Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000206670 | SCV000259820 | likely pathogenic | Familial cancer of breast | 2023-12-07 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 9 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 is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BARD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 219763). Studies have shown that disruption of this splice site is associated with altered splicing resulting in multiple RNA products (Invitae). 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. |
| Ambry Genetics | RCV002408889 | SCV002723705 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2023-06-14 | criteria provided, single submitter | clinical testing | The c.1904-2A>T intronic variant results from an A to T substitution two nucleotides upstream from coding exon 10 in the BARD1 gene. This nucleotide position is highly 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. |
| Myriad Genetics, |
RCV000206670 | SCV004043711 | likely pathogenic | Familial cancer of breast | 2023-05-24 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function. |