The VAAST Variant Prioritizer (VVP): ultrafast, easy to use whole genome variant prioritization tool

BMC Bioinformatics
Steven FlygareMark Yandell

Abstract

Prioritization of sequence variants for diagnosis and discovery of Mendelian diseases is challenging, especially in large collections of whole genome sequences (WGS). Fast, scalable solutions are needed for discovery research, for clinical applications, and for curation of massive public variant repositories such as dbSNP and gnomAD. In response, we have developed VVP, the VAAST Variant Prioritizer. VVP is ultrafast, scales to even the largest variant repositories and genome collections, and its outputs are designed to simplify clinical interpretation of variants of uncertain significance. We show that scoring the entire contents of dbSNP (> 155 million variants) requires only 95 min using a machine with 4 cpus and 16 GB of RAM, and that a 60X WGS can be processed in less than 5 min. We also demonstrate that VVP can score variants anywhere in the genome, regardless of type, effect, or location. It does so by integrating sequence conservation, the type of sequence change, allele frequencies, variant burden, and zygosity. Finally, we also show that VVP scores are consistently accurate, and easily interpreted, traits not shared by many commonly used tools such as SIFT and CADD. VVP provides rapid and scalable means to prioritize a...Continue Reading

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Citations

Aug 1, 2019·Thyroid : Official Journal of the American Thyroid Association·Xiao-Ping QiJian-Qiang Zhao
Oct 19, 2019·Nature Communications·W Scott WatkinsMartin Tristani-Firouzi
Mar 26, 2021·Frontiers in Genetics·Manuel CorpasEdmund Lehmann
Sep 18, 2018·American Journal of Human Genetics·Najmeh AlirezaieToby Dylan Hocking

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Software Mentioned

VEP
VAAST Variant Annotation Tool
Ensembl
ClinVar
gnomAD
VAT
VAAST
ClinVar CLNALLE
SIFT
CADD

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