Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001222167 | SCV001394255 | likely pathogenic | Familial cancer of breast | 2019-08-03 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 8 of the BARD1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. Disruption of this splice site has been observed in an individual with personal or family history of breast cancer (PMID: 29752822). 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. Donor and acceptor splice site variants 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). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. |
| Ambry Genetics | RCV002411819 | SCV002711419 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-28 | criteria provided, single submitter | clinical testing | The c.1811-1G>C intronic variant results from a G to C substitution one nucleotide upstream from coding exon 9 of the BARD1 gene. Alterations that disrupt the canonical splice site are expected to result in aberrant splicing.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. The resulting transcript is predicted to be in-frame and is not expected to trigger nonsense-mediated mRNAdecay; however, direct evidence is unavailable. The exact functional effect of the altered amino acid sequence is unknown. This nucleotide position is highly conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |