Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000130492 | SCV000185361 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2023-05-04 | criteria provided, single submitter | clinical testing | The c.405-1G>C intronic variant results from a G to C substitution one nucleotide upstream from coding exon 3 of the RAD51C gene. This alteration was identified in 2/5054 African American women with breast cancer and 0/4993 unaffected African American women drawn from 10 epidemiologic studies (Palmer JR et al. J Natl Cancer Inst, 2020 12;112:1213-1221). 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 and will result in the creation or strengthening of a novel splice acceptor site; however, direct evidence is insufficient at this time (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. |
| Labcorp Genetics |
RCV000204135 | SCV000259320 | pathogenic | Fanconi anemia complementation group O | 2025-01-31 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 2 of the RAD51C gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or altered protein product. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with breast cancer (PMID: 32427313). ClinVar contains an entry for this variant (Variation ID: 141823). Studies have shown that disruption of this splice site alters mRNA splicing and is expected to lead to the loss of protein expression (PMID: 35740625; internal data). For these reasons, this variant has been classified as Pathogenic. |
| Counsyl | RCV000576619 | SCV000677803 | likely pathogenic | Breast-ovarian cancer, familial, susceptibility to, 3; Fanconi anemia complementation group O | 2016-11-28 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV002291568 | SCV002584296 | likely pathogenic | not provided | 2022-10-11 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); Observed in individuals with breast cancer (Palmer et al., 2020); 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; This variant is associated with the following publications: (PMID: 24800917, 21990120, 20400964, 28152038, 32427313) |
| Fulgent Genetics, |
RCV000576619 | SCV002775985 | likely pathogenic | Breast-ovarian cancer, familial, susceptibility to, 3; Fanconi anemia complementation group O | 2024-06-13 | criteria provided, single submitter | clinical testing | |
| Myriad Genetics, |
RCV003315894 | SCV004019962 | likely pathogenic | Breast-ovarian cancer, familial, susceptibility to, 3 | 2023-04-05 | 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. |
| Baylor Genetics | RCV003315894 | SCV004208013 | likely pathogenic | Breast-ovarian cancer, familial, susceptibility to, 3 | 2023-04-02 | criteria provided, single submitter | clinical testing |