ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.956G>A (p.Arg319Gln) (rs367846829)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000561452 SCV000664917 likely benign Hereditary cancer-predisposing syndrome 2017-10-04 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbsnp, esp, 1000 genomes),Other strong data supporting benign classification
Color RCV000561452 SCV000909736 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000781791 SCV000920118 uncertain significance not specified 2018-01-22 criteria provided, single submitter clinical testing Variant summary: The RAD51C c.956G>A (p.Arg319Gln) variant involves the alteration of a non-conserved nucleotide and is predicted to be benign by 4/4 in silico tools. This variant was found in 5/240596 control chromosomes (gnomAD) at a frequency of 0.0000208, which does not exceed the estimated maximal expected allele frequency of a pathogenic RAD51C variant (0.0000625). Clinical diagnostic laboratories have classified this variant as uncertain significance (1) as well as likely benign (1). The variant of interest has not, to our knowledge, been reported in affected individuals via publications, nor has it been evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.
Invitae RCV000526400 SCV000660372 uncertain significance Fanconi anemia, complementation group O 2018-10-11 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 319 of the RAD51C protein (p.Arg319Gln). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs367846829, ExAC 0.01%). This variant has been reported in an individual affected with ovarian cancer, and in a healthy control individual (PMID: 26261251). ClinVar contains an entry for this variant (Variation ID: 478615). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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