ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.440A>G (p.Gln147Arg) (rs80358674)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 16
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
3DMed Clinical Laboratory Inc RCV000677867 SCV000804028 uncertain significance Cancer of the pancreas 2017-01-16 no assertion criteria provided clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000679172 SCV000602867 likely benign not provided 2017-10-15 criteria provided, single submitter clinical testing The BRCA2 c.440A>G, p.Gln147Arg variant is reported in the medical literature in individuals of Asian descent diagnosed with breast cancer (Carney 2010, Kwong 2008, Purnomosair 2007, Suter 2004, Thirthagiri 2008), but was considered likely benign based on a multifactorial analysis (including segregation, tumor pathology, co-occurrence and family history), and absence of splicing defects (Sanz 2010, Whiley 2014). It is listed in the ClinVar database (Variation ID: 51644), in the dbSNP variant database (rs80358674), and observed in the Exome Aggregation Consortium general population database at a frequency of 0.025 percent (0.35 percent in the Asian population). The glutamine at residue 147 is weakly conserved, and computational algorithms (Align GVGD, Mutation Taster, PolyPhen-2, SIFT) predict that the variant has minimal impact on the protein. Based on the above information, the variant is considered likely benign. References: Carney M et al. Detection of BRCA1 and BRCA2 mutations in a selected Hawaii population. Hawaii Med J. 2010; 69(11):268-71. Kwong A et al. Characterization of the pathogenic mechanism of a novel BRCA2 variant in a Chinese family. Fam Cancer. 2008; 7(2):125-33. Purnomosair D et al. BRCA1 and BRCA2 germline mutation analysis in the Indonesian population. Breast Cancer Res Treat. 2007; 106(2):297-304. Sanz D et al. A high proportion of DNA variants of BRCA1 and BRCA2 is associated with aberrant splicing in breast/ovarian cancer patients. Clin Cancer Res. 2010; 16(6):1957-67. Suter N et al. BRCA1 and BRCA2 mutations in women from Shanghai China. Cancer Epidemiol Biomarkers Prev. 2004; 13(2):181-9. Thirthagiri E et al. Evaluation of BRCA1 and BRCA2 mutations and risk-prediction models in a typical Asian country (Malaysia) with a relatively low incidence of breast cancer. Breast Cancer Res. 2008; 10(4):R59. Whiley P et al. Multifactorial likelihood assessment of BRCA1 and BRCA2 missense variants confirms that BRCA1:c.122A>G(p.His41Arg) is a pathogenic mutation. PLoS One. 2014; 9(1):e86836.
Ambry Genetics RCV000131281 SCV000186250 benign Hereditary cancer-predisposing syndrome 2014-11-19 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077324 SCV000146864 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Cancer Genetics and Genomics Laboratory,British Columbia Cancer Agency RCV000120385 SCV000586916 benign not specified 2017-04-18 criteria provided, single submitter clinical testing
Color RCV000131281 SCV000683619 likely benign Hereditary cancer-predisposing syndrome 2015-04-07 criteria provided, single submitter clinical testing
Counsyl RCV000077324 SCV000220584 likely benign Breast-ovarian cancer, familial 2 2014-08-09 criteria provided, single submitter literature only
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000120385 SCV000591684 benign not specified 2013-04-04 criteria provided, single submitter clinical testing
GeneDx RCV000120385 SCV000210544 benign not specified 2014-06-11 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
ITMI RCV000120385 SCV000084537 not provided not specified 2013-09-19 no assertion provided reference population
Illumina Clinical Services Laboratory,Illumina RCV000044408 SCV000383612 likely benign Hereditary breast and ovarian cancer syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000349768 SCV000383613 likely benign Fanconi anemia 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000044408 SCV000072421 benign Hereditary breast and ovarian cancer syndrome 2017-12-19 criteria provided, single submitter clinical testing
PreventionGenetics RCV000679172 SCV000805706 likely benign not provided 2017-07-07 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000679172 SCV000887817 benign not provided 2018-03-02 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077324 SCV000109121 benign Breast-ovarian cancer, familial 2 2009-02-19 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.