GATK funcotator transcript selection criteria

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Qing Zhang

• July 14, 2021 17:30

Hi,

We used Funcotator to annotate somatic calls and were confused about the transcript selection mode, the default "canonical" mode sometimes chooses a different transcript than what is better known in clinical settings. 

1. If we use the transcript-selection-list (e.g. transcriptList.exact_uniprot_matches.AKT1_CRLF2_FGFR1.txt from public gatk bucket), the BRAF hotspot will be annotated with V640E instead of V600E.

2. With canonical mode, EGFR_ELREA701del|L813R is chosen instead of the more commonly known ELREA746del + L858R.

I wonder

1) how "canonical" is defined for protein change annotation by default? 

2) how is the reference file (transcriptList.exact_uniprot_matches.AKT1_CRLF2_FGFR1.txt) made, and what problem does it address?

Thanks a lot.

 

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  Pamela Bretscher

  • July 14, 2021 19:35

  Hi Qing Zhang,

  I am going to move your post into our Community Discussions -> General Discussion topic, as the somatic topic is for reporting bugs and issues with GATK.

  You can read more about our forum guidelines and the topics here: Forum Guidelines.

  Best,

  Pamela

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  Genevieve Brandt (she/her)

  • July 19, 2021 20:03

  Hi Qing Zhang,

  Thanks for writing into the forum with this question!

  1. We have a description of how canonical is defined in our Funcotator information and tutorial article here. Please let me know if you have follow up questions after taking a look there.
  2. We don't have exact information on how the transcriptList.exact_uniprot_matches.AKT1_CRLF2_FGFR1.txt list file is made. The list contains most relevant transcripts for somatic disease processes. Funcotator will preferentially annotate these transcripts. If there are none, it will fall back on canonical selection mode.

  Hope this helps!

  Best,

  Genevieve

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