Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001039817 | SCV001203365 | pathogenic | Hereditary breast ovarian cancer syndrome | 2021-07-20 | criteria provided, single submitter | clinical testing | This variant disrupts the C-terminus of the BRCA2 protein. Other variant(s) that disrupt this region (p.Tyr3308*) have been determined to be pathogenic (PMID: 18593900, 18607349, 17026620, 22711857). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with BRCA2-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 BRCA2 gene (p.Asn3178Lysfs*39). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 241 amino acids of the BRCA2 protein. |
Ambry Genetics | RCV003283881 | SCV004005451 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-05-16 | criteria provided, single submitter | clinical testing | The c.9534delC pathogenic mutation, located in coding exon 25 of the BRCA2 gene, results from a deletion of one nucleotide at nucleotide position 9534, causing a translational frameshift with a predicted alternate stop codon (p.N3178Kfs*39). This alteration occurs at the 3' terminus of theBRCA2 gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 7% of the protein. However, premature stop codons are typically deleterious in nature and the impacted region is critical for protein function (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |