Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Department of Medical Genetics, |
RCV001249472 | SCV001422495 | pathogenic | 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency | 2019-11-15 | criteria provided, single submitter | clinical testing | This variant, NM_000348.4:c.485A>C, was found in compound heterozygosity with the pathogenic variant NM_000348.4:c.680G>A. |
| Invitae | RCV001249472 | SCV004535299 | likely pathogenic | 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency | 2024-01-12 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with proline, which is neutral and non-polar, at codon 162 of the SRD5A2 protein (p.His162Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with steroid-5 alpha-reductase deficiency (PMID: 31031332, 35386187). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 973099). 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) performed at Invitae indicates that this missense variant is expected to disrupt SRD5A2 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects SRD5A2 function (PMID: 31031332). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |