Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000462224 | SCV000549557 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2024-03-28 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 4 of the BRCA2 gene. It does not directly change the encoded amino acid sequence of the BRCA2 protein. This variant is not present in population databases (gnomAD no frequency). 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: 91816). 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. |
| Ambry Genetics | RCV001022169 | SCV001183870 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-07 | criteria provided, single submitter | clinical testing | The c.426-12_426-9delGTTT intronic variant results from a deletion of 4 nucleotides within intron 3 of the BRCA2 gene. These nucleotide positions are well conserved in available vertebrate species. In silico splice site analysis for this alteration is inconclusive. RNA studies have demonstrated that this alteration results in substantial abnormal splicing in the set of samples tested (Ambry internal data). However, a close-match alteration at BRCA2 c.426-12_426-8delGTTTT, which has a similar splice profile, has been reported in trans with other pathogenic BRCA2 variants in patients of unknown age and phenotype who do not have overt symptoms of Fanconi Anemia (Ambry internal data; Nix, P et al. JCO Prec. Onc. 2020 June;4:790-35).. Since supporting evidence is conflicting at this time, the clinical significance of this alteration remains unclear. |
| Sharing Clinical Reports Project |
RCV000077724 | SCV000109527 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2010-02-25 | no assertion criteria provided | clinical testing |