ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.8149G>T (p.Ala2717Ser) (rs28897747)

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Total submissions: 34
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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) RCV000083145 SCV000244479 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 = 0.00000495
Invitae RCV000045431 SCV000073444 benign Hereditary breast and ovarian cancer syndrome 2020-12-04 criteria provided, single submitter clinical testing
Counsyl RCV000083145 SCV000154080 benign Breast-ovarian cancer, familial 2 2014-03-05 criteria provided, single submitter literature only
GeneDx RCV000120361 SCV000167406 benign not specified 2013-11-26 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 RCV000129099 SCV000183810 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.
Michigan Medical Genetics Laboratories,University of Michigan RCV000083145 SCV000196011 benign Breast-ovarian cancer, familial 2 2014-11-03 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000735609 SCV000219404 likely benign Breast and/or ovarian cancer 2017-07-27 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000120361 SCV000226714 benign not specified 2014-08-15 criteria provided, single submitter clinical testing
Vantari Genetics RCV000129099 SCV000267024 likely benign Hereditary cancer-predisposing syndrome 2015-12-18 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000083145 SCV000383777 likely benign Breast-ovarian cancer, familial 2 2017-04-27 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.
Illumina Clinical Services Laboratory,Illumina RCV000280295 SCV000383778 likely benign Fanconi anemia, complementation group D1 2017-04-27 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000045431 SCV000494362 benign Hereditary breast and ovarian cancer syndrome 2014-04-03 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000120361 SCV000538490 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: Clinvar: 10 labs classify as LB/Ben; ExAC: 0.2% (118/66734) European chromosomes
Fulgent Genetics,Fulgent Genetics RCV000083145 SCV000575734 likely benign Breast-ovarian cancer, familial 2 2015-09-16 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001281758 SCV000602845 benign none provided 2020-08-27 criteria provided, single submitter clinical testing
Color Health, Inc RCV000129099 SCV000683946 likely benign Hereditary cancer-predisposing syndrome 2015-02-11 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000083145 SCV000743343 benign Breast-ovarian cancer, familial 2 2015-08-24 criteria provided, single submitter clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000083145 SCV000744534 benign Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000034461 SCV000805774 likely benign not provided 2017-03-21 criteria provided, single submitter clinical testing
Mendelics RCV000083145 SCV001139206 likely benign Breast-ovarian cancer, familial 2 2019-05-28 criteria provided, single submitter clinical testing
Research and Development, ARUP Laboratories RCV001642548 SCV001852776 benign Breast-ovarian cancer, familial 2; Breast-ovarian cancer, familial 1; Hereditary breast and ovarian cancer syndrome 2020-01-20 criteria provided, single submitter curation
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034461 SCV000043228 probably not pathogenic not provided 2012-07-13 no assertion criteria provided research Converted during submission to Likely benign.
ITMI RCV000120361 SCV000084513 not provided not specified 2013-09-19 no assertion provided reference population
Sharing Clinical Reports Project (SCRP) RCV000083145 SCV000115219 benign Breast-ovarian cancer, familial 2 2012-05-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000083145 SCV000147282 benign Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Pathway Genomics RCV000083145 SCV000207343 benign Breast-ovarian cancer, familial 2 2014-11-06 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353905 SCV000592175 benign Malignant tumor of breast no assertion criteria provided clinical testing The p.Ala2717Ser variant has been identified in five individuals from our laboratory, 36 times in the UMD-BRCA2 database and 112 times in the BIC database. The variant was identified in 19 of 7810 proband chromosomes in individuals with breast, ovarian and prostate cancer patients (Edwards 2003, Diez 2003, Lubinski 2004, Salazar 2006, Giannini 2006, Soegaard 2008, Caux-Moncoutier 2009, Capanu 2011). However, an inadequate number of control chromosomes were tested to establish the variants frequency in the general population. This variant is listed in dbSNP database as coming from a "clinical source" (ID#: rs28897747) and was identified in more than one population with an average heterozygosity of 0.004+/-0.046, increasing the likelihood that this is a low frequency benign variant. The Ala2717 residue is not highly conserved in mammals and neither computational analyses (SIFT, AlignGVGD) nor other in silico protein modeling predictions (Karchin 2008, Spurdle 2008) suggest a high likelihood of impact to the protein. However, this information is not predictive enough to rule out pathogenicity. Finally, this variant was identified in at least three individuals in the UMD database who had a second premature truncating variant that is expected to be pathogenic, increasing the likelihood that the p.Ala2712Ser variant is not clinically significant. In summary, based on the above information this variant is classified as Benign.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000083145 SCV000733313 benign Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000034461 SCV000778717 uncertain significance not provided 2015-10-07 no assertion criteria provided clinical testing
True Health Diagnostics RCV000129099 SCV000787952 likely benign Hereditary cancer-predisposing syndrome 2018-01-05 no assertion criteria provided clinical testing
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735609 SCV000863747 uncertain significance Breast and/or ovarian cancer 2001-02-15 no assertion criteria provided clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000034461 SCV001799396 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000120361 SCV001906396 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000120361 SCV001954450 benign not specified no assertion criteria provided clinical testing

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