TY - JOUR AU - van der Velde, K. Joeri AU - de Boer, Eddy N. AU - van Diemen, Cleo C. AU - Sikkema-Raddatz, Birgit AU - Abbott, Kristin M. AU - Knopperts, Alain AU - Franke, Lude AU - Sijmons, Rolf H. AU - de Koning, Tom J. AU - Wijmenga, Cisca AU - Sinke, Richard J. AU - Swertz, Morris A. PY - 2017 DA - 2017/01/16 TI - GAVIN: Gene-Aware Variant INterpretation for medical sequencing JO - Genome Biology SP - 6 VL - 18 IS - 1 AB - We present Gene-Aware Variant INterpretation (GAVIN), a new method that accurately classifies variants for clinical diagnostic purposes. Classifications are based on gene-specific calibrations of allele frequencies from the ExAC database, likely variant impact using SnpEff, and estimated deleteriousness based on CADD scores for >3000 genes. In a benchmark on 18 clinical gene sets, we achieve a sensitivity of 91.4% and a specificity of 76.9%. This accuracy is unmatched by 12 other tools. We provide GAVIN as an online MOLGENIS service to annotate VCF files and as an open source executable for use in bioinformatic pipelines. It can be found at http://molgenis.org/gavin. SN - 1474-760X UR - https://doi.org/10.1186/s13059-016-1141-7 DO - 10.1186/s13059-016-1141-7 ID - van der Velde2017 ER -