ClinVar Miner

Submissions for variant NM_002878.3(RAD51D):c.715C>T (p.Arg239Trp) (rs770250516)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166936 SCV000217755 uncertain significance Hereditary cancer-predisposing syndrome 2017-08-03 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000166936 SCV000902844 likely benign Hereditary cancer-predisposing syndrome 2015-11-13 criteria provided, single submitter clinical testing
Counsyl RCV000409739 SCV000488994 uncertain significance Breast-ovarian cancer, familial 4 2016-08-02 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000409739 SCV000895089 uncertain significance Breast-ovarian cancer, familial 4 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000236062 SCV000292681 uncertain significance not provided 2018-07-25 criteria provided, single submitter clinical testing This variant is denoted RAD51D c.715C>T at the cDNA level, p.Arg239Trp (R239W) at the protein level, and results in the change of an Arginine to a Tryptophan (CGG>TGG). RAD51D Arg239Trp has been observed in at least five women with ovarian cancer, four of whom are reported to also carry the pathogenic variant RAD51D Arg232Ter (Wickramanayake 2012, Gutierrez-Enr?quez 2014, Song 2015, Sanchez-Bermudez 2018). RAD51D Arg239Trp was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in 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 Arg239Trp is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000409739 SCV000551328 uncertain significance Breast-ovarian cancer, familial 4 2018-12-24 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 239 of the RAD51D protein (p.Arg239Trp). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs770250516, ExAC 0.004%). This variant has been observed in individuals and families affected with ovarian cancer (PMID: 22986143, 26261251, 24130102). In both affected individuals and unaffected siblings, a pathogenic RAD51D variant c.694C>T (p.Arg232*) was also identified (PMID: 22986143, 24130102). ClinVar contains an entry for this variant (Variation ID: 187225). 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.
Mendelics RCV000709437 SCV000839179 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000236062 SCV000888609 uncertain significance not provided 2018-03-07 criteria provided, single submitter clinical testing

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