Hard filtering using using germline-resource

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Shashwat Sahay

• December 11, 2024 18:05

Can some explain the resoning behind using `--germline-resource` i.e. af-only-gnomad  is not used as a hard filter in mutect2.

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  Gökalp Çelik

  • December 11, 2024 18:52

  Hi Shashwat Sahay

  Germline resource is used as a prior for Mutect2 to decide whether there is enough suspicion for a site to be of germline origin. Germline Filter is explained more deeply in our documentation.

  https://github.com/broadinstitute/gatk/blob/master/docs/mutect/mutect.pdf 

  In short allele frequencies given in the Germline source act as a parameter to calculate the probability that a particular site is present in tumor as germline or somatic. Presence of a site in germline resource with a very low allele frequency may also be the reason why that variant could well be a somatic origin. Higher the allele frequency the lesser the probability that a variant is somatic and more likely a germline one. 

  There is also a parameter in Mutect2 to set a threshold for population allele frequency for germline resource variants to be tagged as germline

  --max-population-af,-max-af <Double>
                                Maximum population allele frequency in tumor-only mode.  Default value: 0.01.

  I hope this helps.

  Regards. 

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