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Low VAF somatic variants called across most samples by Mutect2

phoangphoang LondonMember

Dear GATK team,

I have been using MuTect2 to call somatic variants (100x WGS) and I am particularly interested in studying subclones (hence low VAF somatic mutations). After filtering, I realised that there are a significant number of mutations (up to 15-20% of total passed somatic mutations) ranging at low VAF (5-10%) across almost all samples. Could this perhaps be due to MuTect2 have higher sensitivty compared to other tools? I wonder if you have encountered this issue before and if you have any recommedations for (hard) filtering to increase confidence in the low VAF somatic variants called?

Thank you!

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