ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.2957A>G (p.Asn986Ser) (rs28897718)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001080867 SCV000072106 likely benign Hereditary breast and ovarian cancer syndrome 2020-11-12 criteria provided, single submitter clinical testing
Ambry Genetics RCV000129122 SCV000183839 likely benign Hereditary cancer-predisposing syndrome 2018-05-25 criteria provided, single submitter clinical testing Co-occurence with mutation in same gene (phase unknown);In silico models in agreement (benign)
GeneDx RCV000168561 SCV000210583 likely benign not specified 2018-02-16 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.
Counsyl RCV000113119 SCV000488650 uncertain significance Breast-ovarian cancer, familial 2 2016-05-19 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000586870 SCV000694656 uncertain significance not provided 2016-06-07 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.2957A>G (p.Asn986Ser) variant involves the alteration of a non-conserved nucleotide. 4/5 in silico tools predict a benign outcome. This variant was found in 1/120330 control chromosomes at a frequency of 0.0000083, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). However, it could still represent as a very rare polymorphism. It has been reported in two breast cancer patients in literature without strong evidence for or against pathogenicity (Borg_2008, Wong-Brown_2015). It has also been reported by a reputable clinical database (BIC) in seven individuals undergoing BRCA1/2 testing. In one of the individuals, the variant co-occurred with another deleterious variant c. c.2808_2811delACAA, supporting for a benign outcome. In addition, multiple clinical laboratories have classified this variant as benign/likely benign and one lab classified this variant as VUS, all without evidence to independently evaluate. Taken together, this variant has been classified as VUS-possibly benign.
Color Health, Inc RCV000129122 SCV000902858 benign Hereditary cancer-predisposing syndrome 2016-09-07 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000586870 SCV001133729 uncertain significance not provided 2018-10-30 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000168561 SCV001160379 uncertain significance not specified 2019-03-07 criteria provided, single submitter clinical testing The BRCA2 c.2957A>G; p.Asn986Ser variant (rs28897718) is reported in the literature in several individuals affected with breast cancer, although its clinical significance was not determined in these studies (Borg 2010, Wong-Brown 2015). This variant is reported in ClinVar (Variation ID: 51377), and it is found in the non-Finnish European population with an overall allele frequency of 0.01% (13/128448 alleles) in the Genome Aggregation Database. The asparagine at codon 986 is moderately conserved and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. However, given the lack of clinical and functional data, the significance of the p.Asn986Ser variant is uncertain at this time. 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. Wong-Brown MW et al. Prevalence of BRCA1 and BRCA2 germline mutations in patients with triple-negative breast cancer. Breast Cancer Res Treat. 2015 Feb;150(1):71-80.
Mayo Clinic Laboratories, Mayo Clinic RCV000586870 SCV001716147 uncertain significance not provided 2019-04-25 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000113119 SCV000146146 benign Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735534 SCV000863672 uncertain significance Breast and/or ovarian cancer 2002-09-19 no assertion criteria provided clinical testing

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