@article {van der Velde072330, author = {K. Joeri van der Velde and Eddy N. de Boer and Cleo C. van Diemen and Birgit Sikkema-Raddatz and Kristin M. Abbott and Alain Knopperts and Lude Franke and Rolf H. Sijmons and Tom J. de Koning and Cisca Wijmenga and Richard J. Sinke and Morris A. Swertz}, title = {GAVIN - Gene-Aware Variant INterpretation for medical sequencing}, elocation-id = {072330}, year = {2016}, doi = {10.1101/072330}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Here, we present GAVIN, a new method that delivers accurate classification of variants for next-generation sequencing molecular diagnostics. It is based on gene-specific calibrations of allele frequencies (from the ExAC database), effect impact (using SnpEff) and estimated deleteriousness (CADD scores) for \>3,000 genes. In a benchmark on 18 clinical gene sets, we achieved a sensitivity of 91.6\%, with a specificity of 78.2\%. This accuracy was unmatched by 12 other tools we tested. We provide GAVIN as an online MOLGENIS service to annotate VCF files, and as open source executable for use in bioinformatic pipelines. It can be found at http://molgenis.org/gavin.}, URL = {https://www.biorxiv.org/content/early/2016/08/30/072330}, eprint = {https://www.biorxiv.org/content/early/2016/08/30/072330.full.pdf}, journal = {bioRxiv} }