A variant by any name: quantifying annotation discordance across tools and clinical databases

Genome Medicine
Jennifer L YenDeanna M Church


Clinical genomic testing is dependent on the robust identification and reporting of variant-level information in relation to disease. With the shift to high-throughput sequencing, a major challenge for clinical diagnostics is the cross-identification of variants called on their genomic position to resources that rely on transcript- or protein-based descriptions. We evaluated the accuracy of three tools (SnpEff, Variant Effect Predictor, and Variation Reporter) that generate transcript and protein-based variant nomenclature from genomic coordinates according to guidelines by the Human Genome Variation Society (HGVS). Our evaluation was based on transcript-controlled comparisons to a manually curated set of 126 test variants of various types drawn from data sources, each with HGVS-compliant transcript and protein descriptors. We further evaluated the concordance between annotations generated by Snpeff and Variant Effect Predictor and those in major germline and cancer databases: ClinVar and COSMIC, respectively. We find that there is substantial discordance between the annotation tools and databases in the description of insertions and/or deletions. Using our ground truth set of variants, constructed specifically to identify chal...Continue Reading


Dec 29, 1999·Human Mutation·Johan T den Dunnen, Stylianos E Antonarakis
Jan 11, 2000·Nucleic Acids Research·S T SherryK Sirotkin
May 17, 2005·Genome Biology·Karen EilbeckMichael Ashburner
Aug 7, 2008·The Journal of Clinical Endocrinology and Metabolism·Ana Paula AbreuAna Claudia Latronico
Jun 22, 2010·Bioinformatics·William McLarenFiona Cunningham
Jul 6, 2010·Nucleic Acids Research·Kai WangHakon Hakonarson
Feb 11, 2011·Human Mutation·Peter E M Taschner, Johan T den Dunnen
Apr 27, 2011·Human Mutation·Ivo F A C FokkemaJohan T den Dunnen
Oct 4, 2013·The New England Journal of Medicine·Yaping YangChristine M Eng
Nov 22, 2013·Nucleic Acids Research·Kim D PruittJames M Ostell
Nov 29, 2013·Nucleic Acids Research·Jacqueline A L MacArthurFiona Cunningham
Jun 20, 2014·Genome Medicine·Davis J McCarthyPeter Donnelly
Oct 31, 2014·Nucleic Acids Research·Simon A ForbesPeter J Campbell
Jan 16, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Xiaolin ZhuDavid B Goldstein
Feb 24, 2015·Bioinformatics·Adrian TanHyun Min Kang
Mar 6, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Sue RichardsACMG Laboratory Quality Assurance Committee
Apr 4, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Melanie G PepinPeter H Byers
Oct 4, 2015·Nature·1000 Genomes Project ConsortiumGonçalo R Abecasis
Nov 6, 2015·BioMed Research International·Adam Cornish, Chittibabu Guda
Nov 20, 2015·Nucleic Acids Research·Melissa J LandrumDonna R Maglott
Jan 23, 2016·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Katherine L HelbigIngo Helbig
Mar 5, 2016·Human Mutation·Johan T den DunnenPeter E M Taschner
Aug 17, 2016·Nature Reviews. Genetics·Euan A Ashley
Aug 19, 2016·Nature·Monkol LekExome Aggregation Consortium


Jun 24, 2017·Virchows Archiv : an International Journal of Pathology·Doreen Nguyen, Christopher D Gocke
Feb 6, 2018·Nature Reviews. Genetics·Caroline F WrightHelen V Firth
Mar 24, 2017·Bioinformatics·Nikolas PontikosVincent Plagnol
Sep 23, 2017·Current Opinion in Allergy and Clinical Immunology·Giorgia BucciolIsabelle Meyts
Oct 13, 2018·Human Mutation·Piotr PawliczekClinical Genome (ClinGen) Resource
May 1, 2019·Der Pathologe·S Merkelbach-BruseF Klauschen
Nov 19, 2019·Bioinformatics·J Bradley HolmesBrandi Kattman
Jul 24, 2019·Nucleic Acids Research·Nadav BrandesMichal Linial
Nov 11, 2019·Autism Research : Official Journal of the International Society for Autism Research·Manuel BelmadaniSanja Rogic
Oct 5, 2017·Frontiers in Oncology·Hsinyi TsangSean R Davis

Related Concepts

Data Accuracy
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