ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.922G>T (p.Ala308Ser) (rs185057307)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166154 SCV000216927 uncertain significance Hereditary cancer-predisposing syndrome 2018-02-12 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,Conflicting evidence
Color RCV000166154 SCV000686404 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-17 criteria provided, single submitter clinical testing
Counsyl RCV000662381 SCV000784780 uncertain significance Breast-ovarian cancer, familial 3; Fanconi anemia, complementation group O 2017-12-22 criteria provided, single submitter clinical testing
GeneDx RCV000236041 SCV000292727 uncertain significance not provided 2018-11-07 criteria provided, single submitter clinical testing This variant is denoted RAD51C c.922G>T at the cDNA level, p.Ala308Ser (A308S) at the protein level, and results in the change of an Alanine to a Serine (GCT>TCT). This variant was observed in an individual undergoing multi-gene cancer panel testing due to a personal history of a Lynch syndrome-related cancer and/or polyps (Yurgelun 2015). RAD51C Ala308Ser was observed at an allele frequency of 0.07% (18/24,026) in individuals of African ancestry in large population cohorts (Lek 2016). This variant is located in a region that interacts with RAD51B, RAD51C, and XRCC3 (Miller 2004). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether RAD51C Ala308Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000227701 SCV000291255 uncertain significance Fanconi anemia, complementation group O 2019-01-02 criteria provided, single submitter clinical testing This sequence change replaces alanine with serine at codon 308 of the RAD51C protein (p.Ala308Ser). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and serine. This variant is present in population databases (rs185057307, ExAC 0.07%). This variant has been reported in an individual with suspected Lynch syndrome (PMID: 25980754). ClinVar contains an entry for this variant (Variation ID: 186543). 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: "Tolerated"; PolyPhen-2: "Possibly 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000236041 SCV000888608 uncertain significance not provided 2018-01-06 criteria provided, single submitter clinical testing

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