Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001026720 | SCV001189157 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-01-18 | criteria provided, single submitter | clinical testing | The p.D2566E variant (also known as c.7698T>G), located in coding exon 15 of the BRCA2 gene, results from a T to G substitution at nucleotide position 7698. The aspartic acid at codon 2566 is replaced by glutamic acid, an amino acid with highly similar properties. This variant has been identified in an Italian breast/ovarian cancer family (Santonocito C et al. Breast, 2017 Dec;36:74-78). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV001301983 | SCV001491170 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2020-03-05 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with glutamic acid at codon 2566 of the BRCA2 protein (p.Asp2566Glu). The aspartic acid residue is moderately conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of hereditary breast and ovarian cancer syndrome (PMID: 29020660). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. |
| All of Us Research Program, |
RCV004004677 | SCV004835438 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2023-11-20 | criteria provided, single submitter | clinical testing | This missense variant replaces aspartic acid with glutamic acid at codon 2566 of the BRCA2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). A functional study has shown that this variant does not impact BRCA2-DDS1 binding (PMID: 30696104). This variant has been reported in individuals with a personal or family history of BRCA2-related cancer (PMID: 29020660, 35150867). 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. |