ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.904+1G>T

dbSNP: rs1555602159
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000571657 SCV000663791 likely pathogenic Hereditary cancer-predisposing syndrome 2021-05-13 criteria provided, single submitter clinical testing The c.904+1G>T intronic variant results from a G to T substitution one nucleotide after coding exon 6 of the RAD51C gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000986014 SCV001134793 likely pathogenic not provided 2018-11-21 criteria provided, single submitter clinical testing The variant disrupts a canonical splice site, and is therefore predicted to result in the loss of a functional protein. Not found in the total gnomAD dataset, and the data is high quality (0/276968 chr).
Invitae RCV001047716 SCV001211695 likely pathogenic Fanconi anemia complementation group O 2021-07-07 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). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with RAD51C-related conditions. ClinVar contains an entry for this variant (Variation ID: 480510). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 6 of the RAD51C gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.
Sema4, Sema4 RCV000571657 SCV002530030 likely pathogenic Hereditary cancer-predisposing syndrome 2021-02-22 criteria provided, single submitter curation
Baylor Genetics RCV003459305 SCV004208036 likely pathogenic Breast-ovarian cancer, familial, susceptibility to, 3 2022-06-16 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV003459305 SCV004932560 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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