Huaizhi Huang, Chunling Hu, Jie Na, Steven N Hart, Rohan David Gnanaolivu, Mohamed Abozaid, Tara Rao, Yohannes A Tecleab, Tina Pesaran, Paulo Cilas Morais Lyra, Rachid Karam, Siddhartha Yadav, Susan M Domchek, Miguel de la Hoya, Mark Robson, Miika Mehine, Chaitanya Bandlamudi, Diana Mandelker, Alvaro N A Monteiro, Nicholas Boddicker, Wenan Chen, Marcy E Richardson, Fergus J Couch
UNLABELLED: Germline BRCA2 loss-of function (LOF) variants identified by clinical genetic testing predispose to breast, ovarian, prostate and pancreatic cancer. However, variants of uncertain significance (VUS) (n>4000) limit the clinical use of testing results. Thus, there is an urgent need for functional characterization and clinical classification of all BRCA2 variants. Here we report on comprehensive saturation genome editing-based functional characterization of 97% of all possible single nucleotide variants (SNVs) in the BRCA2 DNA Binding Domain hotspot for pathogenic missense variants that is encoded by exons 15 to 26...
December 15, 2023: bioRxiv