Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000413900 | SCV000490673 | pathogenic | not provided | 2022-08-16 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate reduced transactivation activity on CYP11A1 and CYP17A1 promoters (Allali et al., 2011; Malikova et al., 2014); Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25122490, 27169744, 30425642, 30067310, 25383892, 32369823, 22028768) |
Genetic Services Laboratory, |
RCV000504282 | SCV000596055 | likely pathogenic | 46,XY sex reversal 3 | 2015-11-11 | criteria provided, single submitter | clinical testing | |
Invitae | RCV002230747 | SCV000829797 | pathogenic | Oligosynaptic infertility; 46,XY disorder of sex development | 2022-04-04 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 313 of the NR5A1 protein (p.Arg313Cys). 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. ClinVar contains an entry for this variant (Variation ID: 372437). This missense change has been observed in individual(s) with autosomal dominant disorders of sex development (DSD) (PMID: 25122490, 27169744, 30425642). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects NR5A1 function (PMID: 22028768, 25122490, 27169744). |
Center for Reproductive Medicine, |
RCV001662366 | SCV001877156 | likely pathogenic | Genetic non-acquired premature ovarian failure | 2019-10-01 | no assertion criteria provided | research |