ClinVar Miner

Submissions for variant NM_002878.3(RAD51D):c.185C>T (p.Ser62Leu) (rs374357106)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000164390 SCV000215026 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-09 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000164390 SCV000686424 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-08 criteria provided, single submitter clinical testing
GeneDx RCV000236527 SCV000292802 uncertain significance not provided 2018-12-03 criteria provided, single submitter clinical testing This variant is denoted RAD51D c.185C>T at the cDNA level, p.Ser62Leu (S62L) at the protein level, and results in the change of a Serine to a Leucine (TCG>TTG). This variant was observed in two series investigating families with breast and/or ovarian cancer, with observation in one case and one control (Loveday 2011, Song 2015). RAD51D Ser62Leu was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the XRCC2 binding domian (Miller 2004). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether RAD51D Ser62Leu is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000461972 SCV000551366 uncertain significance Breast-ovarian cancer, familial 4 2018-09-26 criteria provided, single submitter clinical testing This sequence change replaces serine with leucine at codon 62 of the RAD51D protein (p.Ser62Leu). The serine residue is moderately conserved and there is a large physicochemical difference between serine and leucine. This variant is present in population databases (rs374357106, ExAC 0.006%). This variant has not been reported in the literature in individuals with RAD51D-related disease. ClinVar contains an entry for this variant (Variation ID: 185036). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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.