ClinVar Miner

Submissions for variant NM_000348.4(SRD5A2):c.680G>A (p.Arg227Gln) (rs9332964)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000288398 SCV000692398 pathogenic 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency 2016-04-12 no assertion criteria provided clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000083663 SCV000340737 pathogenic not provided 2016-04-15 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000288398 SCV000597254 likely pathogenic 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency 2017-05-22 criteria provided, single submitter clinical testing
Invitae RCV000288398 SCV000631431 pathogenic 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency 2018-11-27 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 227 of the SRD5A2 protein (p.Arg227Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs9332964, ExAC 0.6%). This variant has been reported in many individuals affected with steroid 5-alpha-reductase deficiency and is a common cause of disease in individuals of East Asian ancestry (PMID: 25899528, 25605705, 22453073, 20736251, 12843198, 14594182, 19342739). ClinVar contains an entry for this variant (Variation ID: 3351). Experimental studies have shown that this missense change reduces SRD5A2 activity to about 3.2% of wild type (PMID: 10898110). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000003515 SCV000023673 pathogenic Micropenis 2003-07-01 no assertion criteria provided literature only
SIB Swiss Institute of Bioinformatics RCV000288398 SCV000803498 likely pathogenic 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency 2018-05-31 criteria provided, single submitter curation This variant is interpreted as a Likely Pathogenic, for Pseudovaginal perineoscrotal hypospadias, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: PS3 => Well-established functional studies show a deleterious effect (PMID:10898110). PM2-Supporting => PM2 downgraded in strength to Supporting. PS4-Supporting => PS4 downgraded in strength to Supporting. Recurrently seen in non-related affected individuals (PMID:25899528). PM3-Supporting => PM3 downgraded in strength to Supporting (PMID:15064320).
University of Sydney Medical Foundation RCV000083663 SCV000115749 not provided not provided no assertion provided not provided

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