Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001377053 | SCV001574280 | likely pathogenic | Familial cancer of breast | 2020-10-10 | 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. This variant disrupts part of the C-terminal BRCT domain of BARD1 protein, which is required for chromosome stability and homology-directed repair (PMID: 17848578). A different variant (p.Val767fs) that lies downstream of this variant has been reported to affect BARD1 protein function (PMID: 30925164), this suggests that disruption of this region of the protein is causative of disease. This variant has not been reported in the literature in individuals with BARD1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the BARD1 gene (p.Gln701*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 77 amino acid(s) of the BARD1 protein. |
| Ambry Genetics | RCV002420850 | SCV002728361 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2020-11-19 | criteria provided, single submitter | clinical testing | The p.Q701* variant (also known as c.2101C>T), located in coding exon 11 of the BARD1 gene, results from a C to T substitution at nucleotide position 2101. This changes the amino acid from a glutamine to a stop codon within coding exon 11. This alteration occurs at the 3' terminus of BARD1 gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 14% of the protein. However, premature stop codons are typically deleterious in nature and the impacted region is critical for protein function. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |