ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.4061C>T (p.Thr1354Met) (rs80358656)

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Total submissions: 18
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163005 SCV000213493 benign Hereditary cancer-predisposing syndrome 2014-11-19 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077319 SCV000146367 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
CSER_CC_NCGL; University of Washington Medical Center RCV000148432 SCV000190131 likely benign Neoplasm of the breast 2014-06-01 criteria provided, single submitter research
Color RCV000163005 SCV000683597 likely benign Hereditary cancer-predisposing syndrome 2015-03-10 criteria provided, single submitter clinical testing
Counsyl RCV000077319 SCV000154102 likely benign Breast-ovarian cancer, familial 2 2014-04-12 criteria provided, single submitter literature only
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000077319 SCV000744449 benign Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000120326 SCV000591886 likely benign not specified 2016-08-12 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000120326 SCV000334467 likely benign not specified 2015-09-08 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000077319 SCV000244445 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 = 0.0000803
GeneDx RCV000120326 SCV000210601 likely benign not specified 2017-07-17 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.
Genetic Services Laboratory, University of Chicago RCV000120326 SCV000593744 likely benign not specified 2016-04-15 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000077319 SCV000743293 benign Breast-ovarian cancer, familial 2 2014-10-09 criteria provided, single submitter clinical testing
ITMI RCV000120326 SCV000084478 not provided not specified 2013-09-19 no assertion provided reference population
Institute for Biomarker Research,Medical Diagnostic Laboratories, L.L.C. RCV000163005 SCV000679715 likely benign Hereditary cancer-predisposing syndrome 2017-07-12 criteria provided, single submitter clinical testing
Institute for Genomic Medicine (IGM) Clinical Laboratory,Nationwide Children's Hospital RCV000120326 SCV000864300 likely benign not specified 2017-12-29 criteria provided, single submitter clinical testing BP1, BP4, BP6; This alteration is a missense alteration in a gene for which primarily truncating variants are known to cause disease, is predicted to be tolerated by multiple functional prediction tools, and was reported as a benign/likely benign alteration by a reputable source (ClinVar or other correspondence from a clinical testing laboratory).
Integrated Genetics/Laboratory Corporation of America RCV000586934 SCV000694739 likely benign not provided 2016-11-17 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.4061C>T (p.Thr1354Met) variant causes a missense change involving a non-conserved nucleotide, which 2/4 in silico tools (SNPs&GO not captured due to low reliability index) predict a benign outcome, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 15/120580 (1/8038), predominantly in the European (Non-Finnish) cohort, 14/66436 (1/4746), which does not exceed the estimated maximal expected allele frequency for a pathogenic BRCA2 variant of 1/1333. The variant of interest has been reported in multiple affected individuals via publications with limited information (ie, lack of co-occurrence and cosegregation), which majority of authors classify the variant as a "VUS." One publication, Catenacci_2015 does report the variant in patient dx with metastatic gastric cancer to the peritoneum, who carried a germline pathogenic BRCA2 variant, S1982fsX22, however, the variant of interest was not evaluated for germline inheritance. Multiple reputable databases/clinical diagnostic laboratories and publications cite the variant as "likely benign/benign/neutral." Therefore, taking all availble lines of evidence into consideration, the variant of interest has been classified as "Likely Benign."
Invitae RCV000195329 SCV000072352 benign Hereditary breast and ovarian cancer syndrome 2017-12-06 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077319 SCV000109116 benign Breast-ovarian cancer, familial 2 2012-05-01 no assertion criteria provided clinical testing

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