- Cline, Melissa S;
- Babbi, Giulia;
- Bonache, Sandra;
- Cao, Yue;
- Casadio, Rita;
- de la Cruz, Xavier;
- Díez, Orland;
- Gutiérrez‐Enríquez, Sara;
- Katsonis, Panagiotis;
- Lai, Carmen;
- Lichtarge, Olivier;
- Martelli, Pier L;
- Mishne, Gilad;
- Moles‐Fernández, Alejandro;
- Montalban, Gemma;
- Mooney, Sean D;
- O'Conner, Robert;
- Ootes, Lars;
- Özkan, Selen;
- Padilla, Natalia;
- Pagel, Kymberleigh A;
- Pejaver, Vikas;
- Radivojac, Predrag;
- Riera, Casandra;
- Savojardo, Castrense;
- Shen, Yang;
- Sun, Yuanfei;
- Topper, Scott;
- Parsons, Michael T;
- Spurdle, Amanda B;
- Goldgar, David E;
- Consortium, The ENIGMA
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.