Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000003503 | SCV000631419 | pathogenic | 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency | 2016-05-30 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with  glutamine at codon 55 of the SRD5A2 protein (p.Leu55Gln). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and glutamine. This variant is not present in population databases (rs121434245, ExAC no frequency). This variant has been reported as homozygous in many individuals affected with SRD5A2-related disease, and was shown to segregate with disease in an affected family (PMID: 20850730, 8768837, 1522235, 12008688) Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. Algorithms developed to predict the effect of sequence changes on mRNA splicing suggest that this variant may alter mRNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant is a rare missense change that has been clearly associated with 5-alpha reductase deficiency in affected individuals. Therefore, it has been classified as Pathogenic. |
Clinical Genetics and Genomics, |
RCV001269601 | SCV001449697 | likely pathogenic | not provided | 2017-08-18 | criteria provided, single submitter | clinical testing | |
Kariminejad - |
RCV001813943 | SCV001755444 | likely pathogenic | Abnormality of the genitourinary system | 2021-07-10 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000003503 | SCV000023661 | pathogenic | 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency | 1996-08-01 | no assertion criteria provided | literature only |