Triallelic sites in MuTect

3141531415 n/aMember

Hello,

I am running MuTect 1.1.7 on some amplicon data that targeted several specific genes. There's one documented mutation in particular that MuTect correctly identifies, but rejects due to, "triallelic_site," according to the extended output. I have two questions about this rejection:

  1. The description of filters from the 2013 Nature paper says this flag is raised when the normal sample is heterozygous and mutect is considering another alt allele. How am I seeing "triallelic_site" if I am running MuTect without a normal?

  2. Is there a way to stop mutations from being rejected due to triallelic site? I tried passing mutect the --force_alleles option and it successfully marks my particular mutation of interest as KEEP in the mutect.out. However, using --force_alleles causes empty vcf files that only contain the header info. Is --force_alleles supposed to work with MuTect's vcf output?

Thanks,
Karl

java -Xmx4g -jar mutect-1.1.7.jar -T MuTect --reference_sequence genome.fa --enable_extended_output --cosmic cosmic.vcf --dbsnp dbsnp.vcf --input_file:tumor input.realign.recal.bam --vcf mutect.vcf --out mutect.out --coverage_file coverage.wig --gap_events_threshold 50 --fraction_contamination 0 --pir_median_threshold 0 --force_alleles

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Answers

  • Geraldine_VdAuweraGeraldine_VdAuwera Cambridge, MAMember, Administrator, Broadie admin

    Hi Karl,

    I'll have to check with the developer, but I think MuTect may be considering the alleles in the dbsnp file (which is used as a sort of proxy for the normal when you don't have one).

    There's no straightforward way to disable the default filters. I suspect the empty vcf generated when you use --force_alleles is a bug.

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