Juanjiangmeng Du1, Monica Sudarsanam1,2, Eduardo Pérez-Palma1, Andrea Ganna3,4,5, Laurent Francioli3,4, Sumaiya Iqbal3,4, Lisa-Marie Niestroj1, Costin Leu2,3,6, Ben Weisburd3,4,7, Tim Poterba3,4, Peter Nürnberg1,8, Mark J Daly3,4,5, Aarno Palotie3,4,5,9,10, Patrick May11, Dennis Lal1,2,3,4,12. 1. Cologne Center for Genomics, University of Cologne, University Hospital Cologne, Cologne, Germany. 2. Genomic Medicine Institute, Lerner Research Institute Cleveland Clinic, Cleveland, OH, USA. 3. Broad Institute of MIT and Harvard, Cambridge, MA, USA. 4. Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA. 5. Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland. 6. Institute of Neurology, University College London, London, UK. 7. Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA. 8. Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany. 9. Psychiatric & Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA. 10. Department of Neurology, Massachusetts General Hospital, Boston, MA, USA. 11. Luxembourg Centre for Systems Biomedicine, University Luxembourg, Esch-sur-Alzette 4365, Luxembourg. 12. Epilepsy Center, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.
Abstract
MOTIVATION: The correct classification of missense variants as benign or pathogenic remains challenging. Pathogenic variants are expected to have higher deleterious prediction scores than benign variants in the same gene. However, most of the existing variant annotation tools do not reference the score range of benign population variants on gene level. RESULTS: We present a web-application, Variant Score Ranker, which enables users to rapidly annotate variants and perform gene-specific variant score ranking on the population level. We also provide an intuitive example of how gene- and population-calibrated variant ranking scores can improve epilepsy variant prioritization. AVAILABILITY AND IMPLEMENTATION: http://vsranker.broadinstitute.org. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
MOTIVATION: The correct classification of missense variants as benign or pathogenic remains challenging. Pathogenic variants are expected to have higher deleterious prediction scores than benign variants in the same gene. However, most of the existing variant annotation tools do not reference the score range of benign population variants on gene level. RESULTS: We present a web-application, Variant Score Ranker, which enables users to rapidly annotate variants and perform gene-specific variant score ranking on the population level. We also provide an intuitive example of how gene- and population-calibrated variant ranking scores can improve epilepsy variant prioritization. AVAILABILITY AND IMPLEMENTATION: http://vsranker.broadinstitute.org. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Authors: Erin Zampaglione; Matthew Maher; Emily M Place; Naomi E Wagner; Stephanie DiTroia; Katherine R Chao; Eleina England; Broad Cmg; Andrew Catomeris; Sherwin Nassiri; Seraphim Himes; Joey Pagliarulo; Charles Ferguson; Eglé Galdikaité-Braziené; Brian Cole; Eric A Pierce; Kinga M Bujakowska Journal: Genet Med Date: 2021-11-30 Impact factor: 8.864
Authors: Patrick R Blackburn; Matthew J Schultz; Carrie A Lahner; Dong Li; Elizabeth Bhoj; Laura J Fisher; Deborah L Renaud; Amy Kenney; Niema Ibrahim; Mais Hashem; Mohammed Zain Seidahmed; Linda Hasadsri; Samantha A Schrier Vergano; Fowzan S Alkuraya; Brendan C Lanpher Journal: Ann Clin Transl Neurol Date: 2020-06-09 Impact factor: 4.511