Closed ibrahimkurt closed 1 year ago
A related but different serious problem:
A splice-site in intron, a LOW effect variant: PTCH1 c.3306+5G>T
It is returned as Likely Oncogenic
along with FDA-approved drug recommendation with even -q Genomic_Change
flag.
Interestingly, even manual URL/API as shown below returns the same wrong/false information:
curl -X GET "https://www.oncokb.org/api/v1/annotate/mutations/byGenomicChange?genomicLocation=9,95456271,95456271,C,A&tumorType=BREAST&referenceGenome=GRCh38" -H "accept: application/json" -H "Authorization: Bearer ***"
The really problematic thing is, the OncoKB webpage shows the correct information as unknown: https://www.oncokb.org/gene/PTCH1/c.3306+5G%3ET
We believe this shows that both the API and python-based annotator scripts could be problematic?
Even a missense mutation with -q Genomic_Change
gives the wrong output as Likely Oncogenic
and conflicts with the webpage:
BRAF c.1633C>T L545F
@ibrahimkurt few points to your questions
c.
through our website9,95456271,95456271,C,A
is interpretated as X1102_splice
by GenomeNexus, therefore is mapped to Level 3A Sonidegib, Vismodegib
for Truncating Mutations
I hope these address your concerns.
We take annotation quality seriously. Happy to look into other variants if you think they have been interperted incorrectly.
Thanks for the replies. I will in this case close this issue and open another one for HGVSp vs HGVSP_Short inconsistencies.
Hi,
We use
vcf2maf
w/-inhibit-vep
. Our maf file has splice region variants (naturally) without anyHGVSp
orHGVSp_Short
info. When we call themafannotator.py
script with-q HGVSp
or-q HGVSp_Short
; the variants are falsely returned asLikely Oncogenic
, although the variants do not exist in the OncoKB database. It even prints out a PubMed reference claimed to be related to the variant (https://pubmed.ncbi.nlm.nih.gov/21896780/). But it is not. The script works correctly though if we use-q Genomic_Change
flag. We believe there could be a serious bug here for such variants.The line of code:
${mafannotator} -i ${maffile} -o ${outputfile} -t NSCLC -q Genomic_Change -r GRCh38 -b ${token}
And here is the MAF file (changed to .txt to be able to upload to GitHub) showing only one of the problematic variants in it:
sample.txt
Intersting thing is, if you try URL/api manually like the following for the variant, it works correctly:
curl -X GET "https://www.oncokb.org/api/v1/annotate/mutations/byGenomicChange?genomicLocation=17,12107914,12107914,G,T&tumorType=NSCLC&referenceGenome=GRCh38" -H "accept: application/json" -H "Authorization: Bearer ***"
To understand where the bug might be, we added a
print
function to get the actualurl
submitted to OncoKB by theAnnotatorCore.py
script. But for some reason it never prints out anything for any one of the-q
parameter.