ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9382C>T (p.Arg3128Ter) (rs80359212)

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Total submissions: 32
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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) RCV000077469 SCV000282472 pathogenic Breast-ovarian cancer, familial 2 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Invitae RCV000045807 SCV000073820 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg3128*) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs80359212, ExAC 0.02%). This variant has been reported in multiple individuals and families with breast cancer (PMID: 10978364, 24156927, 16683254, 24916970, 15168169, 11400546, 16905680), an individual with ovarian cancer (PMID: 24728189), and individuals with prostate cancer (PMID: 24556621, 20736950). This variant is also known as 9610C>T in the literature. ClinVar contains an entry for this variant (Variation ID: 52826). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000131048 SCV000185978 pathogenic Hereditary cancer-predisposing syndrome 2017-11-24 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000160169 SCV000202307 pathogenic not provided 2014-04-15 criteria provided, single submitter clinical testing
GeneDx RCV000160169 SCV000210506 pathogenic not provided 2018-07-30 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA2 c.9382C>T at the cDNA level and p.Arg3128Ter (R3128X) at the protein level. Using alternate nomenclature, this variant is also defined as BRCA2 9610C>T. The substitution creates a nonsense variant, changing an Arginine to a premature stop codon (CGA>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA2 Arg3128Ter has been reported in multiple families with breast, ovarian, and/or prostate cancer (Plaschke 2000, Simard 2007, Vogel 2007, Sugano 2008, Edwards 2010, Leongamornlert 2014, Peixoto 2015, Rosenthal 2015, Kwong 2016). Based on currently available evidence, we consider this variant to be pathogenic.
Laboratory of Molecular Diagnosis of Cancer,West China Hospital, Sichuan University RCV000240732 SCV000265916 pathogenic Neoplasm of the breast 2015-11-01 criteria provided, single submitter research
Michigan Medical Genetics Laboratories,University of Michigan RCV000077469 SCV000267830 pathogenic Breast-ovarian cancer, familial 2 2016-04-21 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000160169 SCV000296605 pathogenic not provided 2015-10-17 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077469 SCV000328122 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
A.C.Camargo Cancer Center / LGBM, A.C.Camargo Cancer Center RCV000240732 SCV000492448 pathogenic Neoplasm of the breast criteria provided, single submitter research
Baylor Genetics RCV000474912 SCV000540993 pathogenic Familial cancer of breast 2017-02-23 criteria provided, single submitter clinical testing
Genologica Medica RCV000077469 SCV000577977 pathogenic Breast-ovarian cancer, familial 2 2017-01-01 criteria provided, single submitter clinical testing
Bioinformatics dept.,Datar Cancer Genetics Limited, India RCV000077469 SCV000584011 pathogenic Breast-ovarian cancer, familial 2 2017-07-19 criteria provided, single submitter clinical testing
Department of Pathology and Molecular Medicine,Queen's University RCV000045807 SCV000588129 pathogenic Hereditary breast and ovarian cancer syndrome 2017-04-20 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000045807 SCV000592281 pathogenic Hereditary breast and ovarian cancer syndrome 2012-02-09 criteria provided, single submitter clinical testing
Department of Medical Genetics,Oslo University Hospital RCV000077469 SCV000605659 pathogenic Breast-ovarian cancer, familial 2 2015-07-01 criteria provided, single submitter clinical testing
Counsyl RCV000077469 SCV000677708 pathogenic Breast-ovarian cancer, familial 2 2015-07-28 criteria provided, single submitter clinical testing
Color RCV000131048 SCV000684059 pathogenic Hereditary cancer-predisposing syndrome 2016-05-17 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000045807 SCV000695236 pathogenic Hereditary breast and ovarian cancer syndrome 2017-08-14 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.9382C>T (p.Arg3128X) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA2 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g., c.9403delC [p.Leu3135fsX28], c.9435_9436delGT [p.Ser3147fsX2], and c.9672dupA [p.Tyr3225fsX30]). This variant was found in the large control database ExAC at a frequency of 0.0000165 (2/121360 control chromosomes), which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). The variant has been reported in multiple affected individuals and was shown to segregate with the disease in multiple HBOC families. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000077469 SCV000743366 pathogenic Breast-ovarian cancer, familial 2 2014-10-08 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000077469 SCV000744563 pathogenic Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
Mendelics RCV000045807 SCV000838903 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Human Genome Sequencing Center Clinical Lab,Baylor College of Medicine RCV000077469 SCV000839931 pathogenic Breast-ovarian cancer, familial 2 2018-02-06 criteria provided, single submitter clinical testing This c.9382C>T (p.R3128*) missense variant is predicted to result in a premature stop codon and has been reported in multiple individuals with breast, ovarian, and prostate cancer (PMID: 10978364, 24156927, 16683254, 24916970, 15168169, 11400546, 16905680, 24728189, 24556621, 20736950). Therefore, the c.9382C>T (p.R3128*) variant in the BRCA2 gene is classified as pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000763332 SCV000894009 pathogenic Familial cancer of breast; Breast-ovarian cancer, familial 2; Fanconi anemia, complementation group D1; Medulloblastoma; Wilms tumor 1; Malignant tumor of prostate; Pancreatic cancer 2; Glioma susceptibility 3 2018-10-31 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000735625 SCV000902219 pathogenic Breast and/or ovarian cancer 2017-08-17 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077469 SCV000109267 pathogenic Breast-ovarian cancer, familial 2 2013-01-23 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077469 SCV000147627 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Division Human Genetics,Medical University Innsbruck RCV000077469 SCV000212034 pathogenic Breast-ovarian cancer, familial 2 2015-02-11 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000045807 SCV000588001 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000077469 SCV000733337 pathogenic Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing
GenomeConnect, ClinGen RCV000045807 SCV000840274 not provided Hereditary breast and ovarian cancer syndrome no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735625 SCV000863763 pathogenic Breast and/or ovarian cancer 2008-07-17 no assertion criteria provided clinical testing

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