ClinVar Miner

Submissions for variant NM_000348.4(SRD5A2):c.656del (p.Phe219fs)

dbSNP: rs61748127
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000083630 SCV000616885 pathogenic not provided 2017-09-06 criteria provided, single submitter clinical testing The c.656delT variant in the SRD5A2 gene (also referred to as c.655delT) has been reported previously in association with autosomal recessive 5-alpha-reductase deficiency when present in the homozygous state or when in trans with another disease-causing variant (Ko et al., 2010; Fan et al., 2017; Wang et al., 2004). Functional studies on transfected COS-7 cells demonstrated that the pathogenic variant resulted in a dramatic reduction in 5-alpha-reductase activity (Zhang et al., 2011). This frameshift pathogenic variant replaces the typical last 36 amino acid residues in the SRD5A2 protein with 59 different amino acid residues. This change is expected to alter the normal structure and function of the resultant protein. The c.656delT variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.656delT as a pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV003500502 SCV004292406 pathogenic 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency 2024-02-07 criteria provided, single submitter clinical testing This sequence change results in a frameshift in the SRD5A2 gene (p.Phe219Serfs*60). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 36 amino acid(s) of the SRD5A2 protein and extend the protein by 23 additional amino acid residues. This variant is present in population databases (rs9332962, gnomAD 0.01%). This frameshift has been observed in individual(s) with steroid-5 alpha-reductase deficiency (PMID: 20190539, 23329752). This variant is also known as c.Tdel219. ClinVar contains an entry for this variant (Variation ID: 97381). For these reasons, this variant has been classified as Pathogenic.
University of Sydney Medical Foundation RCV000083630 SCV000115716 not provided not provided no assertion provided not provided

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