ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.647A>G (p.Tyr216Cys)

dbSNP: rs746755735
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001025311 SCV001187476 uncertain significance Hereditary cancer-predisposing syndrome 2021-04-19 criteria provided, single submitter clinical testing The p.Y216C variant (also known as c.647A>G), located in coding exon 4 of the RAD51C gene, results from an A to G substitution at nucleotide position 647. The tyrosine at codon 216 is replaced by cysteine, an amino acid with highly dissimilar properties. This variant was reported in 2/60,466 breast cancer cases and in 0/53,461 controls (Dorling et al. N Engl J Med. 2021 02;384:428-439). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001873394 SCV002299413 uncertain significance Fanconi anemia complementation group O 2022-04-08 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 216 of the RAD51C protein (p.Tyr216Cys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RAD51C-related conditions. ClinVar contains an entry for this variant (Variation ID: 826429). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C45"). 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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