Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/174791
Title: Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification
Author: Parsons, Michael T.
Tudini, Emma
Li, Hongyan
Hahnen, Eric
Wappenschmidt, Barbara
Feliubadaló i Elorza, Maria Lídia
Aalfs, Cora M.
Agata, Simona
Aittomäki, Kristiina
Alducci, Elisa
Alonso Cerezo, María Concepción
Salinas, Monica
Sánchez de Abajo, Ana María
Schmidt, Gunnar
Schoenwiese, Ulrike
Seggewiß, Jochen
Cini, Giulia
Kruse, Torben A.
Solanes, Ares
Steinemann, Doris
Wiesmüller, Lisa
Guerrieri Gonzaga, Aliana
Gismondi, Viviana
Calvello, Mariarosaria
Stiller, Mathias
Bartram, Claus R.
Feroce, Irene
Stoppa Lyonnet, Dominique
Keupp, Katharina
Lucci Cordisco, Emanuela
Sullivan, Kelly J.
Susman, Rachel
Guillaud Bataille, Marine
Concolino, Paola
Sutter, Christian
Caliebe, Almuth
Gómez, Carolina
Tavtigian, Sean V.
Lewis, Alexandra L.
Teo, Soo H.
Teulé, Alex
Thomassen, Mads
Kvist, Anders
Gutiérrez Enríquez, Sara
Tibiletti, Maria Grazia
Meindl, Alfons
Fine, Miriam
Tischkowitz, Marc
Blanco, Ana
Varesco, Liliana
Garcia, Encarna B.
Tognazzo, Silvia
Caligo, Maria A.
Kiechle, Marion
Haaf, Thomas
Vargas Parra, Gardenia
Clarke, Edward M.
Lim, Joanna
Bonache, Sandra
Gensini, Francesca
Witzel, Isabell
Wöckel, Achim
Kölbl, Alexandra
Woodward, Emma R.
Bonanni, Bernardo
Hackmann, Karl
Pohl Rescigno, Esther
Zachariae, Silke
Zampiga, Valentina
Michelli, Rodrigo D.
Gross, Eva
Zeder Göß, Christine
Gambino, Gaetana
Loeffler, Markus
Investigators, Kconfab
Peissel, Bernard
Rivera, Daniela
Lázaro García, Conxi
Nicolo, Arcangela
Radice, Paolo
Grau Garcés, Èlia
Moghadasi, Setareh
Engel, Christoph
Revillion, Françoise
Krieger, Sophie
Schmutzler, Rita K.
Goldgar, David E.
Balmaña, Judith
Borg, Åke
López Fernández, Adrià
Spurdle, Amanda B.
Gehrig, Andrea
Capone, Gabriele L.
Moles Fernández, Alejandro
Bortesi, Beatrice
Grill, Sabine
Pérez Segura, Pedro
Caputo, Sandrine M.
Hansen, Thomas V.O.
Lattimore, Vanessa L.
Cops, Elisa J.
Cortesi, Laura
Couch, Fergus J.
Darder, Esther
Hoya, Miguel
Montagna, Marco
Toss, Angela
Dean, Michael
Debatin, Irmgard
Harris, Marion
Rhiem, Kerstin
Marabelli, Monica
Del Valle, Jesús
Lalloo, Fiona
Pfeifer, Katharina
Delnatte, Capucine
Toland, Amanda E.
Viel, Alessandra
Derive, Nicolas
Diez, Orland
Monteiro, Alvaro N.
Ditsch, Nina
Maass, Nicolai
Riboli, Barbara
Domchek, Susan M.
Varon, Raymonda
Dutrannoy, Véronique
Eccles, Diana M.
Ehrencrona, Hans
Trainer, Alison H.
Enders, Ute
Walker, Logan C.
Pineda Riu, Marta
Evans, D. Gareth
Larsen, Mirjam
Gerdes, Anne Marie
Ritter, Julia
Farra, Chantal
Manoukian, Siranoush
Tornero, Eva
Germani, Aldo
Montalban, Gemma
Vega, Ana
Lautrup, Charlotte
Quante, Anne S.
Hauke, Jan
Heinrich, Tilman
Törngren, Therese
Hellebrand, Heide
Arnold, Norbert
Caldés, Trinidad
Herold, Karen N.
Honisch, Ellen
Walters, Rhiannon J.
Rump, Andreas
Horvath, Judit
Poplawski, Nicola K.
Velasco, Àngela
Houdayer, Claude
Brunet, Joan
Hübbel, Verena
Iglesias, Silvia
Izquierdo, Angel
Barbieri, Elena
Wang Gohrke, Shan
James, Paul A.
Carnevali, Ileana
Torres Esquius, Sara
Janssen, Linda A.M.
Jeschke, Udo
Ledig, Susanne
Vesper, Anne Sophie
Kaulfuß, Silke
Porfirio, Berardino
Auber, Bernd
Weber, Bernhard H. F.
Leinert, Elena
Rofes, Paula
Bruzzone, Carla
Matricardi, Laura
Mackelenbergh, Marion T.
Montes, Eva
Mori, Luigi
Austin, Rachel
Moserle, Lidia
Müller, Clemens R.
Weichert, Wilko
Foulkes, William D.
Mundhenke, Christoph
Naldi, Nadia
Carrasco, Estela
Waha, Anke
Nathanson, Katherine L.
Tucker, Katherine M.
Bucksch, Karolin
Navarro, Matilde
Faust, Ulrike
González, Sara
Nevanlinna, Heli
Nichols, Cassandra B.
Niederacher, Dieter
Vreeswijk, Maaike P. G.
Caux Moncoutier, Virginie
Nielsen, Henriette R.
Giesecke, Jutta
Azzollini, Jacopo
Ong, Kai Ren
Pachter, Nicholas
Galvao, Henrique C.R.
Palmero, Edenir I.
Cagnoli, Giulia
Papi, Laura
Asperen, Christi J.
Ramser, Juliane
Cavalli, Pietro
Pedersen, Inge Sokilde
Wagner, Sebastian A.
Felbor, Ute
Reis, Rui M.
Wieland, Kerstin
Blümcke, Britta
Keywords: Proteïnes
Genètica
Tumors
Proteins
Genetics
Tumors
Issue Date: 1-Sep-2019
Publisher: Wiley
Abstract: 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 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification.
Note: Reproducció del document publicat a: https://doi.org/10.1002/humu.23818
It is part of: Human Mutation, 2019, vol. 40, issue. 9, p. 1557-1578
URI: http://hdl.handle.net/2445/174791
Related resource: https://doi.org/10.1002/humu.23818
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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