ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9770A>G (p.Lys3257Arg) (rs55847618)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001082226 SCV000073908 likely benign Hereditary breast and ovarian cancer syndrome 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000129187 SCV000183923 likely benign Hereditary cancer-predisposing syndrome 2018-12-18 criteria provided, single submitter clinical testing Seen in trans with a mutation or in homozygous state in individual without severe disease for that gene;Co-occurence with mutation in same gene (phase unknown);In silico models in agreement (benign)
GeneDx RCV000045895 SCV000210518 likely benign not specified 2018-01-20 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 RCV000077474 SCV000489530 uncertain significance Breast-ovarian cancer, familial 2 2016-10-18 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000586082 SCV000695271 likely benign not provided 2017-02-15 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.9770A>G (p.Lys3257Arg) variant involves the alteration of a non-conserved nucleotide. 4/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). In ExAC, a large control database, this variant was found in 7/121394 control chromosomes at a frequency of 0.0000577, predominantly in the African cohort, 6/10404 (0.0005767), which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). Multiple publications have cited the variant in affected individuals, although with limited information (ie, co-occurrence and cosegregation data). Internal LCA samples have reported the variant to co-occur with another pathogenic BRCA2 variant, c.4712_4713delAG in 2 individuals and ClinVar - SCRP also reports the same co-occurrence in another sample, along with a LCA sample reporting a co-occurrence of a PMS2 variant, c.2186_2187delTC. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign. Taken together, this variant is classified as likely benign.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000045895 SCV000885115 uncertain significance not specified 2019-05-16 criteria provided, single submitter clinical testing The BRCA2 c.9770A>G; p.Lys3257Arg variant (rs55847618), also known as A9998G, is reported in the literature in individuals affected with breast cancer (Fackenthal 2012, Pal 2013). This variant is reported as uncertain significance or likely benign in ClinVar (Variation ID: 52897), and is found in the African population with an allele frequency of 0.072% (18/24972 alleles) in the Genome Aggregation Database. The lysine at codon 3257 is weakly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. However, due to limited information, the clinical significance of the p.Lys3257Arg variant is uncertain at this time. References: Fackenthal JD et al. High prevalence of BRCA1 and BRCA2 mutations in unselected Nigerian breast cancer patients. Int J Cancer. 2012 Sep 1;131(5):1114-23. Pal T et al. Early onset breast cancer in a registry-based sample of African-american women: BRCA mutation prevalence, and other personal and system-level clinical characteristics. Breast J. 2013 Mar-Apr;19(2):189-92.
Color RCV000129187 SCV000902978 benign Hereditary cancer-predisposing syndrome 2016-04-22 criteria provided, single submitter clinical testing
Mendelics RCV000077474 SCV001139275 uncertain significance Breast-ovarian cancer, familial 2 2019-05-28 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077474 SCV000109272 uncertain significance Breast-ovarian cancer, familial 2 2009-08-12 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077474 SCV000147709 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing

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