ClinVar Miner

Submissions for variant NM_002878.3(RAD51D):c.349T>A (p.Cys117Ser) (rs786201358)

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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 RCV000163461 SCV000214012 uncertain significance Hereditary cancer-predisposing syndrome 2017-10-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000163461 SCV000686447 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-29 criteria provided, single submitter clinical testing
Counsyl RCV000410914 SCV000489115 uncertain significance Breast-ovarian cancer, familial 4 2016-08-22 criteria provided, single submitter clinical testing
GeneDx RCV000478670 SCV000565464 uncertain significance not provided 2018-07-09 criteria provided, single submitter clinical testing This variant is denoted RAD51D c.349T>A at the cDNA level, p.Cys117Ser (C117S) at the protein level, and results in the change of a Cysteine to a Serine (TGT>AGT). This variant has been observed in at least one individual with ovarian cancer and one individual with breast cancer (Song 2015, Tung 2015). RAD51D Cys117Ser was not observed 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 Cys117Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000410914 SCV000551381 uncertain significance Breast-ovarian cancer, familial 4 2018-12-07 criteria provided, single submitter clinical testing This sequence change replaces cysteine with serine at codon 117 of the RAD51D protein (p.Cys117Ser). The cysteine residue is highly conserved and there is a moderate physicochemical difference between cysteine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with ovarian cancer (PMID: 26261251) and in an individual affected with breast cancer (PMID: 25186627). ClinVar contains an entry for this variant (Variation ID: 184247). 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"). 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.

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