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000301576 1001_ $$00000-0002-0136-9921$$aZanti, Maria$$b0
000301576 245__ $$aAnalysis of more than 400,000 women provides case-control evidence for BRCA1 and BRCA2 variant classification.
000301576 260__ $$a[London]$$bSpringer Nature$$c2025
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000301576 500__ $$aHamann, Ute: Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ),
000301576 520__ $$aClinical genetic testing identifies variants causal for hereditary cancer, information that is used for risk assessment and clinical management. Unfortunately, some variants identified are of uncertain clinical significance (VUS), complicating patient management. Case-control data is one evidence type used to classify VUS. As an initiative of the Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) Analytical Working Group we analyze germline sequencing data of BRCA1 and BRCA2 from 96,691 female breast cancer cases and 302,116 controls from three studies: the BRIDGES study of the Breast Cancer Association Consortium, the Cancer Risk Estimates Related to Susceptibility consortium, and the UK Biobank. We observe 11,207 BRCA1 and BRCA2 variants, with 6909 being coding, covering 23.4% of BRCA1 and BRCA2 VUS in ClinVar and 19.2% of ClinVar curated (likely) benign or pathogenic variants. Case-control likelihood ratio (ccLR) evidence is highly consistent with ClinVar assertions for (likely) benign or pathogenic variants; exhibiting 99.1% sensitivity and 95.3% specificity for BRCA1 and 93.3% sensitivity and 86.6% specificity for BRCA2. This approach provides case-control evidence for 787 unclassified variants; these include 579 with strong or moderate benign evidence and 10 with strong pathogenic evidence for which ccLR evidence is sufficient to alter clinical classification.
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000301576 650_7 $$2NLM Chemicals$$aBRCA2 Protein
000301576 650_7 $$2NLM Chemicals$$aBRCA1 Protein
000301576 650_7 $$2NLM Chemicals$$aBRCA2 protein, human
000301576 650_7 $$2NLM Chemicals$$aBRCA1 protein, human
000301576 650_2 $$2MeSH$$aHumans
000301576 650_2 $$2MeSH$$aFemale
000301576 650_2 $$2MeSH$$aCase-Control Studies
000301576 650_2 $$2MeSH$$aBRCA2 Protein: genetics
000301576 650_2 $$2MeSH$$aBreast Neoplasms: genetics
000301576 650_2 $$2MeSH$$aBRCA1 Protein: genetics
000301576 650_2 $$2MeSH$$aGenetic Predisposition to Disease
000301576 650_2 $$2MeSH$$aGenetic Testing
000301576 650_2 $$2MeSH$$aGerm-Line Mutation
000301576 650_2 $$2MeSH$$aMiddle Aged
000301576 7001_ $$00000-0002-7212-0920$$aO'Mahony, Denise G$$b1
000301576 7001_ $$00000-0003-3242-8477$$aParsons, Michael T$$b2
000301576 7001_ $$aDorling, Leila$$b3
000301576 7001_ $$00000-0003-4591-1214$$aDennis, Joe$$b4
000301576 7001_ $$aBoddicker, Nicholas J$$b5
000301576 7001_ $$00000-0003-0379-2368$$aChen, Wenan$$b6
000301576 7001_ $$00000-0002-6814-4639$$aHu, Chunling$$b7
000301576 7001_ $$aNaven, Marc$$b8
000301576 7001_ $$aYiangou, Kristia$$b9
000301576 7001_ $$00000-0003-0771-7752$$aAhearn, Thomas U$$b10
000301576 7001_ $$00000-0003-1717-9943$$aAmbrosone, Christine B$$b11
000301576 7001_ $$00000-0002-4226-6435$$aAndrulis, Irene L$$b12
000301576 7001_ $$aAntoniou, Antonis C$$b13
000301576 7001_ $$00000-0003-1735-8044$$aAuer, Paul L$$b14
000301576 7001_ $$aBaynes, Caroline$$b15
000301576 7001_ $$00000-0002-6578-2678$$aBodelon, Clara$$b16
000301576 7001_ $$aBogdanova, Natalia V$$b17
000301576 7001_ $$00000-0002-4061-4133$$aBojesen, Stig E$$b18
000301576 7001_ $$00000-0002-4351-9326$$aBolla, Manjeet K$$b19
000301576 7001_ $$00000-0003-0084-4775$$aBrantley, Kristen D$$b20
000301576 7001_ $$aCamp, Nicola J$$b21
000301576 7001_ $$00000-0003-0198-5078$$aCampbell, Archie$$b22
000301576 7001_ $$aCastelao, Jose E$$b23
000301576 7001_ $$aCessna, Melissa H$$b24
000301576 7001_ $$0P:(DE-He78)c259d6cc99edf5c7bc7ce22c7f87c253$$aChang-Claude, Jenny$$b25
000301576 7001_ $$aChen, Fei$$b26
000301576 7001_ $$aChenevix-Trench, Georgia$$b27
000301576 7001_ $$aNBCS Collaborators$$b28$$eCollaboration Author
000301576 7001_ $$aConroy, Don M$$b29
000301576 7001_ $$aCzene, Kamila$$b30
000301576 7001_ $$00000-0002-7275-5571$$aDe Nicolo, Arcangela$$b31
000301576 7001_ $$aDomchek, Susan M$$b32
000301576 7001_ $$00000-0002-9458-0282$$aDörk, Thilo$$b33
000301576 7001_ $$00000-0001-6651-7166$$aDunning, Alison M$$b34
000301576 7001_ $$00000-0002-3961-6609$$aEliassen, A Heather$$b35
000301576 7001_ $$00000-0002-8482-5784$$aEvans, D Gareth$$b36
000301576 7001_ $$00000-0003-4885-8471$$aFasching, Peter A$$b37
000301576 7001_ $$00000-0002-5100-623X$$aFigueroa, Jonine D$$b38
000301576 7001_ $$aFlyger, Henrik$$b39
000301576 7001_ $$aGago-Dominguez, Manuela$$b40
000301576 7001_ $$aGarcía-Closas, Montserrat$$b41
000301576 7001_ $$aGlendon, Gord$$b42
000301576 7001_ $$aGonzález-Neira, Anna$$b43
000301576 7001_ $$aGrassmann, Felix$$b44
000301576 7001_ $$aHadjisavvas, Andreas$$b45
000301576 7001_ $$00000-0002-0097-9971$$aHaiman, Christopher A$$b46
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000301576 7001_ $$00000-0001-7714-2734$$aHart, Steven N$$b48
000301576 7001_ $$aHartman, Mikael B A$$b49
000301576 7001_ $$00000-0002-8269-7344$$aHo, Weang-Kee$$b50
000301576 7001_ $$aHodge, James M$$b51
000301576 7001_ $$00000-0003-2213-9612$$aHoppe, Reiner$$b52
000301576 7001_ $$00000-0001-8141-6515$$aHowell, Sacha J$$b53
000301576 7001_ $$aInvestigators, kConFab$$b54$$eCollaboration Author
000301576 7001_ $$00000-0002-5650-0501$$aJakubowska, Anna$$b55
000301576 7001_ $$aKhusnutdinova, Elza K$$b56
000301576 7001_ $$aKo, Yon-Dschun$$b57
000301576 7001_ $$00000-0002-4472-8103$$aKraft, Peter$$b58
000301576 7001_ $$00000-0001-5012-7438$$aKristensen, Vessela N$$b59
000301576 7001_ $$aLacey, James V$$b60
000301576 7001_ $$00000-0001-8587-7511$$aLi, Jingmei$$b61
000301576 7001_ $$00000-0002-5296-3437$$aLim, Geok Hoon$$b62
000301576 7001_ $$aLindström, Sara$$b63
000301576 7001_ $$aLophatananon, Artitaya$$b64
000301576 7001_ $$aLuccarini, Craig$$b65
000301576 7001_ $$aMannermaa, Arto$$b66
000301576 7001_ $$aMartinez, Maria Elena$$b67
000301576 7001_ $$aMavroudis, Dimitrios$$b68
000301576 7001_ $$00000-0001-5764-7268$$aMilne, Roger L$$b69
000301576 7001_ $$00000-0001-6429-988X$$aMuir, Kenneth$$b70
000301576 7001_ $$00000-0002-6740-0901$$aNathanson, Katherine L$$b71
000301576 7001_ $$aNuñez-Torres, Rocio$$b72
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000301576 7001_ $$00000-0003-4944-7789$$aOlson, Janet E$$b74
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000301576 7001_ $$aTan, Veronique Kiak-Mien$$b86
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000301576 7001_ $$00000-0002-2943-6786$$aTruong, Thérèse$$b91
000301576 7001_ $$00000-0002-1962-9322$$aVachon, Celine M$$b92
000301576 7001_ $$aWang, Qin$$b93
000301576 7001_ $$00000-0001-6714-092X$$aWeitzel, Jeffrey N$$b94
000301576 7001_ $$00000-0003-4630-9903$$aYadav, Siddhartha$$b95
000301576 7001_ $$00000-0001-9442-1313$$aYao, Song$$b96
000301576 7001_ $$00000-0003-1417-5349$$aZirpoli, Gary R$$b97
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