Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001754834 | SCV001996454 | uncertain significance | not provided | 2019-10-07 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Victorian Clinical Genetics Services, |
RCV002471145 | SCV002768884 | uncertain significance | Microcephaly 2, primary, autosomal recessive, with or without cortical malformations | 2021-05-06 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as 3A-VUS. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with microcephaly 2, primary, with or without cortical malformations (MIM#604317). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from leucine to glutamine. (I) 0252 - This variant is homozygous. (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) 1102 - Strong phenotype match for this individual. (SP) 1207 - Parental origin of the variant is unresolved. While the proband's mother is heterozygous for the variant, a paternal sample was not available for segregation testing. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |