8.243 ATXN10_ATTCT Sarah Leigh Classified STR: ATXN10_ATTCT as Amber List (moderate evidence)
Intellectual disability v8.243 ATXN10_ATTCT Sarah Leigh Str: atxn10_attct has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.242 ATXN10_ATTCT Sarah Leigh reviewed STR: ATXN10_ATTCT: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v8.242 ATXN10_ATTCT Sarah Leigh Tag curated_removed was removed from STR: ATXN10_ATTCT.
Early onset or syndromic epilepsy v7.90 RNU4-2 Hayley Lees reviewed gene: RNU4-2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v8.242 RNU4-2 Hayley Lees reviewed gene: RNU4-2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v7.10 ATXN10_ATTCT Sarah Leigh Tag Q2_25_ promote_green tag was added to STR: ATXN10_ATTCT.
Adult onset neurodegenerative disorder v7.22 ATXN10_ATTCT Sarah Leigh Tag watchlist was removed from STR: ATXN10_ATTCT.
Tag Q2_25_ promote_green tag was added to STR: ATXN10_ATTCT.
Childhood onset hereditary spastic paraplegia v7.10 ATXN10_ATTCT Sarah Leigh edited their review of STR: ATXN10_ATTCT: Changed rating: GREEN
Childhood onset hereditary spastic paraplegia v7.10 ATXN10_ATTCT Sarah Leigh reviewed STR: ATXN10_ATTCT: Rating: ; Mode of pathogenicity: None; Publications: 17420323, 15505178; Phenotypes: ; Mode of inheritance: None
Adult onset neurodegenerative disorder v7.22 ATXN10_ATTCT Sarah Leigh reviewed STR: ATXN10_ATTCT: Rating: GREEN; Mode of pathogenicity: None; Publications: 17420323, 15505178; Phenotypes: ; Mode of inheritance: None
Adult onset neurodegenerative disorder v7.22 ATXN10_ATTCT Sarah Leigh Publications for STR: ATXN10_ATTCT were set to 12164725; 35441258; 36199580; 40067487
Ataxia and cerebellar anomalies - narrow panel v7.27 ATXN10_ATTCT Sarah Leigh Tag watchlist was removed from STR: ATXN10_ATTCT.
Tag Q2_25_ promote_green tag was added to STR: ATXN10_ATTCT.
Ataxia and cerebellar anomalies - narrow panel v7.27 ATXN10_ATTCT Sarah Leigh reviewed STR: ATXN10_ATTCT: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Skeletal dysplasia v7.42 ATXN10_ATTCT Sarah Leigh Classified STR: ATXN10_ATTCT as Red List (low evidence)
Skeletal dysplasia v7.42 ATXN10_ATTCT Sarah Leigh Str: atxn10_attct has been classified as Red List (Low Evidence).
Skeletal dysplasia v7.41 ATXN10_ATTCT Sarah Leigh Tag curated_removed was removed from STR: ATXN10_ATTCT.
Skeletal dysplasia v7.41 ATXN10_ATTCT Sarah Leigh reviewed STR: ATXN10_ATTCT: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Skeletal dysplasia v7.41 ATXN10_ATTCT Sarah Leigh Phenotypes for STR: ATXN10_ATTCT were changed from Spinocerebellar ataxia 10, OMIM:603516 to Spinocerebellar ataxia 10, OMIM:603516; spinocerebellar ataxia type 10, MONDO:0011330
Skeletal dysplasia v7.40 ATXN10_ATTCT Sarah Leigh Publications for STR: ATXN10_ATTCT were set to 12164725
Adult onset neurodegenerative disorder v7.21 ATXN10_ATTCT Sarah Leigh Phenotypes for STR: ATXN10_ATTCT were changed from Spinocerebellar ataxia 10, OMIM:603516 to Spinocerebellar ataxia 10, OMIM:603516; spinocerebellar ataxia type 10, MONDO:0011330
Childhood onset hereditary spastic paraplegia v7.10 ATXN10_ATTCT Sarah Leigh Phenotypes for STR: ATXN10_ATTCT were changed from Spinocerebellar ataxia 10, OMIM:603516 to Spinocerebellar ataxia 10, OMIM:603516; spinocerebellar ataxia type 10, MONDO:0011330
Adult onset neurodegenerative disorder v7.20 ATXN10_ATTCT Sarah Leigh Publications for STR: ATXN10_ATTCT were set to
Childhood onset hereditary spastic paraplegia v7.9 ATXN10_ATTCT Sarah Leigh Publications for STR: ATXN10_ATTCT were set to
Ataxia and cerebellar anomalies - narrow panel v7.27 ATXN10_ATTCT Sarah Leigh Phenotypes for STR: ATXN10_ATTCT were changed from Spinocerebellar ataxia 10, OMIM:603516 to Spinocerebellar ataxia 10, OMIM:603516; spinocerebellar ataxia type 10, MONDO:0011330
Ataxia and cerebellar anomalies - narrow panel v7.26 ATXN10_ATTCT Sarah Leigh Publications for STR: ATXN10_ATTCT were set to 12164725
Hypertrophic cardiomyopathy v4.21 ALPK3 Riyaad Aungraheeta reviewed gene: ALPK3: Rating: GREEN; Mode of pathogenicity: None; Publications: 40255155; Phenotypes: Hypertrophic cardiomyopathy; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Cerebral vascular malformations v3.36 NOS3 Achchuthan Shanmugasundram Classified gene: NOS3 as Amber List (moderate evidence)
Cerebral vascular malformations v3.36 NOS3 Achchuthan Shanmugasundram Gene: nos3 has been classified as Amber List (Moderate Evidence).
Cerebral vascular malformations v3.35 NOS3 Achchuthan Shanmugasundram Tag watchlist tag was added to gene: NOS3.
Cerebral vascular malformations v3.35 NOS3 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: As reviewed by Alexandra Njegic, there are two unrelated cases and some functional evidence available for the association of biallelic variants with MMA. However, there is only one case with monoallelic NOS3 variant. The pathogenicity of this monoallelic variant was not explored in detail in the publication.

Hence, the gene should be rated amber and the MOI should be set to BIALLELIC.

The 'watchlist' tag has been added to review this gene in light of new evidence.
Cerebral vascular malformations v3.35 NOS3 Achchuthan Shanmugasundram Mode of inheritance for gene: NOS3 was changed from Other to BIALLELIC, autosomal or pseudoautosomal
Cerebral vascular malformations v3.34 NOS3 Achchuthan Shanmugasundram Publications for gene: NOS3 were set to 37383439; 36941667
Cerebral vascular malformations v3.33 NOS3 Achchuthan Shanmugasundram Phenotypes for gene: NOS3 were changed from Moyamoya Disease; Moyamoya Angiopathy to Moyamoya disease, MONDO:0016820
Cerebral vascular malformations v3.32 NOS3 Achchuthan Shanmugasundram reviewed gene: NOS3: Rating: AMBER; Mode of pathogenicity: None; Publications: 36941667, 37383439; Phenotypes: Moyamoya disease, MONDO:0016820; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.167 RCC1 Lauren Turton gene: RCC1 was added
gene: RCC1 was added to Hereditary neuropathy or pain disorder. Sources: NHS GMS
Mode of inheritance for gene: RCC1 was set to BIALLELIC, autosomal or pseudoautosomal
Review for gene: RCC1 was set to AMBER
Added comment: Present in medrxiv, https://www.medrxiv.org/content/10.1101/2024.10.04.24314535v1. As not formally published left as amber rating.
24 individuals from 12 families with acute onset axonal neuropathy. Very severe disease in acutely unwell children. Neurological presentation was secondary to infection.
Sources: NHS GMS
Structural eye disease v4.8 ARR3 Sarah Leigh changed review comment from: Six ARR3 variant have been seen in seven unrelated families with Myopia 26, X-linked, female-limited, OMIM:301010. The inheritance of the causative ARR3 variants is X‐linked female limited, in that only the female carriers of the variant display the phenotype - OMIM:301010 (PMID: 35001458;33482870;27829781).; to: Six ARR3 variants have been seen in seven unrelated families with Myopia 26, X-linked, female-limited (OMIM:301010). The inheritance of the causative ARR3 variants is X‐linked female limited, in that only the female carriers of the variant display the phenotype - OMIM:301010 (PMID: 35001458;33482870;27829781).
Cerebral vascular malformations v3.32 CBL Achchuthan Shanmugasundram Phenotypes for gene: CBL were changed from early-onset moyamoya angiopathy; moyamoya disease, MONDO:0016820; Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia, OMIM:613563 to cerebral arterial disease, MONDO:0006693; Moyamoya disease, MONDO:0016820; early-onset moyamoya angiopathy; Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia, OMIM:613563
Cerebral vascular malformations v3.31 CBL Achchuthan Shanmugasundram Publications for gene: CBL were set to 28343148; 25283271; 28589114
Cerebral vascular malformations v3.30 CBL Achchuthan Shanmugasundram Mode of inheritance for gene: CBL was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral vascular malformations v3.29 CBL Achchuthan Shanmugasundram Tag Q2_25_ promote_green tag was added to gene: CBL.
Tag Q2_25_expert_review tag was added to gene: CBL.
Tag Q2_25_ NHS_review tag was added to gene: CBL.
Cerebral vascular malformations v3.29 CBL Achchuthan Shanmugasundram Classified gene: CBL as Amber List (moderate evidence)
Cerebral vascular malformations v3.29 CBL Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Alexandra Njegic, there are five patients from three unrelated families reported with three different CBL variants and cerebral arteriopathy in PMID:32637631, and one patient was reported with the previously identified de novo splice variant in CBL gene in PMID:37778001. The patient from PMID:37778001 also had a maternally inherited VUS variant in RNF213 gene. This is also some functional evidence available.

There is sufficient evidence available for the promotion of this gene to green rating in the next GMS update. However, it has been tagged for expert review from the GMS.
Cerebral vascular malformations v3.29 CBL Achchuthan Shanmugasundram Gene: cbl has been classified as Amber List (Moderate Evidence).
Cerebral vascular malformations v3.28 CBL Achchuthan Shanmugasundram reviewed gene: CBL: Rating: GREEN; Mode of pathogenicity: None; Publications: 32637631, 37778001; Phenotypes: cerebral arterial disease, MONDO:0006693, Moyamoya disease, MONDO:0016820; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral vascular malformations v3.28 FOXM1 Achchuthan Shanmugasundram Classified gene: FOXM1 as Amber List (moderate evidence)
Cerebral vascular malformations v3.28 FOXM1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Alexandra Njegic, PMID:38969938 reported a 60-year-old father and 31-year-old daughter with unilateral Moyamoya Disease and with c.1205 C > A variant in FOXM1 gene (p.(Ala402Glu). There is also functional evidence available for the identified variant from the publication.

This gene should be rated amber with current evidence.
Cerebral vascular malformations v3.28 FOXM1 Achchuthan Shanmugasundram Gene: foxm1 has been classified as Amber List (Moderate Evidence).
Cerebral vascular malformations v3.27 FOXM1 Achchuthan Shanmugasundram Phenotypes for gene: FOXM1 were changed from Moyamoya Disease (Unilateral) to Moyamoya disease, MONDO:0016820
Cerebral vascular malformations v3.26 FOXM1 Achchuthan Shanmugasundram edited their review of gene: FOXM1: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Cerebral vascular malformations v3.26 FOXM1 Achchuthan Shanmugasundram reviewed gene: FOXM1: Rating: AMBER; Mode of pathogenicity: None; Publications: 38969938; Phenotypes: Moyamoya disease, MONDO:0016820; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal ciliopathies v3.20 DLG5 Sarah Leigh Tag Q2_25_ MOI tag was added to gene: DLG5.
Tag Q2_25_expert_review tag was added to gene: DLG5.
Tag Q2_25_ NHS_review tag was added to gene: DLG5.
Renal ciliopathies v3.20 DLG5 Sarah Leigh edited their review of gene: DLG5: Added comment: With reference to the review of the published evidence by Tracy Lester (Genetics laboratory, Oxford UK), a change of mode of inheritance is suggested from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal. Four biallelic DLG5 variants have been reported in three unrelated cases (PMID: 30791088, 32631816). Three monoallelic DLG5 variants have been reported (PMID: 32631816, 35361250). The de novo variant c.745C>T(p.Arg249Trp) is present in 9 heterozygotes and 1 homozygote in gnomad v4.1, while the phenotype is mild for the heterozygous carriers of c.4526AG>TT (p.Gln1509Leu)(PMID: 32631816). A further monoallelic DLG5 variant was reported in a case with Müllerian agenesis (PMID: 35361250).; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal ciliopathies v3.20 DLG5 Sarah Leigh Publications for gene: DLG5 were set to 32631816; 30791088; 17765678
Renal ciliopathies v3.19 DLG5 Sarah Leigh Publications for gene: DLG5 were set to 32631816; 17765678
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.40 JAG2 Lauren Turton changed review comment from: This gene is currently green on the R79 congenital muscular dystrophy panel.
PMID: 33861953 initial paper on this gene. 23 patients from 13 unrelated families.
PMID: 39121631 three additional patients who presented with childhood onset limb girdle myopathy.
PMID: 39649397 two additional patients presenting with childhood onset muscle hypotonia predominatly affecting the pelvic girdle and proximal leg muscles.
Sources: NHS GMS; to: This gene is currently green on the R79 congenital muscular dystrophy panel.
PMID: 33861953 initial paper on this gene. 23 patients from 13 unrelated families.
PMID: 39121631 three additional patients who presented with childhood onset limb girdle myopathy.
PMID: 39649397 two additional patients presenting with childhood onset muscle hypotonia predominantly affecting the pelvic girdle and proximal leg muscles.
Sources: NHS GMS
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.40 JAG2 Lauren Turton gene: JAG2 was added
gene: JAG2 was added to Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies. Sources: NHS GMS
Mode of inheritance for gene: JAG2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: JAG2 were set to 33861953; 39121631; 39649397
Phenotypes for gene: JAG2 were set to Limb-girdle muscular dystrophy-27 (OMIM: 619566)
Review for gene: JAG2 was set to GREEN
gene: JAG2 was marked as current diagnostic
Added comment: This gene is currently green on the R79 congenital muscular dystrophy panel.
PMID: 33861953 initial paper on this gene. 23 patients from 13 unrelated families.
PMID: 39121631 three additional patients who presented with childhood onset limb girdle myopathy.
PMID: 39649397 two additional patients presenting with childhood onset muscle hypotonia predominatly affecting the pelvic girdle and proximal leg muscles.
Sources: NHS GMS
Structural eye disease v4.8 ARR3 Sarah Leigh Tag Q2_25_ promote_green tag was added to gene: ARR3.
Structural eye disease v4.8 ARR3 Sarah Leigh Added comment: Comment on mode of inheritance: X‐linked female limited
Structural eye disease v4.8 ARR3 Sarah Leigh Mode of inheritance for gene: ARR3 was changed from Other to Other
Structural eye disease v4.7 ARR3 Sarah Leigh reviewed gene: ARR3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: Other
Structural eye disease v4.7 ARR3 Sarah Leigh Publications for gene: ARR3 were set to 35001458
Structural eye disease v4.6 ARR3 Sarah Leigh Phenotypes for gene: ARR3 were changed from to Myopia 26, X-linked, female-limited, OMIM:301010; myopia 26, X-linked, female-limited, MONDO:0049221
Structural eye disease v4.5 ARR3 Sarah Leigh Classified gene: ARR3 as Amber List (moderate evidence)
Structural eye disease v4.5 ARR3 Sarah Leigh Gene: arr3 has been classified as Amber List (Moderate Evidence).
Laterality disorders and isomerism v3.22 AL117258.1 Achchuthan Shanmugasundram commented on gene: AL117258.1: The 'new-gene-name' tag has been added as the HGNC approved symbol for this gene is CIROP. This gene was known by the previous symbol LMLN2.
Laterality disorders and isomerism v3.22 AL117258.1 Achchuthan Shanmugasundram Tag new-gene-name tag was added to gene: AL117258.1.
Tag gene-checked tag was added to gene: AL117258.1.
Primary immunodeficiency or monogenic inflammatory bowel disease v7.27 C2 Sarah Leigh Tag Q2_25_ MOI tag was added to gene: C2.
Tag Q2_25_expert_review tag was added to gene: C2.
Primary immunodeficiency or monogenic inflammatory bowel disease v7.27 C2 Sarah Leigh reviewed gene: C2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: C2 deficiency, OMIM:217000, complement component 2 deficiency, MONDO:0009006; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v7.27 C2 Sarah Leigh Publications for gene: C2 were set to 1577763; 8621452; 11079100; 15643297; 7901282
Likely inborn error of metabolism v7.25 IDH1 Sarah Leigh edited their review of gene: IDH1: Added comment: Numerous reports of IDH1 variants associated with OMIM:614875, OMIM:614569 and OMIM:166000 (PMID: 24049096; 22025298; 22057234; 22057236).; Changed rating: GREEN
Mitochondrial disorders v8.31 IDH1 Sarah Leigh edited their review of gene: IDH1: Added comment: Numerous reports of IDH1 variants associated with OMIM:614875, OMIM:614569 and OMIM:166000 (PMID: 24049096; 22025298; 22057234; 22057236).; Changed rating: GREEN
Likely inborn error of metabolism v7.25 IDH1 Sarah Leigh Tag mosaicism tag was added to gene: IDH1.
Tag Q2_25_ promote_green tag was added to gene: IDH1.
Mitochondrial disorders v8.31 IDH1 Sarah Leigh Tag mosaicism tag was added to gene: IDH1.
Tag Q2_25_ promote_green tag was added to gene: IDH1.
Likely inborn error of metabolism v7.25 IDH1 Sarah Leigh Classified gene: IDH1 as Amber List (moderate evidence)
Likely inborn error of metabolism v7.25 IDH1 Sarah Leigh Added comment: Comment on list classification: Somatic variants relevant to this gene, potentially resulting in mosaicism
Likely inborn error of metabolism v7.25 IDH1 Sarah Leigh Gene: idh1 has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v8.31 IDH1 Sarah Leigh Classified gene: IDH1 as Amber List (moderate evidence)
Mitochondrial disorders v8.31 IDH1 Sarah Leigh Added comment: Comment on list classification: Somatic variants relevant to this gene, potentially resulting in mosaicism
Mitochondrial disorders v8.31 IDH1 Sarah Leigh Gene: idh1 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v7.24 IDH1 Sarah Leigh Publications for gene: IDH1 were set to 33340416
Mitochondrial disorders v8.30 IDH1 Sarah Leigh Publications for gene: IDH1 were set to 24049096 22025298 22057234 22057236; 33340416
Mitochondrial disorders v8.29 IDH1 Sarah Leigh Added comment: Comment on mode of pathogenicity: Gain of function variants associated with Maffucci syndrome and Ollier disease (PMID: 22057234)
Mitochondrial disorders v8.29 IDH1 Sarah Leigh Mode of pathogenicity for gene: IDH1 was changed from None to None
Likely inborn error of metabolism v7.23 IDH1 Sarah Leigh Added comment: Comment on mode of inheritance: Somatic variants thought to occur early in development, resulting in mosaicism
Likely inborn error of metabolism v7.23 IDH1 Sarah Leigh Mode of inheritance for gene: IDH1 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mitochondrial disorders v8.28 IDH1 Sarah Leigh Added comment: Comment on mode of inheritance: Somatic variants thought to occur early in development, resulting in mosaicism
Mitochondrial disorders v8.28 IDH1 Sarah Leigh Mode of inheritance for gene: IDH1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Likely inborn error of metabolism v7.22 IDH1 Sarah Leigh Phenotypes for gene: IDH1 were changed from Failure to thrive; Psychomotor delay; Feeding difficulties; Increased D-2-Hydroxyglutaric acid in urine to Metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria OMIM:614875; metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria, MONDO:0013941; Maffucci syndrome, OMIM:614569; Maffucci syndrome, MONDO:0013808; Ollier disease/ Dyschondroplasia, OMIM:166000; Ollier disease, MONDO:0008145
Mitochondrial disorders v8.27 IDH1 Sarah Leigh Phenotypes for gene: IDH1 were changed from Metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria to Metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria OMIM:614875; metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria, MONDO:0013941; Maffucci syndrome, OMIM:614569; Maffucci syndrome, MONDO:0013808; Ollier disease/ Dyschondroplasia, OMIM:166000; Ollier disease, MONDO:0008145
Skeletal dysplasia v7.39 IDH1 Sarah Leigh Phenotypes for gene: IDH1 were changed from Metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria 614875; Maffucci syndrome 614569; Ollier disease/ Dyschondroplasia 166000 to Metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria OMIM:614875; metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria, MONDO:0013941; Maffucci syndrome, OMIM:614569; Maffucci syndrome, MONDO:0013808; Ollier disease/ Dyschondroplasia, OMIM:166000; Ollier disease, MONDO:0008145
Mitochondrial disorders v8.26 IDH1 Sarah Leigh Publications for gene: IDH1 were set to 33340416
Mitochondrial disorders v8.25 SLC13A5 Sarah Leigh Classified gene: SLC13A5 as Red List (low evidence)
Mitochondrial disorders v8.25 SLC13A5 Sarah Leigh Gene: slc13a5 has been classified as Red List (Low Evidence).
Mitochondrial disorders v8.24 SLC13A5 Sarah Leigh reviewed gene: SLC13A5: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
White matter disorders and cerebral calcification - narrow panel v6.10 CMPK2 Sarah Leigh Entity copied from Mitochondrial disorders v8.24
White matter disorders and cerebral calcification - narrow panel v6.10 CMPK2 Sarah Leigh gene: CMPK2 was added
gene: CMPK2 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Literature,Expert Review Amber
Q2_25_ promote_green tags were added to gene: CMPK2.
Mode of inheritance for gene: CMPK2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CMPK2 were set to 33340416; 36443312
Phenotypes for gene: CMPK2 were set to Mitochondrial UMP-CMP kinase 2 deficiency; Developmental delay; Failure to thrive
Mitochondrial disorders v8.24 CMPK2 Sarah Leigh Tag Q2_25_ promote_green tag was added to gene: CMPK2.
Mitochondrial disorders v8.24 CMPK2 Sarah Leigh reviewed gene: CMPK2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Basal ganglia calcification, idiopathic, 10, autosomal recessive, OMIM:621018, basal ganglia calcification, idiopathic, 10, autosomal recessive, MONDO:0975875; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v8.24 CMPK2 Sarah Leigh Classified gene: CMPK2 as Amber List (moderate evidence)
Mitochondrial disorders v8.24 CMPK2 Sarah Leigh Gene: cmpk2 has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v8.23 CMPK2 Sarah Leigh Publications for gene: CMPK2 were set to 33340416
Mitochondrial disorders v8.22 CMPK2 Sarah Leigh Publications for gene: CMPK2 were set to PMID: 33340416
Mitochondrial disorders v8.21 ACSL4 Sarah Leigh reviewed gene: ACSL4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mitochondrial disorders v8.21 ACSL4 Sarah Leigh Classified gene: ACSL4 as Red List (low evidence)
Mitochondrial disorders v8.21 ACSL4 Sarah Leigh Gene: acsl4 has been classified as Red List (Low Evidence).
Laterality disorders and isomerism v3.22 AL117258.1 Achchuthan Shanmugasundram Classified gene: AL117258.1 as Amber List (moderate evidence)
Laterality disorders and isomerism v3.22 AL117258.1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (13 unrelated families) for the promotion of this gene to green rating in the next GMS update.
Laterality disorders and isomerism v3.22 AL117258.1 Achchuthan Shanmugasundram Gene: al117258.1 has been classified as Amber List (Moderate Evidence).
Laterality disorders and isomerism v3.21 AL117258.1 Achchuthan Shanmugasundram Tag Q2_25_ promote_green tag was added to gene: AL117258.1.
Laterality disorders and isomerism v3.21 AL117258.1 Achchuthan Shanmugasundram gene: AL117258.1 was added
gene: AL117258.1 was added to Laterality disorders and isomerism. Sources: Literature
Mode of inheritance for gene: AL117258.1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AL117258.1 were set to 34903892; 39513328
Phenotypes for gene: AL117258.1 were set to Heterotaxy, visceral, 12, autosomal, OMIM:619702
Review for gene: AL117258.1 was set to GREEN
Added comment: PMID:34903892 reported the identification of biallelic variants (either homozygous or compound heterozygous ) in the CIROP gene in 21 patients from 12 unrelated families of different geographic origin with congenital heterotaxy. There were a total of nine variants identified in these patients - 5 missense, 2 nonsense, a frameshift, and a small in-frame deletion. The disorder is characterised by defects in the asymmetric positioning of visceral organs across the left-right axis, known as laterality defects. Functional studies performed on Zebrafish and Xenopus knockout models replicated the heterotaxy phenotype. They also showed that CIROP was essential for left side symmetry and is expressed in ciliated left–right organisers.

PMID:39513328 reported a cohort of 24 patients with heterotaxy from 19 unrelated families, of which two patients from a family were identified with homozygous missense CIROP variant.

This gene has been associated with relevant phenotypes in OMIM (MIM #619702), but not in Gene2Phenotype.
Sources: Literature
Hereditary ataxia with onset in adulthood v7.20 DAB1_ATTTC Sarah Leigh Tag nested STR was removed from STR: DAB1_ATTTC.
Undiagnosed metabolic disorders v1.628 GLS_GCA Sarah Leigh Entity copied from Likely inborn error of metabolism v7.21
Undiagnosed metabolic disorders v1.628 GLS_GCA Sarah Leigh STR: GLS_GCA was added
STR: GLS_GCA was added to Undiagnosed metabolic disorders. Sources: Expert Review Red,Literature
STR, NGS Not Validated tags were added to STR: GLS_GCA.
Mode of inheritance for STR: GLS_GCA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for STR: GLS_GCA were set to 30970188
Phenotypes for STR: GLS_GCA were set to Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412
Hereditary ataxia with onset in adulthood v7.20 ATXN8OS_CTG Sarah Leigh commented on STR: ATXN8OS_CTG: The numbers of ATXN8OS_CTG required for pathogenicity given by https://stripy.org/database are: 2-37 for normal, 38-79 for intermediate and ≥80 for pathogenic and https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r4 gives the repeats as follows: ≤ 50 for normal, 38 - 79 for intermediate and ≥ 71 for pathogenic.
Hereditary ataxia with onset in adulthood v7.20 ATXN8OS_CTG Sarah Leigh STR: ATXN8OS_CTG was added
STR: ATXN8OS_CTG was added to Hereditary ataxia with onset in adulthood. Sources: Literature
STR, NGS Not Validated tags were added to STR: ATXN8OS_CTG.
Mode of inheritance for STR: ATXN8OS_CTG was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for STR: ATXN8OS_CTG were set to 16804541; 10192387
Phenotypes for STR: ATXN8OS_CTG were set to Spinocerebellar ataxia 8, OMIM:608768; spinocerebellar ataxia type 8, MONDO:0012116
Review for STR: ATXN8OS_CTG was set to GREEN
Added comment: ATXN8OS transcribed from the forward strand.

ATXN8OS_CTG is on https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r4

ATXN8OS_CTG is on https://stripy.org/database

ATXN8OS_CTG is on DRAGON 4.02.

The coordinates of the sequence repeats shown above were obtained from DRAGON 4.02, https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r4 and https://stripy.org/database were 4:39348424-39348485 (hg38)
The non-pathogenic and pathogenic ranges of the sequence repeats shown above were obtained from: https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r4

There is enough evidence for this STR to be green on this panel.

This STR has not been approved by NHS STR working group and is not NGS Not Validated
Sources: Literature
Hereditary ataxia with onset in adulthood v7.19 RFC1_AAGGG Sarah Leigh Publications for STR: RFC1_AAGGG were set to 30926972; 35883251; 36250766; 36289003; 36524104; 36478048
Hereditary ataxia with onset in adulthood v7.18 RFC1_AAGGG Sarah Leigh edited their review of STR: RFC1_AAGGG: Added comment: Pathogenicity at the RFC1_AAGGG repeat locus can result from the biallelic replacement of the benign AAAAG repeat with a variable number of AAGGG repeats (PMID: 30926972; 32040566). Furthermore, biallelic expansions of (AAAAG)exp/(AAAGG)exp, (AAAAG)exp/(AAGGG)exp or (AAAGG)exp/(AAGGG)exp were not pathogenic, therefore, it is the biallelic expansions of AAGGG that is pathogenic (PMID: 30926972). An additional pathogenic biallelic expansion :RFC1_ACAGG, was seen in was seen in two Asia-Pacific CANVAS families and a Japanese case (PMID: 33103729, 35355059).; Changed publications to: 30926972, 35883251, 36250766, 36289003, 36524104, 36478048, 32040566, 33103729, 35355059
Hereditary neuropathy or pain disorder v6.167 RFC1_AAGGG Sarah Leigh Publications for STR: RFC1_AAGGG were set to 30926972; 35883251; 36250766; 36289003; 36524104; 36478048
Hereditary neuropathy or pain disorder v6.166 RFC1_AAGGG Sarah Leigh edited their review of STR: RFC1_AAGGG: Added comment: Pathogenicity at the RFC1_AAGGG repeat locus can result from the biallelic replacement of the benign AAAAG repeat with a variable number of AAGGG repeats (PMID: 30926972; 32040566). Furthermore, biallelic expansions of (AAAAG)exp/(AAAGG)exp, (AAAAG)exp/(AAGGG)exp or (AAAGG)exp/(AAGGG)exp were not pathogenic, therefore, it is the biallelic expansions of AAGGG that is pathogenic (PMID: 30926972). An additional pathogenic biallelic expansion :RFC1_ACAGG, was seen in was seen in two Asia-Pacific CANVAS families and a Japanese case (PMID: 33103729, 35355059).; Changed publications to: 30926972, 35883251, 36250766, 36289003, 36524104, 36478048, 32040566, 33103729, 35355059
Hereditary neuropathy or pain disorder v6.166 RFC1_AAGGG Sarah Leigh STR: RFC1_AAGGG was added
STR: RFC1_AAGGG was added to Hereditary neuropathy or pain disorder. Sources: Literature
STR, NGS Not Validated tags were added to STR: RFC1_AAGGG.
Mode of inheritance for STR: RFC1_AAGGG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for STR: RFC1_AAGGG were set to 30926972; 35883251; 36250766; 36289003; 36524104; 36478048
Phenotypes for STR: RFC1_AAGGG were set to Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome, OMIM: 614575
Review for STR: RFC1_AAGGG was set to GREEN
Added comment: RFC1 transcribed from the reverse strand, which means that the repeated sequence is the reverse compliment of the forward strand sequence.

RFC1_AAGGG is on https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r4

RFC1_AAGGG is on https://stripy.org/database

RFC1_AARRG is on DRAGON 4.02.

The coordinates of the sequence repeats shown above were obtained from DRAGON 4.02 and https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r4
The coordinates of the sequence repeats from https://stripy.org/database were 4:39348424-39348485 (hg38)
The non-pathogenic and pathogenic ranges of the sequence repeats shown above were obtained from: https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r4
And https://stripy.org/database

There is enough evidence for this STR to be green on this panel.

This STR has not been approved by NHS STR working group and is not NGS Not Validated
Sources: Literature
Hereditary ataxia with onset in adulthood v7.18 RFC1_AAGGG Sarah Leigh STR: RFC1_AAGGG was added
STR: RFC1_AAGGG was added to Hereditary ataxia with onset in adulthood. Sources: Literature
STR, NGS Not Validated tags were added to STR: RFC1_AAGGG.
Mode of inheritance for STR: RFC1_AAGGG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for STR: RFC1_AAGGG were set to 30926972; 35883251; 36250766; 36289003; 36524104; 36478048
Phenotypes for STR: RFC1_AAGGG were set to Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome, OMIM: 614575
Review for STR: RFC1_AAGGG was set to GREEN
Added comment: RFC1 transcribed from the reverse strand, which means that the repeated sequence is the reverse compliment of the forward strand sequence.

RFC1_AAGGG is on https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r4

RFC1_AAGGG is on https://stripy.org/database

RFC1_AARRG is on DRAGON 4.02.

The coordinates of the sequence repeats shown above were obtained from DRAGON 4.02 and https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r4
The coordinates of the sequence repeats from https://stripy.org/database were 4:39348424-39348485 (hg38)
The non-pathogenic and pathogenic ranges of the sequence repeats shown above were obtained from: https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r4
And https://stripy.org/database

There is enough evidence for this STR to be green on this panel.

This STR has not been approved by NHS STR working group and is not NGS Not Validated
Sources: Literature
Thoracic aortic aneurysm or dissection (GMS) v3.20 SMAD6 Sarah Leigh Tag Q2_25_expert_review tag was added to gene: SMAD6.
Hereditary ataxia with onset in adulthood v7.17 DAB1_ATTTC Sarah Leigh Tag nested STR tag was added to STR: DAB1_ATTTC.
Hereditary ataxia with onset in adulthood v7.17 DAB1_ATTTC Sarah Leigh changed review comment from: This is a Nested STR. Pathogenicity is caused by the inclusion of ATTTC repeat (PMID: 29939198; 28686858) within the reference ATTTT repeat. PMID: 28686858 outlined that the pathogenic confirmation of repeats was: [(ATTTT)60–79(ATTTC)31–75(ATTTT)58–90].; to: This is a Nested STR. Pathogenicity is caused by the inclusion of ATTTC repeat (PMID: 29939198; 28686858) within the reference ATTTT repeat. PMID: 28686858 outlined that the pathogenic confirmation of repeats was: [(ATTTT)60–79(ATTTC)31–75(ATTTT)58–90].
Note that DRAGEN 4.02 lists DAB1_ATTTT and not the ATTTC repeat.
Hereditary ataxia with onset in adulthood v7.17 DAB1_ATTTC Sarah Leigh commented on STR: DAB1_ATTTC: This is a Nested STR. Pathogenicity is caused by the inclusion of ATTTC repeat (PMID: 29939198; 28686858) within the reference ATTTT repeat. PMID: 28686858 outlined that the pathogenic confirmation of repeats was: [(ATTTT)60–79(ATTTC)31–75(ATTTT)58–90].
Cerebral vascular malformations v3.26 CCER2 Alexandra Njegic gene: CCER2 was added
gene: CCER2 was added to Cerebral vascular malformations. Sources: Literature
Mode of inheritance for gene: CCER2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CCER2 were set to 27717682
Phenotypes for gene: CCER2 were set to Moyamoya Disease
Penetrance for gene: CCER2 were set to Incomplete
Mode of pathogenicity for gene: CCER2 was set to Other
Review for gene: CCER2 was set to AMBER
Added comment: 27717682: 2 pedigrees (without RNF213 variants), authors identified a delins and a missense variant (one twin unaffected with same missense variant, suggests reduced penetrance). Additional 135 MMD probands sequenced, identified 1 recurrent and an additional 2 in-frame indels (2 probands had RNF213 p.R4810K, and the other had Graves disease). In silico modelling predicts aggregation or oligomerization of CCER2 protein product; insufficient evidence to suggest LOF or GOF.
Sources: Literature
Hereditary ataxia with onset in adulthood v7.17 DAB1_ATTTC Sarah Leigh STR: DAB1_ATTTC was added
STR: DAB1_ATTTC was added to Hereditary ataxia with onset in adulthood. Sources: Literature
STR, NGS Not Validated tags were added to STR: DAB1_ATTTC.
Mode of inheritance for STR: DAB1_ATTTC was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for STR: DAB1_ATTTC were set to 29939198; 28686858
Phenotypes for STR: DAB1_ATTTC were set to Spinocerebellar ataxia 37, OMIM: 615945
Review for STR: DAB1_ATTTC was set to GREEN
Added comment: DAB1 is transcribed from the reverse strand, which means that the repeated sequence is the reverse compliment of the forward strand sequence.

DAB1_ATTTC is on https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r4

DAB1_ATTTC is on https://stripy.org/database

DAB1_ATTTT is on DRAGON 4.02.

The coordinates of the sequence repeats shown above were the same on:
https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r4 https://stripy.org/database were 8:118366815-118366913 (hg38) and DRAGON 4.02

The non-pathogenic and pathogenic ranges of the sequence repeats shown above were obtained from: https://stripy.org/database

There is enough evidence for this STR to be green on this panel.

This STR has not been approved by NHS STR working group and is not NGS Not Validated
Sources: Literature
Hereditary ataxia with onset in adulthood v7.16 DAB1 Sarah Leigh Phenotypes for gene: DAB1 were changed from Spinocerebellar ataxia 37, 615945; Spinocerebellar ataxia 37 615945 to Spinocerebellar ataxia 37, OMIM: 615945
Cerebral vascular malformations v3.26 SIRT1 Alexandra Njegic gene: SIRT1 was added
gene: SIRT1 was added to Cerebral vascular malformations. Sources: Literature
Mode of inheritance for gene: SIRT1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SIRT1 were set to 30578106
Phenotypes for gene: SIRT1 were set to Vein of Galen Malformation
Penetrance for gene: SIRT1 were set to Incomplete
Review for gene: SIRT1 was set to RED
Added comment: 30578106: 1 family, authors identified 1 de novo frameshift SIRT1 variant in proband, proband also harboured a transmitted CLDN14 variant. Supplementary table suggests relatives have capillary malformations.
Sources: Literature
Thoracic aortic aneurysm or dissection (GMS) v3.20 SMAD6 Sarah Leigh reviewed gene: SMAD6: Rating: RED; Mode of pathogenicity: None; Publications: 39069920, 40133303; Phenotypes: ; Mode of inheritance: None
Fetal anomalies v5.93 SIRT6 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There are four foetuses from a single family and several pieces of functional evidence available in support of the association. This gene is tagged for expert review from the Genomic Laboratory Hubs to decide whether the available evidence is sufficient for promotion to green rating on the next update.; to: Comment on list classification: There are four foetuses from a single family and several pieces of functional evidence available in support of the association. This gene is tagged for expert review from the NHS Genomic Medicine Service to decide whether the available evidence is sufficient for promotion to green rating on the next update.
Fetal anomalies v5.93 SIRT6 Achchuthan Shanmugasundram Classified gene: SIRT6 as Amber List (moderate evidence)
Fetal anomalies v5.93 SIRT6 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are four foetuses from a single family and several pieces of functional evidence available in support of the association. This gene is tagged for expert review from the Genomic Laboratory Hubs to decide whether the available evidence is sufficient for promotion to green rating on the next update.
Fetal anomalies v5.93 SIRT6 Achchuthan Shanmugasundram Gene: sirt6 has been classified as Amber List (Moderate Evidence).
Thoracic aortic aneurysm or dissection (GMS) v3.20 SMAD6 Sarah Leigh Tag Q2_25_ demote_red tag was added to gene: SMAD6.
Tag Q2_25_ NHS_review tag was added to gene: SMAD6.
Thoracic aortic aneurysm or dissection (GMS) v3.20 SMAD6 Sarah Leigh Publications for gene: SMAD6 were set to 30796334; 28659821; 30963242
Fetal anomalies v5.92 SIRT6 Achchuthan Shanmugasundram Tag Q2_25_ promote_green tag was added to gene: SIRT6.
Tag Q2_25_expert_review tag was added to gene: SIRT6.
Fetal anomalies v5.92 SIRT6 Achchuthan Shanmugasundram Phenotypes for gene: SIRT6 were changed from PMID: 29555651 to Fetal anomaly, HP:0034057
Fetal anomalies v5.91 SIRT6 Achchuthan Shanmugasundram Publications for gene: SIRT6 were set to
Fetal anomalies v5.90 SIRT6 Achchuthan Shanmugasundram reviewed gene: SIRT6: Rating: GREEN; Mode of pathogenicity: None; Publications: 29555651, 30135584; Phenotypes: Fetal anomaly, HP:0034057; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral vascular malformations v3.26 ITGB1 Alexandra Njegic gene: ITGB1 was added
gene: ITGB1 was added to Cerebral vascular malformations. Sources: Literature
Mode of inheritance for gene: ITGB1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ITGB1 were set to 37978175
Phenotypes for gene: ITGB1 were set to Vein of Galen Malformation
Penetrance for gene: ITGB1 were set to Incomplete
Review for gene: ITGB1 was set to AMBER
Added comment: 37978175 (including PMID 30578106 cohort): combined 2 probands, 1 unphased frameshift and 1 transmitted splice variant, in silico modelling predicted NMD, pathogenicity given as 'likely damaging'.
Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v7.26 RAP1B Boaz Palterer gene: RAP1B was added
gene: RAP1B was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: RAP1B was set to Other
Publications for gene: RAP1B were set to 39225097
Phenotypes for gene: RAP1B were set to thrombocytopenia; leukopenia; lymphopenia; anemia; splenomegaly; immunodeficiency; preauricular tag; upslanting palpebral fissures; flat midface; scarce eyebrows; low-set and posteriorly rotated ears; hypoplastic teeth; umbilical hernia, and genitourinary abnormalities; hydronephrosis; vesicoureteral reflux; unilateral cryptorchidism
Penetrance for gene: RAP1B were set to unknown
Mode of pathogenicity for gene: RAP1B 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: RAP1B was set to GREEN
Added comment: Heterozygous mutation in RAP1B are associated with Thrombocytopenia 11 with multiple congenital anomalies and dysmorphic facies ( OMIM #620654 ).

Variants have been shown to be gain of function.
Wide spectrum of disease presentation, germline variants associated with full spectrum of disease, reported somatic variants presenting with isolated hematological disease. Varying degree of immunodeficiency, leukopenia and lymphopenia, relevant to this panel.
Sources: Literature
Adult onset leukodystrophy v5.8 CST3 Achchuthan Shanmugasundram Tag Q2_25_ NHS_review tag was added to gene: CST3.
Adult onset neurodegenerative disorder v7.19 CST3 Achchuthan Shanmugasundram Classified gene: CST3 as Amber List (moderate evidence)
Adult onset neurodegenerative disorder v7.19 CST3 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are >3 unrelated cases with Cerebral amyloid angiopathy (MIM #105150), however they were all reported with the same founder variant.

However, there are 18 patients from ten unrelated families with adult-onset leukodystrophy phenotype (not yet reported in OMIM) and with five different monoallelic variants, of which eight patients from five families were reported with cognitive decline and dementia on or before the age of 55.

Hence, there is sufficient evidence available for the promotion of this gene to green rating on the next GMS update.
Adult onset neurodegenerative disorder v7.19 CST3 Achchuthan Shanmugasundram Gene: cst3 has been classified as Amber List (Moderate Evidence).
Adult onset neurodegenerative disorder v7.18 CST3 Achchuthan Shanmugasundram Phenotypes for gene: CST3 were changed from Cerebral amyloid angiopathy, OMIM:105150 to Cerebral amyloid angiopathy, OMIM:105150; leukodystrophy, MONDO:0019046
Adult onset neurodegenerative disorder v7.17 CST3 Achchuthan Shanmugasundram Publications for gene: CST3 were set to
Adult onset neurodegenerative disorder v7.16 CST3 Achchuthan Shanmugasundram Mode of inheritance for gene: CST3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Adult onset neurodegenerative disorder v7.15 CST3 Achchuthan Shanmugasundram Tag Q2_25_ promote_green tag was added to gene: CST3.
Adult onset neurodegenerative disorder v7.15 CST3 Achchuthan Shanmugasundram edited their review of gene: CST3: Added comment: PMID:38489591 reported 16 patients from eight families with a novel adult-onset leukodystrophy disorder and with one of four different stop-gain or frameshift monoallelic variants in the CST3 gene. The reported variants are c.360del, c.357+1del, c.340C>T and c.376C>T, and none of these variants are found in general population (gnomAD). Clinical and radiological features of these patients differ markedly from the previously described Icelandic cerebral amyloid angiopathy found in patients carrying p.Leu68Asn substitution in CST3. The clinical phenotype consists of recurrent episodes of hemiplegic migraine associated with transient unilateral focal deficits and slowly progressing motor symptoms and cognitive decline in mid to older adult ages. Cognitive decline and dementia were present in 11 patients from seven families, of which seven patients from four families were aged below 55.

PMID:38729262 reported two unrelated Chinese individuals with adult-onset leukodystrophy and with monoallelic CST3 variants. One patient had the previously reported c.340C>T variant, while the other had novel c.357+1G>T variant. Memory deterioration and cognitive decline has been noted in the 48-year-old female patient with the novel variant.

This gene has only been reported with Cerebral amyloid angiopathy (MIM #105150) and not yet with the adult-onset leukodystrophy phenotype in OMIM.; Changed rating: GREEN; Changed publications to: 38489591, 38729262; Changed phenotypes to: Cerebral amyloid angiopathy, OMIM:105150, leukodystrophy, MONDO:0019046; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Adult onset leukodystrophy v5.8 CST3 Achchuthan Shanmugasundram Classified gene: CST3 as Amber List (moderate evidence)
Adult onset leukodystrophy v5.8 CST3 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are ten unrelated families reported with a novel adult-onset leukodystrophy disorder. Hence, this gene can be promoted to green rating in the next GMS update.
Adult onset leukodystrophy v5.8 CST3 Achchuthan Shanmugasundram Gene: cst3 has been classified as Amber List (Moderate Evidence).
Adult onset leukodystrophy v5.7 CST3 Achchuthan Shanmugasundram Tag founder-effect was removed from gene: CST3.
Tag Q2_25_ promote_green tag was added to gene: CST3.
Adult onset leukodystrophy v5.7 CST3 Achchuthan Shanmugasundram Phenotypes for gene: CST3 were changed from Cerebral amyloid angiopathy, OMIM:105150; ACys amyloidosis, MONDO:0007098 to leukodystrophy, MONDO:0019046; Cerebral amyloid angiopathy, OMIM:105150; ACys amyloidosis, MONDO:0007098
Adult onset leukodystrophy v5.6 CST3 Achchuthan Shanmugasundram Publications for gene: CST3 were set to 2900981; 3495457; 1352269; 3673496; 7482672; 8108423
Adult onset leukodystrophy v5.5 CST3 Achchuthan Shanmugasundram Mode of inheritance for gene: CST3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Adult onset leukodystrophy v5.4 CST3 Achchuthan Shanmugasundram reviewed gene: CST3: Rating: GREEN; Mode of pathogenicity: None; Publications: 38489591, 38729262; Phenotypes: leukodystrophy, MONDO:0019046; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia with onset in adulthood v7.15 NEU1 Lauren Turton gene: NEU1 was added
gene: NEU1 was added to Hereditary ataxia with onset in adulthood. Sources: NHS GMS
Mode of inheritance for gene: NEU1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NEU1 were set to 10944856; 11063730; 32752208; 31371146; 30023283
Phenotypes for gene: NEU1 were set to Ataxia; myoclonus
Review for gene: NEU1 was set to GREEN
gene: NEU1 was marked as current diagnostic
Added comment: NEU1-related sialidosis type I is a milder form of the disorder, characterised by visual defects, macular cherry-red spot, myoclonus, ataxia, and seizures. Onset can be variable from childhood to adulthood. Disorder has been well characterised for many years, with several unrelated patients reported.
Sources: NHS GMS
Ataxia and cerebellar anomalies - narrow panel v7.25 NEU1 Lauren Turton gene: NEU1 was added
gene: NEU1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: NHS GMS
Mode of inheritance for gene: NEU1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NEU1 were set to 10944856; 11063730; 32752208; 31371146; 30023283
Phenotypes for gene: NEU1 were set to Ataxia; myoclonus
Review for gene: NEU1 was set to GREEN
gene: NEU1 was marked as current diagnostic
Added comment: NEU1-related sialidosis type I is a milder form of the disorder, characterised by visual defects, macular cherry-red spot, myoclonus, ataxia, and seizures. Onset can be variable from childhood to adulthood. Disorder has been well characterised for many years, with several unrelated patients reported.
Sources: NHS GMS
Early onset or syndromic epilepsy v7.90 RNU2-2P Achchuthan Shanmugasundram Classified gene: RNU2-2P as Amber List (moderate evidence)
Early onset or syndromic epilepsy v7.90 RNU2-2P Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the association of this gene with epilepsy. Hence, this gene can be promoted to green rating on the next GMS update.
Early onset or syndromic epilepsy v7.90 RNU2-2P Achchuthan Shanmugasundram Gene: rnu2-2p has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v7.89 RNU2-2P Achchuthan Shanmugasundram Tag Q2_25_ promote_green tag was added to gene: RNU2-2P.
Early onset or syndromic epilepsy v7.89 RNU2-2P Achchuthan Shanmugasundram commented on gene: RNU2-2P: The "new-gene-name" tag has been added as the official HGNC symbol for RNU2-2P is RNU2-2.

In addition, "locus-type-rna-small-nuclear" tag has been added to highlight the biotype for this gene.
Early onset or syndromic epilepsy v7.89 RNU2-2P Achchuthan Shanmugasundram Tag new-gene-name tag was added to gene: RNU2-2P.
Tag locus-type-rna-small-nuclear tag was added to gene: RNU2-2P.
Tag dd_review tag was added to gene: RNU2-2P.
Early onset or syndromic epilepsy v7.89 RNU2-2P Achchuthan Shanmugasundram Phenotypes for gene: RNU2-2P were changed from to neurodevelopmental disorder, MONDO:0700092; epilepsy, MONDO:0005027
Early onset or syndromic epilepsy v7.88 RNU2-2P Achchuthan Shanmugasundram Publications for gene: RNU2-2P were set to
Early onset or syndromic epilepsy v7.87 RNU2-2P Achchuthan Shanmugasundram Mode of inheritance for gene: RNU2-2P was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v7.86 RNU2-2P Achchuthan Shanmugasundram reviewed gene: RNU2-2P: Rating: GREEN; Mode of pathogenicity: None; Publications: 40210679; Phenotypes: neurodevelopmental disorder, MONDO:0700092, epilepsy, MONDO:0005027; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v8.242 RNU2-2P Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient evidence available for the association of this gene with ID and GDD. Hence, this gene can be promoted to green rating on this panel.; to: Comment on list classification: There is sufficient evidence available for the association of this gene with ID and GDD. Hence, this gene can be promoted to green rating on the next GMS update.
Intellectual disability v8.242 RNU2-2P Achchuthan Shanmugasundram Classified gene: RNU2-2P as Amber List (moderate evidence)
Intellectual disability v8.242 RNU2-2P Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the association of this gene with ID and GDD. Hence, this gene can be promoted to green rating on this panel.
Intellectual disability v8.242 RNU2-2P Achchuthan Shanmugasundram Gene: rnu2-2p has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.241 RNU2-2P Achchuthan Shanmugasundram commented on gene: RNU2-2P: The "new-gene-name" tag has been added as the official HGNC symbol for RNU2-2P is RNU2-2.

In addition, "locus-type-rna-small-nuclear" tag has been added to highlight the biotype for this gene.
Intellectual disability v8.241 RNU2-2P Achchuthan Shanmugasundram Tag dd_review tag was added to gene: RNU2-2P.
Tag Q2_25_ promote_green tag was added to gene: RNU2-2P.
Intellectual disability v8.241 RNU2-2P Achchuthan Shanmugasundram Mode of inheritance for gene: RNU2-2P was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v8.240 RNU2-2P Achchuthan Shanmugasundram Publications for gene: RNU2-2P were set to
Intellectual disability v8.239 RNU2-2P Achchuthan Shanmugasundram Phenotypes for gene: RNU2-2P were changed from to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v8.238 RNU2-2P Achchuthan Shanmugasundram changed review comment from: PMID:40210679 reported nine individuals from 100,000 Genomes Project (100KGP) data in the National Genomic Research Library (NGRL) with a neurodevelopmental disorder and with recurrent de novo single-nucleotide variants at nucleotide positions 4 and 35 of RNU2-2 (n.4G>A & n.35A>G).

Monoallelic variants in this gene were also identified in 16 other cases with neurodevelopmental disorder from eight other rare disease collections. All but two of them were confirmed to have a de novo variant and 15 of them had one of the two variants reported from the 100KGP collection. There were no unaffected carriers of either variant. One case had a different variant at position 35 (35A>C).

Detailed clinical information was provided for 15 of these cases, and the disorder is characterised by intellectual disability (ID), autistic behavior, microcephaly, hypotonia, epilepsy and hyperventilation. All cases had ID and global developmental delay, and displayed a severe and complex seizure phenotype.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.; to: PMID:40210679 reported nine individuals from 100,000 Genomes Project (100KGP) data in the National Genomic Research Library (NGRL) with a neurodevelopmental disorder and with recurrent de novo single-nucleotide variants at nucleotide positions 4 and 35 of RNU2-2 (n.4G>A & n.35A>G).

Monoallelic variants in this gene were also identified in 16 other cases with neurodevelopmental disorder from eight other rare disease collections. All but two of them were confirmed to have a de novo variant and 15 of them had one of the two variants reported from the 100KGP collection. There were no unaffected carriers of either variant. One case had a different variant at position 35 (35A>C).

Detailed clinical information was provided for 15 of these cases, and the disorder is characterised by intellectual disability (ID), autistic behaviour, microcephaly, hypotonia, epilepsy and hyperventilation. The phenotype typically manifests from 3 to 6 months of age but is progressive, frequently severe and accompanied by characteristic dysmorphic features. All cases had ID and global developmental delay, and displayed a severe and complex seizure phenotype.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Intellectual disability v8.238 RNU2-2P Achchuthan Shanmugasundram changed review comment from: PMID:40210679 reported nine individuals from 100,000 Genomes Project (100KGP) data in the National Genomic Research Library (NGRL) with a neurodevelopmental disorder and with recurrent de novo single-nucleotide variants at nucleotide positions 4 and 35 of RNU2-2 (n.4G>A & n.35A>G).

Monoallelic variants in this gene were also identified in 16 other cases with neurodevelopmental disorder from eight other rare disease collections. All but two of them were confirmed to have a de novo variant and 15 of them had one of the two variants reported from the 100KGP collection. There were no unaffected carriers of either variant. One case had a different variant at position 35 (35A>C).

Detailed clinical information was provided for 15 of these cases, and the disorder is characterised by intellectual disability, autistic behavior, microcephaly, hypotonia, epilepsy and hyperventilation. All cases display a severe and complex seizure phenotype.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.; to: PMID:40210679 reported nine individuals from 100,000 Genomes Project (100KGP) data in the National Genomic Research Library (NGRL) with a neurodevelopmental disorder and with recurrent de novo single-nucleotide variants at nucleotide positions 4 and 35 of RNU2-2 (n.4G>A & n.35A>G).

Monoallelic variants in this gene were also identified in 16 other cases with neurodevelopmental disorder from eight other rare disease collections. All but two of them were confirmed to have a de novo variant and 15 of them had one of the two variants reported from the 100KGP collection. There were no unaffected carriers of either variant. One case had a different variant at position 35 (35A>C).

Detailed clinical information was provided for 15 of these cases, and the disorder is characterised by intellectual disability (ID), autistic behavior, microcephaly, hypotonia, epilepsy and hyperventilation. All cases had ID and global developmental delay, and displayed a severe and complex seizure phenotype.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Intellectual disability v8.238 RNU2-2P Achchuthan Shanmugasundram Tag new-gene-name tag was added to gene: RNU2-2P.
Tag locus-type-rna-small-nuclear tag was added to gene: RNU2-2P.
Intellectual disability v8.238 RNU2-2P Achchuthan Shanmugasundram reviewed gene: RNU2-2P: Rating: GREEN; Mode of pathogenicity: None; Publications: 40210679; Phenotypes: neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v8.238 DDX39B Achchuthan Shanmugasundram Classified gene: DDX39B as Amber List (moderate evidence)
Intellectual disability v8.238 DDX39B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (four unrelated cases with missense variants) available for the association. Hence, this gene can be promoted to green rating in the next GMS update.
Intellectual disability v8.238 DDX39B Achchuthan Shanmugasundram Gene: ddx39b has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.237 DDX39B Achchuthan Shanmugasundram changed review comment from: As reviewed by Mike Spiller, PMID:39918047 reported the identification of monoallelic DDX39B variants in six patients from five unrelated families presenting with a neurodevelopmental disorder. Intellectual disability was reported in three of four unrelated patients identified with de novo missense variants, of which ID was severe in two and mild in one. The fourth patient had global developmental delay.

This gene has not yet been associated with relevant phenotypes in OMIM or Gene2Phenotype.; to: As reviewed by Mike Spiller, PMID:39918047 reported the identification of monoallelic DDX39B variants in six patients from five unrelated families presenting with a neurodevelopmental disorder. Intellectual disability was reported in three of four unrelated patients identified with de novo missense variants, of which ID was severe in two and mild in one. The fourth patient had global developmental delay.

The two patients from the same family with splice variant did not present with ID.

This gene has not yet been associated with relevant phenotypes in OMIM or Gene2Phenotype.
Intellectual disability v8.237 DDX39B Achchuthan Shanmugasundram changed review comment from: As reviewed by Mike Spiller, PMID:39918047 reported the identification of monoallelic DDX39B variants in six patients from five unrelated families presenting with a neurodevelopmental disorder. Intellectual disability was reported in three of four patients identified with de novo missense variants, of which ID was severe in two and mild in one. The fourth patient had global developmental delay.

This gene has not yet been associated with relevant phenotypes in OMIM or Gene2Phenotype.; to: As reviewed by Mike Spiller, PMID:39918047 reported the identification of monoallelic DDX39B variants in six patients from five unrelated families presenting with a neurodevelopmental disorder. Intellectual disability was reported in three of four unrelated patients identified with de novo missense variants, of which ID was severe in two and mild in one. The fourth patient had global developmental delay.

This gene has not yet been associated with relevant phenotypes in OMIM or Gene2Phenotype.
Intellectual disability v8.237 DDX39B Achchuthan Shanmugasundram commented on gene: DDX39B: As reviewed by Mike Spiller, PMID:39918047 reported the identification of monoallelic DDX39B variants in six patients from five unrelated families presenting with a neurodevelopmental disorder. Intellectual disability was reported in three of four patients identified with de novo missense variants, of which ID was severe in two and mild in one. The fourth patient had global developmental delay.

This gene has not yet been associated with relevant phenotypes in OMIM or Gene2Phenotype.
Intellectual disability v8.237 DDX39B Achchuthan Shanmugasundram Tag Q2_25_ promote_green tag was added to gene: DDX39B.
Tag Q2_25_ NHS_review tag was added to gene: DDX39B.
Intellectual disability v8.237 DDX39B Achchuthan Shanmugasundram Phenotypes for gene: DDX39B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v8.236 DDX39B Achchuthan Shanmugasundram Phenotypes for gene: DDX39B were changed from to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v8.236 DDX39B Achchuthan Shanmugasundram Publications for gene: DDX39B were set to PMID: 39918047
Intellectual disability v8.235 DDX39B Achchuthan Shanmugasundram reviewed gene: DDX39B: Rating: GREEN; Mode of pathogenicity: None; Publications: 39918047; Phenotypes: neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dilated and arrhythmogenic cardiomyopathy v2.37 TAX1BP3 Achchuthan Shanmugasundram Classified gene: TAX1BP3 as Amber List (moderate evidence)
Dilated and arrhythmogenic cardiomyopathy v2.37 TAX1BP3 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated amber with current evidence as there is only one family and functional work in support of the disease association.
Dilated and arrhythmogenic cardiomyopathy v2.37 TAX1BP3 Achchuthan Shanmugasundram Gene: tax1bp3 has been classified as Amber List (Moderate Evidence).
Cerebral vascular malformations v3.26 KEL Alexandra Njegic gene: KEL was added
gene: KEL was added to Cerebral vascular malformations. Sources: Literature
Mode of inheritance for gene: KEL was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KEL were set to 30578106; 37978175
Phenotypes for gene: KEL were set to Vein of Galen Malformation
Penetrance for gene: KEL were set to unknown
Review for gene: KEL was set to AMBER
Added comment: 37978175, 30578106 (same cohort with additional VOGM probands in 37978175): 30578106; 2/55 VOGM probands with a de novo nonsense or missense variant in KEL, absent in unaffected parents and siblings. No in vitro or in vivo studies. Pathogenicity not provided.
37978175: No additional KEL variants.
Sources: Literature
Hereditary ataxia with onset in adulthood v7.15 BEAN1_TGGAA Sarah Leigh Tag STR tag was added to STR: BEAN1_TGGAA.
Hereditary ataxia with onset in adulthood v7.15 BEAN1_TGGAA Sarah Leigh commented on STR: BEAN1_TGGAA: The repeat sequence TAAAA in BEAN1 is benign and seen in healthy controls. Although the TAAAA repeat is expanded in patients, it is the TGGAA repeat that is pathogenic repeats. The TGGAA repeat is not seen in healthy controls (PMID: 19878914). A further pathogenic repeat was also seen in two cases [TCAC (TGGAA)exp(TAGAA)exp(TAAAA TAGAA)exp] (PMID: 19878914).
Hereditary ataxia with onset in adulthood v7.15 BEAN1_TGGAA Sarah Leigh commented on STR: BEAN1_TGGAA: BEAN1 transcribed from the forward strand.
BEAN1_TGGAA is on https://gnomad.broadinstitute.org/short-tandem-repeat/SAMD12?dataset=gnomad_r4
BEAN1_TGGAA is on https://stripy.org/database
BEAN1_TGGAA is DRAGON 4.02

The coordinates of the sequence repeats shown above were obtained from https://gnomad.broadinstitute.org/short-tandem-repeat/SAMD12?dataset=gnomad_r4 the coordinates were the same on DRAGON 4.02. The coordinates from https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r4 were 16:66490398-66490453 (hg38)

The non-pathogenic and pathogenic ranges of the sequence repeats shown above were obtained from: https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r4

There is enough evidence for this STR to be green on this panel.

This STR has not been approved by NHS STR working group and is not NGS Not Validated
Fetal anomalies v5.90 LMNB2 Sarah Leigh Tag Q2_25_ MOI tag was added to gene: LMNB2.
Tag Q2_25_ NHS_review tag was added to gene: LMNB2.
Severe microcephaly v7.25 LMNB2 Sarah Leigh Tag Q2_25_ MOI tag was added to gene: LMNB2.
Severe microcephaly v7.25 LMNB2 Sarah Leigh changed review comment from: PMID: 40011009 reports two related babies who were homozygous for a loss-of-function LMNB2 variant. Both babies shared a similar phenotype of severe brain development abnormalities and died during the perinatal period. This shared phenotype was reflected in the several Lmnb2-deficient mouse models.
Material from the patient’s fibroblasts (obtained at birth) were used in Western blot and immunofluorescence cell labelling, and confirmed the complete absence of lamin B2 and revealed an increase in lamin B1, together with alterations in alpha-tubulin and vimentin organisation. (PMID: 40011009).; to: PMID: 40011009 reports two related babies who were homozygous for a loss-of-function LMNB2 variant. Both babies shared a similar phenotype of severe brain development abnormalities and died during the perinatal period. This shared phenotype was reflected in several Lmnb2-deficient mouse models.
Material from the patient’s fibroblasts (obtained at birth) were used in Western blot and immunofluorescence cell labelling, and confirmed the complete absence of lamin B2 and revealed an increase in lamin B1, together with alterations in alpha-tubulin and vimentin organisation. (PMID: 40011009).
Fetal anomalies v5.90 LMNB2 Sarah Leigh changed review comment from: PMID: 40011009 reports two related babies who were homozygous for a loss-of-function LMNB2 variant. Both babies shared a similar phenotype of severe brain development abnormalities and died during the perinatal period. This shared phenotype was reflected in the several Lmnb2-deficient mouse models.
Material from the patient’s fibroblasts (obtained at birth) were used in Western blot and immunofluorescence cell labelling, and confirmed the complete absence of lamin B2 and revealed an increase in lamin B1, together with alterations in alpha-tubulin and vimentin organisation. (PMID: 40011009).; to: PMID: 40011009 reports two related babies who were homozygous for a loss-of-function LMNB2 variant. Both babies shared a similar phenotype of severe brain development abnormalities and died during the perinatal period. This shared phenotype was reflected in several Lmnb2-deficient mouse models.
Material from the patient’s fibroblasts (obtained at birth) were used in Western blot and immunofluorescence cell labelling, and confirmed the complete absence of lamin B2 and revealed an increase in lamin B1, together with alterations in alpha-tubulin and vimentin organisation. (PMID: 40011009).
Fetal anomalies v5.90 LMNB2 Sarah Leigh reviewed gene: LMNB2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Severe microcephaly v7.25 LMNB2 Sarah Leigh edited their review of gene: LMNB2: Added comment: PMID: 40011009 reports two related babies who were homozygous for a loss-of-function LMNB2 variant. Both babies shared a similar phenotype of severe brain development abnormalities and died during the perinatal period. This shared phenotype was reflected in the several Lmnb2-deficient mouse models.
Material from the patient’s fibroblasts (obtained at birth) were used in Western blot and immunofluorescence cell labelling, and confirmed the complete absence of lamin B2 and revealed an increase in lamin B1, together with alterations in alpha-tubulin and vimentin organisation. (PMID: 40011009).; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Severe microcephaly v7.25 LMNB2 Sarah Leigh Phenotypes for gene: LMNB2 were changed from Microcephaly 27, primary, autosomal dominant, OMIM:619180 to Microcephaly 27, primary, autosomal dominant, OMIM:619180; microcephaly 27, primary, autosomal dominant, MONDO:0030929
Fetal anomalies v5.90 LMNB2 Sarah Leigh Phenotypes for gene: LMNB2 were changed from Microcephaly 27, primary, autosomal dominant, OMIM:619180 to Microcephaly 27, primary, autosomal dominant, OMIM:619180; microcephaly 27, primary, autosomal dominant, MONDO:0030929
Severe microcephaly v7.24 LMNB2 Sarah Leigh Publications for gene: LMNB2 were set to 33033404
Fetal anomalies v5.89 LMNB2 Sarah Leigh Publications for gene: LMNB2 were set to 33033404
Cerebral vascular malformations v3.26 CBL Alexandra Njegic reviewed gene: CBL: Rating: GREEN; Mode of pathogenicity: None; Publications: 32637631, 37778001; Phenotypes: Cerebral arteriopathy, Moyamoya Disease; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Cerebral vascular malformations v3.26 DIAPH1 Sarah Leigh Tag watchlist tag was added to gene: DIAPH1.
Cerebral vascular malformations v3.26 DIAPH1 Sarah Leigh Publications for gene: DIAPH1 were set to 34125151; 37400591
Cerebral vascular malformations v3.25 DIAPH1 Sarah Leigh Deleted their comment
Cerebral vascular malformations v3.25 DIAPH1 Sarah Leigh edited their review of gene: DIAPH1: Added comment: Kundishora et al (PMID: 34125151) reports seven DIAPH1 variants in six patients from two cohorts containing a total of 108 patients with features of Moyamoya disease (MMD). The authors suggest that DIAPH1 variants may be associated with MMD risk gene and impaired vascular cell actin remodeling in MMD pathogenesis. In PMID: 37400591 the authors report that MMD patients with DIAPH1 variants were more likely to have posterior circulation involvement (7/9, 78%) than those without DIAPH1 variants (5/41, 12%). No variant functional studies were presented in these studies.; Changed rating: AMBER
Cerebral vascular malformations v3.25 DIAPH1 Sarah Leigh Added comment: Comment on publications: PMID: 37012328 is not relevant to this gene
Cerebral vascular malformations v3.25 DIAPH1 Sarah Leigh Publications for gene: DIAPH1 were set to 34125151; 37400591; 37012328
Cerebral vascular malformations v3.24 DIAPH1 Sarah Leigh Phenotypes for gene: DIAPH1 were changed from Moyamoya disease to Seizures, cortical blindness, microcephaly syndrome, OMIM:616632; progressive microcephaly-seizures-cortical blindness-developmental delay syndrome, MONDO:0014714
Cerebral vascular malformations v3.23 DIAPH1 Sarah Leigh Classified gene: DIAPH1 as Amber List (moderate evidence)
Cerebral vascular malformations v3.23 DIAPH1 Sarah Leigh Gene: diaph1 has been classified as Amber List (Moderate Evidence).
Cerebral vascular malformations v3.22 ANO1 Sarah Leigh Tag Q2_25_ promote_green tag was added to gene: ANO1.
Tag Q2_25_ NHS_review tag was added to gene: ANO1.
Cerebral vascular malformations v3.22 ANO1 Sarah Leigh edited their review of gene: ANO1: Added comment: Three ANO1 variant have been associated with Moyamoya disease 7 (OMIM:620687) in three unrelated cases (PMID: 37253099). Two of the variants were heterozygous in the patients, while the third was homozygous. For each of the variants, electrophysiologic studies in variant transfected HEK293 cells revealed that the variant channel had an increased Ca(2+) sensitivity resulting in increased membrane Cl- conductance at lower intracellular Ca(2+) levels in comparison to the controls, which is consistent with a gain-of-function effect.; Changed rating: GREEN; Changed publications to: 37253099; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cerebral vascular malformations v3.22 ANO1 Sarah Leigh Added comment: Comment on publications: PMID: 37012328 was not relevant to this gene
Cerebral vascular malformations v3.22 ANO1 Sarah Leigh Publications for gene: ANO1 were set to 37253099
Cerebral vascular malformations v3.21 ANO1 Sarah Leigh Publications for gene: ANO1 were set to 37253099; 37012328
Cerebral vascular malformations v3.20 NOS3 Alexandra Njegic changed review comment from: Conflicting reports of mode of inheritance.
37383439: 1/6 Moyamoya disease patients with a NOS3 heterozygous variant, pathogenicity not provided.
36941667: 6 probands from consanguineous parentage with MMA, 2 NOS3 homozygous variants. In vitro studies, splice donor site variant leads to lack of eNOS in endothelial progenitor cells derived from the affected proband. Missense variant leads to reduced eNOS protein expression (HEK cells).
Sources: Literature; to: 2 papers with a different mode of inheritance shown; pathogenicity of AD variant not explored in detail.
37383439: 1/6 Moyamoya disease patients with a NOS3 heterozygous variant, pathogenicity not provided.
36941667: 6 probands from consanguineous parentage with MMA, 2 NOS3 homozygous variants. In vitro studies, splice donor site variant leads to lack of eNOS in endothelial progenitor cells derived from the affected proband. Missense variant leads to reduced eNOS protein expression (HEK cells).
Sources: Literature
Cerebral vascular malformations v3.20 ANO1 Sarah Leigh Phenotypes for gene: ANO1 were changed from Moyamoya disease 7, 620687 to Moyamoya disease 7, OMIM:620687; moyamoya disease 7, MONDO:0958202
Cerebral vascular malformations v3.19 ANO1 Sarah Leigh Classified gene: ANO1 as Amber List (moderate evidence)
Cerebral vascular malformations v3.19 ANO1 Sarah Leigh Gene: ano1 has been classified as Amber List (Moderate Evidence).
Cerebral vascular malformations v3.18 NOS3 Alexandra Njegic gene: NOS3 was added
gene: NOS3 was added to Cerebral vascular malformations. Sources: Literature
Mode of inheritance for gene: NOS3 was set to Other
Publications for gene: NOS3 were set to 37383439; 36941667
Phenotypes for gene: NOS3 were set to Moyamoya Disease; Moyamoya Angiopathy
Penetrance for gene: NOS3 were set to unknown
Review for gene: NOS3 was set to AMBER
Added comment: Conflicting reports of mode of inheritance.
37383439: 1/6 Moyamoya disease patients with a NOS3 heterozygous variant, pathogenicity not provided.
36941667: 6 probands from consanguineous parentage with MMA, 2 NOS3 homozygous variants. In vitro studies, splice donor site variant leads to lack of eNOS in endothelial progenitor cells derived from the affected proband. Missense variant leads to reduced eNOS protein expression (HEK cells).
Sources: Literature
Paediatric disorders - additional genes v6.18 IGFALS Sarah Leigh Tag Q2_25_ promote_green tag was added to gene: IGFALS.
Tag Q2_25_ NHS_review tag was added to gene: IGFALS.
Paediatric disorders - additional genes v6.18 IGFALS Sarah Leigh reviewed gene: IGFALS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric disorders - additional genes v6.18 IGFALS Sarah Leigh Publications for gene: IGFALS were set to
Paediatric disorders - additional genes v6.17 IGFALS Sarah Leigh Phenotypes for gene: IGFALS were changed from short stature to Acid-labile subunit, deficiency of, OMIM:615961; short stature due to primary acid-labile subunit deficiency, MONDO:0014420
Monogenic short stature v1.16 IGFALS Sarah Leigh Phenotypes for gene: IGFALS were changed from Acid-labile subunit, deficiency of, OMIM:615961 to Acid-labile subunit, deficiency of, OMIM:615961; short stature due to primary acid-labile subunit deficiency, MONDO:0014420
Paediatric disorders - additional genes v6.16 IGFALS Sarah Leigh Classified gene: IGFALS as Amber List (moderate evidence)
Paediatric disorders - additional genes v6.16 IGFALS Sarah Leigh Gene: igfals has been classified as Amber List (Moderate Evidence).
Cerebral vascular malformations v3.18 FOXM1 Alexandra Njegic gene: FOXM1 was added
gene: FOXM1 was added to Cerebral vascular malformations. Sources: Literature
Mode of inheritance for gene: FOXM1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FOXM1 were set to 38969938
Phenotypes for gene: FOXM1 were set to Moyamoya Disease (Unilateral)
Penetrance for gene: FOXM1 were set to unknown
Review for gene: FOXM1 was set to AMBER
Added comment: 38969938: 1 family, affected father and daughter. In vitro studies with hCMEC/D3 cells overexpressing the variant showed reduced migration and tube formation and increased apoptosis proposed to be due to reduced BCL2 transcription.
Sources: Literature
Hereditary Erythrocytosis v2.13 SH2B3 Sarah Leigh Tag Q2_25_ promote_green tag was added to gene: SH2B3.
Tag Q2_25_ NHS_review tag was added to gene: SH2B3.
Hereditary Erythrocytosis v2.13 SH2B3 Sarah Leigh commented on gene: SH2B3: Based on the review by Terri McVeigh (Royal Marsden NHS Foundation Trust), this gene is recommended to be made green.
Hereditary Erythrocytosis v2.13 SH2B3 Sarah Leigh Phenotypes for gene: SH2B3 were changed from Erythrocytosis, somatic, OMIM:133100 to Erythrocytosis, somatic, OMIM:133100; Myelofibrosis, somatic, OMIM:254450; Thrombocythemia, somatic, OMIM:187950
Hereditary Erythrocytosis v2.12 SH2B3 Sarah Leigh Publications for gene: SH2B3 were set to 23812944; 20843259; 34440325; 34021251
Pigmentary skin disorders v3.15 LZTR1 Sarah Leigh reviewed gene: LZTR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 39140257, 39258154; Phenotypes: ; Mode of inheritance: None
Cerebral vascular malformations v3.18 EVL Alexandra Njegic gene: EVL was added
gene: EVL was added to Cerebral vascular malformations. Sources: Literature
Mode of inheritance for gene: EVL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EVL were set to 34125151
Phenotypes for gene: EVL were set to Moyamoya Disease
Penetrance for gene: EVL were set to unknown
Review for gene: EVL was set to RED
Added comment: 34125151: 1 proband with compound heterozygous ‘damaging’ missense variants in EVL, pathogenicity not reported.
No other reports in literature of EVL variants and MMD.
Sources: Literature
Cerebral vascular malformations v3.18 EPHB4 Alexandra Njegic reviewed gene: EPHB4: Rating: GREEN; Mode of pathogenicity: None; Publications: 37978175, 30578106, 29444212, 39367533, 35852613; Phenotypes: Capillary malformation-arteriovenous malformation 2, 618196; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Skeletal dysplasia v7.38 NPR3 Eleanor Williams Publications for gene: NPR3 were set to 30032985; 10468599
Skeletal dysplasia v7.37 NPR3 Eleanor Williams Phenotypes for gene: NPR3 were changed from Tall stature; arachnodactyly; extra epiphyses; aortic dilatation to Boudin-Mortier syndrome, OMIM:619543; Boudin-Mortier syndrome, MONDO:0859194
Skeletal dysplasia v7.36 NPR3 Eleanor Williams edited their review of gene: NPR3: Added comment: Additional cases reported in:

PMID: 35233476 - Lauffer et al 2022 - 2 novel compound heterozygous NPR3 variants c.943G>A p.(Ala315Thr) and c.1294A>T p.(Ile432Phe) in a boy with tall stature and macrodactyly of the halluces. The authors note that compared to other patients with NPR-C (encoded by NPR3) loss-of-function, the phenotype appears to be milder.

PMID: 40171685 - Moffat et al 2025 - 3 siblings with a novel homozygous missense variant in NPR3 that in vitro data shows causes loss-of-function. All had tall stature but in addition 1 sibling had severe scoliosis developed and mild scoliosis was observed in the two others. Scoliosis has not been previously reported in NPR3-related tall stature and therefore extends the phenotype.; Changed publications to: 30032985, 10468599, 35233476, 40171685; Changed phenotypes to: Boudin-Mortier syndrome, OMIM:619543
Primary immunodeficiency or monogenic inflammatory bowel disease v7.26 GCC2 Boaz Palterer gene: GCC2 was added
gene: GCC2 was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: GCC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GCC2 were set to 39813120
Phenotypes for gene: GCC2 were set to NK cell deficiency; recurrent viral infections; immunodeficiency
Penetrance for gene: GCC2 were set to unknown
Review for gene: GCC2 was set to RED
Added comment: Pedroza et al. described 2 patients in two separate kindreds with compound heterozygous GCC2 mutations presenting in childhood with recurrent viral infections, normal NK cell numbers but reduced NK cell function.
During NK cell activation, lytic granules (LGs) converge to the MTOC, enabling precision in cytotoxicity. Pedroza et al. demonstrate that GCC2 maintains convergence via tethering LGs to the Golgi. Absence of GCC2 leads to LG dispersion, non-directed degranulation, and bystander killing, and biallelic missense variants result in human NK cell deficiency.
Sources: Literature
Hereditary ataxia with onset in adulthood v7.15 BEAN1_TGGAA Sarah Leigh STR: BEAN1_TGGAA was added
STR: BEAN1_TGGAA was added to Hereditary ataxia with onset in adulthood. Sources: Literature
NGS Not Validated tags were added to STR: BEAN1_TGGAA.
Mode of inheritance for STR: BEAN1_TGGAA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for STR: BEAN1_TGGAA were set to 19878914
Phenotypes for STR: BEAN1_TGGAA were set to Spinocerebellar ataxia 31, OMIM:117210; spinocerebellar ataxia type 31, MONDO:0007296
Review for STR: BEAN1_TGGAA was set to GREEN
Added comment: Sources: Literature
Pigmentary skin disorders v3.15 LZTR1 Sarah Leigh Publications for gene: LZTR1 were set to 29469822; 25795793
Renal tubulopathies v4.21 ATP6V1B1 Sarah Leigh Tag Q2_25_ MOI tag was added to gene: ATP6V1B1.
Tag Q2_25_ NHS_review tag was added to gene: ATP6V1B1.
Renal tubulopathies v4.21 ATP6V1B1 Sarah Leigh reviewed gene: ATP6V1B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 39837581, 9916796, 12566520, 18798332; Phenotypes: Distal renal tubular acidosis 2 with progressive sensorineural hearing loss, OMIM:267300, renal tubular acidosis, distal, 2, with progressive sensorineural hearing loss, MONDO:0009968; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Nephrocalcinosis or nephrolithiasis v4.22 ATP6V1B1 Sarah Leigh Tag Q2_25_ MOI tag was added to gene: ATP6V1B1.
Tag Q2_25_ NHS_review tag was added to gene: ATP6V1B1.
Monogenic hearing loss v4.84 ATP6V1B1 Sarah Leigh Phenotypes for gene: ATP6V1B1 were changed from hearing loss; Distal Renal Tubular Acidosis with Progressive Nerve Deafness; Renal tubular acidosis with deafness, 267300 to Distal renal tubular acidosis 2 with progressive sensorineural hearing loss, OMIM:267300; renal tubular acidosis, distal, 2, with progressive sensorineural hearing loss, MONDO:0009968
Nephrocalcinosis or nephrolithiasis v4.22 ATP6V1B1 Sarah Leigh Phenotypes for gene: ATP6V1B1 were changed from distal renal tubular acidosis; Renal tubular acidosis with deafness 267300 to Distal renal tubular acidosis 2 with progressive sensorineural hearing loss, OMIM:267300; renal tubular acidosis, distal, 2, with progressive sensorineural hearing loss, MONDO:0009968
Nephrocalcinosis or nephrolithiasis v4.21 ATP6V1B1 Sarah Leigh Publications for gene: ATP6V1B1 were set to 39837581
Monogenic hearing loss v4.83 ATP6V1B1 Sarah Leigh Tag Q2_25_ MOI tag was added to gene: ATP6V1B1.
Tag Q2_25_ NHS_review tag was added to gene: ATP6V1B1.
Nephrocalcinosis or nephrolithiasis v4.20 ATP6V1B1 Sarah Leigh reviewed gene: ATP6V1B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 39837581, 9916796, 12566520, 18798332; Phenotypes: Distal renal tubular acidosis 2 with progressive sensorineural hearing loss, OMIM:267300, renal tubular acidosis, distal, 2, with progressive sensorineural hearing loss, MONDO:0009968; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Monogenic hearing loss v4.83 ATP6V1B1 Sarah Leigh edited their review of gene: ATP6V1B1: Changed phenotypes to: Distal renal tubular acidosis 2 with progressive sensorineural hearing loss, OMIM:267300, renal tubular acidosis, distal, 2, with progressive sensorineural hearing loss, MONDO:0009968
Monogenic hearing loss v4.83 ATP6V1B1 Sarah Leigh reviewed gene: ATP6V1B1: Rating: ; Mode of pathogenicity: None; Publications: 39837581, 9916796, 12566520, 18798332; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Nephrocalcinosis or nephrolithiasis v4.20 ATP6V1B1 Sarah Leigh Publications for gene: ATP6V1B1 were set to
Monogenic hearing loss v4.83 ATP6V1B1 Sarah Leigh Publications for gene: ATP6V1B1 were set to PMID:12566520; 1373501; 18798332; 22509993; 2527371; 2869030; 7945239; 9916796
Rare anaemia v3.10 RPL27 Sarah Leigh Tag Q2_25_ promote_green tag was added to gene: RPL27.
Tag Q2_25_ NHS_review tag was added to gene: RPL27.
Rare anaemia v3.10 RPL27 Sarah Leigh commented on gene: RPL27: PMID: 25424902 and 38988374 report the de novo occurrence of a RPL27 variant (NM_000988.5(RPL27):c.-2-1G>A) in two unrelated, not ethnically matching cases of Diamond-Blackfan anemia 16 (OMIM:617408). Together with the supportive functional studies in Zebra fish (PMID: 25424902), there is sufficient for RPL27 to be green on this panel.
Cytopenia - NOT Fanconi anaemia v3.39 RPL27 Sarah Leigh Tag Q2_25_ promote_green tag was added to gene: RPL27.
Tag Q2_25_ NHS_review tag was added to gene: RPL27.
Cytopenia - NOT Fanconi anaemia v3.39 RPL27 Sarah Leigh reviewed gene: RPL27: Rating: GREEN; Mode of pathogenicity: None; Publications: 25424902, 38988374; Phenotypes: ?Diamond-Blackfan anemia 16, OMIM:617408, Diamond-Blackfan anemia 16, MONDO:0044309; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare anaemia v3.10 RPL27 Sarah Leigh reviewed gene: RPL27: Rating: GREEN; Mode of pathogenicity: None; Publications: 25424902, 38988374; Phenotypes: ?Diamond-Blackfan anemia 16, OMIM:617408, Diamond-Blackfan anemia 16, MONDO:0044309; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cytopenia - NOT Fanconi anaemia v3.39 RPL27 Sarah Leigh Publications for gene: RPL27 were set to 25424902; 38988374
Cytopenia - NOT Fanconi anaemia v3.38 RPL27 Sarah Leigh Phenotypes for gene: RPL27 were changed from Diamond-Blackfan anemia; ?Diamond-Blackfan anemia 16, 617408 to ?Diamond-Blackfan anemia 16, OMIM:617408; Diamond-Blackfan anemia 16, MONDO:0044309
Cytopenia - NOT Fanconi anaemia v3.37 RPL27 Sarah Leigh Publications for gene: RPL27 were set to 25424902
Fetal anomalies v5.88 SCN4A Sarah Leigh Tag Q2_25_ MOI tag was added to gene: SCN4A.
Tag Q2_25_expert_review tag was added to gene: SCN4A.
Fetal anomalies v5.88 SCN4A Sarah Leigh reviewed gene: SCN4A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.88 SCN4A Sarah Leigh Phenotypes for gene: SCN4A were changed from PARAMYOTONIA CONGENITA OF VON EULENBURG; HYPERKALEMIC PERIODIC PARALYSIS TYPE 1; HYPOKALEMIC PERIODIC PARALYSIS to Classic congenital myopathy-22A, OMIM:620351; congenital myopathy 22A, classic,MONDO:0957247:Severe fetal congenital myopathy-22B, OMIM:620369; congenital myopathy 22B, severe fetal, MONDO:0957265
Inherited ovarian cancer (without breast cancer) v4.4 LLGL2 Sarah Leigh Tag Q2_25_ promote_green tag was added to gene: LLGL2.
Tag Q2_25_ NHS_review tag was added to gene: LLGL2.
Inherited ovarian cancer (without breast cancer) v4.4 LLGL2 Sarah Leigh reviewed gene: LLGL2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: High-grade serous ovarian carcinoma; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Inherited ovarian cancer (without breast cancer) v4.4 LLGL2 Sarah Leigh Classified gene: LLGL2 as Amber List (moderate evidence)
Inherited ovarian cancer (without breast cancer) v4.4 LLGL2 Sarah Leigh Gene: llgl2 has been classified as Amber List (Moderate Evidence).
Hereditary ataxia v1.338 RAB3A Andrew Mumford changed review comment from: The association between monoallelic variants in RAB3A and cerebellar ataxia was discovered in large-scale gene association study (PMID 36928819).

This was replicated in an extended European case series of 18 affected individuals from 10 families and supported by structural modelling and functional analyses in cell line and Drosophila models. (PMID 40166812).
Sources: Research; to: The association between monoallelic variants in RAB3A and cerebellar ataxia was discovered in large-scale gene association study (PMID 36928819).

This was replicated in an extended European case series of 18 affected individuals from 10 families and supported by structural modelling and functional analyses in cell line and Drosophila models. (PMID 40166812).

Sources: Research
Hereditary ataxia v1.338 RAB3A Andrew Mumford gene: RAB3A was added
gene: RAB3A was added to Hereditary ataxia. Sources: Research
Mode of inheritance for gene: RAB3A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAB3A were set to PMID:36928819; 40166812
Phenotypes for gene: RAB3A were set to cerebellar ataxia; pyramidal features; neurodevelopmental delay
Penetrance for gene: RAB3A were set to Complete
Review for gene: RAB3A was set to GREEN
Added comment: The association between monoallelic variants in RAB3A and cerebellar ataxia was discovered in large-scale gene association study (PMID 36928819).

This was replicated in an extended European case series of 18 affected individuals from 10 families and supported by structural modelling and functional analyses in cell line and Drosophila models. (PMID 40166812).
Sources: Research
Bilateral congenital or childhood onset cataracts v6.6 HMBS Sharon Whatley gene: HMBS was added
gene: HMBS was added to Bilateral congenital or childhood onset cataracts. Sources: Expert Review
Mode of inheritance for gene: HMBS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HMBS were set to 14262853; 1577472; 15534187; 14970743; 31153822
Phenotypes for gene: HMBS were set to 620711; 620704
Penetrance for gene: HMBS were set to Incomplete
Review for gene: HMBS was set to GREEN
Added comment: Biallelic inheritance of HMBS pathogenic variants is very rare. PMID: 14262853 De Villeneuve, 1577472 Llewellyn, 15534187 Solis, 14970743 Hessels and 31153822 Dixon. It has been reported in six children (from 5 families) four children (from 3 families) children have been reported to have cataracts.
PMID: 1577472 Llewellyn reported two siblings with HMBS biallelic pathogenic variants c.499C>T, p.(Arg167Trp) and c.500G>A, p.(Arg167Gln). At the age of 18 months one patient had ataxia with intention tremor and dysarthria secondary to partial agenesis of the cerebella vermis, bilateral cataracts and right optic nerve hypoplasia. Biochemical studies showed excessive excretion of PBG with normal faecal porphyrin and very low erythrocyte PBG deaminase activity. At 3 years of age, she was admitted to hospital following febrile convulsions. When assessed one year later, she had had no further convulsions and no symptoms of acute porphyria. She died at 8 years of age.
PMID: 15534187 Solis reported a 28 month old patient with homozygous HMBS variants c.499C>T, p.(Arg167Trp), bilateral capsular cataracts and a unique pattern of deep cerebral white matter injury, with relative preservation of the corpus callosum, anterior limb of the internal capsule, cerebral grey matter, and infratentorial structures. He had no history of seizures. Neurologic examination confirmed peripheral neuropathy, psychomotor delay and revealed occasional dystonic head positioning and dystonic arm movements. The proband had approximately 1% of normal mean erythrocyte HMBS activity, and urinary ALA and PBG were markedly elevated. He died at 40 months.
PMID: 34089223 Stutterd reported two siblings (45 and 54 years old) with homozygous HMBS variants c.251C > A, p.(Ala84Asp).
Sibling 1, was diagnosed with cataracts at 4 years of age and slowly progressive ataxia at 7. At 36 years, she had spastic/ataxic paraparesis, distal sensory impairment, mild dysarthria, and normal cognitive function. Nerve conduction studies confirmed a mild generalized sensorimotor peripheral neuropathy with reduction in the sural and ulnar sensory nerve action potentials and mild prolongation of F waves in the lower limbs. She was independent. Over a period of 16 months, her ataxia and dysarthria worsened and she underwent liver transplantation which initially gave some improvement after which her neurological function began to decline.
Sibling 2 was diagnosed with cataracts in early childhood and in late childhood, developed slowly progressive ataxia, dysarthria, and mild cognitive impairment. At 53 he had predominantly truncal ataxia and mild peripheral ataxia. He had lower limb spasticity and evidence of a mild peripheral neuropathy.
Both had extensive, mainly confluent, symmetrical signal abnormalities in the periventricular and deep cerebral white matter with relative sparing of the U-fibers. All individuals had bilateral involvement of the thalami with sparing of the basal nuclei, internal capsule, and corpus callosum.
Careful consideration should be given to the reporting of a single pathogenic variant as an incidental finding in the HMBS gene, due to its low clinical penetrance.
Sources: Expert Review
Childhood onset dystonia, chorea or related movement disorder v6.8 HMBS Sharon Whatley reviewed gene: HMBS: Rating: RED; Mode of pathogenicity: None; Publications: 14262853, 1577472, 15534187, 14970743, 31153822, 15534187; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.165 HMBS Sharon Whatley reviewed gene: HMBS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: 27539938, 38940544, 35584894, 14262853, 1577472, 15534187, 31153822, 14970743, 34089223, 27558376; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Hereditary neuropathy v1.497 HMBS Sharon Whatley reviewed gene: HMBS: Rating: GREEN; Mode of pathogenicity: None; Publications: 27539938, 38940544, 35584894, 14262853, 1577472, 15534187, 31153822, 14970743, 34089223, 27558376; Phenotypes: 176000, 620711, 620704; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Likely inborn error of metabolism v7.21 HMBS Sharon Whatley reviewed gene: HMBS: Rating: GREEN; Mode of pathogenicity: None; Publications: 38940544, 27539938, 14262853, 1577472, 15534187, 14970743, 27558376, 31153822, 34089223; Phenotypes: 176000, 620711, 620704; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Cerebral vascular malformations v3.18 DIAPH1 Alexandra Njegic gene: DIAPH1 was added
gene: DIAPH1 was added to Cerebral vascular malformations. Sources: Literature
Mode of inheritance for gene: DIAPH1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DIAPH1 were set to 34125151; 37400591; 37012328
Phenotypes for gene: DIAPH1 were set to Moyamoya disease
Penetrance for gene: DIAPH1 were set to Incomplete
Mode of pathogenicity for gene: DIAPH1 was set to Other
Review for gene: DIAPH1 was set to AMBER
Added comment: 34125151: Authors suggest MMD risk gene, haploinsufficiency mechanism. Discovery cohort of patients with sporadic, bilateral MMD associated with transfusion dependent thrombocytopenia, found 3/24 variants (2 de novo, 1 transmitted); 4/84 further MMD validation cohort (2 unphased, 1 transmitted). In silico predictions only, no phenotyping of parents. No probands had deafness – AD truncating DIAPH1 associated with deafness 1 with or without thrombocytopenia OMIM: 124900 and AR truncating variants are associated with seizures, cortical blindness, microcephaly syndrome OMIM: 616632.
37400591: 2/50 missense variants (7 synonymous) in an Asian MMD population, authors suggest an association between DIAPH1 mutation and PCA involvement in MMD.
37012328: 3 patients with MMA, DIAPH1 variants identified through WES filtering, no evidence of pathogenicity provided.
Sources: Literature
Undiagnosed metabolic disorders v1.627 HMBS Sharon Whatley reviewed gene: HMBS: Rating: GREEN; Mode of pathogenicity: None; Publications: 38940544, 27539938, 14262853, 1577472, 15534187, 14970743, 27558376, 31153822, 34089223; Phenotypes: 176000, 620711, 620704; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v7.8 HMBS Sharon Whatley reviewed gene: HMBS: Rating: GREEN; Mode of pathogenicity: None; Publications: 14262853; Phenotypes: 620711, 620704; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cutaneous photosensitivity with a likely genetic cause v3.5 HMBS Sharon Whatley reviewed gene: HMBS: Rating: RED; Mode of pathogenicity: None; Publications: 6962637; Phenotypes: 176000, 620711, 620704; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Inherited white matter disorders v1.184 HMBS Sharon Whatley reviewed gene: HMBS: Rating: GREEN; Mode of pathogenicity: None; Publications: 27539938, 31153822, 34089223; Phenotypes: 620711, 620704; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v6.9 HMBS Sharon Whatley changed review comment from: Relevant metabolic investigation: urine porphobilinogen
Although HMBS biallelic pathogenic variants are very rare (8 families worldwide to date) five families have been shown to have white matter anomalies on MRI.
PMID: 15534187 Solis reported a 28 month old patient with homozygous HMBS variants c.499C>T, p.(Arg167Trp), bilateral capsular cataracts and a unique pattern of deep cerebral white matter injury, with relative preservation of the corpus callosum, anterior limb of the internal capsule, cerebral grey matter, and infratentorial structures. He had no history of seizures. Neurologic examination confirmed peripheral neuropathy, psychomotor delay and revealed occasional dystonic head positioning and dystonic arm movements. The proband had approximately 1% of normal mean erythrocyte HMBS activity, and urinary ALA and PBG were markedly elevated. He died at 40 months.
PMID: 27558376 Kevelam reports 3 siblings (between 58, 63 and 57 years old) from a single family see previous review.
PMID: 31153822 Dixon reported an 11 month old patient with biallelic HMBS variants (c.500G > A, p.(Arg167Gln) and c.104C>T, p.(Thr35Met)). At 4-6 weeks of age, he was noted to have developmental delays and later apnoeic episodes. At 3 months he had seizures and feeding difficulty. At 11 months no dysmorphic features were noted. He had an abnormal neurological exam with slight left lower facial droop, hypotonic throughout, absent reflexes in both lower extremities. Magnetic resonance spectroscopy of the brain, revealed an abnormal lactate peak in the cerebral white matter and enlarged bilateral fronto-parietal subarachnoid spaces (BESSI). He had an abnormal electroencephalogram with focal seizure activity but a comprehensive epilepsy panel was negative.
PMID: 34089223 Stutterd reported two siblings see previous review.
Careful consideration should be given to the reporting of a single pathogenic variant as an incidental finding in the HMBS gene, due to its low clinical penetrance.; to: Relevant metabolic investigation: urine porphobilinogen
Although HMBS biallelic pathogenic variants are very rare (8 families worldwide to date) five families have been shown to have white matter anomalies on MRI.
PMID: 15534187 Solis reported a 28 month old patient with homozygous HMBS variants c.499C>T, p.(Arg167Trp), bilateral capsular cataracts and a unique pattern of deep cerebral white matter injury, with relative preservation of the corpus callosum, anterior limb of the internal capsule, cerebral grey matter, and infratentorial structures. He had no history of seizures. Neurologic examination confirmed peripheral neuropathy, psychomotor delay and revealed occasional dystonic head positioning and dystonic arm movements. The proband had approximately 1% of normal mean erythrocyte HMBS activity, and urinary ALA and PBG were markedly elevated. He died at 40 months.
PMID: 27558376 Kevelam reports 3 siblings (between 58, 63 and 57 years old) from a single family see previous review.
PMID: 31153822 Dixon reported an 11 month old patient with biallelic HMBS variants (c.500G > A, p.(Arg167Gln) and c.104C>T, p.(Thr35Met)). At 4-6 weeks of age, he was noted to have developmental delays and later apnoeic episodes. At 3 months he had seizures and feeding difficulty. At 11 months no dysmorphic features were noted. He had an abnormal neurological exam with slight left lower facial droop, hypotonic throughout, absent reflexes in both lower extremities. Magnetic resonance spectroscopy of the brain, revealed an abnormal lactate peak in the cerebral white matter and enlarged bilateral fronto-parietal subarachnoid spaces (BESSI). He had an abnormal electroencephalogram with focal seizure activity but a comprehensive epilepsy panel was negative.
PMID: 34089223 Stutterd reported two siblings see previous review.
Careful consideration should be given to the reporting of a single pathogenic variant as an incidental finding in the HMBS gene, due to its low clinical penetrance.
Non-acute porphyrias v1.24 HMBS Sharon Whatley reviewed gene: HMBS: Rating: RED; Mode of pathogenicity: None; Publications: 37540847, 14262853, 1577472, 15534187, 14970743, 27558376, 31153822, 34089223; Phenotypes: 176000, 620711, 620704; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v7.25 HMBS Sharon Whatley changed review comment from: Relevant metabolic investigation: urine porphobilinogen
Although HMBS biallelic pathogenic variants are very rare (8 families worldwide to date) three families (7 individuals) have been shown to have cerebellar ataxia.
PMID: 1577472 Llewellyn reported two siblings with HMBS biallelic pathogenic variants c.499C>T, p.(Arg167Trp) and c.500G>A, p.(Arg167Gln). At the age of 18 months one patient had ataxia with intention tremor and dysarthria secondary to partial agenesis of the cerebella vermis bilateral cataracts and right optic nerve hypoplasia. Biochemical studies showed excessive excretion of PBG with normal faecal porphyrin and very low erythrocyte PBG deaminase activity. At 3 years of age, she was admitted to hospital following febrile convulsions. When assessed one year later, she had had no further convulsions or symptoms of acute porphyria. She died at 8 years of age.
PMID: 15828996 Sheppard reported on the sibling of the above patient. He had no cataracts or other abnormalities with a normal cerebral ultrasound at birth. Urine PBG was raised and erythrocyte PBG-deaminase activity was very low. Developmental progress was normal up to 18 months old. At 10 years of age clinical signs included severe ataxia, peripheral neuropathy and dysarthria. Urinary porphyrins were continuously elevated in this patient.
PMID: 27558376 Kevelam reports 3 siblings with cerebellar ataxia see previous review.
PMID: 34089223 Stutterd reported two siblings and an unrelated patient with ataxia see previous review.
Careful consideration should be given to the reporting of a single pathogenic variant as an incidental finding in the HMBS gene, due to its low clinical penetrance.; to: Relevant metabolic investigation: urine porphobilinogen
Although HMBS biallelic pathogenic variants are very rare (8 families worldwide to date) three families (7 individuals) have been shown to have cerebellar ataxia.
PMID: 1577472 Llewellyn reported two siblings with HMBS biallelic pathogenic variants c.499C>T, p.(Arg167Trp) and c.500G>A, p.(Arg167Gln). At the age of 18 months one patient had ataxia with intention tremor and dysarthria secondary to partial agenesis of the cerebella vermis, bilateral cataracts and right optic nerve hypoplasia. Biochemical studies showed excessive excretion of PBG with normal faecal porphyrin and very low erythrocyte PBG deaminase activity. At 3 years of age, she was admitted to hospital following febrile convulsions. When assessed one year later, she had had no further convulsions or symptoms of acute porphyria. She died at 8 years of age.
PMID: 15828996 Sheppard reported on the sibling of the above patient. He had no cataracts or other abnormalities with a normal cerebral ultrasound at birth. Urine PBG was raised and erythrocyte PBG-deaminase activity was very low. Developmental progress was normal up to 18 months old. At 10 years of age clinical signs included severe ataxia, peripheral neuropathy and dysarthria. Urinary porphyrins were continuously elevated in this patient.
PMID: 27558376 Kevelam reports 3 siblings with cerebellar ataxia see previous review.
PMID: 34089223 Stutterd reported two siblings and an unrelated patient with ataxia see previous review.
Careful consideration should be given to the reporting of a single pathogenic variant as an incidental finding in the HMBS gene, due to its low clinical penetrance.
Ataxia and cerebellar anomalies - narrow panel v7.25 HMBS Sharon Whatley reviewed gene: HMBS: Rating: GREEN; Mode of pathogenicity: None; Publications: 1577472, 15828996; Phenotypes: Leukoencephalopathy, HP:0002352, cerebellar ataxia, MONDO:0000437; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Erythrocytosis v2.11 SH2B3 Terri McVeigh reviewed gene: SH2B3: Rating: GREEN; Mode of pathogenicity: None; Publications: https://doi.org/10.1182/blood-2024-210339, 10.1016/j.ejcped.2023.100042, PMID: 38024597, PMID: 37981895, https://doi.org/10.1182/blood-2013-08-519843, https://doi.org/10.1016/j.leukres.2024.107566https://doi.org/10.1182/blood-2013-05-500850; Phenotypes: thrombocytosis, myeloproliferative disease, ALL; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cerebral vascular malformations v3.18 ANO1 Alexandra Njegic gene: ANO1 was added
gene: ANO1 was added to Cerebral vascular malformations. Sources: Literature
Mode of inheritance for gene: ANO1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ANO1 were set to 37253099; 37012328
Phenotypes for gene: ANO1 were set to Moyamoya disease 7, 620687
Penetrance for gene: ANO1 were set to Incomplete
Mode of pathogenicity for gene: ANO1 was set to Other
Review for gene: ANO1 was set to AMBER
Added comment: 37253099: 6 families showed AD, 1 patient AR. GOF and LOF implied. 7 variants identified total from 84 unsolved families and additional 150 probands. In vitro modelling of different missense variants in HEK cells shows GOF and LOF mechanisms. GOF variants (p.Met658Val, p.Glu459Lys, p.Thr740Ile p.Glu170Lys) have increased membrane Cl− conductance at lower intracellular Ca2+ levels, determined through patch clamp. Predicted LOF p.Arg890Gln (in gnomAD) as no Ca2+ currents evoked. Some variants show no alteration to Ca2+ sensitivity (p.Arg77Gln [in gnomAD) and p.Ser196Thr) but near binding site for PIP2. Authors note that ANO1 may be paternally imprinted as affected individuals who inherited the variant from their mothers had an earlier age at onset, whereas those who inherited the variant from their father had later onset (families MM137/MM001).
37012328: 88 paediatric MMA patients, 3 patients with mixed clinical presentations had ANO1 variants through WES filtering, no evidence of pathogenicity provided.
Sources: Literature
White matter disorders and cerebral calcification - narrow panel v6.9 HMBS Sharon Whatley reviewed gene: HMBS: Rating: GREEN; Mode of pathogenicity: None; Publications: 15534187, 31153822; Phenotypes: Leukoencephalopathy, HP:0002352; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Acute intermittent porphyria v1.1 HMBS Sharon Whatley reviewed gene: HMBS: Rating: GREEN; Mode of pathogenicity: None; Publications: 27539938, 38940544, 14262853, 1577472, 15534187, 14970743, 27558376, 31153822, 34089223; Phenotypes: 176000; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Dilated and arrhythmogenic cardiomyopathy v2.36 TAX1BP3 Achchuthan Shanmugasundram Deleted their comment
Dilated and arrhythmogenic cardiomyopathy v2.36 TAX1BP3 Achchuthan Shanmugasundram commented on gene: TAX1BP3: PMID:39963794 reported a kindred with multiple members affected by arrhythmogenic cardiomyopathy (ACM) cosegregating with biallelic TAX1BP3 variants (~28 kb deletion encompassing the entire gene and missense variant p.(Met78Thr)). Three affected siblings from the family had the bialleic variants which were absent in an unaffected sister. Carrier parents were normal.

Experimental work on patient-derived induced pluripotent stem cell cardiac myocytes and a knockout mouse model showed that loss of TAX1BP3 causes calcium dysregulation in cardiomyocytes, which is a known mechanism for arrhythmia.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Dilated and arrhythmogenic cardiomyopathy v2.36 TAX1BP3 Achchuthan Shanmugasundram reviewed gene: TAX1BP3: Rating: AMBER; Mode of pathogenicity: None; Publications: 39963794; Phenotypes: Arrhythmogenic cardiomyopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Respiratory ciliopathies including non-CF bronchiectasis v3.37 CFAP46 Achchuthan Shanmugasundram changed review comment from: PMID:29843777 reported a single individual with a heterotaxy syndrome and with a multigenic CNV duplication including CFAP46. This patient also carried a variant in LEFTY1 gene.

PMID:39362668 reported a male patient with compound heterozygous CFAP46 variants and with primary ciliary dyskinesia. The patient presented with chronic respiratory symptoms, bronchiectasis, chronic rhinitis, hearing and ear symptoms, and situs solitus.

This gene has not yet been associated with relevant phenotypes in OMIM or in Gene2Phenotype.

This gene should be rated red with current evidence.; to: PMID:29843777 reported a single individual with a heterotaxy syndrome and with a multigenic CNV duplication including CFAP46. This patient also carried a variant in LEFTY1 gene.

PMID:39362668 reported a male patient with compound heterozygous CFAP46 variants and with primary ciliary dyskinesia. The patient presented with chronic respiratory symptoms, bronchiectasis, chronic rhinitis, hearing and ear symptoms, and situs solitus.

This gene has not yet been associated with relevant phenotypes in OMIM or in Gene2Phenotype.
Respiratory ciliopathies including non-CF bronchiectasis v3.37 CFAP46 Achchuthan Shanmugasundram Phenotypes for gene: CFAP46 were changed from Heterotaxy to primary ciliary dyskinesia, MONDO:0016575
Respiratory ciliopathies including non-CF bronchiectasis v3.36 CFAP46 Achchuthan Shanmugasundram Publications for gene: CFAP46 were set to 29843777
Respiratory ciliopathies including non-CF bronchiectasis v3.35 CFAP46 Achchuthan Shanmugasundram Mode of inheritance for gene: CFAP46 was changed from to BIALLELIC, autosomal or pseudoautosomal
Respiratory ciliopathies including non-CF bronchiectasis v3.34 CFAP46 Achchuthan Shanmugasundram reviewed gene: CFAP46: Rating: RED; Mode of pathogenicity: None; Publications: 29843777, 39362668; Phenotypes: primary ciliary dyskinesia, MONDO:0016575; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Respiratory ciliopathies including non-CF bronchiectasis v3.34 CFAP221 Achchuthan Shanmugasundram Classified gene: CFAP221 as Amber List (moderate evidence)
Respiratory ciliopathies including non-CF bronchiectasis v3.34 CFAP221 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Steven Cowman, there are two unrelated families reported with biallelic CFAP221 variants and with a PCD phenotype including bronchiectasis. Hence, this gene can be rated amber with current evidence.
Respiratory ciliopathies including non-CF bronchiectasis v3.34 CFAP221 Achchuthan Shanmugasundram Gene: cfap221 has been classified as Amber List (Moderate Evidence).
Respiratory ciliopathies including non-CF bronchiectasis v3.33 CFAP221 Achchuthan Shanmugasundram reviewed gene: CFAP221: Rating: AMBER; Mode of pathogenicity: None; Publications: 31636325, 39362668; Phenotypes: primary ciliary dyskinesia, MONDO:0016575; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Respiratory ciliopathies including non-CF bronchiectasis v3.33 CFAP221 Achchuthan Shanmugasundram Publications for gene: CFAP221 were set to 31636325
Early onset or syndromic epilepsy v7.86 STARD7_ATTTC Sarah Leigh commented on STR: STARD7_ATTTC: A long stretch ATTTC repeats is present in conjunction with ATTTT repeats in the intron 1 in the STARD7 gene in patients with OMIM:607876 (Corbett et al. 2019 PMID:31664034). In affected individuals the pathogenic configuration was defined as: (ATTTC)exp(ATTTT )exp. None of the control samples had any repeats of the pathogenic ATTTC motif (PMID:31664034).
Early onset or syndromic epilepsy v7.86 STARD7_ATTTC Sarah Leigh STR: STARD7_ATTTC was added
STR: STARD7_ATTTC was added to Early onset or syndromic epilepsy. Sources: Literature
STR, NGS Not Validated tags were added to STR: STARD7_ATTTC.
Mode of inheritance for STR: STARD7_ATTTC was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for STR: STARD7_ATTTC were set to 31664034
Phenotypes for STR: STARD7_ATTTC were set to Epilepsy, familial adult myoclonic, 2, OMIM:607876; epilepsy, familial adult myoclonic, 2, MONDO:0011930
Review for STR: STARD7_ATTTC was set to GREEN
Added comment: STARD7 transcribed from the reverse strand, which means that the repeated sequence is the reverse compliment of the forward strand sequence.

STARD7_ATTTC is on https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r4

STARD7_ATTTC is on https://stripy.org/database

STARD7_ATTTT is on DRAGON 4.02.

The coordinates of the sequence repeats shown above were the same on DRAGON 4.02, https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r4 and https://stripy.org/database
The non-pathogenic and pathogenic ranges of the sequence repeats shown above were obtained from: https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r4 and https://stripy.org/database

There is enough evidence for this STR to be green on this panel.

This STR has not been approved by NHS STR working group and is not NGS Not Validated
Sources: Literature
Early onset or syndromic epilepsy v7.85 STARD7 Sarah Leigh Phenotypes for gene: STARD7 were changed from Epilepsy, familial adult myoclonic, 2, 607876; Familial adult myoclonic epilepsy-2; FAME-2 to Epilepsy, familial adult myoclonic, 2, OMIM:607876; epilepsy, familial adult myoclonic, 2, MONDO:0011930
Hereditary neuropathy or pain disorder v6.165 VWA1_GGCGCGGAGC Sarah Leigh Tag STR tag was added to STR: VWA1_GGCGCGGAGC.
Hereditary neuropathy or pain disorder v6.165 VWA1_GGCGCGGAGC Sarah Leigh STR: VWA1_GGCGCGGAGC was added
STR: VWA1_GGCGCGGAGC was added to Hereditary neuropathy or pain disorder. Sources: Literature
NGS Not Validated tags were added to STR: VWA1_GGCGCGGAGC.
Mode of inheritance for STR: VWA1_GGCGCGGAGC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for STR: VWA1_GGCGCGGAGC were set to 33559681
Phenotypes for STR: VWA1_GGCGCGGAGC were set to Neuronopathy, distal hereditary motor, autosomal recessive 7, OMIM:619216; neuronopathy, distal hereditary motor, autosomal recessive 7, MONDO:0030977
Review for STR: VWA1_GGCGCGGAGC was set to GREEN
Added comment: VWA1 is transcribed from the forward strand.

VWA1_GGCGCGGAGC is on https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r4

VWA1_GGCGCGGAGC is on https://stripy.org/database

VWA1_GGCGCGGAGC is on DRAGON 4.02.

The coordinates of the sequence repeats shown above were the same on the above resources.

The non-pathogenic and pathogenic ranges of the sequence repeats shown above were obtained from: https://stripy.org/database and https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r4

There is enough evidence for this STR to be green on this panel.

This STR has not been approved by NHS STR working group and is not NGS Not Validated
Sources: Literature
Segmental overgrowth disorders - Deep sequencing v3.19 PADI6 Sarah Leigh Tag Q2_25_ demote_red tag was added to gene: PADI6.
Tag Q2_25_expert_review tag was added to gene: PADI6.
Segmental overgrowth disorders - Deep sequencing v3.19 PADI6 Sarah Leigh edited their review of gene: PADI6: Added comment: Based on review given by Tom Cullup (Great Ormond Street Hospital), PADI6 is not relevant to this panel (Segmental overgrowth disorders - Deep sequencing) and should be demoted to Red. PADI6 variants will be identified using the Multi locus imprinting disorders (R417.2) panel, where this gene is Green.; Changed rating: RED
Polycystic liver disease v1.31 SEC61B Sarah Leigh Tag watchlist tag was added to gene: SEC61B.
Polycystic liver disease v1.31 SEC61B Sarah Leigh reviewed gene: SEC61B: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Fetal anomalies v5.87 LMNB2 Sarah Graham reviewed gene: LMNB2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 40011009; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Monogenic short stature v1.15 RNPC3 Sarah Leigh reviewed gene: RNPC3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Palmoplantar keratodermas v3.27 POMP Arina Puzriakova Deleted their comment
Monogenic short stature v1.15 RNPC3 Sarah Leigh Tag Q2_25_expert_review tag was added to gene: RNPC3.
Monogenic short stature v1.15 RNPC3 Sarah Leigh Tag Q2_25_ demote_red tag was added to gene: RNPC3.
Tag Q2_25_ phenotype tag was added to gene: RNPC3.
Undiagnosed metabolic disorders v1.627 ABCA1 Sarah Leigh Tag Q2_25_ promote_green was removed from gene: ABCA1.
Tag Q2_25_ demote_red was removed from gene: ABCA1.
Tag Q2_25_ MOI was removed from gene: ABCA1.
Tag Q2_25_ demote_amber was removed from gene: ABCA1.
Tag Q2_25_ NHS_review was removed from gene: ABCA1.
Tag Q2_25_ phenotype was removed from gene: ABCA1.
Undiagnosed metabolic disorders v1.627 ABCA1 Sarah Leigh Tag Q2_25_ promote_green tag was added to gene: ABCA1.
Tag Q2_25_ demote_red tag was added to gene: ABCA1.
Tag Q2_25_ MOI tag was added to gene: ABCA1.
Tag Q2_25_ demote_amber tag was added to gene: ABCA1.
Tag Q2_25_ NHS_review tag was added to gene: ABCA1.
Tag Q2_25_ phenotype tag was added to gene: ABCA1.
Respiratory ciliopathies including non-CF bronchiectasis v3.32 CFAP54 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: CFAP54.
Respiratory ciliopathies including non-CF bronchiectasis v3.32 CFAP54 Achchuthan Shanmugasundram Tag Q1_25_ promote_green tag was added to gene: CFAP54.
Respiratory ciliopathies including non-CF bronchiectasis v3.32 CFAP54 Achchuthan Shanmugasundram Phenotypes for gene: CFAP54 were changed from to Ciliary dyskinesia, primary, 54, OMIM:621125
Respiratory ciliopathies including non-CF bronchiectasis v3.31 CFAP54 Achchuthan Shanmugasundram Publications for gene: CFAP54 were set to 26224312
Respiratory ciliopathies including non-CF bronchiectasis v3.30 CFAP54 Achchuthan Shanmugasundram Mode of inheritance for gene: CFAP54 was changed from to BIALLELIC, autosomal or pseudoautosomal
Respiratory ciliopathies including non-CF bronchiectasis v3.29 CFAP54 Achchuthan Shanmugasundram Classified gene: CFAP54 as Amber List (moderate evidence)
Respiratory ciliopathies including non-CF bronchiectasis v3.29 CFAP54 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Steven Cowman and associated with relevant phenotypes in OMIM (MIM #621125), there is sufficient evidence available (five unrelated families and mouse model) for the promotion of this gene to green rating on the next GMS update.
Respiratory ciliopathies including non-CF bronchiectasis v3.29 CFAP54 Achchuthan Shanmugasundram Gene: cfap54 has been classified as Amber List (Moderate Evidence).
Respiratory ciliopathies including non-CF bronchiectasis v3.28 CFAP54 Achchuthan Shanmugasundram reviewed gene: CFAP54: Rating: GREEN; Mode of pathogenicity: None; Publications: 37725231, 39362668; Phenotypes: Ciliary dyskinesia, primary, 54, OMIM:621125; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic short stature v1.15 GH1 Sarah Leigh reviewed gene: GH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 8496314, 8288694, 8552145, 10689634, 18554279, 17726075; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Monogenic short stature v1.15 GH1 Sarah Leigh Tag Q1_25_ NHS_review tag was added to gene: GH1.
Tag Q1_25_ promote_green tag was added to gene: GH1.
Monogenic short stature v1.15 GH1 Sarah Leigh Classified gene: GH1 as Amber List (moderate evidence)
Monogenic short stature v1.15 GH1 Sarah Leigh Gene: gh1 has been classified as Amber List (Moderate Evidence).
Monogenic short stature v1.14 GH1 Sarah Leigh Phenotypes for gene: GH1 were changed from Growth hormone deficiency to Growth hormone deficiency, isolated, type IA, OMIM:262400; Growth hormone deficiency, isolated, type IB, OMIM:612781; Growth hormone deficiency, isolated, type II, OMIM:173100; Growth hormone deficiency; Kowarski syndrome, OMIM:262650
Pituitary hormone deficiency v3.15 GH1 Sarah Leigh Phenotypes for gene: GH1 were changed from Growth hormone deficiency, isolated, type II (173100); Growth hormone deficiency, isolated, type IA (262400); Growth hormone deficiency, isolated, type IB (612781) to Growth hormone deficiency, isolated, type IA, OMIM:262400; Growth hormone deficiency, isolated, type IB, OMIM:612781; Growth hormone deficiency, isolated, type II, OMIM:173100
Corneal dystrophy v3.13 TCF4_CTG Sarah Leigh STR: TCF4_CTG was added
STR: TCF4_CTG was added to Corneal dystrophy. Sources: Literature
STR, NGS Not Validated tags were added to STR: TCF4_CTG.
Mode of inheritance for STR: TCF4_CTG was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for STR: TCF4_CTG were set to 29526280; 26401622; 24255041; 25168903; 25722209; 25593321
Phenotypes for STR: TCF4_CTG were set to Corneal dystrophy, Fuchs endothelial, 3, OMIM:613267; corneal dystrophy, Fuchs endothelial, 3, MONDO:0013203
Review for STR: TCF4_CTG was set to GREEN
Added comment: TCF4 transcribed from the reverse strand, which means that the repeated sequence is the reverse compliment of the forward strand sequence.

TCF4_CTG is on https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r4

TCF4_CTG is on https://stripy.org/database

TCF4_CTG is on DRAGON 4.02.

The coordinates of the sequence repeats shown above were obtained from DRAGON 4.02
The coordinates https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r4 and https://stripy.org/database were the same as above.

The non-pathogenic and pathogenic ranges of the sequence repeats shown above were obtained from: https://stripy.org/database

There is enough evidence for this STR to be green on this panel.

This STR has not been approved by NHS STR working group and is not NGS Not Validated
Sources: Literature
Early onset or syndromic epilepsy v7.84 SAMD12_TTTCA Sarah Leigh changed review comment from: SAMD12 transcribed from the reverse strand, which means that the repeated sequence is the reverse compliment of the forward strand sequence.

SAMD12_TTTCA is on https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r3

SAMD12_TTTCA is on https://stripy.org/database

SAMD12_TTTTA is on DRAGON 4.02.

The coordinates and pathogenic ranges of the sequence repeats shown above were obtained from DRAGON 4.02
The coordinates https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r4 and https://stripy.org/database were 8:118366815-118366913 (hg38)

There is enough evidence for this STR to be green on this panel.

This STR has not been approved by NHS STR working group and is not NGS Not Validated
Sources: Literature; to: SAMD12 transcribed from the reverse strand, which means that the repeated sequence is the reverse compliment of the forward strand sequence.

SAMD12_TTTCA is on https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r3

SAMD12_TTTCA is on https://stripy.org/database

SAMD12_TTTTA is on DRAGON 4.02.

The coordinates of the sequence repeats shown above were obtained from DRAGON 4.02
The coordinates https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r4 and https://stripy.org/database were 8:118366815-118366913 (hg38)

The non-pathogenic and pathogenic ranges of the sequence repeats shown above were obtained from: https://stripy.org/database

There is enough evidence for this STR to be green on this panel.

This STR has not been approved by NHS STR working group and is not NGS Not Validated
Sources: Literature
Early onset or syndromic epilepsy v7.84 SAMD12_TTTCA Sarah Leigh commented on STR: SAMD12_TTTCA: The TTTCA repeat is present in conjunction with TTTTA repeats in patients with OMIM:601068. Ishiura et al., 2018 (PMID: 29507423). In patients the expansions TTTCA and TTTTA combined was estimated to be in the range of 440 to 3680 repeats (one patient had 598 repeats of TTTTA and 458 repeats of TTTCA). In 82 patients the configuration of expansion was interpreted as: (TTTTA)exp(TTTCA)exp and in one family it was given as: (TTTTA)exp(TTTCA)exp(TTTTA)exp. There were no reports of TTTCA expansions in controls, however, 5.9% of healthy individuals had TTTTA expansions, therefore suggesting that the TTTTA expansion does no contribute to the disease (Ishiura et al., 2018).
Early onset or syndromic epilepsy v7.84 SAMD12_TTTCA Sarah Leigh Mode of inheritance for STR: SAMD12_TTTCA was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Early onset or syndromic epilepsy v7.83 SAMD12_TTTCA Sarah Leigh Phenotypes for STR: SAMD12_TTTCA were changed from to Epilepsy, familial adult myoclonic, 1, OMIM:601068; epilepsy, familial adult myoclonic, 1, MONDO:0010985
Early onset or syndromic epilepsy v7.82 SAMD12_TTTCA Sarah Leigh edited their review of STR: SAMD12_TTTCA: Changed rating: GREEN
Early onset or syndromic epilepsy v7.82 SAMD12_TTTCA Sarah Leigh STR: SAMD12_TTTCA was added
STR: SAMD12_TTTCA was added to Early onset or syndromic epilepsy. Sources: Literature
STR, NGS Not Validated tags were added to STR: SAMD12_TTTCA.
Mode of inheritance for STR: SAMD12_TTTCA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for STR: SAMD12_TTTCA were set to 30194086; 29507423; 29939203; 32203200
Review for STR: SAMD12_TTTCA was set to AMBER
Added comment: SAMD12 transcribed from the reverse strand, which means that the repeated sequence is the reverse compliment of the forward strand sequence.

SAMD12_TTTCA is on https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r3

SAMD12_TTTCA is on https://stripy.org/database

SAMD12_TTTTA is on DRAGON 4.02.

The coordinates and pathogenic ranges of the sequence repeats shown above were obtained from DRAGON 4.02
The coordinates https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r4 and https://stripy.org/database were 8:118366815-118366913 (hg38)

There is enough evidence for this STR to be green on this panel.

This STR has not been approved by NHS STR working group and is not NGS Not Validated
Sources: Literature
Intellectual disability v8.235 KDM5B Tracy Lester reviewed gene: KDM5B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual disability, developmental delay; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Respiratory ciliopathies including non-CF bronchiectasis v3.28 CFAP74 Achchuthan Shanmugasundram Classified gene: CFAP74 as Amber List (moderate evidence)
Respiratory ciliopathies including non-CF bronchiectasis v3.28 CFAP74 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Steven Cowman and associated with relevant phenotypes in OMIM (MIM #620197), there is sufficient evidence available (four unrelated families in total) for the promotion of this gene to green rating on the next GMS update.
Respiratory ciliopathies including non-CF bronchiectasis v3.28 CFAP74 Achchuthan Shanmugasundram Gene: cfap74 has been classified as Amber List (Moderate Evidence).
Respiratory ciliopathies including non-CF bronchiectasis v3.27 CFAP74 Achchuthan Shanmugasundram Phenotypes for gene: CFAP74 were changed from Primary ciliary dyskinesia; infertility to Ciliary dyskinesia, primary, 49, without situs inversus, OMIM:620197
Respiratory ciliopathies including non-CF bronchiectasis v3.26 CFAP74 Achchuthan Shanmugasundram Publications for gene: CFAP74 were set to 32555313
Respiratory ciliopathies including non-CF bronchiectasis v3.25 CFAP74 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: CFAP74.
Tag Q1_25_ promote_green tag was added to gene: CFAP74.
Respiratory ciliopathies including non-CF bronchiectasis v3.25 CFAP74 Achchuthan Shanmugasundram reviewed gene: CFAP74: Rating: GREEN; Mode of pathogenicity: None; Publications: 32555313, 36047773, 39362668; Phenotypes: Ciliary dyskinesia, primary, 49, without situs inversus, OMIM:620197; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Inherited phaeochromocytoma and paraganglioma excluding NF1 v3.6 DNMT3A Sarah Leigh Tag Q1_25_ promote_green tag was added to gene: DNMT3A.
Inherited phaeochromocytoma and paraganglioma excluding NF1 v3.6 DNMT3A Sarah Leigh edited their review of gene: DNMT3A: Added comment: Four different DNMT3A variants have so far been associated with carotid paragangliomas in a total of ten cases as part of a syndrome. All of the variants are located within the proline-tryptophan-tryptophan-proline (PWWP) domain of DNMT3A (PMID: 29740169; 33182397; 39166703). De novo occurrence of the DNMT3A variant was proven in one case, one variant was inherited from a mother in another case, three were somatic and the inheritance could not be established in five cases (PMID: 29740169; 33182397; 39166703). The DNMT3A variants had a gain of function mechanism, resulting in hypermethylation of polycomb-marked developmental genes and altered chromatin binding specificity (PMID: 39166703).; Changed rating: GREEN
Inherited phaeochromocytoma and paraganglioma excluding NF1 v3.6 DNMT3A Sarah Leigh Publications for gene: DNMT3A were set to 39166703
Inherited phaeochromocytoma and paraganglioma excluding NF1 v3.5 DNMT3A Sarah Leigh Phenotypes for gene: DNMT3A were changed from Heyn-Sproul-Jackson syndrome, OMIM: 618724 to Heyn-Sproul-Jackson syndrome, OMIM: 618724
Inherited phaeochromocytoma and paraganglioma excluding NF1 v3.4 DNMT3A Sarah Leigh Added comment: Comment on phenotypes: The patient reported in PMID: 39166703 had Heyn-Sproul-Jackson syndrome (OMIM: 618724), with recurrent carotid paragangliomas.
Inherited phaeochromocytoma and paraganglioma excluding NF1 v3.4 DNMT3A Sarah Leigh Phenotypes for gene: DNMT3A were changed from Recurrent carotid paragangliomas to Heyn-Sproul-Jackson syndrome, OMIM: 618724
Inherited phaeochromocytoma and paraganglioma excluding NF1 v3.3 DNMT3A Sarah Leigh Phenotypes for gene: DNMT3A were changed from to Recurrent carotid paragangliomas
Inherited phaeochromocytoma and paraganglioma excluding NF1 v3.2 DNMT3A Sarah Leigh Classified gene: DNMT3A as Amber List (moderate evidence)
Inherited phaeochromocytoma and paraganglioma excluding NF1 v3.2 DNMT3A Sarah Leigh Gene: dnmt3a has been classified as Amber List (Moderate Evidence).
Hereditary Erythrocytosis v2.11 JAK2 Sarah Leigh Tag Q1_25_ NHS_review tag was added to gene: JAK2.
Tag Q1_25_ MOI tag was added to gene: JAK2.
Tag Q1_25_ promote_green tag was added to gene: JAK2.
Hereditary Erythrocytosis v2.11 JAK2 Sarah Leigh changed review comment from: At least four JAK2 variants have been associated with Hereditary erythrocytosis (PMID: 38629639; 37639050; 27389715). Three biallelic JAK2 variants have been reported in in two unrelated cases (one case being compound heterozygous PMID: 27389715, and the other being homozygous (PMID: 37639050), the forth variant occurs as a heterozygote in the proband, her mother and daughter (PMID: 38629639). All of these four variants have a hyperactivating effect on JAK2/STAT5 signaling pathway (PMID: 38629639; 37639050; 27389715).; to: At least four JAK2 variants have been associated with Hereditary erythrocytosis (PMID: 38629639; 37639050; 27389715). Three biallelic JAK2 variants have been reported in two unrelated cases (one case being compound heterozygous PMID: 27389715, and the other being homozygous (PMID: 37639050), the forth variant occurs as a heterozygote in the proband, her mother and daughter (PMID: 38629639). All of these four variants have a hyperactivating effect on JAK2/STAT5 signaling pathway (PMID: 38629639; 37639050; 27389715).
Hereditary Erythrocytosis v2.11 JAK2 Sarah Leigh Mode of inheritance for gene: JAK2 was changed from Other to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary Erythrocytosis v2.10 JAK2 Sarah Leigh edited their review of gene: JAK2: Added comment: At least four JAK2 variants have been associated with Hereditary erythrocytosis (PMID: 38629639; 37639050; 27389715). Three biallelic JAK2 variants have been reported in in two unrelated cases (one case being compound heterozygous PMID: 27389715, and the other being homozygous (PMID: 37639050), the forth variant occurs as a heterozygote in the proband, her mother and daughter (PMID: 38629639). All of these four variants have a hyperactivating effect on JAK2/STAT5 signaling pathway (PMID: 38629639; 37639050; 27389715).; Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Changed phenotypes to: Hereditary erythrocytosis; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary Erythrocytosis v2.10 JAK2 Sarah Leigh Added comment: Comment on mode of pathogenicity: Functional studies demonstrate that the missense JAK2 variants reported in PMID: 38629639; 37639050; 27389715 all have a gain of funtion.
Hereditary Erythrocytosis v2.10 JAK2 Sarah Leigh Mode of pathogenicity for gene: JAK2 was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Hereditary Erythrocytosis v2.9 JAK2 Sarah Leigh Phenotypes for gene: JAK2 were changed from Erythrocytosis, somatic, OMIM:133100; primary familial polycythemia due to EPO receptor mutation, MONDO:0007572 to Hereditary erythrocytosis
Hereditary Erythrocytosis v2.8 JAK2 Sarah Leigh Phenotypes for gene: JAK2 were changed from Erythrocytosis, somatic, OMIM:133100 to Erythrocytosis, somatic, OMIM:133100; primary familial polycythemia due to EPO receptor mutation, MONDO:0007572
Hereditary Erythrocytosis v2.7 JAK2 Sarah Leigh Publications for gene: JAK2 were set to
Segmental overgrowth disorders - Deep sequencing v3.19 PADI6 Tom Cullup reviewed gene: PADI6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Retinal disorders v7.25 C19orf44 Sarah Leigh reviewed gene: C19orf44: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v7.25 C19orf44 Sarah Leigh Phenotypes for gene: C19orf44 were changed from retinal dystrophy; macular dystrophy; cone-rod dystrophy; rod-cone dystrophy to late onset retinal dystrophy
Retinal disorders v7.24 C19orf44 Sarah Leigh Publications for gene: C19orf44 were set to
Retinal disorders v7.23 C19orf44 Sarah Leigh Mode of pathogenicity for gene: C19orf44 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
Retinal disorders v7.22 C19orf44 Sarah Leigh Tag Q1_25_ NHS_review tag was added to gene: C19orf44.
Tag Q1_25_ promote_green tag was added to gene: C19orf44.
Retinal disorders v7.22 C19orf44 Sarah Leigh Classified gene: C19orf44 as Amber List (moderate evidence)
Retinal disorders v7.22 C19orf44 Sarah Leigh Gene: c19orf44 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v7.23 SPOUT1 Sarah Leigh changed review comment from: PMID: 39962046 reports the association of biallelic SPOUT1 variants with SPOUT1 Associated Development delay Microcephaly Seizures Short stature. In this study, a total of 18 SPOUT1 variants were found in 28 individuals from 21 unrelated families. Intellectual disability was evident in 10/10 families where it could be ascertained, seizures were reported in 16/21 of the families and short stature was seen in 13/15 families where it could be measured.
SPOUT1 variant zebra fish models showed reduction in larval head size with concomitant apoptosis and the human SPOUT1 missense variants were pathogenic in complementation assays in zebrafish (PMID: 39962046).
Sources: Literature; to: PMID: 39962046 reports the association of biallelic SPOUT1 variants with SPOUT1 Associated Development delay Microcephaly Seizures Short stature. In this study, a total of 18 SPOUT1 variants were found in 28 individuals from 21 unrelated families. Intellectual disability was evident in 10/10 families where it could be ascertained, seizures were reported in 16/21 of the families, short stature was seen in 13/15 families where it could be measured and microcephaly was evident in 18/21 cases, with clearly severe microcephaly in 5 cases (PMID: 39962046, supplementary table 1).
SPOUT1 variant zebra fish models showed reduction in larval head size with concomitant apoptosis and the human SPOUT1 missense variants were pathogenic in complementation assays in zebrafish (PMID: 39962046).
Sources: Literature
Severe microcephaly v7.23 SPOUT1 Sarah Leigh Entity copied from Early onset or syndromic epilepsy v7.81
Severe microcephaly v7.23 SPOUT1 Sarah Leigh gene: SPOUT1 was added
gene: SPOUT1 was added to Severe microcephaly. Sources: Expert Review Amber,Literature
Q1_25_ promote_green tags were added to gene: SPOUT1.
Mode of inheritance for gene: SPOUT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPOUT1 were set to 39962046
Phenotypes for gene: SPOUT1 were set to SPOUT1 Associated Development delay Microcephaly Seizures Short stature
Fetal anomalies v5.87 AL117258.1 Achchuthan Shanmugasundram changed review comment from: The 'new-gene-name' tag has been added as the HGNC approved symbol for this gene is CIROP.; to: The 'new-gene-name' tag has been added as the HGNC approved symbol for this gene is CIROP. This gene was known by the previous symbol LMLN2.
Polycystic liver disease v1.31 SEC61B Bill Griffiths reviewed gene: SEC61B: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28375157; Phenotypes: Polycystic liver disease; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Retinal disorders v7.21 THRB Romana Izakovicova reviewed gene: THRB: Rating: GREEN; Mode of pathogenicity: Other; Publications: 37547476; Phenotypes: inherited retinal dystrophy, MONDO:0019118; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v8.235 CLCN7 Arina Puzriakova Added comment: Comment on publications: PMID: 39994654 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.235 CLCN7 Arina Puzriakova Publications for gene: CLCN7 were set to
Intellectual disability v8.234 CLCN7 Arina Puzriakova edited their review of gene: CLCN7: Added comment: PMID: 39994654 (2025) - a novel frameshift variant c.175dupA (p.Met59Asnfs*8) in CLCN7 was identified in a family with suspected ADO-II. The proband was homozygous for the variant and presented with intellectual disability, among features of osteopetrosis, deafness, optic atrophy, hepatosplenomegaly, cleft palate and recurrent infection. The variant showed incomplete penetrance in heterozygous family members.

Intellectual disability does not appear to be a typical feature and therefore maintaining the Red rating for now.; Changed publications to: 39994654
Intellectual disability v8.234 TMLHE Arina Puzriakova Classified gene: TMLHE as Amber List (moderate evidence)
Intellectual disability v8.234 TMLHE Arina Puzriakova Added comment: Comment on list classification: Promoting to Amber as two unrelated families have been reported with moderate ID in association with this gene. This gene is otherwise linked to ASD susceptibility and the phenotype in these families may be explained by the more severe consequence (truncating) of their identified variants.

However, caution should be taken in the future if this gene is being considered for a diagnostic panel as pathogenicity remains unclear and it has been listed as non-disease gene.
Intellectual disability v8.234 TMLHE Arina Puzriakova Gene: tmlhe has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.233 TMLHE Arina Puzriakova Added comment: Comment on publications: PMID: 39845198 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.233 TMLHE Arina Puzriakova Publications for gene: TMLHE were set to 39845198; 23092983
Intellectual disability v8.232 TRMT1L Arina Puzriakova Added comment: Comment on publications: PMID: 39786990 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.232 TRMT1L Arina Puzriakova Publications for gene: TRMT1L were set to 39786990
Intellectual disability v8.231 TMLHE Arina Puzriakova Publications for gene: TMLHE were set to
Intellectual disability v8.230 TMLHE Arina Puzriakova reviewed gene: TMLHE: Rating: ; Mode of pathogenicity: None; Publications: 39845198, 23092983; Phenotypes: {Autism, susceptibility to, X-linked 6}, OMIM:300872; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v8.230 TRMT1L Arina Puzriakova gene: TRMT1L was added
gene: TRMT1L was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: TRMT1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRMT1L were set to 39786990
Phenotypes for gene: TRMT1L were set to Early-onset neurodegenerative symptoms
Added comment: PMID: 39786990 (2025) - using GeneMatcher authors identified two siblings with a homozygous missense variant (c.1535C>T, p.(Pro512Leu)) in TRMT1L. Patients exhibited a range of early-onset neurodegenerative symptoms including intellectual disability, distal motor neuropathy, leukodystrophy, generalized hypotonia, and contractures. The variant segregates with the disease in the family and is predicted to be deleterious based upon multiple pathogenicity prediction algorithms.

Additional evidence required prior to making any conclusions about the pathogenicity of this gene and therefore rating Red for now.
Sources: Literature
Intellectual disability v8.229 KCNJ2 Arina Puzriakova Added comment: Comment on publications: PMID: 22155372 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.229 KCNJ2 Arina Puzriakova Publications for gene: KCNJ2 were set to 22155372
Intellectual disability v8.228 KCNJ2 Arina Puzriakova gene: KCNJ2 was added
gene: KCNJ2 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: KCNJ2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KCNJ2 were set to 22155372
Phenotypes for gene: KCNJ2 were set to Short QT syndrome 3, OMIM:609622
Added comment: PMID: 22155372 (2012) - 8-year-old Japanese girl with a markedly short QT interval and a heterozygous KCNJ2 variant (M301K). Authors noted extracardiac features, including severe intellectual disability and seizures, which they suggested might be attributed to the KCNJ2 variant, but they could not exclude the possibility of other mutated genes.

Intellectual disability is not a typical feature and currently there is not enough evidence to conclusively link KCNJ2. Therefore rating Red until more evidence emerges.
Sources: Literature
Ichthyosis and erythrokeratoderma v3.33 VIPAS39 Arina Puzriakova Phenotypes for gene: VIPAS39 were changed from Arthrogryposis, renal dysfunction, and cholestasis 2 (OMIM:613404) to Arthrogryposis, renal dysfunction, and cholestasis 2, OMIM:613404
Ichthyosis and erythrokeratoderma v3.32 VIPAS39 Arina Puzriakova Classified gene: VIPAS39 as Amber List (moderate evidence)
Ichthyosis and erythrokeratoderma v3.32 VIPAS39 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update.
Ichthyosis and erythrokeratoderma v3.32 VIPAS39 Arina Puzriakova Gene: vipas39 has been classified as Amber List (Moderate Evidence).
Ichthyosis and erythrokeratoderma v3.31 VIPAS39 Arina Puzriakova gene: VIPAS39 was added
gene: VIPAS39 was added to Ichthyosis and erythrokeratoderma. Sources: Literature
Q1_23_promote_green tags were added to gene: VIPAS39.
Mode of inheritance for gene: VIPAS39 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VIPAS39 were set to 39736737; 37202112; 32239418; 26019847
Phenotypes for gene: VIPAS39 were set to Arthrogryposis, renal dysfunction, and cholestasis 2 (OMIM:613404)
Review for gene: VIPAS39 was set to GREEN
Added comment: VIPAS39 biallelic variants cause Arthrogryposis, renal dysfunction, and cholestasis 2 (OMIM:613404). At least 11 individuals have been reported in the literature. Ichthyosis is a feature of ARCS and has been reported in at least 7 individuals with VIPAS39 variants (PMID:39736737; 37202112; 32239418; 26019847) which supports inclusion of this gene on the panel.
Sources: Literature
Proteinuric renal disease v4.27 VIPAS39 Arina Puzriakova changed review comment from: VIPAS39 biallelic variants cause Arthrogryposis, renal dysfunction, and cholestasis 2 (OMIM:613404). At least 10 individuals have been reported in the literature. Proteinuria has been reported in at least 8 individuals (PMID:39736737;35151346;37202112;26019847;24071963) which supports inclusion of this gene on the panel.; to: VIPAS39 biallelic variants cause Arthrogryposis, renal dysfunction, and cholestasis 2 (OMIM:613404). At least 11 individuals have been reported in the literature. Proteinuria has been reported in at least 9 individuals (PMID:39736737;35151346;37202112;26019847;24071963;31479177) which supports inclusion of this gene on the panel.
Proteinuric renal disease v4.27 VIPAS39 Arina Puzriakova Publications for gene: VIPAS39 were set to 39736737; 35151346; 37202112; 26019847; 24071963
Proteinuric renal disease v4.26 VIPAS39 Arina Puzriakova Publications for gene: VIPAS39 were set to 20190753
Proteinuric renal disease v4.25 VIPAS39 Arina Puzriakova Classified gene: VIPAS39 as Amber List (moderate evidence)
Proteinuric renal disease v4.25 VIPAS39 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update.
Proteinuric renal disease v4.25 VIPAS39 Arina Puzriakova Gene: vipas39 has been classified as Amber List (Moderate Evidence).
Proteinuric renal disease v4.24 VIPAS39 Arina Puzriakova Tag Q1_25_ promote_green tag was added to gene: VIPAS39.
Proteinuric renal disease v4.24 VIPAS39 Arina Puzriakova reviewed gene: VIPAS39: Rating: ; Mode of pathogenicity: None; Publications: 39736737, 35151346, 37202112, 26019847, 24071963; Phenotypes: Arthrogryposis, renal dysfunction, and cholestasis 2 (OMIM:613404); Mode of inheritance: None
Intellectual disability v8.227 VIPAS39 Arina Puzriakova Added comment: Comment on publications: PMID: 39736737 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.227 VIPAS39 Arina Puzriakova Publications for gene: VIPAS39 were set to
Intellectual disability v8.226 VIPAS39 Arina Puzriakova reviewed gene: VIPAS39: Rating: AMBER; Mode of pathogenicity: None; Publications: 39736737, 35151346, 26019847; Phenotypes: Arthrogryposis, renal dysfunction, and cholestasis 2, OMIM:613404; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v7.21 VIPAS39 Arina Puzriakova Phenotypes for gene: VIPAS39 were changed from Inherited bleeding disorders; ARC Syndrome (Other metabolic disorders); Arthrogryposis to Arthrogryposis, renal dysfunction, and cholestasis 2, OMIM:613404; ARC syndrome
Fetal anomalies v5.87 VIPAS39 Arina Puzriakova Phenotypes for gene: VIPAS39 were changed from ARTHROGRYPOSIS, RENAL DYSFUNCTION, AND CHOLESTASIS 2 to Arthrogryposis, renal dysfunction, and cholestasis 2, OMIM:613404; ARC syndrome
Undiagnosed metabolic disorders v1.627 VIPAS39 Arina Puzriakova Phenotypes for gene: VIPAS39 were changed from ARC Syndrome (Other metabolic disorders); Arthrogryposis; Inherited bleeding disorders to Arthrogryposis, renal dysfunction, and cholestasis 2, OMIM:613404; ARC syndrome; Inherited bleeding disorders
Bleeding and platelet disorders v3.14 VIPAS39 Arina Puzriakova Phenotypes for gene: VIPAS39 were changed from 613404 Arthrogryposis, renal dysfunction, and cholestasis 2 to Arthrogryposis, renal dysfunction, and cholestasis 2, OMIM:613404; ARC syndrome
Arthrogryposis v8.7 VIPAS39 Arina Puzriakova Phenotypes for gene: VIPAS39 were changed from Arthrogryposis, renal dysfunction, and cholestasis 2, 613404; arthrogryposis, renal dysfunction and cholestasis syndrome (ARC) to Arthrogryposis, renal dysfunction, and cholestasis 2, OMIM:613404; ARC syndrome
Unexplained kidney failure in young people v1.120 VIPAS39 Arina Puzriakova Phenotypes for gene: VIPAS39 were changed from Arthrogryposis, renal dysfunction, and cholestasis 2, 613404 to Arthrogryposis, renal dysfunction, and cholestasis 2, OMIM:613404; ARC syndrome
Inherited bleeding disorders v1.179 VIPAS39 Arina Puzriakova Phenotypes for gene: VIPAS39 were changed from ARC syndrome (Arthrogryposis, renal dysfunction, and cholestasis 1) to Arthrogryposis, renal dysfunction, and cholestasis 2, OMIM:613404; ARC syndrome
Cholestasis v3.7 VIPAS39 Arina Puzriakova Phenotypes for gene: VIPAS39 were changed from Arthrogryposis, Renal Dysfunction, and Cholestasis 2; ARC syndrome; Arthrogryposis-renal-cholestasis syndrome; Neonatal and Adult Cholestasis; Arthrogryposis, renal dysfunction, and cholestasis 2, 613404 to Arthrogryposis, renal dysfunction, and cholestasis 2, OMIM:613404; ARC syndrome
Neonatal cholestasis v1.27 VIPAS39 Arina Puzriakova Phenotypes for gene: VIPAS39 were changed from Neonatal and Adult Cholestasis; Arthrogryposis, renal dysfunction, and cholestasis 2, 613404; Arthrogryposis, Renal Dysfunction, and Cholestasis 2; ARC syndrome; Arthrogryposis-renal-cholestasis syndrome to Arthrogryposis, renal dysfunction, and cholestasis 2, OMIM:613404; ARC syndrome
Proteinuric renal disease v4.24 VIPAS39 Arina Puzriakova Mode of inheritance for gene: VIPAS39 was changed from to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v8.226 VIPAS39 Arina Puzriakova Phenotypes for gene: VIPAS39 were changed from Gene2Phenotype confirmed gene with ID HPO to Arthrogryposis, renal dysfunction, and cholestasis 2, OMIM:613404
Proteinuric renal disease v4.23 VIPAS39 Arina Puzriakova Phenotypes for gene: VIPAS39 were changed from Arthrogryposis, renal dysfunction, and cholestasis 2 # 613404 to Arthrogryposis, renal dysfunction, and cholestasis 2, OMIM:613404
Intellectual disability v8.225 WT1 Arina Puzriakova Added comment: Comment on publications: PMID: 39625990 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.225 WT1 Arina Puzriakova Publications for gene: WT1 were set to
Intellectual disability v8.224 WT1 Arina Puzriakova reviewed gene: WT1: Rating: ; Mode of pathogenicity: None; Publications: 39625990; Phenotypes: Denys-Drash syndrome, OMIM:194080; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v8.224 FUT2 Arina Puzriakova Added comment: Comment on publications: PMID: 39350204 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.224 FUT2 Arina Puzriakova Publications for gene: FUT2 were set to 39350204
Early onset or syndromic epilepsy v7.81 FUT2 Arina Puzriakova Added comment: Comment on publications: PMID: 39350204 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Early onset or syndromic epilepsy v7.81 FUT2 Arina Puzriakova Publications for gene: FUT2 were set to 39350204
Rare anaemia v3.10 FUT2 Arina Puzriakova Added comment: Comment on publications: PMID: 39350204 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Rare anaemia v3.10 FUT2 Arina Puzriakova Publications for gene: FUT2 were set to 39350204
Rare anaemia v3.9 FUT2 Arina Puzriakova gene: FUT2 was added
gene: FUT2 was added to Rare anaemia. Sources: Literature
Mode of inheritance for gene: FUT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FUT2 were set to 39350204
Phenotypes for gene: FUT2 were set to Developmental and epileptic encephalopathy
Added comment: PMID: 39350204 (2024) - homozygous missense variant (NC_000019.10:g.48703291C>T) in the FUT2 gene was identified in an infant with vitamin B12-responsive developmental and epileptic encephalopathy and megaloblastic anemia. Although the mechanism of how the FUT2 gene variant affects vitamin B12 absorption is unclear.

Additional evidence is required before conclusively implicating FUT2 in human disease and therefore rating Red for now.
Sources: Literature
Intellectual disability v8.223 FUT2 Arina Puzriakova gene: FUT2 was added
gene: FUT2 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: FUT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FUT2 were set to 39350204
Phenotypes for gene: FUT2 were set to Developmental and epileptic encephalopathy
Added comment: PMID: 39350204 (2024) - homozygous missense variant (NC_000019.10:g.48703291C>T) in the FUT2 gene was identified in an infant with vitamin B12-responsive developmental and epileptic encephalopathy and megaloblastic anemia. Although the mechanism of how the FUT2 gene variant affects vitamin B12 absorption is unclear.

Additional evidence is required before conclusively implicating FUT2 in human disease and therefore rating Red for now.
Sources: Literature
Early onset or syndromic epilepsy v7.80 FUT2 Arina Puzriakova gene: FUT2 was added
gene: FUT2 was added to Early onset or syndromic epilepsy. Sources: Literature
Mode of inheritance for gene: FUT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FUT2 were set to 39350204
Phenotypes for gene: FUT2 were set to Developmental and epileptic encephalopathy
Added comment: PMID: 39350204 (2024) - homozygous missense variant (NC_000019.10:g.48703291C>T) in the FUT2 gene was identified in an infant with vitamin B12-responsive developmental and epileptic encephalopathy and megaloblastic anemia. Although the mechanism of how the FUT2 gene variant affects vitamin B12 absorption is unclear.

Additional evidence is required before conclusively implicating FUT2 in human disease and therefore rating Red for now.
Sources: Literature
Early onset or syndromic epilepsy v7.79 EPM2A Arina Puzriakova Phenotypes for gene: EPM2A were changed from Epilepsy, progressive myoclonic 2A (Lafora) 254780 to Myoclonic epilepsy of Lafora 1, OMIM:254780
Childhood onset dystonia, chorea or related movement disorder v6.8 EPM2A Arina Puzriakova Phenotypes for gene: EPM2A were changed from to Myoclonic epilepsy of Lafora 1, OMIM:254780
Likely inborn error of metabolism v7.20 EPM2A Arina Puzriakova Phenotypes for gene: EPM2A were changed from Epilepsy, progressive myoclonic 2A (Lafora) to Myoclonic epilepsy of Lafora 1, OMIM:254780
Hereditary ataxia with onset in adulthood v7.14 EPM2A Arina Puzriakova Phenotypes for gene: EPM2A were changed from Progressive myoclonic epilepsy 2A, Lafora, 254780; Epilepsy, progressive myoclonic 2A (Lafora) 254780 to Myoclonic epilepsy of Lafora 1, OMIM:254780
Undiagnosed metabolic disorders v1.626 EPM2A Arina Puzriakova Phenotypes for gene: EPM2A were changed from Epilepsy, progressive myoclonic 2A (Lafora) 254780 to Myoclonic epilepsy of Lafora 1, OMIM:254780
Adult onset neurodegenerative disorder v7.15 EPM2A Arina Puzriakova Phenotypes for gene: EPM2A were changed from Epilepsy, progressive myoclonic 2A (Lafora), OMIM:254780 to Myoclonic epilepsy of Lafora 1, OMIM:254780
Hereditary ataxia v1.338 EPM2A Arina Puzriakova Phenotypes for gene: EPM2A were changed from Epilepsy, progressive myoclonic 2A (Lafora) 254780 to Myoclonic epilepsy of Lafora 1, OMIM:254780
Glycogen storage disease v2.5 EPM2A Arina Puzriakova Phenotypes for gene: EPM2A were changed from Epilepsy, progressive myoclonic 2A (Lafora) 254780 to Myoclonic epilepsy of Lafora 1, OMIM:254780
Ataxia and cerebellar anomalies - narrow panel v7.25 EPM2A Arina Puzriakova Phenotypes for gene: EPM2A were changed from Epilepsy, progressive myoclonic 2A (Lafora) to Myoclonic epilepsy of Lafora 1, OMIM:254780
Intellectual disability v8.222 EPM2A Arina Puzriakova Phenotypes for gene: EPM2A were changed from Epilepsy, progressive myoclonic 2A (Lafora) 254780 to Myoclonic epilepsy of Lafora 1, OMIM:254780
Intellectual disability v8.221 EPM2A Arina Puzriakova Added comment: Comment on publications: PMID: 39385815 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.221 EPM2A Arina Puzriakova Publications for gene: EPM2A were set to 21376300
Intellectual disability v8.220 EPM2A Arina Puzriakova reviewed gene: EPM2A: Rating: ; Mode of pathogenicity: None; Publications: 39385815; Phenotypes: ; Mode of inheritance: None
Intellectual disability v8.220 TFG Sarah Leigh Classified gene: TFG as Amber List (moderate evidence)
Intellectual disability v8.220 TFG Sarah Leigh Gene: tfg has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.219 TFG Sarah Leigh edited their review of gene: TFG: Added comment: Biallelic TFG variants have been associated with Spastic paraplegia 57, autosomal recessive (OMIM:615658). Five biallelic TFG variants have been associated with OMIM:615658 in nine families from various ethnicities (PMID: 23479643; 27601211; 27492651; 28124177; 29971521; 30467354; 33767317). A range of phenotypic features were reported (table 2 in PMID: 33767317), with spasticity apparent in 8/8 families examined and intellectual disability in 5/9 families.; Changed rating: GREEN
Intellectual disability v8.219 TFG Sarah Leigh Tag Q1_25_ promote_green tag was added to gene: TFG.
Intellectual disability v8.219 TFG Sarah Leigh Publications for gene: TFG were set to 23479643; 33767317
Intellectual disability v8.218 TFG Sarah Leigh Publications for gene: TFG were set to 33767317
Intellectual disability v8.217 TFG Sarah Leigh Added comment: Comment on publications: PMID: 33767317 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.217 TFG Sarah Leigh Publications for gene: TFG were set to 33767317
Paediatric disorders - additional genes v6.15 DET1 Sarah Leigh Added comment: Comment on publications: PMID: 39937864 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Paediatric disorders - additional genes v6.15 DET1 Sarah Leigh Publications for gene: DET1 were set to 39937864
Fetal anomalies v5.86 DET1 Sarah Leigh Added comment: Comment on publications: PMID: 39937864 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Fetal anomalies v5.86 DET1 Sarah Leigh Publications for gene: DET1 were set to 39937864
Fetal anomalies v5.85 DET1 Sarah Leigh gene: DET1 was added
gene: DET1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: DET1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DET1 were set to 39937864
Phenotypes for gene: DET1 were set to neurological defects and lethality
Review for gene: DET1 was set to RED
Added comment: PMID: 39937864 reports a family where the three affected siblings were homozygous for a variant in DET1 (c.76C>T, p.R26W) and also for a variant in COMMD4 (c.122T>G; p.L41R). These genes are both on chromosome 15, separated by 13 Mb and are likely to co-segregate. The parents of these cases were healthy, heterozygous carriers of the DET1 p.R26W variant. The cases described developed lethal developmental abnormalities and the longest lived sib died at 8 months old. Extensive functional studies were reported in PMID: 39937864 and using Det1-
deficient mice and human-induced pluripotent stem cells (iPSCs) expressing DET1R26W,
the authors were able to show that DET1 is essential for normal neuronal development.
Sources: Literature
Paediatric disorders - additional genes v6.14 DET1 Sarah Leigh gene: DET1 was added
gene: DET1 was added to Paediatric disorders - additional genes. Sources: Literature
Mode of inheritance for gene: DET1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DET1 were set to 39937864
Phenotypes for gene: DET1 were set to neurological defects and lethality
Review for gene: DET1 was set to RED
Added comment: PMID: 39937864 reports a family where the three affected siblings were homozygous for a variant in DET1 (c.76C>T, p.R26W) and also for a variant in COMMD4 (c.122T>G; p.L41R). These genes are both on chromosome 15, separated by 13 Mb and are likely to co-segregate. The parents of these cases were healthy, heterozygous carriers of the DET1 p.R26W variant. The cases described developed lethal developmental abnormalities and the longest lived sib died at 8 months old. Extensive functional studies were reported in PMID: 39937864 and using Det1-
deficient mice and human-induced pluripotent stem cells (iPSCs) expressing DET1R26W,
the authors were able to show that DET1 is essential for normal neuronal development.
Sources: Literature
Malformations of cortical development v7.3 DLGAP4 Arina Puzriakova Added comment: Comment on publications: PMID:35585091 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Malformations of cortical development v7.3 DLGAP4 Arina Puzriakova Publications for gene: DLGAP4 were set to 35585091
Malformations of cortical development v7.2 DLGAP4 Arina Puzriakova gene: DLGAP4 was added
gene: DLGAP4 was added to Malformations of cortical development. Sources: Literature
Mode of inheritance for gene: DLGAP4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DLGAP4 were set to 35585091
Review for gene: DLGAP4 was set to RED
Added comment: PMID: 35585091 (2022) - patient with a de novo variant in DLGAP4 gene was identified (family P616; c.2714_2715insCAGCTGG, N905Qfs). Clinical presentation included extensive subependymal heterotopia, cerebral paralysis, GDD (without ID), spastic diplegia. In an additional family (P477), heterozygous variants were also observed in twins - a paternally inherited missense variant in DLGAP4 (c.2893T>G, p.Ser965Ala) and maternally inherited missense variant in DLGAP1 (c.1397A>G, p.Asp466Gly). The twins presented with DD and parieto-occipital pachygyria.

