ClinVar Miner

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

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Total submissions: 19
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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) 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
Invitae RCV001085458 SCV000072352 benign Hereditary breast and ovarian cancer syndrome 2019-12-31 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
CSER _CC_NCGL, University of Washington RCV000148432 SCV000190131 likely benign Neoplasm of the breast 2014-06-01 criteria provided, single submitter research
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.
Ambry Genetics RCV000163005 SCV000213493 benign Hereditary cancer-predisposing syndrome 2014-11-19 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
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000120326 SCV000591886 likely benign not specified 2016-08-12 criteria provided, single submitter clinical testing
Genetic Services Laboratory,University of Chicago RCV000120326 SCV000593744 likely benign not specified 2016-04-15 criteria provided, single submitter clinical testing
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
Color RCV000163005 SCV000683597 likely benign Hereditary cancer-predisposing syndrome 2015-03-10 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000120326 SCV000694739 benign not specified 2019-12-20 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.4061C>T (p.Thr1354Met) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00014 in 243646 control chromosomes (gnomAD and literature). This frequency is not significantly higher than expected for a pathogenic variant in BRCA2 causing Hereditary Breast and Ovarian Cancer (0.00014 vs 0.00075), allowing no conclusion about variant significance. The variant, c.4061C>T has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (e.g. Arver_2001 , Capalbo_2006 , deSanjose_2003 , Laitman_2011) without strong evidence for causality. Cosegregation studies in a family with a history of breast cancer found that this variant did not segregate with disease (Jalkh_2017). Co-occurrences with other pathogenic variants have been reported [BRCA1 c.2071_2071delA, p.Arg691Aspfs (BIC database), CDH1 c.3G>A, p.Met1Ile (Jalkh_2017)], providing supporting evidence for a benign role. Ten other submitters including one expert panel (ENIGMA) have provided clinical-significance assessments for this variant in ClinVar after 2014 (without evidence for independent evaluation), and classified the variant as benign (n=3) or likely benign (n=7). Based on the evidence outlined above, the variant was classified as benign.
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000077319 SCV000743293 benign Breast-ovarian cancer, familial 2 2014-10-09 criteria provided, single submitter clinical testing
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
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).
Mendelics RCV000077319 SCV001139080 likely benign Breast-ovarian cancer, familial 2 2019-05-28 criteria provided, single submitter clinical testing
ITMI RCV000120326 SCV000084478 not provided not specified 2013-09-19 no assertion provided reference population
Sharing Clinical Reports Project (SCRP) RCV000077319 SCV000109116 benign Breast-ovarian cancer, familial 2 2012-05-01 no assertion criteria provided 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

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