ClinVar Miner

Submissions for variant NM_002878.3(RAD51D):c.823C>T (p.Arg275Trp) (rs752780416)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000561370 SCV000663812 uncertain significance Hereditary cancer-predisposing syndrome 2016-07-14 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or Conflicting Evidence
Color RCV000561370 SCV000903559 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-08 criteria provided, single submitter clinical testing
GeneDx RCV000236684 SCV000292682 uncertain significance not provided 2018-11-26 criteria provided, single submitter clinical testing This variant is denoted RAD51D c.823C>T at the cDNA level, p.Arg275Trp (R275W) at the protein level, and results in the change of an Arginine to a Tryptophan (CGG>TGG). This variant has been reported in at least one individual with a history of epithelial ovarian cancer (Song 2015). RAD51D Arg275Trp 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 Arg275Trp is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000559840 SCV000651784 uncertain significance Breast-ovarian cancer, familial 4 2018-11-01 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 275 of the RAD51D protein (p.Arg275Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs752780416, ExAC 0.001%). This variant has been reported in the literature in an individual affected with ovarian cancer (PMID: 26261251). ClinVar contains an entry for this variant (Variation ID: 245669). 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.
Mendelics RCV000709434 SCV000839176 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing

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