Four popular somatic single nucleotide variant (SNV) calling methods (Varscan, 
SomaticSniper, Strelka and MuTect2) were carefully evaluated on the real whole 
exome sequencing (WES, depth of ~50X) and ultra-deep targeted sequencing 
(UDT-Seq, depth of ~370X) data. The four tools returned poor consensus on 
candidates (only 20% of calls were with multiple hits by the callers). For both 
WES and UDT-Seq, MuTect2 and Strelka obtained the largest proportion of COSMIC 
entries as well as the lowest rate of dbSNP presence and 
high-alternative-alleles-in-control calls, demonstrating their superior 
sensitivity and accuracy. Combining different callers does increase reliability 
of candidates, but narrows the list down to very limited range of tumor read 
depth and variant allele frequency. Calling SNV on UDT-Seq data, which were of 
much higher read-depth, discovered additional true-positive variations, despite 
an even more tremendous growth in false positive predictions. Our findings not 
only provide valuable benchmark for state-of-the-art SNV calling methods, but 
also shed light on the access to more accurate SNV identification in the future.