ClinVar Miner

Submissions for variant NM_000348.4(SRD5A2):c.682G>A (p.Ala228Thr)

dbSNP: rs121434249
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000003508 SCV000597253 pathogenic 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency 2019-05-23 criteria provided, single submitter clinical testing
Invitae RCV000003508 SCV000631432 pathogenic 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency 2024-01-12 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 228 of the SRD5A2 protein (p.Ala228Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with 5α-reductase-2 deficiency (PMID: 8723114, 8784107, 9843052, 23633205; Invitae). 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: 3344). 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%. For these reasons, this variant has been classified as Pathogenic.
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital RCV000003508 SCV000692399 pathogenic 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency 2017-09-08 criteria provided, single submitter clinical testing
Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesota RCV000003508 SCV000890889 pathogenic 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency 2016-09-14 criteria provided, single submitter clinical testing
Clinical Genetics and Genomics, Karolinska University Hospital RCV001270015 SCV001450434 pathogenic not provided 2019-07-22 criteria provided, single submitter clinical testing
GeneDx RCV001270015 SCV001810979 pathogenic not provided 2020-11-27 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; The majority of missense variants in this gene are considered pathogenic (Stenson et al., 2014); Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 8789759, 8723114, 23633205, 9843052, 8784107, 30269266)
OMIM RCV000003508 SCV000023666 pathogenic 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency 1998-11-16 no assertion criteria provided literature only

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