Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000534325 | SCV000631424 | pathogenic | 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency | 2023-09-12 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects SRD5A2 function (PMID: 8110760). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SRD5A2 protein function. ClinVar contains an entry for this variant (Variation ID: 459638). This missense change has been observed in individual(s) with ambiguous genitalia and 5 alpha-reductase deficiency (PMID: 20019388, 20736251, 20850730, 21631525, 23633205, 24665940). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs763296857, gnomAD 0.003%). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 193 of the SRD5A2 protein (p.Asn193Ser). |
Clinical Molecular Genetics Laboratory, |
RCV000534325 | SCV000692392 | pathogenic | 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency | 2017-10-31 | criteria provided, single submitter | clinical testing | |
Clinical Genetics and Genomics, |
RCV001269600 | SCV001449696 | likely pathogenic | not provided | 2017-08-18 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001269600 | SCV002578683 | pathogenic | not provided | 2022-04-04 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect on enzymatic function (Wigley et al., 1994); Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 3441728, 8110760, 31613402, 32894851, 27899157, 7608269, 30695888, 31031332, 32596280, 20850730, 28544750, 34276780) |