I am a bit confused with the causal variants detection method in cancer. I know we can identify the somatic variants by subtractive method (i.e. by removing all the germline variants) from cancer sample. Can someone please explain me the method to identify only germline variants in cancer that could be the driver mutation in itself?
If you are looking for a germline variant you are typically looking for a causal allele in a Hereditary/Familial cancer case, where you have evidence (usually the number of effected in the family over multiple generations) there is some inherited risk with high penetrance. So here you don't necessarily need to do any sequencing in the tumour at all, although it can be useful in downstream analyses. You'll start out with whole exome or whole genome sequencing and follow a relatively standard protocol for identifying a causal allele in rare disease, using typical filters for allele frequencies, etc. If you have family data you may do linkage or a related technique to narrow down the search space further. Typically most Hereditary Cancer Syndromes are dominant, but some are recessive, so you are typically looking for germline heterozygous alleles.
Now, if you also have the tumour sequenced you can look for the canonical "second-hit" in the tumour, which you would expect to find in the dominant case. Either loss of the wild-type copy, a second mutation that is loss of function so you essentially get a new compound heterozygous LOF situation, etc. There are other mechanisms such as hypermethylation and such that may also act as a second hit. My group published a paper in 2014 describing a new potential gene in hereditary gastric cancer Germline Mutations in MAP3K6 Are Associated with Familial Gastric Cancer. The methods and write-up describe one general approach that you could take.
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