Submissions for variant NM_000348.4(SRD5A2):c.16C>T (p.Gln6Ter)

gnomAD frequency: 0.00002  dbSNP: rs9332960

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000500379	SCV000597255	pathogenic	3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency	2017-05-22	criteria provided, single submitter	clinical testing
Invitae	RCV000500379	SCV000631420	pathogenic	3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency	2024-01-11	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln6*) in the SRD5A2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SRD5A2 are known to be pathogenic (PMID: 1406794, 1944596). This variant is present in population databases (rs9332960, gnomAD 0.02%). This premature translational stop signal has been observed in individuals with steroid 5-alpha-reductase deficiency (PMID: 12576851, 18314109, 20190539, 21540559). ClinVar contains an entry for this variant (Variation ID: 436859). For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV000578706	SCV000680882	pathogenic	not provided	2017-09-22	criteria provided, single submitter	clinical testing	The Q6X nonsense variant in the SRD5A2 gene has been reported previously in both the compound heterozgyous and homozgyous state in association with 5-Alpha Reductase Deficiency type 2 (Sasaki et al., 2003; Wang et al., 2004; Sahakitrunguang et al., 2008; Nie et al., 2011; Zhu et al., 2014). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. In addition, the Q6X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016).
PreventionGenetics, part of Exact Sciences	RCV003403177	SCV004120337	pathogenic	SRD5A2-related condition	2022-12-14	criteria provided, single submitter	clinical testing	The SRD5A2 c.16C>T variant is predicted to result in premature protein termination (p.Gln6*). This variant has been reported in many individuals with 46,XY disorder of sex development due to 5α-reductase type 2 deficiency (Nie M et al. 2011. PubMed ID: 20736251; Cheng. 2019. PubMed ID: 31031332 ). This variant is reported in 0.017% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-31805954-G-A). Nonsense variants in SRD5A2 are expected to be pathogenic. This variant is interpreted as pathogenic.
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital	RCV000500379	SCV000692376	pathogenic	3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency	2011-01-26	no assertion criteria provided	clinical testing
Seattle Children's Hospital Molecular Genetics Laboratory, Seattle Children's Hospital	RCV000500379	SCV004174081	pathogenic	3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency		no assertion criteria provided	clinical testing