ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.97C>T (p.Gln33Ter) (rs587782528)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131716 SCV000186754 pathogenic Hereditary cancer-predisposing syndrome 2017-04-07 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
GeneDx RCV000212932 SCV000211638 pathogenic not provided 2017-06-23 criteria provided, single submitter clinical testing This pathogenic variant is denoted RAD51C c.97C>T at the cDNA level and p.Gln33Ter (Q33X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAG>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been observed in at least two individuals with ovarian cancer (Song 2015) and is considered pathogenic.
Invitae RCV000196217 SCV000253965 pathogenic Fanconi anemia, complementation group O 2018-12-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln33*) in the RAD51C gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs587782528, ExAC 0.01%). This variant has been reported in the literature in individuals affected with ovarian cancer and endometrial cancer (PMID: 26261251, 26681312). ClinVar contains an entry for this variant (Variation ID: 142534). Loss-of-function variants in RAD51C are known to be pathogenic (PMID: 20400964, 21990120, 24800917). For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000196217 SCV000489955 pathogenic Fanconi anemia, complementation group O 2016-08-26 criteria provided, single submitter clinical testing
Counsyl RCV000410098 SCV000489956 pathogenic Breast-ovarian cancer, familial 3 2016-08-26 criteria provided, single submitter clinical testing
Color RCV000131716 SCV000537681 pathogenic Hereditary cancer-predisposing syndrome 2016-06-20 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000589795 SCV000699813 pathogenic Hereditary breast and ovarian cancer syndrome 2016-08-08 criteria provided, single submitter clinical testing Variant summary: The RAD51C c.97C>T (p.Gln33X) variant results in a premature termination codon, predicted to cause a truncated or absent RAD51C protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 1/126836, which does not exceed the estimated maximal expected allele frequency for a pathogenic RAD51C variant of 1/16000. The variant of interest has been reported in an affected individual, along with multiple reputable databases/clinical laboratories citing the variant as "pathogenic." Therefore, the variant of interest has been classified as Pathogenic.

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