Question: Database for germline mutations
0
gravatar for kaurravneet4123
5 weeks ago by
kaurravneet412310 wrote:

Hi All,

Please can anyone suggest a database for germline mutations. I am looking at dbSNP and gnomAD- but by using these databases, how can we say whether a mutation is germline or not?

Many thanks,

Rav

snp • 148 views
ADD COMMENTlink modified 5 weeks ago • written 5 weeks ago by kaurravneet412310

I would suggest also using this db. But, consider that this is a Brazilian database! I'm also considering that you do not have a background in genetics so, for germline variants you will expect that the allele frequency in your sample is closer to 50%

Also, check this post

ADD REPLYlink modified 5 weeks ago • written 5 weeks ago by brunobsouzaa260

Many thanks for your reply. The post is interesting. Thanks.

I agree that germline variants will have AF very close to 50%. But somatic variants in a diploid genome can also have AF very close to 50% being heterozygous. Then how can we differentiate these?

ADD REPLYlink written 5 weeks ago by kaurravneet412310

For detecting somatic variants, use tumor-normal matched samples... This will help identifying somatic variants.

ADD REPLYlink written 5 weeks ago by brunobsouzaa260

I've seen ExAC and dbSNP be used as stand-ins where matched normals are not available, but any pipeline doing that needs to be benchmarked against known somatic mutations to be considered valid.

It is an interesting question - how do we know for sure that dbSNP/gnomAD variants (especially those not listed in COSMIC) are definitely germline? IMO, it would be quite rare that someone with an undetected tumor was sequenced as part of germline experiments - plus when this person was sequenced, the tissue used would also had to have contained some tumor, which is pretty improbable.

ADD REPLYlink written 5 weeks ago by RamRS30k
1

Somatic variants are present in all tissues, all the time, also without giving rise to a tumor. However, their frequency would always be pretty low. Except in the case that very early in the development (blastula stage or something like that) a mutation happened. But there is no way to distinguish that from a truly germline variant without segregation analysis, so forget about that on a population/database scale.

I think it is safe to assume that almost all variants in gnomad are germline variants. Why are you concerned about that kaurravneet4123 ?

ADD REPLYlink modified 5 weeks ago by RamRS30k • written 5 weeks ago by WouterDeCoster44k
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