Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000215010 | SCV000275459 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2024-04-22 | criteria provided, single submitter | clinical testing | The c.7436-2_7437delAGAT variant, located in the BRCA2 gene, is caused by the deletion of the first two nucleotides of coding exon 14 as well as the first two nucleotides upstream of this coding exon, causing a disruption of the canonical acceptor splice site. This alteration has been identified in one family whose clinical history was suggestive of hereditary breast and ovarian cancer (van Harssel JJ et al. Fam Cancer. 2010 Jun;9(2):193-201). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This nucleotide region is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site and will result in the creation or strengthening of a novel splice acceptor site. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic. |
| Labcorp Genetics |
RCV001215895 | SCV001387663 | likely pathogenic | Hereditary breast ovarian cancer syndrome | 2020-04-08 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). This variant, also known as "c.7436_7437-2delAGAT" in the literature, has been reported in a family affected with breast and/or ovarian cancer (PMID: 19949876). ClinVar contains an entry for this variant (Variation ID: 231567). This variant is a deletion of the genomic region encompassing part of intron 14 and part of exon 15 (c.7436-2_7437del) of the BRCA2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. |
| Baylor Genetics | RCV004567564 | SCV005059185 | pathogenic | Familial cancer of breast | 2023-11-16 | criteria provided, single submitter | clinical testing |