Functional studies show that DLGAP4 plays a role in maintaining the progenitor pool, regulating neurogenesis and neuronal migration.

Overall more evidence is required before drawing conclusions about the role of DLGAP4 in human disease.
Sources: Literature
Intellectual disability v8.216 YBX3 Arina Puzriakova Added comment: Comment on publications: PMID:39423228 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.216 YBX3 Arina Puzriakova Publications for gene: YBX3 were set to 39423228
Intellectual disability v8.215 YBX3 Arina Puzriakova gene: YBX3 was added
gene: YBX3 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: YBX3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: YBX3 were set to 39423228
Phenotypes for gene: YBX3 were set to Neurological disorder
Review for gene: YBX3 was set to RED
Added comment: PMID: 39423228 (2024) - functional studies in C. elegans indicate that the Y-Box (YBX) RBP family are involved in memory and cognitive processes. Based on this finding, authors identified two unrelated individuals in the Baylor Genetics dataset with the same heterozygous VUS (c.379A>T (p.Asn127Tyr)) in the YBX3 gene and neurological symptoms. However, phenotypic overlap was limited and there was also a third family with the same variant and a metabolic phenotype. Modelling this variant in worms did lead to memory deficits, however given the clinical heterogeneity among human carriers, there is not enough evidence to draw any conclusions about this gene.
Sources: Literature
Adult onset neurodegenerative disorder v7.14 SGIP1 Arina Puzriakova Added comment: Comment on publications: PMID:39332416 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Adult onset neurodegenerative disorder v7.14 SGIP1 Arina Puzriakova Publications for gene: SGIP1 were set to 39332416
Adult onset neurodegenerative disorder v7.13 SGIP1 Arina Puzriakova gene: SGIP1 was added
gene: SGIP1 was added to Adult onset neurodegenerative disorder. Sources: Literature
Mode of inheritance for gene: SGIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SGIP1 were set to 39332416
Phenotypes for gene: SGIP1 were set to Early-onset parkinsonism
Added comment: PMID: 39332416 (2024) - consanguineous Arab family with two affected sisters who manifested young-onset parkinsonism (onset at age 19 and 22). Other features include intellectual/cognitive dysfunction, behavioral problems, and seizures (in one individual). WES revealed a homozygous missense variant (c.2080T>G (p.W694G)) in the SGIP1 gene. Functional studies in Drosophila demonstrated movement defects, synaptic transmission dysfunction, and neurodegeneration, including dopaminergic synapse loss.

Rating Red as only a single family has been reported to date.
Sources: Literature
Mitochondrial disorders v8.20 NDUFA3 Arina Puzriakova Added comment: Comment on publications: PMID:39661167 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Mitochondrial disorders v8.20 NDUFA3 Arina Puzriakova Publications for gene: NDUFA3 were set to
Likely inborn error of metabolism v7.19 NDUFA3 Arina Puzriakova Added comment: Comment on publications: PMID:39661167 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Likely inborn error of metabolism v7.19 NDUFA3 Arina Puzriakova Publications for gene: NDUFA3 were set to
Possible mitochondrial disorder - nuclear genes v3.123 NDUFA3 Arina Puzriakova Added comment: Comment on publications: PMID:39661167 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Possible mitochondrial disorder - nuclear genes v3.123 NDUFA3 Arina Puzriakova Publications for gene: NDUFA3 were set to 39661167
Mitochondrial disorder with complex I deficiency v3.15 NDUFA3 Arina Puzriakova Added comment: Comment on publications: PMID:39661167 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Mitochondrial disorder with complex I deficiency v3.15 NDUFA3 Arina Puzriakova Publications for gene: NDUFA3 were set to 39661167
Mitochondrial disorders v8.19 NDUFA3 Arina Puzriakova Phenotypes for gene: NDUFA3 were changed from Isolated complex I deficiency; No OMIM phenotype to Leigh syndrome
Likely inborn error of metabolism v7.18 NDUFA3 Arina Puzriakova Phenotypes for gene: NDUFA3 were changed from No OMIM phenotype; Isolated complex I deficiency to Leigh syndrome
Possible mitochondrial disorder - nuclear genes v3.122 NDUFA3 Arina Puzriakova Phenotypes for gene: NDUFA3 were changed from No OMIM phenotype to Leigh syndrome
Mitochondrial disorder with complex I deficiency v3.14 NDUFA3 Arina Puzriakova Phenotypes for gene: NDUFA3 were changed from No OMIM phenotype to Leigh syndrome
Mitochondrial disorders v8.18 NDUFA3 Arina Puzriakova Mode of inheritance for gene: NDUFA3 was changed from to BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v7.17 NDUFA3 Arina Puzriakova Mode of inheritance for gene: NDUFA3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Possible mitochondrial disorder - nuclear genes v3.121 NDUFA3 Arina Puzriakova Publications for gene: NDUFA3 were set to
Mitochondrial disorder with complex I deficiency v3.13 NDUFA3 Arina Puzriakova Publications for gene: NDUFA3 were set to
Possible mitochondrial disorder - nuclear genes v3.120 NDUFA3 Arina Puzriakova Mode of inheritance for gene: NDUFA3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorder with complex I deficiency v3.12 NDUFA3 Arina Puzriakova Mode of inheritance for gene: NDUFA3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Possible mitochondrial disorder - nuclear genes v3.119 NDUFA3 Arina Puzriakova reviewed gene: NDUFA3: Rating: ; Mode of pathogenicity: None; Publications: 39661167; Phenotypes: Leigh syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v8.17 NDUFA3 Arina Puzriakova reviewed gene: NDUFA3: Rating: ; Mode of pathogenicity: None; Publications: 39661167; Phenotypes: Leigh syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v7.16 NDUFA3 Arina Puzriakova reviewed gene: NDUFA3: Rating: ; Mode of pathogenicity: None; Publications: 39661167; Phenotypes: Leigh syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorder with complex I deficiency v3.11 NDUFA3 Arina Puzriakova reviewed gene: NDUFA3: Rating: ; Mode of pathogenicity: None; Publications: 39661167; Phenotypes: Leigh syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v7.21 IDH3G Sarah Leigh Classified gene: IDH3G as Amber List (moderate evidence)
Retinal disorders v7.21 IDH3G Sarah Leigh Gene: idh3g has been classified as Amber List (Moderate Evidence).
Retinal disorders v7.20 IDH3G Sarah Leigh gene: IDH3G was added
gene: IDH3G was added to Retinal disorders. Sources: Literature
Q1_25_ promote_green tags were added to gene: IDH3G.
Mode of inheritance for gene: IDH3G 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: IDH3G were set to 40119724
Phenotypes for gene: IDH3G were set to X-linked retinitis pigmentosa
Review for gene: IDH3G was set to GREEN
Added comment: PMID: 40119724 reports four hemizygous IDH3G single nucleotide variants (SNVs) in males with a X-linked retinitis pigmentosa. A further case was reported with a 25kb deletion, which encompassed the entire IDH3G gene, but also included PLXNB3 and SRPK3 genes. In all cases the IDH3G variant segregated with the disease, this was confirmed by sequencing in two of the families (figure 1 in PMID: 40119724). Functional studies showed that the IDH3G SNVs reduced expression of the IDH3G.
Sources: Literature
Adult onset dystonia, chorea or related movement disorder v4.10 XK Arina Puzriakova Classified gene: XK as Amber List (moderate evidence)
Adult onset dystonia, chorea or related movement disorder v4.10 XK Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update.
Adult onset dystonia, chorea or related movement disorder v4.10 XK Arina Puzriakova Gene: xk has been classified as Amber List (Moderate Evidence).
Adult onset dystonia, chorea or related movement disorder v4.9 XK Arina Puzriakova Deleted their comment
Adult onset dystonia, chorea or related movement disorder v4.9 XK Arina Puzriakova Added comment: Comment on publications: PMID:39315078 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Adult onset dystonia, chorea or related movement disorder v4.9 XK Arina Puzriakova Publications for gene: XK were set to 8619554; 21714011; 11761473; 17469188; 23192927; 37720304; 34487382; 35977449; 24098554; 39315078
Adult onset dystonia, chorea or related movement disorder v4.8 XK Arina Puzriakova Classified gene: XK as Amber List (moderate evidence)
Adult onset dystonia, chorea or related movement disorder v4.8 XK Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to green at the next GMS panel update.
Adult onset dystonia, chorea or related movement disorder v4.8 XK Arina Puzriakova Gene: xk has been classified as Amber List (Moderate Evidence).
Adult onset dystonia, chorea or related movement disorder v4.7 XK Arina Puzriakova gene: XK was added
gene: XK was added to Adult onset dystonia, chorea or related movement disorder. Sources: Literature
Q1_25_ promote_green tags were added to gene: XK.
Mode of inheritance for gene: XK 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: XK were set to 8619554; 21714011; 11761473; 17469188; 23192927; 37720304; 34487382; 35977449; 24098554; 39315078
Phenotypes for gene: XK were set to McLeod syndrome, OMIM:300842
Review for gene: XK was set to GREEN
Added comment: Numerous variants have been reported in cases of McLeod syndrome (OMIM:300842), including at least two cases in females; severe symptoms were apparent in the index case (11.1) who had marked skewed X-inactivation favouring the wild type allele (PMID: 8619554).

McLeod syndrome causes a multi-system disorder. The presentation can resemble Huntington Disease. Typically primary manifestations are neurological (e.g. chorea, tics, parkinsonism, dystonia, seizures) and muscular (myopathy, peripheral neuropathy), some patients also exhibited cognitive issues, psychiatric symptoms (psychosis, delusions, depression, obsessive-compulsive features), and emotional lability.

Onset is typically in the 4th decade of life and therefore appropriate for this panel.
Sources: Literature
Retinal disorders v7.19 AP5B1 Sarah Leigh Phenotypes for gene: AP5B1 were changed from Macular dystrophy to Lysosomal macular dystrophy
Retinal disorders v7.18 AP5B1 Sarah Leigh Publications for gene: AP5B1 were set to PMID 40081374
Retinal disorders v7.17 AP5B1 Sarah Leigh Classified gene: AP5B1 as Amber List (moderate evidence)
Retinal disorders v7.17 AP5B1 Sarah Leigh Gene: ap5b1 has been classified as Amber List (Moderate Evidence).
Retinal disorders v7.16 AP5B1 Sarah Leigh reviewed gene: AP5B1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Retinal disorders v7.16 AP5M1 Sarah Leigh reviewed gene: AP5M1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Retinal disorders v7.16 AP5M1 Sarah Leigh Tag Q1_25_ NHS_review tag was added to gene: AP5M1.
Tag Q1_25_ promote_green tag was added to gene: AP5M1.
Retinal disorders v7.16 AP5M1 Sarah Leigh Phenotypes for gene: AP5M1 were changed from to Lysosomal macular dystrophy
Retinal disorders v7.15 AP5M1 Sarah Leigh Publications for gene: AP5M1 were set to
Retinal disorders v7.14 AP5M1 Sarah Leigh Classified gene: AP5M1 as Amber List (moderate evidence)
Retinal disorders v7.14 AP5M1 Sarah Leigh Gene: ap5m1 has been classified as Amber List (Moderate Evidence).
Retinal disorders v7.13 AP5Z1 Sarah Leigh changed review comment from: In PMID: 40081374, Kaminska et al report variants in three of the genes which encode different subunits of the vesicular fifth adaptor protein (AP-5) complex: AP5Z1, AP5M1, and AP5B1, in patients with a specific form of macular degeneration. Seventeen biallelic AP5Z1 variants were been reported in fourteen unrelated families with macular degeneration. Due to the involvement of variants in the AP-5 complex, the authors suggest that the resultant condition should be called lysosomal macular dystrophy.; to: In PMID: 40081374, Kaminska et al report variants in three of the genes which encode different subunits of the vesicular fifth adaptor protein (AP-5) complex: AP5Z1, AP5M1, and AP5B1, in patients with a specific form of macular degeneration. Seventeen biallelic AP5Z1 variants were been reported in fourteen unrelated families, three homozygous AP5M1 variant were found in three unrelated cases and three biallelic AP5B1 variants were found in two unrelated cases. Due to the involvement of variants in the AP-5 complex, the authors suggest that the resultant condition should be called lysosomal macular dystrophy.
Retinal disorders v7.13 AP5Z1 Sarah Leigh reviewed gene: AP5Z1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Retinal disorders v7.13 AP5Z1 Sarah Leigh Phenotypes for gene: AP5Z1 were changed from Hereditary lysosomal macular dystrophy to Lysosomal macular dystrophy
Retinal disorders v7.12 AP5Z1 Sarah Leigh Phenotypes for gene: AP5Z1 were changed from Hereditary macular dystrophy to Hereditary lysosomal macular dystrophy
Retinal disorders v7.11 AP5Z1 Sarah Leigh Phenotypes for gene: AP5Z1 were changed from Macular dystrophy to Hereditary macular dystrophy
Retinal disorders v7.10 AP5Z1 Sarah Leigh Tag Q1_25_ NHS_review tag was added to gene: AP5Z1.
Tag Q1_25_ promote_green tag was added to gene: AP5Z1.
Retinal disorders v7.10 AP5Z1 Sarah Leigh Classified gene: AP5Z1 as Amber List (moderate evidence)
Retinal disorders v7.10 AP5Z1 Sarah Leigh Gene: ap5z1 has been classified as Amber List (Moderate Evidence).
Retinal disorders v7.9 AP5Z1 Sarah Leigh Publications for gene: AP5Z1 were set to PMID: 40081374
Intellectual disability v8.214 ABI2 Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:39774290 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.

PMID:39774290 is a secondary publication and the relevant case described in this publication was originally from the primary publication PMID:28397838.
Intellectual disability v8.214 ABI2 Achchuthan Shanmugasundram Publications for gene: ABI2 were set to 28397838; 39774290
Intellectual disability v8.213 ABI2 Achchuthan Shanmugasundram gene: ABI2 was added
gene: ABI2 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: ABI2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABI2 were set to 28397838; 39774290
Phenotypes for gene: ABI2 were set to intellectual disability, MONDO:0001071
Review for gene: ABI2 was set to RED
Added comment: PMID:28397838 reported the identification of variants in a cohort of 192 multiplex Pakistani and Iranian consanguineous families with non-syndromic ID by combining microarray genotyping, homozygosity-by-descent (HBD) mapping, copy number variation (CNV) analysis, and whole exome sequencing (WES). This study identified a patient with homozygous loss-of-function variant in ABI2 gene (p.(Arg132Ter)).

This gene has not yet been associated with phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v8.212 CYFIP1 Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:39774290 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.

PMID:39774290 is a secondary publication and the relevant case described in this publication was originally from the primary publication PMID:37704042.
Intellectual disability v8.212 CYFIP1 Achchuthan Shanmugasundram Publications for gene: CYFIP1 were set to 37704042; 39774290
Intellectual disability v8.211 CYFIP1 Achchuthan Shanmugasundram gene: CYFIP1 was added
gene: CYFIP1 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: CYFIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYFIP1 were set to 37704042; 39774290
Phenotypes for gene: CYFIP1 were set to intellectual disability, MONDO:0001071
Review for gene: CYFIP1 was set to RED
Added comment: PMID:37704042 reported two individuals from a family with intellectual disability, autism spectrum disorder, spastic tetraparesis, and brain morphology defects. They were identified with compound heterozygous missense variants in the CYFIP1 gene (p.(Ile476Val) and p.(Pro742Leu)).

Functional work from patient fibroblasts showed deficits in actin polymerization. In addition, Drosophila knockin models for these variants exhibited abnormal brain morphology and F-actin loss, and recapitulated the core behavioural symptoms, such as deficits in social interaction and motor coordination.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v7.26 TLR8 Anastasia Vasiliki Madenidou reviewed gene: TLR8: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34981838; Phenotypes: haemolytic anaemia; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Primary immunodeficiency or monogenic inflammatory bowel disease v7.26 TMEM173 Anastasia Vasiliki Madenidou reviewed gene: TMEM173: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25401470; Phenotypes: systemic lupus erythematosus; Mode of inheritance: None
Intellectual disability v8.210 C1QC Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:39196411 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.210 C1QC Achchuthan Shanmugasundram Publications for gene: C1QC were set to 39196411
Intellectual disability v8.209 C1QC Achchuthan Shanmugasundram gene: C1QC was added
gene: C1QC was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: C1QC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C1QC were set to 39196411
Phenotypes for gene: C1QC were set to C1q deficiency 3, OMIM:620322
Review for gene: C1QC was set to RED
Added comment: PMID:39196411 reported 12 patients with C1q deficiency, of which one was identified with homozygous variant in C1QC gene (p.(Arg69Ter)). Intellectual impairment was reported in this patient.
Sources: Literature
Intellectual disability v8.208 C1QA Achchuthan Shanmugasundram changed review comment from: Comment on publications: PMID:39196411 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques; to: Comment on publications: PMID:39196411 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.208 C1QA Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:39196411 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques
Intellectual disability v8.208 C1QA Achchuthan Shanmugasundram Publications for gene: C1QA were set to 39196411
Intellectual disability v8.207 C1QA Achchuthan Shanmugasundram gene: C1QA was added
gene: C1QA was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: C1QA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C1QA were set to 39196411
Phenotypes for gene: C1QA were set to C1q deficiency 1, OMIM:613652
Review for gene: C1QA was set to RED
Added comment: PMID:39196411 reported 12 patients with C1q deficiency, of which 10 of them were identified with homozygous variants in C1QA gene. Global developmental delay was reported in only one of these ten cases.
Sources: Literature
Intellectual disability v8.206 TFG Sarah Leigh Publications for gene: TFG were set to
Intellectual disability v8.205 ATAD2B Arina Puzriakova commented on gene: ATAD2B: PMID: 39313616 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.205 ATAD2B Arina Puzriakova gene: ATAD2B was added
gene: ATAD2B was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: ATAD2B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATAD2B were set to 39313616
Phenotypes for gene: ATAD2B were set to intellectual disability, MONDO:0001071
Added comment: PMID: 39313616 - two unrelated individuals were identified with biallelic variants in the ATAD2B gene. One patient had an affected sibling with the same genotype and a similar phenotype. A fourth individual with biallelic variants was also identified in GeneDx. All had developmental delay or cognitive impairment but otherwise had distinct phenotypes (with exception of the sibs) (summary in Supplementary Table 6).

Given the lack of phenotypic overlap, more evidence is required to implicate ATAD2B and therefore rating Red until more evidence emerges.
Sources: Literature
Distal myopathies v6.4 GIPC1_GGC Sarah Leigh STR: GIPC1_GGC was added
STR: GIPC1_GGC was added to Distal myopathies. Sources: Literature
STR, NGS Not Validated tags were added to STR: GIPC1_GGC.
Mode of inheritance for STR: GIPC1_GGC was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for STR: GIPC1_GGC were set to 32413282; 33374016
Phenotypes for STR: GIPC1_GGC were set to Oculopharyngodistal myopathy 2, OMIM:618940
Review for STR: GIPC1_GGC was set to GREEN
Added comment: GIPC1 transcribed from the reverse strand, which means that the repeated sequence is the reverse compliment of the forward strand sequence.

GIPC1_GGC is on https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r3

GIPC1_GGC is on https://stripy.org/database

GIPC1_GGC is on DRAGON 4.02.

The coordinates and pathogenic ranges of the sequence repeats were obtained from
https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r3 and were the same on https://stripy.org/database and DRAGON 4.02

There is enough evidence for this STR to be green on this panel.

This STR has not been approved by NHS STR working group and is not NGS Not Validated
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v7.24 ZFHX3_GGC Sarah Leigh edited their review of STR: ZFHX3_GGC: Changed rating: GREEN
Ataxia and cerebellar anomalies - narrow panel v7.24 ZFHX3_GGC Sarah Leigh STR: ZFHX3_GGC was added
STR: ZFHX3_GGC was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
STR, NGS Not Validated tags were added to STR: ZFHX3_GGC.
Mode of inheritance for STR: ZFHX3_GGC was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for STR: ZFHX3_GGC were set to Spinocerebellar ataxia 4, OMIM:600223
Review for STR: ZFHX3_GGC was set to AMBER
Added comment: ZFHX3 transcribed from the reverse strand, which means that the repeated sequence is the reverse compliment of the forward strand sequence.

ZFHX3_GGC is on https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r3

ZFHX3_GGC is on https://stripy.org/database

ZFHX3_GGC is not on DRAGON 4.02.

The coordinates and pathogenic ranges of the sequence repeats were obtained from
https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r3 and were the same on https://stripy.org/database

There is enough evidence for this STR to be green on this panel.

This STR has not been approved by NHS STR working group and is not NGS Not Validated
Sources: Literature
Intellectual disability v8.204 ASCC3 Arina Puzriakova Tag Q1_25_ promote_green tag was added to gene: ASCC3.
Intellectual disability v8.204 ASCC3 Arina Puzriakova commented on gene: ASCC3: PMID: 39286456 (2024) - three additional unrelated families identified with biallelic variants in the ASCC3 gene. All affected individuals had developmental delay and muscle fatigue. Other features included intellectual disability, hypotonia, motor impairment, feeding difficulties, and proximal/truncal muscle weakness.

Review of all reported cases (21 individuals) to date showed clinical heterogeneity, however most patients did exhibit intellectual disability of varying severity which can be the main presenting feature. Overall this supports inclusion of this gene on the panel.
Congenital myopathy v5.16 ASCC3 Arina Puzriakova Publications for gene: ASCC3 were set to 21937992; 35047834
Intellectual disability v8.204 ASCC3 Arina Puzriakova Added comment: Comment on publications: PMID: 39286456 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.204 ASCC3 Arina Puzriakova Publications for gene: ASCC3 were set to 21937992; 26350204; https://doi.org/10.1016/j.xhgg.2021.100024
Mitochondrial disorders v8.17 SUPV3L1 Sarah Leigh Classified gene: SUPV3L1 as Amber List (moderate evidence)
Mitochondrial disorders v8.17 SUPV3L1 Sarah Leigh Gene: supv3l1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.203 SUPV3L1 Sarah Leigh Classified gene: SUPV3L1 as Amber List (moderate evidence)
Intellectual disability v8.203 SUPV3L1 Sarah Leigh Gene: supv3l1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.202 SUPV3L1 Sarah Leigh edited their review of gene: SUPV3L1: Changed rating: GREEN
Intellectual disability v8.202 SUPV3L1 Sarah Leigh changed review comment from: Three SUPV3L1 variants have been reported in two unrelated cases with a syndrome that includes ataxia, spasticity, optic atrophy and skin hypopigmentation (ASOASH) and also intellectual disability (PMID: 35023579;39596606).
The homozygous terminating SUPV3L1 variant (NM_003171.3: c.2215C>T, p.Gln739*) reported in the siblings in PMID: 35023579, was shown to results in reduced expression of the truncated protein in the proband's fibroblasts, resulting in a reduction of the mature ND6 mRNA species and also the accumulation of double-stranded RNA. This effect was partly restored using full-length SUPV3L1 cDNA (PMID: 35023579). This variant and the compound heterozygous SUPV3L1 variants (NM_003171.5: c.272-2A>G and c.1924A>C; p.(Ser642Arg) reported in PMID: 39596606 were each inherited from the parents of the proband (PMID: 35023579;39596606).
Sources: Literature; to: Three SUPV3L1 variants have been reported in two unrelated cases with a syndrome that includes ataxia, spasticity, optic atrophy and skin hypopigmentation (ASOASH) and also intellectual disability (PMID: 35023579;39596606).
The homozygous terminating SUPV3L1 variant (NM_003171.3: c.2215C>T, p.Gln739*) reported in the siblings in PMID: 35023579, was shown to results in reduced expression of the truncated protein in the proband's fibroblasts, resulting in a reduction of the mature ND6 mRNA species and also the accumulation of double-stranded RNA. This effect was partly restored using full-length SUPV3L1 cDNA (PMID: 35023579). This variant and the compound heterozygous SUPV3L1 variants (NM_003171.5: c.272-2A>G and c.1924A>C; p.(Ser642Arg) reported in PMID: 39596606 were each inherited from the parents of the proband (PMID: 35023579;39596606). Supportive functional studies were presented in PMID: 35023579 and 39596606.
Sources: Literature
Mitochondrial disorders v8.16 SUPV3L1 Sarah Leigh edited their review of gene: SUPV3L1: Changed rating: GREEN
Mitochondrial disorders v8.16 SUPV3L1 Sarah Leigh changed review comment from: Three SUPV3L1 variants have been reported in two unrelated cases with a syndrome that includes ataxia, spasticity, optic atrophy and skin hypopigmentation (ASOASH) and also intellectual disability (PMID: 35023579;39596606).
The homozygous terminating SUPV3L1 variant (NM_003171.3: c.2215C>T, p.Gln739*) reported in the siblings in PMID: 35023579, was shown to results in reduced expression of the truncated protein in the proband's fibroblasts, resulting in a reduction of the mature ND6 mRNA species and also the accumulation of double-stranded RNA. This effect was partly restored using full-length SUPV3L1 cDNA (PMID: 35023579). This variant and the compound heterozygous SUPV3L1 variants (NM_003171.5: c.272-2A>G and c.1924A>C; p.(Ser642Arg) reported in PMID: 39596606 were each inherited from the parents of the proband (PMID: 35023579;39596606).
Sources: Literature; to: Three SUPV3L1 variants have been reported in two unrelated cases with a syndrome that includes ataxia, spasticity, optic atrophy and skin hypopigmentation (ASOASH) and also intellectual disability (PMID: 35023579;39596606).
The homozygous terminating SUPV3L1 variant (NM_003171.3: c.2215C>T, p.Gln739*) reported in the siblings in PMID: 35023579, was shown to results in reduced expression of the truncated protein in the proband's fibroblasts, resulting in a reduction of the mature ND6 mRNA species and also the accumulation of double-stranded RNA. This effect was partly restored using full-length SUPV3L1 cDNA (PMID: 35023579). This variant and the compound heterozygous SUPV3L1 variants (NM_003171.5: c.272-2A>G and c.1924A>C; p.(Ser642Arg) reported in PMID: 39596606 were each inherited from the parents of the proband (PMID: 35023579;39596606). Supportive functional studies were presented in PMID: 35023579 and 39596606.
Sources: Literature
Mitochondrial disorders v8.16 SUPV3L1 Sarah Leigh Added comment: Comment on publications: PMID: 39596606 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Mitochondrial disorders v8.16 SUPV3L1 Sarah Leigh Publications for gene: SUPV3L1 were set to 35023579; 39596606
Intellectual disability v8.202 SUPV3L1 Sarah Leigh Added comment: Comment on publications: PMID: 39596606 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.202 SUPV3L1 Sarah Leigh Publications for gene: SUPV3L1 were set to 35023579; 39596606
Mitochondrial disorders v8.15 SUPV3L1 Sarah Leigh gene: SUPV3L1 was added
gene: SUPV3L1 was added to Mitochondrial disorders. Sources: Literature
Q1_25_ promote_green tags were added to gene: SUPV3L1.
Mode of inheritance for gene: SUPV3L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUPV3L1 were set to 35023579; 39596606
Phenotypes for gene: SUPV3L1 were set to Mitochondrial RNA Helicase SUPV3L1-Associated neurodegenerative syndrome
Review for gene: SUPV3L1 was set to AMBER
Added comment: Three SUPV3L1 variants have been reported in two unrelated cases with a syndrome that includes ataxia, spasticity, optic atrophy and skin hypopigmentation (ASOASH) and also intellectual disability (PMID: 35023579;39596606).
The homozygous terminating SUPV3L1 variant (NM_003171.3: c.2215C>T, p.Gln739*) reported in the siblings in PMID: 35023579, was shown to results in reduced expression of the truncated protein in the proband's fibroblasts, resulting in a reduction of the mature ND6 mRNA species and also the accumulation of double-stranded RNA. This effect was partly restored using full-length SUPV3L1 cDNA (PMID: 35023579). This variant and the compound heterozygous SUPV3L1 variants (NM_003171.5: c.272-2A>G and c.1924A>C; p.(Ser642Arg) reported in PMID: 39596606 were each inherited from the parents of the proband (PMID: 35023579;39596606).
Sources: Literature
Intellectual disability v8.201 SUPV3L1 Sarah Leigh gene: SUPV3L1 was added
gene: SUPV3L1 was added to Intellectual disability. Sources: Literature
Q1_25_ promote_green tags were added to gene: SUPV3L1.
Mode of inheritance for gene: SUPV3L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUPV3L1 were set to 35023579; 39596606
Phenotypes for gene: SUPV3L1 were set to Mitochondrial RNA Helicase SUPV3L1-Associated neurodegenerative syndrome
Review for gene: SUPV3L1 was set to AMBER
Added comment: Three SUPV3L1 variants have been reported in two unrelated cases with a syndrome that includes ataxia, spasticity, optic atrophy and skin hypopigmentation (ASOASH) and also intellectual disability (PMID: 35023579;39596606).
The homozygous terminating SUPV3L1 variant (NM_003171.3: c.2215C>T, p.Gln739*) reported in the siblings in PMID: 35023579, was shown to results in reduced expression of the truncated protein in the proband's fibroblasts, resulting in a reduction of the mature ND6 mRNA species and also the accumulation of double-stranded RNA. This effect was partly restored using full-length SUPV3L1 cDNA (PMID: 35023579). This variant and the compound heterozygous SUPV3L1 variants (NM_003171.5: c.272-2A>G and c.1924A>C; p.(Ser642Arg) reported in PMID: 39596606 were each inherited from the parents of the proband (PMID: 35023579;39596606).
Sources: Literature
Intellectual disability v8.200 MARS2 Achchuthan Shanmugasundram changed review comment from: Comment on publications: PMID:39995633 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.

The patient reported in PMID:39995633 presented with psychomotor developmental delay, growth failure, and generalized skeletal alterations. Genetic analyses showed novel biallelic variants, c.277G > A; p.(Asp93Asn) and c.409C > T; p.(Arg137Cys) in the MARS2 gene. These variants were inherited from the patient's parents, with one variant detected in the mother and the other in the father, both heterozygous.; to: Comment on publications: PMID:39995633 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.

The patient reported in PMID:39995633 presented with psychomotor developmental delay, growth failure, and generalized skeletal alterations. However, this patient was not reported with intellectual disability in the publication.

Genetic analyses showed novel biallelic variants, c.277G > A; p.(Asp93Asn) and c.409C > T; p.(Arg137Cys) in the MARS2 gene. These variants were inherited from the patient's parents, with one variant detected in the mother and the other in the father, both heterozygous.
Intellectual disability v8.200 MARS2 Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:39995633 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.

The patient reported in PMID:39995633 presented with psychomotor developmental delay, growth failure, and generalized skeletal alterations. Genetic analyses showed novel biallelic variants, c.277G > A; p.(Asp93Asn) and c.409C > T; p.(Arg137Cys) in the MARS2 gene. These variants were inherited from the patient's parents, with one variant detected in the mother and the other in the father, both heterozygous.
Intellectual disability v8.200 MARS2 Achchuthan Shanmugasundram Publications for gene: MARS2 were set to 25754315
Intellectual disability v8.199 MARS2 Achchuthan Shanmugasundram reviewed gene: MARS2: Rating: RED; Mode of pathogenicity: None; Publications: 39995633; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v8.199 HNRNPC Achchuthan Shanmugasundram Classified gene: HNRNPC as Amber List (moderate evidence)
Intellectual disability v8.199 HNRNPC Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (14 unrelated cases) for the promotion of this gene to green rating in the next GMS update.
Intellectual disability v8.199 HNRNPC Achchuthan Shanmugasundram Gene: hnrnpc has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.198 HNRNPC Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:40004505 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.198 HNRNPC Achchuthan Shanmugasundram Publications for gene: HNRNPC were set to 37541189; 40004505
Intellectual disability v8.197 HNRNPC Achchuthan Shanmugasundram changed review comment from: PMID:37541189 reported a cohort of 13 individuals with heterozygous germline variants in HNRNPC gene, including a recurrent de novo in-frame deletion in five individuals (c.850_876del/ p.(Arg284_Asp292del) for HNRNPC-iso1 and c.889_915del/ p.(Arg297_Asp305del) for HNRNPC-iso2). They all presented with a neurodevelopmental disorder characterised by global developmental delay, intellectual disability, behavioural abnormalities, and subtle facial dysmorphic features in most individuals.

PMID:40004505 reported the identification of the missense variant, p.(Arg99Gln) in a patient showing a unique clinical presentation characterized by DD/ID, distinctive facial features, cochlear aplasia, and bilateral colobomatous microphthalmia. This variant was previously reported in an individual in PMID:37541189. The clinical phenotype of this individual fit that of the previously described individual and only partially overlaps with the clinical spectrum of the disease.

This gene has already been associated with relevant phenotypes in OMIM (MIM #620688), but not yet in Gene2Phenotype.
Sources: Literature; to: PMID:37541189 reported a cohort of 13 individuals with heterozygous germline variants in HNRNPC gene, including a recurrent de novo in-frame deletion in five individuals (c.850_876del/ p.(Arg284_Asp292del) for HNRNPC-iso1 and c.889_915del/ p.(Arg297_Asp305del) for HNRNPC-iso2). They all presented with a neurodevelopmental disorder characterised by global developmental delay, intellectual disability, behavioural abnormalities, and subtle facial dysmorphic features in most individuals.

PMID:40004505 reported the identification of the missense variant, p.(Arg99Gln) in a patient showing a unique clinical presentation characterised by DD/ID, distinctive facial features, cochlear aplasia, and bilateral colobomatous microphthalmia. This variant was previously reported in an individual in PMID:37541189. The clinical phenotype of this individual fit that of the previously described individual and only partially overlaps with the clinical spectrum of the disease.

This gene has already been associated with relevant phenotypes in OMIM (MIM #620688), but not yet in Gene2Phenotype.
Sources: Literature
Intellectual disability v8.197 HNRNPC Achchuthan Shanmugasundram gene: HNRNPC was added
gene: HNRNPC was added to Intellectual disability. Sources: Literature
Q1_25_ promote_green tags were added to gene: HNRNPC.
Mode of inheritance for gene: HNRNPC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HNRNPC were set to 37541189; 40004505
Phenotypes for gene: HNRNPC were set to Intellectual developmental disorder, autosomal dominant 74, OMIM:620688
Review for gene: HNRNPC was set to GREEN
Added comment: PMID:37541189 reported a cohort of 13 individuals with heterozygous germline variants in HNRNPC gene, including a recurrent de novo in-frame deletion in five individuals (c.850_876del/ p.(Arg284_Asp292del) for HNRNPC-iso1 and c.889_915del/ p.(Arg297_Asp305del) for HNRNPC-iso2). They all presented with a neurodevelopmental disorder characterised by global developmental delay, intellectual disability, behavioural abnormalities, and subtle facial dysmorphic features in most individuals.

PMID:40004505 reported the identification of the missense variant, p.(Arg99Gln) in a patient showing a unique clinical presentation characterized by DD/ID, distinctive facial features, cochlear aplasia, and bilateral colobomatous microphthalmia. This variant was previously reported in an individual in PMID:37541189. The clinical phenotype of this individual fit that of the previously described individual and only partially overlaps with the clinical spectrum of the disease.

This gene has already been associated with relevant phenotypes in OMIM (MIM #620688), but not yet in Gene2Phenotype.
Sources: Literature
Early onset or syndromic epilepsy v7.78 KCNH8 Sarah Leigh Added comment: Comment on publications: PMID: 39156922 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Early onset or syndromic epilepsy v7.78 KCNH8 Sarah Leigh Publications for gene: KCNH8 were set to 39156922
Early onset or syndromic epilepsy v7.77 RTEL1 Sarah Leigh Added comment: Comment on publications: PMID: 39156922 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Early onset or syndromic epilepsy v7.77 RTEL1 Sarah Leigh Publications for gene: RTEL1 were set to 39156922
Early onset or syndromic epilepsy v7.76 RTEL1 Sarah Leigh gene: RTEL1 was added
gene: RTEL1 was added to Early onset or syndromic epilepsy. Sources: Literature
Mode of inheritance for gene: RTEL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RTEL1 were set to 39156922
Phenotypes for gene: RTEL1 were set to Familial Progressive Myoclonus Epilepsy
Review for gene: RTEL1 was set to RED
Added comment: PMID: 39156922 reports two sibling from a consanguineous family who had familial progressive myoclonus epilepsy. Both of the sibling were homozygous for a KCNH8 variant (NM_144633.3:c.298T>C; p.Tyr100His) and a RTEL1 variant (NM_032957.5:c.691G>T; p.Asp231Tyr).
Sources: Literature
Early onset or syndromic epilepsy v7.75 KCNH8 Sarah Leigh gene: KCNH8 was added
gene: KCNH8 was added to Early onset or syndromic epilepsy. Sources: Literature
Mode of inheritance for gene: KCNH8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KCNH8 were set to 39156922
Phenotypes for gene: KCNH8 were set to Familial Progressive Myoclonus Epilepsy
Review for gene: KCNH8 was set to RED
Added comment: PMID: 39156922 reports two sibling from a consanguineous family who had familial progressive myoclonus epilepsy. Both of the sibling were homozygous for a KCNH8 variant (NM_144633.3:c.298T>C; p.Tyr100His) and a RTEL1 variant (NM_032957.5:c.691G>T; p.Asp231Tyr).
Sources: Literature
Skeletal dysplasia v7.36 VPS33A Sarah Leigh Added comment: Comment on publications: PMID: 39273517 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Skeletal dysplasia v7.36 VPS33A Sarah Leigh Publications for gene: VPS33A were set to 27547915; 28013294; 31070736; 39273517
Intellectual disability v8.196 VPS33A Sarah Leigh Added comment: Comment on publications: PMID: 39273517 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.196 VPS33A Sarah Leigh Publications for gene: VPS33A were set to 27547915; 28013294; 31070736; 39273517
Intellectual disability v8.195 VPS33A Sarah Leigh Classified gene: VPS33A as Amber List (moderate evidence)
Intellectual disability v8.195 VPS33A Sarah Leigh Gene: vps33a has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v7.35 VPS33A Sarah Leigh Classified gene: VPS33A as Amber List (moderate evidence)
Skeletal dysplasia v7.35 VPS33A Sarah Leigh Gene: vps33a has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v7.34 VPS33A Sarah Leigh gene: VPS33A was added
gene: VPS33A was added to Skeletal dysplasia. Sources: Literature
Q1_25_ promote_green tags were added to gene: VPS33A.
Mode of inheritance for gene: VPS33A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS33A were set to 27547915; 28013294; 31070736; 39273517
Phenotypes for gene: VPS33A were set to Mucopolysaccharidosis-plus syndrome, OMIM:617303; mucopolysaccharidosis-plus syndrome, MONDO:0015012
Review for gene: VPS33A was set to GREEN
Added comment: There are numerous reports of the homozygous VPS33A variant: NM 022916.5: c.1492C > T, p.Arg498Trp in cases of Mucopolysaccharidosis-plus syndrome (OMIM:617303)(PMID: 27547915;28013294;31070736;39273517). Common features of this syndrome include: hepatomegaly, splenomegaly, respiratory difficulties, developmental delay including limited cognitive abilities and various skeletal issues (PMID: 27547915;28013294;31070736;39273517).
Sources: Literature
Intellectual disability v8.194 VPS33A Sarah Leigh gene: VPS33A was added
gene: VPS33A was added to Intellectual disability. Sources: Literature
Q1_25_ promote_green tags were added to gene: VPS33A.
Mode of inheritance for gene: VPS33A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS33A were set to 27547915; 28013294; 31070736; 39273517
Phenotypes for gene: VPS33A were set to Mucopolysaccharidosis-plus syndrome, OMIM:617303; mucopolysaccharidosis-plus syndrome, MONDO:0015012
Review for gene: VPS33A was set to GREEN
Added comment: There are numerous reports of the homozygous VPS33A variant: NM 022916.5: c.1492C > T, p.Arg498Trp in cases of Mucopolysaccharidosis-plus syndrome (OMIM:617303)(PMID: 27547915;28013294;31070736;39273517). Common features of this syndrome include: hepatomegaly, splenomegaly, respiratory difficulties, developmental delay including limited cognitive abilities and various skeletal issues (PMID: 27547915;28013294;31070736;39273517).
Sources: Literature
Intellectual disability v8.193 CRMP1 Achchuthan Shanmugasundram Classified gene: CRMP1 as Amber List (moderate evidence)
Intellectual disability v8.193 CRMP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are three unrelated cases reported with moderate intellectual disability and with monoallelic CRMP1 variants. However, one patient with a different monoallelic CRMP1 variant had normal IQ. Hence, this gene should be rated amber with current evidence.

The 'watchlist' tag has been added to review this gene in light of any new evidence in the future.
Intellectual disability v8.193 CRMP1 Achchuthan Shanmugasundram Gene: crmp1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.192 CRMP1 Achchuthan Shanmugasundram Tag watchlist tag was added to gene: CRMP1.
Intellectual disability v8.192 CRMP1 Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:39758889 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.192 CRMP1 Achchuthan Shanmugasundram Publications for gene: CRMP1 were set to 36511780; 39758889
Intellectual disability v8.191 CRMP1 Achchuthan Shanmugasundram gene: CRMP1 was added
gene: CRMP1 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: CRMP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CRMP1 were set to 36511780; 39758889
Phenotypes for gene: CRMP1 were set to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Review for gene: CRMP1 was set to AMBER
Added comment: PMID:36511780 reported the identification of three different heterozygous de novo variants in the CRMP1 gene (p.(Pro589Leu), p.(Thr427Met) & p.(Phe351Ser)) in three unrelated individuals with a neurodevelopmental disorder presenting with muscular hypotonia, intellectual disability, and/or autism spectrum disorder. ID was moderate in two of them, while IQ was normal in one. There is also functional evidence available for these variants.

PMID:39758889 reported the identification of a novel heterozygous de novo frameshift variant in CRMP1 (p.(Lys586fs)) in a 9-year-old male patient presenting with phenotypes such as autism, language delay, hyperactivity, and learning disabilities. This patient was reported with moderate ID.
Sources: Literature
Monogenic short stature v1.13 GAP43 Achchuthan Shanmugasundram changed review comment from: PMID:39738362 reported the identification of a heterozygous missense variant in the GAP43 gene (p.(Glu146Lys)) in a 15-year-old female patient with moderate intellectual disability, neurodevelopmental disorders, short stature, and skeletal abnormalities such as left-right difference in legs and digital deformities.

The variant GAP43 protein was found to be unstable in neuronal cells and the disruption of Gap43 in mouse embryonic cortical neurons impaired axonal elongation and dendrite formation.

There were six previous cases reported with GAP43 abnormalities (4 involving deletion of a region including GAP43, one duplication and one SNV). Only one of these cases with region deletion had moderate ID, while two others had mild ID.
Sources: Literature; to: PMID:39738362 reported the identification of a heterozygous missense variant in the GAP43 gene (p.(Glu146Lys)) in a 15-year-old female patient with moderate intellectual disability, neurodevelopmental disorders, short stature, and skeletal abnormalities such as left-right difference in legs and digital deformities.

The variant GAP43 protein was found to be unstable in neuronal cells and the disruption of Gap43 in mouse embryonic cortical neurons impaired axonal elongation and dendrite formation.

There were six previous cases reported with GAP43 abnormalities (3 involving deletion of a region including GAP43, two siblings with duplication and one SNV). Only one of the siblings with region duplication had moderate ID, while the other sibling and another patient with region deletion had mild ID.

This gene has not yet been associated with phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Monogenic short stature v1.13 GAP43 Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:39738362 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Monogenic short stature v1.13 GAP43 Achchuthan Shanmugasundram Publications for gene: GAP43 were set to 39738362
Intellectual disability v8.190 GAP43 Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:39738362 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.190 GAP43 Achchuthan Shanmugasundram Publications for gene: GAP43 were set to 39738362
Intellectual disability v8.189 GAP43 Achchuthan Shanmugasundram changed review comment from: PMID:39738362 reported the identification of a heterozygous missense variant in the GAP43 gene (p.(Glu146Lys)) in a 15-year-old female patient with moderate intellectual disability, neurodevelopmental disorders, short stature, and skeletal abnormalities such as left-right difference in legs and digital deformities.

The variant GAP43 protein was found to be unstable in neuronal cells and the disruption of Gap43 in mouse embryonic cortical neurons impaired axonal elongation and dendrite formation.

There were six previous cases reported with GAP43 abnormalities (3 involving deletion of a region including GAP43, two siblings with duplication and one SNV). Only one of the siblings with region duplication had moderate ID, while the other sibling and another patient with region deletion had mild ID.
Sources: Literature; to: PMID:39738362 reported the identification of a heterozygous missense variant in the GAP43 gene (p.(Glu146Lys)) in a 15-year-old female patient with moderate intellectual disability, neurodevelopmental disorders, short stature, and skeletal abnormalities such as left-right difference in legs and digital deformities.

The variant GAP43 protein was found to be unstable in neuronal cells and the disruption of Gap43 in mouse embryonic cortical neurons impaired axonal elongation and dendrite formation.

There were six previous cases reported with GAP43 abnormalities (3 involving deletion of a region including GAP43, two siblings with duplication and one SNV). Only one of the siblings with region duplication had moderate ID, while the other sibling and another patient with region deletion had mild ID.

This gene has not yet been associated with phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v8.189 ERCC4 Sarah Leigh Added comment: Comment on publications: PMID: 39769235 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.189 ERCC4 Sarah Leigh Publications for gene: ERCC4 were set to 39769235
Intellectual disability v8.188 GAP43 Achchuthan Shanmugasundram changed review comment from: PMID:39738362 reported the identification of a heterozygous missense variant in the GAP43 gene (p.(Glu146Lys)) in a 15-year-old female patient with moderate intellectual disability, neurodevelopmental disorders, short stature, and skeletal abnormalities such as left-right difference in legs and digital deformities.

The variant GAP43 protein was found to be unstable in neuronal cells and the disruption of Gap43 in mouse embryonic cortical neurons impaired axonal elongation and dendrite formation.

There were six previous cases reported with GAP43 abnormalities (4 involving deletion of a region including GAP43, one duplication and one SNV). Only one of these cases with region deletion had moderate ID, while two others had mild ID.
Sources: Literature; to: PMID:39738362 reported the identification of a heterozygous missense variant in the GAP43 gene (p.(Glu146Lys)) in a 15-year-old female patient with moderate intellectual disability, neurodevelopmental disorders, short stature, and skeletal abnormalities such as left-right difference in legs and digital deformities.

The variant GAP43 protein was found to be unstable in neuronal cells and the disruption of Gap43 in mouse embryonic cortical neurons impaired axonal elongation and dendrite formation.

There were six previous cases reported with GAP43 abnormalities (3 involving deletion of a region including GAP43, two siblings with duplication and one SNV). Only one of the siblings with region duplication had moderate ID, while the other sibling and another patient with region deletion had mild ID.
Sources: Literature
Structural eye disease v4.4 TOMM7 Sarah Leigh Added comment: Comment on publications: PMID: 39615461 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Structural eye disease v4.4 TOMM7 Sarah Leigh Publications for gene: TOMM7 were set to 39615461
Structural eye disease v4.3 TOMM7 Sarah Leigh Classified gene: TOMM7 as Amber List (moderate evidence)
Structural eye disease v4.3 TOMM7 Sarah Leigh Gene: tomm7 has been classified as Amber List (Moderate Evidence).
Monogenic short stature v1.12 GAP43 Achchuthan Shanmugasundram gene: GAP43 was added
gene: GAP43 was added to Monogenic short stature. Sources: Literature
Mode of inheritance for gene: GAP43 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GAP43 were set to 39738362
Phenotypes for gene: GAP43 were set to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Review for gene: GAP43 was set to RED
Added comment: PMID:39738362 reported the identification of a heterozygous missense variant in the GAP43 gene (p.(Glu146Lys)) in a 15-year-old female patient with moderate intellectual disability, neurodevelopmental disorders, short stature, and skeletal abnormalities such as left-right difference in legs and digital deformities.

The variant GAP43 protein was found to be unstable in neuronal cells and the disruption of Gap43 in mouse embryonic cortical neurons impaired axonal elongation and dendrite formation.

There were six previous cases reported with GAP43 abnormalities (4 involving deletion of a region including GAP43, one duplication and one SNV). Only one of these cases with region deletion had moderate ID, while two others had mild ID.
Sources: Literature
Intellectual disability v8.188 GAP43 Achchuthan Shanmugasundram gene: GAP43 was added
gene: GAP43 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: GAP43 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GAP43 were set to 39738362
Phenotypes for gene: GAP43 were set to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Review for gene: GAP43 was set to RED
Added comment: PMID:39738362 reported the identification of a heterozygous missense variant in the GAP43 gene (p.(Glu146Lys)) in a 15-year-old female patient with moderate intellectual disability, neurodevelopmental disorders, short stature, and skeletal abnormalities such as left-right difference in legs and digital deformities.

The variant GAP43 protein was found to be unstable in neuronal cells and the disruption of Gap43 in mouse embryonic cortical neurons impaired axonal elongation and dendrite formation.

There were six previous cases reported with GAP43 abnormalities (4 involving deletion of a region including GAP43, one duplication and one SNV). Only one of these cases with region deletion had moderate ID, while two others had mild ID.
Sources: Literature
Intellectual disability v8.187 HINT1 Sarah Leigh Added comment: Comment on publications: PMID: 39596683 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.187 HINT1 Sarah Leigh Publications for gene: HINT1 were set to 22961002; 34694653; 39596683
Skeletal dysplasia v7.33 LRRC8C Achchuthan Shanmugasundram Classified gene: LRRC8C as Amber List (moderate evidence)
Skeletal dysplasia v7.33 LRRC8C Achchuthan Shanmugasundram Gene: lrrc8c has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v7.32 LRRC8C Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:39623139 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Skeletal dysplasia v7.32 LRRC8C Achchuthan Shanmugasundram Publications for gene: LRRC8C were set to 39623139
Severe microcephaly v7.22 LRRC8C Achchuthan Shanmugasundram Classified gene: LRRC8C as Amber List (moderate evidence)
Severe microcephaly v7.22 LRRC8C Achchuthan Shanmugasundram Gene: lrrc8c has been classified as Amber List (Moderate Evidence).
Severe microcephaly v7.21 LRRC8C Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:39623139 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Severe microcephaly v7.21 LRRC8C Achchuthan Shanmugasundram Publications for gene: LRRC8C were set to 39623139
Optic neuropathy v4.43 LRRC8C Achchuthan Shanmugasundram Classified gene: LRRC8C as Amber List (moderate evidence)
Optic neuropathy v4.43 LRRC8C Achchuthan Shanmugasundram Gene: lrrc8c has been classified as Amber List (Moderate Evidence).
Optic neuropathy v4.42 LRRC8C Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:39623139 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Optic neuropathy v4.42 LRRC8C Achchuthan Shanmugasundram Publications for gene: LRRC8C were set to 39623139
Monogenic short stature v1.11 LRRC8C Achchuthan Shanmugasundram Classified gene: LRRC8C as Amber List (moderate evidence)
Monogenic short stature v1.11 LRRC8C Achchuthan Shanmugasundram Gene: lrrc8c has been classified as Amber List (Moderate Evidence).
Monogenic short stature v1.10 LRRC8C Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:39623139 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Monogenic short stature v1.10 LRRC8C Achchuthan Shanmugasundram Publications for gene: LRRC8C were set to 39623139
Intellectual disability v8.186 LRRC8C Achchuthan Shanmugasundram changed review comment from: Comment on publications: PMID:39623139 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques; to: Comment on publications: PMID:39623139 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.186 LRRC8C Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:39623139 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques
Intellectual disability v8.186 LRRC8C Achchuthan Shanmugasundram Publications for gene: LRRC8C were set to 39623139
Intellectual disability v8.185 LRRC8C Achchuthan Shanmugasundram Classified gene: LRRC8C as Amber List (moderate evidence)
Intellectual disability v8.185 LRRC8C Achchuthan Shanmugasundram Gene: lrrc8c has been classified as Amber List (Moderate Evidence).
Monogenic short stature v1.9 LRRC8C Achchuthan Shanmugasundram gene: LRRC8C was added
gene: LRRC8C was added to Monogenic short stature. Sources: Literature
Mode of inheritance for gene: LRRC8C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LRRC8C were set to 39623139
Phenotypes for gene: LRRC8C were set to TIMES syndrome, OMIM:621056
Mode of pathogenicity for gene: LRRC8C 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: LRRC8C was set to AMBER
Added comment: PMID:39623139 reported two unrelated individuals with a multisystem disorder characterised by considerable phenotypic variability, but with overlapping features including telangiectasia, impaired intellectual development, microcephaly, metaphyseal dysplasia, eye abnormalities, and short stature.

One patient had a 1-bp heterozygous insertion (p.(Leu400IlefsTer8)) in LRRC8C gene, while the other one had a heterozygous missense variant in the same gene (p.(Val390Leu)). There is also evidence from in vitro functional assay available. The evidence also suggests that both variants result in gain-of-function effect.

`This gene has been associated with relevant phenotype in OMIM (MIM #621056), but not yet in Gene2Phenotype.
Sources: Literature
Optic neuropathy v4.41 LRRC8C Achchuthan Shanmugasundram gene: LRRC8C was added
gene: LRRC8C was added to Optic neuropathy. Sources: Literature
Mode of inheritance for gene: LRRC8C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LRRC8C were set to 39623139
Phenotypes for gene: LRRC8C were set to TIMES syndrome, OMIM:621056
Mode of pathogenicity for gene: LRRC8C 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: LRRC8C was set to AMBER
Added comment: PMID:39623139 reported two unrelated individuals with a multisystem disorder characterised by considerable phenotypic variability, but with overlapping features including telangiectasia, impaired intellectual development, microcephaly, metaphyseal dysplasia, eye abnormalities, and short stature.

One patient had a 1-bp heterozygous insertion (p.(Leu400IlefsTer8)) in LRRC8C gene, while the other one had a heterozygous missense variant in the same gene (p.(Val390Leu)). There is also evidence from in vitro functional assay available. The evidence also suggests that both variants result in gain-of-function effect.

`This gene has been associated with relevant phenotype in OMIM (MIM #621056), but not yet in Gene2Phenotype.
Sources: Literature
Severe microcephaly v7.20 LRRC8C Achchuthan Shanmugasundram gene: LRRC8C was added
gene: LRRC8C was added to Severe microcephaly. Sources: Literature
Mode of inheritance for gene: LRRC8C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LRRC8C were set to 39623139
Phenotypes for gene: LRRC8C were set to TIMES syndrome, OMIM:621056
Mode of pathogenicity for gene: LRRC8C 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: LRRC8C was set to AMBER
Added comment: PMID:39623139 reported two unrelated individuals with a multisystem disorder characterised by considerable phenotypic variability, but with overlapping features including telangiectasia, impaired intellectual development, microcephaly, metaphyseal dysplasia, eye abnormalities, and short stature.

One patient had a 1-bp heterozygous insertion (p.(Leu400IlefsTer8)) in LRRC8C gene, while the other one had a heterozygous missense variant in the same gene (p.(Val390Leu)). There is also evidence from in vitro functional assay available. The evidence also suggests that both variants result in gain-of-function effect.

`This gene has been associated with relevant phenotype in OMIM (MIM #621056), but not yet in Gene2Phenotype.
Sources: Literature
Skeletal dysplasia v7.31 LRRC8C Achchuthan Shanmugasundram gene: LRRC8C was added
gene: LRRC8C was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: LRRC8C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LRRC8C were set to 39623139
Phenotypes for gene: LRRC8C were set to TIMES syndrome, OMIM:621056
Mode of pathogenicity for gene: LRRC8C 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: LRRC8C was set to AMBER
Added comment: PMID:39623139 reported two unrelated individuals with a multisystem disorder characterised by considerable phenotypic variability, but with overlapping features including telangiectasia, impaired intellectual development, microcephaly, metaphyseal dysplasia, eye abnormalities, and short stature.

One patient had a 1-bp heterozygous insertion (p.(Leu400IlefsTer8)) in LRRC8C gene, while the other one had a heterozygous missense variant in the same gene (p.(Val390Leu)). There is also evidence from in vitro functional assay available. The evidence also suggests that both variants result in gain-of-function effect.

`This gene has been associated with relevant phenotype in OMIM (MIM #621056), but not yet in Gene2Phenotype.
Sources: Literature
Intellectual disability v8.184 LRRC8C Achchuthan Shanmugasundram gene: LRRC8C was added
gene: LRRC8C was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: LRRC8C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LRRC8C were set to 39623139
Phenotypes for gene: LRRC8C were set to TIMES syndrome, OMIM:621056
Mode of pathogenicity for gene: LRRC8C 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: LRRC8C was set to AMBER
Added comment: PMID:39623139 reported two unrelated individuals with a multisystem disorder characterised by considerable phenotypic variability, but with overlapping features including telangiectasia, impaired intellectual development, microcephaly, metaphyseal dysplasia, eye abnormalities, and short stature.

One patient had a 1-bp heterozygous insertion (p.(Leu400IlefsTer8)) in LRRC8C gene, while the other one had a heterozygous missense variant in the same gene (p.(Val390Leu)). There is also evidence from in vitro functional assay available. The evidence also suggests that both variants result in gain-of-function effect.

`This gene has been associated with relevant phenotype in OMIM (MIM #621056), but not yet in Gene2Phenotype.
Sources: Literature
Intellectual disability v8.183 WFS1 Achchuthan Shanmugasundram changed review comment from: PMID:39767643 reported the identification of an ultra-rare, mono-allelic missense variant in the WFS1 gene (p. Asp711Asn) in a nine-year-old girl that showed phenotypic manifestations of intellectual impairment, microcephaly, and epilepsy. There was a positive family history in previous generations for cognitive impairment.; to: PMID:39767643 reported the identification of an ultra-rare, mono-allelic missense variant in the WFS1 gene (p. Asp711Asn) in a nine-year-old girl that showed phenotypic manifestations of intellectual impairment, microcephaly, and epilepsy. There was a positive family history in previous generations for cognitive impairment.

Although there are multiple phenotypes available for this gene in OMIM, mental retardation/ cognitive impairment has been recorded as a clinical manifestation seen in some patients with the autosomal recessive Wolfram syndrome 1 (MIM #222300). However, ID has not been associated with any autosomal dominant syndromes. In addition, ID forms part of a broader phenotype.

Hence, this gene can only be rated red for both monoallelic and biallelic disease associations in this panel.
Intellectual disability v8.183 WFS1 Achchuthan Shanmugasundram edited their review of gene: WFS1: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v8.183 WFS1 Achchuthan Shanmugasundram edited their review of gene: WFS1: Changed rating: RED
Intellectual disability v8.183 WFS1 Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:39767643 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.183 WFS1 Achchuthan Shanmugasundram Publications for gene: WFS1 were set to
Intellectual disability v8.182 WFS1 Achchuthan Shanmugasundram reviewed gene: WFS1: Rating: AMBER; Mode of pathogenicity: None; Publications: 39767643; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v8.182 LMNA Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:39767643 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.182 LMNA Achchuthan Shanmugasundram Publications for gene: LMNA were set to 25529582; 39767643
Intellectual disability v8.181 LMNA Achchuthan Shanmugasundram Classified gene: LMNA as Amber List (moderate evidence)
Intellectual disability v8.181 LMNA Achchuthan Shanmugasundram Gene: lmna has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.180 LMNA Achchuthan Shanmugasundram changed review comment from: PMID:39767643 reported the identification of a heterozygous missense variant in LMNA gene (p. Glu443Gly) in a 16-year-old boy affected with intellectual impairment, cardiac manifestation, diabetes mellitus, a cataract in the right eye, epilepsy, and skin atrophy on his back. This family showed no positive history of neurodevelopmental disorders (NDDs) in the five previous generations, while one sibling was affected by a NDD phenotype.

There are four cases reported in the Decipher database with sequence variants in LMNA gene (https://www.deciphergenomics.org/gene/LMNA/patient-overlap/snvs), of which the patient with frameshift variant (p.Glu223AspfsTer7) was reported with a number of phenotypes including global developmental delay.; to: PMID:39767643 reported the identification of a heterozygous missense variant in LMNA gene (p. Glu443Gly) in a 16-year-old boy affected with intellectual impairment, cardiac manifestation, diabetes mellitus, a cataract in the right eye, epilepsy, and skin atrophy on his back. This family showed no positive history of neurodevelopmental disorders (NDDs) in the five previous generations, while one sibling was affected by a NDD phenotype.

There are four cases reported in the Decipher database with sequence variants in LMNA gene (https://www.deciphergenomics.org/gene/LMNA/patient-overlap/snvs), of which the patient with frameshift variant (p.Glu223AspfsTer7) was reported with a number of phenotypes including global developmental delay. This variant is annotated to be likely pathogenic and with the contribution of the variant to phenotype is uncertain.
Intellectual disability v8.180 LMNA Achchuthan Shanmugasundram Publications for gene: LMNA were set to
Intellectual disability v8.179 LMNA Achchuthan Shanmugasundram Mode of inheritance for gene: LMNA was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v8.178 LMNA Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v8.178 LMNA Achchuthan Shanmugasundram commented on gene: LMNA: PMID:39767643 reported the identification of a heterozygous missense variant in LMNA gene (p. Glu443Gly) in a 16-year-old boy affected with intellectual impairment, cardiac manifestation, diabetes mellitus, a cataract in the right eye, epilepsy, and skin atrophy on his back. This family showed no positive history of neurodevelopmental disorders (NDDs) in the five previous generations, while one sibling was affected by a NDD phenotype.

There are four cases reported in the Decipher database with sequence variants in LMNA gene (https://www.deciphergenomics.org/gene/LMNA/patient-overlap/snvs), of which the patient with frameshift variant (p.Glu223AspfsTer7) was reported with a number of phenotypes including global developmental delay.
Intellectual disability v8.178 LMNA Achchuthan Shanmugasundram reviewed gene: LMNA: Rating: AMBER; Mode of pathogenicity: None; Publications: 25529582, 39767643; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v8.178 ERCC4 Sarah Leigh reviewed gene: ERCC4: Rating: RED; Mode of pathogenicity: None; Publications: 39769235; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v8.178 ERCC4 Sarah Leigh Publications for gene: ERCC4 were set to
Intellectual disability v8.178 ERCC4 Sarah Leigh Phenotypes for gene: ERCC4 were changed from Xeroderma pigmentosum, group F, 278760; XFE progeroid syndrome, 610965; Fanconi anemia, complementation group Q, 615272; Xeroderma pigmentosum, type F/Cockayne syndrome, 278760 to Xeroderma pigmentosum, group F 278760; XFE progeroid syndrome, OMIM: 610965
Structural eye disease v4.2 TOMM7 Sarah Leigh gene: TOMM7 was added
gene: TOMM7 was added to Structural eye disease. Sources: Literature
Q1_25_ promote_green tags were added to gene: TOMM7.
Mode of inheritance for gene: TOMM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TOMM7 were set to 39615461
Phenotypes for gene: TOMM7 were set to Garg-Mishra progeroid syndrome, OMIM:620601
Review for gene: TOMM7 was set to GREEN
Added comment: Ocular features are reported in nine members of seven unrelated Chinese families, who all are homozygous for the same TOMM7 variant ( NM_019059.5:c.86C>T; NP_061932.1:p.P29L)(PMID: 39615461). The common features were Maculopathy (7/9 individuals), Amblyobia (6/9 individuals) and hyperopia (6/9 individuals).
Sources: Literature
Intellectual disability v8.177 HINT1 Sarah Leigh reviewed gene: HINT1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuromyotonia and axonal neuropathy, autosomal recessive, OMIM:137200, Gamstorp-Wohlfart syndrome, MONDO:0007646; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v8.177 HINT1 Sarah Leigh Publications for gene: HINT1 were set to 22961002; 34694653; 39596683
Intellectual disability v8.176 HINT1 Sarah Leigh Phenotypes for gene: HINT1 were changed from Neuromyotonia and axonal neuropathy, autosomal recessive, 137200 to Neuromyotonia and axonal neuropathy, autosomal recessive, OMIM:137200; Gamstorp-Wohlfart syndrome, MONDO:0007646
Intellectual disability v8.175 HINT1 Sarah Leigh Publications for gene: HINT1 were set to
Distal myopathies v6.3 TIA1 Cassandra Smith reviewed gene: TIA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Deafness and congenital structural abnormalities v1.30 DAP3 Achchuthan Shanmugasundram changed review comment from: PMID:39701103 reported the identification of biallelic variants in DAP3 gene in five unrelated individuals presenting with variable clinical presentations ranging from Perrault syndrome (sensorineural hearing loss and ovarian insufficiency) to an early childhood neurometabolic phenotype. All five individuals had bilateral sensorineural hearing loss and the severity was profound in three of them, while not reported in the other two. Severe intellectual disability was reported in one individual and mild ID was reported in two individuals. There is also functional evidence available.

This gene has been associated with relevant phenotypes in OMIM (MIM #621101).; to: PMID:39701103 reported the identification of biallelic variants in DAP3 gene in five unrelated individuals presenting with variable clinical presentations ranging from Perrault syndrome (sensorineural hearing loss and ovarian insufficiency) to an early childhood neurometabolic phenotype. All five individuals had bilateral sensorineural hearing loss and the severity was profound in three of them, while not reported in the other two. Severe intellectual disability was reported in one individual and mild ID was reported in two individuals. There is also functional evidence available.

This gene has been associated with relevant phenotypes in OMIM (MIM #621101), but not yet in Gene2Phenotype.
Monogenic hearing loss v4.82 DAP3 Achchuthan Shanmugasundram changed review comment from: PMID:39701103 reported the identification of biallelic variants in DAP3 gene in five unrelated individuals presenting with variable clinical presentations ranging from Perrault syndrome (sensorineural hearing loss and ovarian insufficiency) to an early childhood neurometabolic phenotype. All five individuals had bilateral sensorineural hearing loss and the severity was profound in three of them, while not reported in the other two. Severe intellectual disability was reported in one individual and mild ID was reported in two individuals. There is also functional evidence available.

This gene has been associated with relevant phenotypes in OMIM (MIM #621101).
Sources: Literature; to: PMID:39701103 reported the identification of biallelic variants in DAP3 gene in five unrelated individuals presenting with variable clinical presentations ranging from Perrault syndrome (sensorineural hearing loss and ovarian insufficiency) to an early childhood neurometabolic phenotype. All five individuals had bilateral sensorineural hearing loss and the severity was profound in three of them, while not reported in the other two. Severe intellectual disability was reported in one individual and mild ID was reported in two individuals. There is also functional evidence available.

This gene has been associated with relevant phenotypes in OMIM (MIM #621101), but not yet in Gene2Phenotype.
Sources: Literature
Intellectual disability v8.174 DAP3 Achchuthan Shanmugasundram changed review comment from: PMID:39701103 reported the identification of biallelic variants in DAP3 gene in five unrelated individuals presenting with variable clinical presentations ranging from Perrault syndrome (sensorineural hearing loss and ovarian insufficiency) to an early childhood neurometabolic phenotype. All five individuals had bilateral sensorineural hearing loss and the severity was profound in three of them, while not reported in the other two. Severe intellectual disability was reported in one individual and mild ID was reported in two individuals. There is also functional evidence available.

This gene has been associated with relevant phenotypes in OMIM (MIM #621101).
Sources: Literature; to: PMID:39701103 reported the identification of biallelic variants in DAP3 gene in five unrelated individuals presenting with variable clinical presentations ranging from Perrault syndrome (sensorineural hearing loss and ovarian insufficiency) to an early childhood neurometabolic phenotype. All five individuals had bilateral sensorineural hearing loss and the severity was profound in three of them, while not reported in the other two. Severe intellectual disability was reported in one individual and mild ID was reported in two individuals. There is also functional evidence available.

This gene has been associated with relevant phenotypes in OMIM (MIM #621101), but not yet in Gene2Phenotype.
Sources: Literature
Intellectual disability v8.174 PLAT Achchuthan Shanmugasundram changed review comment from: PMID:39574431 reported the identification of three different homozygous truncating variants in PLAT gene in four individuals from three unrelated families. All of them presented with tetraventricular hydrocephalus. Dandy–Walker malformation was reported in three unrelated cases, of which mild intellectual disability was reported in one (family 2). Global developmental delay was reported in another (family 3), but this could partially be explained by a co-occurring Cohen syndrome diagnosis. Mild ID was also reported in the proband from family 1 that did not show Dandy–Walker malformation.

This gene has not yet been associated with any relevant phenotypes in OMIM or in Gene2Phenotype.
Sources: Literature; to: PMID:39574431 reported the identification of three different homozygous truncating variants in PLAT gene in four cases from three unrelated families. All of them presented with tetraventricular hydrocephalus. Dandy–Walker malformation was reported in three unrelated cases (two individuals and one foetus), of which mild intellectual disability was reported in one (family 2). Global developmental delay was reported in another (family 3), but this could partially be explained by a co-occurring Cohen syndrome diagnosis. Mild ID was also reported in the proband from family 1 that did not show Dandy–Walker malformation.

This gene has not yet been associated with any relevant phenotypes in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v8.174 PLAT Achchuthan Shanmugasundram changed review comment from: PMID:39574431 reported the identification of three different homozygous truncating variants in PLAT gene in four individuals from three unrelated families. All of them presented with tetraventricular hydrocephalus. Dandy–Walker malformation was reported in three unrelated cases, of which mild intellectual disability was reported in two. Global developmental delay was reported in the third one.

This gene has not yet been associated with any relevant phenotypes in OMIM or in Gene2Phenotype.
Sources: Literature; to: PMID:39574431 reported the identification of three different homozygous truncating variants in PLAT gene in four individuals from three unrelated families. All of them presented with tetraventricular hydrocephalus. Dandy–Walker malformation was reported in three unrelated cases, of which mild intellectual disability was reported in one (family 2). Global developmental delay was reported in another (family 3), but this could partially be explained by a co-occurring Cohen syndrome diagnosis. Mild ID was also reported in the proband from family 1 that did not show Dandy–Walker malformation.

This gene has not yet been associated with any relevant phenotypes in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v8.174 DAP3 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: This gene is currently rated amber as there is only case identified with severe ID, while two other cases had only mild ID.; to: Comment on list classification: This gene is currently rated amber as there is only one case identified with severe ID, while two other cases had only mild ID.
Intellectual disability v8.174 PLAT Achchuthan Shanmugasundram Classified gene: PLAT as Amber List (moderate evidence)
Intellectual disability v8.174 PLAT Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated amber with current evidence as there is one case reported with GDD and two cases reported with only mild ID.
Intellectual disability v8.174 PLAT Achchuthan Shanmugasundram Gene: plat has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.173 DAP3 Achchuthan Shanmugasundram Classified gene: DAP3 as Amber List (moderate evidence)
Intellectual disability v8.173 DAP3 Achchuthan Shanmugasundram Gene: dap3 has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.172 DAP3 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: This gene is currently rated amber as there is only case identified with severe ID, while two other cases had only mild ID.; to: Comment on list classification: This gene is currently rated amber as there is only case identified with severe ID, while two other cases had only mild ID.
Intellectual disability v8.172 DAP3 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: This gene is currently rated red as there is only case identified with severe ID, while two other cases had only mild ID.; to: Comment on list classification: This gene is currently rated amber as there is only case identified with severe ID, while two other cases had only mild ID.
Intellectual disability v8.172 DAP3 Achchuthan Shanmugasundram edited their review of gene: DAP3: Changed rating: AMBER
Intellectual disability v8.172 PLAT Achchuthan Shanmugasundram gene: PLAT was added
gene: PLAT was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: PLAT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLAT were set to 39574431
Phenotypes for gene: PLAT were set to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Review for gene: PLAT was set to AMBER
Added comment: PMID:39574431 reported the identification of three different homozygous truncating variants in PLAT gene in four individuals from three unrelated families. All of them presented with tetraventricular hydrocephalus. Dandy–Walker malformation was reported in three unrelated cases, of which mild intellectual disability was reported in two. Global developmental delay was reported in the third one.

This gene has not yet been associated with any relevant phenotypes in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v8.171 IARS2 Achchuthan Shanmugasundram Publications for gene: IARS2 were set to 25130867; 28328135; 39169373
Intellectual disability v8.170 IARS2 Achchuthan Shanmugasundram Phenotypes for gene: IARS2 were changed from Cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia, 616007 to Cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia, OMIM:616007
Intellectual disability v8.170 IARS2 Achchuthan Shanmugasundram Publications for gene: IARS2 were set to 25130867; 28328135
Intellectual disability v8.169 IARS2 Achchuthan Shanmugasundram reviewed gene: IARS2: Rating: RED; Mode of pathogenicity: None; Publications: 39169373; Phenotypes: Cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia, OMIM:616007; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v8.169 NHLRC2 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: NHLRC2.
Intellectual disability v8.169 DAP3 Achchuthan Shanmugasundram Classified gene: DAP3 as Red List (low evidence)
Intellectual disability v8.169 DAP3 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene is currently rated red as there is only case identified with severe ID, while two other cases had only mild ID.
Intellectual disability v8.169 DAP3 Achchuthan Shanmugasundram Gene: dap3 has been classified as Red List (Low Evidence).
Intellectual disability v8.168 DAP3 Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:39701103 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.168 DAP3 Achchuthan Shanmugasundram Publications for gene: DAP3 were set to 39701103
Intellectual disability v8.167 DAP3 Achchuthan Shanmugasundram gene: DAP3 was added
gene: DAP3 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: DAP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DAP3 were set to 39701103
Phenotypes for gene: DAP3 were set to Perrault syndrome 7, OMIM:621101
Review for gene: DAP3 was set to RED
Added comment: PMID:39701103 reported the identification of biallelic variants in DAP3 gene in five unrelated individuals presenting with variable clinical presentations ranging from Perrault syndrome (sensorineural hearing loss and ovarian insufficiency) to an early childhood neurometabolic phenotype. All five individuals had bilateral sensorineural hearing loss and the severity was profound in three of them, while not reported in the other two. Severe intellectual disability was reported in one individual and mild ID was reported in two individuals. There is also functional evidence available.

This gene has been associated with relevant phenotypes in OMIM (MIM #621101).
Sources: Literature
Deafness and congenital structural abnormalities v1.30 DAP3 Achchuthan Shanmugasundram Classified gene: DAP3 as Green List (high evidence)
Deafness and congenital structural abnormalities v1.30 DAP3 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (five unrelated cases and functional work) for the promotion of this gene to green rating on this panel.
Deafness and congenital structural abnormalities v1.30 DAP3 Achchuthan Shanmugasundram Gene: dap3 has been classified as Green List (High Evidence).
Deafness and congenital structural abnormalities v1.29 DAP3 Achchuthan Shanmugasundram Publications for gene: DAP3 were set to PMID:39701103
Deafness and congenital structural abnormalities v1.28 DAP3 Achchuthan Shanmugasundram Phenotypes for gene: DAP3 were changed from Sensorineural hearing loss; primary ovarian insufficiency; lactic acidosis; intellectual disability to Perrault syndrome 7, OMIM:621101
Deafness and congenital structural abnormalities v1.27 DAP3 Achchuthan Shanmugasundram reviewed gene: DAP3: Rating: GREEN; Mode of pathogenicity: None; Publications: 39701103; Phenotypes: Perrault syndrome 7, OMIM:621101; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v4.82 DAP3 Achchuthan Shanmugasundram Classified gene: DAP3 as Amber List (moderate evidence)
Monogenic hearing loss v4.82 DAP3 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (five unrelated cases and functional work) for the association of this gene to hearing loss. Hence, this gene can be promoted to green rating in the next GMS update.
Monogenic hearing loss v4.82 DAP3 Achchuthan Shanmugasundram Gene: dap3 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v4.81 DAP3 Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:39701103 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Monogenic hearing loss v4.81 DAP3 Achchuthan Shanmugasundram Publications for gene: DAP3 were set to 39701103
Monogenic hearing loss v4.80 DAP3 Achchuthan Shanmugasundram Tag Q1_25_ promote_green tag was added to gene: DAP3.
Monogenic hearing loss v4.80 DAP3 Achchuthan Shanmugasundram changed review comment from: PMID:39701103 reported the identification of biallelic variants in DAP3 gene in five unrelated individuals presenting with variable clinical presentations ranging from Perrault syndrome (sensorineural hearing loss and ovarian insufficiency) to an early childhood neurometabolic phenotype. All five individuals had bilateral sensorineural hearing loss and the severity was profound in three of them, while not reported in the other two. Severe intellectual disability was reported in one individual and mild ID was reported in two individuals. There is also functional evidence available for this gene.

This gene has been associated with relevant phenotypes in OMIM (MIM #621101).
Sources: Literature; to: PMID:39701103 reported the identification of biallelic variants in DAP3 gene in five unrelated individuals presenting with variable clinical presentations ranging from Perrault syndrome (sensorineural hearing loss and ovarian insufficiency) to an early childhood neurometabolic phenotype. All five individuals had bilateral sensorineural hearing loss and the severity was profound in three of them, while not reported in the other two. Severe intellectual disability was reported in one individual and mild ID was reported in two individuals. There is also functional evidence available.

This gene has been associated with relevant phenotypes in OMIM (MIM #621101).
Sources: Literature
Monogenic hearing loss v4.80 DAP3 Achchuthan Shanmugasundram gene: DAP3 was added
gene: DAP3 was added to Monogenic hearing loss. Sources: Literature
Mode of inheritance for gene: DAP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DAP3 were set to 39701103
Phenotypes for gene: DAP3 were set to Perrault syndrome 7, OMIM:621101
Review for gene: DAP3 was set to GREEN
Added comment: PMID:39701103 reported the identification of biallelic variants in DAP3 gene in five unrelated individuals presenting with variable clinical presentations ranging from Perrault syndrome (sensorineural hearing loss and ovarian insufficiency) to an early childhood neurometabolic phenotype. All five individuals had bilateral sensorineural hearing loss and the severity was profound in three of them, while not reported in the other two. Severe intellectual disability was reported in one individual and mild ID was reported in two individuals. There is also functional evidence available for this gene.

This gene has been associated with relevant phenotypes in OMIM (MIM #621101).
Sources: Literature
Intellectual disability v8.166 NHLRC2 Achchuthan Shanmugasundram Classified gene: NHLRC2 as Amber List (moderate evidence)
Intellectual disability v8.166 NHLRC2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (>15 unrelated cases with moderate/ severe GDD/ ID) for the promotion of this gene to green rating in the next GMS update.
Intellectual disability v8.166 NHLRC2 Achchuthan Shanmugasundram Gene: nhlrc2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.165 NHLRC2 Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:39328589 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.165 NHLRC2 Achchuthan Shanmugasundram Publications for gene: NHLRC2 were set to 37188825; 39328589
Intellectual disability v8.164 NHLRC2 Achchuthan Shanmugasundram Tag Q1_25_ promote_green tag was added to gene: NHLRC2.
Intellectual disability v8.164 NHLRC2 Achchuthan Shanmugasundram gene: NHLRC2 was added
gene: NHLRC2 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: NHLRC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NHLRC2 were set to 37188825; 39328589
Phenotypes for gene: NHLRC2 were set to FINCA syndrome, OMIM:618278
Review for gene: NHLRC2 was set to GREEN
Added comment: PMID:37188825 reported 15 patients ranging in age from 22 months to 19 years, from 12 unrelated families with an overlapping phenotype with FINCA syndrome (MIM #618278). They were identified with nine novel NHLRC2 variants via exome sequencing. All these patients presented with moderate to severe global developmental delay and variable disease progression. Seizures, truncal hypotonia and movement disorders were also frequently observed.

PMID:39328589 reported two siblings of Chinese decent with FINCA syndrome and they were identified with the same compound heterozygous variants in NHLRC2 gene. Both of them presented with developmental delay, of which the younger brother was evaluated with a development quotient (DQ) of 39 at four months of age (normal range >85), indicating moderate intellectual disability.

This gene has also been associated with relevant phenotype on the DD panel of Gene2Phenotype, with a definitive rating.
Sources: Literature
Intellectual disability v8.163 DDX39B Mike Spiller gene: DDX39B was added
gene: DDX39B was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: DDX39B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DDX39B were set to PMID: 39918047
Review for gene: DDX39B was set to GREEN
Added comment: PMID: 39918047 - report 4 de novo missense variants in individuals with phenotypes of ID ranging from mild to severe (2 severe, 1 mild, 1 severity not stated but phenotype of GDD).
Hypotonia, short stature and skeletal abnormalities are also observed frequently.
Variants absent from gnomad, affect highly conserved amino acids in constrained regions of DEAD/DEAH box helicase domain.

Splice variant causing inframe deletion also identified in fifth family (proband and mother), but significance of this unclear as neither has ID.

Supported by functional studies:
Transcriptome profiling shows significant increase in abberant splicing events, consistent with DDX39B role as splicing factor.
Drosophila experiments - overexpression of WT human gene is lethal, but flies overexpressing variants were healthy, suggesting these variants cause loss of / reduced protein function.

Overall good evidence for DEAD box helicase missenses causing an autosomal dominant syndromic ID disorder.
Sources: Literature
Respiratory ciliopathies including non-CF bronchiectasis v3.25 CFAP54 Steven Cowman reviewed gene: CFAP54: Rating: GREEN; Mode of pathogenicity: None; Publications: 39362668, 37725231; Phenotypes: Primary ciliary dyskinesia, bronchiectasis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v8.163 AFF2_GCC Sarah Leigh STR: AFF2_GCC was added
STR: AFF2_GCC was added to Intellectual disability. Sources: Literature
STR, NGS Not Validated tags were added to STR: AFF2_GCC.
Mode of inheritance for STR: AFF2_GCC was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for STR: AFF2_GCC were set to 8334699; 8023854; 21739600; 9299237; 11171404; 11923441; 19136466; 2356291
Phenotypes for STR: AFF2_GCC were set to Intellectual developmental disorder, X-linked 109, OMIM:309548; FRAXE intellectual disability, MONDO:0010659
Review for STR: AFF2_GCC was set to GREEN
Added comment: AFF2 transcribed from the forwards strand, which means that the repeated sequence is the forward strand sequence.

AFF2_GCC is on https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r3

AFF2_GCC is on https://stripy.org/database

AFF2_GCC is on DRAGON 4.02.

The coordinates and pathogenic ranges of the sequence repeats were obtained from
https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r3 and DRAGON 4.02/

There is enough evidence for this STR to be green on this panel.

This STR has not been approved by NHS STR working group and is not NGS Not Validated
Sources: Literature
DDG2P v5.48 TNFRSF13B Ronnie Wright reviewed gene: TNFRSF13B: Rating: RED; Mode of pathogenicity: Other; Publications: ; Phenotypes: ; Mode of inheritance: Other
Skeletal dysplasia v7.30 XYLT1_GCC Sarah Leigh changed review comment from: XYLT1 transcribed from the reverse strand, which means that the repeated sequence is the reverse compliment of the forward strand sequence.

XYLT1_GCC is on https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r3

XYLT1_GCC is on https://stripy.org/database

XYLT1_GCC is on DRAGON 4.02.

The coordinates and pathogenic ranges of the sequence repeats were obtained from
https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r3 and were the same on https://stripy.org/database/ and DRAGON 4.02/

This STR has not been approved by NHS STR working group and is not NGS Not Validated
Sources: Literature; to: XYLT1 transcribed from the reverse strand, which means that the repeated sequence is the reverse compliment of the forward strand sequence.

XYLT1_GCC is on https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r3

XYLT1_GCC is on https://stripy.org/database

XYLT1_GCC is on DRAGON 4.02.

The coordinates and pathogenic ranges of the sequence repeats were obtained from
https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r3 and were the same on https://stripy.org/database/ and DRAGON 4.02/

There is enough evidence for XYLT1_GGC to be green on this panel. At least ten patients from at least eight families have either homozygous or compound heterozygous (with other XYLT1 variants) XYLT1_GGC expansions (PMID: 22711505;30554721).

This STR has not been approved by NHS STR working group and is not NGS Not Validated
Sources: Literature
Skeletal dysplasia v7.30 XYLT1_GCC Sarah Leigh STR: XYLT1_GCC was added
STR: XYLT1_GCC was added to Skeletal dysplasia. Sources: Literature
STR, NGS Not Validated tags were added to STR: XYLT1_GCC.
Mode of inheritance for STR: XYLT1_GCC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for STR: XYLT1_GCC were set to 22711505; 30554721
Phenotypes for STR: XYLT1_GCC were set to Desbuquois dysplasia 2, OMIM:615777; Desbuquois dysplasia 2, MONDO:0014343
Review for STR: XYLT1_GCC was set to GREEN
Added comment: XYLT1 transcribed from the reverse strand, which means that the repeated sequence is the reverse compliment of the forward strand sequence.

XYLT1_GCC is on https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r3

XYLT1_GCC is on https://stripy.org/database

XYLT1_GCC is on DRAGON 4.02.

The coordinates and pathogenic ranges of the sequence repeats were obtained from
https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r3 and were the same on https://stripy.org/database/ and DRAGON 4.02/

This STR has not been approved by NHS STR working group and is not NGS Not Validated
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v7.23 THAP11_CAG Sarah Leigh commented on STR: THAP11_CAG: PMID: 37148549 - 2 Chinese cases but one case had unaffected father with same number of repeats, PMID: 38113319 - 1 European case but inconclusive due to additional STR.

Also PMID: 38757579 and PMID: 39441143 report no cases with this repeat.
Intellectual disability v8.162 THAP11_CAG Sarah Leigh commented on STR: THAP11_CAG: PMID: 37148549 - 2 Chinese cases but one case had unaffected father with same number of repeats, PMID: 38113319 - 1 European case but inconclusive due to additional STR.

Also PMID: 38757579 and PMID: 39441143 report no cases with this repeat.
Intellectual disability v8.162 THAP11_CAG Sarah Leigh Classified STR: THAP11_CAG as Red List (low evidence)
Intellectual disability v8.162 THAP11_CAG Sarah Leigh Added comment: Comment on list classification: This STR has not been approved by NHS STR working group and is not NGS Not Validated
Intellectual disability v8.162 THAP11_CAG Sarah Leigh Str: thap11_cag has been classified as Red List (Low Evidence).
Ataxia and cerebellar anomalies - narrow panel v7.23 THAP11_CAG Sarah Leigh Classified STR: THAP11_CAG as Red List (low evidence)
Ataxia and cerebellar anomalies - narrow panel v7.23 THAP11_CAG Sarah Leigh Added comment: Comment on list classification: This STR has not been approved by NHS STR working group and is not NGS Not Validated
Ataxia and cerebellar anomalies - narrow panel v7.23 THAP11_CAG Sarah Leigh Str: thap11_cag has been classified as Red List (Low Evidence).
Intellectual disability v8.161 THAP11_CAG Sarah Leigh STR: THAP11_CAG was added
STR: THAP11_CAG was added to Intellectual disability. Sources: Literature
STR, NGS Not Validated tags were added to STR: THAP11_CAG.
Mode of inheritance for STR: THAP11_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for STR: THAP11_CAG were set to 37148549; 38757579; 39441143
Phenotypes for STR: THAP11_CAG were set to Spinocerebellar ataxia 51, OMIM:620947
Review for STR: THAP11_CAG was set to RED
Added comment: THAP11 transcribed from the forward strand.
THAP11_CAG is not on https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r3
THAP11_CAG is not is not DRAGON 4.02 or other previous versions.
The coordinates and pathogenic ranges of the sequence repeats were obtained from https://stripy.org/database/THAP11

This STR has not been approved by NHS STR working group and is not NGS Not Validated
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v7.22 THAP11_CAG Sarah Leigh STR: THAP11_CAG was added
STR: THAP11_CAG was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
STR, NGS Not Validated tags were added to STR: THAP11_CAG.
Mode of inheritance for STR: THAP11_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for STR: THAP11_CAG were set to 37148549; 38757579; 39441143
Phenotypes for STR: THAP11_CAG were set to Spinocerebellar ataxia 51, OMIM:620947
Review for STR: THAP11_CAG was set to RED
Added comment: THAP11 transcribed from the forward strand.
THAP11_CAG is not on https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r3
THAP11_CAG is not is not DRAGON 4.02 or other previous versions.
The coordinates and pathogenic ranges of the sequence repeats were obtained from https://stripy.org/database/THAP11.

This STR has not been approved by NHS STR working group and is not NGS Not Validated
Sources: Literature
Intellectual disability v8.160 PPP2R2B Sarah Leigh Mode of pathogenicity for gene: PPP2R2B 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
Intellectual disability v8.159 PPP2R2B Sarah Leigh Classified gene: PPP2R2B as Amber List (moderate evidence)
Intellectual disability v8.159 PPP2R2B Sarah Leigh Gene: ppp2r2b has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v7.74 PPP2R2B Sarah Leigh Classified gene: PPP2R2B as Amber List (moderate evidence)
Early onset or syndromic epilepsy v7.74 PPP2R2B Sarah Leigh Gene: ppp2r2b has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v7.73 PPP2R2B Sarah Leigh Added comment: Comment on publications: PMID: 39565297 and 25356899 were identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Early onset or syndromic epilepsy v7.73 PPP2R2B Sarah Leigh Publications for gene: PPP2R2B were set to 39565297; 25356899
Early onset or syndromic epilepsy v7.72 PPP2R2B Sarah Leigh Added comment: Comment on phenotypes: The PPP2R2B_CAG variant is associated with Spinocerebellar ataxia 12, OMIM:604326
Early onset or syndromic epilepsy v7.72 PPP2R2B Sarah Leigh Phenotypes for gene: PPP2R2B were changed from neurodevelopmental syndrome to neurodevelopmental syndrome
Early onset or syndromic epilepsy v7.71 PPP2R2B Sarah Leigh gene: PPP2R2B was added
gene: PPP2R2B was added to Early onset or syndromic epilepsy. Sources: Literature
Q1_25_ promote_green tags were added to gene: PPP2R2B.
Mode of inheritance for gene: PPP2R2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPP2R2B were set to 39565297; 25356899
Phenotypes for gene: PPP2R2B were set to neurodevelopmental syndrome
Review for gene: PPP2R2B was set to GREEN
Added comment: Sources: Literature
Intellectual disability v8.158 PPP2R2B Sarah Leigh Added comment: Comment on phenotypes: The PPP2R2B_CAG variant is associated with Spinocerebellar ataxia 12, OMIM:604326
Intellectual disability v8.158 PPP2R2B Sarah Leigh Phenotypes for gene: PPP2R2B were changed from Spinocerebellar ataxia 12, OMIM:604326 to neurodevelopmental syndrome
Intellectual disability v8.157 PPP2R2B Sarah Leigh Added comment: Comment on publications: PMID: 39565297 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.157 PPP2R2B Sarah Leigh Publications for gene: PPP2R2B were set to 25356899
Intellectual disability v8.156 PPP2R2B Sarah Leigh edited their review of gene: PPP2R2B: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v8.156 PPP2R2B Sarah Leigh Tag nucleotide-repeat-expansion was removed from gene: PPP2R2B.
Tag currently-ngs-unreportable was removed from gene: PPP2R2B.
Tag Q1_25_ promote_green tag was added to gene: PPP2R2B.
Intellectual disability v8.156 PPP2R2B Sarah Leigh reviewed gene: PPP2R2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 39565297, 25356899; Phenotypes: neurodevelopmental syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v8.156 PPP2R2B_CAG Sarah Leigh reviewed STR: PPP2R2B_CAG: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Respiratory ciliopathies including non-CF bronchiectasis v3.25 CFAP46 Steven Cowman reviewed gene: CFAP46: Rating: AMBER; Mode of pathogenicity: None; Publications: 39362668; Phenotypes: Primary ciliary dyskinesia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Respiratory ciliopathies including non-CF bronchiectasis v3.25 CFAP221 Steven Cowman reviewed gene: CFAP221: Rating: AMBER; Mode of pathogenicity: None; Publications: 31636325, 39362668; Phenotypes: Primary ciliary dyskinesia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital hypothyroidism v2.23 STRTS Sarah Leigh changed review comment from: This is an intergenic STR. The STR can be seen using the coordinates 15:88569434-88569449 http://may2024.archive.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000144218;r=15:88569412-88569475; to: This is an intergenic STR. The STR can be seen using the coordinates 15:88569434-88569449 http://may2024.archive.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000144218;r=15:88569412-88569475

The pathogenic variant of this STR is NOT an expansion, it is a reduction: normal is 4 repeats and disease is 3 repeats or a base change in one of the 4 repeats.
Adult onset leukodystrophy v5.4 CST3 David Lynch reviewed gene: CST3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38489591, PMID: 38729262; Phenotypes: leukodystrophy without amyloid angiopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v7.70 RYR3 Sarah Leigh Added comment: Comment on publications: PMID: 39220738 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Early onset or syndromic epilepsy v7.70 RYR3 Sarah Leigh Publications for gene: RYR3 were set to 25262651; 29667327; 29498452; 31230720; 39220738; 39840699
Early onset or syndromic epilepsy v7.69 RYR3 Sarah Leigh Phenotypes for gene: RYR3 were changed from Epileptic encephalopathy to idiopathic(non-lesional) partial epilepsy/susceptibility of seizures
Early onset or syndromic epilepsy v7.68 RYR3 Sarah Leigh edited their review of gene: RYR3: Changed phenotypes to: idiopathic(non-lesional) partial epilepsy/susceptibility of seizures
Early onset or syndromic epilepsy v7.68 RYR3 Sarah Leigh Classified gene: RYR3 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v7.68 RYR3 Sarah Leigh Gene: ryr3 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v7.67 RYR3 Sarah Leigh Tag Q1_25_ promote_green tag was added to gene: RYR3.
Early onset or syndromic epilepsy v7.67 RYR3 Sarah Leigh edited their review of gene: RYR3: Added comment: Previously there have been four reports of seizures in patients with biallelic RYR3 variants (PMID: 25262651; 29667327; 39220738). Using a cohort of patients with idiopathic(non-lesional) partial epilepsy/susceptibility of seizures, authors of PMID: 39840699 report thirteen RYR3 variants in seven cases. In all but one of the cases, the variants are compound heterozygotes, with the remaining case having a de novo heterozygous RYR3 variant. Seizure onset was in childhood (1 to 7 years), brain MRIs were normal in all cases, there was no evidence of myopathy and there was a single case of intellectual disability (table 1, PMID: 39840699).; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v8.156 HMGXB4 Arina Puzriakova gene: HMGXB4 was added
gene: HMGXB4 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: HMGXB4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HMGXB4 were set to 39166056
Phenotypes for gene: HMGXB4 were set to Intellectual disability, developmental delay, and dysmorphic features
Added comment: PMID: 39166056 (2024) report three affected individuals from a single family with ID/GDD, obesity and dysmorphic facial features. WGS revealed a homozygous frameshift variant (c.1193_1196del; p.(Lys398Argfs*25)) in exon 5 of the HMGXB4 gene which completely segregated with disease. RT-qPCR revealed a substantial decrease in the HMGXB4 gene expression in affected individuals as compared to unaffected individuals of the family.

Rating Red for now as only a single family has been identified to date.
Sources: Literature
Mitochondrial disorder with complex I deficiency v3.11 NDUFB7 Arina Puzriakova Tag watchlist was removed from gene: NDUFB7.
Tag Q1_25_ promote_green tag was added to gene: NDUFB7.
Possible mitochondrial disorder - nuclear genes v3.119 NDUFB7 Arina Puzriakova Classified gene: NDUFB7 as Amber List (moderate evidence)
Possible mitochondrial disorder - nuclear genes v3.119 NDUFB7 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update.

Although only two unrelated cases have been reported to date (PMID: 33502047, 40025060) there is strong functional data and an animal model that support the association. The existence of a therapeutic strategy further supports timely inclusion of this gene on a diagnostic panel.
Possible mitochondrial disorder - nuclear genes v3.119 NDUFB7 Arina Puzriakova Gene: ndufb7 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v7.16 NDUFB7 Arina Puzriakova Tag watchlist was removed from gene: NDUFB7.
Tag Q1_25_ promote_green tag was added to gene: NDUFB7.
Possible mitochondrial disorder - nuclear genes v3.118 NDUFB7 Arina Puzriakova Tag Q1_25_ promote_green tag was added to gene: NDUFB7.
Fetal anomalies v5.84 NDUFB7 Arina Puzriakova Tag Q1_25_ expert_review tag was added to gene: NDUFB7.
Fetal anomalies v5.84 NDUFB7 Arina Puzriakova changed review comment from: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update.

Although only two unrelated cases have been reported to date (PMID: 33502047, 40025060) there is strong functional data and an animal model that support the association. The existence of a therapeutic strategy further supports timely inclusion of this gene on a diagnostic panel.; to: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update but this will be flagged for expert review prior to inclusion.

Although only two unrelated cases have been reported to date (PMID: 33502047, 40025060) there is strong functional data and an animal model that support the association. The existence of a therapeutic strategy further supports timely inclusion of this gene on a diagnostic panel.
Likely inborn error of metabolism v7.16 NDUFB7 Arina Puzriakova Phenotypes for gene: NDUFB7 were changed from ?Mitochondrial complex I deficiency, nuclear type 39, OMIM:620135 to Mitochondrial complex I deficiency, nuclear type 39, OMIM:620135
Mitochondrial disorder with complex I deficiency v3.11 NDUFB7 Arina Puzriakova edited their review of gene: NDUFB7: Changed rating: GREEN; Changed publications to: 40025060; Changed phenotypes to: Mitochondrial complex I deficiency, nuclear type 39, OMIM:620135; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Possible mitochondrial disorder - nuclear genes v3.118 NDUFB7 Arina Puzriakova edited their review of gene: NDUFB7: Changed publications to: 40025060; Changed phenotypes to: Mitochondrial complex I deficiency, nuclear type 39, OMIM:620135; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.84 NDUFB7 Arina Puzriakova edited their review of gene: NDUFB7: Changed publications to: 40025060; Changed phenotypes to: Mitochondrial complex I deficiency, nuclear type 39, OMIM:620135; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorder with complex I deficiency v3.11 NDUFB7 Arina Puzriakova Classified gene: NDUFB7 as Amber List (moderate evidence)
Mitochondrial disorder with complex I deficiency v3.11 NDUFB7 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update.

Although only two unrelated cases have been reported to date (PMID: 33502047, 40025060) there is strong functional data and an animal model that support the association. The existence of a therapeutic strategy further supports timely inclusion of this gene on a diagnostic panel.
Mitochondrial disorder with complex I deficiency v3.11 NDUFB7 Arina Puzriakova Gene: ndufb7 has been classified as Amber List (Moderate Evidence).
Possible mitochondrial disorder - nuclear genes v3.118 NDUFB7 Arina Puzriakova edited their review of gene: NDUFB7: Changed rating: GREEN
Fetal anomalies v5.84 NDUFB7 Arina Puzriakova edited their review of gene: NDUFB7: Changed rating: GREEN
Possible mitochondrial disorder - nuclear genes v3.118 NDUFB7 Arina Puzriakova Classified gene: NDUFB7 as Amber List (moderate evidence)
Possible mitochondrial disorder - nuclear genes v3.118 NDUFB7 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update.

Although only two unrelated cases have been reported to date (PMID: 33502047, 40025060) there is strong functional data and an animal model that support the association. The existence of a therapeutic strategy further supports timely inclusion of this gene on a diagnostic panel.
Possible mitochondrial disorder - nuclear genes v3.118 NDUFB7 Arina Puzriakova Gene: ndufb7 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v5.84 NDUFB7 Arina Puzriakova Classified gene: NDUFB7 as Amber List (moderate evidence)
Fetal anomalies v5.84 NDUFB7 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update.

Although only two unrelated cases have been reported to date (PMID: 33502047, 40025060) there is strong functional data and an animal model that support the association. The existence of a therapeutic strategy further supports timely inclusion of this gene on a diagnostic panel.
Fetal anomalies v5.84 NDUFB7 Arina Puzriakova Gene: ndufb7 has been classified as Amber List (Moderate Evidence).
Mitochondrial disorder with complex I deficiency v3.10 NDUFB7 Arina Puzriakova commented on gene: NDUFB7: PMID: 40025060 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Likely inborn error of metabolism v7.15 NDUFB7 Arina Puzriakova commented on gene: NDUFB7: PMID: 40025060 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Possible mitochondrial disorder - nuclear genes v3.117 NDUFB7 Arina Puzriakova commented on gene: NDUFB7: PMID: 40025060 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Mitochondrial disorder with complex I deficiency v3.10 NDUFB7 Arina Puzriakova commented on gene: NDUFB7
Likely inborn error of metabolism v7.15 NDUFB7 Arina Puzriakova commented on gene: NDUFB7
Possible mitochondrial disorder - nuclear genes v3.117 NDUFB7 Arina Puzriakova commented on gene: NDUFB7
Fetal anomalies v5.83 NDUFB7 Arina Puzriakova commented on gene: NDUFB7
Fetal anomalies v5.83 NDUFB7 Arina Puzriakova Tag Q1_25_ promote_green tag was added to gene: NDUFB7.
Early onset or syndromic epilepsy v7.67 RYR3 Sarah Leigh Publications for gene: RYR3 were set to 25262651; 29667327; 39220738; 39840699
Mitochondrial disorder with complex I deficiency v3.10 NDUFB7 Arina Puzriakova Phenotypes for gene: NDUFB7 were changed from ?Mitochondrial complex I deficiency, nuclear type 39, OMIM:620135 to Mitochondrial complex I deficiency, nuclear type 39, OMIM:620135
Likely inborn error of metabolism v7.15 NDUFB7 Arina Puzriakova Publications for gene: NDUFB7 were set to 33502047; 27626371
Possible mitochondrial disorder - nuclear genes v3.117 NDUFB7 Arina Puzriakova Phenotypes for gene: NDUFB7 were changed from ?Mitochondrial complex I deficiency, nuclear type 39, OMIM:620135 to Mitochondrial complex I deficiency, nuclear type 39, OMIM:620135
Fetal anomalies v5.83 NDUFB7 Arina Puzriakova Phenotypes for gene: NDUFB7 were changed from ?Mitochondrial complex I deficiency, nuclear type 39, OMIM:620135 to Mitochondrial complex I deficiency, nuclear type 39, OMIM:620135
Mitochondrial disorder with complex I deficiency v3.9 NDUFB7 Arina Puzriakova Publications for gene: NDUFB7 were set to 33502047; 27626371
Possible mitochondrial disorder - nuclear genes v3.116 NDUFB7 Arina Puzriakova Publications for gene: NDUFB7 were set to
Fetal anomalies v5.82 NDUFB7 Arina Puzriakova Publications for gene: NDUFB7 were set to 33502047
Mitochondrial disorders v8.14 NDUFB7 Arina Puzriakova Classified gene: NDUFB7 as Amber List (moderate evidence)
Mitochondrial disorders v8.14 NDUFB7 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update.

Although only two unrelated cases have been reported to date (PMID: 33502047, 40025060), there is strong functional data and animal model to support the association. The existence of a therapeutic strategy further supports timely inclusion of this gene on a diagnostic panel.
Mitochondrial disorders v8.14 NDUFB7 Arina Puzriakova Gene: ndufb7 has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v8.13 NDUFB7 Arina Puzriakova Phenotypes for gene: NDUFB7 were changed from ?Mitochondrial complex I deficiency, nuclear type 39, OMIM:620135 to Mitochondrial complex I deficiency, nuclear type 39, OMIM:620135
Mitochondrial disorders v8.12 NDUFB7 Arina Puzriakova Publications for gene: NDUFB7 were set to 33502047; 27626371
Mitochondrial disorders v8.11 NDUFB7 Arina Puzriakova Tag watchlist was removed from gene: NDUFB7.
Tag Q1_25_ promote_green tag was added to gene: NDUFB7.
Mitochondrial disorders v8.11 NDUFB7 Arina Puzriakova commented on gene: NDUFB7: PMID: 40025060 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Early onset or syndromic epilepsy v7.66 RYR3 Sarah Leigh Publications for gene: RYR3 were set to 25262651; 29667327
Mitochondrial disorders v8.11 NDUFB7 Arina Puzriakova reviewed gene: NDUFB7: Rating: GREEN; Mode of pathogenicity: None; Publications: 40025060; Phenotypes: Mitochondrial complex I deficiency, nuclear type 39, OMIM:620135; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v7.8 AP5B1 Siying Lin gene: AP5B1 was added
gene: AP5B1 was added to Retinal disorders. Sources: Literature
Mode of inheritance for gene: AP5B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP5B1 were set to PMID 40081374
Phenotypes for gene: AP5B1 were set to Macular dystrophy
Mode of pathogenicity for gene: AP5B1 was set to Other
Review for gene: AP5B1 was set to GREEN
Added comment: 2 individuals from 2 families with biallelic loss of function variants and macular dystrophy
Sources: Literature
Retinal disorders v7.8 AP5Z1 Siying Lin gene: AP5Z1 was added
gene: AP5Z1 was added to Retinal disorders. Sources: Literature
Mode of inheritance for gene: AP5Z1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP5Z1 were set to PMID: 40081374
Phenotypes for gene: AP5Z1 were set to Macular dystrophy
Mode of pathogenicity for gene: AP5Z1 was set to Other
Review for gene: AP5Z1 was set to GREEN
Added comment: 14 families affected with macular dystrophy with biallelic AP5Z1 variants (mostly loss of function variants)
Sources: Literature
Intellectual disability v8.155 NAV3 Sarah Leigh Added comment: Comment on publications: PMID: 39708122 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.155 NAV3 Sarah Leigh Publications for gene: NAV3 were set to 38977784; 39038237; 39708122
Intellectual disability v8.154 NAV3 Sarah Leigh Classified gene: NAV3 as Amber List (moderate evidence)
Intellectual disability v8.154 NAV3 Sarah Leigh Gene: nav3 has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.153 NAV3 Sarah Leigh gene: NAV3 was added
gene: NAV3 was added to Intellectual disability. Sources: Literature
Q1_25_ promote_green, Q1_25_ expert_review tags were added to gene: NAV3.
Mode of inheritance for gene: NAV3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: NAV3 were set to 38977784; 39038237; 39708122
Phenotypes for gene: NAV3 were set to recessive neurodevelopmental disorder
Review for gene: NAV3 was set to GREEN
Added comment: At least 11 NAV3 variants have been reported in 11 unrelated families with a neurodevelopmental disorder, with dysmorphism and other features (PMIDs: 38977784;39038237;39708122). The NAV3 variants were homozygous in the affected members of eight of these families, de novo heterozygous NAV3 variants were found in two families (PED4263 & MI01 in PMID: 38977784) and in one case the heterozygous NAV3 variant was inherited from the mother (FM1 in PMID: 38977784). A nav3 knock-zebrafish model resulted in severe morphological defects, microcephaly, impaired neuronal growth, and behavioral impairment, this phenotype was rescued with co-injection of WT NAV3 mRNA, but not pathogenic variant NAV3 mRNA (PMID: 38977784). Varying degrees of intellectual disability was evident in the patients carrying NAV3 variants (severe 2/11, moderate 2/11, mild 7/11)(PMIDs: 38977784;39038237;39708122).
Sources: Literature
Intellectual disability v8.152 TUBGCP2 Arina Puzriakova Tag watchlist was removed from gene: TUBGCP2.
Tag Q1_25_ promote_green tag was added to gene: TUBGCP2.
Intellectual disability v8.152 TUBGCP2 Arina Puzriakova edited their review of gene: TUBGCP2: Added comment: PMID: 40017707 (2025) - reports a 6-year-old girl with lissencephaly caused by compound heterozygous variants in TUBGCP2 (two paternal missense variants: c.178 C>T, c.538T>C and one maternal exon variant: 2–14 deletion). The patient presented with microcephaly, developmental delay, intellectual disability, and seizures. A literature review of 8 patients (including the reported case) with TUBGCP2 variants showed that all exhibited lissencephaly, microcephaly and developmental delay, with most having intellectual disability, seizures, and dysmorphic facial features.

This publication supports inclusion of the TUBGCP2 gene on the intellectual disability panel at the next GMS panel update.; Changed rating: GREEN
Intellectual disability v8.152 TUBGCP2 Arina Puzriakova Added comment: Comment on publications: PMID: 40017707 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.152 TUBGCP2 Arina Puzriakova Publications for gene: TUBGCP2 were set to 31630790
Severe microcephaly v7.19 GTF3C3 Arina Puzriakova Entity copied from Intellectual disability v8.151
Severe microcephaly v7.19 GTF3C3 Arina Puzriakova gene: GTF3C3 was added
gene: GTF3C3 was added to Severe microcephaly. Sources: Expert Review Amber,Victorian Clinical Genetics Services,Literature
Q1_25_ promote_green tags were added to gene: GTF3C3.
Mode of inheritance for gene: GTF3C3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTF3C3 were set to 28940097; 28097321; 30552426; 40040844
Phenotypes for gene: GTF3C3 were set to Global developmental delay; Intellectual disability; Seizures
Early onset or syndromic epilepsy v7.65 GTF3C3 Arina Puzriakova Entity copied from Intellectual disability v8.151
Early onset or syndromic epilepsy v7.65 GTF3C3 Arina Puzriakova gene: GTF3C3 was added
gene: GTF3C3 was added to Early onset or syndromic epilepsy. Sources: Expert Review Amber,Victorian Clinical Genetics Services,Literature
Q1_25_ promote_green tags were added to gene: GTF3C3.
Mode of inheritance for gene: GTF3C3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTF3C3 were set to 28940097; 28097321; 30552426; 40040844
Phenotypes for gene: GTF3C3 were set to Global developmental delay; Intellectual disability; Seizures
Intellectual disability v8.151 GTF3C3 Arina Puzriakova Classified gene: GTF3C3 as Amber List (moderate evidence)
Intellectual disability v8.151 GTF3C3 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update.
Intellectual disability v8.151 GTF3C3 Arina Puzriakova Gene: gtf3c3 has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.150 GTF3C3 Arina Puzriakova Tag watchlist was removed from gene: GTF3C3.
Tag Q1_25_ promote_green tag was added to gene: GTF3C3.
Intellectual disability v8.150 GTF3C3 Arina Puzriakova edited their review of gene: GTF3C3: Added comment: - PMID: 39636576 (2025) - 12 individuals from 7 unrelated families were identified with homozygous or compound heterozygous missense variants in GTF3C3 (8 unpublished individuals combined with newly ascertained information from 4 published individuals). The cohort presented with intellectual disability, variable nonfamilial facial features, motor impairments, seizures, and cerebellar/corpus callosum malformations.

- PMID: 40040844 (2025) - 4 patients from 3 unrelated families with biallelic variants in this gene and microcephaly, developmental delay, intellectual disability, seizures and distinctive dysmorphic facies. Knockout zebrafish recapitulated the key clinical symptoms including microcephaly, brain anomalies and seizure susceptibility.; Changed rating: GREEN; Changed publications to: 39636576, 40040844; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v8.150 GTF3C3 Arina Puzriakova Added comment: Comment on publications: PMID: 40040844 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.150 GTF3C3 Arina Puzriakova Publications for gene: GTF3C3 were set to 28940097, 28097321; 30552426
Intellectual disability v8.149 C12orf66 Arina Puzriakova Classified gene: C12orf66 as Amber List (moderate evidence)
Intellectual disability v8.149 C12orf66 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green the next GMS panel update.
Intellectual disability v8.149 C12orf66 Arina Puzriakova Gene: c12orf66 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v7.64 C12orf66 Arina Puzriakova Classified gene: C12orf66 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v7.64 C12orf66 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green the next GMS panel update.
Early onset or syndromic epilepsy v7.64 C12orf66 Arina Puzriakova Gene: c12orf66 has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.148 C12orf66 Arina Puzriakova commented on gene: C12orf66: Added new-gene-name tag, new approved HGNC gene symbol for C12orf66 is KICS2
Early onset or syndromic epilepsy v7.63 C12orf66 Arina Puzriakova commented on gene: C12orf66: Added new-gene-name tag, new approved HGNC gene symbol for C12orf66 is KICS2
Intellectual disability v8.148 C12orf66 Arina Puzriakova commented on gene: C12orf66: PMID: 39824192 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Early onset or syndromic epilepsy v7.63 C12orf66 Arina Puzriakova commented on gene: C12orf66: PMID: 39824192 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.148 C12orf66 Arina Puzriakova Deleted their comment
Intellectual disability v8.148 C12orf66 Arina Puzriakova Classified gene: C12orf66 as Amber List (moderate evidence)
Intellectual disability v8.148 C12orf66 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update.
Intellectual disability v8.148 C12orf66 Arina Puzriakova Gene: c12orf66 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v7.63 C12orf66 Arina Puzriakova gene: C12orf66 was added
gene: C12orf66 was added to Early onset or syndromic epilepsy. Sources: Literature
new-gene-name, Q1_25_ promote_green tags were added to gene: C12orf66.
Mode of inheritance for gene: C12orf66 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C12orf66 were set to 39824192
Phenotypes for gene: C12orf66 were set to Intellectual developmental disorder, autosomal recessive 83, OMIM:621100
Review for gene: C12orf66 was set to GREEN
Added comment: This gene is associated with a relevant phenotype in OMIM (MIM# 621100)

- PMID: 39824192 (2025) - biallelic variants in KICS2 in 11 individuals from 8 families with intellectual disability. All affected individuals had mild to severe intellectual disability, with 8 individuals also presenting with seizures and 3 (2 families) with hearing impairment. Functional studies in cell culture and zebrafish models provided evidence of pathogenicity, showing impaired mTORC1 regulation and effects on ciliogenesis.
Sources: Literature
Intellectual disability v8.147 C12orf66 Arina Puzriakova gene: C12orf66 was added
gene: C12orf66 was added to Intellectual disability. Sources: Literature
new-gene-name, Q1_25_ promote_green tags were added to gene: C12orf66.
Mode of inheritance for gene: C12orf66 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C12orf66 were set to 39824192
Phenotypes for gene: C12orf66 were set to Intellectual developmental disorder, autosomal recessive 83, OMIM:621100
Review for gene: C12orf66 was set to GREEN
Added comment: This gene is associated with a relevant phenotype in OMIM (MIM# 621100)

- PMID: 39824192 (2025) - biallelic variants in KICS2 in 11 individuals from 8 families with intellectual disability. All affected individuals had mild to severe intellectual disability, with 8 individuals also presenting with seizures and 3 (2 families) with hearing impairment. Functional studies in cell culture and zebrafish models provided evidence of pathogenicity, showing impaired mTORC1 regulation and effects on ciliogenesis.
Sources: Literature
Retinal disorders v7.8 UNC119 Ronnie Wright reviewed gene: UNC119: Rating: AMBER; Mode of pathogenicity: Other; Publications: PMID:30910914; Phenotypes: ; Mode of inheritance: Unknown
Skeletal dysplasia v7.29 SLC13A1 Sarah Leigh Added comment: Comment on publications: PMID: 39925707 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Skeletal dysplasia v7.29 SLC13A1 Sarah Leigh Publications for gene: SLC13A1 were set to 39925707
Skeletal dysplasia v7.29 SLC13A1 Sarah Leigh Classified gene: SLC13A1 as Amber List (moderate evidence)
Skeletal dysplasia v7.29 SLC13A1 Sarah Leigh Gene: slc13a1 has been classified as Amber List (Moderate Evidence).
Monogenic short stature v1.8 SLC13A1 Sarah Leigh Added comment: Comment on publications: PMID: 39925707 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Monogenic short stature v1.8 SLC13A1 Sarah Leigh Publications for gene: SLC13A1 were set to 39925707
Monogenic short stature v1.7 SLC13A1 Sarah Leigh Classified gene: SLC13A1 as Amber List (moderate evidence)
Monogenic short stature v1.7 SLC13A1 Sarah Leigh Gene: slc13a1 has been classified as Amber List (Moderate Evidence).
Monogenic short stature v1.6 SLC13A1 Sarah Leigh gene: SLC13A1 was added
gene: SLC13A1 was added to Monogenic short stature. Sources: Literature
Q1_25_ promote_green tags were added to gene: SLC13A1.
Mode of inheritance for gene: SLC13A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC13A1 were set to 39925707
Phenotypes for gene: SLC13A1 were set to impaired sulfate transport and skeletal dysplasia
Review for gene: SLC13A1 was set to GREEN
Added comment: PMID: 39925707 reports five biallelic SLC13A1 variants in five children with skeletal phenotypes from four unrelated families. Inheritance of the variants from the parents has been established in all cases. Functional studies suggested that the SLC13A1 variants resulted in complete loss of sulfate transport activity, evidence of this was seen when two of the probands were tested and found to have reduction in plasma sulfate level and/or increase in urinary sulfate excretion (PMID: 39925707).
Sources: Literature
Skeletal dysplasia v7.28 SLC13A1 Sarah Leigh gene: SLC13A1 was added
gene: SLC13A1 was added to Skeletal dysplasia. Sources: Literature
Q1_25_ promote_green tags were added to gene: SLC13A1.
Mode of inheritance for gene: SLC13A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC13A1 were set to 39925707
Phenotypes for gene: SLC13A1 were set to impaired sulfate transport and skeletal dysplasia
Review for gene: SLC13A1 was set to GREEN
Added comment: PMID: 39925707 reports five biallelic SLC13A1 variants in five children with skeletal phenotypes from four unrelated families. Inheritance of the variants from the parents has been established in all cases. Functional studies suggested that the SLC13A1 variants resulted in complete loss of sulfate transport activity, evidence of this was seen when two of the probands were tested and found to have reduction in plasma sulfate level and/or increase in urinary sulfate excretion (PMID: 39925707).
Sources: Literature
Hereditary neuropathy or pain disorder v6.164 NOTCH2NL Arina Puzriakova commented on gene: NOTCH2NL
Hereditary neuropathy or pain disorder v6.164 NOTCH2NL Arina Puzriakova Tag new-gene-name tag was added to gene: NOTCH2NL.
Early onset or syndromic epilepsy v7.62 SPOUT1 Sarah Leigh Classified gene: SPOUT1 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v7.62 SPOUT1 Sarah Leigh Gene: spout1 has been classified as Amber List (Moderate Evidence).
Monogenic short stature v1.5 SPOUT1 Sarah Leigh Classified gene: SPOUT1 as Amber List (moderate evidence)
Monogenic short stature v1.5 SPOUT1 Sarah Leigh Gene: spout1 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v7.62 SPOUT1 Sarah Leigh Added comment: Comment on publications: PMID: 39962046 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Early onset or syndromic epilepsy v7.62 SPOUT1 Sarah Leigh Publications for gene: SPOUT1 were set to 39962046
Intellectual disability v8.146 SPOUT1 Sarah Leigh Added comment: Comment on publications: PMID: 39962046 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.146 SPOUT1 Sarah Leigh Publications for gene: SPOUT1 were set to 39962046
Monogenic short stature v1.4 SPOUT1 Sarah Leigh Added comment: Comment on publications: PMID: 39962046 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Monogenic short stature v1.4 SPOUT1 Sarah Leigh Publications for gene: SPOUT1 were set to 39962046
Intellectual disability v8.145 SPOUT1 Sarah Leigh Classified gene: SPOUT1 as Amber List (moderate evidence)
Intellectual disability v8.145 SPOUT1 Sarah Leigh Gene: spout1 has been classified as Amber List (Moderate Evidence).
Monogenic short stature v1.3 SPOUT1 Sarah Leigh gene: SPOUT1 was added
gene: SPOUT1 was added to Monogenic short stature. Sources: Literature
Q1_25_ promote_green tags were added to gene: SPOUT1.
Mode of inheritance for gene: SPOUT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPOUT1 were set to 39962046
Phenotypes for gene: SPOUT1 were set to SPOUT1 Associated Development delay Microcephaly Seizures Short stature
Review for gene: SPOUT1 was set to GREEN
Added comment: PMID: 39962046 reports the association of biallelic SPOUT1 variants with SPOUT1 Associated Development delay Microcephaly Seizures Short stature. In this study, a total of 18 SPOUT1 variants were found in 28 individuals from 21 unrelated families. Intellectual disability was evident in 10/10 families where it could be ascertained, seizures were reported in 16/21 of the families and short stature was seen in 13/15 families where it could be measured.
SPOUT1 variant zebra fish models showed reduction in larval head size with concomitant apoptosis and the human SPOUT1 missense variants were pathogenic in complementation assays in zebrafish (PMID: 39962046).
Sources: Literature
Early onset or syndromic epilepsy v7.61 SPOUT1 Sarah Leigh gene: SPOUT1 was added
gene: SPOUT1 was added to Early onset or syndromic epilepsy. Sources: Literature
Q1_25_ promote_green tags were added to gene: SPOUT1.
Mode of inheritance for gene: SPOUT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPOUT1 were set to 39962046
Phenotypes for gene: SPOUT1 were set to SPOUT1 Associated Development delay Microcephaly Seizures Short stature
Review for gene: SPOUT1 was set to GREEN
Added comment: PMID: 39962046 reports the association of biallelic SPOUT1 variants with SPOUT1 Associated Development delay Microcephaly Seizures Short stature. In this study, a total of 18 SPOUT1 variants were found in 28 individuals from 21 unrelated families. Intellectual disability was evident in 10/10 families where it could be ascertained, seizures were reported in 16/21 of the families and short stature was seen in 13/15 families where it could be measured.
SPOUT1 variant zebra fish models showed reduction in larval head size with concomitant apoptosis and the human SPOUT1 missense variants were pathogenic in complementation assays in zebrafish (PMID: 39962046).
Sources: Literature
Intellectual disability v8.144 SPOUT1 Sarah Leigh gene: SPOUT1 was added
gene: SPOUT1 was added to Intellectual disability. Sources: Literature
Q1_25_ promote_green tags were added to gene: SPOUT1.
Mode of inheritance for gene: SPOUT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPOUT1 were set to 39962046
Phenotypes for gene: SPOUT1 were set to SPOUT1 Associated Development delay Microcephaly Seizures Short stature
Review for gene: SPOUT1 was set to GREEN
Added comment: PMID: 39962046 reports the association of biallelic SPOUT1 variants with SPOUT1 Associated Development delay Microcephaly Seizures Short stature. In this study, a total of 18 SPOUT1 variants were found in 28 individuals from 21 unrelated families. Intellectual disability was evident in 10/10 families where it could be ascertained, seizures were reported in 16/21 of the families and short stature was seen in 13/15 families where it could be measured.
SPOUT1 variant zebra fish models showed reduction in larval head size with concomitant apoptosis and the human SPOUT1 missense variants were pathogenic in complementation assays in zebrafish (PMID: 39962046).
Sources: Literature
Differences in sex development v4.12 DMRT1 Sarah Leigh Publications for gene: DMRT1 were set to 11870074; 26139570; 24934491; 39936125
Differences in sex development v4.11 DMRT1 Sarah Leigh edited their review of gene: DMRT1: Added comment: Variants affecting DMRT1 have been reported in cases with 46,XY disorders/differences of sex development. PMID: 24934491 reports NM_021951.3(DMRT1):c.671A>G (p.Asn224Ser) in 2 unrelated azoospermic men with complete bilateral Sertoli cell-only syndrome and decreased testicular volume by ultrasound. PMID: 26139570 reports NM_021951.2 c.-223_-219CGAAA>T in the promoter of DMRT1, which is a region shown to be involved in the repression of Dmrt1 expression in rat and mouse Sertoli cells (PMID:11870074). Therefore this promoter variants could result in disruption of DMRT1 regulation. PMID: 39936125 reports four different deletions, which all encompass the DMRT1 region (9p24.3p23 - 9p24) in four unrelated cases with gonadal dysgenesis and .; Changed rating: AMBER
Differences in sex development v4.11 DMRT1 Sarah Leigh Added comment: Comment on publications: PMID: 39936125 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Differences in sex development v4.11 DMRT1 Sarah Leigh Publications for gene: DMRT1 were set to 26139570; 24934491; 39936125
Differences in sex development v4.10 DMRT1 Sarah Leigh Classified gene: DMRT1 as Amber List (moderate evidence)
Differences in sex development v4.10 DMRT1 Sarah Leigh Gene: dmrt1 has been classified as Amber List (Moderate Evidence).
Differences in sex development v4.9 DMRT1 Sarah Leigh Phenotypes for gene: DMRT1 were changed from Gender Assignment Gene Panel (UKGTN) to 46,XY disorders/differences of sex development
Differences in sex development v4.8 DMRT1 Sarah Leigh Publications for gene: DMRT1 were set to 26139570
Differences in sex development v4.7 DMRT1 Sarah Leigh Mode of inheritance for gene: DMRT1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Monogenic short stature v1.2 RSPRY1 Arina Puzriakova Entity copied from Intellectual disability v8.143
Monogenic short stature v1.2 RSPRY1 Arina Puzriakova gene: RSPRY1 was added
gene: RSPRY1 was added to Monogenic short stature. Sources: Expert Review Amber,Literature
Q1_25_ promote_green tags were added to gene: RSPRY1.
Mode of inheritance for gene: RSPRY1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RSPRY1 were set to 26365341; 30063090; 38562122; 39940902
Phenotypes for gene: RSPRY1 were set to Spondyloepimetaphyseal dysplasia, Faden-Alkuraya type, OMIM:616723
Skeletal dysplasia v7.27 RSPRY1 Arina Puzriakova Entity copied from Intellectual disability v8.143
Skeletal dysplasia v7.27 RSPRY1 Arina Puzriakova gene: RSPRY1 was added
gene: RSPRY1 was added to Skeletal dysplasia. Sources: Expert Review Amber,Literature
Q1_25_ promote_green tags were added to gene: RSPRY1.
Mode of inheritance for gene: RSPRY1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RSPRY1 were set to 26365341; 30063090; 38562122; 39940902
Phenotypes for gene: RSPRY1 were set to Spondyloepimetaphyseal dysplasia, Faden-Alkuraya type, OMIM:616723
Intellectual disability v8.142 RSPRY1 Arina Puzriakova Tag watchlist was removed from gene: RSPRY1.
Tag Q1_25_ promote_green tag was added to gene: RSPRY1.
Intellectual disability v8.142 RSPRY1 Arina Puzriakova Classified gene: RSPRY1 as Amber List (moderate evidence)
Intellectual disability v8.142 RSPRY1 Arina Puzriakova Added comment: Comment on list classification: At least 5 unrelated families have been reported in the literature with biallelic variants in this gene, presenting with spondyloepimetaphyseal dysplasia. Sufficient to rate Green at the next GMS panel update.
Intellectual disability v8.142 RSPRY1 Arina Puzriakova Gene: rspry1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.141 RSPRY1 Arina Puzriakova Added comment: Comment on publications: PMID: 39940902 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.141 RSPRY1 Arina Puzriakova Publications for gene: RSPRY1 were set to 26365341; 30063090; 38562122; 39940902
Intellectual disability v8.140 RSPRY1 Arina Puzriakova Phenotypes for gene: RSPRY1 were changed from Spondyloepimetaphyseal dysplasia, Faden-Alkuraya type, 616585 to Spondyloepimetaphyseal dysplasia, Faden-Alkuraya type, OMIM:616723
Intellectual disability v8.139 RSPRY1 Arina Puzriakova Publications for gene: RSPRY1 were set to 26365341; 30914295
Intellectual disability v8.138 RSPRY1 Arina Puzriakova reviewed gene: RSPRY1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26365341, 30063090, 38562122, 39940902; Phenotypes: Spondyloepimetaphyseal dysplasia, Faden-Alkuraya type, OMIM:616723; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v7.60 DALRD3 Arina Puzriakova Tag watchlist tag was added to gene: DALRD3.
Intellectual disability v8.138 DALRD3 Arina Puzriakova Classified gene: DALRD3 as Amber List (moderate evidence)
Intellectual disability v8.138 DALRD3 Arina Puzriakova Added comment: Comment on list classification: Maintaining Amber rating as only 2 families have been reported to date.
Intellectual disability v8.138 DALRD3 Arina Puzriakova Gene: dalrd3 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v7.60 DALRD3 Arina Puzriakova Classified gene: DALRD3 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v7.60 DALRD3 Arina Puzriakova Added comment: Comment on list classification: Maintaining Amber rating as only 2 families have been reported to date.
Early onset or syndromic epilepsy v7.60 DALRD3 Arina Puzriakova Gene: dalrd3 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v7.59 DALRD3 Arina Puzriakova Added comment: Comment on publications: PMID: 39482881 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Early onset or syndromic epilepsy v7.59 DALRD3 Arina Puzriakova Publications for gene: DALRD3 were set to 32427860
Early onset or syndromic epilepsy v7.58 DALRD3 Arina Puzriakova commented on gene: DALRD3: PMID: 39482881 - second family identified with an individual with a homozygous missense variant in DALRD3 (c.1549C>T, p.(Arg517Cys)) who displayed severe developmental delay, cognitive deficiencies, and multifocal epilepsy. Phenotype was consistent with previously reported cases but less severe which is consistent with the variant types identified. Patient fibroblasts showed reduced levels of DALRD3 protein compared to WT indicating the variant alters the structure of DALRD3.
Intellectual disability v8.137 DALRD3 Arina Puzriakova Added comment: Comment on publications: PMID: 39482881 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.137 DALRD3 Arina Puzriakova Publications for gene: DALRD3 were set to 32427860
Intellectual disability v8.136 DALRD3 Arina Puzriakova changed review comment from: Second family identified with an individual with a homozygous missense variant in DALRD3 (c.1549C>T, p.(Arg517Cys)) who displayed severe developmental delay, cognitive deficiencies, and multifocal epilepsy. Phenotype was consistent with previously reported cases but less severe which is consistent with the variant types identified. Patient fibroblasts showed reduced levels of DALRD3 protein compared to WT indicating the variant alters the structure of DALRD3.; to: PMID: 39482881 - second family identified with an individual with a homozygous missense variant in DALRD3 (c.1549C>T, p.(Arg517Cys)) who displayed severe developmental delay, cognitive deficiencies, and multifocal epilepsy. Phenotype was consistent with previously reported cases but less severe which is consistent with the variant types identified. Patient fibroblasts showed reduced levels of DALRD3 protein compared to WT indicating the variant alters the structure of DALRD3.
Intellectual disability v8.136 DALRD3 Arina Puzriakova commented on gene: DALRD3: Second family identified with an individual with a homozygous missense variant in DALRD3 (c.1549C>T, p.(Arg517Cys)) who displayed severe developmental delay, cognitive deficiencies, and multifocal epilepsy. Phenotype was consistent with previously reported cases but less severe which is consistent with the variant types identified. Patient fibroblasts showed reduced levels of DALRD3 protein compared to WT indicating the variant alters the structure of DALRD3.
Early onset or syndromic epilepsy v7.58 DALRD3 Arina Puzriakova Deleted their comment
Hereditary ataxia with onset in adulthood v7.13 SPR Arina Puzriakova Tag Q1_25_ MOI tag was added to gene: SPR.
Tag watchlist_moi tag was added to gene: SPR.
Adult onset dystonia, chorea or related movement disorder v4.6 SPR Arina Puzriakova Tag Q1_25_ MOI tag was added to gene: SPR.
Tag watchlist_moi tag was added to gene: SPR.
Adult onset dystonia, chorea or related movement disorder v4.6 SPR Arina Puzriakova Added comment: Comment on mode of inheritance: Sepiapterin reductase deficiency typically follows an autosomal recessive pattern of inheritance. Two cases with different heterozygous variants have been reported (PMID: 29147684, 15241655) although with reduced penetrance in the familial cases and mild form of the disorder in the singleton.

Overall additional evidence is required to conclusively make an association with monoallelic variants and therefore suggesting the MOI is also changed from 'Both mono- and biallelic' to 'Biallelic', with a watchlist_moi tag to monitor for more dominant cases.
Adult onset dystonia, chorea or related movement disorder v4.6 SPR Arina Puzriakova Mode of inheritance for gene: SPR was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary ataxia with onset in adulthood v7.13 SPR Arina Puzriakova Added comment: Comment on mode of inheritance: Sepiapterin reductase deficiency typically follows an autosomal recessive pattern of inheritance. Two cases with different heterozygous variants have been reported (PMID: 29147684, 15241655) although with reduced penetrance in the familial cases and mild form of the disorder in the singleton.

Overall additional evidence is required to conclusively make an association with monoallelic variants and therefore suggesting the MOI is also changed from 'Both mono- and biallelic' to 'Biallelic', with a watchlist_moi tag to monitor for more dominant cases.
Hereditary ataxia with onset in adulthood v7.13 SPR Arina Puzriakova Mode of inheritance for gene: SPR was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v7.58 SPR Arina Puzriakova Added comment: Comment on mode of inheritance: Sepiapterin reductase deficiency typically follows an autosomal recessive pattern of inheritance. Two cases with different heterozygous variants have been reported (PMID: 29147684, 15241655) although with reduced penetrance in the familial cases and mild form of the disorder in the singleton.

Overall additional evidence is required to conclusively make an association with monoallelic variants and therefore updating the MOI from 'Both mono- and biallelic' to 'Biallelic'
Early onset or syndromic epilepsy v7.58 SPR Arina Puzriakova Mode of inheritance for gene: SPR was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Adult onset neurodegenerative disorder v7.12 SPR Arina Puzriakova Added comment: Comment on mode of inheritance: Sepiapterin reductase deficiency typically follows an autosomal recessive pattern of inheritance. Two cases with different heterozygous variants have been reported (PMID: 29147684, 15241655) although with reduced penetrance in the familial cases and mild form of the disorder in the singleton.

Overall additional evidence is required to conclusively make an association with monoallelic variants and therefore updating the MOI from 'Both mono- and biallelic' to 'Biallelic'
Adult onset neurodegenerative disorder v7.12 SPR Arina Puzriakova Mode of inheritance for gene: SPR was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Paroxysmal central nervous system disorders v3.15 SPR Arina Puzriakova Added comment: Comment on mode of inheritance: Sepiapterin reductase deficiency typically follows an autosomal recessive pattern of inheritance. Two cases with different heterozygous variants have been reported (PMID: 29147684, 15241655) although with reduced penetrance in the familial cases and mild form of the disorder in the singleton.

Overall additional evidence is required to conclusively make an association with monoallelic variants and therefore updating the MOI from 'Both mono- and biallelic' to 'Biallelic'
Paroxysmal central nervous system disorders v3.15 SPR Arina Puzriakova Mode of inheritance for gene: SPR was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Brain channelopathy v1.82 SPR Arina Puzriakova Added comment: Comment on mode of inheritance: Sepiapterin reductase deficiency typically follows an autosomal recessive pattern of inheritance. Two cases with different heterozygous variants have been reported (PMID: 29147684, 15241655) although with reduced penetrance in the familial cases and mild form of the disorder in the singleton.

Overall additional evidence is required to conclusively make an association with monoallelic variants and therefore updating the MOI from 'Both mono- and biallelic' to 'Biallelic'
Brain channelopathy v1.82 SPR Arina Puzriakova Mode of inheritance for gene: SPR was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder v6.7 SPR Arina Puzriakova Tag Q1_25_ MOI tag was added to gene: SPR.
Tag watchlist_moi tag was added to gene: SPR.
Childhood onset dystonia, chorea or related movement disorder v6.7 SPR Arina Puzriakova Added comment: Comment on mode of inheritance: Sepiapterin reductase deficiency typically follows an autosomal recessive pattern of inheritance. Two cases with different heterozygous variants have been reported (PMID: 29147684, 15241655) although with reduced penetrance in the familial cases and mild form of the disorder in the singleton.

Overall additional evidence is required to conclusively make an association with monoallelic variants and therefore suggesting the MOI is changed from 'Both mono- and biallelic' to 'Biallelic' at the next GMS panel update, with a watchlist_moi tag to monitor for more dominant cases.
Childhood onset dystonia, chorea or related movement disorder v6.7 SPR Arina Puzriakova Mode of inheritance for gene: SPR was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Adult onset dystonia, chorea or related movement disorder v4.5 SPR Arina Puzriakova Tag Q1_25_ demote_red tag was added to gene: SPR.
Tag Q1_25_ expert_review tag was added to gene: SPR.
Hereditary ataxia with onset in adulthood v7.12 SPR Arina Puzriakova Tag Q1_25_ demote_red tag was added to gene: SPR.
Tag Q1_25_ expert_review tag was added to gene: SPR.
Hereditary ataxia with onset in adulthood v7.12 SPR Arina Puzriakova reviewed gene: SPR: Rating: ; Mode of pathogenicity: None; Publications: 26131547; Phenotypes: Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, OMIM:612716; Mode of inheritance: None
Adult onset dystonia, chorea or related movement disorder v4.5 SPR Arina Puzriakova reviewed gene: SPR: Rating: ; Mode of pathogenicity: None; Publications: 26131547; Phenotypes: Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, OMIM:612716; Mode of inheritance: None
Childhood onset dystonia, chorea or related movement disorder v6.6 SPR Arina Puzriakova Phenotypes for gene: SPR were changed from Dopa-Responsive Dystonia; Movement disorder, autonomic dysfunction, developmental delay, behavioural difficulties; Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, 612716; Sepiapterin reductase deficiency; paediatric form of dopa responsive dystonia to Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, OMIM:612716
Intellectual disability v8.136 SPR Arina Puzriakova Phenotypes for gene: SPR were changed from DOPA-RESPONSIVE DYSTONIA DUE TO SEPIAPTERIN REDUCTASE DEFICIENCY to Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, OMIM:612716
Hereditary ataxia with onset in adulthood v7.12 SPR Arina Puzriakova Phenotypes for gene: SPR were changed from Dystonia, dopa-responsive, due to sepiapterin reductase deficiency 612716; Dopa-responsive dystonia due to sepiaterin reductase deficiency, 612716 to Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, OMIM:612716
Early onset or syndromic epilepsy v7.57 SPR Arina Puzriakova Phenotypes for gene: SPR were changed from Dystonia, dopa-responsive, due to sepiapterin reductase deficiency 612716 to Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, OMIM:612716
Fetal anomalies v5.81 SPR Arina Puzriakova Phenotypes for gene: SPR were changed from DOPA-RESPONSIVE DYSTONIA DUE TO SEPIAPTERIN REDUCTASE DEFICIENCY to Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, OMIM:612716
Likely inborn error of metabolism v7.14 SPR Arina Puzriakova Phenotypes for gene: SPR were changed from Intellectual disability; Early onset dystonia; Sepiapterin reductase deficiency (Disorders of pterin metabolism); Parkinson Disease and Complex Parkinsonism to Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, OMIM:612716; Sepiapterin reductase deficiency (Disorders of pterin metabolism)
Undiagnosed metabolic disorders v1.625 SPR Arina Puzriakova Phenotypes for gene: SPR were changed from Sepiapterin reductase deficiency (Disorders of pterin metabolism); Early onset dystonia; Intellectual disability; Parkinson Disease and Complex Parkinsonism to Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, OMIM:612716; Sepiapterin reductase deficiency (Disorders of pterin metabolism)
Adult onset neurodegenerative disorder v7.11 SPR Arina Puzriakova Phenotypes for gene: SPR were changed from paediatric form of dopa responsive dystonia; Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, 612716; Dystonia, dopa-responsive, due to sepiapterin reductase deficiency 612716; Dopa-Responsive Dystonia to Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, OMIM:612716
Paroxysmal central nervous system disorders v3.14 SPR Arina Puzriakova Phenotypes for gene: SPR were changed from Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, 612716 to Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, OMIM:612716
Early onset dystonia v1.148 SPR Arina Puzriakova Phenotypes for gene: SPR were changed from Dopa-Responsive Dystonia; Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, 612716; paediatric form of dopa responsive dystonia to Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, OMIM:612716; paediatric form of dopa responsive dystonia
Brain channelopathy v1.81 SPR Arina Puzriakova Phenotypes for gene: SPR were changed from Dystonia, dopa-responsive, due to sepiapterin reductase deficiency 612716 to Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, OMIM:612716
Parkinson Disease and Complex Parkinsonism v1.127 SPR Arina Puzriakova Phenotypes for gene: SPR were changed from Dopa-Responsive Dystonia; Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, 612716; paediatric form of dopa responsive dystonia to Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, OMIM:612716; paediatric form of dopa responsive dystonia
Neurotransmitter disorders v1.10 SPR Arina Puzriakova Phenotypes for gene: SPR were changed from Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, 612716; Movement disorder, autonomic dysfunction, developmental delay, behavioural difficulties; Dopa-Responsive Dystonia; Sepiapterin reductase deficiency to Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, OMIM:612716; Movement disorder, autonomic dysfunction, developmental delay, behavioural difficulties; Sepiapterin reductase deficiency
Retinal disorders v7.8 AP5M1 Cassandra Smith gene: AP5M1 was added
gene: AP5M1 was added to Retinal disorders. Sources: Literature
Mode of inheritance for gene: AP5M1 was set to BIALLELIC, autosomal or pseudoautosomal
Review for gene: AP5M1 was set to GREEN
Added comment: Not yet findable in PubMed

Paper: https://www.cell.com/ajhg/fulltext/S0002-9297(25)00062-X

Identified three patients from three different families with biallelic LOF variants and macular dystrophy
Sources: Literature
Congenital hypothyroidism v2.23 STRTS Sarah Leigh commented on Region: STRTS: The curator_removed tag has been added to this entry on PanelApp, because this entity is a short tandem repeat (STR) and not a region. This STR will be added to PanelApp in the future.
Congenital hypothyroidism v2.23 STRTS Sarah Leigh Tag curated_removed tag was added to Region: STRTS.
Hereditary spastic paraplegia v1.314 SPAST Sarah Leigh Added comment: Comment on publications: PMID: 39731306 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Hereditary spastic paraplegia v1.314 SPAST Sarah Leigh Publications for gene: SPAST were set to 26094131; 23897027; 10610178; 10891911; 11039577; 34935948
Hereditary neuropathy v1.497 SPAST Sarah Leigh Added comment: Comment on publications: PMID: 39731306 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Hereditary neuropathy v1.497 SPAST Sarah Leigh Publications for gene: SPAST were set to 28572275
Hereditary neuropathy v1.496 SPAST Sarah Leigh Mode of inheritance for gene: SPAST was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v7.8 SPAST Sarah Leigh Added comment: Comment on publications: PMID: 39731306 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Childhood onset hereditary spastic paraplegia v7.8 SPAST Sarah Leigh Publications for gene: SPAST were set to Hazan et al (1999); 10610178; 10699187; 11039577; 10980739; 15210521; 16832076
Childhood onset hereditary spastic paraplegia v7.7 SPAST Sarah Leigh Tag Q1_25_ MOI tag was added to gene: SPAST.
Hereditary neuropathy or pain disorder v6.164 SPAST Sarah Leigh Added comment: Comment on publications: PMID: 39731306 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Hereditary neuropathy or pain disorder v6.164 SPAST Sarah Leigh Publications for gene: SPAST were set to 28572275
Hereditary neuropathy or pain disorder v6.163 SPAST Sarah Leigh Tag Q1_25_ MOI tag was added to gene: SPAST.
Hereditary neuropathy or pain disorder v6.163 SPAST Sarah Leigh edited their review of gene: SPAST: Added comment: Numerous heterozygous SPAST variants have been associated with Spastic paraplegia 4, autosomal dominant (OMIM:182601). PMID: 39731306 reports five homozygous SPAST variants in nine individuals from six families with spastic paraplegia and neurodegeneration. Amongst the homozygous children, all had lower limb spasticity, 5/6 had upper limb spasticity and 3/6 had severe intellectual disability. Evidence of consanguinity was evident in five of the families and the parents of the homozygous children were heterozygous for the SPAST variant found in the child, these carrier parents were asymptomatic in all but one the families studied.; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary spastic paraplegia v1.313 SPAST Sarah Leigh Mode of inheritance for gene: SPAST was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary spastic paraplegia v1.312 SPAST Sarah Leigh reviewed gene: SPAST: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary neuropathy v1.495 SPAST Sarah Leigh reviewed gene: SPAST: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v7.7 SPAST Sarah Leigh reviewed gene: SPAST: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v8.135 SPAST Sarah Leigh Tag Q1_25_ MOI tag was added to gene: SPAST.
Tag Q1_25_ promote_green tag was added to gene: SPAST.
Intellectual disability v8.135 SPAST Sarah Leigh edited their review of gene: SPAST: Added comment: Numerous heterozygous SPAST variants have been associated with Spastic paraplegia 4, autosomal dominant (OMIM:182601). PMID: 39731306 reports five homozygous SPAST variants in nine individuals from six families with spastic paraplegia and neurodegeneration. Amongst the homozygous children, all had lower limb spasticity, 5/6 had upper limb spasticity and 3/6 had severe intellectual disability. Evidence of consanguinity was evident in five of the families and the parents of the homozygous children were heterozygous for the SPAST variant found in the child, these carrier parents were asymptomatic in all but one the families studied.; Changed rating: GREEN; Changed publications to: 39731306; Changed phenotypes to: Spastic paraplegia 4, autosomal dominant, OMIM:182601; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v7.56 PTPMT1 Arina Puzriakova Classified gene: PTPMT1 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v7.56 PTPMT1 Arina Puzriakova Gene: ptpmt1 has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v8.11 PTPMT1 Arina Puzriakova Classified gene: PTPMT1 as Amber List (moderate evidence)
Mitochondrial disorders v8.11 PTPMT1 Arina Puzriakova Gene: ptpmt1 has been classified as Amber List (Moderate Evidence).
Possible mitochondrial disorder - nuclear genes v3.115 PTPMT1 Arina Puzriakova Classified gene: PTPMT1 as Amber List (moderate evidence)
Possible mitochondrial disorder - nuclear genes v3.115 PTPMT1 Arina Puzriakova Gene: ptpmt1 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v7.18 PTPMT1 Arina Puzriakova Classified gene: PTPMT1 as Amber List (moderate evidence)
Severe microcephaly v7.18 PTPMT1 Arina Puzriakova Gene: ptpmt1 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v7.21 PTPMT1 Arina Puzriakova Classified gene: PTPMT1 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v7.21 PTPMT1 Arina Puzriakova Gene: ptpmt1 has been classified as Amber List (Moderate Evidence).
Possible mitochondrial disorder - nuclear genes v3.114 PTPMT1 Arina Puzriakova gene: PTPMT1 was added
gene: PTPMT1 was added to Possible mitochondrial disorder - nuclear genes. Sources: Literature
watchlist tags were added to gene: PTPMT1.
Mode of inheritance for gene: PTPMT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTPMT1 were set to 39279645
Phenotypes for gene: PTPMT1 were set to neurodevelopmental disorder, MONDO:0700092
Review for gene: PTPMT1 was set to AMBER
Added comment: New gene-disease association. Currently not associated with any phenotype in OMIM or G2P.

PMID:39279645 (2025) - 6 individuals from 3 unrelated families identified with biallelic variants in this gene. All patients presented with a complex, neonatal/infantile onset neurological and neurodevelopmental syndrome, however there was variability in the overall clinical presentation between families. Features include developmental delay, microcephaly, facial dysmorphism, epilepsy, spasticity, cerebellar ataxia and nystagmus, sensorineural hearing loss, optic atrophy and bulbar dysfunction. Brain MRI revealed a variable combination of corpus callosum thinning, cerebellar atrophy and white matter changes.

Patient from Family 1 harboured a homozygous missense variant (c.65A>C) while Family 2 and 3 carried the same homozygous variant (c.255G>C) and were shown to share some common ancestry using DNA microarray analysis.

Knockout zebrafish model displayed abnormalities in body size, developmental alterations, decreased total cardiolipin levels and OXPHOS deficiency.

Overall can be classified as Amber on the basis that two families were shown to be distantly related and no specific features were observed universally across all cases (GDD was mild in 5/6 individuals so outside the scope of the ID panel).
Sources: Literature
Severe microcephaly v7.17 PTPMT1 Arina Puzriakova gene: PTPMT1 was added
gene: PTPMT1 was added to Severe microcephaly. Sources: Literature
watchlist tags were added to gene: PTPMT1.
Mode of inheritance for gene: PTPMT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTPMT1 were set to 39279645
Phenotypes for gene: PTPMT1 were set to neurodevelopmental disorder, MONDO:0700092
Review for gene: PTPMT1 was set to AMBER
Added comment: New gene-disease association. Currently not associated with any phenotype in OMIM or G2P.

PMID:39279645 (2025) - 6 individuals from 3 unrelated families identified with biallelic variants in this gene. All patients presented with a complex, neonatal/infantile onset neurological and neurodevelopmental syndrome, however there was variability in the overall clinical presentation between families. Features include developmental delay, microcephaly, facial dysmorphism, epilepsy, spasticity, cerebellar ataxia and nystagmus, sensorineural hearing loss, optic atrophy and bulbar dysfunction. Brain MRI revealed a variable combination of corpus callosum thinning, cerebellar atrophy and white matter changes.

Patient from Family 1 harboured a homozygous missense variant (c.65A>C) while Family 2 and 3 carried the same homozygous variant (c.255G>C) and were shown to share some common ancestry using DNA microarray analysis.

Knockout zebrafish model displayed abnormalities in body size, developmental alterations, decreased total cardiolipin levels and OXPHOS deficiency.

Overall can be classified as Amber on the basis that two families were shown to be distantly related and no specific features were observed universally across all cases (GDD was mild in 5/6 individuals so outside the scope of the ID panel).
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v7.20 PTPMT1 Arina Puzriakova gene: PTPMT1 was added
gene: PTPMT1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
watchlist tags were added to gene: PTPMT1.
Mode of inheritance for gene: PTPMT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTPMT1 were set to 39279645
Phenotypes for gene: PTPMT1 were set to neurodevelopmental disorder, MONDO:0700092
Review for gene: PTPMT1 was set to AMBER
Added comment: New gene-disease association. Currently not associated with any phenotype in OMIM or G2P.

PMID:39279645 (2025) - 6 individuals from 3 unrelated families identified with biallelic variants in this gene. All patients presented with a complex, neonatal/infantile onset neurological and neurodevelopmental syndrome, however there was variability in the overall clinical presentation between families. Features include developmental delay, microcephaly, facial dysmorphism, epilepsy, spasticity, cerebellar ataxia and nystagmus, sensorineural hearing loss, optic atrophy and bulbar dysfunction. Brain MRI revealed a variable combination of corpus callosum thinning, cerebellar atrophy and white matter changes.

Patient from Family 1 harboured a homozygous missense variant (c.65A>C) while Family 2 and 3 carried the same homozygous variant (c.255G>C) and were shown to share some common ancestry using DNA microarray analysis.

Knockout zebrafish model displayed abnormalities in body size, developmental alterations, decreased total cardiolipin levels and OXPHOS deficiency.

Overall can be classified as Amber on the basis that two families were shown to be distantly related and no specific features were observed universally across all cases (GDD was mild in 5/6 individuals so outside the scope of the ID panel).
Sources: Literature
Early onset or syndromic epilepsy v7.55 PTPMT1 Arina Puzriakova gene: PTPMT1 was added
gene: PTPMT1 was added to Early onset or syndromic epilepsy. Sources: Literature
watchlist tags were added to gene: PTPMT1.
Mode of inheritance for gene: PTPMT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTPMT1 were set to 39279645
Phenotypes for gene: PTPMT1 were set to neurodevelopmental disorder, MONDO:0700092
Review for gene: PTPMT1 was set to AMBER
Added comment: New gene-disease association. Currently not associated with any phenotype in OMIM or G2P.

PMID:39279645 (2025) - 6 individuals from 3 unrelated families identified with biallelic variants in this gene. All patients presented with a complex, neonatal/infantile onset neurological and neurodevelopmental syndrome, however there was variability in the overall clinical presentation between families. Features include developmental delay, microcephaly, facial dysmorphism, epilepsy, spasticity, cerebellar ataxia and nystagmus, sensorineural hearing loss, optic atrophy and bulbar dysfunction. Brain MRI revealed a variable combination of corpus callosum thinning, cerebellar atrophy and white matter changes.

Patient from Family 1 harboured a homozygous missense variant (c.65A>C) while Family 2 and 3 carried the same homozygous variant (c.255G>C) and were shown to share some common ancestry using DNA microarray analysis.

Knockout zebrafish model displayed abnormalities in body size, developmental alterations, decreased total cardiolipin levels and OXPHOS deficiency.

Overall can be classified as Amber on the basis that two families were shown to be distantly related and no specific features were observed universally across all cases (GDD was mild in 5/6 individuals so outside the scope of the ID panel).
Sources: Literature
Mitochondrial disorders v8.10 PTPMT1 Arina Puzriakova gene: PTPMT1 was added
gene: PTPMT1 was added to Mitochondrial disorders. Sources: Literature
watchlist tags were added to gene: PTPMT1.
Mode of inheritance for gene: PTPMT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTPMT1 were set to 39279645
Phenotypes for gene: PTPMT1 were set to neurodevelopmental disorder, MONDO:0700092
Review for gene: PTPMT1 was set to AMBER
Added comment: New gene-disease association. Currently not associated with any phenotype in OMIM or G2P.

PMID:39279645 (2025) - 6 individuals from 3 unrelated families identified with biallelic variants in this gene. All patients presented with a complex, neonatal/infantile onset neurological and neurodevelopmental syndrome, however there was variability in the overall clinical presentation between families. Features include developmental delay, microcephaly, facial dysmorphism, epilepsy, spasticity, cerebellar ataxia and nystagmus, sensorineural hearing loss, optic atrophy and bulbar dysfunction. Brain MRI revealed a variable combination of corpus callosum thinning, cerebellar atrophy and white matter changes.

Patient from Family 1 harboured a homozygous missense variant (c.65A>C) while Family 2 and 3 carried the same homozygous variant (c.255G>C) and were shown to share some common ancestry using DNA microarray analysis.

Knockout zebrafish model displayed abnormalities in body size, developmental alterations, decreased total cardiolipin levels and OXPHOS deficiency.

Overall can be classified as Amber on the basis that two families were shown to be distantly related and no specific features were observed universally across all cases (GDD was mild in 5/6 individuals so outside the scope of the ID panel).
Sources: Literature
Intellectual disability v8.135 PTPMT1 Arina Puzriakova gene: PTPMT1 was added
gene: PTPMT1 was added to Intellectual disability. Sources: Literature
watchlist tags were added to gene: PTPMT1.
Mode of inheritance for gene: PTPMT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTPMT1 were set to 39279645
Phenotypes for gene: PTPMT1 were set to neurodevelopmental disorder, MONDO:0700092
Review for gene: PTPMT1 was set to AMBER
Added comment: New gene-disease association. Currently not associated with any phenotype in OMIM or G2P.

PMID:39279645 (2025) - 6 individuals from 3 unrelated families identified with biallelic variants in this gene. All patients presented with a complex, neonatal/infantile onset neurological and neurodevelopmental syndrome, however there was variability in the overall clinical presentation between families. Features include developmental delay, microcephaly, facial dysmorphism, epilepsy, spasticity, cerebellar ataxia and nystagmus, sensorineural hearing loss, optic atrophy and bulbar dysfunction. Brain MRI revealed a variable combination of corpus callosum thinning, cerebellar atrophy and white matter changes.

Patient from Family 1 harboured a homozygous missense variant (c.65A>C) while Family 2 and 3 carried the same homozygous variant (c.255G>C) and were shown to share some common ancestry using DNA microarray analysis.

Knockout zebrafish model displayed abnormalities in body size, developmental alterations, decreased total cardiolipin levels and OXPHOS deficiency.

Overall can be classified as Amber on the basis that two families were shown to be distantly related and no specific features were observed universally across all cases (GDD was mild in 5/6 individuals so outside the scope of the ID panel).
Sources: Literature
Intellectual disability v8.134 SPAST Sarah Leigh Phenotypes for gene: SPAST were changed from Spastic paraplegia 4, autosomal dominant, 182601 to Spastic paraplegia 4, autosomal dominant, OMIM:182601; hereditary spastic paraplegia 4, MONDO:0008438
Intellectual disability v8.133 SPAST Sarah Leigh Added comment: Comment on publications: PMID: 39731306 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.133 SPAST Sarah Leigh Publications for gene: SPAST were set to
Intellectual disability v8.132 SPAST Sarah Leigh Classified gene: SPAST as Amber List (moderate evidence)
Intellectual disability v8.132 SPAST Sarah Leigh Gene: spast has been classified as Amber List (Moderate Evidence).
Childhood onset hereditary spastic paraplegia v7.7 LSM7 Arina Puzriakova Entity copied from White matter disorders and cerebral calcification - narrow panel v6.9
Childhood onset hereditary spastic paraplegia v7.7 LSM7 Arina Puzriakova gene: LSM7 was added
gene: LSM7 was added to Childhood onset hereditary spastic paraplegia. Sources: Literature,Expert Review Amber
watchlist tags were added to gene: LSM7.
Mode of inheritance for gene: LSM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LSM7 were set to 35047835; 39420558
Phenotypes for gene: LSM7 were set to Leukodystrophy, MONDO:0019046
Ataxia and cerebellar anomalies - narrow panel v7.19 LSM7 Arina Puzriakova Entity copied from White matter disorders and cerebral calcification - narrow panel v6.9
Ataxia and cerebellar anomalies - narrow panel v7.19 LSM7 Arina Puzriakova gene: LSM7 was added
gene: LSM7 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature,Expert Review Amber
watchlist tags were added to gene: LSM7.
Mode of inheritance for gene: LSM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LSM7 were set to 35047835; 39420558
Phenotypes for gene: LSM7 were set to Leukodystrophy, MONDO:0019046
Intellectual disability v8.131 LSM7 Arina Puzriakova Entity copied from White matter disorders and cerebral calcification - narrow panel v6.9
Intellectual disability v8.131 LSM7 Arina Puzriakova gene: LSM7 was added
gene: LSM7 was added to Intellectual disability. Sources: Literature,Expert Review Amber
watchlist tags were added to gene: LSM7.
Mode of inheritance for gene: LSM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LSM7 were set to 35047835; 39420558
Phenotypes for gene: LSM7 were set to Leukodystrophy, MONDO:0019046
White matter disorders and cerebral calcification - narrow panel v6.9 LSM7 Arina Puzriakova Tag watchlist tag was added to gene: LSM7.
White matter disorders and cerebral calcification - narrow panel v6.9 LSM7 Arina Puzriakova Classified gene: LSM7 as Amber List (moderate evidence)
White matter disorders and cerebral calcification - narrow panel v6.9 LSM7 Arina Puzriakova Added comment: Comment on list classification: Rating Amber as one individual died in utero and their phenotype could not be compared to the other two cases. Additionally, although likely homozygous based on the carrier status of the parents, the genotype of this individual is presumed and not confirmed. Overall the evidence is borderline Amber/Green so adding a watchlist tag to monitor for additional studies.
White matter disorders and cerebral calcification - narrow panel v6.9 LSM7 Arina Puzriakova Gene: lsm7 has been classified as Amber List (Moderate Evidence).
White matter disorders and cerebral calcification - narrow panel v6.8 LSM7 Arina Puzriakova edited their review of gene: LSM7: Added comment: Additional family identified with compound heterozygous missense variants in this gene (PMID:39420558). The proband presented with neurodevelopmental defects, leukodystrophy, spastic quadriparesis, and cerebellar atrophy. Authors state that this individual harboured heterozygous variants of each of the previously reported homozygous variants identified in patients from PMID:35047835.; Changed publications to: 35047835, 39420558; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Adult onset neurodegenerative disorder v7.10 POLG Sarah Leigh Added comment: Comment on publications: PMID: 39498811 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Adult onset neurodegenerative disorder v7.10 POLG Sarah Leigh Publications for gene: POLG were set to
Adult onset neurodegenerative disorder v7.9 POLG Sarah Leigh Classified gene: POLG as Amber List (moderate evidence)
Adult onset neurodegenerative disorder v7.9 POLG Sarah Leigh Gene: polg has been classified as Amber List (Moderate Evidence).
Adult onset neurodegenerative disorder v7.8 POLG Sarah Leigh Tag Q1_25_ promote_green tag was added to gene: POLG.
Adult onset neurodegenerative disorder v7.8 POLG Sarah Leigh edited their review of gene: POLG: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Adult onset neurodegenerative disorder v7.8 POLG Sarah Leigh changed review comment from: In their study of a 1185 Spanish Parkinson disease patients, PMID: 39498811 report eleven individuals carrying heterozygous POLG variants. Seven POLG variants were identified in the patients, including the co-occurrence of c.752C>T, p.Thr251Ile and c.1760C>Tp.Pro587Leu (NM_002693.3), which are in cis. The phenotypic features of these patients included motor fluctuations (81.8%), dyskinesias (70%), cognitive impairment (80%), rapid eye movement sleep behavior disorder (70%) and olfactory dysfunction (71.4%). Ataxia or peripheral neuropathy were not reported for these patients (PMID: 39498811).; to: In their study of a 1185 Spanish Parkinson disease patients, PMID: 39498811 report eleven individuals carrying heterozygous POLG variants. Seven POLG variants were identified in the patients, including the co-occurrence of c.752C>T, p.Thr251Ile and c.1760C>Tp.Pro587Leu (NM_002693.3), which are in cis. The phenotypic features of these patients included motor fluctuations (81.8%), dyskinesias (70%), cognitive impairment (80%), rapid eye movement sleep behavior disorder (70%) and olfactory dysfunction (71.4%). Ataxia or peripheral neuropathy were not reported for these patients (PMID: 39498811).
Adult onset neurodegenerative disorder v7.8 POLG Sarah Leigh reviewed gene: POLG: Rating: GREEN; Mode of pathogenicity: None; Publications: 39498811; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
DDG2P v5.48 TMEM199 Eleanor Williams commented on gene: TMEM199
DDG2P v5.48 TMEM199 Eleanor Williams Tag new-gene-name tag was added to gene: TMEM199.
Likely inborn error of metabolism v7.13 TMEM199 Eleanor Williams commented on gene: TMEM199
Likely inborn error of metabolism v7.13 TMEM199 Eleanor Williams Tag new-gene-name tag was added to gene: TMEM199.
Congenital disorders of glycosylation v6.11 TMEM199 Eleanor Williams commented on gene: TMEM199
Congenital disorders of glycosylation v6.11 TMEM199 Eleanor Williams Tag new-gene-name tag was added to gene: TMEM199.
White matter disorders and cerebral calcification - narrow panel v6.8 LSM7 Arina Puzriakova Added comment: Comment on publications: PMID: 39420558 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
White matter disorders and cerebral calcification - narrow panel v6.8 LSM7 Arina Puzriakova Publications for gene: LSM7 were set to https://doi.org/10.1016/j.xhgg.2021.100034
Fetal anomalies v5.80 EFCAB1 Eleanor Williams changed review comment from: Added new-gene-name tag, new approved HGNC gene symbol forEFCAB1 is CLXN; to: Added new-gene-name tag, new approved HGNC gene symbol for EFCAB1 is CLXN
Fetal anomalies v5.80 EFCAB1 Eleanor Williams commented on gene: EFCAB1
Childhood onset dystonia, chorea or related movement disorder v6.5 CCDC115 Eleanor Williams commented on gene: CCDC115
Childhood onset dystonia, chorea or related movement disorder v6.5 CCDC115 Eleanor Williams Tag new-gene-name tag was added to gene: CCDC115.
Intellectual disability v8.130 CCDC115 Eleanor Williams commented on gene: CCDC115
Intellectual disability v8.130 CCDC115 Eleanor Williams Tag new-gene-name tag was added to gene: CCDC115.
DDG2P v5.48 CCDC115 Eleanor Williams commented on gene: CCDC115
DDG2P v5.48 CCDC115 Eleanor Williams Tag new-gene-name tag was added to gene: CCDC115.
Fetal anomalies v5.80 CCDC115 Eleanor Williams commented on gene: CCDC115
Fetal anomalies v5.80 CCDC115 Eleanor Williams Tag new-gene-name tag was added to gene: CCDC115.
Intellectual disability v8.130 ZNRF3 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: ZNRF3.
Paediatric disorders - additional genes v6.13 ZNRF3 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: ZNRF3.
Likely inborn error of metabolism v7.13 CCDC115 Eleanor Williams commented on gene: CCDC115
Likely inborn error of metabolism v7.13 CCDC115 Eleanor Williams Tag new-gene-name tag was added to gene: CCDC115.
DDG2P v5.48 USP14 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: USP14.
Fetal anomalies v5.80 USP14 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: USP14.
Undiagnosed metabolic disorders v1.624 CCDC115 Eleanor Williams commented on gene: CCDC115
Undiagnosed metabolic disorders v1.624 CCDC115 Eleanor Williams Tag new-gene-name tag was added to gene: CCDC115.
Fetal anomalies v5.80 TSHZ3 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: TSHZ3.
Paediatric or syndromic cardiomyopathy v6.7 TAF1A Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: TAF1A.
DDG2P v5.48 SLC12A9 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: SLC12A9.
Congenital disorders of glycosylation v6.11 CCDC115 Eleanor Williams commented on gene: CCDC115
Intellectual disability v8.130 RBBP5 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: RBBP5.
DDG2P v5.48 RBBP5 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: RBBP5.
Congenital disorders of glycosylation v6.11 CCDC115 Eleanor Williams Tag new-gene-name tag was added to gene: CCDC115.
DDG2P v5.48 RAB1A Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: RAB1A.
Intellectual disability v8.130 PSMC5 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: PSMC5.
Fetal anomalies v5.80 PAN2 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: PAN2.
Hereditary neuropathy or pain disorder v6.163 NDC1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: NDC1.
Fetal anomalies v5.80 MYBBP1A Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: MYBBP1A.
Early onset or syndromic epilepsy v7.54 MARK2 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: MARK2.
Intellectual disability v8.130 MARK2 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: MARK2.
Hereditary neuropathy or pain disorder v6.163 ADPRHL2 Eleanor Williams commented on gene: ADPRHL2
Fetal anomalies v5.80 MAP4K4 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: MAP4K4.
Hereditary neuropathy or pain disorder v6.163 ADPRHL2 Eleanor Williams Tag new-gene-name tag was added to gene: ADPRHL2.
Intellectual disability v8.130 LRRC7 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: LRRC7.
Fetal anomalies v5.80 KIF5B Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: KIF5B.
Skeletal dysplasia v7.26 KIF5B Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: KIF5B.
Fetal anomalies v5.80 KIF24 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: KIF24.
Fetal anomalies v5.80 KDM2B Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: KDM2B.
Intellectual disability v8.130 HDAC3 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: HDAC3.
DDG2P v5.48 HDAC3 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: HDAC3.
Fetal anomalies v5.80 GON4L Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: GON4L.
DDG2P v5.48 FEM1B Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: FEM1B.
DDG2P v5.48 EPB41L3 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: EPB41L3.
DDG2P v5.48 DIP2C Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: DIP2C.
Intellectual disability v8.130 DDX17 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: DDX17.
DDG2P v5.48 CCT6A Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: CCT6A.
Fetal anomalies v5.80 CBY1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: CBY1.
Fetal anomalies v5.80 AMOTL1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: AMOTL1.
DDG2P v5.48 ZSCAN10 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: ZSCAN10.
DDG2P v5.48 ZSCAN10 Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene has now been associated with relevant phenotypes in OMIM (MIM #620910).
DDG2P v5.48 ZSCAN10 Achchuthan Shanmugasundram Phenotypes for gene: ZSCAN10 were changed from ZSCAN10-related neurodevelopmental disorder with oto-facial malformations to ZSCAN10-related neurodevelopmental disorder with oto-facial malformations
Intellectual disability v8.130 WDR83OS Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene has now been associated with relevant phenotypes in OMIM (MIM #621016).
Intellectual disability v8.130 WDR83OS Achchuthan Shanmugasundram Phenotypes for gene: WDR83OS were changed from complex neurodevelopmental disorder, MONDO:0100038; intellectual disability, MONDO:0001071 to Neurodevelopmental disorder with variable familial hypercholanemia, OMIM:621016
Intellectual disability v8.129 WDR83OS Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: WDR83OS.
Fetal anomalies v5.80 WDR44 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: WDR44.
Intellectual disability v8.129 RNU4-2 Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene has now been associated with relevant phenotypes in OMIM (MIM #620851).
Intellectual disability v8.129 RNU4-2 Achchuthan Shanmugasundram Phenotypes for gene: RNU4-2 were changed from Neurodevelopmental disorder, MONDO:0700092, RNU4-2 related to ReNU syndrome, OMIM:620851
DDG2P v5.47 RNU4-2 Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene has now been associated with relevant phenotypes in OMIM (MIM #620851).
DDG2P v5.47 RNU4-2 Achchuthan Shanmugasundram Phenotypes for gene: RNU4-2 were changed from RNU4-2 related neurodevelopmental disorder with microcephaly and seizures to RNU4-2 related neurodevelopmental disorder with microcephaly and seizures
Early onset or syndromic epilepsy v7.54 RNU4-2 Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene has now been associated with relevant phenotypes in OMIM (MIM #620851).
Early onset or syndromic epilepsy v7.54 RNU4-2 Achchuthan Shanmugasundram Phenotypes for gene: RNU4-2 were changed from Neurodevelopmental disorder, MONDO:0700092, RNU4-2 related to ReNU syndrome, OMIM:620851
Severe microcephaly v7.16 RNU4-2 Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene has now been associated with relevant phenotypes in OMIM (MIM #620851).
Severe microcephaly v7.16 RNU4-2 Achchuthan Shanmugasundram Phenotypes for gene: RNU4-2 were changed from Neurodevelopmental disorder, MONDO:0700092, RNU4-2 related to ReNU syndrome, OMIM:620851
Fetal anomalies v5.80 RNU4-2 Achchuthan Shanmugasundram Tag locus-type-rna-small-nuclear tag was added to gene: RNU4-2.
Tag gene-checked tag was added to gene: RNU4-2.
Fetal anomalies v5.80 PSMF1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: PSMF1.
Intellectual disability v8.128 LINC01578 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: LINC01578.
Fetal anomalies v5.80 HECTD4 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: HECTD4.
Hereditary neuropathy or pain disorder v6.163 FICD Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: FICD.
Childhood onset hereditary spastic paraplegia v7.6 FICD Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: FICD.
Fetal anomalies v5.80 EFCAB1 Achchuthan Shanmugasundram Tag new-gene-name tag was added to gene: EFCAB1.
Fetal anomalies v5.80 EFCAB1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: EFCAB1.
Intellectual disability v8.128 DHRSX Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene has now been associated with relevant phenotypes in OMIM (MIM #301133).
Intellectual disability v8.128 DHRSX Achchuthan Shanmugasundram Phenotypes for gene: DHRSX were changed from congenital disorder of glycosylation, MONDO:0015286; intellectual disability, MONDO:0001071 to Congenital disorder of glycosylation, type 1DD, OMIM:301133
Intellectual disability v8.127 DHRSX Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: DHRSX.
Early onset or syndromic epilepsy v7.53 DHRSX Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene has now been associated with relevant phenotypes in OMIM (MIM #301133).
Early onset or syndromic epilepsy v7.53 DHRSX Achchuthan Shanmugasundram Phenotypes for gene: DHRSX were changed from congenital disorder of glycosylation, MONDO:0015286; epilepsy, MONDO:0005027 to Congenital disorder of glycosylation, type 1DD, OMIM:301133
Early onset or syndromic epilepsy v7.52 DHRSX Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: DHRSX.
Monogenic hearing loss v4.79 DHRSX Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene has now been associated with relevant phenotypes in OMIM (MIM #301133).
Monogenic hearing loss v4.79 DHRSX Achchuthan Shanmugasundram Phenotypes for gene: DHRSX were changed from congenital disorder of glycosylation, MONDO:0015286; hearing loss disorder, MONDO:0005365 to Congenital disorder of glycosylation, type 1DD, OMIM:301133
Likely inborn error of metabolism v7.13 DHRSX Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene has now been associated with relevant phenotypes in OMIM (MIM #301133).
Likely inborn error of metabolism v7.13 DHRSX Achchuthan Shanmugasundram Phenotypes for gene: DHRSX were changed from congenital disorder of glycosylation, MONDO:0015286 to Congenital disorder of glycosylation, type 1DD, OMIM:301133
Monogenic hearing loss v4.78 DHRSX Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: DHRSX.
Likely inborn error of metabolism v7.12 DHRSX Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: DHRSX.
Congenital disorders of glycosylation v6.11 DHRSX Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene has now been associated with relevant phenotypes in OMIM (MIM #301133).
Congenital disorders of glycosylation v6.11 DHRSX Achchuthan Shanmugasundram Phenotypes for gene: DHRSX were changed from congenital disorder of glycosylation, MONDO:0015286 to Congenital disorder of glycosylation, type 1DD, OMIM:301133
Congenital disorders of glycosylation v6.10 DHRSX Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: DHRSX.
Fetal anomalies v5.80 DAW1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: DAW1.
Fetal anomalies v5.80 C16orf62 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: C16orf62.
Intellectual disability v8.127 ATXN7L3 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: ATXN7L3.
Fetal anomalies v5.80 AL117258.1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: AL117258.1.
Hereditary neuropathy or pain disorder v6.163 DHX9 Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene has now been associated with relevant phenotypes in OMIM (MIM #620988).
Hereditary neuropathy or pain disorder v6.163 DHX9 Achchuthan Shanmugasundram Phenotypes for gene: DHX9 were changed from Adult-onset axonal neuropathy; Charcot-Marie-Tooth disease, MONDO:0015626 to Intellectual developmental disorder, autosomal dominant 75, OMIM:620988
Hereditary neuropathy or pain disorder v6.162 DHX9 Achchuthan Shanmugasundram Tag gene-checked was removed from gene: DHX9.
Intellectual disability v8.127 DHX9 Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene has now been associated with relevant phenotypes in OMIM (MIM #620988).
Intellectual disability v8.127 DHX9 Achchuthan Shanmugasundram Phenotypes for gene: DHX9 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to Intellectual developmental disorder, autosomal dominant 75, OMIM:620988
DDG2P v5.46 DHX9 Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene has now been associated with relevant phenotypes in OMIM (MIM #620988).
DDG2P v5.46 DHX9 Achchuthan Shanmugasundram Phenotypes for gene: DHX9 were changed from DHX9-related neurodevelopmental disorder and Charcot-Marie-Tooth disease to DHX9-related neurodevelopmental disorder and Charcot-Marie-Tooth disease
DDG2P v5.45 DHX9 Achchuthan Shanmugasundram Tag gene-checked was removed from gene: DHX9.
Intellectual disability v8.126 DHX9 Achchuthan Shanmugasundram Tag gene-checked was removed from gene: DHX9.
Paediatric disorders - additional genes v6.13 HYAL2 Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene has now been associated with relevant phenotypes in OMIM (MIM #621063).
Paediatric disorders - additional genes v6.13 HYAL2 Achchuthan Shanmugasundram Phenotypes for gene: HYAL2 were changed from cor triatriatum; congenital cardiac malformations to Muggenthaler-Chowdhury-Chioza syndrome, OMIM:621063
Paediatric disorders - additional genes v6.12 HYAL2 Achchuthan Shanmugasundram Tag gene-checked was removed from gene: HYAL2.
Clefting v6.5 HYAL2 Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene has now been associated with relevant phenotypes in OMIM (MIM #621063).
Clefting v6.5 HYAL2 Achchuthan Shanmugasundram Phenotypes for gene: HYAL2 were changed from cleft lip/palate MONDO:0016044; triatrial heart MONDO:0015450 to Muggenthaler-Chowdhury-Chioza syndrome, OMIM:621063
Clefting v6.4 HYAL2 Achchuthan Shanmugasundram Tag gene-checked was removed from gene: HYAL2.
DDG2P v5.45 HYAL2 Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene has now been associated with relevant phenotypes in OMIM (MIM #621063).
DDG2P v5.45 HYAL2 Achchuthan Shanmugasundram Phenotypes for gene: HYAL2 were changed from HYAL2-related syndrome with cleft lip and palate and congenital cardiac anomalies to HYAL2-related syndrome with cleft lip and palate and congenital cardiac anomalies
DDG2P v5.44 HYAL2 Achchuthan Shanmugasundram Tag gene-checked was removed from gene: HYAL2.
Fetal anomalies v5.80 HYAL2 Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene has now been associated with relevant phenotypes in OMIM (MIM #621063).
Fetal anomalies v5.80 HYAL2 Achchuthan Shanmugasundram Phenotypes for gene: HYAL2 were changed from congenital cardiac malformations; Cleft lip and palate; cor triatriatum to Muggenthaler-Chowdhury-Chioza syndrome, OMIM:621063
Fetal anomalies v5.79 HYAL2 Achchuthan Shanmugasundram Tag gene-checked was removed from gene: HYAL2.
Familial non syndromic congenital heart disease v1.87 HYAL2 Achchuthan Shanmugasundram Phenotypes for gene: HYAL2 were changed from cor triatriatum; congenital cardiac malformations to Muggenthaler-Chowdhury-Chioza syndrome, OMIM:621063
Familial non syndromic congenital heart disease v1.86 HYAL2 Achchuthan Shanmugasundram Tag gene-checked was removed from gene: HYAL2.
Congenital hypothyroidism v2.23 STRTS Sarah Leigh commented on Region: STRTS
Congenital hypothyroidism v2.23 STRTS Sarah Leigh Publications for Region: STRTS were set to PMID: 38714869; 15870119
Early onset or syndromic epilepsy v7.52 CTSF Sarah Leigh Added comment: Comment on publications: PMID: 39720560 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Early onset or syndromic epilepsy v7.52 CTSF Sarah Leigh Publications for gene: CTSF were set to 16508006; 39720560
Early onset or syndromic epilepsy v7.51 CTSF Sarah Leigh Tag Q1_25_ promote_green tag was added to gene: CTSF.
Early onset or syndromic epilepsy v7.51 CTSF Sarah Leigh reviewed gene: CTSF: Rating: GREEN; Mode of pathogenicity: None; Publications: 39720560; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v7.51 MARK2 Arina Puzriakova Classified gene: MARK2 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v7.51 MARK2 Arina Puzriakova Gene: mark2 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v7.50 MARK2 Sarah Leigh Deleted their comment
Early onset or syndromic epilepsy v7.50 MARK2 Arina Puzriakova Tag Q1_25_ promote_green tag was added to gene: MARK2.
Early onset or syndromic epilepsy v7.50 MARK2 Arina Puzriakova Entity copied from Intellectual disability v8.126
Early onset or syndromic epilepsy v7.50 MARK2 Arina Puzriakova gene: MARK2 was added
gene: MARK2 was added to Early onset or syndromic epilepsy. Sources: Expert Review Green,NHS GMS,Literature
Mode of inheritance for gene: MARK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MARK2 were set to 39419027; 39436150
Phenotypes for gene: MARK2 were set to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Early onset or syndromic epilepsy v7.49 CTSF Sarah Leigh Publications for gene: CTSF were set to 16508006
Early onset or syndromic epilepsy v7.48 CTSF Sarah Leigh Phenotypes for gene: CTSF were changed from Ceroid lipofuscinosis, neuronal, 13, Kufs type, 615362 to Ceroid lipofuscinosis, neuronal, 13, Kufs type, OMIM:615362; neuronal ceroid lipofuscinosis 13, MONDO:0014147
Intellectual disability v8.126 XPA Sarah Leigh Tag Q1_25_ promote_green tag was added to gene: XPA.
Monogenic hearing loss v4.78 XPA Sarah Leigh Tag Q1_25_ promote_green tag was added to gene: XPA.
Monogenic hearing loss v4.78 XPA Sarah Leigh Classified gene: XPA as Amber List (moderate evidence)
Monogenic hearing loss v4.78 XPA Sarah Leigh Gene: xpa has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v4.77 XPA Sarah Leigh Mode of inheritance for gene: XPA was changed from to BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v4.76 XPA Sarah Leigh Phenotypes for gene: XPA were changed from to Xeroderma pigmentosum, group A, OMIM: 278700
Monogenic hearing loss v4.75 XPA Sarah Leigh Added comment: Comment on publications: PMID: 39621777 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Monogenic hearing loss v4.75 XPA Sarah Leigh Publications for gene: XPA were set to
Intellectual disability v8.126 XPA Sarah Leigh Added comment: Comment on publications: PMID: 39621777 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.126 XPA Sarah Leigh Publications for gene: XPA were set to 26302748; 25566891; 24135642
Intellectual disability v8.125 XPA Sarah Leigh Phenotypes for gene: XPA were changed from mental retardation; progressive intellectual impariment to Xeroderma pigmentosum, group A, OMIM: 278700
Monogenic hearing loss v4.74 XPA Sarah Leigh reviewed gene: XPA: Rating: GREEN; Mode of pathogenicity: None; Publications: 39621777; Phenotypes: Xeroderma pigmentosum, group A, OMIM: 278700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v8.124 XPA Sarah Leigh changed review comment from: PMID: 39621777 reports 16 XPA variants in 18 patients with Xeroderma pigmentosum, group A (OMIM:278700). Amongst the cohort, the authors were able to classify the patients into three severity groups based on the extent of their neurological abnormalities at age 10 years (8 severe, 6 intermediate and 4 mild). The severe phenotype included developmental delay and mild to profound hearing loss, was associated with terminating variants in exons 3 and 5 of XPA, which resulted in reducing the XPA protein to undetectable levels.; to: PMID: 39621777 reports 16 XPA variants in 18 patients with Xeroderma pigmentosum, group A (OMIM:278700). Amongst the cohort, the authors were able to classify the patients into three severity groups based on the extent of their neurological abnormalities at age 10 years. There were 8 severe, 6 intermediate and 4 mild patients. The severe phenotype included developmental delay and mild to profound hearing loss, and was associated with terminating variants in exons 3 and 5 of XPA, which resulting in undetectable levels of XPA protein.
Intellectual disability v8.124 XPA Sarah Leigh reviewed gene: XPA: Rating: GREEN; Mode of pathogenicity: None; Publications: 39621777; Phenotypes: Xeroderma pigmentosum, group A, OMIM: 278700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v7.47 INPP4A Arina Puzriakova Entity copied from Intellectual disability v8.124
Early onset or syndromic epilepsy v7.47 INPP4A Arina Puzriakova gene: INPP4A was added
gene: INPP4A was added to Early onset or syndromic epilepsy. Sources: Expert Review Amber
Q1_25_ promote_green tags were added to gene: INPP4A.
Mode of inheritance for gene: INPP4A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INPP4A were set to 21937992; 31978615; 31938306; 25338135; 20011524; 36653678
Phenotypes for gene: INPP4A were set to Intellectual disability; Seizures
Penetrance for gene: INPP4A were set to Complete
Intellectual disability v8.124 MAG Sarah Leigh Added comment: Comment on publications: PMID: 39336794 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.124 MAG Sarah Leigh Publications for gene: MAG were set to 39336794
Intellectual disability v8.123 MAG Sarah Leigh Classified gene: MAG as Amber List (moderate evidence)
Intellectual disability v8.123 MAG Sarah Leigh Gene: mag has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.122 MAG Sarah Leigh gene: MAG was added
gene: MAG was added to Intellectual disability. Sources: Literature
Q1_25_ promote_green tags were added to gene: MAG.
Mode of inheritance for gene: MAG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAG were set to 39336794
Phenotypes for gene: MAG were set to Spastic paraplegia 75, autosomal recessive, OMIM:616680; hereditary spastic paraplegia 75, MONDO:0014729
Review for gene: MAG was set to GREEN
Added comment: AT least six MAG variants have been associated with Spastic paraplegia 75, autosomal recessive, OMIM:616680 in at least five unrelated cases (PMID: 24482476; 26179919; 27606346; 31402626; 39336794). It would appear that intellectual disability is a common feature in cases of OMIM:616680, although this may be mild to moderate.
Sources: Literature
White matter disorders and cerebral calcification - narrow panel v6.7 ATP11A Arina Puzriakova Tag watchlist was removed from gene: ATP11A.
Inherited white matter disorders v1.184 ATP11A Arina Puzriakova Tag watchlist was removed from gene: ATP11A.
Inherited white matter disorders v1.184 ATP11A Arina Puzriakova Publications for gene: ATP11A were set to 34403372
Inherited white matter disorders v1.183 ATP11A Arina Puzriakova Phenotypes for gene: ATP11A were changed from Leukodystrophy, hypomyelinating, 24 , OMIM:619851 to Leukodystrophy, hypomyelinating, 24, OMIM:619851
White matter disorders and cerebral calcification - narrow panel v6.7 ATP11A Arina Puzriakova Phenotypes for gene: ATP11A were changed from Neurodevelopmental disorder to Leukodystrophy, hypomyelinating, 24, OMIM:619851
Inherited white matter disorders v1.182 ATP11A Arina Puzriakova Phenotypes for gene: ATP11A were changed from Neurodevelopmental disorder to Leukodystrophy, hypomyelinating, 24 , OMIM:619851
Inherited white matter disorders v1.181 ATP11A Arina Puzriakova Classified gene: ATP11A as Amber List (moderate evidence)
Inherited white matter disorders v1.181 ATP11A Arina Puzriakova Added comment: Comment on list classification: Green recommendation on GMS panel and therefore rating Green on this 100K equivalent panel for consistency,
Inherited white matter disorders v1.181 ATP11A Arina Puzriakova Gene: atp11a has been classified as Amber List (Moderate Evidence).
Inherited white matter disorders v1.180 ATP11A Arina Puzriakova edited their review of gene: ATP11A: Changed rating: GREEN
Inherited white matter disorders v1.180 ATP11A Arina Puzriakova commented on gene: ATP11A
Hereditary ataxia with onset in adulthood v7.11 FGF14_TTC Sarah Leigh commented on STR: FGF14_TTC: The name of this STR has been changed from FGF14_GAA to FGF14_TTC as FGF14 is transcribed from the reverse strand of the sequence.
The coordinates for the repeated sequence have been updated to those shown in https://stripy.org/database/FGF14. Previously, the coordinates were for the whole gene, rather than the repeated sequence.
Hereditary neuropathy or pain disorder v6.162 FGF14_TTC Sarah Leigh commented on STR: FGF14_TTC: The name of this STR has been changed from FGF14_GAA to FGF14_TTC as FGF14 is transcribed from the reverse strand of the sequence.
The coordinates for the repeated sequence have been updated to those shown in https://stripy.org/database/FGF14. Previously, the coordinates were for the whole gene, rather than the repeated sequence.
Hereditary neuropathy or pain disorder v6.162 FGF14_TTC Sarah Leigh Tag NGS Not Validated tag was added to STR: FGF14_TTC.
Hereditary ataxia with onset in adulthood v7.11 FGF14_TTC Sarah Leigh Tag NGS Not Validated tag was added to STR: FGF14_TTC.
Hereditary neuropathy or pain disorder v6.162 FGF14_TTC Sarah Leigh FGF14_GAA was changed to FGF14_TTC
GRCh38 position for FGF14_TTC was changed from 101710804-102402443 to 102161576-102161726.
Repeated Sequence for FGF14_TTC was changed from GAA to TTC.
Source Literature was removed from STR: FGF14_TTC.
Hereditary ataxia with onset in adulthood v7.11 FGF14_TTC Sarah Leigh FGF14_GAA was changed to FGF14_TTC
GRCh38 position for FGF14_TTC was changed from 101710804-102402443 to 102161576-102161726.
Repeated Sequence for FGF14_TTC was changed from GAA to TTC.
Source Literature was removed from STR: FGF14_TTC.
Fetal anomalies v5.79 CNBP_CCTG Achchuthan Shanmugasundram commented on STR: CNBP_CCTG: The repeated sequence of this STR has been updated from 'CAGG' to 'CCTG' to match the sequence on the coding strand of the gene. This update was made following NHS Genomic Medicine Service approval.
Fetal anomalies v5.79 CNBP_CCTG Achchuthan Shanmugasundram Repeated Sequence for CNBP_CCTG was changed from CAGG to CCTG.
Skeletal muscle channelopathy v3.6 CNBP_CCTG Achchuthan Shanmugasundram commented on STR: CNBP_CCTG: The repeated sequence of this STR has been updated from 'CAGG' to 'CCTG' to match the sequence on the coding strand of the gene. This update was made following NHS Genomic Medicine Service approval.
Skeletal Muscle Channelopathies v1.47 CNBP_CCTG Achchuthan Shanmugasundram changed review comment from: The repeated sequence of this STR has been updated from 'CAGG' to 'CCTG' to match the sequence on the coding strand of the gene.; to: The repeated sequence of this STR has been updated from 'CAGG' to 'CCTG' to match the sequence on the coding strand of the gene. This update was made following NHS Genomic Medicine Service approval.
Skeletal Muscle Channelopathies v1.47 CNBP_CCTG Achchuthan Shanmugasundram commented on STR: CNBP_CCTG
Distal myopathies v6.3 CNBP_CCTG Achchuthan Shanmugasundram commented on STR: CNBP_CCTG: The repeated sequence of this STR has been updated from 'CAGG' to 'CCTG' to match the sequence on the coding strand of the gene. This update was made following NHS Genomic Medicine Service approval.
Skeletal muscle channelopathy v3.6 CNBP_CCTG Achchuthan Shanmugasundram Repeated Sequence for CNBP_CCTG was changed from CAGG to CCTG.
Distal myopathies v6.3 CNBP_CCTG Achchuthan Shanmugasundram Repeated Sequence for CNBP_CCTG was changed from CAGG to CCTG.
Skeletal Muscle Channelopathies v1.47 CNBP_CCTG Achchuthan Shanmugasundram Repeated Sequence for CNBP_CCTG was changed from CAGG to CCTG.
Congenital myopathy v5.15 GFER Achchuthan Shanmugasundram Classified gene: GFER as Green List (high evidence)
Congenital myopathy v5.15 GFER Achchuthan Shanmugasundram Gene: gfer has been classified as Green List (High Evidence).
Congenital myopathy v5.14 GFER Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE was removed from gene: GFER.
Congenital myopathy v5.14 GFER Achchuthan Shanmugasundram edited their review of gene: GFER: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v8.121 CCDC88A Arina Puzriakova Publications for gene: CCDC88A were set to 26917597; 30392057; 37798908; 39334473
Intellectual disability v8.120 AFF3_GGC Sarah Leigh AFF3_GCC was changed to AFF3_GGC
Repeated Sequence for AFF3_GGC was changed from GCC to GGC.
Congenital hypothyroidism v2.22 STRTS Nadia Schoenmakers reviewed Region: STRTS: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38714869, 38714868; Phenotypes: congenital hypothyroidism, subclinical hypothyroidism, TSH Resistance (RTSH), multi nodular goitre; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v8.119 LINC01578 Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene has now been associated with relevant phenotype in OMIM (MIM #621012), but not yet in Gene2Phenotype.
Intellectual disability v8.119 LINC01578 Achchuthan Shanmugasundram Phenotypes for gene: LINC01578 were changed from Neurodevelopmental disorder, MONDO:0700092, CHASERR-related to Neurodevelopmental disorder with dysmorphic facies, absent speech and ambulation, and brain abnormalities, OMIM:621012
Intellectual disability v8.118 LINC01578 Achchuthan Shanmugasundram Tag locus-type-rna-long-non-coding tag was added to gene: LINC01578.
Congenital hypothyroidism v2.22 STRTS Adam Gunning Region: STRTS was added
Region: STRTS was added to Congenital hypothyroidism. Sources: Literature,NHS GMS
Mode of inheritance for Region: STRTS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: STRTS were set to PMID: 38714869; 15870119
Phenotypes for Region: STRTS were set to Congenital hypothyroidism; Small thyroid (in children); Multinodular goitre (with age, if untreated); Elevated serum TSH
Penetrance for Region: STRTS were set to Complete
Review for Region: STRTS was set to GREEN
Added comment: Sources: Literature, NHS GMS
Familial hypoparathyroidism v2.18 STX16 Eleanor Williams changed review comment from: The rating of this gene has was initially changed to green (but not in the signed off version of the panel) but after further review it has been decided to keep it as amber. GLH review notes: STX16 deletions are associated with pseudohypoparathroidism (1b). Clinically this means hypocalcaemia but PTH levels are elevated – which is the normal response to low serum calcium (hence the pseudo and indicating defective response to PTH levels rather than defective PTH production as in hypoparathyroidism ).

R153 Familial hypoparathyroidism testing criteria are: Non-syndromic hypoparathyroidism with low calcium levels and low or inappropriately normal serum PTH, with no detectable cause. Clinically R153 requires hypocalcaemia and low PTH levels (/ inappropriately normal in ADH) due to defective PTH production in the main) - so patients with STX16 wont clinically fulfil R153 test criteria.

following NHS Genomic Medicine Service approval.; to: The rating of this gene has was initially changed to green (but not in the signed off version of the panel) but after further review it has been decided to keep it as amber (see review by Treena Cranston) . The clinical phenotype of pseudohypoparathroidism 1b does not fit with the testing criteria of the panel: R153 requires hypocalcaemia and low PTH levels (/ inappropriately normal in ADH) due to defective PTH production in the main) - so patients with STX16 wont clinically fulfil R153 test criteria.

Therefore this gene remains amber following NHS Genomic Medicine Service review.
Familial hypoparathyroidism v2.18 STX16 Eleanor Williams edited their review of gene: STX16: Changed rating: AMBER
Familial hypoparathyroidism v2.18 STX16 Eleanor Williams changed review comment from: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; to: The rating of this gene has was initially changed to green (but not in the signed off version of the panel) but after further review it has been decided to keep it as amber. GLH review notes: STX16 deletions are associated with pseudohypoparathroidism (1b). Clinically this means hypocalcaemia but PTH levels are elevated – which is the normal response to low serum calcium (hence the pseudo and indicating defective response to PTH levels rather than defective PTH production as in hypoparathyroidism ).

R153 Familial hypoparathyroidism testing criteria are: Non-syndromic hypoparathyroidism with low calcium levels and low or inappropriately normal serum PTH, with no detectable cause. Clinically R153 requires hypocalcaemia and low PTH levels (/ inappropriately normal in ADH) due to defective PTH production in the main) - so patients with STX16 wont clinically fulfil R153 test criteria.

following NHS Genomic Medicine Service approval.
Monogenic hearing loss v4.74 HGF Achchuthan Shanmugasundram changed review comment from: Three different biallelic variants in HGF gene were identified in more than 60 unrelated families reported in PMIDs:19576567 and 30303587 with profound prelingual deafness. There is also mouse model available in support of the disease association. These evidence suggest that the gene should be promoted to green rating in the next GMS review. However, the previous review from Eleanor Williams note it was decided to rate this gene to amber with the 'watchlist' tag after review with the GMS hearing specialist test group in a Webex on 2019-02-13 and consultation with the Genomics England clinical team. So, I am requesting expert review from the GMS to decide whether this gene can be promoted to green rating now.; to: Three different biallelic variants in HGF gene were identified in more than 60 unrelated families reported in PMIDs:19576567 and 30303587 with profound prelingual deafness. There is also mouse model available in support of the disease association. These evidence suggest that the gene should be promoted to green rating in the next GMS review. However, the previous review from Eleanor Williams note that it was decided to rate this gene to amber with the 'watchlist' tag after review with the GMS hearing specialist test group in a Webex on 2019-02-13 and consultation with the Genomics England clinical team. So, I am requesting expert review from the GMS to decide whether this gene can be promoted to green rating now.
Familial hypoparathyroidism v2.18 STX16 Achchuthan Shanmugasundram Classified gene: STX16 as Amber List (moderate evidence)
Familial hypoparathyroidism v2.18 STX16 Achchuthan Shanmugasundram Gene: stx16 has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.118 TDP1 Sarah Leigh Classified gene: TDP1 as Amber List (moderate evidence)
Intellectual disability v8.118 TDP1 Sarah Leigh Added comment: Comment on list classification: This gene remains amber, as there are only two disease associated variants have been reported (PMID: 12244316;31182267;39576382).
Intellectual disability v8.118 TDP1 Sarah Leigh Gene: tdp1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.117 TDP1 Sarah Leigh Added comment: Comment on publications: PMID: 39576382 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.117 TDP1 Sarah Leigh Publications for gene: TDP1 were set to 12244316; 31182267; 39576382
Hereditary neuropathy or pain disorder v6.161 TDP1 Sarah Leigh Added comment: Comment on publications: PMID: 39576382 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Hereditary neuropathy or pain disorder v6.161 TDP1 Sarah Leigh Publications for gene: TDP1 were set to 12244316; 31182267; 39576382
Hereditary neuropathy or pain disorder v6.160 TDP1 Sarah Leigh Classified gene: TDP1 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v6.160 TDP1 Sarah Leigh Added comment: Comment on list classification: This gene remains amber, as there are only two disease associated variants have been reported (PMID: 12244316;31182267;39576382)
Hereditary neuropathy or pain disorder v6.160 TDP1 Sarah Leigh Gene: tdp1 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v6.159 TDP1 Sarah Leigh Publications for gene: TDP1 were set to 12244316; 31182267; 39576382
Intellectual disability v8.116 TDP1 Sarah Leigh Entity copied from Hereditary neuropathy or pain disorder v6.158
Intellectual disability v8.116 TDP1 Sarah Leigh gene: TDP1 was added
gene: TDP1 was added to Intellectual disability. Sources: Expert Review Amber,South West GLH,UKGTN,Emory Genetics Laboratory,Expert list,NHS GMS
founder-effect tags were added to gene: TDP1.
Mode of inheritance for gene: TDP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TDP1 were set to 12244316; 31182267; 39576382
Phenotypes for gene: TDP1 were set to ?Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1, OMIM:607250
Hereditary neuropathy or pain disorder v6.157 TDP1 Sarah Leigh reviewed gene: TDP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 39576382; Phenotypes: ?Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1, OMIM:607250, spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1, MONDO:0011801; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.157 TDP1 Sarah Leigh Publications for gene: TDP1 were set to 12244316; 31182267
Intellectual disability v8.115 PPP2R5C Sarah Leigh Publications for gene: PPP2R5C were set to 25972378; 39500882; 39978342
Early onset or syndromic epilepsy v7.46 PPP2R5C Sarah Leigh Classified gene: PPP2R5C as Amber List (moderate evidence)
Early onset or syndromic epilepsy v7.46 PPP2R5C Sarah Leigh Gene: ppp2r5c has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v7.45 PPP2R5C Sarah Leigh Added comment: Comment on publications: PMID: 39696819 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Early onset or syndromic epilepsy v7.45 PPP2R5C Sarah Leigh Publications for gene: PPP2R5C were set to 25972378; 39696819; 39978342
Early onset or syndromic epilepsy v7.44 PPP2R5C Sarah Leigh edited their review of gene: PPP2R5C: Changed publications to: 25972378, 39696819, 39978342
Intellectual disability v8.114 PPP2R5C Sarah Leigh edited their review of gene: PPP2R5C: Changed publications to: 25972378, 39696819, 39978342
Intellectual disability v8.114 PPP2R5C Sarah Leigh changed review comment from: PMIDs 25972378; 39500882; 39978342 report twenty one PPP2R5C variants in 30 unrelated individuals with macrocephaly, intellectual disability, seizures and hypotonia (PMIDs 39500882 table 1 & 39978342 table 1 ). Most of these heterozygous variants were de novo (there was one case where this could not be established, PMID: 39696819).
Sources: Literature; to: PMIDs 25972378; 39696819; 39978342 report twenty one PPP2R5C variants in 30 unrelated individuals with macrocephaly, intellectual disability, seizures and hypotonia (PMIDs 39696819 table 1 & 39978342 table 1 ). Most of these heterozygous variants were de novo (there was one case where this could not be established, PMID: 39696819).
Early onset or syndromic epilepsy v7.44 PPP2R5C Sarah Leigh changed review comment from: PMIDs 25972378; 39696819; 39978342 report twenty one PPP2R5C variants in 30 unrelated individuals with macrocephaly, intellectual disability, seizures and hypotonia (PMIDs 39500882 table 1 & 39978342 table 1 ). Most of these heterozygous variants were de novo (there was one case where this could not be established, PMID: 39696819).
Sources: Literature; to: PMIDs 25972378; 39696819; 39978342 report twenty one PPP2R5C variants in 30 unrelated individuals with macrocephaly, intellectual disability, seizures and hypotonia (PMIDs 39696819 table 1 & 39978342 table 1 ). Most of these heterozygous variants were de novo (there was one case where this could not be established, PMID: 39696819).
Sources: Literature
Early onset or syndromic epilepsy v7.44 PPP2R5C Sarah Leigh changed review comment from: PMIDs 25972378; 39500882; 39978342 report twenty one PPP2R5C variants in 30 unrelated individuals with macrocephaly, intellectual disability, seizures and hypotonia (PMIDs 39500882 table 1 & 39978342 table 1 ). Most of these heterozygous variants were de novo (there was one case where this could not be established, PMID: 39696819).
Sources: Literature; to: PMIDs 25972378; 39696819; 39978342 report twenty one PPP2R5C variants in 30 unrelated individuals with macrocephaly, intellectual disability, seizures and hypotonia (PMIDs 39500882 table 1 & 39978342 table 1 ). Most of these heterozygous variants were de novo (there was one case where this could not be established, PMID: 39696819).
Sources: Literature
Early onset or syndromic epilepsy v7.44 PPP2R5C Sarah Leigh Publications for gene: PPP2R5C were set to 25972378; 39500882; 39978342
Intellectual disability v8.114 PPP2R5C Sarah Leigh Added comment: Comment on publications: PMID: 39696819 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.114 PPP2R5C Sarah Leigh Publications for gene: PPP2R5C were set to 25972378; 39500882; 39978342
Intellectual disability v8.113 PPP2R5C Sarah Leigh Classified gene: PPP2R5C as Amber List (moderate evidence)
Intellectual disability v8.113 PPP2R5C Sarah Leigh Gene: ppp2r5c has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v7.43 PPP2R5C Sarah Leigh gene: PPP2R5C was added
gene: PPP2R5C was added to Early onset or syndromic epilepsy. Sources: Literature
Q1_25_ promote_green tags were added to gene: PPP2R5C.
Mode of inheritance for gene: PPP2R5C was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PPP2R5C were set to 25972378; 39500882; 39978342
Phenotypes for gene: PPP2R5C were set to neurodevelopmental disorder
Review for gene: PPP2R5C was set to GREEN
Added comment: PMIDs 25972378; 39500882; 39978342 report twenty one PPP2R5C variants in 30 unrelated individuals with macrocephaly, intellectual disability, seizures and hypotonia (PMIDs 39500882 table 1 & 39978342 table 1 ). Most of these heterozygous variants were de novo (there was one case where this could not be established, PMID: 39696819).
Sources: Literature
Intellectual disability v8.112 PPP2R5C Sarah Leigh gene: PPP2R5C was added
gene: PPP2R5C was added to Intellectual disability. Sources: Literature
Q1_25_ promote_green tags were added to gene: PPP2R5C.
Mode of inheritance for gene: PPP2R5C was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PPP2R5C were set to 25972378; 39500882; 39978342
Phenotypes for gene: PPP2R5C were set to neurodevelopmental disorder
Review for gene: PPP2R5C was set to GREEN
Added comment: PMIDs 25972378; 39500882; 39978342 report twenty one PPP2R5C variants in 30 unrelated individuals with macrocephaly, intellectual disability, seizures and hypotonia (PMIDs 39500882 table 1 & 39978342 table 1 ). Most of these heterozygous variants were de novo (there was one case where this could not be established, PMID: 39696819).
Sources: Literature
Intellectual disability v8.111 GON4L Sarah Leigh Added comment: Comment on publications: PMID: 39500882 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.111 GON4L Sarah Leigh Publications for gene: GON4L were set to 21937992; 26350204; 24896178; 39500882
Intellectual disability v8.110 GON4L Sarah Leigh Phenotypes for gene: GON4L were changed from AUTOSOMAL RECESSIVE MENTAL RETARDATION to prenatal-onset growth impairment and developmental delay
Intellectual disability v8.110 GON4L Sarah Leigh Classified gene: GON4L as Amber List (moderate evidence)
Intellectual disability v8.110 GON4L Sarah Leigh Added comment: Comment on list classification: This gene is rated as amber, as only mild intellectual disability has been associated with GON4L variants (PMID: 39500882).
Intellectual disability v8.110 GON4L Sarah Leigh Gene: gon4l has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.109 GON4L Sarah Leigh edited their review of gene: GON4L: Added comment: PMID: 39500882 reports two consanguineous families where children who are homozygous for terminating GON4L variants, have prenatal-onset growth impairment, developmental delay, and mild intellectual disability. The unaffected parents of both children and an unaffected sibling were heterozygous for the GON4L variants identified. Microcephaly was reported in the affected cases, however, it was now severe. Functional studies in gon4lb-knockout and knockdown zebrafish
revealed distinct morphological and size abnormalities, which were reminiscent of the human phenotype. Human wild type GON4L mRNA was able to rescue the craniofacial cartilage phenotypic in zebrafish larvae PMID: 39500882.; Changed rating: AMBER; Changed publications to: 39500882; Changed phenotypes to: prenatal-onset growth impairment and developmental delay; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hypertrophic cardiomyopathy v4.21 MT-TI Eleanor Williams changed review comment from: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval. However, reviewers note that only the m.4300A>G variant should be looked at.; to: The rating of this gene was initially updated to green following NHS Genomic Medicine Service approval, but after later review it was demoted to amber again before the panel was signed off for GMS use, with the comment that it would be better to be analysed through the WGS panel R135 Paediatric or syndromic cardiomyopathy. Reviewers also noted that only the m.4300A>G variant should be looked at.
Deafness and congenital structural abnormalities v1.27 KIAA0391 Bill Newman gene: KIAA0391 was added
gene: KIAA0391 was added to Deafness and congenital structural abnormalities. Sources: Literature
Mode of inheritance for gene: KIAA0391 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA0391 were set to PMID:34715011; 37558808
Phenotypes for gene: KIAA0391 were set to Sensorineural hearing loss; primary ovarian insufficiency; leukodystrophy
Penetrance for gene: KIAA0391 were set to Complete
Review for gene: KIAA0391 was set to GREEN
Added comment: Note this gene should be called PRORP (also known as MRPP3)

Biallelic hylomorphic missense variants in the metallonuclease domain associated with this phenotype
Sources: Literature
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.40 ACTN2 Cassandra Smith reviewed gene: ACTN2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38311799; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Deafness and congenital structural abnormalities v1.27 DAP3 Bill Newman gene: DAP3 was added
gene: DAP3 was added to Deafness and congenital structural abnormalities. Sources: Literature
Mode of inheritance for gene: DAP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DAP3 were set to PMID:39701103
Phenotypes for gene: DAP3 were set to Sensorineural hearing loss; primary ovarian insufficiency; lactic acidosis; intellectual disability
Penetrance for gene: DAP3 were set to Complete
Mode of pathogenicity for gene: DAP3 was set to Other
Review for gene: DAP3 was set to GREEN
Added comment: This is a new description of hypomorphic biallelic variants resulting in a multi system disorder including SNHL
Biallelic LoF variants are unlikely to viable
Sources: Literature
Respiratory ciliopathies including non-CF bronchiectasis v3.25 CFAP74 Steven Cowman reviewed gene: CFAP74: Rating: GREEN; Mode of pathogenicity: None; Publications: 32555313, 36047773, 39362668; Phenotypes: Primary ciliary dyskinesia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v4.74 HGF Achchuthan Shanmugasundram Phenotypes for gene: HGF were changed from Nonsyndromic Hearing Loss, Mixed; Deafness, autosomal recessive 39, 608265 to Deafness, autosomal recessive 39, OMIM:608265
Monogenic hearing loss v4.73 HGF Achchuthan Shanmugasundram Publications for gene: HGF were set to PMID:11343646; 11564764; 11565020; 12574630; 1386343; 14556002; 14691191; 1531136; 1535333; 15545993; 17467663; 1824873; 1831266; 1837534; 19188684; 19576567; 2142751; 21988987; 21988988; 22763439; 22763448; 2528952; 2531289; 3276728; 7624797; 7854452; 7854453; 8804995; 8898205; 19576567; 27610647
Monogenic hearing loss v4.72 HGF Achchuthan Shanmugasundram Tag Q1_25_ promote_green tag was added to gene: HGF.
Tag Q1_25_ expert_review tag was added to gene: HGF.
Monogenic hearing loss v4.72 HGF Achchuthan Shanmugasundram reviewed gene: HGF: Rating: GREEN; Mode of pathogenicity: None; Publications: 19576567, 30303587; Phenotypes: Deafness, autosomal recessive 39, OMIM:608265; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Familial hypoparathyroidism v2.17 STX16 Treena Cranston reviewed gene: STX16: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v8.109 GON4L Sarah Leigh Publications for gene: GON4L were set to 21937992
Intellectual disability v8.108 PNPLA8 Sarah Leigh Added comment: Comment on publications: PMID: 39082157 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.108 PNPLA8 Sarah Leigh Publications for gene: PNPLA8 were set to 39082157
Early onset or syndromic epilepsy v7.42 PNPLA8 Sarah Leigh Added comment: Comment on publications: PMID: 39082157 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Early onset or syndromic epilepsy v7.42 PNPLA8 Sarah Leigh Publications for gene: PNPLA8 were set to 39082157
Intellectual disability v8.107 PNPLA8 Sarah Leigh Classified gene: PNPLA8 as Amber List (moderate evidence)
Intellectual disability v8.107 PNPLA8 Sarah Leigh Gene: pnpla8 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v7.41 PNPLA8 Sarah Leigh Classified gene: PNPLA8 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v7.41 PNPLA8 Sarah Leigh Gene: pnpla8 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v7.15 PNPLA8 Sarah Leigh Added comment: Comment on publications: PMID: 39082157 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Severe microcephaly v7.15 PNPLA8 Sarah Leigh Publications for gene: PNPLA8 were set to 39082157
Severe microcephaly v7.14 PNPLA8 Sarah Leigh Classified gene: PNPLA8 as Amber List (moderate evidence)
Severe microcephaly v7.14 PNPLA8 Sarah Leigh Gene: pnpla8 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v7.13 PNPLA8 Sarah Leigh gene: PNPLA8 was added
gene: PNPLA8 was added to Severe microcephaly. Sources: Literature
Q1_25_ promote_green tags were added to gene: PNPLA8.
Mode of inheritance for gene: PNPLA8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PNPLA8 were set to 39082157
Phenotypes for gene: PNPLA8 were set to ?Mitochondrial myopathy with lactic acidosis, OMIM:251950; mitochondrial myopathy-lactic acidosis-deafness syndrome MONDO:0016825
Review for gene: PNPLA8 was set to GREEN
Added comment: Biallelic PNPLA8 variants have previously been associated with Mitochondrial myopathy with lactic acidosis, (OMIM:251950). PMID: 39082157 reports a study were microcephaly, global delay and seizures are associated with biallelic PNPLA8 variants. Amongst the unrelated individuals studied, 8/11 had severe microcephaly, 9/11 had epileptic seizures and 8/11 had severe global delay and intellectual disability where it could be measured, 3/11 cases died in childhood and affected siblings (but not genotyped) had died in two other families. Using cerebral organoids generated from human induced pluripotent stem cells, the authors were able to assert that the loss of PNPLA8 led to
developmental defects by reducing the number of basal radial glial cells and upper-layer neurons (PMID: 39082157).
Sources: Literature
Early onset or syndromic epilepsy v7.40 PNPLA8 Sarah Leigh gene: PNPLA8 was added
gene: PNPLA8 was added to Early onset or syndromic epilepsy. Sources: Literature
Q1_25_ promote_green tags were added to gene: PNPLA8.
Mode of inheritance for gene: PNPLA8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PNPLA8 were set to 39082157
Phenotypes for gene: PNPLA8 were set to ?Mitochondrial myopathy with lactic acidosis, OMIM:251950; mitochondrial myopathy-lactic acidosis-deafness syndrome MONDO:0016825
Review for gene: PNPLA8 was set to GREEN
Added comment: Biallelic PNPLA8 variants have previously been associated with Mitochondrial myopathy with lactic acidosis, (OMIM:251950). PMID: 39082157 reports a study were microcephaly, global delay and seizures are associated with biallelic PNPLA8 variants. Amongst the unrelated individuals studied, 8/11 had severe microcephaly, 9/11 had epileptic seizures and 8/11 had severe global delay and intellectual disability where it could be measured, 3/11 cases died in childhood and affected siblings (but not genotyped) had died in two other families. Using cerebral organoids generated from human induced pluripotent stem cells, the authors were able to assert that the loss of PNPLA8 led to
developmental defects by reducing the number of basal radial glial cells and upper-layer neurons (PMID: 39082157).
Sources: Literature
Intellectual disability v8.106 PNPLA8 Sarah Leigh gene: PNPLA8 was added
gene: PNPLA8 was added to Intellectual disability. Sources: Literature
Q1_25_ promote_green tags were added to gene: PNPLA8.
Mode of inheritance for gene: PNPLA8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PNPLA8 were set to 39082157
Phenotypes for gene: PNPLA8 were set to ?Mitochondrial myopathy with lactic acidosis, OMIM:251950; mitochondrial myopathy-lactic acidosis-deafness syndrome MONDO:0016825
Review for gene: PNPLA8 was set to GREEN
Added comment: Biallelic PNPLA8 variants have previously been associated with Mitochondrial myopathy with lactic acidosis, (OMIM:251950). PMID: 39082157 reports a study were microcephaly, global delay and seizures are associated with biallelic PNPLA8 variants. Amongst the unrelated individuals studied, 8/11 had severe microcephaly, 9/11 had epileptic seizures and 8/11 had severe global delay and intellectual disability where it could be measured, 3/11 cases died in childhood and affected siblings (but not genotyped) had died in two other families. Using cerebral organoids generated from human induced pluripotent stem cells, the authors were able to assert that the loss of PNPLA8 led to
developmental defects by reducing the number of basal radial glial cells and upper-layer neurons (PMID: 39082157).
Sources: Literature
Hypogonadotropic hypogonadism (GMS) v3.25 RNF216 Sarah Leigh Classified gene: RNF216 as Amber List (moderate evidence)
Hypogonadotropic hypogonadism (GMS) v3.25 RNF216 Sarah Leigh Gene: rnf216 has been classified as Amber List (Moderate Evidence).
Hypogonadotropic hypogonadism (GMS) v3.24 RNF216 Sarah Leigh Added comment: Comment on publications: PMID: 39444518 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Hypogonadotropic hypogonadism (GMS) v3.24 RNF216 Sarah Leigh Publications for gene: RNF216 were set to 39444518; 23656588; 25841028
Hypogonadotropic hypogonadism (GMS) v3.23 RNF216 Sarah Leigh gene: RNF216 was added
gene: RNF216 was added to Hypogonadotropic hypogonadism (GMS). Sources: Literature
Q1_25_ promote_green tags were added to gene: RNF216.
Mode of inheritance for gene: RNF216 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNF216 were set to 39444518; 23656588; 25841028
Phenotypes for gene: RNF216 were set to Cerebellar ataxia and hypogonadotropic hypogonadism, OMIM:212840; cerebellar ataxia-hypogonadism syndrome, MONDO:0008935
Review for gene: RNF216 was set to GREEN
Added comment: RNF216 variants are associated with Cerebellar ataxia and hypogonadotropic hypogonadism (OMIM:212840). At least seven RNF216 variants have been reported in five unrelated cases of OMIM:212840 (PMID: 39444518; 23656588;25841028).
Sources: Literature
Intellectual disability v8.105 PLEKHG1 Sarah Leigh Added comment: Comment on publications: PMID: 39202455 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques
Intellectual disability v8.105 PLEKHG1 Sarah Leigh Publications for gene: PLEKHG1 were set to 39202455; 30659137
Intellectual disability v8.104 PLEKHG1 Sarah Leigh gene: PLEKHG1 was added
gene: PLEKHG1 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: PLEKHG1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PLEKHG1 were set to 39202455; 30659137
Phenotypes for gene: PLEKHG1 were set to Spastic diplegia and psychomotor developmental delay
Review for gene: PLEKHG1 was set to RED
Added comment: PMID: 39202455 reports a de novo heterozygous PLEKHG1 variant (NM_001029884.3 c.370A>G, p.Thr124Ala) in a child with spastic diplegia and psychomotor developmental delay. The child also had cystic fibrosis, due causative CFTR variants inherited from the parents.
A genome-wide association meta-analysis has previously associated the PLEKHG1 locus with white matter hyperintensities (PMID: 30659137).
Sources: Literature
Skeletal dysplasia v7.26 ISCA-37447-Loss Arina Puzriakova edited their review of Region: ISCA-37447-Loss: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Intellectual disability v8.103 ISCA-37447-Loss Arina Puzriakova Classified Region: ISCA-37447-Loss as Green List (high evidence)
Intellectual disability v8.103 ISCA-37447-Loss Arina Puzriakova Region: isca-37447-loss has been classified as Green List (High Evidence).
Skeletal dysplasia v7.26 ISCA-37447-Loss Arina Puzriakova Classified Region: ISCA-37447-Loss as Green List (high evidence)
Skeletal dysplasia v7.26 ISCA-37447-Loss Arina Puzriakova Region: isca-37447-loss has been classified as Green List (High Evidence).
Skeletal dysplasia v7.25 ISCA-37447-Loss Arina Puzriakova Added comment: Comment on mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed) has been agreed for the R104 Skeletal dysplasia panel as only Kagami-Ogata syndrome includes skeletal abnormalities.
Skeletal dysplasia v7.25 ISCA-37447-Loss Arina Puzriakova Mode of inheritance for Region: ISCA-37447-Loss was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Intellectual disability v8.102 ISCA-37447-Loss Arina Puzriakova Added comment: Comment on mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown has been agreed for the R29 Intellectual disability panel. This would capture both imprinting patterns where there is clinical overlap between Kagami-Ogata and Temple syndrome which are both relevant to this panel.

These disorders are suitable for R27 Paediatric disorders and R69 Hypotonic infant super panels (included via R29)
Intellectual disability v8.102 ISCA-37447-Loss Arina Puzriakova Mode of inheritance for Region: ISCA-37447-Loss was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v8.101 ARHGEF40 Sarah Leigh Tag watchlist tag was added to gene: ARHGEF40.
Skeletal dysplasia v7.24 ISCA-37447-Loss Arina Puzriakova Region: ISCA-37447-Loss was added
Region: ISCA-37447-Loss was added to Skeletal dysplasia. Sources: ClinGen
Mode of inheritance for Region: ISCA-37447-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-37447-Loss were set to 20585555; 24801763; 27406249; 33579810; 18176563; 28640239
Phenotypes for Region: ISCA-37447-Loss were set to Kagami-Ogata syndrome, OMIM:608149; Temple syndrome, OMIM:616222
Review for Region: ISCA-37447-Loss was set to GREEN
Added comment: Multiple unrelated cases curated in ClinGen - sufficient evidence to add this region (https://search.clinicalgenome.org/kb/gene-dosage/region/ISCA-37447)

DLK1-MEG3 Intergenic Region includes the paternally expressed DLK1 gene, the 2 differentially methylated regions (DMRs) DLK1/MEG3:IG-DMR and MEG3:TSS-DMR, and the 5' end of the maternally expressed gene MEG3 (4 exons).

The phenotype depends on the parental origin: Kagami Ogata syndrome/KOS (maternally derived imprinting) or Temple syndrome/TS (paternally derived imprinting)

Kagami-Ogata syndrome is characterized by typical facial features, skeletal abnormalities (including ""coat-hanger ribs"", and bell-shaped thorax), abdominal wall defects, and developmental delay.

Temple syndrome is a less specific phenotype including intrauterine and postnatal growth restriction, hypotonia, feeding difficulties in infancy, truncal obesity, and small feet and hands.
Sources: ClinGen
Intellectual disability v8.101 ISCA-37447-Loss Arina Puzriakova Region: ISCA-37447-Loss was added
Region: ISCA-37447-Loss was added to Intellectual disability. Sources: ClinGen
Mode of inheritance for Region: ISCA-37447-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-37447-Loss were set to 20585555; 24801763; 27406249; 33579810; 18176563; 28640239
Phenotypes for Region: ISCA-37447-Loss were set to Kagami-Ogata syndrome, OMIM:608149; Temple syndrome, OMIM:616222
Review for Region: ISCA-37447-Loss was set to GREEN
Added comment: Multiple unrelated cases curated in ClinGen - sufficient evidence to add this region (https://search.clinicalgenome.org/kb/gene-dosage/region/ISCA-37447)

DLK1-MEG3 Intergenic Region includes the paternally expressed DLK1 gene, the 2 differentially methylated regions (DMRs) DLK1/MEG3:IG-DMR and MEG3:TSS-DMR, and the 5' end of the maternally expressed gene MEG3 (4 exons).

The phenotype depends on the parental origin: Kagami Ogata syndrome/KOS (maternally derived imprinting) or Temple syndrome/TS (paternally derived imprinting)

Kagami-Ogata syndrome is characterized by typical facial features, skeletal abnormalities (including ""coat-hanger ribs"", and bell-shaped thorax), abdominal wall defects, and developmental delay.

Temple syndrome is a less specific phenotype including intrauterine and postnatal growth restriction, hypotonia, feeding difficulties in infancy, truncal obesity, and small feet and hands.
Sources: ClinGen
Skeletal dysplasia v7.23 EXOC6B Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: EXOC6B.
Skeletal dysplasia v7.23 TOMM7 Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: TOMM7.
Tag Q3_24_NHS_review was removed from gene: TOMM7.
Early onset or syndromic epilepsy v7.39 TRPM7 Achchuthan Shanmugasundram Tag Q1_23_promote_green was removed from gene: TRPM7.
Tag Q1_25_ promote_green tag was added to gene: TRPM7.
Likely inborn error of metabolism v7.12 TRPM7 Achchuthan Shanmugasundram Tag Q1_23_promote_green was removed from gene: TRPM7.
Tag Q1_25_ promote_green tag was added to gene: TRPM7.
Fetal anomalies v5.78 ESAM Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ESAM.
Tag Q4_23_NHS_review was removed from gene: ESAM.
Intellectual disability v8.100 ATP11A Sarah Leigh Publications for gene: ATP11A were set to 34403372; 39432785
Intellectual disability v8.99 ATP11A Sarah Leigh Added comment: Comment on publications: PMID: 39432785 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.99 ATP11A Sarah Leigh Publications for gene: ATP11A were set to 34403372; 39432785
Intellectual disability v8.98 ATP11A Sarah Leigh reviewed gene: ATP11A: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
White matter disorders and cerebral calcification - narrow panel v6.6 ATP11A Sarah Leigh Added comment: Comment on publications: PMID: 39432785 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques
White matter disorders and cerebral calcification - narrow panel v6.6 ATP11A Sarah Leigh Publications for gene: ATP11A were set to 34403372; 39432785
White matter disorders and cerebral calcification - narrow panel v6.5 ATP11A Sarah Leigh Tag Q1_25_ promote_green tag was added to gene: ATP11A.
White matter disorders and cerebral calcification - narrow panel v6.5 ATP11A Sarah Leigh reviewed gene: ATP11A: Rating: GREEN; Mode of pathogenicity: None; Publications: 34403372, 39432785; Phenotypes: Leukodystrophy, hypomyelinating, 24, OMIM:619851, leukodystrophy, hypomyelinating, 24 MONDO:0859242; Mode of inheritance: None
Fetal anomalies v5.78 CNBP_CCTG Achchuthan Shanmugasundram Tag Q1_24_promote_green was removed from STR: CNBP_CCTG.
Fetal anomalies v5.78 CNBP_CCTG Achchuthan Shanmugasundram edited their review of STR: CNBP_CCTG: Changed rating: AMBER
Intellectual disability v8.98 ATP11A Sarah Leigh Publications for gene: ATP11A were set to 34403372
White matter disorders and cerebral calcification - narrow panel v6.5 ATP11A Sarah Leigh Publications for gene: ATP11A were set to 34403372
Fetal anomalies v5.78 CNBP_CCTG Achchuthan Shanmugasundram commented on STR: CNBP_CCTG
Fetal anomalies v5.78 KIF26A Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: KIF26A.
Tag Q1_25_ promote_green was removed from gene: KIF26A.
Fetal anomalies v5.78 DAW1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: DAW1.
Tag Q1_25_ promote_green was removed from gene: DAW1.
Fetal anomalies v5.78 ZRSR2 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: ZRSR2.
Tag Q1_25_ promote_green was removed from gene: ZRSR2.
Fetal anomalies v5.78 ZFX Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: ZFX.
Tag Q1_25_ promote_green was removed from gene: ZFX.
Fetal anomalies v5.78 WDR44 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: WDR44.
Tag Q1_25_ promote_green was removed from gene: WDR44.
Fetal anomalies v5.78 WBP4 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: WBP4.
Tag Q1_25_ promote_green was removed from gene: WBP4.
Fetal anomalies v5.78 WASHC5 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: WASHC5.
Tag Q1_25_ promote_green was removed from gene: WASHC5.
Fetal anomalies v5.78 USP14 Achchuthan Shanmugasundram Tag Q2_24_promote_green was removed from gene: USP14.
Fetal anomalies v5.78 UFSP2 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: UFSP2.
Tag Q1_25_ promote_green was removed from gene: UFSP2.
Fetal anomalies v5.78 U2AF2 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: U2AF2.
Tag Q1_25_ promote_green was removed from gene: U2AF2.
Fetal anomalies v5.78 TSHZ3 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: TSHZ3.
Tag Q1_25_ promote_green was removed from gene: TSHZ3.
Fetal anomalies v5.78 TRIT1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: TRIT1.
Tag Q1_25_ promote_green was removed from gene: TRIT1.
Fetal anomalies v5.78 TONSL Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: TONSL.
Tag Q1_25_ promote_green was removed from gene: TONSL.
Fetal anomalies v5.78 TOGARAM1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: TOGARAM1.
Tag Q1_25_ promote_green was removed from gene: TOGARAM1.
Fetal anomalies v5.78 THSD1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: THSD1.
Tag Q1_25_ promote_green was removed from gene: THSD1.
Fetal anomalies v5.78 TBR1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: TBR1.
Tag Q1_25_ promote_green was removed from gene: TBR1.
Fetal anomalies v5.78 TAF8 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: TAF8.
Tag Q1_25_ promote_green was removed from gene: TAF8.
Fetal anomalies v5.78 SNF8 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: SNF8.
Tag Q1_23_promote_green was removed from gene: SNF8.
Fetal anomalies v5.78 SNAP25 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: SNAP25.
Tag Q1_25_ promote_green was removed from gene: SNAP25.
Fetal anomalies v5.78 SMPD1 Achchuthan Shanmugasundram Tag Q1_25_ demote_amber was removed from gene: SMPD1.
Tag Q1_25_ NHS_review was removed from gene: SMPD1.
Fetal anomalies v5.78 SLC4A10 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: SLC4A10.
Tag Q1_25_ promote_green was removed from gene: SLC4A10.
Fetal anomalies v5.78 SLC34A1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: SLC34A1.
Tag Q1_25_ promote_green was removed from gene: SLC34A1.
Fetal anomalies v5.78 SLC25A4 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: SLC25A4.
Tag Q1_25_ promote_green was removed from gene: SLC25A4.
Fetal anomalies v5.78 SETD1A Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: SETD1A.
Tag Q1_25_ promote_green was removed from gene: SETD1A.
Fetal anomalies v5.78 SCYL2 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: SCYL2.
Tag Q1_25_ promote_green was removed from gene: SCYL2.
Fetal anomalies v5.78 SASS6 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: SASS6.
Tag Q1_25_ promote_green was removed from gene: SASS6.
Fetal anomalies v5.78 RSPRY1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: RSPRY1.
Tag Q1_25_ promote_green was removed from gene: RSPRY1.
Fetal anomalies v5.78 RSPO2 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: RSPO2.
Tag Q1_25_ promote_green was removed from gene: RSPO2.
Fetal anomalies v5.78 RRAS Achchuthan Shanmugasundram Tag Q2_24_promote_green was removed from gene: RRAS.
Tag Q1_25_ promote_green was removed from gene: RRAS.
Fetal anomalies v5.78 RRAGC Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: RRAGC.
Tag Q1_25_ promote_green was removed from gene: RRAGC.
Fetal anomalies v5.78 RPL13 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: RPL13.
Tag Q1_25_ promote_green was removed from gene: RPL13.
Fetal anomalies v5.78 ROBO1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: ROBO1.
Tag Q1_24_MOI was removed from gene: ROBO1.
Fetal anomalies v5.78 RNU4-2 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: RNU4-2.
Tag Q1_25_ promote_green was removed from gene: RNU4-2.
Fetal anomalies v5.78 RFWD3 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: RFWD3.
Tag Q1_25_ promote_green was removed from gene: RFWD3.
Fetal anomalies v5.78 RAP1B Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: RAP1B.
Tag Q1_25_ promote_green was removed from gene: RAP1B.
Fetal anomalies v5.78 RAB34 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: RAB34.
Tag Q1_25_ promote_green was removed from gene: RAB34.
Fetal anomalies v5.78 PUM1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: PUM1.
Tag Q1_25_ promote_green was removed from gene: PUM1.
Fetal anomalies v5.78 PSMF1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: PSMF1.
Tag Q1_25_ promote_green was removed from gene: PSMF1.
Fetal anomalies v5.78 PLS3 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: PLS3.
Tag Q1_25_ promote_green was removed from gene: PLS3.
Rhabdomyolysis and metabolic muscle disorders v5.4 ATP2A2 Sarah Leigh Classified gene: ATP2A2 as Amber List (moderate evidence)
Rhabdomyolysis and metabolic muscle disorders v5.4 ATP2A2 Sarah Leigh Gene: atp2a2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v5.78 PLD1 Achchuthan Shanmugasundram Tag Q1_25_ demote_amber was removed from gene: PLD1.
Tag Q1_25_ NHS_review was removed from gene: PLD1.
Tag Q2_24_expert_review was removed from gene: PLD1.
Fetal anomalies v5.78 PKDCC Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: PKDCC.
Tag Q1_25_ promote_green was removed from gene: PKDCC.
Fetal anomalies v5.78 PIP5K1C Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: PIP5K1C.
Tag Q1_25_ promote_green was removed from gene: PIP5K1C.
Fetal anomalies v5.78 PIGS Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: PIGS.
Tag Q1_25_ promote_green was removed from gene: PIGS.
Fetal anomalies v5.78 PI4K2A Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: PI4K2A.
Tag Q1_25_ promote_green was removed from gene: PI4K2A.
Fetal anomalies v5.78 PAN2 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: PAN2.
Tag Q1_25_ promote_green was removed from gene: PAN2.
Rhabdomyolysis and metabolic muscle disorders v5.3 ATP2A2 Sarah Leigh gene: ATP2A2 was added
gene: ATP2A2 was added to Rhabdomyolysis and metabolic muscle disorders. Sources: Literature
Q1_25_ promote_green tags were added to gene: ATP2A2.
Mode of inheritance for gene: ATP2A2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ATP2A2 were set to 39970126
Phenotypes for gene: ATP2A2 were set to Dominant rhabdomyolysis
Review for gene: ATP2A2 was set to GREEN
Added comment: PMID: 39970126 reports a rare heterozygous missense ATP2A2 (alias symbol: SERCA2) variant (12:110777348G>A, c.1583G>A, p.R528Q) in 14 affected individuals from three unrelated families with recurrent rhabdomyolysis (an unaffected 6 year old child also carried the variant, however, symptoms of rhabdomyolysis may develop as he gets older). Haplotype analysis confirmed that the families were not related. In vitro and in vivo studies suggest that the variant affects ATP2A2 normal function, resulting in abnormal intracellular Ca2+ homeostasis in skeletal muscle, resulting in rhabdomyolysis.
Morphant zebrafish embryos (atp2a2a knockdown) had morphological and functional muscle abnormalities, including a reduced body length and trunk muscle area and a reduced locomotor activity in zebrafish larvae. This phenotype was rescued by wild-type human ATP2A2 mRNA but not variant ATP2A2 mRNA.
Sources: Literature
Fetal anomalies v5.78 NUDT2 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: NUDT2.
Tag Q1_25_ promote_green was removed from gene: NUDT2.
Fetal anomalies v5.78 NSUN6 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: NSUN6.
Tag Q1_25_ promote_green was removed from gene: NSUN6.
Fetal anomalies v5.78 NLRP3 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: NLRP3.
Tag Q1_25_ promote_green was removed from gene: NLRP3.
Fetal anomalies v5.78 MYBBP1A Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: MYBBP1A.
Tag Q3_24_NHS_review was removed from gene: MYBBP1A.
Fetal anomalies v5.78 MSTO1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: MSTO1.
Tag Q1_24_MOI was removed from gene: MSTO1.
Fetal anomalies v5.78 MDFIC Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: MDFIC.
Tag Q2_24_promote_green was removed from gene: MDFIC.
Fetal anomalies v5.78 MAX Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: MAX.
Tag Q1_25_ promote_green was removed from gene: MAX.
Fetal anomalies v5.78 MAP4K4 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: MAP4K4.
Tag Q1_25_ promote_green was removed from gene: MAP4K4.
Fetal anomalies v5.78 LOX Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: LOX.
Tag Q1_25_ promote_green was removed from gene: LOX.
Fetal anomalies v5.78 LNPK Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: LNPK.
Tag Q1_25_ promote_green was removed from gene: LNPK.
Fetal anomalies v5.78 LIPT2 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: LIPT2.
Tag Q1_25_ promote_green was removed from gene: LIPT2.
Fetal anomalies v5.78 LAMB2 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: LAMB2.
Tag Q1_25_ promote_green was removed from gene: LAMB2.
Fetal anomalies v5.78 LAMA5 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: LAMA5.
Tag Q1_25_ promote_green was removed from gene: LAMA5.
Fetal anomalies v5.78 KMT2B Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: KMT2B.
Tag Q1_25_ promote_green was removed from gene: KMT2B.
Fetal anomalies v5.78 KIF5B Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: KIF5B.
Tag Q1_25_ promote_green was removed from gene: KIF5B.
Fetal anomalies v5.78 KIF24 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: KIF24.
Tag Q1_25_ promote_green was removed from gene: KIF24.
Fetal anomalies v5.78 KDM2B Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: KDM2B.
Tag Q1_25_ promote_green was removed from gene: KDM2B.
Fetal anomalies v5.78 KDELR2 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: KDELR2.
Tag Q1_25_ promote_green was removed from gene: KDELR2.
Fetal anomalies v5.78 KCNK9 Achchuthan Shanmugasundram Tag Q2_24_promote_green was removed from gene: KCNK9.
Tag Q2_24_NHS_review was removed from gene: KCNK9.
Fetal anomalies v5.78 KCNK3 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: KCNK3.
Tag Q1_25_ promote_green was removed from gene: KCNK3.
Fetal anomalies v5.78 INTS11 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: INTS11.
Tag Q1_25_ promote_green was removed from gene: INTS11.
Fetal anomalies v5.78 HECTD4 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: HECTD4.
Tag Q1_25_ promote_green was removed from gene: HECTD4.
Fetal anomalies v5.78 GON4L Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: GON4L.
Tag Q1_25_ promote_green was removed from gene: GON4L.
Fetal anomalies v5.78 GNB2 Achchuthan Shanmugasundram Tag Q2_24_promote_green was removed from gene: GNB2.
Tag Q2_24_NHS_review was removed from gene: GNB2.
Fetal anomalies v5.78 FUZ Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: FUZ.
Tag Q1_25_ promote_green was removed from gene: FUZ.
Fetal anomalies v5.78 FTO Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: FTO.
Tag Q1_25_ promote_green was removed from gene: FTO.
Fetal anomalies v5.78 FOXP4 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: FOXP4.
Tag Q1_25_ promote_green was removed from gene: FOXP4.
Fetal anomalies v5.78 FOSL2 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: FOSL2.
Tag Q1_25_ promote_green was removed from gene: FOSL2.
Fetal anomalies v5.78 FN1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: FN1.
Tag Q1_25_ promote_green was removed from gene: FN1.
Fetal anomalies v5.78 FILIP1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: FILIP1.
Tag Q1_25_ promote_green was removed from gene: FILIP1.
Fetal anomalies v5.78 FAS Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: FAS.
Tag Q1_25_ promote_green was removed from gene: FAS.
Fetal anomalies v5.78 ERI1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: ERI1.
Tag Q1_25_ promote_green was removed from gene: ERI1.
Fetal anomalies v5.78 ENG Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: ENG.
Tag Q1_25_ promote_green was removed from gene: ENG.
Fetal anomalies v5.78 EMG1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: EMG1.
Tag Q1_23_promote_green was removed from gene: EMG1.
Fetal anomalies v5.78 EFCAB1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: EFCAB1.
Tag Q1_25_ promote_green was removed from gene: EFCAB1.
Fetal anomalies v5.78 DRG1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: DRG1.
Tag Q1_25_ promote_green was removed from gene: DRG1.
Fetal anomalies v5.78 DPYSL5 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: DPYSL5.
Tag Q1_25_ promote_green was removed from gene: DPYSL5.
Fetal anomalies v5.78 DLG5 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: DLG5.
Tag Q1_25_ promote_green was removed from gene: DLG5.
Fetal anomalies v5.78 DHX30 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: DHX30.
Tag Q1_25_ promote_green was removed from gene: DHX30.
Fetal anomalies v5.78 DDRGK1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: DDRGK1.
Tag Q1_25_ promote_green was removed from gene: DDRGK1.
Fetal anomalies v5.78 CSGALNACT1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: CSGALNACT1.
Tag Q1_25_ promote_green was removed from gene: CSGALNACT1.
Fetal anomalies v5.78 CNOT2 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: CNOT2.
Tag Q1_25_ promote_green was removed from gene: CNOT2.
Fetal anomalies v5.78 CEP295 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: CEP295.
Tag Q1_25_ promote_green was removed from gene: CEP295.
Fetal anomalies v5.78 CDK10 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: CDK10.
Tag Q1_25_ promote_green was removed from gene: CDK10.
Fetal anomalies v5.78 CDH2 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: CDH2.
Tag Q1_25_ promote_green was removed from gene: CDH2.
Fetal anomalies v5.78 CBY1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: CBY1.
Tag Q1_25_ promote_green was removed from gene: CBY1.
Fetal anomalies v5.78 CASP2 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: CASP2.
Tag Q1_25_ promote_green was removed from gene: CASP2.
Fetal anomalies v5.78 CACNA1S Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: CACNA1S.
Tag Q1_25_ promote_green was removed from gene: CACNA1S.
Fetal anomalies v5.78 C16orf62 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: C16orf62.
Tag Q1_25_ promote_green was removed from gene: C16orf62.
Fetal anomalies v5.78 ATG7 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: ATG7.
Tag Q1_25_ promote_green was removed from gene: ATG7.
Fetal anomalies v5.78 ASXL3 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: ASXL3.
Tag Q1_25_ promote_green was removed from gene: ASXL3.
Fetal anomalies v5.78 AMOTL1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: AMOTL1.
Tag Q1_25_ promote_green was removed from gene: AMOTL1.
Fetal anomalies v5.78 AL117258.1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: AL117258.1.
Tag Q1_25_ promote_green was removed from gene: AL117258.1.
Fetal anomalies v5.78 ADD1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: ADD1.
Tag Q1_25_ promote_green was removed from gene: ADD1.
Fetal anomalies v5.78 ADAMTS15 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: ADAMTS15.
Tag Q1_25_ promote_green was removed from gene: ADAMTS15.
Fetal anomalies v5.78 ACBD6 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: ACBD6.
Tag Q1_25_ promote_green was removed from gene: ACBD6.
Fetal anomalies v5.78 ZRSR2 Achchuthan Shanmugasundram edited their review of gene: ZRSR2: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to X-LINKED: hemizygous mutation in males, biallelic mutations in females following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v5.78 ZFX Achchuthan Shanmugasundram edited their review of gene: ZFX: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) in females following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Fetal anomalies v5.78 WDR44 Achchuthan Shanmugasundram edited their review of gene: WDR44: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to X-LINKED: hemizygous mutation in males, biallelic mutations in females following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v5.78 WBP4 Achchuthan Shanmugasundram edited their review of gene: WBP4: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 WASHC5 Achchuthan Shanmugasundram edited their review of gene: WASHC5: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 USP14 Achchuthan Shanmugasundram commented on gene: USP14: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Fetal anomalies v5.78 UFSP2 Achchuthan Shanmugasundram edited their review of gene: UFSP2: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.78 U2AF2 Achchuthan Shanmugasundram edited their review of gene: U2AF2: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.78 TSHZ3 Achchuthan Shanmugasundram edited their review of gene: TSHZ3: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.78 TRIT1 Achchuthan Shanmugasundram edited their review of gene: TRIT1: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 TONSL Achchuthan Shanmugasundram edited their review of gene: TONSL: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 TOGARAM1 Achchuthan Shanmugasundram edited their review of gene: TOGARAM1: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 THSD1 Achchuthan Shanmugasundram edited their review of gene: THSD1: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 TBR1 Achchuthan Shanmugasundram edited their review of gene: TBR1: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.78 TAF8 Achchuthan Shanmugasundram edited their review of gene: TAF8: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 SNF8 Achchuthan Shanmugasundram edited their review of gene: SNF8: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 SNAP25 Achchuthan Shanmugasundram edited their review of gene: SNAP25: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.78 SMPD1 Achchuthan Shanmugasundram edited their review of gene: SMPD1: Added comment: The rating of this gene has been updated to amber following NHS Genomic Medicine Service approval.; Changed rating: AMBER
Fetal anomalies v5.78 SLC4A10 Achchuthan Shanmugasundram edited their review of gene: SLC4A10: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 SLC34A1 Achchuthan Shanmugasundram edited their review of gene: SLC34A1: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 SLC25A4 Achchuthan Shanmugasundram edited their review of gene: SLC25A4: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.78 SETD1A Achchuthan Shanmugasundram edited their review of gene: SETD1A: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v5.78 SCYL2 Achchuthan Shanmugasundram edited their review of gene: SCYL2: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 SASS6 Achchuthan Shanmugasundram edited their review of gene: SASS6: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 RSPRY1 Achchuthan Shanmugasundram edited their review of gene: RSPRY1: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 RSPO2 Achchuthan Shanmugasundram edited their review of gene: RSPO2: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 RRAS Achchuthan Shanmugasundram edited their review of gene: RRAS: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v5.78 RRAGC Achchuthan Shanmugasundram edited their review of gene: RRAGC: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.78 RPL13 Achchuthan Shanmugasundram edited their review of gene: RPL13: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v5.78 ROBO1 Achchuthan Shanmugasundram edited their review of gene: ROBO1: Added comment: The mode of inheritance of this gene has been updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 RNU4-2 Achchuthan Shanmugasundram edited their review of gene: RNU4-2: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.78 RFWD3 Achchuthan Shanmugasundram edited their review of gene: RFWD3: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 RAP1B Achchuthan Shanmugasundram edited their review of gene: RAP1B: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.78 RAB34 Achchuthan Shanmugasundram edited their review of gene: RAB34: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 PUM1 Achchuthan Shanmugasundram edited their review of gene: PUM1: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.78 PSMF1 Achchuthan Shanmugasundram edited their review of gene: PSMF1: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 PLS3 Achchuthan Shanmugasundram edited their review of gene: PLS3: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) in females following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Fetal anomalies v5.78 PLD1 Achchuthan Shanmugasundram edited their review of gene: PLD1: Added comment: The rating of this gene has been updated to amber following NHS Genomic Medicine Service approval.; Changed rating: AMBER
Fetal anomalies v5.78 PKDCC Achchuthan Shanmugasundram edited their review of gene: PKDCC: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 PIP5K1C Achchuthan Shanmugasundram edited their review of gene: PIP5K1C: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 PIGS Achchuthan Shanmugasundram edited their review of gene: PIGS: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 PI4K2A Achchuthan Shanmugasundram edited their review of gene: PI4K2A: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 PAN2 Achchuthan Shanmugasundram edited their review of gene: PAN2: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 NUDT2 Achchuthan Shanmugasundram edited their review of gene: NUDT2: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 NSUN6 Achchuthan Shanmugasundram edited their review of gene: NSUN6: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 NLRP3 Achchuthan Shanmugasundram edited their review of gene: NLRP3: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.78 MYBBP1A Achchuthan Shanmugasundram reviewed gene: MYBBP1A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 MSTO1 Achchuthan Shanmugasundram edited their review of gene: MSTO1: Added comment: The mode of inheritance of this gene has been updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 MDFIC Achchuthan Shanmugasundram commented on gene: MDFIC: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Fetal anomalies v5.78 MAX Achchuthan Shanmugasundram edited their review of gene: MAX: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.78 MAP4K4 Achchuthan Shanmugasundram edited their review of gene: MAP4K4: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.78 LOX Achchuthan Shanmugasundram edited their review of gene: LOX: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 LNPK Achchuthan Shanmugasundram edited their review of gene: LNPK: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 LIPT2 Achchuthan Shanmugasundram edited their review of gene: LIPT2: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 LAMB2 Achchuthan Shanmugasundram edited their review of gene: LAMB2: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 LAMA5 Achchuthan Shanmugasundram edited their review of gene: LAMA5: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 KMT2B Achchuthan Shanmugasundram edited their review of gene: KMT2B: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.78 KIF5B Achchuthan Shanmugasundram edited their review of gene: KIF5B: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.78 KIF26A Achchuthan Shanmugasundram edited their review of gene: KIF26A: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 KIF24 Achchuthan Shanmugasundram edited their review of gene: KIF24: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 KDM2B Achchuthan Shanmugasundram edited their review of gene: KDM2B: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.78 KDELR2 Achchuthan Shanmugasundram edited their review of gene: KDELR2: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 KCNK9 Achchuthan Shanmugasundram commented on gene: KCNK9: The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed) following NHS Genomic Medicine Service approval.
Fetal anomalies v5.78 KCNK3 Achchuthan Shanmugasundram edited their review of gene: KCNK3: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.78 KCNC3 Achchuthan Shanmugasundram edited their review of gene: KCNC3: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.78 INTS11 Achchuthan Shanmugasundram edited their review of gene: INTS11: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 HECTD4 Achchuthan Shanmugasundram edited their review of gene: HECTD4: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 GON4L Achchuthan Shanmugasundram edited their review of gene: GON4L: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 GNB2 Achchuthan Shanmugasundram commented on gene: GNB2: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Fetal anomalies v5.78 FUZ Achchuthan Shanmugasundram edited their review of gene: FUZ: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 FTO Achchuthan Shanmugasundram edited their review of gene: FTO: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 FOXP4 Achchuthan Shanmugasundram edited their review of gene: FOXP4: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v5.78 FOSL2 Achchuthan Shanmugasundram edited their review of gene: FOSL2: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.78 FN1 Achchuthan Shanmugasundram edited their review of gene: FN1: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v5.78 FILIP1 Achchuthan Shanmugasundram edited their review of gene: FILIP1: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 FAS Achchuthan Shanmugasundram edited their review of gene: FAS: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v5.78 ESAM Achchuthan Shanmugasundram commented on gene: ESAM: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Fetal anomalies v5.78 ERI1 Achchuthan Shanmugasundram edited their review of gene: ERI1: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 ENG Achchuthan Shanmugasundram edited their review of gene: ENG: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.78 EMG1 Achchuthan Shanmugasundram edited their review of gene: EMG1: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 EFCAB1 Achchuthan Shanmugasundram edited their review of gene: EFCAB1: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 DRG1 Achchuthan Shanmugasundram edited their review of gene: DRG1: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 DPYSL5 Achchuthan Shanmugasundram edited their review of gene: DPYSL5: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.78 DLG5 Achchuthan Shanmugasundram edited their review of gene: DLG5: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 DHX30 Achchuthan Shanmugasundram edited their review of gene: DHX30: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.78 DDRGK1 Achchuthan Shanmugasundram edited their review of gene: DDRGK1: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 DAW1 Achchuthan Shanmugasundram edited their review of gene: DAW1: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 CSGALNACT1 Achchuthan Shanmugasundram edited their review of gene: CSGALNACT1: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 CNOT2 Achchuthan Shanmugasundram edited their review of gene: CNOT2: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.78 CEP295 Achchuthan Shanmugasundram edited their review of gene: CEP295: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 CDK10 Achchuthan Shanmugasundram edited their review of gene: CDK10: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 CDH2 Achchuthan Shanmugasundram edited their review of gene: CDH2: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v5.78 CBY1 Achchuthan Shanmugasundram edited their review of gene: CBY1: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 CASP2 Achchuthan Shanmugasundram edited their review of gene: CASP2: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 CACNA1S Achchuthan Shanmugasundram edited their review of gene: CACNA1S: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 C16orf62 Achchuthan Shanmugasundram edited their review of gene: C16orf62: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 ATG7 Achchuthan Shanmugasundram edited their review of gene: ATG7: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 ASXL3 Achchuthan Shanmugasundram edited their review of gene: ASXL3: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.78 AMOTL1 Achchuthan Shanmugasundram edited their review of gene: AMOTL1: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.78 AL117258.1 Achchuthan Shanmugasundram edited their review of gene: AL117258.1: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 ADD1 Achchuthan Shanmugasundram edited their review of gene: ADD1: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v5.78 ADAMTS15 Achchuthan Shanmugasundram edited their review of gene: ADAMTS15: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.78 ACBD6 Achchuthan Shanmugasundram edited their review of gene: ACBD6: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.77 ZRSR2 Achchuthan Shanmugasundram Source Expert Review Green was added to ZRSR2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 ZFX Achchuthan Shanmugasundram Source Expert Review Green was added to ZFX.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 WDR44 Achchuthan Shanmugasundram Source Expert Review Green was added to WDR44.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 WBP4 Achchuthan Shanmugasundram Source Expert Review Green was added to WBP4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 WASHC5 Achchuthan Shanmugasundram Source Expert Review Green was added to WASHC5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 USP14 Achchuthan Shanmugasundram Source NHS GMS was added to USP14.
Source Expert Review Green was added to USP14.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 UFSP2 Achchuthan Shanmugasundram Source Expert Review Green was added to UFSP2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 U2AF2 Achchuthan Shanmugasundram Source Expert Review Green was added to U2AF2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 TSHZ3 Achchuthan Shanmugasundram Source Expert Review Green was added to TSHZ3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 TRIT1 Achchuthan Shanmugasundram Source Expert Review Green was added to TRIT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 TONSL Achchuthan Shanmugasundram Source Expert Review Green was added to TONSL.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 TOGARAM1 Achchuthan Shanmugasundram Source Expert Review Green was added to TOGARAM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 THSD1 Achchuthan Shanmugasundram Source Expert Review Green was added to THSD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 TBR1 Achchuthan Shanmugasundram Source Expert Review Green was added to TBR1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 TAF8 Achchuthan Shanmugasundram Source Expert Review Green was added to TAF8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 SNF8 Achchuthan Shanmugasundram Source Expert Review Green was added to SNF8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 SNAP25 Achchuthan Shanmugasundram Source Expert Review Green was added to SNAP25.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 SMPD1 Achchuthan Shanmugasundram Source Expert Review Amber was added to SMPD1.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Fetal anomalies v5.77 SLC4A10 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC4A10.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 SLC34A1 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC34A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 SLC25A4 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC25A4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 SETD1A Achchuthan Shanmugasundram Source Expert Review Green was added to SETD1A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 SCYL2 Achchuthan Shanmugasundram Source Expert Review Green was added to SCYL2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 SASS6 Achchuthan Shanmugasundram Source Expert Review Green was added to SASS6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 RSPRY1 Achchuthan Shanmugasundram Source Expert Review Green was added to RSPRY1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 RSPO2 Achchuthan Shanmugasundram Source Expert Review Green was added to RSPO2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 RRAS Achchuthan Shanmugasundram Source Expert Review Green was added to RRAS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 RRAGC Achchuthan Shanmugasundram Source Expert Review Green was added to RRAGC.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 RPL13 Achchuthan Shanmugasundram Source Expert Review Green was added to RPL13.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 ROBO1 Achchuthan Shanmugasundram Mode of inheritance for gene ROBO1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.77 RNU4-2 Achchuthan Shanmugasundram Source Expert Review Green was added to RNU4-2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 RFWD3 Achchuthan Shanmugasundram Source Expert Review Green was added to RFWD3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 RAP1B Achchuthan Shanmugasundram Source Expert Review Green was added to RAP1B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 RAB34 Achchuthan Shanmugasundram Source Expert Review Green was added to RAB34.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 PUM1 Achchuthan Shanmugasundram Source Expert Review Green was added to PUM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 PSMF1 Achchuthan Shanmugasundram Source Expert Review Green was added to PSMF1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 PLS3 Achchuthan Shanmugasundram Source Expert Review Green was added to PLS3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 PLD1 Achchuthan Shanmugasundram Source Expert Review Amber was added to PLD1.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Fetal anomalies v5.77 PKDCC Achchuthan Shanmugasundram Source Expert Review Green was added to PKDCC.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 PIP5K1C Achchuthan Shanmugasundram Source Expert Review Green was added to PIP5K1C.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 PIGS Achchuthan Shanmugasundram Source Expert Review Green was added to PIGS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 PI4K2A Achchuthan Shanmugasundram Source Expert Review Green was added to PI4K2A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 PAN2 Achchuthan Shanmugasundram Source Expert Review Green was added to PAN2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 NUDT2 Achchuthan Shanmugasundram Source Expert Review Green was added to NUDT2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 NSUN6 Achchuthan Shanmugasundram Source Expert Review Green was added to NSUN6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 NLRP3 Achchuthan Shanmugasundram Source Expert Review Green was added to NLRP3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 MYBBP1A Achchuthan Shanmugasundram Source NHS GMS was added to MYBBP1A.
Source Expert Review Green was added to MYBBP1A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 MSTO1 Achchuthan Shanmugasundram Mode of inheritance for gene MSTO1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.77 MDFIC Achchuthan Shanmugasundram Source Expert Review Green was added to MDFIC.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 MAX Achchuthan Shanmugasundram Source Expert Review Green was added to MAX.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 MAP4K4 Achchuthan Shanmugasundram Source Expert Review Green was added to MAP4K4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 LOX Achchuthan Shanmugasundram Source Expert Review Green was added to LOX.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 LNPK Achchuthan Shanmugasundram Source Expert Review Green was added to LNPK.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 LIPT2 Achchuthan Shanmugasundram Source Expert Review Green was added to LIPT2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 LAMB2 Achchuthan Shanmugasundram Source Expert Review Green was added to LAMB2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 LAMA5 Achchuthan Shanmugasundram Source Expert Review Green was added to LAMA5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 KMT2B Achchuthan Shanmugasundram Source Expert Review Green was added to KMT2B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 KIF5B Achchuthan Shanmugasundram Source Expert Review Green was added to KIF5B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 KIF26A Achchuthan Shanmugasundram Source Expert Review Green was added to KIF26A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 KIF24 Achchuthan Shanmugasundram Source Expert Review Green was added to KIF24.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 KDM2B Achchuthan Shanmugasundram Source Expert Review Green was added to KDM2B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 KDELR2 Achchuthan Shanmugasundram Source Expert Review Green was added to KDELR2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 KCNK9 Achchuthan Shanmugasundram Source Expert Review Green was added to KCNK9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 KCNK3 Achchuthan Shanmugasundram Source Expert Review Green was added to KCNK3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 KCNC3 Achchuthan Shanmugasundram Source Expert Review Green was added to KCNC3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 INTS11 Achchuthan Shanmugasundram Source Expert Review Green was added to INTS11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 HECTD4 Achchuthan Shanmugasundram Source Expert Review Green was added to HECTD4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 GON4L Achchuthan Shanmugasundram Source Expert Review Green was added to GON4L.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 GNB2 Achchuthan Shanmugasundram Source Expert Review Green was added to GNB2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 FUZ Achchuthan Shanmugasundram Source Expert Review Green was added to FUZ.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 FTO Achchuthan Shanmugasundram Source Expert Review Green was added to FTO.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 FOXP4 Achchuthan Shanmugasundram Source Expert Review Green was added to FOXP4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 FOSL2 Achchuthan Shanmugasundram Source Expert Review Green was added to FOSL2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 FN1 Achchuthan Shanmugasundram Source Expert Review Green was added to FN1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 FILIP1 Achchuthan Shanmugasundram Source Expert Review Green was added to FILIP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 FAS Achchuthan Shanmugasundram Source Expert Review Green was added to FAS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 ESAM Achchuthan Shanmugasundram Source Expert Review Green was added to ESAM.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 ERI1 Achchuthan Shanmugasundram Source Expert Review Green was added to ERI1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 ENG Achchuthan Shanmugasundram Source Expert Review Green was added to ENG.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 EMG1 Achchuthan Shanmugasundram Source Expert Review Green was added to EMG1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 EFCAB1 Achchuthan Shanmugasundram Source Expert Review Green was added to EFCAB1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 DRG1 Achchuthan Shanmugasundram Source Expert Review Green was added to DRG1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 DPYSL5 Achchuthan Shanmugasundram Source Expert Review Green was added to DPYSL5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 DLG5 Achchuthan Shanmugasundram Source Expert Review Green was added to DLG5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 DHX30 Achchuthan Shanmugasundram Source Expert Review Green was added to DHX30.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 DDRGK1 Achchuthan Shanmugasundram Source Expert Review Green was added to DDRGK1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 DAW1 Achchuthan Shanmugasundram Source Expert Review Green was added to DAW1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 CSGALNACT1 Achchuthan Shanmugasundram Source Expert Review Green was added to CSGALNACT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 CNOT2 Achchuthan Shanmugasundram Source Expert Review Green was added to CNOT2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 CEP295 Achchuthan Shanmugasundram Source Expert Review Green was added to CEP295.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 CDK10 Achchuthan Shanmugasundram Source Expert Review Green was added to CDK10.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 CDH2 Achchuthan Shanmugasundram Source Expert Review Green was added to CDH2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 CBY1 Achchuthan Shanmugasundram Source Expert Review Green was added to CBY1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 CASP2 Achchuthan Shanmugasundram Source Expert Review Green was added to CASP2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 CACNA1S Achchuthan Shanmugasundram Source Expert Review Green was added to CACNA1S.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 C16orf62 Achchuthan Shanmugasundram Source Expert Review Green was added to C16orf62.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 ATG7 Achchuthan Shanmugasundram Source Expert Review Green was added to ATG7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 ASXL3 Achchuthan Shanmugasundram Source Expert Review Green was added to ASXL3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 AMOTL1 Achchuthan Shanmugasundram Source Expert Review Green was added to AMOTL1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 AL117258.1 Achchuthan Shanmugasundram Source Expert Review Green was added to AL117258.1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 ADD1 Achchuthan Shanmugasundram Source Expert Review Green was added to ADD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 ADAMTS15 Achchuthan Shanmugasundram Source Expert Review Green was added to ADAMTS15.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v5.77 ACBD6 Achchuthan Shanmugasundram Source Expert Review Green was added to ACBD6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.156 FMR1_CGG Sarah Leigh Tag Q3_24_promote_green was removed from STR: FMR1_CGG.
Tag Q3_24_NHS_review was removed from STR: FMR1_CGG.
Hereditary neuropathy or pain disorder v6.156 FMR1_CGG Sarah Leigh Classified STR: FMR1_CGG as Green List (high evidence)
Hereditary neuropathy or pain disorder v6.156 FMR1_CGG Sarah Leigh Str: fmr1_cgg has been classified as Green List (High Evidence).
Hereditary neuropathy or pain disorder v6.155 FMR1_CGG Sarah Leigh commented on STR: FMR1_CGG: The rating of this STR has been updated to green following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v6.155 ATXN7_CAG Sarah Leigh Classified STR: ATXN7_CAG as Green List (high evidence)
Hereditary neuropathy or pain disorder v6.155 ATXN7_CAG Sarah Leigh Str: atxn7_cag has been classified as Green List (High Evidence).
Hereditary neuropathy or pain disorder v6.154 ATXN7_CAG Sarah Leigh Tag Q3_24_promote_green was removed from STR: ATXN7_CAG.
Tag Q3_24_NHS_review was removed from STR: ATXN7_CAG.
Hereditary neuropathy or pain disorder v6.154 ATXN7_CAG Sarah Leigh commented on STR: ATXN7_CAG: The rating of this STR has been updated to green following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v6.154 ATXN3_CAG Sarah Leigh Classified STR: ATXN3_CAG as Green List (high evidence)
Hereditary neuropathy or pain disorder v6.154 ATXN3_CAG Sarah Leigh Str: atxn3_cag has been classified as Green List (High Evidence).
Hereditary neuropathy or pain disorder v6.153 ATXN3_CAG Sarah Leigh Tag Q3_24_promote_green was removed from STR: ATXN3_CAG.
Tag Q3_24_NHS_review was removed from STR: ATXN3_CAG.
Hereditary neuropathy or pain disorder v6.153 ATXN3_CAG Sarah Leigh commented on STR: ATXN3_CAG: The rating of this STR has been updated to green following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v6.153 ATXN2_CAG Sarah Leigh Classified STR: ATXN2_CAG as Green List (high evidence)
Hereditary neuropathy or pain disorder v6.153 ATXN2_CAG Sarah Leigh Str: atxn2_cag has been classified as Green List (High Evidence).
Hereditary neuropathy or pain disorder v6.152 ATXN2_CAG Sarah Leigh Tag Q3_24_promote_green was removed from STR: ATXN2_CAG.
Tag Q3_24_NHS_review was removed from STR: ATXN2_CAG.
Hereditary neuropathy or pain disorder v6.152 ATXN2_CAG Sarah Leigh commented on STR: ATXN2_CAG: The rating of this STR has been updated to green following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v6.152 ATXN1_CAG Sarah Leigh Classified STR: ATXN1_CAG as Green List (high evidence)
Hereditary neuropathy or pain disorder v6.152 ATXN1_CAG Sarah Leigh Str: atxn1_cag has been classified as Green List (High Evidence).
Hereditary neuropathy or pain disorder v6.151 ATXN1_CAG Sarah Leigh Tag Q3_24_promote_green was removed from STR: ATXN1_CAG.
Tag Q3_24_NHS_review was removed from STR: ATXN1_CAG.
Hereditary neuropathy or pain disorder v6.151 ATXN1_CAG Sarah Leigh commented on STR: ATXN1_CAG: The rating of this STR has been updated to green following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v6.151 ATXN10_ATTCT Sarah Leigh changed review comment from: The rating of this STR has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; to: The rating of this STR has been updated to green following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v6.151 ATXN10_ATTCT Sarah Leigh Classified STR: ATXN10_ATTCT as Green List (high evidence)
Hereditary neuropathy or pain disorder v6.151 ATXN10_ATTCT Sarah Leigh Str: atxn10_attct has been classified as Green List (High Evidence).
Hereditary neuropathy or pain disorder v6.150 ATXN10_ATTCT Sarah Leigh Tag Q3_24_promote_green was removed from STR: ATXN10_ATTCT.
Tag Q3_24_NHS_review was removed from STR: ATXN10_ATTCT.
Hereditary neuropathy or pain disorder v6.150 ATXN10_ATTCT Sarah Leigh commented on STR: ATXN10_ATTCT: The rating of this STR has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v6.150 FXN_GAA Sarah Leigh Tag Q3_24_promote_green was removed from STR: FXN_GAA.
Tag Q3_24_NHS_review was removed from STR: FXN_GAA.
Hereditary neuropathy or pain disorder v6.150 NOP56_GGCCTG Sarah Leigh changed review comment from: The rating of this gene has been updated to green and the mode of inheritance set to following NHS Genomic Medicine Service approval. This change has been checked with NTGLH and Alex Rosser confirmed rationale for inclusion.; to: The rating of this STR has been updated to green and the mode of inheritance set to following NHS Genomic Medicine Service approval. This change has been checked with NTGLH and Alex Rosser confirmed rationale for inclusion.
Hereditary neuropathy or pain disorder v6.150 FXN_GAA Sarah Leigh Classified STR: FXN_GAA as Green List (high evidence)
Hereditary neuropathy or pain disorder v6.150 FXN_GAA Sarah Leigh Str: fxn_gaa has been classified as Green List (High Evidence).
Hereditary neuropathy or pain disorder v6.149 FXN_GAA Sarah Leigh commented on STR: FXN_GAA: The rating of this STR has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval (added as per previous conversations with James Polke).
Hereditary neuropathy or pain disorder v6.149 NOP56_GGCCTG Sarah Leigh changed review comment from: The rating of this gene has been updated to green and the mode of inheritance set to following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to following NHS Genomic Medicine Service approval. This change has been checked with NTGLH and Alex Rosser confirmed rationale for inclusion.
Hereditary neuropathy or pain disorder v6.149 NOP56_GGCCTG Sarah Leigh Tag Q3_24_promote_green was removed from STR: NOP56_GGCCTG.
Tag Q3_24_NHS_review was removed from STR: NOP56_GGCCTG.
Tag Q3_24_expert_review was removed from STR: NOP56_GGCCTG.
Hereditary neuropathy or pain disorder v6.149 NOP56_GGCCTG Sarah Leigh Classified STR: NOP56_GGCCTG as Green List (high evidence)
Hereditary neuropathy or pain disorder v6.149 NOP56_GGCCTG Sarah Leigh Str: nop56_ggcctg has been classified as Green List (High Evidence).
Hereditary neuropathy or pain disorder v6.148 NOP56_GGCCTG Sarah Leigh reviewed STR: NOP56_GGCCTG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v6.148 MAPK8IP3 Sarah Leigh changed review comment from: The request for MAPK8IP3 to be rated as green was refused by the NHS Genomic Medicine Service. This decision was made because the phenotype associated with MAPK8IP3 variants is broader than this panel (Hereditary neuropathy or pain disorder, R78) and is covered by the Paediatric disorders (R27) and Intellectual disability (R29) panels, where MAPK8IP3 already has a green rating.; to: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber. This decision was made because the phenotype associated with MAPK8IP3 variants is broader than this panel (Hereditary neuropathy or pain disorder, R78) and is covered by the Paediatric disorders (R27) and Intellectual disability (R29) panels, where MAPK8IP3 already has a green rating.
Intellectual disability v8.97 RBBP5 Sarah Leigh Tag Q3_24_promote_green was removed from gene: RBBP5.
Intellectual disability v8.97 SLC4A10 Sarah Leigh Tag Q3_24_promote_green was removed from gene: SLC4A10.
Intellectual disability v8.97 SRPK3 Sarah Leigh Tag Q3_24_promote_green was removed from gene: SRPK3.
Intellectual disability v8.97 TBC1D7 Sarah Leigh Tag Q3_24_promote_green was removed from gene: TBC1D7.
Tag Q3_24_NHS_review was removed from gene: TBC1D7.
Intellectual disability v8.97 TRMT5 Sarah Leigh Tag Q3_24_promote_green was removed from gene: TRMT5.
Intellectual disability v8.97 WDR83OS Sarah Leigh Tag Q3_24_promote_green was removed from gene: WDR83OS.
Intellectual disability v8.97 GEMIN4 Sarah Leigh Tag Q3_24_promote_green was removed from gene: GEMIN4.
Intellectual disability v8.97 GNAI2 Sarah Leigh Tag Q3_24_promote_green was removed from gene: GNAI2.
Intellectual disability v8.97 HDAC3 Sarah Leigh Tag Q3_24_promote_green was removed from gene: HDAC3.
Intellectual disability v8.97 IREB2 Sarah Leigh Tag watchlist was removed from gene: IREB2.
Tag Q3_24_promote_green was removed from gene: IREB2.
Intellectual disability v8.97 LINC01578 Sarah Leigh Tag Q3_24_promote_green was removed from gene: LINC01578.
Tag Q3_24_NHS_review was removed from gene: LINC01578.
Intellectual disability v8.97 LRRC7 Sarah Leigh Tag Q3_24_promote_green was removed from gene: LRRC7.
Tag Q3_24_NHS_review was removed from gene: LRRC7.
Intellectual disability v8.97 MAPKAPK5 Sarah Leigh Tag watchlist was removed from gene: MAPKAPK5.
Tag Q3_24_promote_green was removed from gene: MAPKAPK5.
Intellectual disability v8.97 MARK2 Sarah Leigh Tag Q3_24_promote_green was removed from gene: MARK2.
Intellectual disability v8.97 MSL2 Sarah Leigh Tag Q3_24_promote_green was removed from gene: MSL2.
Tag Q3_24_NHS_review was removed from gene: MSL2.
Intellectual disability v8.97 PI4K2A Sarah Leigh Tag Q3_24_promote_green was removed from gene: PI4K2A.
Tag Q3_24_NHS_review was removed from gene: PI4K2A.
Intellectual disability v8.97 PLEKHG2 Sarah Leigh Tag Q3_24_promote_green was removed from gene: PLEKHG2.
Intellectual disability v8.97 PSMC5 Sarah Leigh Tag Q3_24_promote_green was removed from gene: PSMC5.
Intellectual disability v8.97 ATXN7L3 Sarah Leigh Tag Q3_24_promote_green was removed from gene: ATXN7L3.
Intellectual disability v8.97 B9D1 Sarah Leigh Tag Q3_24_promote_green was removed from gene: B9D1.
Intellectual disability v8.97 BORCS8 Sarah Leigh Tag Q3_24_promote_green was removed from gene: BORCS8.
Intellectual disability v8.97 CCDC88A Sarah Leigh Tag Q3_24_promote_green was removed from gene: CCDC88A.
Intellectual disability v8.97 CIAO1 Sarah Leigh Tag Q3_24_promote_green was removed from gene: CIAO1.
Tag Q3_24_NHS_review was removed from gene: CIAO1.
Intellectual disability v8.97 CRELD1 Sarah Leigh Tag Q3_24_promote_green was removed from gene: CRELD1.
Intellectual disability v8.97 DDX17 Sarah Leigh Tag Q3_24_promote_green was removed from gene: DDX17.
Tag Q3_24_NHS_review was removed from gene: DDX17.
Intellectual disability v8.97 DHRSX Sarah Leigh Tag Q3_24_promote_green was removed from gene: DHRSX.
Intellectual disability v8.97 FIBP Sarah Leigh Tag Q3_24_promote_green was removed from gene: FIBP.
Tag Q3_24_NHS_review was removed from gene: FIBP.
Intellectual disability v8.97 FOSL2 Sarah Leigh Tag Q3_24_promote_green was removed from gene: FOSL2.
Intellectual disability v8.97 FRA10AC1 Sarah Leigh Tag Q3_24_promote_green was removed from gene: FRA10AC1.
Intellectual disability v8.97 FUK Sarah Leigh Tag watchlist was removed from gene: FUK.
Tag Q3_24_promote_green was removed from gene: FUK.
Intellectual disability v8.97 FZR1 Sarah Leigh Tag Q3_24_promote_green was removed from gene: FZR1.
Likely inborn error of metabolism v7.12 SLC13A3 Sarah Leigh Tag Q3_24_promote_green was removed from gene: SLC13A3.
Likely inborn error of metabolism v7.12 NT5E Sarah Leigh Tag Q3_24_promote_green was removed from gene: NT5E.
Tag Q3_24_NHS_review was removed from gene: NT5E.
Likely inborn error of metabolism v7.12 LFNG Sarah Leigh Tag Q3_24_promote_green was removed from gene: LFNG.
Likely inborn error of metabolism v7.12 FUK Sarah Leigh Tag watchlist was removed from gene: FUK.
Tag Q3_24_promote_green was removed from gene: FUK.
Likely inborn error of metabolism v7.12 DHRSX Sarah Leigh Tag Q3_24_promote_green was removed from gene: DHRSX.
Likely inborn error of metabolism v7.12 DDOST Sarah Leigh Tag Q3_24_promote_green was removed from gene: DDOST.
Likely inborn error of metabolism v7.12 ARSK Sarah Leigh Tag Q3_24_promote_green was removed from gene: ARSK.
Likely inborn error of metabolism v7.12 SLC13A3 Sarah Leigh reviewed gene: SLC13A3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v7.12 NT5E Sarah Leigh edited their review of gene: NT5E: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v7.12 LFNG Sarah Leigh reviewed gene: LFNG: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v7.12 FUK Sarah Leigh edited their review of gene: FUK: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v7.12 DHRSX Sarah Leigh reviewed gene: DHRSX: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v7.12 DDOST Sarah Leigh reviewed gene: DDOST: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v7.12 ARSK Sarah Leigh edited their review of gene: ARSK: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v7.12 SLC13A3 Sarah Leigh Source NHS GMS was added to SLC13A3.
Source Expert Review Green was added to SLC13A3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v7.12 NT5E Sarah Leigh Source Expert Review Green was added to NT5E.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v7.12 LFNG Sarah Leigh Source Expert Review Green was added to LFNG.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v7.12 FUK Sarah Leigh Source NHS GMS was added to FUK.
Source Expert Review Green was added to FUK.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v7.12 DHRSX Sarah Leigh Source NHS GMS was added to DHRSX.
Source Expert Review Green was added to DHRSX.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v7.12 DDOST Sarah Leigh Source NHS GMS was added to DDOST.
Source Expert Review Green was added to DDOST.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v7.12 ARSK Sarah Leigh Source NHS GMS was added to ARSK.
Source Expert Review Green was added to ARSK.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Limb disorders v6.10 MAPKAPK5 Sarah Leigh Tag Q3_24_promote_green was removed from gene: MAPKAPK5.
Limb disorders v6.10 MAPKAPK5 Sarah Leigh reviewed gene: MAPKAPK5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Limb disorders v6.9 MAPKAPK5 Sarah Leigh Source NHS GMS was added to MAPKAPK5.
Source Expert Review Green was added to MAPKAPK5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v8.9 SLC13A3 Sarah Leigh Tag Q3_24_promote_green was removed from gene: SLC13A3.
Mitochondrial disorders v8.9 MRPL39 Sarah Leigh Tag Q3_24_promote_green was removed from gene: MRPL39.
Tag Q3_24_NHS_review was removed from gene: MRPL39.
Mitochondrial disorders v8.9 SLC13A3 Sarah Leigh reviewed gene: SLC13A3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v8.9 MRPL39 Sarah Leigh reviewed gene: MRPL39: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v8.8 SLC13A3 Sarah Leigh Source NHS GMS was added to SLC13A3.
Source Expert Review Green was added to SLC13A3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v8.8 MRPL39 Sarah Leigh Source NHS GMS was added to MRPL39.
Source Expert Review Green was added to MRPL39.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Neurological ciliopathies v5.3 FAM149B1 Sarah Leigh Tag Q3_24_promote_green was removed from gene: FAM149B1.
Neurological ciliopathies v5.3 FAM149B1 Sarah Leigh reviewed gene: FAM149B1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Neurological ciliopathies v5.2 FAM149B1 Sarah Leigh Source Expert Review Green was added to FAM149B1.
Source NHS GMS was added to FAM149B1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v6.4 SLC13A3 Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: SLC13A3.
White matter disorders and cerebral calcification - narrow panel v6.4 HPDL Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: HPDL.
White matter disorders and cerebral calcification - narrow panel v6.4 SLC13A3 Achchuthan Shanmugasundram reviewed gene: SLC13A3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v6.4 HPDL Achchuthan Shanmugasundram reviewed gene: HPDL: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v6.3 SLC13A3 Achchuthan Shanmugasundram Source NHS GMS was added to SLC13A3.
Source Expert Review Green was added to SLC13A3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v6.3 HPDL Achchuthan Shanmugasundram Source NHS GMS was added to HPDL.
Source Expert Review Green was added to HPDL.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v7.23 RIPPLY2 Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: RIPPLY2.
Skeletal dysplasia v7.23 NT5E Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: NT5E.
Tag Q3_24_NHS_review was removed from gene: NT5E.
Skeletal dysplasia v7.23 LFNG Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: LFNG.
Skeletal dysplasia v7.23 KIF5B Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: KIF5B.
Intellectual disability v8.97 WDR83OS Sarah Leigh reviewed gene: WDR83OS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v8.97 TRMT5 Sarah Leigh reviewed gene: TRMT5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v8.97 TBC1D7 Sarah Leigh reviewed gene: TBC1D7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v8.97 SRPK3 Sarah Leigh reviewed gene: SRPK3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v8.97 SLC4A10 Sarah Leigh reviewed gene: SLC4A10: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v8.97 RBBP5 Sarah Leigh reviewed gene: RBBP5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v8.97 PSMC5 Sarah Leigh reviewed gene: PSMC5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v8.97 PLEKHG2 Sarah Leigh commented on gene: PLEKHG2: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Intellectual disability v8.97 PI4K2A Sarah Leigh reviewed gene: PI4K2A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v8.97 MSL2 Sarah Leigh reviewed gene: MSL2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v8.97 MARK2 Sarah Leigh reviewed gene: MARK2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v8.97 MAPKAPK5 Sarah Leigh reviewed gene: MAPKAPK5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v8.97 LRRC7 Sarah Leigh reviewed gene: LRRC7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v8.97 LINC01578 Sarah Leigh commented on gene: LINC01578: The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Intellectual disability v8.97 IREB2 Sarah Leigh reviewed gene: IREB2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v8.97 HDAC3 Sarah Leigh reviewed gene: HDAC3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v8.97 GNAI2 Sarah Leigh reviewed gene: GNAI2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v8.97 GEMIN4 Sarah Leigh reviewed gene: GEMIN4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v8.97 FZR1 Sarah Leigh reviewed gene: FZR1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v8.97 FUK Sarah Leigh reviewed gene: FUK: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v8.97 FRA10AC1 Sarah Leigh reviewed gene: FRA10AC1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v8.97 FOSL2 Sarah Leigh reviewed gene: FOSL2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v8.97 FIBP Sarah Leigh commented on gene: FIBP: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Intellectual disability v8.97 DHRSX Sarah Leigh reviewed gene: DHRSX: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v8.97 DDX17 Sarah Leigh reviewed gene: DDX17: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v8.97 CRELD1 Sarah Leigh reviewed gene: CRELD1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v8.97 CIAO1 Sarah Leigh commented on gene: CIAO1: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Intellectual disability v8.97 CCDC88A Sarah Leigh reviewed gene: CCDC88A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v8.97 BORCS8 Sarah Leigh reviewed gene: BORCS8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v8.97 B9D1 Sarah Leigh edited their review of gene: B9D1: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v8.97 ATXN7L3 Sarah Leigh commented on gene: ATXN7L3: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Intellectual disability v8.97 WDR83OS Sarah Leigh Source NHS GMS was added to WDR83OS.
Source Expert Review Green was added to WDR83OS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 TRMT5 Sarah Leigh Source NHS GMS was added to TRMT5.
Source Expert Review Green was added to TRMT5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 TBC1D7 Sarah Leigh Source NHS GMS was added to TBC1D7.
Source Expert Review Green was added to TBC1D7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 SRPK3 Sarah Leigh Source NHS GMS was added to SRPK3.
Source Expert Review Green was added to SRPK3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 SLC4A10 Sarah Leigh Source NHS GMS was added to SLC4A10.
Source Expert Review Green was added to SLC4A10.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 RBBP5 Sarah Leigh Source NHS GMS was added to RBBP5.
Source Expert Review Green was added to RBBP5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 PSMC5 Sarah Leigh Source NHS GMS was added to PSMC5.
Source Expert Review Green was added to PSMC5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 PLEKHG2 Sarah Leigh Source NHS GMS was added to PLEKHG2.
Source Expert Review Green was added to PLEKHG2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 PI4K2A Sarah Leigh Source Expert Review Green was added to PI4K2A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 MSL2 Sarah Leigh Source NHS GMS was added to MSL2.
Source Expert Review Green was added to MSL2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 MARK2 Sarah Leigh Source NHS GMS was added to MARK2.
Source Expert Review Green was added to MARK2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 MAPKAPK5 Sarah Leigh Source NHS GMS was added to MAPKAPK5.
Source Expert Review Green was added to MAPKAPK5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 LRRC7 Sarah Leigh Source NHS GMS was added to LRRC7.
Source Expert Review Green was added to LRRC7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 LINC01578 Sarah Leigh Source NHS GMS was added to LINC01578.
Source Expert Review Green was added to LINC01578.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 IREB2 Sarah Leigh Source NHS GMS was added to IREB2.
Source Expert Review Green was added to IREB2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 HDAC3 Sarah Leigh Source NHS GMS was added to HDAC3.
Source Expert Review Green was added to HDAC3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 GNAI2 Sarah Leigh Source NHS GMS was added to GNAI2.
Source Expert Review Green was added to GNAI2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 GEMIN4 Sarah Leigh Source NHS GMS was added to GEMIN4.
Source Expert Review Green was added to GEMIN4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 FZR1 Sarah Leigh Source NHS GMS was added to FZR1.
Source Expert Review Green was added to FZR1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 FUK Sarah Leigh Source NHS GMS was added to FUK.
Source Expert Review Green was added to FUK.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 FRA10AC1 Sarah Leigh Source NHS GMS was added to FRA10AC1.
Source Expert Review Green was added to FRA10AC1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 FOSL2 Sarah Leigh Source NHS GMS was added to FOSL2.
Source Expert Review Green was added to FOSL2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 FIBP Sarah Leigh Source NHS GMS was added to FIBP.
Source Expert Review Green was added to FIBP.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 DHRSX Sarah Leigh Source NHS GMS was added to DHRSX.
Source Expert Review Green was added to DHRSX.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 DDX17 Sarah Leigh Source NHS GMS was added to DDX17.
Source Expert Review Green was added to DDX17.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 CRELD1 Sarah Leigh Source NHS GMS was added to CRELD1.
Source Expert Review Green was added to CRELD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 CIAO1 Sarah Leigh Source NHS GMS was added to CIAO1.
Source Expert Review Green was added to CIAO1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 CCDC88A Sarah Leigh Source NHS GMS was added to CCDC88A.
Source Expert Review Green was added to CCDC88A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 BORCS8 Sarah Leigh Source NHS GMS was added to BORCS8.
Source Expert Review Green was added to BORCS8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 B9D1 Sarah Leigh Source NHS GMS was added to B9D1.
Source Expert Review Green was added to B9D1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 ATXN7L3 Sarah Leigh Source NHS GMS was added to ATXN7L3.
Source Expert Review Green was added to ATXN7L3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v7.23 DCC Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: DCC.
Skeletal dysplasia v7.23 COL27A1 Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: COL27A1.
Hereditary ataxia with onset in adulthood v7.10 TUBA4A Sarah Leigh Tag Q3_24_promote_green was removed from gene: TUBA4A.
Tag Q3_24_NHS_review was removed from gene: TUBA4A.
Skeletal dysplasia v7.23 BGN Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: BGN.
Tag Q3_24_NHS_review was removed from gene: BGN.
Hereditary ataxia with onset in adulthood v7.10 TUBA4A Sarah Leigh edited their review of gene: TUBA4A: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v7.23 ARSK Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: ARSK.
Hereditary ataxia with onset in adulthood v7.9 TUBA4A Sarah Leigh Source NHS GMS was added to TUBA4A.
Source Expert Review Green was added to TUBA4A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v7.23 TOMM7 Achchuthan Shanmugasundram reviewed gene: TOMM7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v7.23 RIPPLY2 Achchuthan Shanmugasundram reviewed gene: RIPPLY2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v7.23 NT5E Achchuthan Shanmugasundram reviewed gene: NT5E: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v7.23 LFNG Achchuthan Shanmugasundram commented on gene: LFNG: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Skeletal dysplasia v7.23 KIF5B Achchuthan Shanmugasundram commented on gene: KIF5B: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Skeletal dysplasia v7.23 EXOC6B Achchuthan Shanmugasundram commented on gene: EXOC6B: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Skeletal dysplasia v7.23 DCC Achchuthan Shanmugasundram commented on gene: DCC: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Skeletal dysplasia v7.23 COL27A1 Achchuthan Shanmugasundram commented on gene: COL27A1: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Skeletal dysplasia v7.23 BGN Achchuthan Shanmugasundram commented on gene: BGN: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Skeletal dysplasia v7.23 ARSK Achchuthan Shanmugasundram reviewed gene: ARSK: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v7.39 CUX1 Sarah Leigh Tag Q3_24_promote_green was removed from gene: CUX1.
Tag Q3_24_NHS_review was removed from gene: CUX1.
Skeletal dysplasia v7.22 TOMM7 Achchuthan Shanmugasundram Source NHS GMS was added to TOMM7.
Source Expert Review Green was added to TOMM7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v7.22 RIPPLY2 Achchuthan Shanmugasundram Source Expert Review Green was added to RIPPLY2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v7.22 NT5E Achchuthan Shanmugasundram Source Expert Review Green was added to NT5E.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v7.22 LFNG Achchuthan Shanmugasundram Source Expert Review Green was added to LFNG.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v7.22 KIF5B Achchuthan Shanmugasundram Source NHS GMS was added to KIF5B.
Source Expert Review Green was added to KIF5B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v7.39 FUK Sarah Leigh Tag Q3_24_promote_green was removed from gene: FUK.
Skeletal dysplasia v7.22 EXOC6B Achchuthan Shanmugasundram Source NHS GMS was added to EXOC6B.
Source Expert Review Green was added to EXOC6B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v7.22 DCC Achchuthan Shanmugasundram Source Expert Review Green was added to DCC.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v7.22 COL27A1 Achchuthan Shanmugasundram Source NHS GMS was added to COL27A1.
Source Expert Review Green was added to COL27A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v7.22 BGN Achchuthan Shanmugasundram Source Expert Review Green was added to BGN.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v7.22 ARSK Achchuthan Shanmugasundram Source NHS GMS was added to ARSK.
Source Expert Review Green was added to ARSK.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v7.39 FZR1 Sarah Leigh Tag Q3_24_promote_green was removed from gene: FZR1.
Early onset or syndromic epilepsy v7.39 LNPK Sarah Leigh Tag Q3_24_promote_green was removed from gene: LNPK.
Early onset or syndromic epilepsy v7.39 PI4K2A Sarah Leigh Tag Q3_24_promote_green was removed from gene: PI4K2A.
Tag Q3_24_NHS_review was removed from gene: PI4K2A.
Early onset or syndromic epilepsy v7.39 SLC13A3 Sarah Leigh Tag Q3_24_promote_green was removed from gene: SLC13A3.
Early onset or syndromic epilepsy v7.39 SLC4A10 Sarah Leigh Tag Q3_24_promote_green was removed from gene: SLC4A10.
Skeletal ciliopathies v5.4 FAM149B1 Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: FAM149B1.
Skeletal ciliopathies v5.4 FAM149B1 Achchuthan Shanmugasundram commented on gene: FAM149B1: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v7.39 AASS Sarah Leigh Tag Q3_24_promote_green was removed from gene: AASS.
Early onset or syndromic epilepsy v7.39 CCDC88A Sarah Leigh Tag Q3_24_promote_green was removed from gene: CCDC88A.
Early onset or syndromic epilepsy v7.39 CNTN2 Sarah Leigh Tag Q3_24_promote_green was removed from gene: CNTN2.
Tag Q3_24_NHS_review was removed from gene: CNTN2.
Skeletal ciliopathies v5.3 FAM149B1 Achchuthan Shanmugasundram Source NHS GMS was added to FAM149B1.
Source Expert Review Green was added to FAM149B1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v7.12 SLC4A10 Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: SLC4A10.
Severe microcephaly v7.12 FRA10AC1 Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: FRA10AC1.
Early onset or syndromic epilepsy v7.39 SLC4A10 Sarah Leigh reviewed gene: SLC4A10: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v7.39 SLC13A3 Sarah Leigh reviewed gene: SLC13A3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v7.39 PI4K2A Sarah Leigh reviewed gene: PI4K2A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v7.39 LNPK Sarah Leigh edited their review of gene: LNPK: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v7.39 FZR1 Sarah Leigh reviewed gene: FZR1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v7.39 FUK Sarah Leigh reviewed gene: FUK: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v7.39 CUX1 Sarah Leigh commented on gene: CUX1: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v7.39 CNTN2 Sarah Leigh reviewed gene: CNTN2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v7.39 CCDC88A Sarah Leigh edited their review of gene: CCDC88A: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v7.39 AASS Sarah Leigh reviewed gene: AASS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly v7.12 CCDC88A Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: CCDC88A.
Early onset or syndromic epilepsy v7.38 SLC4A10 Sarah Leigh Source NHS GMS was added to SLC4A10.
Source Expert Review Green was added to SLC4A10.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v7.38 SLC13A3 Sarah Leigh Source NHS GMS was added to SLC13A3.
Source Expert Review Green was added to SLC13A3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v7.38 PI4K2A Sarah Leigh Source Expert Review Green was added to PI4K2A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v7.38 LNPK Sarah Leigh Source Expert Review Green was added to LNPK.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v7.38 FZR1 Sarah Leigh Source NHS GMS was added to FZR1.
Source Expert Review Green was added to FZR1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v7.38 FUK Sarah Leigh Source Expert Review Green was added to FUK.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v7.38 CUX1 Sarah Leigh Source NHS GMS was added to CUX1.
Source Expert Review Green was added to CUX1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v7.38 CNTN2 Sarah Leigh Source Expert Review Green was added to CNTN2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v7.38 CCDC88A Sarah Leigh Source Expert Review Green was added to CCDC88A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v7.38 AASS Sarah Leigh Source NHS GMS was added to AASS.
Source Expert Review Green was added to AASS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v7.12 SLC4A10 Achchuthan Shanmugasundram reviewed gene: SLC4A10: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly v7.12 FRA10AC1 Achchuthan Shanmugasundram commented on gene: FRA10AC1: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Severe microcephaly v7.12 CCDC88A Achchuthan Shanmugasundram reviewed gene: CCDC88A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cystic kidney disease v7.12 CYP24A1 Sarah Leigh Tag Q3_24_promote_green was removed from gene: CYP24A1.
Tag Q3_24_NHS_review was removed from gene: CYP24A1.
Severe microcephaly v7.11 SLC4A10 Achchuthan Shanmugasundram Source NHS GMS was added to SLC4A10.
Source Expert Review Green was added to SLC4A10.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v7.11 FRA10AC1 Achchuthan Shanmugasundram Source NHS GMS was added to FRA10AC1.
Source Expert Review Green was added to FRA10AC1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v7.11 CCDC88A Achchuthan Shanmugasundram Source Expert Review Green was added to CCDC88A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Cystic kidney disease v7.12 CYP24A1 Sarah Leigh edited their review of gene: CYP24A1: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cystic kidney disease v7.11 CYP24A1 Sarah Leigh Source NHS GMS was added to CYP24A1.
Source Expert Review Green was added to CYP24A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v7.8 STX3 Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: STX3.
Retinal disorders v7.8 MAN2B1 Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: MAN2B1.
Tag Q3_24_NHS_review was removed from gene: MAN2B1.
Retinal disorders v7.8 DCT Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: DCT.
Tag Q3_24_NHS_review was removed from gene: DCT.
Retinal disorders v7.8 COQ8B Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: COQ8B.
Tag Q3_24_NHS_review was removed from gene: COQ8B.
Retinal disorders v7.8 CLEC3B Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: CLEC3B.
Retinal disorders v7.8 AHR Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: AHR.
Tag Q3_24_NHS_review was removed from gene: AHR.
Retinal disorders v7.8 STX3 Achchuthan Shanmugasundram commented on gene: STX3: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Retinal disorders v7.8 MAN2B1 Achchuthan Shanmugasundram reviewed gene: MAN2B1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v7.8 DCT Achchuthan Shanmugasundram reviewed gene: DCT: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v7.8 COQ8B Achchuthan Shanmugasundram commented on gene: COQ8B: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Retinal disorders v7.8 CLEC3B Achchuthan Shanmugasundram commented on gene: CLEC3B: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Retinal disorders v7.8 AHR Achchuthan Shanmugasundram reviewed gene: AHR: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.148 UCHL1 Sarah Leigh Tag Q3_24_promote_green was removed from gene: UCHL1.
Tag Q3_24_NHS_review was removed from gene: UCHL1.
Hereditary neuropathy or pain disorder v6.148 VPS13D Sarah Leigh Tag Q3_24_promote_green was removed from gene: VPS13D.
Tag Q3_24_NHS_review was removed from gene: VPS13D.
Hereditary neuropathy or pain disorder v6.148 XPA Sarah Leigh Tag Q3_24_promote_green was removed from gene: XPA.
Tag Q3_24_NHS_review was removed from gene: XPA.
Hereditary neuropathy or pain disorder v6.148 ZFYVE26 Sarah Leigh Tag Q3_24_promote_green was removed from gene: ZFYVE26.
Tag Q3_24_NHS_review was removed from gene: ZFYVE26.
Retinal disorders v7.7 STX3 Achchuthan Shanmugasundram Source NHS GMS was added to STX3.
Source Expert Review Green was added to STX3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v7.7 MAN2B1 Achchuthan Shanmugasundram Source NHS GMS was added to MAN2B1.
Source Expert Review Green was added to MAN2B1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v7.7 DCT Achchuthan Shanmugasundram Source NHS GMS was added to DCT.
Source Expert Review Green was added to DCT.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v7.7 COQ8B Achchuthan Shanmugasundram Source NHS GMS was added to COQ8B.
Source Expert Review Green was added to COQ8B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v7.7 CLEC3B Achchuthan Shanmugasundram Source NHS GMS was added to CLEC3B.
Source Expert Review Green was added to CLEC3B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v7.7 AHR Achchuthan Shanmugasundram Source Expert Review Green was added to AHR.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.148 SAMD9L Sarah Leigh Tag Q3_24_promote_green was removed from gene: SAMD9L.
Tag Q3_24_NHS_review was removed from gene: SAMD9L.
Hereditary neuropathy or pain disorder v6.148 SOX10 Sarah Leigh Tag Q3_24_promote_green was removed from gene: SOX10.
Tag Q3_24_NHS_review was removed from gene: SOX10.
Renal ciliopathies v3.18 PSKH1 Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: PSKH1.
Hereditary neuropathy or pain disorder v6.148 SPAST Sarah Leigh Tag Q3_24_promote_green was removed from gene: SPAST.
Tag Q3_24_NHS_review was removed from gene: SPAST.
Hereditary neuropathy or pain disorder v6.148 TBCE Sarah Leigh Tag Q3_24_promote_green was removed from gene: TBCE.
Tag Q3_24_NHS_review was removed from gene: TBCE.
Hereditary neuropathy or pain disorder v6.148 TRMT5 Sarah Leigh Tag Q3_24_promote_green was removed from gene: TRMT5.
Tag Q3_24_NHS_review was removed from gene: TRMT5.
Renal ciliopathies v3.18 GLIS2 Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: GLIS2.
Renal ciliopathies v3.18 PSKH1 Achchuthan Shanmugasundram commented on gene: PSKH1: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Renal ciliopathies v3.18 GLIS2 Achchuthan Shanmugasundram commented on gene: GLIS2: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v6.148 OPA3 Sarah Leigh Tag Q3_24_promote_green was removed from gene: OPA3.
Tag Q3_24_NHS_review was removed from gene: OPA3.
Hereditary neuropathy or pain disorder v6.148 PDHA1 Sarah Leigh Tag Q3_24_promote_green was removed from gene: PDHA1.
Tag Q3_24_NHS_review was removed from gene: PDHA1.
Hereditary neuropathy or pain disorder v6.148 PHYH Sarah Leigh Tag Q3_24_promote_green was removed from gene: PHYH.
Tag Q3_24_NHS_review was removed from gene: PHYH.
Hereditary neuropathy or pain disorder v6.148 PIEZO2 Sarah Leigh Tag Q3_24_promote_green was removed from gene: PIEZO2.
Tag Q3_24_NHS_review was removed from gene: PIEZO2.
Hereditary neuropathy or pain disorder v6.148 PLA2G16 Sarah Leigh Tag Q3_24_promote_green was removed from gene: PLA2G16.
Tag Q3_24_NHS_review was removed from gene: PLA2G16.
Hereditary neuropathy or pain disorder v6.148 PLA2G6 Sarah Leigh Tag Q3_24_promote_green was removed from gene: PLA2G6.
Tag Q3_24_NHS_review was removed from gene: PLA2G6.
Hereditary neuropathy or pain disorder v6.148 PNPT1 Sarah Leigh Tag Q3_24_promote_green was removed from gene: PNPT1.
Tag Q3_24_NHS_review was removed from gene: PNPT1.
Hereditary neuropathy or pain disorder v6.148 POLG Sarah Leigh Tag Q3_24_promote_green was removed from gene: POLG.
Tag Q3_24_NHS_review was removed from gene: POLG.
Hereditary neuropathy or pain disorder v6.148 PRNP Sarah Leigh Tag Q3_24_promote_green was removed from gene: PRNP.
Tag Q3_24_NHS_review was removed from gene: PRNP.
Hereditary neuropathy or pain disorder v6.148 PTRH2 Sarah Leigh Tag Q3_24_promote_green was removed from gene: PTRH2.
Tag Q3_24_NHS_review was removed from gene: PTRH2.
Congenital disorders of glycosylation v6.10 LFNG Arina Puzriakova Tag Q3_24_promote_green was removed from gene: LFNG.
Congenital disorders of glycosylation v6.10 FUK Arina Puzriakova Tag watchlist was removed from gene: FUK.
Tag Q3_24_promote_green was removed from gene: FUK.
Congenital disorders of glycosylation v6.10 DHRSX Arina Puzriakova Tag Q3_24_promote_green was removed from gene: DHRSX.
Congenital disorders of glycosylation v6.10 DDOST Arina Puzriakova Tag Q3_24_promote_green was removed from gene: DDOST.
Hereditary neuropathy or pain disorder v6.148 GLA Sarah Leigh Tag Q3_24_promote_green was removed from gene: GLA.
Tag Q3_24_NHS_review was removed from gene: GLA.
Hereditary neuropathy or pain disorder v6.148 HADHA Sarah Leigh Tag Q3_24_promote_green was removed from gene: HADHA.
Tag Q3_24_NHS_review was removed from gene: HADHA.
Hereditary neuropathy or pain disorder v6.148 HADHB Sarah Leigh Tag Q3_24_promote_green was removed from gene: HADHB.
Tag Q3_24_NHS_review was removed from gene: HADHB.
Hereditary neuropathy or pain disorder v6.148 HPDL Sarah Leigh Tag Q3_24_promote_green was removed from gene: HPDL.
Tag Q3_24_NHS_review was removed from gene: HPDL.
Hereditary neuropathy or pain disorder v6.148 NARS Sarah Leigh Tag Q3_24_promote_green was removed from gene: NARS.
Tag Q3_24_NHS_review was removed from gene: NARS.
Hereditary neuropathy or pain disorder v6.148 NDC1 Sarah Leigh Tag Q3_24_promote_green was removed from gene: NDC1.
Tag Q3_24_NHS_review was removed from gene: NDC1.
Hereditary neuropathy or pain disorder v6.148 NDUFS6 Sarah Leigh Tag Q3_24_promote_green was removed from gene: NDUFS6.
Tag Q3_24_NHS_review was removed from gene: NDUFS6.
Renal ciliopathies v3.16 PSKH1 Achchuthan Shanmugasundram Source NHS GMS was added to PSKH1.
Source Expert Review Green was added to PSKH1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Renal ciliopathies v3.16 GLIS2 Achchuthan Shanmugasundram Source NHS GMS was added to GLIS2.
Source Expert Review Green was added to GLIS2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.148 NFASC Sarah Leigh Tag Q3_24_promote_green was removed from gene: NFASC.
Tag Q3_24_NHS_review was removed from gene: NFASC.
Congenital disorders of glycosylation v6.10 LFNG Arina Puzriakova reviewed gene: LFNG: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital disorders of glycosylation v6.10 FUK Arina Puzriakova reviewed gene: FUK: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital disorders of glycosylation v6.10 DHRSX Arina Puzriakova reviewed gene: DHRSX: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital disorders of glycosylation v6.10 DDOST Arina Puzriakova reviewed gene: DDOST: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.148 NUDT2 Sarah Leigh Tag Q3_24_promote_green was removed from gene: NUDT2.
Tag Q3_24_NHS_review was removed from gene: NUDT2.
Congenital disorders of glycosylation v6.9 LFNG Arina Puzriakova Source Expert Review Green was added to LFNG.
Source NHS GMS was added to LFNG.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Congenital disorders of glycosylation v6.9 FUK Arina Puzriakova Source Expert Review Green was added to FUK.
Source NHS GMS was added to FUK.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Congenital disorders of glycosylation v6.9 DHRSX Arina Puzriakova Source Expert Review Green was added to DHRSX.
Source NHS GMS was added to DHRSX.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Congenital disorders of glycosylation v6.9 DDOST Arina Puzriakova Source Expert Review Green was added to DDOST.
Source NHS GMS was added to DDOST.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v5.3 RNU12 Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: RNU12.
Hereditary neuropathy or pain disorder v6.148 EMILIN1 Sarah Leigh Tag Q3_24_promote_green was removed from gene: EMILIN1.
Tag Q3_24_NHS_review was removed from gene: EMILIN1.
Hereditary neuropathy or pain disorder v6.148 ERCC6 Sarah Leigh Tag Q3_24_promote_green was removed from gene: ERCC6.
Tag Q3_24_NHS_review was removed from gene: ERCC6.
Rare syndromic craniosynostosis or isolated multisuture synostosis v5.3 RNU12 Achchuthan Shanmugasundram reviewed gene: RNU12: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.148 ERCC8 Sarah Leigh Tag Q3_24_promote_green was removed from gene: ERCC8.
Tag Q3_24_NHS_review was removed from gene: ERCC8.
Hereditary neuropathy or pain disorder v6.148 ETFDH Sarah Leigh Tag Q3_24_promote_green was removed from gene: ETFDH.
Tag Q3_24_NHS_review was removed from gene: ETFDH.
Hereditary neuropathy or pain disorder v6.148 EXOSC3 Sarah Leigh Tag Q3_24_promote_green was removed from gene: EXOSC3.
Tag Q3_24_NHS_review was removed from gene: EXOSC3.
Hereditary neuropathy or pain disorder v6.148 FA2H Sarah Leigh Tag Q3_24_promote_green was removed from gene: FA2H.
Tag Q3_24_NHS_review was removed from gene: FA2H.
Hereditary neuropathy or pain disorder v6.148 FAH Sarah Leigh Tag Q3_24_promote_green was removed from gene: FAH.
Tag Q3_24_NHS_review was removed from gene: FAH.
Hereditary neuropathy or pain disorder v6.148 FAM126A Sarah Leigh Tag Q3_24_promote_green was removed from gene: FAM126A.
Tag Q3_24_NHS_review was removed from gene: FAM126A.
Hereditary neuropathy or pain disorder v6.148 FDXR Sarah Leigh Tag Q3_24_promote_green was removed from gene: FDXR.
Tag Q3_24_NHS_review was removed from gene: FDXR.
Rare syndromic craniosynostosis or isolated multisuture synostosis v5.2 RNU12 Achchuthan Shanmugasundram Source Expert Review Green was added to RNU12.
Source NHS GMS was added to RNU12.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.148 FICD Sarah Leigh Tag Q3_24_promote_green was removed from gene: FICD.
Hereditary neuropathy or pain disorder v6.148 CTDP1 Sarah Leigh Tag Q3_24_promote_green was removed from gene: CTDP1.
Tag Q3_24_NHS_review was removed from gene: CTDP1.
Hereditary neuropathy or pain disorder v6.148 CYP2U1 Sarah Leigh Tag Q3_24_promote_green was removed from gene: CYP2U1.
Tag Q3_24_NHS_review was removed from gene: CYP2U1.
Hereditary neuropathy or pain disorder v6.148 DARS2 Sarah Leigh Tag Q3_24_promote_green was removed from gene: DARS2.
Tag Q3_24_NHS_review was removed from gene: DARS2.
Hereditary neuropathy or pain disorder v6.148 DHH Sarah Leigh Tag Q3_24_promote_green was removed from gene: DHH.
Tag Q3_24_NHS_review was removed from gene: DHH.
Hereditary neuropathy or pain disorder v6.148 DMXL2 Sarah Leigh Tag Q3_24_promote_green was removed from gene: DMXL2.
Tag Q3_24_NHS_review was removed from gene: DMXL2.
Primary immunodeficiency or monogenic inflammatory bowel disease v7.26 TRAF3 Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: TRAF3.
Childhood onset hereditary spastic paraplegia v7.6 RINT1 Arina Puzriakova Tag Q3_24_promote_green was removed from gene: RINT1.
Hereditary neuropathy or pain disorder v6.148 COA7 Sarah Leigh Tag Q3_24_promote_green was removed from gene: COA7.
Tag Q3_24_NHS_review was removed from gene: COA7.
Childhood onset hereditary spastic paraplegia v7.6 FICD Arina Puzriakova Tag Q3_24_promote_green was removed from gene: FICD.
Primary immunodeficiency or monogenic inflammatory bowel disease v7.26 TET2 Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: TET2.
Tag Q3_24_NHS_review was removed from gene: TET2.
Childhood onset hereditary spastic paraplegia v7.6 BORCS8 Arina Puzriakova Tag Q3_24_promote_green was removed from gene: BORCS8.
Hereditary neuropathy or pain disorder v6.148 CNTNAP1 Sarah Leigh Tag Q3_24_promote_green was removed from gene: CNTNAP1.
Tag Q3_24_NHS_review was removed from gene: CNTNAP1.
Primary immunodeficiency or monogenic inflammatory bowel disease v7.26 SAMD9 Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: SAMD9.
Tag Q3_24_NHS_review was removed from gene: SAMD9.
Hereditary neuropathy or pain disorder v6.148 CLP1 Sarah Leigh Tag Q3_24_promote_green was removed from gene: CLP1.
Tag Q3_24_NHS_review was removed from gene: CLP1.
Hereditary neuropathy or pain disorder v6.148 CD59 Sarah Leigh Tag Q3_24_promote_green was removed from gene: CD59.
Tag Q3_24_NHS_review was removed from gene: CD59.
Childhood onset hereditary spastic paraplegia v7.6 RINT1 Arina Puzriakova reviewed gene: RINT1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v7.6 FICD Arina Puzriakova reviewed gene: FICD: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v7.6 BORCS8 Arina Puzriakova reviewed gene: BORCS8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.148 CAPN1 Sarah Leigh Tag Q3_24_promote_green was removed from gene: CAPN1.
Tag Q3_24_NHS_review was removed from gene: CAPN1.
Hereditary neuropathy or pain disorder v6.148 C12orf65 Sarah Leigh Tag Q3_24_promote_green was removed from gene: C12orf65.
Tag Q3_24_NHS_review was removed from gene: C12orf65.
Childhood onset hereditary spastic paraplegia v7.5 RINT1 Arina Puzriakova Source Expert Review Green was added to RINT1.
Source NHS GMS was added to RINT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset hereditary spastic paraplegia v7.5 FICD Arina Puzriakova Source Expert Review Green was added to FICD.
Source NHS GMS was added to FICD.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset hereditary spastic paraplegia v7.5 BORCS8 Arina Puzriakova Source Expert Review Green was added to BORCS8.
Source NHS GMS was added to BORCS8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v7.26 RELB Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: RELB.
Hereditary neuropathy or pain disorder v6.148 BAG3 Sarah Leigh Tag Q3_24_promote_green was removed from gene: BAG3.
Tag Q3_24_NHS_review was removed from gene: BAG3.
Primary immunodeficiency or monogenic inflammatory bowel disease v7.26 ITPR3 Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: ITPR3.
Hereditary neuropathy or pain disorder v6.148 ATP13A2 Sarah Leigh Tag Q3_24_promote_green was removed from gene: ATP13A2.
Tag Q3_24_NHS_review was removed from gene: ATP13A2.
Hereditary neuropathy or pain disorder v6.148 ATM Sarah Leigh Tag Q3_24_promote_green was removed from gene: ATM.
Tag Q3_24_NHS_review was removed from gene: ATM.
Hereditary neuropathy or pain disorder v6.148 ATL3 Sarah Leigh Tag Q3_24_promote_green was removed from gene: ATL3.
Tag Q3_24_NHS_review was removed from gene: ATL3.
Hereditary neuropathy or pain disorder v6.148 ATAD3A Sarah Leigh Tag Q3_24_promote_green was removed from gene: ATAD3A.
Tag Q3_24_NHS_review was removed from gene: ATAD3A.
Hereditary neuropathy or pain disorder v6.148 ASAH1 Sarah Leigh Tag Q3_24_promote_green was removed from gene: ASAH1.
Tag Q3_24_NHS_review was removed from gene: ASAH1.
Hereditary neuropathy or pain disorder v6.148 ARSA Sarah Leigh Tag Q3_24_promote_green was removed from gene: ARSA.
Tag Q3_24_NHS_review was removed from gene: ARSA.
Hereditary neuropathy or pain disorder v6.148 ARL6IP1 Sarah Leigh Tag Q3_24_promote_green was removed from gene: ARL6IP1.
Tag Q3_24_NHS_review was removed from gene: ARL6IP1.
Hereditary neuropathy or pain disorder v6.148 APTX Sarah Leigh Tag Q3_24_promote_green was removed from gene: APTX.
Tag Q3_24_NHS_review was removed from gene: APTX.
Hereditary neuropathy or pain disorder v6.148 AP5Z1 Sarah Leigh Tag Q3_24_promote_green was removed from gene: AP5Z1.
Tag Q3_24_NHS_review was removed from gene: AP5Z1.
Hereditary neuropathy or pain disorder v6.148 AP1S1 Sarah Leigh Tag Q3_24_promote_green was removed from gene: AP1S1.
Hereditary neuropathy or pain disorder v6.148 AMACR Sarah Leigh Tag Q3_24_promote_green was removed from gene: AMACR.
Tag Q3_24_NHS_review was removed from gene: AMACR.
Hereditary neuropathy or pain disorder v6.148 ADPRHL2 Sarah Leigh Tag Q3_24_promote_green was removed from gene: ADPRHL2.
Tag Q3_24_NHS_review was removed from gene: ADPRHL2.
Hereditary neuropathy or pain disorder v6.148 ADGRG6 Sarah Leigh Tag Q3_24_promote_green was removed from gene: ADGRG6.
Tag Q3_24_NHS_review was removed from gene: ADGRG6.
Hereditary neuropathy or pain disorder v6.148 ADCY6 Sarah Leigh Tag Q3_24_promote_green was removed from gene: ADCY6.
Tag Q3_24_NHS_review was removed from gene: ADCY6.
Hereditary neuropathy or pain disorder v6.148 ADA2 Sarah Leigh Tag Q3_24_promote_green was removed from gene: ADA2.
Tag Q3_24_NHS_review was removed from gene: ADA2.
Hereditary neuropathy or pain disorder v6.148 ABCD1 Sarah Leigh Tag Q3_24_promote_green was removed from gene: ABCD1.
Tag Q3_24_NHS_review was removed from gene: ABCD1.
Hereditary neuropathy or pain disorder v6.148 AAAS Sarah Leigh Tag Q3_24_promote_green was removed from gene: AAAS.
Tag Q3_24_NHS_review was removed from gene: AAAS.
Childhood onset dystonia, chorea or related movement disorder v6.5 NUS1 Arina Puzriakova Tag Q3_24_promote_green was removed from gene: NUS1.
Childhood onset dystonia, chorea or related movement disorder v6.5 DCC Arina Puzriakova Tag Q3_24_promote_green was removed from gene: DCC.
Childhood onset dystonia, chorea or related movement disorder v6.5 NUS1 Arina Puzriakova reviewed gene: NUS1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Childhood onset dystonia, chorea or related movement disorder v6.5 DCC Arina Puzriakova reviewed gene: DCC: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Childhood onset dystonia, chorea or related movement disorder v6.4 NUS1 Arina Puzriakova Source NHS GMS was added to NUS1.
Source Expert Review Green was added to NUS1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v6.4 DCC Arina Puzriakova Source NHS GMS was added to DCC.
Source Expert Review Green was added to DCC.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.148 FLVCR1 Sarah Leigh Tag Q3_24_promote_green was removed from gene: FLVCR1.
Tag Q3_24_NHS_review was removed from gene: FLVCR1.
Hereditary neuropathy or pain disorder v6.148 TTPA Sarah Leigh Tag Q3_24_promote_green was removed from gene: TTPA.
Tag Q3_24_NHS_review was removed from gene: TTPA.
Hereditary neuropathy or pain disorder v6.148 TWNK Sarah Leigh Tag Q3_24_promote_green was removed from gene: TWNK.
Tag Q3_24_NHS_review was removed from gene: TWNK.
Hereditary neuropathy or pain disorder v6.148 TUBB3 Sarah Leigh Tag Q3_24_promote_green was removed from gene: TUBB3.
Tag Q3_24_NHS_review was removed from gene: TUBB3.
Bilateral congenital or childhood onset cataracts v6.6 GEMIN4 Arina Puzriakova Tag watchlist was removed from gene: GEMIN4.
Tag Q3_24_promote_green was removed from gene: GEMIN4.
Bilateral congenital or childhood onset cataracts v6.6 FOSL2 Arina Puzriakova Tag Q3_24_promote_green was removed from gene: FOSL2.
Bilateral congenital or childhood onset cataracts v6.6 GEMIN4 Arina Puzriakova reviewed gene: GEMIN4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bilateral congenital or childhood onset cataracts v6.6 FOSL2 Arina Puzriakova reviewed gene: FOSL2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Bilateral congenital or childhood onset cataracts v6.5 GEMIN4 Arina Puzriakova Source NHS GMS was added to GEMIN4.
Source Expert Review Green was added to GEMIN4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Bilateral congenital or childhood onset cataracts v6.5 FOSL2 Arina Puzriakova Source NHS GMS was added to FOSL2.
Source Expert Review Green was added to FOSL2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v7.18 PNPT1 Arina Puzriakova Tag Q3_24_promote_green was removed from gene: PNPT1.
Ataxia and cerebellar anomalies - narrow panel v7.18 NUS1 Arina Puzriakova Tag Q3_24_promote_green was removed from gene: NUS1.
Ataxia and cerebellar anomalies - narrow panel v7.18 FDXR Arina Puzriakova Tag Q3_24_promote_green was removed from gene: FDXR.
Ataxia and cerebellar anomalies - narrow panel v7.18 PNPT1 Arina Puzriakova reviewed gene: PNPT1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia and cerebellar anomalies - narrow panel v7.18 NUS1 Arina Puzriakova reviewed gene: NUS1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia and cerebellar anomalies - narrow panel v7.18 FDXR Arina Puzriakova commented on gene: FDXR: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Ataxia and cerebellar anomalies - narrow panel v7.17 PNPT1 Arina Puzriakova Source NHS GMS was added to PNPT1.
Source Expert Review Green was added to PNPT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v7.17 NUS1 Arina Puzriakova Source NHS GMS was added to NUS1.
Source Expert Review Green was added to NUS1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v7.17 FDXR Arina Puzriakova Source NHS GMS was added to FDXR.
Source Expert Review Green was added to FDXR.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Arthrogryposis v8.6 MET Arina Puzriakova Tag Q3_24_promote_green was removed from gene: MET.
Arthrogryposis v8.6 MET Arina Puzriakova reviewed gene: MET: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Arthrogryposis v8.5 MET Arina Puzriakova Source NHS GMS was added to MET.
Source Expert Review Green was added to MET.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.148 ZFYVE26 Sarah Leigh reviewed gene: ZFYVE26: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.148 XPA Sarah Leigh reviewed gene: XPA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.148 VPS13D Sarah Leigh reviewed gene: VPS13D: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.148 UCHL1 Sarah Leigh reviewed gene: UCHL1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.148 TWNK Sarah Leigh reviewed gene: TWNK: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.148 TUBB3 Sarah Leigh reviewed gene: TUBB3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v6.148 TTPA Sarah Leigh commented on gene: TTPA: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v6.148 TRMT5 Sarah Leigh reviewed gene: TRMT5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.148 TBCE Sarah Leigh reviewed gene: TBCE: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.148 SPAST Sarah Leigh reviewed gene: SPAST: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary neuropathy or pain disorder v6.148 SOX10 Sarah Leigh reviewed gene: SOX10: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v6.148 SAMD9L Sarah Leigh reviewed gene: SAMD9L: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary neuropathy or pain disorder v6.148 PTRH2 Sarah Leigh reviewed gene: PTRH2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.148 PRNP Sarah Leigh reviewed gene: PRNP: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v6.148 POLG Sarah Leigh reviewed gene: POLG: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.148 PNPT1 Sarah Leigh reviewed gene: PNPT1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v6.148 PLA2G6 Sarah Leigh reviewed gene: PLA2G6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.148 PLA2G16 Sarah Leigh reviewed gene: PLA2G16: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.148 PIEZO2 Sarah Leigh reviewed gene: PIEZO2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.148 PHYH Sarah Leigh reviewed gene: PHYH: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.148 PDHA1 Sarah Leigh reviewed gene: PDHA1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Hereditary neuropathy or pain disorder v6.148 OPA3 Sarah Leigh reviewed gene: OPA3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary neuropathy or pain disorder v6.148 NUDT2 Sarah Leigh reviewed gene: NUDT2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.148 NFASC Sarah Leigh reviewed gene: NFASC: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.148 NDUFS6 Sarah Leigh reviewed gene: NDUFS6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.148 NDC1 Sarah Leigh edited their review of gene: NDC1: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.148 NARS Sarah Leigh reviewed gene: NARS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.148 HPDL Sarah Leigh reviewed gene: HPDL: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.148 HADHB Sarah Leigh reviewed gene: HADHB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.148 HADHA Sarah Leigh reviewed gene: HADHA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.148 GLA Sarah Leigh commented on gene: GLA: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v6.148 FLVCR1 Sarah Leigh edited their review of gene: FLVCR1: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.148 FICD Sarah Leigh reviewed gene: FICD: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.148 FDXR Sarah Leigh reviewed gene: FDXR: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.148 FAM126A Sarah Leigh commented on gene: FAM126A: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v6.148 FAH Sarah Leigh commented on gene: FAH: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v6.148 FA2H Sarah Leigh reviewed gene: FA2H: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.148 EXOSC3 Sarah Leigh reviewed gene: EXOSC3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.148 ETFDH Sarah Leigh commented on gene: ETFDH: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v6.148 ERCC8 Sarah Leigh edited their review of gene: ERCC8: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.148 ERCC6 Sarah Leigh commented on gene: ERCC6: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v6.148 EMILIN1 Sarah Leigh reviewed gene: EMILIN1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v6.148 DMXL2 Sarah Leigh edited their review of gene: DMXL2: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.148 DHH Sarah Leigh edited their review of gene: DHH: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.148 DARS2 Sarah Leigh commented on gene: DARS2: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v6.148 CYP2U1 Sarah Leigh commented on gene: CYP2U1: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v6.148 CTDP1 Sarah Leigh commented on gene: CTDP1: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v6.148 COA7 Sarah Leigh commented on gene: COA7: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v6.148 CNTNAP1 Sarah Leigh commented on gene: CNTNAP1: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v6.148 CLP1 Sarah Leigh commented on gene: CLP1: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v6.148 CD59 Sarah Leigh commented on gene: CD59: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v6.148 CAPN1 Sarah Leigh commented on gene: CAPN1: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v6.148 C12orf65 Sarah Leigh commented on gene: C12orf65: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v6.148 BAG3 Sarah Leigh commented on gene: BAG3: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v6.148 ATP13A2 Sarah Leigh commented on gene: ATP13A2: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v6.148 ATM Sarah Leigh commented on gene: ATM: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v6.148 ATL3 Sarah Leigh commented on gene: ATL3: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v6.148 ATAD3A Sarah Leigh commented on gene: ATAD3A: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v6.148 ASAH1 Sarah Leigh commented on gene: ASAH1: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v6.148 ARSA Sarah Leigh edited their review of gene: ARSA: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.148 ARL6IP1 Sarah Leigh commented on gene: ARL6IP1: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v6.148 APTX Sarah Leigh edited their review of gene: APTX: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.148 AP5Z1 Sarah Leigh commented on gene: AP5Z1: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v6.148 AP1S1 Sarah Leigh reviewed gene: AP1S1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.148 AMACR Sarah Leigh edited their review of gene: AMACR: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.148 ADPRHL2 Sarah Leigh edited their review of gene: ADPRHL2: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.148 ADGRG6 Sarah Leigh edited their review of gene: ADGRG6: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.148 ADCY6 Sarah Leigh edited their review of gene: ADCY6: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.148 ADA2 Sarah Leigh edited their review of gene: ADA2: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.148 ABCD1 Sarah Leigh edited their review of gene: ABCD1: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Hereditary neuropathy or pain disorder v6.148 AAAS Sarah Leigh edited their review of gene: AAAS: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Adult onset neurodegenerative disorder v7.8 TUBA4A Arina Puzriakova Tag Q3_24_promote_green was removed from gene: TUBA4A.
Tag Q3_24_NHS_review was removed from gene: TUBA4A.
Adult onset neurodegenerative disorder v7.8 RAB32 Arina Puzriakova Tag Q3_24_promote_green was removed from gene: RAB32.
Adult onset neurodegenerative disorder v7.8 TUBA4A Arina Puzriakova reviewed gene: TUBA4A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Adult onset neurodegenerative disorder v7.8 RAB32 Arina Puzriakova reviewed gene: RAB32: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Adult onset neurodegenerative disorder v7.7 NOP56_GGCCTG Arina Puzriakova Tag watchlist was removed from STR: NOP56_GGCCTG.
Tag Q3_24_promote_green was removed from STR: NOP56_GGCCTG.
Tag Q3_24_expert_review was removed from STR: NOP56_GGCCTG.
Adult onset neurodegenerative disorder v7.7 NOP56_GGCCTG Arina Puzriakova edited their review of STR: NOP56_GGCCTG: Added comment: After GMS expert consideration, the rating of this STR has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Adult onset neurodegenerative disorder v7.7 NOP56_GGCCTG Arina Puzriakova Classified STR: NOP56_GGCCTG as Green List (high evidence)
Adult onset neurodegenerative disorder v7.7 NOP56_GGCCTG Arina Puzriakova Str: nop56_ggcctg has been classified as Green List (High Evidence).
Adult onset neurodegenerative disorder v7.6 TUBA4A Arina Puzriakova Source Expert Review Green was added to TUBA4A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset neurodegenerative disorder v7.6 RAB32 Arina Puzriakova Source NHS GMS was added to RAB32.
Source Expert Review Green was added to RAB32.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 ZFYVE26 Sarah Leigh Source Expert Review Green was added to ZFYVE26.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 XPA Sarah Leigh Source Expert Review Green was added to XPA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 VPS13D Sarah Leigh Source NHS GMS was added to VPS13D.
Source Expert Review Green was added to VPS13D.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 UCHL1 Sarah Leigh Source NHS GMS was added to UCHL1.
Source Expert Review Green was added to UCHL1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 TWNK Sarah Leigh Source Expert Review Green was added to TWNK.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 TUBB3 Sarah Leigh Source Expert Review Green was added to TUBB3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 TTPA Sarah Leigh Source Expert Review Green was added to TTPA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 TRMT5 Sarah Leigh Source NHS GMS was added to TRMT5.
Source Expert Review Green was added to TRMT5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 TBCE Sarah Leigh Source NHS GMS was added to TBCE.
Source Expert Review Green was added to TBCE.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 SPAST Sarah Leigh Source Expert Review Green was added to SPAST.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 SOX10 Sarah Leigh Source Expert Review Green was added to SOX10.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 SAMD9L Sarah Leigh Source NHS GMS was added to SAMD9L.
Source Expert Review Green was added to SAMD9L.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 PTRH2 Sarah Leigh Source Expert Review Green was added to PTRH2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 PRNP Sarah Leigh Source Expert Review Green was added to PRNP.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 POLG Sarah Leigh Source Expert Review Green was added to POLG.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 PNPT1 Sarah Leigh Source NHS GMS was added to PNPT1.
Source Expert Review Green was added to PNPT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 PLA2G6 Sarah Leigh Source NHS GMS was added to PLA2G6.
Source Expert Review Green was added to PLA2G6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 PLA2G16 Sarah Leigh Source NHS GMS was added to PLA2G16.
Source Expert Review Green was added to PLA2G16.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 PIEZO2 Sarah Leigh Source NHS GMS was added to PIEZO2.
Source Expert Review Green was added to PIEZO2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 PHYH Sarah Leigh Source Expert Review Green was added to PHYH.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 PDHA1 Sarah Leigh Source Expert Review Green was added to PDHA1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 OPA3 Sarah Leigh Source Expert Review Green was added to OPA3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 NUDT2 Sarah Leigh Source NHS GMS was added to NUDT2.
Source Expert Review Green was added to NUDT2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 NFASC Sarah Leigh Source NHS GMS was added to NFASC.
Source Expert Review Green was added to NFASC.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 NDUFS6 Sarah Leigh Source NHS GMS was added to NDUFS6.
Source Expert Review Green was added to NDUFS6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 NDC1 Sarah Leigh Source NHS GMS was added to NDC1.
Source Expert Review Green was added to NDC1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 NARS Sarah Leigh Source NHS GMS was added to NARS.
Source Expert Review Green was added to NARS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 HPDL Sarah Leigh Source NHS GMS was added to HPDL.
Source Expert Review Green was added to HPDL.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 HADHB Sarah Leigh Source Expert Review Green was added to HADHB.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 HADHA Sarah Leigh Source Expert Review Green was added to HADHA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 GLA Sarah Leigh Source Expert Review Green was added to GLA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 FLVCR1 Sarah Leigh Source Expert Review Green was added to FLVCR1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 FICD Sarah Leigh Source NHS GMS was added to FICD.
Source Expert Review Green was added to FICD.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 FDXR Sarah Leigh Source NHS GMS was added to FDXR.
Source Expert Review Green was added to FDXR.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 FAM126A Sarah Leigh Source Expert Review Green was added to FAM126A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 FAH Sarah Leigh Source Expert Review Green was added to FAH.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 FA2H Sarah Leigh Source Expert Review Green was added to FA2H.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 EXOSC3 Sarah Leigh Source NHS GMS was added to EXOSC3.
Source Expert Review Green was added to EXOSC3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 ETFDH Sarah Leigh Source Expert Review Green was added to ETFDH.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 ERCC8 Sarah Leigh Source Expert Review Green was added to ERCC8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 ERCC6 Sarah Leigh Source Expert Review Green was added to ERCC6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 EMILIN1 Sarah Leigh Source NHS GMS was added to EMILIN1.
Source Expert Review Green was added to EMILIN1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 DMXL2 Sarah Leigh Source NHS GMS was added to DMXL2.
Source Expert Review Green was added to DMXL2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 DHH Sarah Leigh Source Expert Review Green was added to DHH.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 DARS2 Sarah Leigh Source Expert Review Green was added to DARS2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 CYP2U1 Sarah Leigh Source NHS GMS was added to CYP2U1.
Source Expert Review Green was added to CYP2U1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 CTDP1 Sarah Leigh Source Expert Review Green was added to CTDP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 COA7 Sarah Leigh Source Expert Review Green was added to COA7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 CNTNAP1 Sarah Leigh Source Expert Review Green was added to CNTNAP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 CLP1 Sarah Leigh Source NHS GMS was added to CLP1.
Source Expert Review Green was added to CLP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 CD59 Sarah Leigh Source Expert Review Green was added to CD59.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 CAPN1 Sarah Leigh Source NHS GMS was added to CAPN1.
Source Expert Review Green was added to CAPN1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 C12orf65 Sarah Leigh Source Expert Review Green was added to C12orf65.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 BAG3 Sarah Leigh Source Expert Review Green was added to BAG3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 ATP13A2 Sarah Leigh Source NHS GMS was added to ATP13A2.
Source Expert Review Green was added to ATP13A2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 ATM Sarah Leigh Source Expert Review Green was added to ATM.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 ATL3 Sarah Leigh Source Expert Review Green was added to ATL3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 ATAD3A Sarah Leigh Source NHS GMS was added to ATAD3A.
Source Expert Review Green was added to ATAD3A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 ASAH1 Sarah Leigh Source NHS GMS was added to ASAH1.
Source Expert Review Green was added to ASAH1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 ARSA Sarah Leigh Source Expert Review Green was added to ARSA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 ARL6IP1 Sarah Leigh Source Expert Review Green was added to ARL6IP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 APTX Sarah Leigh Source Expert Review Green was added to APTX.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 AP5Z1 Sarah Leigh Source NHS GMS was added to AP5Z1.
Source Expert Review Green was added to AP5Z1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 AP1S1 Sarah Leigh Source Expert Review Green was added to AP1S1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 AMACR Sarah Leigh Source NHS GMS was added to AMACR.
Source Expert Review Green was added to AMACR.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 ADPRHL2 Sarah Leigh Source NHS GMS was added to ADPRHL2.
Source Expert Review Green was added to ADPRHL2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 ADGRG6 Sarah Leigh Source NHS GMS was added to ADGRG6.
Source Expert Review Green was added to ADGRG6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 ADCY6 Sarah Leigh Source NHS GMS was added to ADCY6.
Source Expert Review Green was added to ADCY6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 ADA2 Sarah Leigh Source NHS GMS was added to ADA2.
Source Expert Review Green was added to ADA2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 ABCD1 Sarah Leigh Source NHS GMS was added to ABCD1.
Source Expert Review Green was added to ABCD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.147 AAAS Sarah Leigh Source NHS GMS was added to AAAS.
Source Expert Review Green was added to AAAS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset leukodystrophy v5.4 ABCD1 Arina Puzriakova Tag Q3_24_NHS_review was removed from gene: ABCD1.
Tag Q3_24_MOI was removed from gene: ABCD1.
Ophthalmological ciliopathies v4.8 FAM149B1 Sarah Leigh Tag Q3_24_promote_green was removed from gene: FAM149B1.
Adult onset leukodystrophy v5.4 ABCD1 Arina Puzriakova reviewed gene: ABCD1: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Adult onset leukodystrophy v5.3 ABCD1 Arina Puzriakova Mode of inheritance for gene ABCD1 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Ophthalmological ciliopathies v4.8 FAM149B1 Sarah Leigh Source Expert Review Green was added to FAM149B1.
Source NHS GMS was added to FAM149B1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset hereditary spastic paraplegia v5.5 BICD2 Arina Puzriakova Tag Q3_24_promote_green was removed from gene: BICD2.
Tag Q3_24_NHS_review was removed from gene: BICD2.
Adult onset hereditary spastic paraplegia v5.5 BICD2 Arina Puzriakova Source Expert Review Green was added to BICD2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset hereditary spastic paraplegia v5.4 BICD2 Arina Puzriakova reviewed gene: BICD2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v6.146 MAPK8IP3 Sarah Leigh Tag Q3_24_promote_green was removed from gene: MAPK8IP3.
Tag Q3_24_NHS_review was removed from gene: MAPK8IP3.
Tag Q3_24_expert_review was removed from gene: MAPK8IP3.
Hereditary neuropathy or pain disorder v6.146 MAPK8IP3 Sarah Leigh Publications for gene: MAPK8IP3 were set to 37462082: 30945334
Hereditary neuropathy or pain disorder v6.145 MAPK8IP3 Sarah Leigh reviewed gene: MAPK8IP3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Adult onset dystonia, chorea or related movement disorder v4.5 ARSA Arina Puzriakova Tag Q3_24_promote_green was removed from gene: ARSA.
Adult onset dystonia, chorea or related movement disorder v4.5 ARSA Arina Puzriakova reviewed gene: ARSA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Adult onset dystonia, chorea or related movement disorder v4.4 ARSA Arina Puzriakova Source Expert Review Green was added to ARSA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ophthalmological ciliopathies v4.7 FAM149B1 Sarah Leigh reviewed gene: FAM149B1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Pigmentary skin disorders v3.14 LZTR1 Frankie Macrae reviewed gene: LZTR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35361920, 39140257, 39258154; Phenotypes: Multiple café au lait macules; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Primary immunodeficiency or monogenic inflammatory bowel disease v7.26 IL7 Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: IL7.
Primary immunodeficiency or monogenic inflammatory bowel disease v7.26 IL6ST Achchuthan Shanmugasundram Tag Q3_24_MOI was removed from gene: IL6ST.
Primary immunodeficiency or monogenic inflammatory bowel disease v7.26 GNAI2 Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: GNAI2.
Primary immunodeficiency or monogenic inflammatory bowel disease v7.26 EP300 Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: EP300.
Pigmentary skin disorders v3.14 LZTR1 Frankie Macrae Deleted their review
Pigmentary skin disorders v3.14 LZTR1 Frankie Macrae reviewed gene: LZTR1: Rating: GREEN; Mode of pathogenicity: Other; Publications: ; Phenotypes: cafe-au-lait; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v7.26 CREBBP Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: CREBBP.
Primary immunodeficiency or monogenic inflammatory bowel disease v7.26 CASP10 Achchuthan Shanmugasundram Tag Q3_24_expert_review was removed from gene: CASP10.
Tag Q3_24_demote_amber was removed from gene: CASP10.
Tag Q3_24_MOI was removed from gene: CASP10.
Primary immunodeficiency or monogenic inflammatory bowel disease v7.26 TRAF3 Achchuthan Shanmugasundram commented on gene: TRAF3: The rating of this gene has been updated to green and the mode of inheritance updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Primary immunodeficiency or monogenic inflammatory bowel disease v7.26 TET2 Achchuthan Shanmugasundram reviewed gene: TET2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v7.26 SAMD9 Achchuthan Shanmugasundram commented on gene: SAMD9: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Primary immunodeficiency or monogenic inflammatory bowel disease v7.26 RELB Achchuthan Shanmugasundram commented on gene: RELB: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Primary immunodeficiency or monogenic inflammatory bowel disease v7.26 ITPR3 Achchuthan Shanmugasundram commented on gene: ITPR3: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Primary immunodeficiency or monogenic inflammatory bowel disease v7.26 IL7 Achchuthan Shanmugasundram commented on gene: IL7: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Primary immunodeficiency or monogenic inflammatory bowel disease v7.26 IL6ST Achchuthan Shanmugasundram commented on gene: IL6ST: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Primary immunodeficiency or monogenic inflammatory bowel disease v7.26 GNAI2 Achchuthan Shanmugasundram reviewed gene: GNAI2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v7.26 EP300 Achchuthan Shanmugasundram reviewed gene: EP300: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary immunodeficiency or monogenic inflammatory bowel disease v7.26 CREBBP Achchuthan Shanmugasundram reviewed gene: CREBBP: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary immunodeficiency or monogenic inflammatory bowel disease v7.26 CASP10 Achchuthan Shanmugasundram reviewed gene: CASP10: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v7.25 TRAF3 Achchuthan Shanmugasundram Source NHS GMS was added to TRAF3.
Source Expert Review Green was added to TRAF3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v7.25 TET2 Achchuthan Shanmugasundram Source NHS GMS was added to TET2.
Source Expert Review Green was added to TET2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v7.25 SAMD9 Achchuthan Shanmugasundram Source NHS GMS was added to SAMD9.
Source Expert Review Green was added to SAMD9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v7.25 RELB Achchuthan Shanmugasundram Source NHS GMS was added to RELB.
Source Expert Review Green was added to RELB.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v7.25 ITPR3 Achchuthan Shanmugasundram Source NHS GMS was added to ITPR3.
Source Expert Review Green was added to ITPR3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v7.25 IL7 Achchuthan Shanmugasundram Source NHS GMS was added to IL7.
Source Expert Review Green was added to IL7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v7.25 IL6ST Achchuthan Shanmugasundram Source NHS GMS was added to IL6ST.
Mode of inheritance for gene IL6ST was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v7.25 GNAI2 Achchuthan Shanmugasundram Source NHS GMS was added to GNAI2.
Source Expert Review Green was added to GNAI2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v7.25 EP300 Achchuthan Shanmugasundram Source NHS GMS was added to EP300.
Source Expert Review Green was added to EP300.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v7.25 CREBBP Achchuthan Shanmugasundram Source NHS GMS was added to CREBBP.
Source Expert Review Green was added to CREBBP.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v7.25 CASP10 Achchuthan Shanmugasundram Source Expert Review Amber was added to CASP10.
Mode of inheritance for gene CASP10 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Paediatric or syndromic cardiomyopathy v6.7 MYZAP Achchuthan Shanmugasundram Tag Q4_24_promote_green was removed from gene: MYZAP.
Paediatric or syndromic cardiomyopathy v6.7 FKRP Achchuthan Shanmugasundram Tag Q4_24_promote_green was removed from gene: FKRP.
Paediatric or syndromic cardiomyopathy v6.7 TAF1A Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: TAF1A.
Tag Q3_24_NHS_review was removed from gene: TAF1A.
Paediatric or syndromic cardiomyopathy v6.7 MAP3K7 Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: MAP3K7.
Tag Q3_24_NHS_review was removed from gene: MAP3K7.
Paediatric or syndromic cardiomyopathy v6.7 ALPK3 Achchuthan Shanmugasundram Tag Q3_24_NHS_review was removed from gene: ALPK3.
Tag Q3_24_MOI was removed from gene: ALPK3.
Paediatric or syndromic cardiomyopathy v6.7 MYZAP Achchuthan Shanmugasundram reviewed gene: MYZAP: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric or syndromic cardiomyopathy v6.7 FKRP Achchuthan Shanmugasundram reviewed gene: FKRP: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric or syndromic cardiomyopathy v6.7 TAF1A Achchuthan Shanmugasundram reviewed gene: TAF1A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric or syndromic cardiomyopathy v6.7 MAP3K7 Achchuthan Shanmugasundram reviewed gene: MAP3K7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric or syndromic cardiomyopathy v6.7 ALPK3 Achchuthan Shanmugasundram reviewed gene: ALPK3: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Paediatric or syndromic cardiomyopathy v6.6 MYZAP Achchuthan Shanmugasundram Source NHS GMS was added to MYZAP.
Source Expert Review Green was added to MYZAP.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric or syndromic cardiomyopathy v6.6 FKRP Achchuthan Shanmugasundram Source Expert Review Green was added to FKRP.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric or syndromic cardiomyopathy v6.6 TAF1A Achchuthan Shanmugasundram Source NHS GMS was added to TAF1A.
Source Expert Review Green was added to TAF1A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric or syndromic cardiomyopathy v6.6 MAP3K7 Achchuthan Shanmugasundram Source NHS GMS was added to MAP3K7.
Source Expert Review Green was added to MAP3K7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric or syndromic cardiomyopathy v6.6 ALPK3 Achchuthan Shanmugasundram Mode of inheritance for gene ALPK3 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Paediatric disorders - additional genes v6.12 COL5A1 Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: COL5A1.
Tag Q3_24_NHS_review was removed from gene: COL5A1.
Tag Q3_24_expert_review was removed from gene: COL5A1.
Paediatric disorders - additional genes v6.12 ZNRF3 Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: ZNRF3.
Paediatric disorders - additional genes v6.12 MYH11 Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: MYH11.
Paediatric disorders - additional genes v6.12 COL5A1 Achchuthan Shanmugasundram reviewed gene: COL5A1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Paediatric disorders - additional genes v6.12 ZNRF3 Achchuthan Shanmugasundram commented on gene: ZNRF3: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Paediatric disorders - additional genes v6.12 MYH11 Achchuthan Shanmugasundram reviewed gene: MYH11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric disorders - additional genes v6.11 ZNRF3 Achchuthan Shanmugasundram Source Expert Review Green was added to ZNRF3.
Source NHS GMS was added to ZNRF3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v6.11 MYH11 Achchuthan Shanmugasundram Source Expert Review Green was added to MYH11.
Source NHS GMS was added to MYH11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v5.44 CRYAB Achchuthan Shanmugasundram changed review comment from: The DDG2P confidence category for the disease CRYAB-related alpha-related B crystallinopathy is definitive. The allelic requirement and mutation consequence are monoallelic_autosomal and altered gene product structure (PMID: 14681890;21130652;21337604;570292;28493373;9731540;23590293;19597569;30681346;16877416;16505043;38212463;32420686;11577372;21920752). The DDG2P confidence category for the disease CRYAB-related myopathy, myofibrillar, fatal infantile hypertonic, alpha-B crystallin-related, OMIM:613869 is limited. The allelic requirement and mutation consequence are biallelic_autosomal and absent gene product (PMID: 21337604).; to: The DDG2P confidence category for the disease CRYAB-related alpha-related B crystallinopathy is definitive. The allelic requirement, mutation consequence and cross cutting modifier are monoallelic_autosomal, altered gene product structure and typified by age related penetrance (PMID: 14681890;21130652;21337604;570292;28493373;9731540;23590293;19597569;30681346;16877416;16505043;38212463;32420686;11577372;21920752). The DDG2P confidence category for the disease CRYAB-related myopathy, myofibrillar, fatal infantile hypertonic, alpha-B crystallin-related, OMIM:613869 is limited. The allelic requirement and mutation consequence are biallelic_autosomal and absent gene product (PMID: 21337604).
DDG2P v5.44 LAMP2 Achchuthan Shanmugasundram changed review comment from: The DDG2P confidence category for the disease LAMP2-related Danon disease is definitive. The allelic requirement and mutation consequence are monoallelic_X_het and absent gene product;altered gene product structure;decreased gene product level (PMID: 19057086;3087571;8504498;15253947;30681346;19588270;20173215;10972294;15673802;12112061;15907287;30857840;16217705).; to: The DDG2P confidence category for the disease LAMP2-related Danon disease is definitive. The allelic requirement and mutation consequence are monoallelic_X_het and absent gene product;altered gene product structure;decreased gene product level. This gene is typified by age related penetrance (PMID: 19057086;3087571;8504498;15253947;30681346;19588270;20173215;10972294;15673802;12112061;15907287;30857840;16217705).
DDG2P v5.44 FXN Achchuthan Shanmugasundram changed review comment from: The DDG2P confidence category for the disease FXN-related Friedreich ataxia is definitive. The allelic requirement and mutation consequence are biallelic_autosomal and altered gene product structure;decreased gene product level (PMID: 28405347;25566998;30681346;24705334;10633128;22409940;26704351;22691228).; to: The DDG2P confidence category for the disease FXN-related Friedreich ataxia is definitive. The allelic requirement and mutation consequence are biallelic_autosomal and altered gene product structure;decreased gene product level. This gene is typified by age related penetrance (PMID: 28405347;25566998;30681346;24705334;10633128;22409940;26704351;22691228).
DDG2P v5.44 TCP1 Achchuthan Shanmugasundram Tag de novo tag was added to gene: TCP1.
DDG2P v5.44 RBBP5 Achchuthan Shanmugasundram Tag de novo tag was added to gene: RBBP5.
DDG2P v5.44 HDAC3 Achchuthan Shanmugasundram Tag de novo tag was added to gene: HDAC3.
DDG2P v5.44 GNAI1 Achchuthan Shanmugasundram Tag de novo tag was added to gene: GNAI1.
DDG2P v5.44 GABRD Achchuthan Shanmugasundram Tag de novo tag was added to gene: GABRD.
DDG2P v5.44 FEM1B Achchuthan Shanmugasundram Tag de novo tag was added to gene: FEM1B.
DDG2P v5.44 CCT6A Achchuthan Shanmugasundram Tag de novo tag was added to gene: CCT6A.
DDG2P v5.44 AFF3 Achchuthan Shanmugasundram changed review comment from: The DDG2P confidence category for the disease AFF3-related intellectual disability is moderate. The allelic requirement and mutation consequence are monoallelic_autosomal and decreased gene product level (PMID: 38811945). The DDG2P confidence category for the disease AFF3-related KINSSHIP syndrome, OMIM:619297 is strong. The allelic requirement and mutation consequence are monoallelic_autosomal and altered gene product structure (PMID: 33961779;36576140;38811945).; to: The DDG2P confidence category for the disease AFF3-related intellectual disability is moderate. The allelic requirement and mutation consequence are monoallelic_autosomal and decreased gene product level. It shows incomplete penetrance (PMID: 38811945). The DDG2P confidence category for the disease AFF3-related KINSSHIP syndrome, OMIM:619297 is strong. The allelic requirement and mutation consequence are monoallelic_autosomal and altered gene product structure (PMID: 33961779;36576140;38811945).
DDG2P v5.44 NPRL3 Achchuthan Shanmugasundram changed review comment from: The DDG2P confidence category for the disease NPRL3-related familial focal epilepsy with or without focal cortical dysplasia is strong. The allelic requirement and mutation consequence are monoallelic_autosomal and absent gene product;decreased gene product level (PMID: 27173016;34965576;26786403;35136953;34868250;26285051;26505888).; to: The DDG2P confidence category for the disease NPRL3-related familial focal epilepsy with or without focal cortical dysplasia is strong. The allelic requirement and mutation consequence are monoallelic_autosomal and absent gene product;decreased gene product level. This gene shows incomplete penetrance (PMID: 27173016;34965576;26786403;35136953;34868250;26285051;26505888).
DDG2P v5.44 NPRL2 Achchuthan Shanmugasundram changed review comment from: The DDG2P confidence category for the disease NPRL2-related familial focal epilepsy with or without focal cortical dysplasia is strong. The allelic requirement and mutation consequence are monoallelic_autosomal and absent gene product;decreased gene product level (PMID: 37259768;28199897;34965576;34376795;26505888;30093711;31835056;27173016).; to: The DDG2P confidence category for the disease NPRL2-related familial focal epilepsy with or without focal cortical dysplasia is strong. The allelic requirement and mutation consequence are monoallelic_autosomal and absent gene product;decreased gene product level. This gene shows incomplete penetrance (PMID: 37259768;28199897;34965576;34376795;26505888;30093711;31835056;27173016).
DDG2P v5.44 KCNK4 Achchuthan Shanmugasundram Phenotypes for gene: KCNK4 were changed from FHEIG (facial dysmorphism, hypertrichosis, epilepsy, intellectual disability/developmental delay, and gingival overgrowth); Facial dysmorphism, hypertrichosis, epilepsy, intellectual disability/developmental delay, and gingival overgrowth to KCNK4-related facial dysmorphism, hypertrichosis, epilepsy, intellectual and developmental delay, and gingival overgrowth syndrome, OMIM:618381
DDG2P v5.43 KCNK4 Achchuthan Shanmugasundram edited their review of gene: KCNK4: Changed phenotypes to: KCNK4-related facial dysmorphism, hypertrichosis, epilepsy, intellectual and developmental delay, and gingival overgrowth syndrome, OMIM:618381
DDG2P v5.43 CCT8 Achchuthan Shanmugasundram changed review comment from: The DDG2P confidence category for the disease CCT8-related neurodevelopmental disorder with brain abnormalities is limited. The allelic requirement and mutation consequence are monoallelic_autosomal and absent gene product;altered gene product structure;decreased gene product level (PMID: ).; to: The DDG2P confidence category for the disease CCT8-related neurodevelopmental disorder with brain abnormalities is limited. The allelic requirement and mutation consequence are monoallelic_autosomal and absent gene product;altered gene product structure;decreased gene product level.
DDG2P v5.43 XYLT1 Achchuthan Shanmugasundram Phenotypes for gene: XYLT1 were changed from DESBUQUOIS DYSPLASIA 2, OMIM:615777; Baratela Scott Syndrome, OMIM:615777 to XYLT1-related Desbuquois dysplasia, OMIM:615777
DDG2P v5.43 XYLT1 Achchuthan Shanmugasundram Publications for gene: XYLT1 were set to 23982343; 24581741; 22711505; 30554721
DDG2P v5.42 XYLT1 Achchuthan Shanmugasundram edited their review of gene: XYLT1: Changed phenotypes to: XYLT1-related Desbuquois dysplasia, OMIM:615777
DDG2P v5.42 WRAP53 Achchuthan Shanmugasundram Phenotypes for gene: WRAP53 were changed from DYSKERATOSIS CONGENITA, AUTOSOMAL RECESSIVE 3 613988 to WRAP53-related dyskeratosis congenita, OMIM:613988
DDG2P v5.41 WRAP53 Achchuthan Shanmugasundram Publications for gene: WRAP53 were set to 21205863
DDG2P v5.40 WRAP53 Achchuthan Shanmugasundram edited their review of gene: WRAP53: Changed phenotypes to: WRAP53-related dyskeratosis congenita, OMIM:613988
DDG2P v5.40 USP14 Achchuthan Shanmugasundram Phenotypes for gene: USP14 were changed from DISTAL ARTHROGRYPOSIS to USP14-related syndromic neurodevelopmental disorder with arthrogryposis
DDG2P v5.39 USP14 Achchuthan Shanmugasundram Publications for gene: USP14 were set to 35066879
DDG2P v5.38 USP14 Achchuthan Shanmugasundram edited their review of gene: USP14: Changed phenotypes to: USP14-related syndromic neurodevelopmental disorder with arthrogryposis
DDG2P v5.38 SMARCA2 Achchuthan Shanmugasundram Phenotypes for gene: SMARCA2 were changed from COFFIN SIRIS 135900; NICOLAIDES-BARAITSER SYNDROME 601358 to SMARCA2-related Nicolaides-Baraitser syndrome, OMIM:601358
DDG2P v5.37 SMARCA2 Achchuthan Shanmugasundram Publications for gene: SMARCA2 were set to 32694869; 19606471; 22366787; 22426308
DDG2P v5.36 SMARCA2 Achchuthan Shanmugasundram edited their review of gene: SMARCA2: Changed phenotypes to: SMARCA2-related Nicolaides-Baraitser syndrome, OMIM:601358
DDG2P v5.36 PIK3CA Achchuthan Shanmugasundram Phenotypes for gene: PIK3CA were changed from HEMIMEGALENCEPHALY PIK3CA; CLOVES: CONGENITAL LIPOMATOUS OVERGROWTH, VASCULAR MALFORMATIONS, AND EPIDERMAL NEVI, OMIM:612918; MEGALENCEPHALY-CAPILLARY MALFORMATION-POLYMICROGYRIA SYNDROME, SOMATIC 3, OMIM:602501 to PIK3CA-related overgrowth spectrum disorder with or without megalencephaly, capillary malformation, polymicrogyria and lipomatous overgrowth
DDG2P v5.35 PIK3CA Achchuthan Shanmugasundram edited their review of gene: PIK3CA: Changed phenotypes to: PIK3CA-related overgrowth spectrum disorder with or without megalencephaly, capillary malformation, polymicrogyria and lipomatous overgrowth
DDG2P v5.35 PIGN Achchuthan Shanmugasundram Phenotypes for gene: PIGN were changed from MULTIPLE CONGENITAL ANOMALIES-HYPOTONIA-SEIZURES SYNDROME 614080 to PIGN-related multiple congenital anomalies-hypotonia-seizures syndrome, OMIM:614080
DDG2P v5.34 PIGN Achchuthan Shanmugasundram Publications for gene: PIGN were set to 21493957; 36322149
DDG2P v5.33 PIGN Achchuthan Shanmugasundram edited their review of gene: PIGN: Changed phenotypes to: PIGN-related multiple congenital anomalies-hypotonia-seizures syndrome, OMIM:614080
DDG2P v5.33 PCGF2 Achchuthan Shanmugasundram Publications for gene: PCGF2 were set to 30526864
DDG2P v5.32 PCGF2 Achchuthan Shanmugasundram Phenotypes for gene: PCGF2 were changed from INTELLECTUAL DUSBILITY; Craniofacial Neurological Cardiovascular and Skeletal Features to PCGF2-related craniofacial neurological cardiovascular and skeletal features (Turnpenny-Fry syndrome), OMIM:618371
DDG2P v5.31 PCGF2 Achchuthan Shanmugasundram edited their review of gene: PCGF2: Changed phenotypes to: PCGF2-related craniofacial neurological cardiovascular and skeletal features (Turnpenny-Fry syndrome), OMIM:618371
DDG2P v5.31 OPHN1 Achchuthan Shanmugasundram Phenotypes for gene: OPHN1 were changed from MENTAL RETARDATION X-LINKED OPHN1-RELATED 300486 to OPHN1-related intellectual developmental disorder, OMIM:300486
DDG2P v5.31 OPHN1 Achchuthan Shanmugasundram Publications for gene: OPHN1 were set to 20528889; 12805098; 12807966; 9582072; 16158428
DDG2P v5.30 OPHN1 Achchuthan Shanmugasundram edited their review of gene: OPHN1: Changed phenotypes to: OPHN1-related intellectual developmental disorder, OMIM:300486
DDG2P v5.30 NUP107 Achchuthan Shanmugasundram Phenotypes for gene: NUP107 were changed from GALLOWAY-MOWAT SYNDROME 7, OMIM:618348 to NUP107-related steroid resistant nephrotic syndrome with microcephaly, developmental delay and simplified gyration (Galloway-Mowat syndrome), OMIM:618348
DDG2P v5.29 NUP107 Achchuthan Shanmugasundram Publications for gene: NUP107 were set to 28280135; 26411495
DDG2P v5.28 NUP107 Achchuthan Shanmugasundram edited their review of gene: NUP107: Changed phenotypes to: NUP107-related steroid resistant nephrotic syndrome with microcephaly, developmental delay and simplified gyration (Galloway-Mowat syndrome), OMIM:618348
DDG2P v5.28 NOP10 Achchuthan Shanmugasundram Phenotypes for gene: NOP10 were changed from DYSKERATOSIS CONGENITA, AUTOSOMAL RECESSIVE 1 224230; NOP10-RELATED DYSKERATOSIS CONGENITA 318811 to NOP10-related dyskeratosis congenita, OMIM:224230
DDG2P v5.27 NOP10 Achchuthan Shanmugasundram edited their review of gene: NOP10: Changed phenotypes to: NOP10-related dyskeratosis congenita, OMIM:224230
DDG2P v5.27 NHP2 Achchuthan Shanmugasundram Phenotypes for gene: NHP2 were changed from DYSKERATOSIS CONGENITA, AUTOSOMAL RECESSIVE 2 613987 to NHP2-related dyskeratosis congenita, OMIM:613987
DDG2P v5.27 NHP2 Achchuthan Shanmugasundram Publications for gene: NHP2 were set to 18523010
DDG2P v5.26 NHP2 Achchuthan Shanmugasundram edited their review of gene: NHP2: Changed phenotypes to: NHP2-related dyskeratosis congenita, OMIM:613987
DDG2P v5.26 NECTIN1 Achchuthan Shanmugasundram Phenotypes for gene: NECTIN1 were changed from CLEFT LIP/PALATE-ECTODERMAL DYSPLASIA SYNDROME 225060 to NECTIN1-related cleft lip/palate-ectodermal dysplasia syndrome, OMIM:225060
DDG2P v5.25 NECTIN1 Achchuthan Shanmugasundram edited their review of gene: NECTIN1: Changed phenotypes to: NECTIN1-related cleft lip/palate-ectodermal dysplasia syndrome, OMIM:225060
DDG2P v5.25 MYH9 Achchuthan Shanmugasundram Phenotypes for gene: MYH9 were changed from DEAFNESS AUTOSOMAL DOMINANT TYPE 17 603622; SEBASTIAN SYNDROME 155100; MACROTHROMBOCYTOPENIA WITH PROGRESSIVE SENSORINEURAL DEAFNESS 155100; EPSTEIN SYNDROME 155100; MAY-HEGGLIN ANOMALY 155100; FECHTNER SYNDROME 155100 to MYH9-related macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss, OMIM:155100
DDG2P v5.24 MYH9 Achchuthan Shanmugasundram edited their review of gene: MYH9: Changed phenotypes to: MYH9-related macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss, OMIM:155100
DDG2P v5.24 MAF Achchuthan Shanmugasundram Phenotypes for gene: MAF were changed from Ayme-Gripp syndrome: CATARACT, DEAFNESS, INTELLECTUAL DISABILITY, SEIZURES, AND A DOWN SYNDROME-LIKE FACIES; CATARACT PULVERULENT JUVENILE-ONSET MAF-RELATED 610202; CATARACT CONGENITAL CERULEAN TYPE 4 610202 to MAF-related cataracts, congenital, with sensorineural deafness, down syndrome-like facial appearance, short stature, and mental retardation, OMIM:601088; MAF-related cataract, OMIM:610202
DDG2P v5.23 MAF Achchuthan Shanmugasundram Publications for gene: MAF were set to 11772997; 24664492; 16470690
DDG2P v5.22 MAF Achchuthan Shanmugasundram edited their review of gene: MAF: Changed phenotypes to: MAF-related cataracts, congenital, with sensorineural deafness, down syndrome-like facial appearance, short stature, and mental retardation, OMIM:601088, MAF-related cataract, OMIM:610202
DDG2P v5.22 LFNG Achchuthan Shanmugasundram Phenotypes for gene: LFNG were changed from SPONDYLOCOSTAL DYSOSTOSIS TYPE 3 609813 to SPONDYLOCOSTAL DYSOSTOSIS TYPE 3, OMIM:609813
DDG2P v5.21 LAMP2 Achchuthan Shanmugasundram Publications for gene: LAMP2 were set to 15907287; 8504498; 12112061; 10972294; 15253947; 15673802; 3087571
DDG2P v5.20 LAMP2 Achchuthan Shanmugasundram Phenotypes for gene: LAMP2 were changed from DANON DISEASE 300257 to Danon disease, OMIM:300257
DDG2P v5.19 LAMP2 Achchuthan Shanmugasundram edited their review of gene: LAMP2: Changed phenotypes to: LAMP2-related Danon disease
DDG2P v5.19 H3F3A Achchuthan Shanmugasundram Phenotypes for gene: H3F3A were changed from Craniofacial with neurodevelopment disorders to H3-3A-related Bryant-Li-Bhoj neurodevelopmental syndrome, OMIM:619720
DDG2P v5.18 H3F3A Achchuthan Shanmugasundram edited their review of gene: H3F3A: Changed phenotypes to: H3-3A-related Bryant-Li-Bhoj neurodevelopmental syndrome, OMIM:619720
DDG2P v5.18 GNAI1 Achchuthan Shanmugasundram edited their review of gene: GNAI1: Changed phenotypes to: GNAI1-related neurodevelopmental disorder with hypotonia, impaired speech, and behavioural abnormalities, OMIM:619854
DDG2P v5.18 GFER Achchuthan Shanmugasundram Phenotypes for gene: GFER were changed from MITOCHONDRIAL PROGRESSIVE MYOPATHY WITH CONGENITAL CATARACT HEARING LOSS AND DEVELOPMENTAL DELAY (MPMCHD 613076 to GFER-related mitochondrial progressive myopathy with congenital cataract, hearing loss and developmental delay, OMIM:613076
DDG2P v5.17 GFER Achchuthan Shanmugasundram Publications for gene: GFER were set to 19409522
DDG2P v5.16 GFER Achchuthan Shanmugasundram edited their review of gene: GFER: Changed phenotypes to: GFER-related mitochondrial progressive myopathy with congenital cataract, hearing loss and developmental delay, OMIM:613076
DDG2P v5.16 DLL1 Achchuthan Shanmugasundram Phenotypes for gene: DLL1 were changed from INTELLECTUAL DISABILITY 616579 to DLL1-related neurodevelopmental disorder with nonspecific brain abnormalities, with or without seizures, OMIM:618709
DDG2P v5.15 DLL1 Achchuthan Shanmugasundram Publications for gene: DLL1 were set to 31353024
DDG2P v5.14 DLL1 Achchuthan Shanmugasundram edited their review of gene: DLL1: Changed phenotypes to: DLL1-related neurodevelopmental disorder with nonspecific brain abnormalities, with or without seizures, OMIM:618709
DDG2P v5.14 CRYGD Achchuthan Shanmugasundram Phenotypes for gene: CRYGD were changed from Cataract 2, multiple types, OMIM:115700 to CRYGD-related cataract, OMIM:115700
DDG2P v5.13 CRYGD Achchuthan Shanmugasundram Publications for gene: CRYGD were set to 9927684; 17564961; 12011157; 10915766; 10521291
DDG2P v5.12 CRYGD Achchuthan Shanmugasundram edited their review of gene: CRYGD: Changed phenotypes to: CRYGD-related cataract, OMIM:115700
DDG2P v5.12 CRYBB2 Achchuthan Shanmugasundram Publications for gene: CRYBB2 were set to 8812489; 11424921
DDG2P v5.11 CRYBB2 Achchuthan Shanmugasundram Phenotypes for gene: CRYBB2 were changed from CATARACT, CONGENITAL, CERULEAN TYPE, 2 601547; CATARACT, COPPOCK-LIKE 604307 to CRYBB2-related cataract, OMIM:601547
DDG2P v5.10 CRYBB2 Achchuthan Shanmugasundram edited their review of gene: CRYBB2: Changed phenotypes to: CRYBB2-related cataract, OMIM:601547
DDG2P v5.10 CRYAB Achchuthan Shanmugasundram Publications for gene: CRYAB were set to 11577372; 21337604
DDG2P v5.9 CRYAB Achchuthan Shanmugasundram Phenotypes for gene: CRYAB were changed from MYOPATHY, MYOFIBRILLAR, FATAL INFANTILE HYPERTONIC, ALPHA-B CRYSTALLIN-RELATED 613869; CATARACT POSTERIOR POLAR TYPE 2 613763 to CRYAB-related alpha-related B crystallinopathy; CRYAB-related myopathy, myofibrillar, fatal infantile hypertonic, alpha-B crystallin-related, OMIM:613869
DDG2P v5.8 CRYAB Achchuthan Shanmugasundram edited their review of gene: CRYAB: Changed phenotypes to: CRYAB-related alpha-related B crystallinopathy, CRYAB-related myopathy, myofibrillar, fatal infantile hypertonic, alpha-B crystallin-related, OMIM:613869
DDG2P v5.8 CRELD1 Achchuthan Shanmugasundram Phenotypes for gene: CRELD1 were changed from HETEROTAXY SYNDROME 207574 to CRELD1-related neurodevelopmental disorder with hypotonia and seizures, OMIM:620771; CRELD1-related atrioventricular septal defect susceptibility, OMIM:606217
DDG2P v5.7 CRELD1 Achchuthan Shanmugasundram Publications for gene: CRELD1 were set to
DDG2P v5.6 CRELD1 Achchuthan Shanmugasundram edited their review of gene: CRELD1: Changed phenotypes to: CRELD1-related neurodevelopmental disorder with hypotonia and seizures, OMIM:620771, CRELD1-related atrioventricular septal defect susceptibility, OMIM:606217
DDG2P v5.6 ATOH7 Achchuthan Shanmugasundram Phenotypes for gene: ATOH7 were changed from RETINAL NON-ATTACHMENT CONGENITAL NON-SYNDROMIC 221900 to ATOH7-related persistent hyperplastic primary vitreous, OMIM:221900
DDG2P v5.6 ATOH7 Achchuthan Shanmugasundram Publications for gene: ATOH7 were set to
DDG2P v5.5 ATOH7 Achchuthan Shanmugasundram edited their review of gene: ATOH7: Changed phenotypes to: ATOH7-related persistent hyperplastic primary vitreous, OMIM:221900
DDG2P v5.5 AFF3 Achchuthan Shanmugasundram Phenotypes for gene: AFF3 were changed from Skeletal dysplasia with severe neurological disease to AFF3-related KINSSHIP syndrome, OMIM:619297; AFF3-related intellectual disability
DDG2P v5.4 AFF3 Achchuthan Shanmugasundram Publications for gene: AFF3 were set to 36576140; 33961779; 100000
DDG2P v5.3 AFF3 Achchuthan Shanmugasundram edited their review of gene: AFF3: Changed phenotypes to: AFF3-related KINSSHIP syndrome, OMIM:619297, AFF3-related intellectual disability
DDG2P v5.3 CYHR1 Achchuthan Shanmugasundram reviewed gene: CYHR1: Rating: RED; Mode of pathogenicity: Other; Publications: 38641995; Phenotypes: ZFTRAF1-related neurodevelopmental disorder; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
DDG2P v5.3 SGSM3 Achchuthan Shanmugasundram reviewed gene: SGSM3: Rating: RED; Mode of pathogenicity: ; Publications: 37833060; Phenotypes: SGSM3-related intellectual disability; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
DDG2P v5.3 PLA2G16 Achchuthan Shanmugasundram reviewed gene: PLA2G16: Rating: RED; Mode of pathogenicity: ; Publications: 37919452; Phenotypes: PLAAT3-related lipodystrophy syndrome with neurological features, OMIM:620683; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
DDG2P v5.3 KCNK4 Achchuthan Shanmugasundram edited their review of gene: KCNK4: Added comment: The DDG2P confidence category for the disease KCNK4-related facial dysmorphism, hypertrichosis, epilepsy, intellectual and developmental delay, and gingival overgrowth syndrome, OMIM:618381 is limited. The allelic requirement and mutation consequence are monoallelic_autosomal and altered gene product structure (PMID: 30290154).; Changed rating: RED; Changed phenotypes to: FHEIG (facial dysmorphism, hypertrichosis, epilepsy, intellectual disability/developmental delay, and gingival overgrowth), Facial dysmorphism, hypertrichosis, epilepsy, intellectual disability/developmental delay, and gingival overgrowth, KCNK4-related facial dysmorphism, hypertrichosis, epilepsy, intellectual and developmental delay, and gingival overgrowth syndrome, OMIM:618381
DDG2P v5.3 DLG2 Achchuthan Shanmugasundram reviewed gene: DLG2: Rating: RED; Mode of pathogenicity: Other; Publications: 37860969; Phenotypes: DLG2-related neurodevelopmental disorder; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
DDG2P v5.3 COX18 Achchuthan Shanmugasundram reviewed gene: COX18: Rating: RED; Mode of pathogenicity: Other; Publications: 37468577, 39006432, 38960055; Phenotypes: COX18-related peripheral neuropathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
DDG2P v5.3 CELSR1 Achchuthan Shanmugasundram reviewed gene: CELSR1: Rating: RED; Mode of pathogenicity: Other; Publications: 38272662; Phenotypes: CELSR1-related fetal hydrops; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
DDG2P v5.3 CCT8 Achchuthan Shanmugasundram reviewed gene: CCT8: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: CCT8-related neurodevelopmental disorder with brain abnormalities; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
DDG2P v5.3 CCT7 Achchuthan Shanmugasundram reviewed gene: CCT7: Rating: RED; Mode of pathogenicity: ; Publications: 39480921; Phenotypes: CCT7-related neurodevelopmental disorder with brain abnormalities; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
DDG2P v5.3 CCT5 Achchuthan Shanmugasundram reviewed gene: CCT5: Rating: RED; Mode of pathogenicity: ; Publications: 39480921; Phenotypes: CCT5-related neurodevelopmental disorder with brain abnormalities; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
DDG2P v5.3 CCT4 Achchuthan Shanmugasundram reviewed gene: CCT4: Rating: RED; Mode of pathogenicity: ; Publications: 39480921; Phenotypes: CCT4-related neurodevelopmental disorder with brain abnormalities; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
DDG2P v5.3 ANO3 Achchuthan Shanmugasundram reviewed gene: ANO3: Rating: RED; Mode of pathogenicity: Other; Publications: 38079528, 33502045; Phenotypes: ANO3-related dystonia, OMIM:615034; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
DDG2P v5.3 ZSCAN10 Achchuthan Shanmugasundram reviewed gene: ZSCAN10: Rating: GREEN; Mode of pathogenicity: Other; Publications: 38386308; Phenotypes: ZSCAN10-related neurodevelopmental disorder with oto-facial malformations; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
DDG2P v5.3 ZNF699 Achchuthan Shanmugasundram reviewed gene: ZNF699: Rating: GREEN; Mode of pathogenicity: ; Publications: 39424669, 36801247, 33875846, 34374989, 35205213; Phenotypes: ZNF699-related developmental delay with gastrointestinal, cardiovascular, genitourinary, and skeletal abnormalities (DEGCAGS syndrome), OMIM:619488; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
DDG2P v5.3 ZMYND8 Achchuthan Shanmugasundram commented on gene: ZMYND8: The DDG2P confidence category for the disease ZMYND8-related neurodevelopmental disorder is moderate. The allelic requirement and mutation consequence are monoallelic_autosomal and absent gene product;altered gene product structure (PMID: 35916866).
DDG2P v5.3 ZFX Achchuthan Shanmugasundram reviewed gene: ZFX: Rating: GREEN; Mode of pathogenicity: ; Publications: 38325380; Phenotypes: ZFX-related neurodevelopmental disorder with hypotonia, congenital anomalies and facial dysmorphism with or without hyperparathyroidism; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
DDG2P v5.3 XYLT1 Achchuthan Shanmugasundram edited their review of gene: XYLT1: Added comment: The DDG2P confidence category for the disease XYLT1-related Desbuquois dysplasia, OMIM:615777 is strong. The allelic requirement and mutation consequence are biallelic_autosomal and absent gene product;cis-regulatory or promotor mutation (PMID: 35081921;24581741;23982343;30554721).; Changed publications to: 35081921, 23982343, 24581741, 30554721; Changed phenotypes to: DESBUQUOIS DYSPLASIA 2, OMIM:615777, XYLT1-related Desbuquois dysplasia, OMIM:615777, Baratela Scott Syndrome, OMIM:615777
DDG2P v5.3 WRAP53 Achchuthan Shanmugasundram edited their review of gene: WRAP53: Added comment: The DDG2P confidence category for the disease WRAP53-related dyskeratosis congenita, OMIM:613988 is strong. The allelic requirement and mutation consequence are biallelic_autosomal and absent gene product;altered gene product structure (PMID: 29514627;34599657;32303682;21205863).; Changed publications to: 34599657, 29514627, 21205863, 32303682; Changed phenotypes to: DYSKERATOSIS CONGENITA, AUTOSOMAL RECESSIVE 3, OMIM:613988, WRAP53-related dyskeratosis congenita, OMIM:613988
DDG2P v5.3 USP14 Achchuthan Shanmugasundram edited their review of gene: USP14: Added comment: The DDG2P confidence category for the disease USP14-related syndromic neurodevelopmental disorder with arthrogryposis is moderate. The allelic requirement and mutation consequence are biallelic_autosomal and absent gene product;altered gene product structure;decreased gene product level (PMID: 38469793;35066879).; Changed rating: GREEN; Changed publications to: 38469793, 35066879; Changed phenotypes to: DISTAL ARTHROGRYPOSIS, USP14-related syndromic neurodevelopmental disorder with arthrogryposis
DDG2P v5.3 UBA2 Achchuthan Shanmugasundram reviewed gene: UBA2: Rating: GREEN; Mode of pathogenicity: ; Publications: 32758660, 28110515, 34159400, 31587267, 39149811, 31332306, 37221169, 34040189; Phenotypes: UBA2-related congenital anomalies with or without aplasia cutis congenita and ectrodactyly and variable developmental delay, OMIM:619959; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
DDG2P v5.3 TCP1 Achchuthan Shanmugasundram reviewed gene: TCP1: Rating: GREEN; Mode of pathogenicity: ; Publications: 39480921; Phenotypes: TCP1-related neurodevelopmental disorder with polymicrogyria; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
DDG2P v5.3 SNF8 Achchuthan Shanmugasundram reviewed gene: SNF8: Rating: GREEN; Mode of pathogenicity: ; Publications: 38423010; Phenotypes: SNF8-related disease spectrum (severe developmental and epileptic encephalopathy to syndromic optic atrophy); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
DDG2P v5.3 SMARCA2 Achchuthan Shanmugasundram edited their review of gene: SMARCA2: Added comment: The DDG2P confidence category for the disease SMARCA2-related Nicolaides-Baraitser syndrome , OMIM:601358 is definitive. The allelic requirement and mutation consequence are monoallelic_autosomal and absent gene product;altered gene product structure (PMID: 31813144;34521483;34296532;31288860;25169058;27665729;22366787;22426308;32694869;35811451;32657847;22822383;28948053).; Changed publications to: 28948053, 32657847, 31813144, 25169058, 22426308, 34521483, 22366787, 34296532, 32694869, 31288860, 27665729, 22822383, 35811451; Changed phenotypes to: NICOLAIDES-BARAITSER SYNDROME, OMIM:601358, SMARCA2-related Nicolaides-Baraitser syndrome , OMIM:601358
DDG2P v5.3 SLC4A10 Achchuthan Shanmugasundram reviewed gene: SLC4A10: Rating: GREEN; Mode of pathogenicity: ; Publications: 38054405, 37459438, 31130284; Phenotypes: SLC4A10-related neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, OMIM:620746; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
DDG2P v5.3 SLC12A9 Achchuthan Shanmugasundram reviewed gene: SLC12A9: Rating: GREEN; Mode of pathogenicity: Other; Publications: 38334070; Phenotypes: SLC12A9-related syndromic neurodevelopmental disorder with lysosome defects; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
DDG2P v5.3 SASS6 Achchuthan Shanmugasundram reviewed gene: SASS6: Rating: GREEN; Mode of pathogenicity: Other; Publications: 38501757, 24951542, 30639237, 36739862; Phenotypes: SASS6-related severe microcephaly with brain abnormalities; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
DDG2P v5.3 RBBP5 Achchuthan Shanmugasundram reviewed gene: RBBP5: Rating: GREEN; Mode of pathogenicity: ; Publications: 39036895; Phenotypes: RBBP5-related neurodevelopmental disorder; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
DDG2P v5.3 RAB1A Achchuthan Shanmugasundram reviewed gene: RAB1A: Rating: GREEN; Mode of pathogenicity: ; Publications: 37924809, 38091987; Phenotypes: RAB1A-related neurodevelopmental disorder with speech and motor delay and spasticity; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
DDG2P v5.3 PNPLA8 Achchuthan Shanmugasundram reviewed gene: PNPLA8: Rating: GREEN; Mode of pathogenicity: ; Publications: 29681094, 37671596, 34177434, 39082157, 37057294, 25512002; Phenotypes: PNPLA8-related progressive microcephaly with seizures and neurodegeneration; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
DDG2P v5.3 PLS3 Achchuthan Shanmugasundram reviewed gene: PLS3: Rating: GREEN; Mode of pathogenicity: ; Publications: 35752817, 28777485, 28748388, 29736964, 38043102, 37751738, 28620780, 25209159, 24616189, 24088043; Phenotypes: PLS3-related osteoporosis with fractures, OMIM:300910, PLS3-related diaphragmatic hernia and body-wall defects; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
DDG2P v5.3 PIK3CA Achchuthan Shanmugasundram edited their review of gene: PIK3CA: Added comment: The DDG2P confidence category for the disease PIK3CA-related overgrowth spectrum disorder with or without megalencephaly, capillary malformation, polymicrogyria and lipomatous overgrowth is definitive. The allelic requirement and mutation consequence are monoallelic_autosomal and altered gene product structure (PMID: 22658544;22729224).; Changed phenotypes to: MEGALENCEPHALY-CAPILLARY MALFORMATION-POLYMICROGYRIA SYNDROME, SOMATIC 3, OMIM:602501, CLOVES: CONGENITAL LIPOMATOUS OVERGROWTH, VASCULAR MALFORMATIONS, AND EPIDERMAL NEVI, OMIM:612918, HEMIMEGALENCEPHALY PIK3CA, PIK3CA-related overgrowth spectrum disorder with or without megalencephaly, capillary malformation, polymicrogyria and lipomatous overgrowth
DDG2P v5.3 PIGN Achchuthan Shanmugasundram edited their review of gene: PIGN: Added comment: The DDG2P confidence category for the disease PIGN-related multiple congenital anomalies-hypotonia-seizures syndrome, OMIM:614080 is strong. The allelic requirement and mutation consequence are biallelic_autosomal and absent gene product;altered gene product structure (PMID: 26364997;35468813;34051595;32585529;33193741;27300081;27038415;24852103;33966742;21493957;29096607;26419326;26394714;29330547;24253414;36363484;35812661;36322149).; Changed publications to: 33966742, 26364997, 29330547, 35468813, 34051595, 29096607, 26419326, 36322149, 24852103, 35812661, 27038415, 36363484, 26394714, 27300081, 21493957, 33193741, 24253414, 32585529; Changed phenotypes to: PIGN-related multiple congenital anomalies-hypotonia-seizures syndrome, OMIM:614080, MULTIPLE CONGENITAL ANOMALIES-HYPOTONIA-SEIZURES SYNDROME, OMIM:614080
DDG2P v5.3 PCGF2 Achchuthan Shanmugasundram edited their review of gene: PCGF2: Added comment: The DDG2P confidence category for the disease PCGF2-related craniofacial neurological cardiovascular and skeletal features (Turnpenny-Fry syndrome), OMIM:618371 is strong. The allelic requirement and mutation consequence are monoallelic_autosomal and altered gene product structure (PMID: 30526864;34750959;36105049;30343942).; Changed publications to: 36105049, 34750959, 30343942, 30526864; Changed phenotypes to: Craniofacial Neurological Cardiovascular and Skeletal Features, INTELLECTUAL DISABILITY, PCGF2-related craniofacial neurological cardiovascular and skeletal features (Turnpenny-Fry syndrome), OMIM:618371
DDG2P v5.3 OPHN1 Achchuthan Shanmugasundram edited their review of gene: OPHN1: Added comment: The DDG2P confidence category for the disease OPHN1-related intellectual developmental disorder , OMIM:300486 is definitive. The allelic requirement and mutation consequence are monoallelic_X_het and absent gene product (PMID: 30534410;29510240;24105372;20528889;12805098;12807966;32872024;33638601;9582072;18261018;29960046;27390894;16158428).; Changed publications to: 12805098, 20528889, 12807966, 30534410, 24105372, 29510240, 33638601, 9582072, 16158428, 32872024, 18261018, 29960046, 27390894; Changed phenotypes to: INTELLECTUAL DEVELOPMENTAL DISORDER X-LINKED OPHN1-RELATED, OMIM:300486, OPHN1-related intellectual developmental disorder , OMIM:300486; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
DDG2P v5.3 NUP107 Achchuthan Shanmugasundram edited their review of gene: NUP107: Added comment: The DDG2P confidence category for the disease NUP107-related steroid resistant nephrotic syndrome with microcephaly, developmental delay and simplified gyration (Galloway-Mowat syndrome), OMIM:618348 is strong. The allelic requirement and mutation consequence are biallelic_autosomal and absent gene product;altered gene product structure;decreased gene product level (PMID: 30179222;28280135;26411495).; Changed rating: GREEN; Changed publications to: 28280135, 26411495, 30179222; Changed phenotypes to: NUP107-related steroid resistant nephrotic syndrome with microcephaly, developmental delay and simplified gyration (Galloway-Mowat syndrome), OMIM:618348, GALLOWAY-MOWAT SYNDROME 7, OMIM:618348
DDG2P v5.3 NPRL3 Achchuthan Shanmugasundram reviewed gene: NPRL3: Rating: GREEN; Mode of pathogenicity: ; Publications: 26786403, 26285051, 34965576, 35136953, 27173016, 34868250, 26505888; Phenotypes: NPRL3-related familial focal epilepsy with or without focal cortical dysplasia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
DDG2P v5.3 NPRL2 Achchuthan Shanmugasundram reviewed gene: NPRL2: Rating: GREEN; Mode of pathogenicity: ; Publications: 37259768, 31835056, 34965576, 27173016, 28199897, 34376795, 30093711, 26505888; Phenotypes: NPRL2-related familial focal epilepsy with or without focal cortical dysplasia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
DDG2P v5.3 NOP10 Achchuthan Shanmugasundram edited their review of gene: NOP10: Added comment: The DDG2P confidence category for the disease NOP10-related dyskeratosis congenita, OMIM:224230 is moderate. The allelic requirement and mutation consequence are biallelic_autosomal and absent gene product;altered gene product structure (PMID: 17507419).; Changed rating: GREEN; Changed phenotypes to: NOP10-related dyskeratosis congenita, OMIM:224230, DYSKERATOSIS CONGENITA, AUTOSOMAL RECESSIVE 1, OMIM:224230
DDG2P v5.3 NHP2 Achchuthan Shanmugasundram edited their review of gene: NHP2: Added comment: The DDG2P confidence category for the disease NHP2-related dyskeratosis congenita, OMIM:613987 is moderate. The allelic requirement and mutation consequence are biallelic_autosomal and absent gene product;altered gene product structure (PMID: 37440454;30472699;18523010;31985013).; Changed publications to: 37440454, 31985013, 30472699, 18523010; Changed phenotypes to: NHP2-related dyskeratosis congenita, OMIM:613987, DYSKERATOSIS CONGENITA, AUTOSOMAL RECESSIVE 2, OMIM:613987
DDG2P v5.3 NECTIN1 Achchuthan Shanmugasundram edited their review of gene: NECTIN1: Added comment: The DDG2P confidence category for the disease NECTIN1-related cleft lip/palate-ectodermal dysplasia syndrome, OMIM:225060 is moderate. The allelic requirement and mutation consequence are biallelic_autosomal and absent gene product (PMID: 10932188).; Changed rating: GREEN; Changed phenotypes to: CLEFT LIP/PALATE-ECTODERMAL DYSPLASIA SYNDROME, OMIM:225060, NECTIN1-related cleft lip/palate-ectodermal dysplasia syndrome, OMIM:225060
DDG2P v5.3 MYH9 Achchuthan Shanmugasundram edited their review of gene: MYH9: Added comment: The DDG2P confidence category for the disease MYH9-related macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss, OMIM:155100 is definitive. The allelic requirement and mutation consequence are monoallelic_autosomal and absent gene product;altered gene product structure (PMID: 25077172;10973259).; Changed phenotypes to: MACROTHROMBOCYTOPENIA AND GRANULOCYTE INCLUSIONS WITH OR WITHOUT NEPHRITIS OR SENSORINEURAL HEARING LOSS, OMIM:155100, MYH9-related macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss, OMIM:155100
DDG2P v5.3 MAF Achchuthan Shanmugasundram edited their review of gene: MAF: Added comment: The DDG2P confidence category for the disease MAF-related cataract, OMIM:610202 is definitive. The allelic requirement and mutation consequence are monoallelic_autosomal and altered gene product structure (PMID: 29314435;30659945;11772997;24664492;16470690). The DDG2P confidence category for the disease MAF-related cataracts, congenital, with sensorineural deafness, down syndrome-like facial appearance, short stature, and mental retardation, OMIM:601088 is definitive. The allelic requirement and mutation consequence are monoallelic_autosomal and altered gene product structure (PMID: 25865493).; Changed publications to: 29314435, 24664492, 11772997, 16470690, 25865493, 30659945; Changed phenotypes to: MAF-related cataracts, congenital, with sensorineural deafness, down syndrome-like facial appearance, short stature, and mental retardation, OMIM:601088, CATARACT 21, MULTIPLE TYPES, OMIM:610202, MAF-related cataract, OMIM:610202
DDG2P v5.3 LFNG Achchuthan Shanmugasundram commented on gene: LFNG: The DDG2P confidence category for the disease SPONDYLOCOSTAL DYSOSTOSIS TYPE 3, OMIM:609813 is definitive. The allelic requirement and mutation consequence are biallelic_autosomal and absent gene product;altered gene product structure (PMID: 16385447).
DDG2P v5.3 LAMP2 Achchuthan Shanmugasundram edited their review of gene: LAMP2: Added comment: The DDG2P confidence category for the disease LAMP2-related Danon disease is definitive. The allelic requirement and mutation consequence are monoallelic_X_het and absent gene product;altered gene product structure;decreased gene product level (PMID: 19057086;3087571;8504498;15253947;30681346;19588270;20173215;10972294;15673802;12112061;15907287;30857840;16217705).; Changed publications to: 8504498, 12112061, 15673802, 15253947, 30857840, 16217705, 20173215, 15907287, 19588270, 30681346, 3087571, 19057086, 10972294; Changed phenotypes to: DANON DISEASE, OMIM:300257, LAMP2-related Danon disease; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
DDG2P v5.3 JPH1 Achchuthan Shanmugasundram reviewed gene: JPH1: Rating: GREEN; Mode of pathogenicity: ; Publications: 39209426; Phenotypes: JPH1-related congenital myopathy with ptosis, OMIM:620964; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
DDG2P v5.3 HDAC3 Achchuthan Shanmugasundram reviewed gene: HDAC3: Rating: GREEN; Mode of pathogenicity: Other; Publications: 39047730; Phenotypes: HDAC3-related neurodevelopmental disorder; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
DDG2P v5.3 H3F3A Achchuthan Shanmugasundram edited their review of gene: H3F3A: Added comment: The DDG2P confidence category for the disease H3-3A-related Bryant-Li-Bhoj neurodevelopmental syndrome, OMIM:619720 is strong. The allelic requirement and mutation consequence are monoallelic_autosomal and altered gene product structure (PMID: 33057194;31942419;33268356).; Changed publications to: 33057194, 31942419, 33268356; Changed phenotypes to: Craniofacial with neurodevelopment disorders, H3F3A associated neurodevelopmental disorder, H3-3A-related Bryant-Li-Bhoj neurodevelopmental syndrome, OMIM:619720
DDG2P v5.3 GNAI1 Achchuthan Shanmugasundram edited their review of gene: GNAI1: Added comment: The DDG2P confidence category for the disease GNAI1-related neurodevelopmental disorder with hypotonia, impaired speech, and behavioural abnormalities, OMIM:619854 is moderate. The allelic requirement and mutation consequence are monoallelic_autosomal and altered gene product structure (PMID: 34819662;33473207).; Changed mode of pathogenicity: Other; Changed publications to: 34819662, 33473207; Changed phenotypes to: GNAI1-related neurodevelopmental disorder with hypotonia, impaired speech, and behavioural abnormalities, OMIM:619854, GNAI1 syndrome
DDG2P v5.3 GFER Achchuthan Shanmugasundram edited their review of gene: GFER: Added comment: The DDG2P confidence category for the disease GFER-related mitochondrial progressive myopathy with congenital cataract, hearing loss and developmental delay, OMIM:613076 is moderate. The allelic requirement and mutation consequence are biallelic_autosomal and absent gene product (PMID: 19409522;26018198;28155230).; Changed rating: GREEN; Changed publications to: 19409522, 26018198, 28155230; Changed phenotypes to: MITOCHONDRIAL PROGRESSIVE MYOPATHY WITH CONGENITAL CATARACT HEARING LOSS AND DEVELOPMENTAL DELAY (MPMCHD, OMIM:613076, GFER-related mitochondrial progressive myopathy with congenital cataract, hearing loss and developmental delay, OMIM:613076
DDG2P v5.3 GABRD Achchuthan Shanmugasundram reviewed gene: GABRD: Rating: GREEN; Mode of pathogenicity: Other; Publications: 25156961, 34633442; Phenotypes: GABRD-related neurodevelopmental disorder with epilepsy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
DDG2P v5.3 FXN Achchuthan Shanmugasundram reviewed gene: FXN: Rating: GREEN; Mode of pathogenicity: Other; Publications: 22691228, 10633128, 26704351, 25566998, 28405347, 30681346, 22409940, 24705334; Phenotypes: FXN-related Friedreich ataxia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
DDG2P v5.3 FEM1B Achchuthan Shanmugasundram reviewed gene: FEM1B: Rating: GREEN; Mode of pathogenicity: Other; Publications: 31036916, 38465576; Phenotypes: FEM1B-related neurodevelopmental disorder with or without brain abnormalities; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
DDG2P v5.3 EXOSC8 Achchuthan Shanmugasundram reviewed gene: EXOSC8: Rating: GREEN; Mode of pathogenicity: ; Publications: 38017281, 24989451, 34210538; Phenotypes: EXOSC8-related pontocerebellar hypoplasia, OMIM:616081; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
DDG2P v5.3 EPB41L3 Achchuthan Shanmugasundram reviewed gene: EPB41L3: Rating: GREEN; Mode of pathogenicity: Other; Publications: 39292993; Phenotypes: EPB41L3-related developmental disorder with delayed myelination and seizures; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
DDG2P v5.3 DLL1 Achchuthan Shanmugasundram edited their review of gene: DLL1: Added comment: The DDG2P confidence category for the disease DLL1-related neurodevelopmental disorder with nonspecific brain abnormalities, with or without seizures, OMIM:618709 is moderate. The allelic requirement and mutation consequence are monoallelic_autosomal and absent gene product;altered gene product structure;decreased gene product level (PMID: 36590296;31353024;37204857).; Changed rating: GREEN; Changed publications to: 37204857, 36590296, 31353024; Changed phenotypes to: DLL1-related neurodevelopmental disorder with nonspecific brain abnormalities, with or without seizures, OMIM:618709, INTELLECTUAL DISABILITY, OMIM:616579
DDG2P v5.3 DIP2C Achchuthan Shanmugasundram reviewed gene: DIP2C: Rating: GREEN; Mode of pathogenicity: Other; Publications: 38421105; Phenotypes: DIP2C-related developmental disorder with speech delay; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
DDG2P v5.3 CRYGD Achchuthan Shanmugasundram edited their review of gene: CRYGD: Added comment: The DDG2P confidence category for the disease CRYGD-related cataract, OMIM:115700 is definitive. The allelic requirement and mutation consequence are monoallelic_autosomal and absent gene product (PMID: 12676897;12011157;17564961;18079686;10915766;10521291;9927684;20508808).; Changed rating: GREEN; Changed publications to: 18079686, 17564961, 10521291, 9927684, 12676897, 12011157, 20508808, 10915766; Changed phenotypes to: Cataract 2, multiple types, OMIM:115700, CRYGD-related cataract, OMIM:115700
DDG2P v5.3 CRYBB2 Achchuthan Shanmugasundram edited their review of gene: CRYBB2: Added comment: The DDG2P confidence category for the disease CRYBB2-related cataract, OMIM:601547 is definitive. The allelic requirement and mutation consequence are monoallelic_autosomal and absent gene product;altered gene product structure (PMID: 21245961;8812489;24312286;9158139;11424921;18449377;16179907;10634616;27385965).; Changed publications to: 27385965, 24312286, 8812489, 10634616, 9158139, 21245961, 18449377, 11424921, 16179907; Changed phenotypes to: CATARACT, COPPOCK-LIKE, OMIM:604307, CATARACT, CONGENITAL, CERULEAN TYPE, 2, OMIM:601547, CRYBB2-related cataract, OMIM:601547
DDG2P v5.3 CRYAB Achchuthan Shanmugasundram edited their review of gene: CRYAB: Added comment: The DDG2P confidence category for the disease CRYAB-related alpha-related B crystallinopathy is definitive. The allelic requirement and mutation consequence are monoallelic_autosomal and altered gene product structure (PMID: 14681890;21130652;21337604;570292;28493373;9731540;23590293;19597569;30681346;16877416;16505043;38212463;32420686;11577372;21920752). The DDG2P confidence category for the disease CRYAB-related myopathy, myofibrillar, fatal infantile hypertonic, alpha-B crystallin-related, OMIM:613869 is limited. The allelic requirement and mutation consequence are biallelic_autosomal and absent gene product (PMID: 21337604).; Changed rating: GREEN; Changed publications to: 570292, 9731540, 11577372, 21130652, 38212463, 19597569, 16877416, 14681890, 30681346, 21920752, 16505043, 21337604, 28493373, 23590293, 32420686; Changed phenotypes to: CRYAB-related alpha-related B crystallinopathy, CRYAB-related myopathy, myofibrillar, fatal infantile hypertonic, alpha-B crystallin-related, OMIM:613869, MYOPATHY, MYOFIBRILLAR, FATAL INFANTILE HYPERTONIC, ALPHA-B CRYSTALLIN-RELATED, OMIM:613869, CATARACT POSTERIOR POLAR TYPE 2, OMIM:613763; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
DDG2P v5.3 CRELD1 Achchuthan Shanmugasundram edited their review of gene: CRELD1: Added comment: The DDG2P confidence category for the disease CRELD1-related neurodevelopmental disorder with hypotonia and seizures, OMIM:620771 is moderate. The allelic requirement and mutation consequence are biallelic_autosomal and altered gene product structure;decreased gene product level (PMID: 37947183). The DDG2P confidence category for the disease CRELD1-related atrioventricular septal defect susceptibility, OMIM:606217 is limited. The allelic requirement and mutation consequence are monoallelic_autosomal and altered gene product structure (PMID: 12632326;22740159;21080147).; Changed publications to: 37947183, 21080147, 22740159, 12632326; Changed phenotypes to: CRELD1-related neurodevelopmental disorder with hypotonia and seizures, OMIM:620771, HETEROTAXY SYNDROME, OMIM:207574, CRELD1-related neurodevelopmental disorder with hypotonia and seizures, CRELD1-related atrioventricular septal defect susceptibility, OMIM:606217; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
DDG2P v5.3 CCT6A Achchuthan Shanmugasundram reviewed gene: CCT6A: Rating: GREEN; Mode of pathogenicity: ; Publications: 39480921; Phenotypes: CCT6A-related neurodevelopmental disorder with or without brain abnormalities; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
DDG2P v5.3 CCT3 Achchuthan Shanmugasundram reviewed gene: CCT3: Rating: GREEN; Mode of pathogenicity: ; Publications: 39480921; Phenotypes: CCT3-related neurodevelopmental disorder with hypomyelination of white matter, OMIM:621034; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
DDG2P v5.3 ATOH7 Achchuthan Shanmugasundram edited their review of gene: ATOH7: Added comment: The DDG2P confidence category for the disease ATOH7-related persistent hyperplastic primary vitreous, OMIM:221900 is strong. The allelic requirement and mutation consequence are biallelic_autosomal and absent gene product;cis-regulatory or promotor mutation (PMID: 28192794;22068589;22645276;21441919;26933893).; Changed rating: GREEN; Changed publications to: 28192794, 22645276, 22068589, 26933893, 21441919; Changed phenotypes to: ATOH7-related persistent hyperplastic primary vitreous, OMIM:221900, RETINAL NON-ATTACHMENT CONGENITAL NON-SYNDROMIC, OMIM:221900
DDG2P v5.3 AFF3 Achchuthan Shanmugasundram edited their review of gene: AFF3: Added comment: The DDG2P confidence category for the disease AFF3-related intellectual disability is moderate. The allelic requirement and mutation consequence are monoallelic_autosomal and decreased gene product level (PMID: 38811945). The DDG2P confidence category for the disease AFF3-related KINSSHIP syndrome, OMIM:619297 is strong. The allelic requirement and mutation consequence are monoallelic_autosomal and altered gene product structure (PMID: 33961779;36576140;38811945).; Changed publications to: 38811945, 33961779, 36576140; Changed phenotypes to: Skeletal dysplasia with severe neurological disease, AFF3-related KINSSHIP syndrome, OMIM:619297, AFF3-related intellectual disability
DDG2P v5.2 GNAI1 Achchuthan Shanmugasundram Mode of pathogenicity for gene GNAI1 was changed from to Other
DDG2P v5.2 OPHN1 Achchuthan Shanmugasundram Mode of inheritance for gene OPHN1 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
DDG2P v5.2 LAMP2 Achchuthan Shanmugasundram Mode of inheritance for gene LAMP2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
DDG2P v5.2 KCNK4 Achchuthan Shanmugasundram Source Expert Review Red was added to KCNK4.
Rating Changed from Green List (high evidence) to Red List (low evidence)
DDG2P v5.2 USP14 Achchuthan Shanmugasundram Source Expert Review Green was added to USP14.
Rating Changed from Red List (low evidence) to Green List (high evidence)
DDG2P v5.2 NUP107 Achchuthan Shanmugasundram Source Expert Review Green was added to NUP107.
Rating Changed from Red List (low evidence) to Green List (high evidence)
DDG2P v5.2 NOP10 Achchuthan Shanmugasundram Source Expert Review Green was added to NOP10.
Rating Changed from Red List (low evidence) to Green List (high evidence)
DDG2P v5.2 NECTIN1 Achchuthan Shanmugasundram Source Expert Review Green was added to NECTIN1.
Rating Changed from Red List (low evidence) to Green List (high evidence)
DDG2P v5.2 GFER Achchuthan Shanmugasundram Source Expert Review Green was added to GFER.
Rating Changed from Red List (low evidence) to Green List (high evidence)
DDG2P v5.2 DLL1 Achchuthan Shanmugasundram Source Expert Review Green was added to DLL1.
Rating Changed from Red List (low evidence) to Green List (high evidence)
DDG2P v5.2 CRYGD Achchuthan Shanmugasundram Source Expert Review Green was added to CRYGD.
Rating Changed from Red List (low evidence) to Green List (high evidence)
DDG2P v5.2 CRYAB Achchuthan Shanmugasundram Source Expert Review Green was added to CRYAB.
Mode of inheritance for gene CRYAB was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Rating Changed from Red List (low evidence) to Green List (high evidence)
DDG2P v5.2 CRELD1 Achchuthan Shanmugasundram Mode of inheritance for gene CRELD1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal
DDG2P v5.2 ATOH7 Achchuthan Shanmugasundram Source Expert Review Green was added to ATOH7.
Rating Changed from Red List (low evidence) to Green List (high evidence)
DDG2P v5.2 CYHR1 Achchuthan Shanmugasundram gene: CYHR1 was added
gene: CYHR1 was added to DDG2P. Sources: Expert Review Red,DD-Gene2Phenotype
Mode of inheritance for gene: CYHR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYHR1 were set to 38641995
Phenotypes for gene: CYHR1 were set to ZFTRAF1-related neurodevelopmental disorder
Mode of pathogenicity for gene: CYHR1 was set to Other
DDG2P v5.2 SGSM3 Achchuthan Shanmugasundram gene: SGSM3 was added
gene: SGSM3 was added to DDG2P. Sources: Expert Review Red,DD-Gene2Phenotype
Mode of inheritance for gene: SGSM3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SGSM3 were set to 37833060
Phenotypes for gene: SGSM3 were set to SGSM3-related intellectual disability
DDG2P v5.2 PLA2G16 Achchuthan Shanmugasundram gene: PLA2G16 was added
gene: PLA2G16 was added to DDG2P. Sources: Expert Review Red,DD-Gene2Phenotype
Mode of inheritance for gene: PLA2G16 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLA2G16 were set to 37919452
Phenotypes for gene: PLA2G16 were set to PLAAT3-related lipodystrophy syndrome with neurological features, OMIM:620683
DDG2P v5.2 DLG2 Achchuthan Shanmugasundram gene: DLG2 was added
gene: DLG2 was added to DDG2P. Sources: Expert Review Red,DD-Gene2Phenotype
Mode of inheritance for gene: DLG2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DLG2 were set to 37860969
Phenotypes for gene: DLG2 were set to DLG2-related neurodevelopmental disorder
Mode of pathogenicity for gene: DLG2 was set to Other
DDG2P v5.2 COX18 Achchuthan Shanmugasundram gene: COX18 was added
gene: COX18 was added to DDG2P. Sources: Expert Review Red,DD-Gene2Phenotype
Mode of inheritance for gene: COX18 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COX18 were set to 38960055; 37468577; 39006432
Phenotypes for gene: COX18 were set to COX18-related peripheral neuropathy
Mode of pathogenicity for gene: COX18 was set to Other
DDG2P v5.2 CELSR1 Achchuthan Shanmugasundram gene: CELSR1 was added
gene: CELSR1 was added to DDG2P. Sources: Expert Review Red,DD-Gene2Phenotype
Mode of inheritance for gene: CELSR1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CELSR1 were set to 38272662
Phenotypes for gene: CELSR1 were set to CELSR1-related fetal hydrops
Mode of pathogenicity for gene: CELSR1 was set to Other
DDG2P v5.2 CCT8 Achchuthan Shanmugasundram gene: CCT8 was added
gene: CCT8 was added to DDG2P. Sources: Expert Review Red,DD-Gene2Phenotype
Mode of inheritance for gene: CCT8 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: CCT8 were set to CCT8-related neurodevelopmental disorder with brain abnormalities
DDG2P v5.2 CCT7 Achchuthan Shanmugasundram gene: CCT7 was added
gene: CCT7 was added to DDG2P. Sources: Expert Review Red,DD-Gene2Phenotype
Mode of inheritance for gene: CCT7 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CCT7 were set to 39480921
Phenotypes for gene: CCT7 were set to CCT7-related neurodevelopmental disorder with brain abnormalities
DDG2P v5.2 CCT5 Achchuthan Shanmugasundram gene: CCT5 was added
gene: CCT5 was added to DDG2P. Sources: Expert Review Red,DD-Gene2Phenotype
Mode of inheritance for gene: CCT5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CCT5 were set to 39480921
Phenotypes for gene: CCT5 were set to CCT5-related neurodevelopmental disorder with brain abnormalities
DDG2P v5.2 CCT4 Achchuthan Shanmugasundram gene: CCT4 was added
gene: CCT4 was added to DDG2P. Sources: Expert Review Red,DD-Gene2Phenotype
Mode of inheritance for gene: CCT4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CCT4 were set to 39480921
Phenotypes for gene: CCT4 were set to CCT4-related neurodevelopmental disorder with brain abnormalities
DDG2P v5.2 ANO3 Achchuthan Shanmugasundram gene: ANO3 was added
gene: ANO3 was added to DDG2P. Sources: Expert Review Red,DD-Gene2Phenotype
Mode of inheritance for gene: ANO3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ANO3 were set to 38079528; 33502045
Phenotypes for gene: ANO3 were set to ANO3-related dystonia, OMIM:615034
Mode of pathogenicity for gene: ANO3 was set to Other
DDG2P v5.2 ZSCAN10 Achchuthan Shanmugasundram gene: ZSCAN10 was added
gene: ZSCAN10 was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype
Mode of inheritance for gene: ZSCAN10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZSCAN10 were set to 38386308
Phenotypes for gene: ZSCAN10 were set to ZSCAN10-related neurodevelopmental disorder with oto-facial malformations
Mode of pathogenicity for gene: ZSCAN10 was set to Other
DDG2P v5.2 ZNF699 Achchuthan Shanmugasundram gene: ZNF699 was added
gene: ZNF699 was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype
Mode of inheritance for gene: ZNF699 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNF699 were set to 34374989; 39424669; 35205213; 33875846; 36801247
Phenotypes for gene: ZNF699 were set to ZNF699-related developmental delay with gastrointestinal, cardiovascular, genitourinary, and skeletal abnormalities (DEGCAGS syndrome), OMIM:619488
DDG2P v5.2 ZFX Achchuthan Shanmugasundram gene: ZFX was added
gene: ZFX was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype
Mode of inheritance for gene: ZFX 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: ZFX were set to 38325380
Phenotypes for gene: ZFX were set to ZFX-related neurodevelopmental disorder with hypotonia, congenital anomalies and facial dysmorphism with or without hyperparathyroidism
DDG2P v5.2 UBA2 Achchuthan Shanmugasundram gene: UBA2 was added
gene: UBA2 was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype
Mode of inheritance for gene: UBA2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: UBA2 were set to 31587267; 28110515; 34040189; 37221169; 32758660; 31332306; 34159400; 39149811
Phenotypes for gene: UBA2 were set to UBA2-related congenital anomalies with or without aplasia cutis congenita and ectrodactyly and variable developmental delay, OMIM:619959
DDG2P v5.2 TCP1 Achchuthan Shanmugasundram gene: TCP1 was added
gene: TCP1 was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype
Mode of inheritance for gene: TCP1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TCP1 were set to 39480921
Phenotypes for gene: TCP1 were set to TCP1-related neurodevelopmental disorder with polymicrogyria
DDG2P v5.2 SNF8 Achchuthan Shanmugasundram gene: SNF8 was added
gene: SNF8 was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype
Mode of inheritance for gene: SNF8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNF8 were set to 38423010
Phenotypes for gene: SNF8 were set to SNF8-related disease spectrum (severe developmental and epileptic encephalopathy to syndromic optic atrophy)
DDG2P v5.2 SLC4A10 Achchuthan Shanmugasundram gene: SLC4A10 was added
gene: SLC4A10 was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype
Mode of inheritance for gene: SLC4A10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC4A10 were set to 31130284; 37459438; 38054405
Phenotypes for gene: SLC4A10 were set to SLC4A10-related neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, OMIM:620746
DDG2P v5.2 SLC12A9 Achchuthan Shanmugasundram gene: SLC12A9 was added
gene: SLC12A9 was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype
Mode of inheritance for gene: SLC12A9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC12A9 were set to 38334070
Phenotypes for gene: SLC12A9 were set to SLC12A9-related syndromic neurodevelopmental disorder with lysosome defects
Mode of pathogenicity for gene: SLC12A9 was set to Other
DDG2P v5.2 SASS6 Achchuthan Shanmugasundram gene: SASS6 was added
gene: SASS6 was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype
Mode of inheritance for gene: SASS6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SASS6 were set to 38501757; 24951542; 30639237; 36739862
Phenotypes for gene: SASS6 were set to SASS6-related severe microcephaly with brain abnormalities
Mode of pathogenicity for gene: SASS6 was set to Other
DDG2P v5.2 RBBP5 Achchuthan Shanmugasundram gene: RBBP5 was added
gene: RBBP5 was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype
Mode of inheritance for gene: RBBP5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RBBP5 were set to 39036895
Phenotypes for gene: RBBP5 were set to RBBP5-related neurodevelopmental disorder
DDG2P v5.2 RAB1A Achchuthan Shanmugasundram gene: RAB1A was added
gene: RAB1A was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype
Mode of inheritance for gene: RAB1A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RAB1A were set to 37924809; 38091987
Phenotypes for gene: RAB1A were set to RAB1A-related neurodevelopmental disorder with speech and motor delay and spasticity
DDG2P v5.2 PNPLA8 Achchuthan Shanmugasundram gene: PNPLA8 was added
gene: PNPLA8 was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype
Mode of inheritance for gene: PNPLA8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PNPLA8 were set to 25512002; 34177434; 37671596; 37057294; 39082157; 29681094
Phenotypes for gene: PNPLA8 were set to PNPLA8-related progressive microcephaly with seizures and neurodegeneration
DDG2P v5.2 PLS3 Achchuthan Shanmugasundram gene: PLS3 was added
gene: PLS3 was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype
Mode of inheritance for gene: PLS3 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: PLS3 were set to 24088043; 37751738; 29736964; 25209159; 38043102; 35752817; 24616189; 28620780; 28777485; 28748388
Phenotypes for gene: PLS3 were set to PLS3-related diaphragmatic hernia and body-wall defects; PLS3-related osteoporosis with fractures, OMIM:300910
DDG2P v5.2 NPRL3 Achchuthan Shanmugasundram gene: NPRL3 was added
gene: NPRL3 was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype
Mode of inheritance for gene: NPRL3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NPRL3 were set to 35136953; 34965576; 34868250; 26285051; 26786403; 27173016; 26505888
Phenotypes for gene: NPRL3 were set to NPRL3-related familial focal epilepsy with or without focal cortical dysplasia
DDG2P v5.2 NPRL2 Achchuthan Shanmugasundram gene: NPRL2 was added
gene: NPRL2 was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype
Mode of inheritance for gene: NPRL2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NPRL2 were set to 28199897; 34965576; 37259768; 34376795; 30093711; 31835056; 27173016; 26505888
Phenotypes for gene: NPRL2 were set to NPRL2-related familial focal epilepsy with or without focal cortical dysplasia
DDG2P v5.2 JPH1 Achchuthan Shanmugasundram gene: JPH1 was added
gene: JPH1 was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype
Mode of inheritance for gene: JPH1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: JPH1 were set to 39209426
Phenotypes for gene: JPH1 were set to JPH1-related congenital myopathy with ptosis, OMIM:620964
DDG2P v5.2 HDAC3 Achchuthan Shanmugasundram gene: HDAC3 was added
gene: HDAC3 was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype
Mode of inheritance for gene: HDAC3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: HDAC3 were set to 39047730
Phenotypes for gene: HDAC3 were set to HDAC3-related neurodevelopmental disorder
Mode of pathogenicity for gene: HDAC3 was set to Other
DDG2P v5.2 GABRD Achchuthan Shanmugasundram gene: GABRD was added
gene: GABRD was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype
Mode of inheritance for gene: GABRD was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: GABRD were set to 25156961; 34633442
Phenotypes for gene: GABRD were set to GABRD-related neurodevelopmental disorder with epilepsy
Mode of pathogenicity for gene: GABRD was set to Other
DDG2P v5.2 FXN Achchuthan Shanmugasundram gene: FXN was added
gene: FXN was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype
Mode of inheritance for gene: FXN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FXN were set to 22691228; 24705334; 26704351; 22409940; 28405347; 25566998; 10633128; 30681346
Phenotypes for gene: FXN were set to FXN-related Friedreich ataxia
Mode of pathogenicity for gene: FXN was set to Other
DDG2P v5.2 FEM1B Achchuthan Shanmugasundram gene: FEM1B was added
gene: FEM1B was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype
Mode of inheritance for gene: FEM1B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FEM1B were set to 31036916; 38465576
Phenotypes for gene: FEM1B were set to FEM1B-related neurodevelopmental disorder with or without brain abnormalities
Mode of pathogenicity for gene: FEM1B was set to Other
DDG2P v5.2 EXOSC8 Achchuthan Shanmugasundram gene: EXOSC8 was added
gene: EXOSC8 was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype
Mode of inheritance for gene: EXOSC8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOSC8 were set to 24989451; 34210538; 38017281
Phenotypes for gene: EXOSC8 were set to EXOSC8-related pontocerebellar hypoplasia, OMIM:616081
DDG2P v5.2 EPB41L3 Achchuthan Shanmugasundram gene: EPB41L3 was added
gene: EPB41L3 was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype
Mode of inheritance for gene: EPB41L3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EPB41L3 were set to 39292993
Phenotypes for gene: EPB41L3 were set to EPB41L3-related developmental disorder with delayed myelination and seizures
Mode of pathogenicity for gene: EPB41L3 was set to Other
DDG2P v5.2 DIP2C Achchuthan Shanmugasundram gene: DIP2C was added
gene: DIP2C was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype
Mode of inheritance for gene: DIP2C was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DIP2C were set to 38421105
Phenotypes for gene: DIP2C were set to DIP2C-related developmental disorder with speech delay
Mode of pathogenicity for gene: DIP2C was set to Other
DDG2P v5.2 CCT6A Achchuthan Shanmugasundram gene: CCT6A was added
gene: CCT6A was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype
Mode of inheritance for gene: CCT6A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CCT6A were set to 39480921
Phenotypes for gene: CCT6A were set to CCT6A-related neurodevelopmental disorder with or without brain abnormalities
DDG2P v5.2 CCT3 Achchuthan Shanmugasundram gene: CCT3 was added
gene: CCT3 was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype
Mode of inheritance for gene: CCT3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CCT3 were set to 39480921
Phenotypes for gene: CCT3 were set to CCT3-related neurodevelopmental disorder with hypomyelination of white matter, OMIM:621034
Hereditary ataxia with onset in adulthood v7.8 FAT2 Jenna Ridley gene: FAT2 was added
gene: FAT2 was added to Hereditary ataxia with onset in adulthood. Sources: Literature
Mode of inheritance for gene: FAT2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FAT2 were set to 29053796; 36339299; 33884300
Phenotypes for gene: FAT2 were set to Spinocerebellar ataxia 45, OMIM:617769
Penetrance for gene: FAT2 were set to Complete
Mode of pathogenicity for gene: FAT2 was set to Other
Review for gene: FAT2 was set to GREEN
Added comment: PMID: 29053796 reported a family (RF14) in which 6 patients spanning 2 generations had late-onset spinocerebellar ataxia after age 40. The proband was noted to have a relatively pure cerebellar syndrome with limb and gait ataxia, downbeat nystagmus, and dysarthria. No detailed clinical information was available for the remaining affected family members. Testing of 5 of the affected individuals was undertaken and c.10758G>C p.(Lys3586Asn) variant was identified in all. Two unaffected members were tested and did not harbour the variant.

An unrelated patient (case DNA056251) had onset of slowly progressive gait and limb ataxia and dysarthria at around 50 years of age. He did not have nystagmus. Brain MRI showed atrophy of the cerebellar vermis and hemosiderin deposits in the mesencephalon. This individual harboured c.10946G>A p.(Ar3649Glu)

PMID: 36339299 reported an 82yo male with a strong f/h of gait imbalance, horizontal gaze evoked nystagmus and ataxic dysarthria. A missense FAT2 variant p.(Met1705Thr) was identified. The variant also detected in his symptomatic surviving brother.

PMID: 33884300 reported 2 siblings with late onset cerebellar ataxia and mild cerebellar atrophy, both with a FAT2 p.(Tyr3636Asp) variant

Only missense variants have been reported.
Sources: Literature
Fetal anomalies v5.76 DRC1 Achchuthan Shanmugasundram commented on gene: DRC1
Fetal anomalies v5.76 DPYSL5 Achchuthan Shanmugasundram commented on gene: DPYSL5
Fetal anomalies v5.76 DOHH Achchuthan Shanmugasundram commented on gene: DOHH
Fetal anomalies v5.76 DLX3 Achchuthan Shanmugasundram commented on gene: DLX3
Fetal anomalies v5.76 DLG5 Achchuthan Shanmugasundram commented on gene: DLG5
Fetal anomalies v5.76 DLG4 Achchuthan Shanmugasundram commented on gene: DLG4
Fetal anomalies v5.76 DHX30 Achchuthan Shanmugasundram commented on gene: DHX30
Fetal anomalies v5.76 DDRGK1 Achchuthan Shanmugasundram commented on gene: DDRGK1
Fetal anomalies v5.76 DCDC2 Achchuthan Shanmugasundram commented on gene: DCDC2
Fetal anomalies v5.76 DAW1 Achchuthan Shanmugasundram commented on gene: DAW1
Fetal anomalies v5.76 CYP2R1 Achchuthan Shanmugasundram commented on gene: CYP2R1
Fetal anomalies v5.76 CYP27B1 Achchuthan Shanmugasundram commented on gene: CYP27B1
Fetal anomalies v5.76 CYB5R3 Achchuthan Shanmugasundram commented on gene: CYB5R3
Fetal anomalies v5.75 DRC1 Elizabeth Wall reviewed gene: DRC1: Rating: AMBER; Mode of pathogenicity: ; Publications: 39152285, 34851034, 39462806; Phenotypes: Ciliary dyskinesia, primary, 21, MIM#615294; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.75 DPYSL5 Elizabeth Wall reviewed gene: DPYSL5: Rating: GREEN; Mode of pathogenicity: ; Publications: 33894126; Phenotypes: Ritscher-Schinzel syndrome 4, MIM#619435; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.75 DOHH Elizabeth Wall reviewed gene: DOHH: Rating: AMBER; Mode of pathogenicity: ; Publications: 35858628; Phenotypes: Neurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairment, MIM#620066; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.75 DLX3 Elizabeth Wall reviewed gene: DLX3: Rating: RED; Mode of pathogenicity: ; Publications: 26762616, 26104267; Phenotypes: Trichodontoosseous syndrome, MIM#190320, Amelogenesis imperfecta, type IV, MIM#104510; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.75 DLG5 Elizabeth Wall reviewed gene: DLG5: Rating: GREEN; Mode of pathogenicity: ; Publications: 32631816, 30791088; Phenotypes: Yuksel-Vogel-Bauser syndrome, MIM#620703; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.75 DLG4 Elizabeth Wall reviewed gene: DLG4: Rating: AMBER; Mode of pathogenicity: ; Publications: 37347881; Phenotypes: Intellectual developmental disorder, autosomal dominant 62, MIM#618793; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.75 DHX30 Elizabeth Wall reviewed gene: DHX30: Rating: GREEN; Mode of pathogenicity: ; Publications: 38366977, 37094863, 34020708, 34180050, 34145223, 36643085; Phenotypes: Neurodevelopmental disorder with variable motor and language impairment, MIM#617804; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.75 DDRGK1 Elizabeth Wall reviewed gene: DDRGK1: Rating: GREEN; Mode of pathogenicity: ; Publications: 35377455, 28263186, 35670300, 36243336; Phenotypes: Spondyloepimetaphyseal dysplasia, Shohat type, MIM#602557; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.75 DCDC2 Elizabeth Wall reviewed gene: DCDC2: Rating: AMBER; Mode of pathogenicity: ; Publications: 35570614, 34155636, 36938759, 37296768, 36816379; Phenotypes: Sclerosing cholangitis, neonatal, MIM#617394; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.75 DAW1 Elizabeth Wall reviewed gene: DAW1: Rating: GREEN; Mode of pathogenicity: ; Publications: 36074124, 28991257; Phenotypes: Ciliary dyskinesia, primary, 52, MIM#620570; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.75 CYP2R1 Elizabeth Wall reviewed gene: CYP2R1: Rating: RED; Mode of pathogenicity: ; Publications: 28548312, 15128933; Phenotypes: Rickets due to defect in vitamin D 25-hydroxylation deficiency, MIM#600081; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.75 CYP27B1 Elizabeth Wall reviewed gene: CYP27B1: Rating: RED; Mode of pathogenicity: ; Publications: 34492747, 9486994, 27473561, 9415400, 33823104, 12050193; Phenotypes: Vitamin D-dependent rickets, type I, MIM#264700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.75 CYB5R3 Elizabeth Wall reviewed gene: CYB5R3: Rating: AMBER; Mode of pathogenicity: ; Publications: 34467556; Phenotypes: Methemoglobinemia, type II, MIM#250800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.74 DRC1 Achchuthan Shanmugasundram Deleted their review
Fetal anomalies v5.74 DPYSL5 Achchuthan Shanmugasundram Deleted their review
Fetal anomalies v5.74 DOHH Achchuthan Shanmugasundram Deleted their review
Fetal anomalies v5.74 DLX3 Achchuthan Shanmugasundram Deleted their review
Fetal anomalies v5.74 DLG5 Achchuthan Shanmugasundram Deleted their review
Fetal anomalies v5.74 DLG4 Achchuthan Shanmugasundram Deleted their review
Fetal anomalies v5.74 DHX30 Achchuthan Shanmugasundram Deleted their review
Fetal anomalies v5.74 DDRGK1 Achchuthan Shanmugasundram Deleted their review
Fetal anomalies v5.74 DCDC2 Achchuthan Shanmugasundram Deleted their review
Fetal anomalies v5.74 DAW1 Achchuthan Shanmugasundram Deleted their review
Fetal anomalies v5.74 CYP2R1 Achchuthan Shanmugasundram Deleted their review
Fetal anomalies v5.74 CYP27B1 Achchuthan Shanmugasundram Deleted their review
Fetal anomalies v5.74 CYB5R3 Achchuthan Shanmugasundram Deleted their review
Fetal anomalies v5.74 ROBO1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: ROBO1.
Fetal anomalies v5.74 MSTO1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: MSTO1.
Fetal anomalies v5.74 SMPD1 Achchuthan Shanmugasundram Tag Q1_25_ demote_amber tag was added to gene: SMPD1.
Tag Q1_25_ NHS_review tag was added to gene: SMPD1.
Fetal anomalies v5.74 PLD1 Achchuthan Shanmugasundram Tag Q2_24_demote_red was removed from gene: PLD1.
Tag Q1_25_ demote_amber tag was added to gene: PLD1.
Tag Q1_25_ NHS_review tag was added to gene: PLD1.
Fetal anomalies v5.74 ZRSR2 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: ZRSR2.
Tag Q1_25_ promote_green tag was added to gene: ZRSR2.
Fetal anomalies v5.74 WDR44 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: WDR44.
Tag Q1_25_ promote_green tag was added to gene: WDR44.
Fetal anomalies v5.74 ZFX Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: ZFX.
Tag Q1_25_ promote_green tag was added to gene: ZFX.
Fetal anomalies v5.74 WBP4 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: WBP4.
Tag Q1_25_ promote_green tag was added to gene: WBP4.
Fetal anomalies v5.74 WASHC5 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: WASHC5.
Tag Q1_25_ promote_green tag was added to gene: WASHC5.
Fetal anomalies v5.74 UFSP2 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: UFSP2.
Tag Q1_25_ promote_green tag was added to gene: UFSP2.
Fetal anomalies v5.74 U2AF2 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: U2AF2.
Tag Q1_25_ promote_green tag was added to gene: U2AF2.
Fetal anomalies v5.74 TSHZ3 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: TSHZ3.
Tag Q1_25_ promote_green tag was added to gene: TSHZ3.
Fetal anomalies v5.74 TRIT1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: TRIT1.
Tag Q1_25_ promote_green tag was added to gene: TRIT1.
Fetal anomalies v5.74 TONSL Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: TONSL.
Tag Q1_25_ promote_green tag was added to gene: TONSL.
Fetal anomalies v5.74 TOGARAM1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: TOGARAM1.
Tag Q1_25_ promote_green tag was added to gene: TOGARAM1.
Fetal anomalies v5.74 THSD1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: THSD1.
Tag Q1_25_ promote_green tag was added to gene: THSD1.
Fetal anomalies v5.74 TBR1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: TBR1.
Tag Q1_25_ promote_green tag was added to gene: TBR1.
Fetal anomalies v5.74 TAF8 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: TAF8.
Tag Q1_25_ promote_green tag was added to gene: TAF8.
Fetal anomalies v5.74 SNF8 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: SNF8.
Tag Q1_23_promote_green tag was added to gene: SNF8.
Fetal anomalies v5.74 SNAP25 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: SNAP25.
Tag Q1_25_ promote_green tag was added to gene: SNAP25.
Fetal anomalies v5.74 SLC4A10 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: SLC4A10.
Tag Q1_25_ promote_green tag was added to gene: SLC4A10.
Fetal anomalies v5.74 SLC34A1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: SLC34A1.
Tag Q1_25_ promote_green tag was added to gene: SLC34A1.
Fetal anomalies v5.74 SLC25A4 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: SLC25A4.
Tag Q1_25_ promote_green tag was added to gene: SLC25A4.
Fetal anomalies v5.74 SETD1A Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: SETD1A.
Tag Q1_25_ promote_green tag was added to gene: SETD1A.
Fetal anomalies v5.74 SCYL2 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: SCYL2.
Tag Q1_25_ promote_green tag was added to gene: SCYL2.
Fetal anomalies v5.74 SASS6 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: SASS6.
Tag Q1_25_ promote_green tag was added to gene: SASS6.
Fetal anomalies v5.74 RSPRY1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: RSPRY1.
Tag Q1_25_ promote_green tag was added to gene: RSPRY1.
Fetal anomalies v5.74 RSPO2 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: RSPO2.
Tag Q1_25_ promote_green tag was added to gene: RSPO2.
Fetal anomalies v5.74 RRAS Achchuthan Shanmugasundram Tag Q1_25_ promote_green tag was added to gene: RRAS.
Fetal anomalies v5.74 RRAGC Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: RRAGC.
Tag Q1_25_ promote_green tag was added to gene: RRAGC.
Fetal anomalies v5.74 RPL13 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: RPL13.
Tag Q1_25_ promote_green tag was added to gene: RPL13.
Fetal anomalies v5.74 RNU4-2 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: RNU4-2.
Tag Q1_25_ promote_green tag was added to gene: RNU4-2.
Fetal anomalies v5.74 RFWD3 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: RFWD3.
Tag Q1_25_ promote_green tag was added to gene: RFWD3.
Fetal anomalies v5.74 RAP1B Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: RAP1B.
Tag Q1_25_ promote_green tag was added to gene: RAP1B.
Fetal anomalies v5.74 RAB34 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: RAB34.
Tag Q1_25_ promote_green tag was added to gene: RAB34.
Fetal anomalies v5.74 PUM1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: PUM1.
Tag Q1_25_ promote_green tag was added to gene: PUM1.
Fetal anomalies v5.74 PSMF1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: PSMF1.
Tag Q1_25_ promote_green tag was added to gene: PSMF1.
Fetal anomalies v5.74 PLS3 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: PLS3.
Tag Q1_25_ promote_green tag was added to gene: PLS3.
Fetal anomalies v5.74 PKDCC Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: PKDCC.
Tag Q1_25_ promote_green tag was added to gene: PKDCC.
Fetal anomalies v5.74 PIP5K1C Achchuthan Shanmugasundram Tag Q1_23_promote_green was removed from gene: PIP5K1C.
Tag Q1_25_ promote_green tag was added to gene: PIP5K1C.
Fetal anomalies v5.74 PIP5K1C Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: PIP5K1C.
Tag Q1_23_promote_green tag was added to gene: PIP5K1C.
Fetal anomalies v5.74 PIGS Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: PIGS.
Tag Q1_25_ promote_green tag was added to gene: PIGS.
Fetal anomalies v5.74 PI4K2A Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: PI4K2A.
Tag Q1_25_ promote_green tag was added to gene: PI4K2A.
Fetal anomalies v5.74 PAN2 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: PAN2.
Tag Q1_25_ promote_green tag was added to gene: PAN2.
Fetal anomalies v5.74 NUDT2 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: NUDT2.
Tag Q1_25_ promote_green tag was added to gene: NUDT2.
Fetal anomalies v5.74 NSUN6 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: NSUN6.
Tag Q1_25_ promote_green tag was added to gene: NSUN6.
Fetal anomalies v5.74 NLRP3 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: NLRP3.
Tag Q1_25_ promote_green tag was added to gene: NLRP3.
Fetal anomalies v5.74 MDFIC Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: MDFIC.
Fetal anomalies v5.74 MAX Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: MAX.
Tag Q1_25_ promote_green tag was added to gene: MAX.
Fetal anomalies v5.74 MAP4K4 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: MAP4K4.
Tag Q1_25_ promote_green tag was added to gene: MAP4K4.
Fetal anomalies v5.74 LOX Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: LOX.
Tag Q1_25_ promote_green tag was added to gene: LOX.
Fetal anomalies v5.74 LNPK Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: LNPK.
Tag Q1_25_ promote_green tag was added to gene: LNPK.
Fetal anomalies v5.74 LIPT2 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: LIPT2.
Tag Q1_25_ promote_green tag was added to gene: LIPT2.
Fetal anomalies v5.74 LAMB2 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: LAMB2.
Tag Q1_25_ promote_green tag was added to gene: LAMB2.
Fetal anomalies v5.74 LAMA5 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: LAMA5.
Tag Q1_25_ promote_green tag was added to gene: LAMA5.
Fetal anomalies v5.74 KMT2B Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: KMT2B.
Tag Q1_25_ promote_green tag was added to gene: KMT2B.
Fetal anomalies v5.74 KIF5B Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: KIF5B.
Tag Q1_25_ promote_green tag was added to gene: KIF5B.
Fetal anomalies v5.74 KIF26A Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: KIF26A.
Tag Q1_25_ promote_green tag was added to gene: KIF26A.
Fetal anomalies v5.74 KIF24 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: KIF24.
Tag Q1_25_ promote_green tag was added to gene: KIF24.
Fetal anomalies v5.74 KDM2B Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: KDM2B.
Tag Q1_25_ promote_green tag was added to gene: KDM2B.
Fetal anomalies v5.74 KDELR2 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: KDELR2.
Tag Q1_25_ promote_green tag was added to gene: KDELR2.
Fetal anomalies v5.74 KCNK3 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: KCNK3.
Tag Q1_25_ promote_green tag was added to gene: KCNK3.
Hereditary ataxia with onset in adulthood v7.8 NPTX1 Jenna Ridley changed review comment from: Eight unrelated families/cases reported with heterozygous missense variants with cerebellar ataxia, oculomotor apraxia, downbeat nystagmus, cognitive impairment reminiscent of cerebellar cognitive affective syndrome, myoclonic tremor and mild cerebellar vermian atrophy on brain imaging.
One of these cases is childhood onset.

PMID:34788392 reported a large multigenerational family with late onset slowly progressive cerebellar ataxia (along with other clinical manifestations) in which 9 members and 6 additional patients from four families harboured c.1165G>A p.(Gly389Arg) variant. Unaffected individuals that were tested did not harbour the variant. An additional patient from another unrelated family harboured c.980A>G p.(Glu327Gly) variant.

PMID:35285082 reported a male patient with slowly progressive late-onset ataxia with c.428G>T p.(Arg143Leu).

PMID: 35288776 report a 58-year-old woman from one of the families reported by Coutelier et al. (2022) (family LUEB01) who presented with oculomotor apraxia at 43 years of age. Her visual disturbances were progressive and severe, with an inability to initiate horizontal saccades or smooth pursuit eye movements. She did not have nystagmus or oculomotor cerebellar signs. Functional MRI studies showed abnormally reduced structural connectivity within the defined oculomotor network of each hemisphere (intrahemispheric dysfunction).

Please note that PMID:35560436 reported a six years old girl with early-onset ataxia with c.1109A>G p.(Gln370Arg)

Only missense variants appear to be reported for this gene.
Sources: Literature; to: Eight unrelated families/cases reported with heterozygous missense variants with cerebellar ataxia, oculomotor apraxia, downbeat nystagmus, cognitive impairment reminiscent of cerebellar cognitive affective syndrome, myoclonic tremor and mild cerebellar vermian atrophy on brain imaging.
One of these cases is childhood onset.

PMID:34788392 reported a large multigenerational family with late onset slowly progressive cerebellar ataxia (along with other clinical manifestations) in which 9 members and 6 additional patients from four families harboured c.1165G>A p.(Gly389Arg) variant. Unaffected individuals that were tested did not harbour the variant. An additional patient from another unrelated family harboured c.980A>G p.(Glu327Gly) variant. Functional work undertaken also support pathogenicity for these variants.

PMID:35285082 reported a male patient with slowly progressive late-onset ataxia with c.428G>T p.(Arg143Leu).

PMID: 35288776 report a 58-year-old woman from one of the families reported by Coutelier et al. (2022) (family LUEB01) who presented with oculomotor apraxia at 43 years of age. Her visual disturbances were progressive and severe, with an inability to initiate horizontal saccades or smooth pursuit eye movements. She did not have nystagmus or oculomotor cerebellar signs. Functional MRI studies showed abnormally reduced structural connectivity within the defined oculomotor network of each hemisphere (intrahemispheric dysfunction).

Please note that PMID:35560436 reported a six years old girl with early-onset ataxia with c.1109A>G p.(Gln370Arg)

Only missense variants appear to be reported for this gene.
Sources: Literature
Hereditary ataxia with onset in adulthood v7.8 NPTX1 Jenna Ridley gene: NPTX1 was added
gene: NPTX1 was added to Hereditary ataxia with onset in adulthood. Sources: Literature
Mode of inheritance for gene: NPTX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NPTX1 were set to 34788392; 35285082; 35288776; 35560436
Phenotypes for gene: NPTX1 were set to Spinocerebellar ataxia 50, OMIM:620158
Penetrance for gene: NPTX1 were set to Complete
Mode of pathogenicity for gene: NPTX1 was set to Other
Review for gene: NPTX1 was set to GREEN
gene: NPTX1 was marked as current diagnostic
Added comment: Eight unrelated families/cases reported with heterozygous missense variants with cerebellar ataxia, oculomotor apraxia, downbeat nystagmus, cognitive impairment reminiscent of cerebellar cognitive affective syndrome, myoclonic tremor and mild cerebellar vermian atrophy on brain imaging.
One of these cases is childhood onset.

PMID:34788392 reported a large multigenerational family with late onset slowly progressive cerebellar ataxia (along with other clinical manifestations) in which 9 members and 6 additional patients from four families harboured c.1165G>A p.(Gly389Arg) variant. Unaffected individuals that were tested did not harbour the variant. An additional patient from another unrelated family harboured c.980A>G p.(Glu327Gly) variant.

PMID:35285082 reported a male patient with slowly progressive late-onset ataxia with c.428G>T p.(Arg143Leu).

PMID: 35288776 report a 58-year-old woman from one of the families reported by Coutelier et al. (2022) (family LUEB01) who presented with oculomotor apraxia at 43 years of age. Her visual disturbances were progressive and severe, with an inability to initiate horizontal saccades or smooth pursuit eye movements. She did not have nystagmus or oculomotor cerebellar signs. Functional MRI studies showed abnormally reduced structural connectivity within the defined oculomotor network of each hemisphere (intrahemispheric dysfunction).

Please note that PMID:35560436 reported a six years old girl with early-onset ataxia with c.1109A>G p.(Gln370Arg)

Only missense variants appear to be reported for this gene.
Sources: Literature
Fetal anomalies v5.74 INTS11 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: INTS11.
Tag Q1_25_ promote_green tag was added to gene: INTS11.
Fetal anomalies v5.74 HECTD4 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: HECTD4.
Tag Q1_25_ promote_green tag was added to gene: HECTD4.
Fetal anomalies v5.74 GON4L Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: GON4L.
Tag Q1_25_ promote_green tag was added to gene: GON4L.
Fetal anomalies v5.74 FUZ Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: FUZ.
Tag Q1_25_ promote_green tag was added to gene: FUZ.
Fetal anomalies v5.74 FTO Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: FTO.
Tag Q1_25_ promote_green tag was added to gene: FTO.
Fetal anomalies v5.74 FOXP4 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: FOXP4.
Tag Q1_25_ promote_green tag was added to gene: FOXP4.
Fetal anomalies v5.74 FOSL2 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: FOSL2.
Tag Q1_25_ promote_green tag was added to gene: FOSL2.
Fetal anomalies v5.74 FN1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: FN1.
Tag Q1_25_ promote_green tag was added to gene: FN1.
Fetal anomalies v5.74 FILIP1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: FILIP1.
Tag Q1_25_ promote_green tag was added to gene: FILIP1.
Fetal anomalies v5.74 FAS Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: FAS.
Tag Q1_25_ promote_green tag was added to gene: FAS.
Fetal anomalies v5.74 ERI1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: ERI1.
Tag Q1_25_ promote_green tag was added to gene: ERI1.
Fetal anomalies v5.74 ENG Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: ENG.
Tag Q1_25_ promote_green tag was added to gene: ENG.
Fetal anomalies v5.74 EMG1 Achchuthan Shanmugasundram Tag watchlist was removed from gene: EMG1.
Tag Q1_25_ NHS_review tag was added to gene: EMG1.
Tag Q1_23_promote_green tag was added to gene: EMG1.
Fetal anomalies v5.74 EFCAB1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: EFCAB1.
Tag Q1_25_ promote_green tag was added to gene: EFCAB1.
Fetal anomalies v5.74 DRG1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: DRG1.
Tag Q1_25_ promote_green tag was added to gene: DRG1.
Fetal anomalies v5.74 DPYSL5 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: DPYSL5.
Tag Q1_25_ promote_green tag was added to gene: DPYSL5.
Fetal anomalies v5.74 DLG5 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: DLG5.
Tag Q1_25_ promote_green tag was added to gene: DLG5.
Fetal anomalies v5.74 DHX30 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: DHX30.
Tag Q1_25_ promote_green tag was added to gene: DHX30.
Fetal anomalies v5.74 DDRGK1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: DDRGK1.
Tag Q1_25_ promote_green tag was added to gene: DDRGK1.
Fetal anomalies v5.74 CSGALNACT1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: CSGALNACT1.
Fetal anomalies v5.74 CNOT2 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: CNOT2.
Fetal anomalies v5.74 CEP295 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: CEP295.
Fetal anomalies v5.74 CDK10 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: CDK10.
Fetal anomalies v5.74 CDH2 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: CDH2.
Fetal anomalies v5.74 CBY1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: CBY1.
Fetal anomalies v5.74 CASP2 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: CASP2.
Fetal anomalies v5.74 CACNA1S Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: CACNA1S.
Fetal anomalies v5.74 C16orf62 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: C16orf62.
Fetal anomalies v5.74 ATG7 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: ATG7.
Fetal anomalies v5.74 ASXL3 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: ASXL3.
Fetal anomalies v5.74 AMOTL1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: AMOTL1.
Fetal anomalies v5.74 AL117258.1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: AL117258.1.
Fetal anomalies v5.74 ADD1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: ADD1.
Fetal anomalies v5.74 ADAMTS15 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: ADAMTS15.
Fetal anomalies v5.74 ACBD6 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: ACBD6.
Fetal anomalies v5.74 DAW1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: DAW1.
Fetal anomalies v5.74 DAW1 Achchuthan Shanmugasundram Tag Q1_25_ promote_green tag was added to gene: DAW1.
Fetal anomalies v5.74 CSGALNACT1 Achchuthan Shanmugasundram Tag Q1_25_ promote_green tag was added to gene: CSGALNACT1.
Fetal anomalies v5.74 CNOT2 Achchuthan Shanmugasundram Tag Q1_25_ promote_green tag was added to gene: CNOT2.
Fetal anomalies v5.74 CEP295 Achchuthan Shanmugasundram Tag Q1_25_ promote_green tag was added to gene: CEP295.
Fetal anomalies v5.74 CDK10 Achchuthan Shanmugasundram Tag Q1_25_ promote_green tag was added to gene: CDK10.
Fetal anomalies v5.74 CDH2 Achchuthan Shanmugasundram Tag Q1_25_ promote_green tag was added to gene: CDH2.
Fetal anomalies v5.74 CBY1 Achchuthan Shanmugasundram Tag Q1_25_ promote_green tag was added to gene: CBY1.
Fetal anomalies v5.74 CASP2 Achchuthan Shanmugasundram Tag Q1_25_ promote_green tag was added to gene: CASP2.
Fetal anomalies v5.74 CACNA1S Achchuthan Shanmugasundram Tag Q1_25_ promote_green tag was added to gene: CACNA1S.
Fetal anomalies v5.74 C16orf62 Achchuthan Shanmugasundram Tag Q1_25_ promote_green tag was added to gene: C16orf62.
Fetal anomalies v5.74 ATG7 Achchuthan Shanmugasundram Tag Q1_25_ promote_green tag was added to gene: ATG7.
Fetal anomalies v5.74 ASXL3 Achchuthan Shanmugasundram Phenotypes for gene: ASXL3 were changed from Bainbridge-Ropers syndrome, OMIM:615485; Arthrogryposis to Bainbridge-Ropers syndrome, OMIM:615485
Fetal anomalies v5.73 ASXL3 Achchuthan Shanmugasundram Tag Q1_25_ promote_green tag was added to gene: ASXL3.
Fetal anomalies v5.73 AMOTL1 Achchuthan Shanmugasundram Tag Q1_25_ promote_green tag was added to gene: AMOTL1.
Fetal anomalies v5.73 AL117258.1 Achchuthan Shanmugasundram Tag Q1_25_ promote_green tag was added to gene: AL117258.1.
Fetal anomalies v5.73 ADD1 Achchuthan Shanmugasundram Tag Q1_25_ promote_green tag was added to gene: ADD1.
Fetal anomalies v5.73 ADAMTS15 Achchuthan Shanmugasundram Tag Q1_25_ promote_green tag was added to gene: ADAMTS15.
Fetal anomalies v5.73 ACBD6 Achchuthan Shanmugasundram Tag Q1_25_ promote_green tag was added to gene: ACBD6.
Fetal anomalies v5.73 ZNF750 Achchuthan Shanmugasundram Phenotypes for gene: ZNF750 were changed from Seborrhea-like dermatitis with psoriasiform elements, OMIM:610227; SEBORRHEA-LIKE DERMATITIS WITH PSORIASIFORM ELEMENTS to Seborrhea-like dermatitis with psoriasiform elements, OMIM:610227
Fetal anomalies v5.72 WASHC5 Achchuthan Shanmugasundram Phenotypes for gene: WASHC5 were changed from Ritscher-Schinzel syndrome 1 220210; Ritscher-Schinzel syndrome 1, OMIM:220210; Spastic paraplegia 8, autosomal dominant 603563 to Ritscher-Schinzel syndrome 1, OMIM:220210
Fetal anomalies v5.71 TUFM Achchuthan Shanmugasundram Phenotypes for gene: TUFM were changed from Combined oxidative phosphorylation deficiency 4, OMIM:610678; COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 4 to Combined oxidative phosphorylation deficiency 4, OMIM:610678
Fetal anomalies v5.70 TTC25 Achchuthan Shanmugasundram Phenotypes for gene: TTC25 were changed from Ciliary dyskinesia, primary, 35, OMIM:617092; Primary Ciliary Dyskinesia with Left-Right Body Asymmetry Randomization to Ciliary dyskinesia, primary, 35, OMIM:617092
Fetal anomalies v5.69 TOGARAM1 Achchuthan Shanmugasundram Phenotypes for gene: TOGARAM1 were changed from Joubert syndrome 37, OMIM:619185; Cleft of the lip and palate; Hydrocephalus; Microphthalmia; Cerebral dysgenesis to Joubert syndrome 37, OMIM:619185
Fetal anomalies v5.68 TNFRSF13B Achchuthan Shanmugasundram Phenotypes for gene: TNFRSF13B were changed from Immunodeficiency, common variable, 2, OMIM:240500; IMMUNODEFICIENCY, COMMON VARIABLE, 2 to Immunodeficiency, common variable, 2, OMIM:240500
Fetal anomalies v5.67 THSD1 Achchuthan Shanmugasundram Phenotypes for gene: THSD1 were changed from ?Hydrops fetalis; Intracerebral aneurysms; Lymphatic malformation 13, OMIM:620244 to Lymphatic malformation 13, OMIM:620244
Fetal anomalies v5.66 TBR1 Achchuthan Shanmugasundram Phenotypes for gene: TBR1 were changed from AUTISM; Intellectual developmental disorder with autism and speech delay, OMIM:606053 to Intellectual developmental disorder with autism and speech delay, OMIM:606053
Fetal anomalies v5.65 TACR3 Achchuthan Shanmugasundram Phenotypes for gene: TACR3 were changed from HYPOGONADOTROPIC HYPOGONADISM; Hypogonadotropic hypogonadism 11 with or without anosmia, OMIM:614840 to Hypogonadotropic hypogonadism 11 with or without anosmia, OMIM:614840
Fetal anomalies v5.64 TAC3 Achchuthan Shanmugasundram Phenotypes for gene: TAC3 were changed from Hypogonadotropic hypogonadism 10 with or without anosmia, OMIM:614839; HYPOGONADOTROPIC HYPOGONADISM to Hypogonadotropic hypogonadism 10 with or without anosmia, OMIM:614839
Fetal anomalies v5.63 STAG1 Achchuthan Shanmugasundram Phenotypes for gene: STAG1 were changed from Intellectual developmental disorder, autosomal dominant 47, OMIM:617635; STAG1 syndromic intellectual disability to Intellectual developmental disorder, autosomal dominant 47, OMIM:617635
Fetal anomalies v5.62 SNAP25 Achchuthan Shanmugasundram Phenotypes for gene: SNAP25 were changed from Epilepsy and intellectual disability; Myasthenic syndrome, congenital, 18, OMIM:616330 to Myasthenic syndrome, congenital, 18, OMIM:616330
Fetal anomalies v5.61 SMPD1 Achchuthan Shanmugasundram Phenotypes for gene: SMPD1 were changed from Niemann-Pick disease, type B, OMIM:607616; NIEMANN-PICK DISEASE TYPE A; NIEMANN-PICK DISEASE TYPE B; Niemann-Pick disease, type A, OMIM:257200 to Niemann-Pick disease, type B, OMIM:607616; Niemann-Pick disease, type A, OMIM:257200
Fetal anomalies v5.60 SMOC2 Achchuthan Shanmugasundram Phenotypes for gene: SMOC2 were changed from DENTIN DYSPLASIA, TYPE I, WITH MICRODONTIA AND MISSHAPEN TEETH; Dentin dysplasia, type I, with microdontia and misshapen teeth, OMIM:125400 to Dentin dysplasia, type I, with microdontia and misshapen teeth, OMIM:125400
Fetal anomalies v5.59 SLC35A1 Achchuthan Shanmugasundram Phenotypes for gene: SLC35A1 were changed from CONGENITAL DISORDERS OF GLYCOSYLATION; Congenital disorder of glycosylation, type IIf, OMIM:603585 to Congenital disorder of glycosylation, type IIf, OMIM:603585
Fetal anomalies v5.58 SLC25A4 Achchuthan Shanmugasundram Phenotypes for gene: SLC25A4 were changed from Severe Early-Onset Mitochondrial Disease and Loss of Mitochondrial DNA Copy Number; Mitochondrial DNA depletion syndrome 12A (cardiomyopathic type) AD, OMIM:617184 to Mitochondrial DNA depletion syndrome 12A (cardiomyopathic type) AD, OMIM:617184
Fetal anomalies v5.57 SLC24A4 Achchuthan Shanmugasundram Phenotypes for gene: SLC24A4 were changed from Amelogenesis imperfecta, type IIA5, OMIM:615887; AMELOGENESIS IMPERFECTA. to Amelogenesis imperfecta, type IIA5, OMIM:615887
Fetal anomalies v5.56 SETD1A Achchuthan Shanmugasundram Phenotypes for gene: SETD1A were changed from INTELLECTUAL DISABILITY; Neurodevelopmental disorder with speech impairment and dysmorphic facies, OMIM:619056 to Neurodevelopmental disorder with speech impairment and dysmorphic facies, OMIM:619056
Fetal anomalies v5.55 SASS6 Achchuthan Shanmugasundram Phenotypes for gene: SASS6 were changed from Microcephaly 14, primary, autosomal recessive, OMIM:616402; ?Microcephaly 14, primary, autosomal recessive 616402 to Microcephaly 14, primary, autosomal recessive, OMIM:616402
Fetal anomalies v5.54 RSPRY1 Achchuthan Shanmugasundram Phenotypes for gene: RSPRY1 were changed from PROGRESSIVE SPONDYLOEPIMETAPHYSEAL DYSPLASIA; Spondyloepimetaphyseal dysplasia, Faden-Alkuraya type, OMIM:616723 to Spondyloepimetaphyseal dysplasia, Faden-Alkuraya type, OMIM:616723
Fetal anomalies v5.53 RRAS Achchuthan Shanmugasundram Phenotypes for gene: RRAS were changed from Noonan syndrome, MONDO:0018997; RRAS-related atypical Noonan syndrome to Noonan syndrome, MONDO:0018997
Fetal anomalies v5.52 NUAK2 Achchuthan Shanmugasundram Phenotypes for gene: NUAK2 were changed from Anencephaly; ?Anencephaly 2, OMIM:619452 to ?Anencephaly 2, OMIM:619452
Fetal anomalies v5.51 NHP2 Achchuthan Shanmugasundram Phenotypes for gene: NHP2 were changed from DYSKERATOSIS CONGENITA, AUTOSOMAL RECESSIVE 2; Dyskeratosis congenita, autosomal recessive 2, OMIM:613987 to Dyskeratosis congenita, autosomal recessive 2, OMIM:613987
Fetal anomalies v5.50 LRBA Achchuthan Shanmugasundram Phenotypes for gene: LRBA were changed from Immunodeficiency, common variable, 8, with autoimmunity, OMIM:614700; CHILDHOOD-ONSET HYPOGAMMAGLOBULINEMIA to Immunodeficiency, common variable, 8, with autoimmunity, OMIM:614700
Fetal anomalies v5.49 LRAT Achchuthan Shanmugasundram Phenotypes for gene: LRAT were changed from Leber congenital amaurosis 14, OMIM:613341; LEBER CONGENITAL AMAUROSIS to Leber congenital amaurosis 14, OMIM:613341
Fetal anomalies v5.48 LOX Achchuthan Shanmugasundram Phenotypes for gene: LOX were changed from Aortopathy; Aortic aneurysm, familial thoracic 10, OMIM:617168 to Aortic aneurysm, familial thoracic 10, OMIM:617168
Fetal anomalies v5.47 LIPT2 Achchuthan Shanmugasundram Phenotypes for gene: LIPT2 were changed from Mitochondrial Lipoylation Defect Associated with Severe Neonatal Encephalopathy; Encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities, OMIM:617668 to Encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities, OMIM:617668
Fetal anomalies v5.46 LIPN Achchuthan Shanmugasundram Phenotypes for gene: LIPN were changed from ICHTHYOSIS, LAMELLAR, 4; Ichthyosis, congenital, autosomal recessive 8, OMIM:613943 to Ichthyosis, congenital, autosomal recessive 8, OMIM:613943
Fetal anomalies v5.45 KCNT1 Achchuthan Shanmugasundram Phenotypes for gene: KCNT1 were changed from SEVERE AUTOSOMAL DOMINANT NOCTURNAL FRONTAL LOBE EPILEPSY; MALIGNANT MIGRATING PARTIAL SEIZURES OF INFANCY; Developmental and epileptic encephalopathy 14, OMIM:614959 to Developmental and epileptic encephalopathy 14, OMIM:614959
Fetal anomalies v5.44 KCNJ6 Achchuthan Shanmugasundram Phenotypes for gene: KCNJ6 were changed from Keppen-Lubinsky syndrome, OMIM:614098; KEPPEN-LUBINSKY SYNDROME to Keppen-Lubinsky syndrome, OMIM:614098
Fetal anomalies v5.43 KCNC3 Achchuthan Shanmugasundram Phenotypes for gene: KCNC3 were changed from Spinocerebellar ataxia 13, OMIM:605259; SPINOCEREBELLAR ATAXIA TYPE 13 to Spinocerebellar ataxia 13, OMIM:605259
Fetal anomalies v5.42 ITCH Achchuthan Shanmugasundram Phenotypes for gene: ITCH were changed from Autoimmune disease, multisystem, with facial dysmorphism, OMIM:613385; AUTOIMMUNE DISEASE, SYNDROMIC MULTISYSTEM to Autoimmune disease, multisystem, with facial dysmorphism, OMIM:613385
Fetal anomalies v5.41 INPP5K Achchuthan Shanmugasundram Phenotypes for gene: INPP5K were changed from Muscular dystrophy, congenital, with cataracts and intellectual disability, OMIM:617404; Muscular dystrophy, congenital, with cataracts and intellectual disability to Muscular dystrophy, congenital, with cataracts and intellectual disability, OMIM:617404
Fetal anomalies v5.40 GPAA1 Achchuthan Shanmugasundram Phenotypes for gene: GPAA1 were changed from Developmental Delay, Epilepsy, Cerebellar Atrophy, and Osteopenia; Glycosylphosphatidylinositol biosynthesis defect 15, OMIM:617810 to Glycosylphosphatidylinositol biosynthesis defect 15, OMIM:617810
Fetal anomalies v5.39 GNAQ Achchuthan Shanmugasundram Phenotypes for gene: GNAQ were changed from Sturge-Weber syndrome, somatic, mosaic, OMIM:185300; Congenital Hemangioma; Capillary malformations, congenital, 1, somatic, mosaic, OMIM:163000 to Sturge-Weber syndrome, somatic, mosaic, OMIM:185300; Capillary malformations, congenital, 1, somatic, mosaic, OMIM:163000
Fetal anomalies v5.38 GNA11 Achchuthan Shanmugasundram Phenotypes for gene: GNA11 were changed from Congenital Hemangioma; Hypocalciuric hypercalcemia, type II, OMIM:145981; Hypocalcemia, autosomal dominant 2, OMIM:615361 to Hypocalciuric hypercalcemia, type II, OMIM:145981; Hypocalcemia, autosomal dominant 2, OMIM:615361
Fetal anomalies v5.37 GLIS2 Achchuthan Shanmugasundram Phenotypes for gene: GLIS2 were changed from NEPHRONOPHTHISIS 7; Nephronophthisis 7, OMIM:611498 to Nephronophthisis 7, OMIM:611498
Fetal anomalies v5.36 GDF2 Achchuthan Shanmugasundram Phenotypes for gene: GDF2 were changed from hydrops; Lymphatic dysplasia; Telangiectasia, hereditary hemorrhagic, type 5, OMIM:615506; hydrothorax to Telangiectasia, hereditary hemorrhagic, type 5, OMIM:615506
Fetal anomalies v5.35 FUZ Achchuthan Shanmugasundram Phenotypes for gene: FUZ were changed from Skeletal ciliopathy, MONDO:0005308; Neural tube defects 182940 to Skeletal ciliopathy, MONDO:0005308
Fetal anomalies v5.34 FTO Achchuthan Shanmugasundram Phenotypes for gene: FTO were changed from Growth retardation, developmental delay, facial dysmorphism; Growth retardation, developmental delay, facial dysmorphism, OMIM: 612938 to Growth retardation, developmental delay, facial dysmorphism, OMIM: 612938
Fetal anomalies v5.33 FN1 Achchuthan Shanmugasundram Phenotypes for gene: FN1 were changed from Spondylometaphyseal dysplasia, corner fracture type, OMIM:184255; Spondylometaphyseal Dysplasia with Corner Fractures to Spondylometaphyseal dysplasia, corner fracture type, OMIM:184255
Fetal anomalies v5.32 DRC1 Achchuthan Shanmugasundram Phenotypes for gene: DRC1 were changed from Ciliary dyskinesia, primary, 21, OMIM:615294; PRIMARY CILARY DYSKINEASIA to Ciliary dyskinesia, primary, 21, OMIM:615294
Fetal anomalies v5.31 DLG4 Achchuthan Shanmugasundram Phenotypes for gene: DLG4 were changed from DLG4 related intellectual disability; Intellectual developmental disorder, autosomal dominant 62, OMIM:618793 to Intellectual developmental disorder, autosomal dominant 62, OMIM:618793
Fetal anomalies v5.30 DHX30 Achchuthan Shanmugasundram Phenotypes for gene: DHX30 were changed from Neurodevelopmental Disorder; Neurodevelopmental disorder with variable motor and speech impairment, OMIM:617804 to Neurodevelopmental disorder with variable motor and speech impairment, OMIM:617804
Fetal anomalies v5.29 DCDC2 Achchuthan Shanmugasundram Phenotypes for gene: DCDC2 were changed from RENAL-HEPATIC CILIOPATHY; Sclerosing cholangitis, neonatal, OMIM:617394 to Sclerosing cholangitis, neonatal, OMIM:617394
Fetal anomalies v5.28 CSTA Achchuthan Shanmugasundram Phenotypes for gene: CSTA were changed from EXFOLIATIVE ICHTHYOSIS, AUTOSOMAL RECESSIVE, ICHTHYOSIS BULLOSA OF SIEMENS-LIKE; Peeling skin syndrome 4, OMIM:607936 to Peeling skin syndrome 4, OMIM:607936
Fetal anomalies v5.27 CRELD1 Achchuthan Shanmugasundram Phenotypes for gene: CRELD1 were changed from Jeffries-Lakhani neurodevelopmental syndrome, OMIM:620771; HETEROTAXY SYNDROME to Jeffries-Lakhani neurodevelopmental syndrome, OMIM:620771
Fetal anomalies v5.26 CLPP Achchuthan Shanmugasundram Phenotypes for gene: CLPP were changed from Perrault syndrome 3, OMIM:614129; PERRAULT SYNDROME to Perrault syndrome 3, OMIM:614129
Fetal anomalies v5.25 CHD8 Achchuthan Shanmugasundram Phenotypes for gene: CHD8 were changed from AUTISM; Intellectual developmental disorder with autism and macrocephaly, OMIM:615032 to Intellectual developmental disorder with autism and macrocephaly, OMIM:615032
Fetal anomalies v5.24 CHD3 Achchuthan Shanmugasundram Phenotypes for gene: CHD3 were changed from Apraxia of speech; Snijders Blok-Campeau syndrome, OMIM:618205 to Snijders Blok-Campeau syndrome, OMIM:618205
Fetal anomalies v5.23 CD151 Achchuthan Shanmugasundram Phenotypes for gene: CD151 were changed from Epidermolysis bullosa simplex 7, with nephropathy and deafness, OMIM:609057; NEPHROPATHY WITH PRETIBIAL EPIDERMOLYSIS BULLOSA AND DEAFNESS to Epidermolysis bullosa simplex 7, with nephropathy and deafness, OMIM:609057
Fetal anomalies v5.22 CAMTA1 Achchuthan Shanmugasundram Phenotypes for gene: CAMTA1 were changed from Cerebellar dysfunction with variable cognitive and behavioral abnormalities, OMIM:614756; CEREBELLAR ATAXIA, NONPROGRESSIVE, WITH MENTAL RETARDATION to Cerebellar dysfunction with variable cognitive and behavioral abnormalities, OMIM:614756
Fetal anomalies v5.21 CAMK2B Achchuthan Shanmugasundram Phenotypes for gene: CAMK2B were changed from INTELLECTUAL DISABILITY; Intellectual developmental disorder, autosomal dominant 54, OMIM:617799 to Intellectual developmental disorder, autosomal dominant 54, OMIM:617799
Fetal anomalies v5.20 CACNA1S Achchuthan Shanmugasundram Phenotypes for gene: CACNA1S were changed from Congenital myopathy 18 due to dihydropyridine receptor defect, OMIM:620246; Congenital myopathy; arthrogryposis to Congenital myopathy 18 due to dihydropyridine receptor defect, OMIM:620246
Fetal anomalies v5.19 BPTF Achchuthan Shanmugasundram Phenotypes for gene: BPTF were changed from Developmental and Speech Delay, Postnatal Microcephaly, and Dysmorphic Features; Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies, OMIM:617755 to Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies, OMIM:617755
Fetal anomalies v5.18 ALG13 Achchuthan Shanmugasundram Phenotypes for gene: ALG13 were changed from CONGENITAL DISORDER OF GLYCOSYLATION, TYPE IS; EPILEPTIC ENCEPHALOPATHY; EPILEPTIC ENCEPHALOPATHIES.; Developmental and epileptic encephalopathy 36, OMIM:300884 to Developmental and epileptic encephalopathy 36, OMIM:300884
Fetal anomalies v5.17 ALG11 Achchuthan Shanmugasundram Phenotypes for gene: ALG11 were changed from ALG11-CDG; Congenital disorder of glycosylation, type Ip, OMIM:613661 to Congenital disorder of glycosylation, type Ip, OMIM:613661
Fetal anomalies v5.16 C16orf62 Achchuthan Shanmugasundram commented on gene: C16orf62: The 'new-gene-name' tag has been added as the HGNC approved gene symbol is VPS35L.
Fetal anomalies v5.16 C16orf62 Achchuthan Shanmugasundram Tag new-gene-name tag was added to gene: C16orf62.
Fetal anomalies v5.16 AL117258.1 Achchuthan Shanmugasundram commented on gene: AL117258.1: The 'new-gene-name' tag has been added as the HGNC approved symbol for this gene is CIROP.
Fetal anomalies v5.16 AL117258.1 Achchuthan Shanmugasundram Tag new-gene-name tag was added to gene: AL117258.1.
Fetal anomalies v5.16 ZSCAN10 Achchuthan Shanmugasundram commented on gene: ZSCAN10
Fetal anomalies v5.16 ZRSR2 Achchuthan Shanmugasundram commented on gene: ZRSR2
Fetal anomalies v5.16 ZNF750 Achchuthan Shanmugasundram commented on gene: ZNF750
Fetal anomalies v5.16 ZNF687 Achchuthan Shanmugasundram commented on gene: ZNF687
Fetal anomalies v5.16 ZNF423 Achchuthan Shanmugasundram commented on gene: ZNF423
Fetal anomalies v5.16 ZMYND8 Achchuthan Shanmugasundram commented on gene: ZMYND8
Fetal anomalies v5.16 ZFX Achchuthan Shanmugasundram commented on gene: ZFX
Fetal anomalies v5.16 XPNPEP3 Achchuthan Shanmugasundram commented on gene: XPNPEP3
Fetal anomalies v5.16 WNT9B Achchuthan Shanmugasundram commented on gene: WNT9B
Fetal anomalies v5.16 WISP3 Achchuthan Shanmugasundram commented on gene: WISP3
Fetal anomalies v5.16 WDR44 Achchuthan Shanmugasundram commented on gene: WDR44
Fetal anomalies v5.16 WBP4 Achchuthan Shanmugasundram commented on gene: WBP4
Fetal anomalies v5.16 WASHC5 Achchuthan Shanmugasundram commented on gene: WASHC5
Fetal anomalies v5.16 VHL Achchuthan Shanmugasundram commented on gene: VHL
Fetal anomalies v5.16 UQCC2 Achchuthan Shanmugasundram commented on gene: UQCC2