Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000465619 | SCV000563930 | pathogenic | Hereditary breast ovarian cancer syndrome | 2016-10-11 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exons 2-3 of the BRCA2 gene, which includes the initiator codon. The 5' end of this event is unknown as it extends beyond the assayed region for this gene and therefore may encompass additional genes. The 3' boundary is likely confined to intron 3 of the BRCA2 gene. This is expected to result in an absent or disrupted protein product. Loss-of-function variants including gross deletions in BRCA2 are known to be pathogenic. Deletion of exons 2-3 has been observed in an individual affected with breast cancer (Invitae database). In addition, a smaller gross deletion of exon 2 including the initiator codon has been reported in individuals affected with hereditary breast and/or ovarian cancer (PMID: 17063271). Four different variants involving the initiation codon (c.2T>A, c.2T>C, c.2T>G, and c.3G>A) have been reported in individuals affected with hereditary breast and/or ovarian cancer (PMID: 24607278, 24156927, 14647210, 18182601), indicating that this start site is critical for translation of a functional BRCA2 protein. For these reasons, this variant has been classified as Pathogenic. |