# Mathematical Notes on Mutect.pdf For germline hom alts, both the tumor and normal allele fractions

Member ✭✭

why they are similar large at that assuption.

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• Member ✭✭

I looked https://software.broadinstitute.org/gatk/documentation/tooldocs/4.0.6.0/org_broadinstitute_hellbender_tools_walkers_mutect_FilterMutectCalls.php, the default --heterozygosity is 0.001, but from your Mathematical of mutect2, it is when there is no genomeAD, when I supply genomeAD in mutect2 command, should I change the default --heterozygosity value.

• Member ✭✭

always say
"
Suppose our tumor bam has contamination fraction α and that at some site we have a alt reads out of d total reads. Suppose further that the alt allele has population allele frequency f
"

means in the vcf, the alt reads should multiply alt fraction?

• BostonMember, Broadie, Dev ✭✭✭

should I change the default --heterozygosity value.

You should only change the defaults if you have very good reason and really know what you're doing. All of our internal and external evaluations, as well as the Broad Institute's work with outside collaborators, is run with the defaults.

• BostonMember, Broadie, Dev ✭✭✭

means in the vcf, the alt reads should multiply alt fraction?

I'm not sure what the question is. The sentences you cited were just definitions of variables.

• BostonMember, Broadie, Dev ✭✭✭

why they are similar large at that assuption.

Why wouldn't a germline hom alt have a large allele fraction?

• Member ✭✭

I also do not know, it is hard to understand thanks @davidben

• BostonMember, Broadie, Dev ✭✭✭

"Homozygous alt" means that there are two copies of the alt allele, hence the allele fraction is 1.0, which is as large as possible.

• Member ✭✭

@davidben thanks a lot.
so is AF =1 is very less common or common in mutaion?

• BostonMember, Broadie, Dev ✭✭✭

Homozygous germline alts are reasonably common; homozygous somatic mutations are very rare.