{"id":"W2789006266","doi":"10.1002/humu.23406","title":"Mutational spectrum in a worldwide study of 29,700 families with<i>BRCA1</i>or<i>BRCA2</i>mutations","year":2018,"lang":"en","type":"article","venue":"Human Mutation","topic":"BRCA gene mutations in cancer","field":"Biochemistry, Genetics and Molecular Biology","cited_by":314,"is_retracted":false,"has_abstract":true,"ca_institutions":"McGill University; Université Laval; Lunenfeld-Tanenbaum Research Institute; Mount Sinai Hospital; Centre hospitalier universitaire de Québec; Hôpital du Saint-Sacrement; University of Toronto","funders":"Jonsson Comprehensive Cancer Center; National Center for Advancing Translational Sciences; Instituto de Salud Carlos III; Canadian Institutes of Health Research; lékařská fakulta Univerzity Karlovy; National Institutes of Health; Centro de Investigación Biomédica en Red de Cáncer; Fox Chase Cancer Center; Ministero dello Sviluppo Economico; Medical Research Council; Uppsala Universitet; Hospices Civils de Lyon; Radboud Universitair Medisch Centrum; Sahlgrenska Universitetssjukhuset; Institut National Du Cancer; Leids Universitair Medisch Centrum; Associazione Italiana per la Ricerca sul Cancro; Financiadora de Estudos e Projetos; KWF Kankerbestrijding; Lietuvos Mokslo Taryba; Linköpings Universitet; Hungarian Scientific Research Fund; Lunds Universitet; Pontificia Universidad Javeriana; Nederlandse Organisatie voor Wetenschappelijk Onderzoek; Ministero della Salute; Institut Català de la Salut; Institut Gustave-Roussy; University of Pennsylvania; Consejo Nacional de Investigaciones Científicas y Técnicas; Norway Grants; Generalitat de Catalunya; Erasmus Medisch Centrum; Vrije Universiteit Amsterdam; Fundación Mutua Madrileña; Ministère du Développement Économique, de l’Innovation et de l’Exportation; Radboud Universiteit; National Medical Research Council; Maastricht Universitair Medisch Centrum; Universiteit Leiden; Cancer Association of South Africa; Ministerstvo Školství, Mládeže a Tělovýchovy; National Breast Cancer Foundation; Nemzeti Kutatási Fejlesztési és Innovációs Hivatal; National Institute for Health and Care Research; Canadian Breast Cancer Research Alliance; Centre Léon Bérard; Government of Canada; National Cancer Institute; Liga Portuguesa Contra o Cancro; Hospital de Câncer de Barretos; Fundação de Amparo à Pesquisa do Estado de São Paulo; European Commission; NorthShore University HealthSystem; Cancer Research UK; Memorial Sloan-Kettering Cancer Center; Fondation du cancer du sein du Québec; Wellcome Trust; David F. and Margaret T. Grohne Family Foundation; McGill University; Breast Cancer Research Foundation; Univerzita Karlova v Praze; Unicancer; Deutsches Krebsforschungszentrum; Cancer Center, University of Kansas; Cancerfonden; Istituto Oncologico Veneto; Umeå Universitet; Royal Marsden NHS Foundation Trust; Deutsche Krebshilfe; Lee Foundation; Genome Canada; Rijksuniversiteit Groningen; University of California, San Francisco; Creighton University; NRG Oncology; Dr. Ralph and Marian Falk Medical Research Trust; Kansas Bioscience Authority; National Health and Medical Research Council; Jewish General Hospital; Fisher Center for Alzheimer's Research Foundation; Fundación Cellex; European Regional Development Fund; Jess and Mildred Fisher Center for Familial Cancer Research; Istituto Pasteur-Fondazione Cenci Bolognetti; Cancer Australia; Landspítali Háskólasjúkrahús; Ministerio de Economía y Competitividad; Ovarian Cancer Research Fund; Universiteit Maastricht; European Social Fund; University of Chicago; Susan G. Komen for the Cure; Georgetown University; Fonds Wetenschappelijk Onderzoek; American Cancer Society","keywords":"Founder effect; Genetics; Biology; Genotyping; Mutation; Germline mutation; Allele frequency; Population; Germline; Evolutionary biology; Allele; Genotype; Haplotype; Gene; Demography","routes":{"ca_aff":true,"ca_fund":true,"ca_venue":false,"about_ca":false,"invisible_to_affiliation_only":false},"retraction":null,"screen":null,"direct_labels":[],"prediction":{"model_version":"metacan-v3-hybrid-931329e0061c","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.0004988178,0.000438838,0.0003569718,0.001640643,0.0006370631,0.0005123011,0.0003271049,0.0003732058,0.00159449],"category_scores_gemma":[0.002049091,0.0002694457,0.0002615591,0.001411204,0.0004364128,0.0003860779,0.0007300955,0.0003507501,0.0003193926],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0003518479,"about_ca_system_score_gemma":0.0002419222,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.01102207,"about_ca_topic_score_gemma":0.008731845,"domain_scores_codex":[0.999562,0.0001046841,0.00003906546,0.0001497281,0.00006983245,0.00007467489],"domain_scores_gemma":[0.9993606,0.0001603121,0.0001627589,0.00006090667,0.00008550975,0.0001699071],"domain_codex":null,"domain_gemma":null,"domain_candidate":null,"domain_consensus":null,"study_design_codex":"observational","study_design_gemma":"observational","study_design_scores_codex":[0.00006520286,0.00007316859,0.992997,0.000009642291,0.0000493945,0.001405943,0.0008118811,0.00005127446,0.001498966,0.00003891503,0.0001856059,0.002812936],"study_design_scores_gemma":[0.00001072855,0.00008728063,0.9948295,0.00001060368,0.00003328297,0.003647243,0.0006846917,0.0001108184,0.0002173427,0.00002999113,0.000332005,0.000006577342],"study_design_candidate":"observational","study_design_consensus":"observational","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9993286,0.0001112701,0.00007363746,0.00001507466,0.000001145352,0.000004091088,0.000185453,0.000003083069,0.0002775142],"genre_scores_gemma":[0.9989003,0.0001801805,0.00009787,0.00004388595,0.000004464629,0.00001008293,0.0006009976,0.000008005239,0.0001542148],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.01102207,"threshold_uncertainty_score":0.02191579,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.01771490151778242,"score_gpt":0.2984924882005481,"score_spread":0.2807775866827657,"validation_status":"score_only:v0-immature-baseline","note":"Baseline scores from an immature model (maturity gate not passed). Scores rank; they never assert a category."}}