Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV000776377 | SCV000911816 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-04 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with proline at codon 2476 of the BRCA2 protein. To our knowledge, functional studies have not been reported for this variant. In a large breast cancer case-control study conducted by the Breast Cancer Association Consortium, this variant was reported in 2/60464 cases and 0/53461 controls, showing inconclusive association with disease (p-value=0.502) (PMID: 33471991). This variant has also been reported in individuals affected with ovarian cancer (PMID: 28692638). 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. |
| Labcorp Genetics |
RCV000814272 | SCV000954674 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2024-08-31 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with proline, which is neutral and non-polar, at codon 2476 of the BRCA2 protein (p.Glu2476Pro). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This missense change has been observed in individual(s) with personal and/or family history of hereditary breast and ovarian cancer (PMID: 28692638, 30702160; internal data). ClinVar contains an entry for this variant (Variation ID: 630547). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The proline amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000985584 | SCV001133896 | uncertain significance | not provided | 2018-11-12 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000776377 | SCV001188802 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-12 | criteria provided, single submitter | clinical testing | The c.7426_7427delGAinsCC variant (also known as p.E2476P) located in coding exon 13 of the BRCA2 gene, results from an in-frame deletion of GA and insertion of CC at nucleotide positions 7426 to 7427. This results in the substitution of the glutamic acid residue for a proline residue at codon 2476, an amino acid with similar properties. This variant was identified in 1/826 unselected Chinese ovarian cancer patients (Wu X et al. Int J Gynecol Cancer, 2017 10;27:1650-1657). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be neutral 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. |
| Baylor Genetics | RCV004569465 | SCV005059134 | uncertain significance | Familial cancer of breast | 2023-12-26 | criteria provided, single submitter | clinical testing |