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large drop in variants in GATK 4.1.0.0 Mutect2

igorigor New YorkMember ✭✭

I recently switched to GATK 4.1.0.0. I ran Mutect2 on a small (~1Mb) targeted panel. I am using a normal control that is not the same individual (basically to exclude technical artifacts), so I do expect to see more variants than with a proper matched normal. I was getting around 100-300 variants per sample with GATK 4.0.6.0. I am still roughly in the same range for some samples, but for some I am getting 0.

The problem seems to be at the FilterMutectCalls stage where I am seeing the following error:

[March 19, 2019 10:43:17 PM EDT] org.broadinstitute.hellbender.tools.walkers.mutect.FilterMutectCalls done. Elapsed time: 0.04 minutes.
Runtime.totalMemory()=8851030016
java.lang.IllegalArgumentException: errorRate must be good probability but got NaN
    at org.broadinstitute.hellbender.utils.Utils.validateArg(Utils.java:730)
    at org.broadinstitute.hellbender.utils.QualityUtils.errorProbToQual(QualityUtils.java:227)
    at org.broadinstitute.hellbender.utils.QualityUtils.errorProbToQual(QualityUtils.java:211)
    at org.broadinstitute.hellbender.tools.walkers.mutect.Mutect2FilteringEngine.applyContaminationFilter(Mutect2FilteringEngine.java:79)
    at org.broadinstitute.hellbender.tools.walkers.mutect.Mutect2FilteringEngine.calculateFilters(Mutect2FilteringEngine.java:518)
    at org.broadinstitute.hellbender.tools.walkers.mutect.FilterMutectCalls.firstPassApply(FilterMutectCalls.java:130)
    at org.broadinstitute.hellbender.engine.TwoPassVariantWalker.lambda$traverseVariants$0(TwoPassVariantWalker.java:76)
    at java.util.stream.ForEachOps$ForEachOp$OfRef.accept(ForEachOps.java:184)
    at java.util.stream.ReferencePipeline$2$1.accept(ReferencePipeline.java:175)
    at java.util.Iterator.forEachRemaining(Iterator.java:116)
    at java.util.Spliterators$IteratorSpliterator.forEachRemaining(Spliterators.java:1801)
    at java.util.stream.AbstractPipeline.copyInto(AbstractPipeline.java:481)
    at java.util.stream.AbstractPipeline.wrapAndCopyInto(AbstractPipeline.java:471)
    at java.util.stream.ForEachOps$ForEachOp.evaluateSequential(ForEachOps.java:151)
    at java.util.stream.ForEachOps$ForEachOp$OfRef.evaluateSequential(ForEachOps.java:174)
    at java.util.stream.AbstractPipeline.evaluate(AbstractPipeline.java:234)
    at java.util.stream.ReferencePipeline.forEach(ReferencePipeline.java:418)
    at org.broadinstitute.hellbender.engine.TwoPassVariantWalker.traverseVariants(TwoPassVariantWalker.java:74)
    at org.broadinstitute.hellbender.engine.TwoPassVariantWalker.traverse(TwoPassVariantWalker.java:27)
    at org.broadinstitute.hellbender.engine.GATKTool.doWork(GATKTool.java:966)
    at org.broadinstitute.hellbender.cmdline.CommandLineProgram.runTool(CommandLineProgram.java:138)
    at org.broadinstitute.hellbender.cmdline.CommandLineProgram.instanceMainPostParseArgs(CommandLineProgram.java:191)
    at org.broadinstitute.hellbender.cmdline.CommandLineProgram.instanceMain(CommandLineProgram.java:210)
    at org.broadinstitute.hellbender.Main.runCommandLineProgram(Main.java:162)
    at org.broadinstitute.hellbender.Main.mainEntry(Main.java:205)
    at org.broadinstitute.hellbender.Main.main(Main.java:291)

Do you know what may be causing this problem?

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