ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.4068G>A (p.Leu1356=)

gnomAD frequency: 0.00295  dbSNP: rs28897724
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Total submissions: 40
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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) RCV000113269 SCV000578007 benign Breast-ovarian cancer, familial, susceptibility to, 2 2017-06-29 reviewed by expert panel curation Synonymous substitution variant, with low bioinformatic likelihood to alter mRNA splicing (splicing prior 0.02; http://priors.hci.utah.edu/PRIORS/) and frequency 0.0047 (Non-Finnish European), 0.0023 (Finnish), 0.0029 (Admixed American/Latino), derived from ExAC (2014-12-17).
Invitae RCV000044340 SCV000072353 benign Hereditary breast ovarian cancer syndrome 2024-02-01 criteria provided, single submitter clinical testing
Counsyl RCV000113269 SCV000154069 likely benign Breast-ovarian cancer, familial, susceptibility to, 2 2014-02-07 criteria provided, single submitter literature only
Michigan Medical Genetics Laboratories, University of Michigan RCV000113269 SCV000195979 benign Breast-ovarian cancer, familial, susceptibility to, 2 2014-11-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV000162367 SCV000212675 benign Hereditary cancer-predisposing syndrome 2014-07-15 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, 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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV000768629 SCV000219334 benign Breast and/or ovarian cancer 2019-04-23 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000168569 SCV000225166 benign not specified 2014-08-22 criteria provided, single submitter clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C. RCV000044340 SCV000267843 likely benign Hereditary breast ovarian cancer syndrome 2016-04-25 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000385860 SCV000383691 likely benign Fanconi anemia complementation group D1 2018-05-15 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 Laboratory Services, Illumina RCV000113269 SCV000383692 likely benign Breast-ovarian cancer, familial, susceptibility to, 2 2018-05-15 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 RCV000044340 SCV000494322 benign Hereditary breast ovarian cancer syndrome 2014-03-17 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000113269 SCV000575765 benign Breast-ovarian cancer, familial, susceptibility to, 2 2016-02-25 criteria provided, single submitter clinical testing
Cancer Genetics and Genomics Laboratory, British Columbia Cancer Agency RCV000168569 SCV000586947 benign not specified 2017-04-18 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000168569 SCV000593714 benign not specified 2019-06-10 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000513194 SCV000602805 benign not provided 2023-11-17 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000513194 SCV000608679 likely benign not provided 2024-04-01 criteria provided, single submitter clinical testing BRCA2: BP4, BP7, BS2
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C. RCV000162367 SCV000679716 likely benign Hereditary cancer-predisposing syndrome 2017-07-12 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000162367 SCV000683598 benign Hereditary cancer-predisposing syndrome 2015-04-15 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000113269 SCV000743294 likely benign Breast-ovarian cancer, familial, susceptibility to, 2 2014-10-10 criteria provided, single submitter clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000113269 SCV000744450 likely benign Breast-ovarian cancer, familial, susceptibility to, 2 2015-09-21 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV000168569 SCV000805703 benign not specified 2016-11-30 criteria provided, single submitter clinical testing
Mendelics RCV000113269 SCV001139081 likely benign Breast-ovarian cancer, familial, susceptibility to, 2 2019-05-28 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV001262741 SCV001440719 likely benign Familial cancer of breast 2019-01-01 criteria provided, single submitter clinical testing
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State RCV000044340 SCV002026098 benign Hereditary breast ovarian cancer syndrome 2021-11-16 criteria provided, single submitter clinical testing
Genetics Program, Instituto Nacional de Cancer RCV000044340 SCV002515269 benign Hereditary breast ovarian cancer syndrome 2021-11-01 criteria provided, single submitter research
Sema4, Sema4 RCV000162367 SCV002533844 benign Hereditary cancer-predisposing syndrome 2021-03-25 criteria provided, single submitter curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV000168569 SCV002550332 benign not specified 2023-08-15 criteria provided, single submitter clinical testing
Genetics and Molecular Pathology, SA Pathology RCV000113269 SCV002761726 benign Breast-ovarian cancer, familial, susceptibility to, 2 2020-02-17 criteria provided, single submitter clinical testing The BRCA2 c.4068G>A variant is classified as Benign (BA1) This BRCA2 c.4068G>A variant is synonymous (silent). The frequency of this variant in population databases is higher than expected for this disorder indicating this variant is a benign polymorphism (BA1). Population frequency of .29% for this variant greater than expected for pathogenic BRCA2 variants (expected to be 0.45% for all BRCA2 pathogenic variants). ENIGMA BRCA1/2 Classification Criteria (2017-06-29): benign
KCCC/NGS Laboratory, Kuwait Cancer Control Center RCV000113269 SCV004016823 benign Breast-ovarian cancer, familial, susceptibility to, 2 2023-07-07 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000113269 SCV000146368 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2004-02-20 no assertion criteria provided clinical testing
Sharing Clinical Reports Project (SCRP) RCV000113269 SCV000189305 benign Breast-ovarian cancer, familial, susceptibility to, 2 2011-03-14 no assertion criteria provided clinical testing
Department of Medical Genetics, University Hospital of North Norway RCV000113269 SCV000301447 benign Breast-ovarian cancer, familial, susceptibility to, 2 2016-05-01 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001353901 SCV000591887 benign Malignant tumor of breast no assertion criteria provided clinical testing The p.Leu1356Leu variant has been reported in the literature in 29/16512 proband chromosomes and 0/80 control chromosomes. However, an insufficient number of controls were typed to establish the variants' allele frequency in the general population (Edwards 2003, Haffty 2006, Infante 2006, Stagel 2011, Van der Hout 2006, Yang 2009). This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located near a splice junction and is reported in dbSNP (ID#:rs28897724) with a global allele frequency of 0.001 (1000 genomes) increasing the likelihood this variant is benign. In addition, this variant is reported by Myriad Genetics as benign as of Oct 2008 (personal communication). In summary, this variant meets our laboratories' criteria for a benign variant.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000113269 SCV000733252 likely benign Breast-ovarian cancer, familial, susceptibility to, 2 no assertion criteria provided clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000513194 SCV000778670 benign not provided 2017-08-22 no assertion criteria provided clinical testing
True Health Diagnostics RCV000162367 SCV000805242 likely benign Hereditary cancer-predisposing syndrome 2018-05-03 no assertion criteria provided clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000513194 SCV001798902 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute RCV000168569 SCV001905840 benign not specified no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000168569 SCV001959526 benign not specified no assertion criteria provided clinical testing
BRCAlab, Lund University RCV000113269 SCV004243619 benign Breast-ovarian cancer, familial, susceptibility to, 2 2020-03-02 no assertion criteria provided clinical testing

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