Different SNPs found: WGS aligned to WES

Question

[ramiro.barrantes]

I have two WGS for the same tumor sample using two different library preps (I will call them prep1WGS, prep2WGS).

Furthermore, I did a tumor/normal alignment where the tumor is WGS and the normal is WES (unfortunately that is what I had), and then did variant calling. The schema would be like this:

1. prep1WGS / normalWES alignment and variant calling pipeline
2. prep2WGS / normalWES alignment and variant calling pipeline

I am finding that the variants found in (1) and (2) differ significantly (only 10-15% in common), I am thinking that it might be because the WGS is so large in comparison to the WES that it might somehow align slightly different and give different variants. Anybody have any ideas why are the results so different?

Upon looking at this more closely, consider this IGV view of both alignments:

The three variants (red, blue and green) all "PASS" for the bottom alignment (34, 33 and 33 reads) but do not even make it to the list on the top alignment (22,21 and 21 reads). Is that just due to the number of reads?

I just find it amazing that two different preps for the same tumor against the same normal would have so few SNPs in common. It might be the WGS vs WES but if anyone has any suggestions please let me know.