Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003111271 | SCV003793291 | pathogenic | Familial cancer of breast | 2022-08-19 | criteria provided, single submitter | clinical testing | This variant results in the deletion of exons 2-9 and part of exon 1 (c.35_1903+171del) of the BARD1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in BARD1 are known to be pathogenic (PMID: 20077502, 21344236). This variant has not been reported in the literature in individuals affected with BARD1-related conditions. This variant disrupts a region of the BARD1 protein in which other variant(s) (p.Cys71Tyr) have been determined to be pathogenic (PMID: 26350354, 29367421; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |