ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.97_98del (p.Gln33fs)

dbSNP: rs587780840
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000123379 SCV000166702 pathogenic Fanconi anemia complementation group O 2024-01-09 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln33Aspfs*3) in the RAD51C gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RAD51C are known to be pathogenic (PMID: 20400964, 21990120, 24800917, 29278735). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with hereditary breast and/or ovarian cancer (PMID: 26270727). ClinVar contains an entry for this variant (Variation ID: 136163). RNA analysis performed to evaluate the impact of this premature translational stop signal on mRNA splicing indicates it does not significantly alter splicing (Invitae). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV002371958 SCV002690595 likely pathogenic Hereditary cancer-predisposing syndrome 2022-09-27 criteria provided, single submitter clinical testing The c.97_98delCA variant, located in coding exon 1 of the RAD51C gene, results from a deletion of two nucleotides at nucleotide positions 97 to 98, causing a translational frameshift with a predicted alternate stop codon (p.Q33Dfs*3). The predicted stop codon occurs in the 5’ end of theRAD51C gene. Premature termination codons in the 5’ end of a gene have been reported to escape nonsense-mediated mRNAdecay and/or lead to re-initiation (Rivas et al. Science. 2015 May 8;348(6235):666-9; Lindeboom et al. Nat Genet. 2016 Oct;48(10):1112-8; Rhee et al. Sci Rep. 2017 May 10;7(1):1653). Direct evidence for this alteration is unavailable, however premature termination codons are typically deleterious in nature. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Myriad Genetics, Inc. RCV004019712 SCV004932463 pathogenic Breast-ovarian cancer, familial, susceptibility to, 3 2024-01-02 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.

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