Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000648253 | SCV000770067 | pathogenic | Fanconi anemia complementation group O | 2017-12-14 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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 creates a premature translational stop signal (p.Phe17Serfs*9) in the RAD51C gene. It is expected to result in an absent or disrupted protein product. |
| Ambry Genetics | RCV002343334 | SCV002645802 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2022-09-12 | criteria provided, single submitter | clinical testing | The c.50delT variant, located in coding exon 1 of the RAD51C gene, results from a deletion of one nucleotide at nucleotide position 50, causing a translational frameshift with a predicted alternate stop codon (p.F17Sfs*9). The predicted stop codon occurs in the 5’ end of theRAD51C gene. Premature termination codons in the 5’ end of a gene have been reported to escape nonsense-mediated mRNAdecay and/or lead to re-initiation (Rivas et al. Science. 2015 May 8;348(6235):666-9; Lindeboom et al. Nat Genet. 2016 Oct;48(10):1112-8; Rhee et al. Sci Rep. 2017 May 10;7(1):1653). Direct evidence for this alteration is unavailable, however premature termination codons are typically deleterious in nature. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |