ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.10234A>G (p.Ile3412Val) (rs1801426)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 35
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000112853 SCV000245314 benign Breast-ovarian cancer, familial 2 2015-01-12 reviewed by expert panel curation Class 1 not pathogenic based on frequency >1% in an outbred sampleset. Frequency 0.02972 (Asian), 0.126 (African), derived from 1000 genomes (2012-04-30).
Counsyl RCV000112853 SCV000154054 benign Breast-ovarian cancer, familial 2 2014-01-02 criteria provided, single submitter literature only
Ambry Genetics RCV000130982 SCV000185899 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 RCV000112853 SCV000196032 benign Breast-ovarian cancer, familial 2 2014-11-03 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000120373 SCV000202310 benign not specified 2015-03-19 criteria provided, single submitter clinical testing
Vantari Genetics RCV000130982 SCV000267029 benign Hereditary cancer-predisposing syndrome 2016-01-06 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000120373 SCV000301751 likely benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000361728 SCV000383811 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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Clinical Services Laboratory,Illumina RCV000112853 SCV000383812 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). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
A.C.Camargo Cancer Center / LGBM, A.C.Camargo Cancer Center RCV000414645 SCV000492484 uncertain significance Breast neoplasm criteria provided, single submitter research
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000267039 SCV000494298 benign Hereditary breast and ovarian cancer syndrome 2014-01-13 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000034426 SCV000511440 benign not provided 2016-06-28 criteria provided, single submitter clinical testing
Color Health, Inc RCV000130982 SCV000537369 benign Hereditary cancer-predisposing syndrome 2014-11-05 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000120373 SCV000538466 benign 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: Frequency
Baylor Genetics RCV000460200 SCV000541023 benign Familial cancer of breast 2017-02-23 criteria provided, single submitter clinical testing
Invitae RCV000267039 SCV000560423 benign Hereditary breast and ovarian cancer syndrome 2020-12-06 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000112853 SCV000575738 likely benign Breast-ovarian cancer, familial 2 2015-09-03 criteria provided, single submitter clinical testing
Cancer Genetics and Genomics Laboratory,British Columbia Cancer Agency RCV000120373 SCV000586996 benign not specified 2017-04-18 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001282433 SCV000602768 benign none provided 2020-08-27 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000112853 SCV000743531 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 RCV000112853 SCV000744797 benign Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769708 SCV000901127 benign Breast and/or ovarian cancer 2015-07-10 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000120373 SCV001470191 benign not specified 2020-06-15 criteria provided, single submitter clinical testing
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034426 SCV000043241 no known pathogenicity not provided 2012-07-13 no assertion criteria provided research Converted during submission to Benign.
ITMI RCV000120373 SCV000084525 not provided not specified 2013-09-19 no assertion provided reference population
Breast Cancer Information Core (BIC) (BRCA2) RCV000112853 SCV000145770 uncertain significance Breast-ovarian cancer, familial 2 2013-02-05 no assertion criteria provided clinical testing
Sharing Clinical Reports Project (SCRP) RCV000112853 SCV000189292 benign Breast-ovarian cancer, familial 2 2011-03-14 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000120373 SCV000588020 benign not specified 2014-01-31 no assertion criteria provided research
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353766 SCV000592321 benign Malignant tumor of breast no assertion criteria provided clinical testing The p.Ile3412Val variant has been previously reported in the literature in 59 of 4707 (frequency of 0.006) probands with breast or esophageal cancer and was also identified in 33 of 5486 (frequency of 0.003) controls increasing the likelihood that this is a low frequency benign variant (Capanu_2011_21520273, Vehmanen_1997_ 9150152, Freedman_2004_15317758, Johnson_2007­_17341484, Bergthorsson_2001_11389159, Kuusisto_2011_­21356067, Palmieri_2002_12453858, Hu_2004_14647438). The variant was also identified in the LOVD (4X), UMD (30X), and BIC (111X) databases. It is listed in dbSNP database as coming from a "clinical source" (ID#: rs1801426) with a global minor allele frequency (MAF) of 0.043 (1000 genomes), increasing the likelihood that this is a low frequency benign variant. The Ile3412 residue is not highly conserved in mammals and computational analyses (SIFT, AlignGVGD) do not predict any effect on the protein function. In the UMD database, this variant has been identified in three individuals with a second pathogenic variant with a breast or ovarian cancer phenotype, and also found co-occurring with a deleterious BRCA2 mutation 1493delA in a cell line derived from a primary breast cancer (Teng 1996), thereby increasing the likelihood that this variant does not have clinical significance. In addition, Myriad genetics has reported this variant as a polymorphism increasing the likelihood this variant is benign (personal communication). In summary, based on the above information, this variant is classified as benign
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000112853 SCV000733345 benign Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000034426 SCV000778729 benign not provided 2016-12-19 no assertion criteria provided clinical testing
True Health Diagnostics RCV000130982 SCV000787916 benign Hereditary cancer-predisposing syndrome 2018-03-02 no assertion criteria provided clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000120373 SCV001798663 benign not specified no assertion criteria provided clinical testing
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000120373 SCV001905736 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000120373 SCV001956884 benign not specified no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.