Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000564400 | SCV000667133 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-21 | criteria provided, single submitter | clinical testing | The c.966-1G>T intronic variant results from a G to T substitution one nucleotide upstream from coding exon 8 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 acceptor site. RNA studies have demonstrated that this alteration results in a transcript predicted to lead to a protein with an in-frame insertion of 1 amino acid; however, the exact functional impact of the inserted amino acid is unknown at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV001378259 | SCV001575793 | uncertain significance | Fanconi anemia complementation group O | 2022-01-27 | criteria provided, single submitter | clinical testing | This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change affects an acceptor splice site in intron 7 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). This variant has not been reported in the literature in individuals affected with RAD51C-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Studies have shown that this variant is associated with altered splicing, but the impact on the resulting protein product is unknown (PMID: 33333735). ClinVar contains an entry for this variant (Variation ID: 482180). |
| Laboratory for Genotyping Development, |
RCV003159964 | SCV002758222 | pathogenic | Gastric cancer | 2021-07-01 | no assertion criteria provided | research |