Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000569389 | SCV000660931 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2023-10-13 | criteria provided, single submitter | clinical testing | The c.1810+2T>G intronic variant results from a T to G substitution two nucleotides after coding exon 8 in the BARD1 gene. 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. In silico splice site analysis predicts that this alteration will weaken the native splice donor 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. |
| Labcorp Genetics |
RCV000635609 | SCV000757028 | likely pathogenic | Familial cancer of breast | 2018-11-06 | criteria provided, single submitter | clinical testing | 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. This variant has not been reported in the literature in individuals with BARD1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor 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. 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. |
| Color Diagnostics, |
RCV000569389 | SCV000912314 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2020-02-26 | criteria provided, single submitter | clinical testing | This variant causes a T to G nucleotide substitution at the +2 position of intron 8 of the BARD1 gene. Splice site prediction tools predict that this variant may have a significant impact on RNA splicing. Although this prediction has not been confirmed in published RNA studies, this variant is expected to result in an absent or disrupted protein product. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BARD1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Likely Pathogenic. |
| Myriad Genetics, |
RCV000635609 | SCV004043470 | 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. |
| CZECANCA consortium | RCV001270957 | SCV001451761 | likely pathogenic | Breast and/or ovarian cancer | 2019-06-11 | no assertion criteria provided | clinical testing |