Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002345180 | SCV002652041 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-04-20 | criteria provided, single submitter | clinical testing | The c.564G>A variant (also known as p.V188V) is located in coding exon 6 of the BRCA2 gene. This variant results from a G to A substitution at nucleotide position 564. This nucleotide substitution does not change the at codon 188. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration may weaken the native splice acceptor site. RNA studies have demonstrated that this alteration results in an incomplete splice defect; the clinical impact of this abnormal splicing is unknown at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003645293 | SCV004425275 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2024-05-29 | criteria provided, single submitter | clinical testing | This sequence change affects codon 188 of the BRCA2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the BRCA2 protein. This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1748851). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |