ACMG assignment tools

Question

[Eugene A]

Hi, I've been asked to semi automate (as far as full automation of the process seems to be impossible) the ACMG annotations of WGS data for our clinicians.

What are the options here? I've checked several:

varsome (paid full access, closed code)

InterVar (seems nice, but works only with annovar, and I need to annotate ACMG terms on VEP output).

TAPES ( (recent paper, supposedly support VEP), but github page is dead and no response to the issues, crashes on exapmle files, so not an option.

Charger (investigating it right now - but the documentation is sparse :( ).

Am I missing something else here? Did anyone, by chance, had a luck to fit the VEP output to InterVar?

Best, Eugene

[brunobsouzaa]

Hey man... I'm stuck on the same subject as you! Did you find something usefull?

[Eugene A]

Hi, eventually I decided for IntarVar (because of open source code + long git history) I re-write the code to make it cleaner for my pourpuses and used in combination with OpenCravat suit.

[Vivek Todur]

That sounds interesting.. But how are you managing with the background databases???? I could not find documentation to upgrade it... Any thoughts???

Thanks, Vt

[Eugene A]

Which one? InterVar internal db (lists of lof genes etc?) are still the same I have in mind to update these in the future. For cravat you need several available annotators and several custome, which I assembled from open sources (like dbnsfp)

[Paul]

Hi @Eugene, I try to solve the same task - add ACMG rule to my output form VEP. Did you finally find some solution? IntarVar seems to be working to you? Thank you for any hint! Best Paul.

[Eugene A]

Hi, yes, but eventually I switched to other annotator (openCravat) from VEP

[daianagan]

Hi Eugene! I am trying to do the same thing here. I was wondering if you could share how you managed to combine Intervar and OpenCravat. Thank you!

[Eugene A]

Hi, unfortunatly I cannot share the code, but basically you need to re-write intervar almost cmpletely for that. You need it to accept annotation from oc.

Answer 1

[AtenaLia]

Hi, free ACMG implementation without restrictions can be found at https://genebe.net . AFAIK there is also a free API coming.

[Damianos P. Melidis]

thanks for sharing! Is there a related biorxiv/publication to explain the implementation?

[AtenaLia]

No, not yet. But next to each ACMG entry there is an explanation why it is (or not) called.

I'll contact with authors to ask them to at least describe their implementation on the website.

[zasnuty]

GeneBe provides API for single and batch queries. It also supports VCF annotation (one can upload VCF and download it with ACMG points and other useful annotations, including VEP).

[Zuber]

Genebe.net: Implementation and validation of an automatic ACMG variant pathogenicity criteria assignment

Answer 2

[Damianos P. Melidis]

Hey, if you are still searching for ideas on how to implement the semi-automation, that you have described, you may also check autoPVS1 tool.

• autoPVS1 paper
• autoPVS1 github

Edit: got to know some more ACMG tools! (also on 25.02.2021)

General Mendelian disease:

• Sherloc
• ClinGen Pathogenicity Calculator
• (25.02) Ella
• (25.02) EVIDENCE

Cancer disease:

• CPSR
• CharGer
• PathoMAN
• ClinVAP

Hope it helps :)

[Eugene A]

Thanks - I'll have a look!

Answer 3

[akoussounadis]

Hi, you can try varsome.com, there is an implementation of ACMG rules and you can query variants for free.

[Eugene A]

It has too many restriction in the free version and in general has lack of flexability.