ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1460C>A (p.Ala487Glu) (rs56390402)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 11
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000679155 SCV000602832 likely benign not provided 2017-07-31 criteria provided, single submitter clinical testing The BRCA2 c.1406C>A, p.Ala487Glu variant (rs56390402) has been reported in patients diagnosed with breast cancer (Borg 2010, Soegaard 2008). However, multifactorial assessment, taking into account tumor pathology, co-segregation and co-occurrence with a pathogenic variant, suggests this variant is unlikely to be disease-causing (Capanu 2011, Lindor 2012). The variant is observed in the general population databases with overall allele frequencies of 0.008 percent (1/13004 alleles) in the Exome Variant Server, and 0.009 percent (24/269856 alleles) in the Genome Aggregation Database. The alanine at residue 487 is weakly conserved, and computational algorithms (GV/GD, Mutation Taster, PolyPhen-2, SIFT) predict that the variant has no impact on the protein. Based on the above information, the variant is considered likely benign. References: Borg A et al. Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study. Hum Mutat. 2010 Mar;31(3):E1200-40. Capanu M et al. Assessment of rare BRCA1 and BRCA2 variants of unknown significance using hierarchical modeling. Genet Epidemiol. 2011 Jul;35(5):389-97. Lindor N et al. A review of a multifactorial probability-based model for classification of BRCA1 and BRCA2 variants of uncertain significance (VUS). Hum Mutat. 2012 Jan;33(1):8-21. Soegaard M et al. BRCA1 and BRCA2 mutation prevalence and clinical characteristics of a population-based series of ovarian cancer cases from Denmark. Clin Cancer Res. 2008 Jun 15;14(12):3761-7.
Ambry Genetics RCV000131573 SCV000186579 benign Hereditary cancer-predisposing syndrome 2014-11-19 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031322 SCV000145875 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Color RCV000131573 SCV000910624 benign Hereditary cancer-predisposing syndrome 2015-12-15 criteria provided, single submitter clinical testing
Counsyl RCV000031322 SCV000220591 likely benign Breast-ovarian cancer, familial 2 2014-08-12 criteria provided, single submitter literature only
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000043812 SCV000591745 likely benign not specified 2015-03-18 criteria provided, single submitter clinical testing
GeneDx RCV000043812 SCV000210560 likely benign not specified 2017-08-25 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.
Institute for Biomarker Research,Medical Diagnostic Laboratories, L.L.C. RCV000131573 SCV000679708 likely benign Hereditary cancer-predisposing syndrome 2017-07-12 criteria provided, single submitter clinical testing
Invitae RCV000167837 SCV000071825 benign Hereditary breast and ovarian cancer syndrome 2018-01-11 criteria provided, single submitter clinical testing
PreventionGenetics RCV000679155 SCV000805653 likely benign not provided 2017-08-17 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031322 SCV000053927 benign Breast-ovarian cancer, familial 2 2011-03-03 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.