ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.4585G>A (p.Gly1529Arg) (rs28897728)

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Total submissions: 21
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000160225 SCV000602833 likely benign not specified 2016-11-29 criteria provided, single submitter clinical testing
Ambry Genetics RCV000162670 SCV000213117 benign Hereditary cancer-predisposing syndrome 2014-11-19 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000113324 SCV000146453 benign Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
CSER_CC_NCGL; University of Washington Medical Center RCV000148413 SCV000190112 likely benign Breast and/or ovarian cancer 2014-06-01 no assertion criteria provided research
Color RCV000162670 SCV000683634 likely benign Hereditary cancer-predisposing syndrome 2015-04-02 criteria provided, single submitter clinical testing
Counsyl RCV000113324 SCV000154094 benign Breast-ovarian cancer, familial 2 2014-04-02 criteria provided, single submitter literature only
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000113324 SCV000744459 benign Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000160225 SCV000591912 likely benign not specified 2016-08-23 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000113324 SCV000244450 benign Breast-ovarian cancer, familial 2 2015-08-10 reviewed by expert panel curation IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.000000000166
GeneDx RCV000160225 SCV000210607 likely benign not specified 2018-01-16 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.
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000113324 SCV000743301 likely benign Breast-ovarian cancer, familial 2 2015-06-15 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000353459 SCV000383702 likely benign Fanconi anemia 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000044446 SCV000383703 likely benign Hereditary breast and ovarian cancer syndrome 2016-06-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000044446 SCV000494387 benign Hereditary breast and ovarian cancer syndrome 2015-04-06 criteria provided, single submitter clinical testing Variant summary: The variant of interest causes a missense change in a conserved position with 4/4 in silico programs predicting a "deleterious" outcome (SNPs&Go not captured here due to low reliability index). The variant of interest has an observed allele frequency of 57/121370 (1/2127) in controls, which does not significantly exceed the maximum expect allele frequency for a pathogenic BRCA2 variant, 1/1333. However, the variant of interest has been found in cases to co-occur with multiple potential pathogenic BRCA2 (1 - c.5350_5351delAA (p.Asn1784HisfsX2) and 1 - c.8755_10257del (p.Gly2919fsX15)) and BRCA1 (1 - c.3226A>T (p.Arg1076X)) variants including internal LCA sample that co-occurred with a BRCA1 variant, c.3358_3359delGT (p.Val1120X scored DV). Although, functional studies show no impairment on exon splicing but conflicting evidence for a role in homologous recombination via recruitment of RAD51, however, this functional analysis has not been indepdently reproduced by other laboratories and their relevance to in-vivo mechanisms of pathogenicity have not been unequivocally established. Furthermore, multiple reputable databases (ARUP, UMD, BIC, SCRP, GeneDx and Ambry Genetics) and publications (Easton_2007 and Lindor_2012) classify the variant as likely benign/benign/neutral. . Therefore, taken together, the variant of interest is classified as benign.
Invitae RCV000044446 SCV000072459 benign Hereditary breast and ovarian cancer syndrome 2018-01-08 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000160225 SCV000538486 uncertain significance not specified 2016-03-28 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: ExAC: 0.1%(42/66226) European; ClinVar: 8 B/LB
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000656605 SCV000778676 likely benign not provided 2015-10-07 no assertion criteria provided clinical testing
Michigan Medical Genetics Laboratories,University of Michigan RCV000113324 SCV000267766 likely benign Breast-ovarian cancer, familial 2 2016-04-21 criteria provided, single submitter clinical testing
Pathway Genomics RCV000113324 SCV000223766 likely benign Breast-ovarian cancer, familial 2 2014-10-30 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000113324 SCV000054096 benign Breast-ovarian cancer, familial 2 2011-03-01 no assertion criteria provided clinical testing
True Health Diagnostics RCV000162670 SCV000787932 likely benign Hereditary cancer-predisposing syndrome 2017-09-11 no assertion criteria provided clinical testing

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