Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV004788463 | SCV005398001 | likely pathogenic | Neurodevelopmental disorder | 2024-09-21 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with autosomal recessive intellectual disability 65 (MIM#618109) and autosomal dominant neurodevelopmental disorder (MONDO:0700092), KDM5B-related. (I) 0108 - This gene is associated with both recessive and dominant disease. Biallelic pathogenic variants are associated with a more severe, syndromic intellectual disability (PMID: 29276005; DECIPHER). Individuals with heterozygous variants have also been reported, with developmental delay, intellectual disability and/or autistic features (PMIDs: 29276005, 30217758, 30409806). (I) 0112 - The condition associated with this gene has incomplete penetrance. While the recessive condition is fully penetrant, incomplete penetrance has been suggested for the autosomal dominant condition, where unaffected carriers of loss of function variants have been reported (PMIDs: 30217758, 30409806). (I) 0200 - Variant is predicted to result in a missense amino acid change from glutamic acid to lysine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed) (by trio analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |