{"id":"W2947227562","doi":"10.1002/humu.23818","title":"Large scale multifactorial likelihood quantitative analysis of <i>BRCA1</i> and <i>BRCA2</i> variants: An ENIGMA resource to support clinical variant classification","year":2019,"lang":"en","type":"article","venue":"Human Mutation","topic":"BRCA gene mutations in cancer","field":"Biochemistry, Genetics and Molecular Biology","cited_by":152,"is_retracted":false,"has_abstract":true,"ca_institutions":"McGill University","funders":"National Cancer Institute; International Graduate School in Molecular Medicine Ulm; Cancer Council Tasmania; Cancer Council NSW; Cancer Council South Australia; Manchester Biomedical Research Centre; National Institutes of Health; Seventh Framework Programme; Centro de Investigación Biomédica en Red de Cáncer; Cancer Council Victoria; Deutsche Krebshilfe; Associazione Italiana per la Ricerca sul Cancro; Financiadora de Estudos e Projetos; Max-Planck-Gesellschaft; Conselho Nacional de Desenvolvimento Científico e Tecnológico; Universität Ulm; Universiteit Leiden; Unicancer; Newcastle University; Royal Society Te Apārangi; National Breast Cancer Foundation; Wellcome Trust; Cancer Research UK; Cancer Australia; Huntsman Cancer Institute; Nederlandse Organisatie voor Wetenschappelijk Onderzoek; European Commission; Breast Cancer Research Foundation; Canadian Institutes of Health Research; Fundación Mutua Madrileña; Generalitat de Catalunya; Medical Research Council; Fondazione Pisa; National Institute for Health and Care Research; Instituto de Salud Carlos III; Ohio State University; Hospital de Câncer de Barretos; QIMR Berghofer Medical Research Institute; National Health and Medical Research Council; AstraZeneca","keywords":"Biology; Pathogenicity; Genetics; Missense mutation; Computational biology; RNA splicing; Gene; Population; Bioinformatics; Mutation; Medicine","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":"codex-gemma-dda1882f352a","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.0009937192,0.0001744162,0.0003319148,0.0002248918,0.0001094946,0.00004590463,0.000191826,0.0002269608,0.0001110197],"category_scores_gemma":[0.0001390823,0.0001870518,0.0001326587,0.0004417596,0.00007569048,0.00002584269,0.00007933511,0.0001129171,0.00002520061],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.00005311763,"about_ca_system_score_gemma":0.0001424449,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.00003103594,"about_ca_topic_score_gemma":0.0004607314,"domain_scores_codex":[0.9978741,0.0002958909,0.0006391471,0.000704236,0.0002504042,0.0002361684],"domain_scores_gemma":[0.9986101,0.0000628138,0.0003185488,0.0005823684,0.0002846406,0.0001414655],"domain_codex":null,"domain_gemma":null,"domain_candidate":null,"domain_consensus":null,"study_design_codex":"bench_or_experimental","study_design_gemma":"observational","study_design_scores_codex":[0.0008535462,0.0009438823,0.04819872,0.00006341348,0.001687204,0.000005636196,0.009941338,0.001928739,0.9233541,0.003841636,0.002076698,0.007105075],"study_design_scores_gemma":[0.006236197,0.00580456,0.901439,0.00004008194,0.001924617,0.00001384088,0.008225296,0.0191489,0.03305972,0.0006104731,0.02243853,0.001058826],"study_design_candidate":"bench_or_experimental","study_design_consensus":null,"genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9819303,0.00004022234,0.01623839,0.00007273004,0.0003009178,0.0004402979,0.0001900387,0.00001840686,0.000768724],"genre_scores_gemma":[0.9924327,0.00001263035,0.004875678,0.0003094358,0.0002236104,0.00003593367,0.001943766,0.00003018059,0.0001360467],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.8902944,"threshold_uncertainty_score":0.7627752,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.0321462148493669,"score_gpt":0.3566227953207491,"score_spread":0.3244765804713822,"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."}}