ClinVar Miner

Submissions for variant NM_002878.3(RAD51D):c.607G>A (p.Val203Met) (rs730881947)

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 RCV000570494 SCV000667143 uncertain significance Hereditary cancer-predisposing syndrome 2018-04-16 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000570494 SCV000686473 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-08 criteria provided, single submitter clinical testing
GeneDx RCV000160949 SCV000211656 uncertain significance not provided 2018-12-10 criteria provided, single submitter clinical testing This variant is denoted RAD51D c.607G>A at the cDNA level, p.Val203Met (V203M) at the protein level, and results in the change of a Valine to a Methionine (GTG>ATG). This variant has been reported in at least one individual undergoing multigene hereditary cancer panel testing (Mu 2016). RAD51D Val203Met was not observed at a significant allele frequency in large population cohorts (Lek 2016). Since Valine and Methionine share similar properties, this is considered a conservative amino acid substitution. RAD51D Val203Met is located in the walker B ATPase motif and the RAD51C binding domain (Miller 2004). In silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure or function. Based on currently available evidence, it is unclear whether RAD51D Val203Met is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000545735 SCV000651763 uncertain significance Breast-ovarian cancer, familial 4 2018-12-18 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 203 of the RAD51D protein (p.Val203Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs730881947, ExAC 0.006%). This variant has been reported in individuals undergoing multigene hereditary cancer panel testing (PMID: 27720647). ClinVar contains an entry for this variant (Variation ID: 182860). 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: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional 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.

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.