ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.4585G>A (p.Gly1529Arg) (rs28897728)

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Total submissions: 22
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
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
Invitae RCV000044446 SCV000072459 benign Hereditary breast and ovarian cancer syndrome 2019-12-31 criteria provided, single submitter clinical testing
Counsyl RCV000113324 SCV000154094 benign Breast-ovarian cancer, familial 2 2014-04-02 criteria provided, single submitter literature only
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.
Ambry Genetics RCV000162670 SCV000213117 benign Hereditary cancer-predisposing syndrome 2014-11-19 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
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
Illumina Clinical Services Laboratory,Illumina RCV000353459 SCV000383702 likely benign Fanconi anemia, complementation group D1 2019-09-23 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Clinical Services Laboratory,Illumina RCV000113324 SCV000383703 likely benign Breast-ovarian cancer, familial 2 2019-09-23 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
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.
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
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000160225 SCV000591912 likely benign not specified 2016-08-23 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000160225 SCV000602833 likely benign not specified 2019-06-27 criteria provided, single submitter clinical testing
Color RCV000162670 SCV000683634 likely benign Hereditary cancer-predisposing syndrome 2015-04-02 criteria provided, single submitter clinical testing
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
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
Mendelics RCV000113324 SCV001139093 likely benign Breast-ovarian cancer, familial 2 2019-05-28 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
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 RCV000148413 SCV000190112 likely benign Breast and/or ovarian cancer 2014-06-01 no assertion criteria provided research
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000656605 SCV000778676 likely benign not provided 2015-10-07 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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