Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000218589 | SCV000278726 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-04-18 | criteria provided, single submitter | clinical testing | The p.Q1502R variant (also known as c.4505A>G), located in coding exon 10 of the BRCA2 gene, results from an A to G substitution at nucleotide position 4505. The glutamine at codon 1502 is replaced by arginine, an amino acid with highly similar properties. In a population-based study of Chinese women, this variant was detected in 1/645 breast cancer patients but was not seen in 342 women with benign breast disease or 319 healthy controls (Suter NM et al. Cancer Epidemiol Biomarkers Prev. 2004 Feb;13:181-9). This variant was also identified in 1 of 1009 patients amongst a cohort of Chinese patients with a personal history of pancreatic ductal adenocarcinoma (Yin L et al. JAMA Netw Open, 2022 Feb;5:e2148721). This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |
University of Washington Department of Laboratory Medicine, |
RCV000218589 | SCV003850565 | 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 | RCV003477777 | SCV004219636 | uncertain significance | not provided | 2022-12-28 | criteria provided, single submitter | clinical testing | It has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In the published literature, the variant has been reported in breast cancer association studies (PMIDs: 14973102 (2004) and 31825140 (2019)). Additionally, the variant has been reported both as likely deleterious (PMID: 14973102 (2004)) and as having a decreased association with disease (PMID: 31853058 (2020)). 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. |