Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001032263 | SCV001195570 | pathogenic | Hereditary breast ovarian cancer syndrome | 2019-10-28 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exon 23 of the BRCA1 gene. The 5' boundary is likely confined to intron 22. 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 protein product or disrupt mRNA translation. Deletions of exon 23 have been reported in individuals with a personal or family history of breast and ovarian cancer (PMID: 24825132, 25428789, 18431737). A deletion of exon 23 is also known as a deletion of exon 24 in the literature. This deletion is expected to partially remove the C-terminal BRCT domain of the BRCA1 protein, which is important for DNA repair activity (PMID: 14576433, 15133503). A different deleterious variant (p.Tyr1853*) within the deleted sequence of this variant has been shown to disrupt BRCA1 protein function (PMID: 8942979, 20681793, 10811118, 11256609, 17308087), suggesting that although this particular variant may not result in nonsense mediated decay, it is expected to affect BRCA1 protein function. For these reasons, this variant has been classified as Pathogenic. |