ClinVar Miner

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

dbSNP: rs1555602159
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000777004 SCV000912682 likely pathogenic Hereditary cancer-predisposing syndrome 2020-02-27 criteria provided, single submitter clinical testing This variant causes a G to A nucleotide substitution at the +1 position of intron 6 of the RAD51C gene. Splice site prediction tools predict that this variant may have a significant impact on RNA splicing. Although this prediction has not been confirmed in published RNA studies, this variant is expected to result in an absent or disrupted protein product. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in 1 individual affected with breast cancer (AACR 2017 poster). 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 RCV001873162 SCV002264870 likely pathogenic Fanconi anemia complementation group O 2021-09-08 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 630978). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with RAD51C-related conditions. 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. Variants that disrupt the donor or acceptor splice site 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).
Ambry Genetics RCV000777004 SCV002688056 likely pathogenic Hereditary cancer-predisposing syndrome 2022-09-22 criteria provided, single submitter clinical testing The c.904+1G>A intronic variant results from a G to A 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 and may result in the creation or strengthening of a novel splice donor site; however, direct evidence is insufficient (Ambry internal data). 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.
Myriad Genetics, Inc. RCV004027301 SCV004933013 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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