Skip to content
New issue

Have a question about this project? Sign up for a free GitHub account to open an issue and contact its maintainers and the community.

By clicking “Sign up for GitHub”, you agree to our terms of service and privacy statement. We’ll occasionally send you account related emails.

Already on GitHub? Sign in to your account

Improve selection of variant annotation for the variants.tsv #124

Open
malachig opened this issue Jun 5, 2023 · 1 comment
Open

Improve selection of variant annotation for the variants.tsv #124

malachig opened this issue Jun 5, 2023 · 1 comment

Comments

@malachig
Copy link
Member

malachig commented Jun 5, 2023

Currently we sometimes get a sub-optimal variant annotation being selected in the TSV. While this doesn't impact the VCF or the pVACtools analysis ... it is handy to have a table of variants where the "top" variant annotation is selected (one row per variant).

@malachig
Copy link
Member Author

Further investigation of this issue has revealed that we are likely experiencing a bug in VEP v105 that has since been fixed.

We have been noticing annoying discrepancies between the variant annotations that get prioritized in pVACview compared to those coming out of VEP --flag_pick

For example, a variant like this: chr9 21970920 CA C.

This is a frameshift variant on the MANE select transcript of the cancer gene: CDKN2A.

But the "picked" variant annotation is an intron variant for another nearby predicted gene (ENSG00000264545) that doesn't even have a name.

When you dig into this example, its clear that VEP is not even following its own stated rules for prioritizing the annotation that gets picked.

And if you use the latest version of VEP (even with the same v105 annotations we are using), the problem goes away.

To resolve this issue we should consider updating to Ensembl v110 (both software and annotations).

Sign up for free to join this conversation on GitHub. Already have an account? Sign in to comment
Labels
None yet
Projects
None yet
Development

No branches or pull requests

1 participant