Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002353077 | SCV002620099 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-01-08 | criteria provided, single submitter | clinical testing | The c.3790_3800del11insTTATC variant (also known as p.K1264_D1267delinsLS), located in coding exon 10 of the BRCA2 gene, results from an in-frame deletion of 11 nucleotides and insertion of TTATC at nucleotide positions 3790 to 3800. This results in the substitution of lysine, cysteine, histidine and aspartic acid residues for a lysine and serine residue at codons 1264 through 1267. These amino acid positions are not well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| All of Us Research Program, |
RCV004005640 | SCV004841229 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2023-10-23 | criteria provided, single submitter | clinical testing | This variant deletes 11 nucleotides and inserts 5 nucleotides, causing an in-frame deletion of cysteine 1265, histidine 1266 and aspartic acid 1267, and insertion of a serine residue in the BRCA2 protein. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BRCA2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |