ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.9586A>G (p.Lys3196Glu) (rs80359228)

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Total submissions: 15
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001080657 SCV000073875 benign Hereditary breast and ovarian cancer syndrome 2020-12-07 criteria provided, single submitter clinical testing
Ambry Genetics RCV000129724 SCV000184529 benign Hereditary cancer-predisposing syndrome 2014-11-19 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GeneDx RCV000045862 SCV000210690 likely benign not specified 2017-08-23 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.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000045862 SCV000538501 uncertain significance not specified 2016-08-11 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Reported in 1 male breast cancer patient - multiple other publications report as nonpathogenic; ClinVar: 5 B/LB, 1 VUS
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000586984 SCV000600869 likely benign not provided 2020-02-04 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000586984 SCV000695254 likely benign not provided 2017-07-06 criteria provided, single submitter clinical testing
Color Health, Inc RCV000129724 SCV000902714 benign Hereditary cancer-predisposing syndrome 2016-07-23 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000045862 SCV001158350 likely benign not specified 2019-04-06 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000586984 SCV001502178 likely benign not provided 2020-12-01 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031834 SCV000054442 benign Breast-ovarian cancer, familial 2 2012-05-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031834 SCV000147670 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
CSER _CC_NCGL, University of Washington RCV000148420 SCV000190119 likely benign Breast neoplasm 2014-06-01 no assertion criteria provided research
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001269375 SCV000592294 benign Malignant tumor of breast no assertion criteria provided clinical testing The BRCA2 p.Lys3196Glu variant was identified in 1 of 74 proband chromosomes (frequency: 0.014) from individuals or families with male breast cancer, and was not identified in 200 control chromosomes from healthy individuals (Kwiatkowska 2000); however, an insufficient number of controls were included in these studies to determine the frequency of this variant in the general population. The variant was also identified in dbSNP (ID: rs80359228) “With uncertain significance”, with a minor allele frequency of 0.000/1 (1000 Genomes Project), NHLBI Exome Sequencing Project (Exome Variant Server), HGMD, ClinVar database, the BIC database (8 X with unknown clinical importance), and UMD (7 X as an unknown variant). The variant was classified as a benign variant by the Sharing Clinical Reports Project (SCRP) (submitted within the ClinVar database and derived from Myriad reports). The variant was identified by the Exome Variant Server project in 1 of 8600 European American alleles (frequency: 0.0001), although this low number of observations and low frequency is not substantive enough to determine the prevalence of the variant in the general population and its relationship to disease. The p.Lys3196 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. One study (Santos 2014), found the variant co-occurring with a pathogenic BRCA2 variant c.8488-1G>A, increasing the likelihood that the p.Lys3196Glu variant does not have clinical significance. In summary, based on the above information, this variant meets our laboratory's criteria to be classified as benign.
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735631 SCV000863769 uncertain significance Breast and/or ovarian cancer 2003-02-11 no assertion criteria provided clinical testing
Center of Medical Genetics and Primary Health Care RCV001269375 SCV001448723 benign Malignant tumor of breast no assertion criteria provided clinical testing

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