As the title says, I'm working on variant calling for somatic variant discovery where I have tumour samples, but no normal samples to compare with.

Previously I've been using GATK's UnifiedGenotyper for variant calling, but as this tool is deprecated, I want to switch to the newer GATK variant calling tools. However, I can't decide whether it would be more appropriate to use HaplotypeCaller or Mutect2.

On the one hand, HaplotypeCaller can be run without requiring a normal sample for comparison, but the documentation for HaplotypeCaller states that:
> the algorithms used to calculate variant likelihoods is not well suited to extreme allele frequencies (relative to ploidy) so its use is not recommended for somatic (cancer) variant discovery. For that purpose, use MuTect2 instead.

However, Mutect2 is still in Beta, and although it can be run on tumour samples only, and in the Mutect2 documentation it says:
> Tumor-only variant calling is possible but it is NOT supported and we will not answer any questions about it until it becomes a supported feature.

So neither tool is ideal for my purposes, but I'm having trouble deciding which will be the most applicable to my data.
Any suggestions or advice would be greatly appreciated.
Some resources that address your question more broadly:

- Evaluating Variant Calling Tools for Non-Matched Next-Generation Sequencing Data: https://www.nature.com/articles/srep43169
- https://www.biostars.org/p/207536/

