Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000199233 | SCV000254204 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-12-15 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2356 of the BRCA2 protein (p.Phe2356Val). 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: 216254). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA2 protein function with a negative predictive value of 95%. 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 | RCV000221818 | SCV000275306 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-01-26 | criteria provided, single submitter | clinical testing | The p.F2356V variant (also known as c.7066T>G), located in coding exon 13 of the BRCA2 gene, results from a T to G substitution at nucleotide position 7066. The phenylalanine at codon 2356 is replaced by valine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003387801 | SCV004100275 | uncertain significance | not specified | 2023-09-05 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.7066T>G (p.Phe2356Val) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 5.7e-06 in 351076 control chromosomes (gnomAD, Momozawa_2018, Okawa_2023). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.7066T>G in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. The following publications have been ascertained in the context of this evaluation (PMID: 30287823, 36243179). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Both submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| St. |
RCV004786535 | SCV005402397 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2023-12-13 | criteria provided, single submitter | clinical testing | The BRCA2 c.7066T>G (p.Phe2356Val) missense change is absent in gnomAD v2.1.1 (https://gnomad.broadinstitute.org). The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function, and to our knowledge functional studies have not been performed. To our knowledge, this variant has not been reported in individuals with Fanconi anemia. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. |