Testing for variation in BRCA1 and BRCA2 (commonly referred to as BRCA1/2), has emerged as a standard clinical practice and is helping countless women better understand and manage their heritable risk of breast and ovarian cancer. Yet the increased rate of BRCA1/2 testing has led to an increasing number of Variants of Uncertain Significance (VUS), and the rate of VUS discovery currently outpaces the rate of clinical variant interpretation. Computational prediction is a key component of the variant interpretation pipeline. In the CAGI5 ENIGMA Challenge, six prediction teams submitted predictions on 326 newly-interpreted variants from the ENIGMA Consortium. By evaluating these predictions against the new interpretations, we have gained a number of insights on the state of the art of variant prediction and specific steps to further advance this state of the art.

Assessment of blind predictions of the clinical significance of BRCA1 and BRCA2 variants

Giulia Babbi;Rita Casadio;Pier L. Martelli;Castrense Savojardo;
2019

Abstract

Testing for variation in BRCA1 and BRCA2 (commonly referred to as BRCA1/2), has emerged as a standard clinical practice and is helping countless women better understand and manage their heritable risk of breast and ovarian cancer. Yet the increased rate of BRCA1/2 testing has led to an increasing number of Variants of Uncertain Significance (VUS), and the rate of VUS discovery currently outpaces the rate of clinical variant interpretation. Computational prediction is a key component of the variant interpretation pipeline. In the CAGI5 ENIGMA Challenge, six prediction teams submitted predictions on 326 newly-interpreted variants from the ENIGMA Consortium. By evaluating these predictions against the new interpretations, we have gained a number of insights on the state of the art of variant prediction and specific steps to further advance this state of the art.
Melissa S. Cline,Giulia Babbi,Sandra Bonache,Yue Cao,Rita Casadio,Xavier de la Cruz,Orland Díez,Sara Gutiérrez‐Enríquez,Panagiotis Katsonis,Carmen Lai,Olivier Lichtarge,Pier L. Martelli,Gilad Mishne,Alejandro Moles‐Fernández,Gemma Montalban,Sean D. Mooney,Robert O'Conner,Lars Ootes,Selen Özkan,Natalia Padilla,Kymberleigh A. Pagel,Vikas Pejaver,Predrag Radivojac,Casandra Riera,Castrense Savojardo,Yang Shen,Yuanfei Sun,Scott Topper,Michael T. Parsons,Amanda B. Spurdle,David E. Goldgar,The ENIGMA Consortium
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/712238
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