Germline variants in Cancer

Question

[prs]

I need to design a workflow to identify pathogenic germline variants from tumor-only or tumor-normal sample data.Please suggest a workflow design or any specific tools that can be used for this purpose.

[Ram]

pathogenic

You need ClinVar, SIFT and PolyPhen2 annotations.

germline variants

Use MuTect2 with the option --genotype-germline-sites to call variants. If necessary, use --genotype-pon-sites as well.

[prs]

And I think I should add a step to filter out the common polymorphism before proceeding to find the pathogenic variants. Also, is there any database which has listed pathogenic variants for different cancer type?

[Ram]

Look at COSMIC - that's also a good source to annotate with. ClinVar is good for germline. Post gnomAD annotation, I use gnomAD non-cancer allele frequencies to filter variants.