This workshop will focus on the core steps involved in calling variants with the Broad’s Genome Analysis Toolkit, using the Best Practices developed by the GATK team. You will learn why each step is essential to the variant discovery process, what are the operations performed on the data at each step, and how to use the GATK tools to get the most accurate and reliable results out of your dataset. In the course of this workshop, we highlight key functionalities such as the GVCF workflow for joint variant discovery in cohorts, RNAseq-specific processing, and somatic variant discovery using MuTect2. We also preview capabilities of the upcoming GATK version 4, including a new workflow for CNV discovery, and we demonstrate the use of pipelining tools to assemble and execute GATK workflows.