Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000206097 | SCV000261170 | likely pathogenic | Hereditary breast ovarian cancer syndrome | 2024-01-15 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 15 of the BRCA2 gene. It does not directly change the encoded amino acid sequence of the BRCA2 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with breast cancer (PMID: 35264596). ClinVar contains an entry for this variant (Variation ID: 220547). Studies have shown that this variant results in activation of a cryptic splice site and introduces a premature termination codon (Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. 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. |
| Mendelics | RCV000206097 | SCV000838857 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2018-07-02 | criteria provided, single submitter | clinical testing | |
| Mendelics | RCV000989067 | SCV001139190 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV003343703 | SCV004052498 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2023-08-02 | criteria provided, single submitter | clinical testing | The c.7618-10T>G intronic variant results from a T to G substitution 10 nucleotides upstream from coding exon 15 in the BRCA2 gene. This alteration was detected in a cohort of 1663 Brazilian breast cancer patients who underwent hereditary multigene panel testing (Guindalini RSC et al. Sci Rep, 2022 Mar;12:4190). This nucleotide position 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. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |