Question: Database for germline mutations
0
gravatar for kaurravneet4123
5 months ago by
kaurravneet412320 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 • 287 views
ADD COMMENTlink modified 5 months ago • written 5 months ago by kaurravneet412320

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 months ago • written 5 months ago by brunobsouzaa490

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 months ago by kaurravneet412320

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

ADD REPLYlink written 5 months ago by brunobsouzaa490

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 months ago by _r_am32k
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 months ago by _r_am32k • written 5 months ago by WouterDeCoster45k
Please log in to add an answer.

Help
Access

Use of this site constitutes acceptance of our User Agreement and Privacy Policy.
Powered by Biostar version 2.3.0
Traffic: 1008 users visited in the last hour
_