Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000204084 | SCV000261256 | pathogenic | Fanconi anemia complementation group O | 2016-10-12 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exons 5-9 of the RAD51C gene. The 5' boundary is likely confined to the intronic region between exons 4 and 5. The 3' end of this event is unknown as it extends through the termination codon beyond the assayed region for this gene and may encompass additional genes. While this deletion is not predicted to result in nonsense mediated decay, it is expected to create a truncated RAD51C protein. A similar deletion of exons 5-9 has been reported in individuals affected with breast cancer and ovarian cancer (PMID: 24359560). This deletion is predicted to result in the loss of 141 C-terminal amino acid residues of the RAD51C protein, including the nuclear localization signal. In vitro analyses have shown that deletion of the nuclear localization signal leads to improper cellular distribution of the protein and increased sensitivity to DNA cross-linking agents (PMID: 12966089). For these reasons, this variant has been classified as Pathogenic. |