ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.964del (p.Arg322fs)

dbSNP: rs1555603056
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000584392 SCV000691294 likely pathogenic Hereditary cancer-predisposing syndrome 2021-09-01 criteria provided, single submitter clinical testing This variant deletes 1 nucleotide in exon 7 of the RAD51C gene, creating a frameshift and premature translation stop signal in the last coding exon. While this mutant transcript is predicted to escape nonsense-mediated decay and be expressed as a truncated protein, it is expected to have disrupted or deleted ATPase domain (amino acid 100-347) (PMID: 1731253), RAD51 paralog binding domain (amino acid 79-376) (PMID: 14704354), and nuclear localization signal (amino acid 366-370) (PMID: 12966089). While functional studies have not been reported for this variant, cells carrying a mutant RAD51C protein without the nuclear localization signal showed increased sensitivity to a DNA cross-linking agent (PMID: 12966089). To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of RAD51C function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Likely Pathogenic.
Invitae RCV000701832 SCV000830651 likely pathogenic Fanconi anemia complementation group O 2023-01-25 criteria provided, single submitter clinical testing 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. This variant disrupts a region of the RAD51C protein in which other variant(s) (p.Ser353Hisfs*8) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 492399). This variant has not been reported in the literature in individuals affected with RAD51C-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg322Glyfs*42) in the RAD51C gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 55 amino acid(s) of the RAD51C protein.
Myriad Genetics, Inc. RCV003451314 SCV004189600 likely pathogenic Breast-ovarian cancer, familial, susceptibility to, 3 2023-12-06 criteria provided, single submitter clinical testing This variant is considered likely pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.

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