Submissions for variant NM_058216.2(RAD51C):c.572-?_*120del

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000204454	SCV000261507	pathogenic	Fanconi anemia complementation group O	2016-11-18	criteria provided, single submitter	clinical testing	This variant is a gross deletion of the genomic region encompassing exons 4-9 of the RAD51C gene. The 5' boundary is likely confined to intron 3. 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 anticipated to result in nonsense mediated decay, it is expected to create a truncated RAD51C protein. While this particular variant has not been reported in the literature, loss-of-function variants in RAD51C are known to be pathogenic (PMID: 20400964, 21990120, 24800917). In addition, deletion of exons 5-9 has been reported in individuals affected with breast and ovarian cancer (PMID: 24359560). This deletion eliminates ~50% of the amino acid sequence encoded by RAD51C, resulting in the loss of C-terminal regions of the protein that are known to be involved in complex formation and proper nuclear localization of the RAD51C protein (PMID: 14704354, 12966089). For these reasons, this variant has been classified as Pathogenic.