Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004703092 | SCV005202860 | pathogenic | Hereditary breast ovarian cancer syndrome | 2024-07-24 | criteria provided, single submitter | clinical testing | Variant summary: The variant involves the deletion of exons 6-9 in the RAD51C gene. A presumed nomenclature of c.(837+1_838-1)_(*1390_?)del has been designated for the purposes of this classification. The exact breakpoint at the distal 3' end of this variant is unknown, therefore this deletion may extend downstream of the annotated region of the gene. As it encompasses the termination codon, it is predicted to escape nonsense mediated decay (NMD). A large deletion matching exons 6-9 of the RAD51C gene was found at a frequency of 8.6e-06 in 462879 control chromosomes gnomAD database (CNVs v4.1 dataset). The deletion of exons 6-9 in the RAD51C gene has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer Syndrome, and other tumor phenotypes (e.g. Sato_2017, Ring_2016). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. However, missense variants in the deleted region have been reported in affected individuals (HGMD) and been classified as pathogenic by our laboratory in ClinVar (e.g. variation ID 182836), indicating the clinical/functional importance of the deleted region. The following publications have been ascertained in the context of this evaluation (PMID: 28796317, 27443514). ClinVar contains an entry for this variant (Variation ID: 832995). Based on the evidence outlined above, the variant was classified as likely pathogenic. |