ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.773G>A (p.Arg258His) (rs267606997)

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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 RCV000131703 SCV000186741 likely pathogenic Hereditary cancer-predisposing syndrome 2018-02-28 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Deficient protein function in appropriate functional assay(s),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Invitae RCV000007224 SCV000550214 likely pathogenic Fanconi anemia, complementation group O 2018-12-27 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 258 of the RAD51C protein (p.Arg258His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs267606997, ExAC 0.003%). This variant has been reported to segregate in individuals with features of Fanconi anemia in a single family (PMID: 20400963). It has also been reported in individuals affected with breast and/or ovarian cancer (PMID: 25154786, 26740214). ClinVar contains an entry for this variant (Variation ID: 6822). Experimental studies have shown that this missense change results in increased chromosomal disruption and G2 arrest (PMID: 20400963, 22167183). Wild-type RAD51C cDNA was able to rescue G2 arrest, while cDNA carrying this variant failed to rescue. Another study showed that this missense change results in decreased replication restart at stalled replication forks, which may result in increased replication-associated double-stranded breaks (PMID: 26354865). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000506412 SCV000602145 likely pathogenic not provided 2017-07-21 criteria provided, single submitter clinical testing
Color RCV000131703 SCV000686387 likely pathogenic Hereditary cancer-predisposing syndrome 2018-09-05 criteria provided, single submitter clinical testing
OMIM RCV000007224 SCV000027420 pathogenic Fanconi anemia, complementation group O 2010-05-01 no assertion criteria provided literature only

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