title: GAVIN: Gene-Aware Variant INterpretation for medical sequencing.
abstract: 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 .
authors.affiliation: University of Groningen, University Medical Center Groningen, Genomics Coordination Center, Groningen, The Netherlands.|Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: K Joeri
authors.initials: KJ
authors.lastname: van der Velde
authors.affiliation: Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Eddy N
authors.initials: EN
authors.lastname: de Boer
authors.affiliation: Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Cleo C
authors.initials: CC
authors.lastname: van Diemen
authors.affiliation: Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Birgit
authors.initials: B
authors.lastname: Sikkema-Raddatz
authors.affiliation: Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Abbott
authors.affiliation: Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Alain
authors.initials: A
authors.lastname: Knopperts
authors.affiliation: Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Lude
authors.initials: L
authors.lastname: Franke
authors.affiliation: Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Rolf H
authors.initials: RH
authors.lastname: Sijmons
authors.affiliation: Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Tom J
authors.initials: TJ
authors.lastname: de Koning
authors.affiliation: Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Cisca
authors.initials: C
authors.lastname: Wijmenga
authors.affiliation: Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Sinke
authors.affiliation: University of Groningen, University Medical Center Groningen, Genomics Coordination Center, Groningen, The Netherlands. m.a.swertz@gmail.com.|Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. m.a.swertz@gmail.com.
authors.forename: Morris A
authors.initials: MA
authors.lastname: Swertz
mesh_terms: D019295:Computational Biology / Q000379:methods*; D005787:Gene Frequency; D056726:Genetic Association Studies / Q000379:methods; D014644:Genetic Variation; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D012984:Software
keywords: Allele frequency; Automated protocol; Clinical next-generation sequencing; Gene-specific calibration; Pathogenicity prediction; Protein impact; Variant classification