Accurate variant calling in next generation sequencing (NGS) is critical to 
understand cancer genomes better. Here we present VarDict, a novel and versatile 
variant caller for both DNA- and RNA-sequencing data. VarDict simultaneously 
calls SNV, MNV, InDels, complex and structural variants, expanding the detected 
genetic driver landscape of tumors. It performs local realignments on the fly 
for more accurate allele frequency estimation. VarDict performance scales 
linearly to sequencing depth, enabling ultra-deep sequencing used to explore 
tumor evolution or detect tumor DNA circulating in blood. In addition, VarDict 
performs amplicon aware variant calling for polymerase chain reaction 
(PCR)-based targeted sequencing often used in diagnostic settings, and is able 
to detect PCR artifacts. Finally, VarDict also detects differences in somatic 
and loss of heterozygosity variants between paired samples. VarDict reprocessing 
of The Cancer Genome Atlas (TCGA) Lung Adenocarcinoma dataset called known 
driver mutations in KRAS, EGFR, BRAF, PIK3CA and MET in 16% more patients than 
previously published variant calls. We believe VarDict will greatly facilitate 
application of NGS in clinical cancer research.