ClinVar Miner

Submissions for variant NM_000348.4(SRD5A2):c.698+1G>T

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Clinical Biochemistry Laboratory, Health Services Laboratory RCV003459924 SCV004190309 pathogenic 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency 2023-11-20 criteria provided, single submitter clinical testing ACMG:PVS1 PM2 PP4 PP5
Labcorp Genetics (formerly Invitae), Labcorp RCV003459924 SCV004292404 pathogenic 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency 2023-12-21 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 4 of the SRD5A2 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is present in population databases (rs747672984, gnomAD 0.01%). Disruption of this splice site has been observed in individual(s) with steroid-5 alpha-reductase deficiency (PMID: 1522235, 28938747, 30132287, 30668521, 31130284, 33516834). This variant is also known as 725+1G>T. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts a region of the SRD5A2 protein in which other variant(s) (p.Tyr235Phe) have been determined to be pathogenic (PMID: 8110760, 16181229, 17609295, 27070133). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV003459924 SCV005663643 likely pathogenic 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency 2024-03-26 criteria provided, single submitter clinical testing

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