ClinVar Miner

Submissions for variant NM_002878.3(RAD51D):c.629C>T (p.Ala210Val) (rs376855484)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130714 SCV000185601 uncertain significance Hereditary cancer-predisposing syndrome 2017-10-04 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Counsyl RCV000412230 SCV000489288 uncertain significance Breast-ovarian cancer, familial 4 2016-09-13 criteria provided, single submitter clinical testing
Color RCV000130714 SCV000537602 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-15 criteria provided, single submitter clinical testing
Invitae RCV000412230 SCV000551348 uncertain significance Breast-ovarian cancer, familial 4 2018-11-20 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 210 of the RAD51D protein (p.Ala210Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs376855484, ExAC 0.01%). This variant has been reported in individuals affected with ovarian cancer, breast cancer, and an individual undergoing Lynch syndrome testing (PMID: 24130102, 26057125, 26261251, 25452441, 25980754). ClinVar contains an entry for this variant (Variation ID: 141969). 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. 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.
GeneDx RCV000657049 SCV000567621 uncertain significance not provided 2018-09-14 criteria provided, single submitter clinical testing This variant is denoted RAD51D c.629C>T at the cDNA level, p.Ala210Val (A210V) at the protein level, and results in the change of an Alanine to a Valine (GCG>GTG). This variant has been reported in at least five individuals with breast and/or ovarian cancer (Gutierrez-Enriquez 2014, Couch 2015, Janatova 2015, Song 2015). It was also reported in at least one individual with early-onset colon cancer, in an individual with a personal history of a Lynch syndrome-associated cancer and/or colon polyps, and in an individual with a personal and family history of pancreatic cancer (Yurgelun 2015, Pearlman 2017, Chaffee 2018). RAD51D Ala210Val was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the RAD51C binding domain (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 Ala210Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000484961 SCV000602163 uncertain significance not specified 2017-02-28 criteria provided, single submitter clinical testing

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.