Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000459896 | SCV000549719 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2018-12-10 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 409536). This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with leucine at codon 2130 of the BRCA2 protein (p.Phe2130Leu). The phenylalanine residue is weakly conserved and there is a small physicochemical difference between phenylalanine and leucine. |
| Ambry Genetics | RCV001025207 | SCV001187351 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-06-12 | criteria provided, single submitter | clinical testing | The p.F2130L variant (also known as c.6388T>C), located in coding exon 10 of the BRCA2 gene, results from a T to C substitution at nucleotide position 6388. The phenylalanine at codon 2130 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Color Diagnostics, |
RCV001025207 | SCV001340820 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-06-27 | criteria provided, single submitter | clinical testing | |
| University of Washington Department of Laboratory Medicine, |
RCV001025207 | SCV003852483 | likely benign | Hereditary cancer-predisposing syndrome | 2023-03-23 | criteria provided, single submitter | curation | Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673). |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV004999464 | SCV005624498 | uncertain significance | not provided | 2024-09-19 | criteria provided, single submitter | clinical testing | The BRCA2 c.6388T>C (p.Phe2130Leu) variant has been reported in the published literature to be located in a region of the BRCA2 gene that is tolerant to missense sequence changes (PMID: 31911673 (2020)). To the best of our knowledge, this variant has not been reported in individuals with BRCA2-related disorders. The frequency of this variant in the general population, 0.0000041 (1/242050 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |