Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002390189 | SCV002669094 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-04-17 | criteria provided, single submitter | clinical testing | The p.F2504L variant (also known as c.7512T>G), located in coding exon 14 of the BRCA2 gene, results from a T to G substitution at nucleotide position 7512. The phenylalanine at codon 2504 is replaced by leucine, an amino acid with highly similar properties. In a study utilizing a bioinformatics method that integrates information about protein sequence, conservation, and structure in a protein likelihood ratio, the effect of this alteration was predicted to be neutral (Karchin R et al. Cancer Inform. 2008;6:203-16). 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. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV004998157 | SCV005625288 | uncertain significance | not provided | 2024-04-25 | criteria provided, single submitter | clinical testing | The BRCA2 c.7512T>G (p.Phe2504Leu) variant has been reported in the published literature as neutral in a multifactorial likelihood analysis (PMID: 19043619 (2008)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). 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. |
Breast Cancer Information Core |
RCV000113771 | SCV000147111 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2001-01-17 | no assertion criteria provided | clinical testing |