Journal article

Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

Michael T Parsons, Emma Tudini, Hongyan Li, Eric Hahnen, Barbara Wappenschmidt, Lidia Feliubadalo, Cora M Aalfs, Simona Agata, Kristiina Aittomaki, Elisa Alducci, Maria Concepcion Alonso-Cerezo, Norbert Arnold, Bernd Auber, Rachel Austin, Jacopo Azzollini, Judith Balmana, Elena Barbieri, Claus R Bartram, Ana Blanco, Britta Bluemcke Show all

Human Mutation | WILEY | Published : 2019


The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1395 BRCA1/2 predominantly intronic and missense variants, e..

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