Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001379969 | SCV001577885 | likely pathogenic | Familial cancer of breast | 2020-12-04 | 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. 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). This variant has been observed in individual(s) with ovarian cancer (PMID: 30322717). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 2 of the BARD1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. |
| Ambry Genetics | RCV003169942 | SCV003854320 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2022-11-23 | criteria provided, single submitter | clinical testing | The c.215+1G>A intronic variant results from a G to A substitution one nucleotide after coding exon 2 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 donor 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; however the impacted region is critical for protein function (Ambry internal data). This variant was identified in a cohort of 4439 women with ovarian cancer undergoing multigene panel testing at one laboratory (Carter NJ et al. Gynecol Oncol, 2018 Dec;151:481-488). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This nucleotide position is highly conserved in available vertebrate species. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |