ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.838-2A>G

dbSNP: rs748589398
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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 RCV000561624 SCV000663789 likely pathogenic Hereditary cancer-predisposing syndrome 2021-11-22 criteria provided, single submitter clinical testing The c.838-2A>G intronic variant results from an A to G substitution two nucleotides upstream from coding exon 6 in the RAD51C gene. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD).This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic mutation.
Invitae RCV000648242 SCV000770056 likely pathogenic Fanconi anemia complementation group O 2017-10-10 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. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in RAD51C are known to be pathogenic (PMID: 20400964, 21990120, 24800917). This variant has not been reported in the literature in individuals with RAD51C-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 5 of the RAD51C gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.
GeneDx RCV002259351 SCV002538904 likely pathogenic not provided 2022-06-13 criteria provided, single submitter clinical testing Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge
Baylor Genetics RCV003470841 SCV004208038 likely pathogenic Breast-ovarian cancer, familial, susceptibility to, 3 2022-06-07 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV003470841 SCV004931055 likely pathogenic Breast-ovarian cancer, familial, susceptibility to, 3 2024-01-03 criteria provided, single submitter clinical testing This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function.

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