ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.8567A>C (p.Glu2856Ala) (rs11571747)

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Total submissions: 32
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000167825 SCV000073571 benign Hereditary breast and ovarian cancer syndrome 2020-12-04 criteria provided, single submitter clinical testing
Counsyl RCV000031751 SCV000154095 likely benign Breast-ovarian cancer, familial 2 2014-04-08 criteria provided, single submitter literature only
GeneDx RCV000152885 SCV000167412 benign not specified 2014-01-07 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 RCV000131022 SCV000185950 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 RCV000031751 SCV000196016 benign Breast-ovarian cancer, familial 2 2014-11-03 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000152885 SCV000202304 likely benign not specified 2014-05-01 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000735613 SCV000219411 likely benign Breast and/or ovarian cancer 2019-04-18 criteria provided, single submitter clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C. RCV000167825 SCV000267847 likely benign Hereditary breast and ovarian cancer syndrome 2016-04-25 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000371112 SCV000383788 likely benign Fanconi anemia, complementation group D1 2018-02-28 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 RCV000031751 SCV000383789 likely benign Breast-ovarian cancer, familial 2 2018-02-28 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000167825 SCV000494364 benign Hereditary breast and ovarian cancer syndrome 2014-09-29 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000152885 SCV000538491 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: 0.1% (94/66682) European chromosomes
Cancer Genetics and Genomics Laboratory,British Columbia Cancer Agency RCV000152885 SCV000586982 benign not specified 2017-04-19 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001282957 SCV000602794 benign none provided 2020-06-26 criteria provided, single submitter clinical testing
Color Health, Inc RCV000131022 SCV000683983 likely benign Hereditary cancer-predisposing syndrome 2014-11-25 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000031751 SCV000743349 benign Breast-ovarian cancer, familial 2 2014-10-09 criteria provided, single submitter clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000031751 SCV000744542 benign Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C. RCV000131022 SCV000747808 likely benign Hereditary cancer-predisposing syndrome 2018-05-23 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000034464 SCV000805782 likely benign not provided 2017-08-25 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000034464 SCV001148998 likely benign not provided 2021-04-01 criteria provided, single submitter clinical testing
Research and Development, ARUP Laboratories RCV001642482 SCV001852801 likely 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 RCV000034464 SCV000043231 probably not pathogenic not provided 2012-07-13 no assertion criteria provided research Converted during submission to Likely benign.
Sharing Clinical Reports Project (SCRP) RCV000031751 SCV000054359 benign Breast-ovarian cancer, familial 2 2012-05-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031751 SCV000147403 benign Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Pathway Genomics RCV000031751 SCV000207353 likely benign Breast-ovarian cancer, familial 2 2014-11-06 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000152885 SCV000592209 benign not specified no assertion criteria provided clinical testing The p.Glu2856Ala variant is identified in the literature in 26 out of 7714 proband chromosomes (frequency 0.003) with breast, ovarian and prostate cancers, however it is also identified in 16 out of 5286 control chromosomes (frequency 0.003) (Spitzer 2000, Borg 2010, Soegaard 2008, Edwards 2003, Chenevix-Trench 2006, Evans 2008), and listed in dbSNP database as coming from a "clinical source" (ID#: rs11571747) with an average heterozygosity of 0.002+/-0.031 in various human populations, therefore increasing the likelihood of this variant to be benign. In the UMD database, this variant has been identified in two (out of 23) individuals with breast or ovarian cancers, where a second pathogenic BRCA1 or BRCA2 mutation was also detected, and also found in an breast cancer individual in the homozygous state (Chenevix-Trench 2006), further suggesting the benign nature of this variant. The p.Glu2856 residue is conserved in mammals and computational analyses (PolyPhen2, SIFT, AlignGVGD) provide inconsistent predictions regarding the impact to the protein, leaning more towards deleterious, but this information is not predictive enough to assume pathogenicity. Furthermore, Myriad genetics has reported this variant as a polymorphism increasing the likelihood this variant is benign (personal communication). Based on the above information, this variant is classified as Benign.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000031751 SCV000733319 benign Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing
True Health Diagnostics RCV000131022 SCV000787955 likely benign Hereditary cancer-predisposing syndrome 2017-08-14 no assertion criteria provided clinical testing
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735613 SCV000863751 uncertain significance Breast and/or ovarian cancer 2001-08-16 no assertion criteria provided clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000034464 SCV001800804 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000152885 SCV001906421 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000152885 SCV001951665 benign not specified no assertion criteria provided clinical testing

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