How to select a "representative" transcript in multiple transcript variants from annotation with ANNOVAR and gencode
0
0
Entering edit mode
5 months ago
svlachavas ▴ 740

Dear Biostars,

based on a recent annotation of resulted vcf files regarding the identification of somatic point alterations in a specific cancer of interest, I used ANNOVAR default settings with gencode annotation. Based on the relative output of files, I noticed the following pattern in a specific column (ANNOVAR_TRANSCRIPTS) regarding multiple variant transcripts for each variant/specific gene, for example:

BRAF:ENST00000479537.1:exon2:c.T83A:p.V28E,BRAF:ENST00000288602.6:exon15:c.T1799A:p.V600E,

However, this poses a general problem in which of the transcripts to select/consider as the “main transcript variant”, as in this example we have two "different" mutations (exon 2 mutation distinct from exon 15 and V600E mutation)-this is for really important for my downstream analysis, as we are searching specific mutations regarding KRAS/BRAF genes-

from previous posts (Only the longest transcript while annotating with Annovar?) I saw that a suggestion would be to choose the longest transcript-however, are there any additional selection criteria to choose one transcript per mutation ?

Thank you in advance,

Efstathios

annovar gencode transcript SNP annotation • 468 views
ADD COMMENT
3
Entering edit mode

NCBI/EBI's MANE project is trying to address this for specific reasons. One happens to be a MANE plus clinical variant which would be used for

MANE Plus Clinical: Transcripts chosen to supplement MANE Select when needed for clinical variant reporting.

ADD REPLY
0
Entering edit mode

Dear GenoMax,

thank you very much for your interesting suggestion- I have never heard it before-do you know or you have used it ? I could use gencode annotations, or you would go alternatively with selected gene symbols to check which are the most "representative" transcripts ?

ADD REPLY
0
Entering edit mode

I have not MANE specifically for clinical variant calling but the project is being worked on precisely to provide a clinically stable locations. While that may not strictly reflect biology it should help the situation you are describing in original question.

ADD REPLY
1
Entering edit mode

I don't think so. The closest I've gotten is with the canonical transcript option in VEP.

ADD REPLY
0
Entering edit mode

Dear Ram, thank you for your reply-unfortunately already I know the VEP option, we utilize ANNOVAR with an additional custom pipeline, thus we could not change in this current phase of the project

ADD REPLY

Login before adding your answer.

Traffic: 1639 users visited in the last hour
Help About
FAQ
Access RSS
API
Stats

Use of this site constitutes acceptance of our User Agreement and Privacy Policy.

Powered by the version 2.3.6