ClinVar Miner

Submissions for variant NM_000348.4(SRD5A2):c.692A>G (p.His231Arg) (rs121434251)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000003510 SCV000692400 pathogenic 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency 2017-06-12 no assertion criteria provided clinical testing
Invitae RCV000003510 SCV000830869 pathogenic 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency 2018-03-16 criteria provided, single submitter clinical testing This sequence change replaces histidine with arginine at codon 231 of the SRD5A2 protein (p.His231Arg). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and arginine. This variant is present in population databases (rs121434251, ExAC 0.03%). This variant has been reported to segregate with 5 alpha-reductase 2 deficiency in several families (PMID: 9745434, 28544750, 27899157) and had also been reported in several unrelated, affected individuals (PMID: 1522235, 8706317, 7608269, 8723114). ClinVar contains an entry for this variant (Variation ID: 3346). Experimental studies have shown that this missense change impairs binding of testosterone to the enzyme and reduces enzyme activity (PMID: 8110760.1522235). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000003510 SCV000023668 pathogenic 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency 1998-09-01 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.