Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000561594 | SCV000665999 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-10-31 | criteria provided, single submitter | clinical testing | The c.68-5A>G intronic variant results from an A to G substitution 5 nucleotides upstream from coding exon 2 in the BRCA2 gene. This nucleotide position is poorly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to create a new alternate splice acceptor site. Quantitative RTPCR studies from patient material show that this alteration leads to the use of this cryptic acceptor site resulting in a transcript with an additional four nucleotides from intron 1 included leading to a frameshift (Gelli E et al. Cancers (Basel), 2019 Mar;11:). Based on the majority of available evidence to date, this alteration is classified as a disease-causing mutation. |
Labcorp Genetics |
RCV001243342 | SCV001416495 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2020-06-06 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 30832263). This variant has not been reported in the literature in individuals with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 481516). This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 2 of the BRCA2 gene. It does not directly change the encoded amino acid sequence of the BRCA2 protein. |
Baylor Genetics | RCV004569147 | SCV005059061 | uncertain significance | Familial cancer of breast | 2024-02-12 | criteria provided, single submitter | clinical testing |