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| Intellectual disability syndromic and non-syndromic v1.346 | SF1 |
Sarah Milton changed review comment from: SF1 is involved in the first step of spliceosome complex assembly by recognizing the intron branchpoint consensus sequence at the 3′ splice site of the pre-mRNA. It is also involved in regulating alternative splicing PMID: 40987292 describes 15 affected individuals with a neurodevelopmental disorder with monoallelic variants in SF1. Affected individuals had developmental delay, mild to moderate ID, behavioural disorders, seizures (3/15), brachydactyly (5/15), nail hypoplasia (5/15). Variant types included missense and high impact LOF (nonsense and frameshift). Most variants were appropriately rare in gnomAD v4 however one reported variant had 9 hets. pLI for SF1 is 1 with overall few LOF variants in gene. Supportive functional studies reported in publication. SF1 deficient neural progenitor cells showed altered gene expression in genes involved in neuronal differentiation/synaptic transmission and axonal guidance. Sources: Literature; to: SF1 is involved in the first step of spliceosome complex assembly by recognizing the intron branchpoint consensus sequence at the 3′ splice site of the pre-mRNA. It is also involved in regulating alternative splicing PMID: 40987292 describes 15 affected individuals with a neurodevelopmental disorder with monoallelic variants in SF1. Affected individuals had developmental delay, mild to moderate ID, behavioural disorders, seizures (3/15), brachydactyly (5/15), nail hypoplasia (5/15). 12 confirmed to have de novo variants including missense and high impact LOF (nonsense and frameshift). Most variants were appropriately rare in gnomAD v4 however one reported variant had 9 hets. pLI for SF1 is 1 with overall few LOF variants in gene. Supportive functional studies reported in publication. SF1 deficient neural progenitor cells showed altered gene expression in genes involved in neuronal differentiation/synaptic transmission and axonal guidance. Sources: Literature |
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| Intellectual disability syndromic and non-syndromic v1.346 | SF1 |
Sarah Milton gene: SF1 was added gene: SF1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature Mode of inheritance for gene: SF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SF1 were set to PMID: 40987292 Phenotypes for gene: SF1 were set to Neurodevelopmental disorder, MONDO:0700092, SF1-related Review for gene: SF1 was set to GREEN Added comment: SF1 is involved in the first step of spliceosome complex assembly by recognizing the intron branchpoint consensus sequence at the 3′ splice site of the pre-mRNA. It is also involved in regulating alternative splicing PMID: 40987292 describes 15 affected individuals with a neurodevelopmental disorder with monoallelic variants in SF1. Affected individuals had developmental delay, mild to moderate ID, behavioural disorders, seizures (3/15), brachydactyly (5/15), nail hypoplasia (5/15). Variant types included missense and high impact LOF (nonsense and frameshift). Most variants were appropriately rare in gnomAD v4 however one reported variant had 9 hets. pLI for SF1 is 1 with overall few LOF variants in gene. Supportive functional studies reported in publication. SF1 deficient neural progenitor cells showed altered gene expression in genes involved in neuronal differentiation/synaptic transmission and axonal guidance. Sources: Literature |
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| Intellectual disability syndromic and non-syndromic v0.5340 | SRSF1 | Zornitza Stark Phenotypes for gene: SRSF1 were changed from Neurodevelopmental disorder, SRSF1-related MONDO:0700092 to Neurodevelopmental disorder with dysmorphic facies and behavioral abnormalities, MIM# 620489 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.5339 | SRSF1 | Zornitza Stark reviewed gene: SRSF1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with dysmorphic facies and behavioral abnormalities, MIM# 620489; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.5218 | SRSF1 | Zornitza Stark Classified gene: SRSF1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.5218 | SRSF1 | Zornitza Stark Gene: srsf1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.5218 | SRSF1 | Zornitza Stark Marked gene: SRSF1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.5218 | SRSF1 | Zornitza Stark Gene: srsf1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.5218 | SRSF1 | Zornitza Stark Classified gene: SRSF1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.5218 | SRSF1 | Zornitza Stark Gene: srsf1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.5216 | SRSF1 | Paul De Fazio edited their review of gene: SRSF1: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.5216 | SRSF1 |
Paul De Fazio gene: SRSF1 was added gene: SRSF1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature Mode of inheritance for gene: SRSF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SRSF1 were set to 37071997 Phenotypes for gene: SRSF1 were set to Neurodevelopmental disorder, SRSF1-related MONDO:0700092 Review for gene: SRSF1 was set to GREEN gene: SRSF1 was marked as current diagnostic Added comment: 17 individuals from 16 families reported with mostly de novo variants. Variants were a mixture of missense, nonsense/frameshift (both NMD-predicted and not NMD-predicted) and microdeletions. In one family, only one parent was available for testing. In another family, 2 affected siblings had the variant but the variant was not identified in either parent suggesting germline mosaicism. Functional testing of a subset of variants in Drosophila supported pathogenicity in most, but 2 missense variants showed no functional effect and were classified VUS. Episignature analysis (EpiSign) on patient DNA from blood showed a specific DNA methylation signature in patients with the variants classified pathogenic but not those classified VUS. Phenotypes included mainly neurological abnormalities (mild to moderate ID/dev delay, motor delay, speech delay, and behavioural disorders) and facial dysmorphisms. Other features included hypotonia (11/16), variable brain abnormalities on MRI (6/12), variable cardiac malformations (6/14). urogenital malformations e.g. hypospadias, cryptorchidism (6/13), scoliosis (5/17) and/or variable other skeletal abnormalities (10/17). Sources: Literature |
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| Intellectual disability syndromic and non-syndromic v0.4770 | WASF1 | Zornitza Stark Phenotypes for gene: WASF1 were changed from to Neurodevelopmental disorder with absent language and variable seizures , MIM#618707 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.4769 | WASF1 | Zornitza Stark Publications for gene: WASF1 were set to PMID: 29961568 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.4768 | WASF1 | Zornitza Stark reviewed gene: WASF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29961568, 34845217, 34478686, 34356165; Phenotypes: Neurodevelopmental disorder with absent language and variable seizures , MIM#618707; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.4255 | CSF1R | Zornitza Stark Marked gene: CSF1R as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.4255 | CSF1R | Zornitza Stark Gene: csf1r has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.4255 | CSF1R | Zornitza Stark Classified gene: CSF1R as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.4255 | CSF1R | Zornitza Stark Gene: csf1r has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.4254 | CSF1R |
Zornitza Stark gene: CSF1R was added gene: CSF1R was added to Intellectual disability syndromic and non-syndromic. Sources: Literature Mode of inheritance for gene: CSF1R was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CSF1R were set to 30982609; 33749994; 34135456 Phenotypes for gene: CSF1R were set to Brain abnormalities, neurodegeneration, and dysosteosclerosis, MIM# 618476; BANDDOS Review for gene: CSF1R was set to AMBER Added comment: Brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS) is an autosomal recessive disorder characterized by brain abnormalities, progressive neurologic deterioration, and sclerotic bone dysplasia similar to dysosteosclerosis (DOS). The age at onset is highly variable: some patients may present in infancy with hydrocephalus, global developmental delay, and hypotonia, whereas others may have onset of symptoms in the late teens or early twenties after normal development. Neurologic features include loss of previous motor and language skills, cognitive impairment, spasticity, and focal seizures. Brain imaging shows periventricular white matter abnormalities and calcifications, large cisterna magna or Dandy-Walker malformation, and sometimes agenesis of the corpus callosum. Four unrelated families reported. Note mono-allelic variants cause an adult-onset disorder. Sources: Literature |
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| Intellectual disability syndromic and non-syndromic v0.1255 | WASF1 | Zornitza Stark Marked gene: WASF1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.1255 | WASF1 | Zornitza Stark Gene: wasf1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.363 | WASF1 | Chirag Patel Classified gene: WASF1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.363 | WASF1 | Chirag Patel Gene: wasf1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.362 | WASF1 | Chirag Patel edited their review of gene: WASF1: Added comment: 5 unrelated individuals with moderate to profound intellectual disability with autistic features and seizures. Functional studies using fibroblast cells from two affected individuals showed a truncated WASF1 and a defect in actin remodeling.; Changed phenotypes: No OMIM phenotype # yet. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.362 | WASF1 |
Chirag Patel gene: WASF1 was added gene: WASF1 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert list Mode of inheritance for gene: WASF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: WASF1 were set to PMID: 29961568 Review for gene: WASF1 was set to GREEN Added comment: Sources: Expert list |
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