cpsr-gene-annotate - INFO - NO VEP BLOCK FOUND

[ShimaaSherif]

Hello, I'm getting this error, while running the CPSR v2.03. However; the v1.02 was working fine on the same vcf file.

• cpsr-summarise - INFO - CPSR - STEP 3: Cancer gene annotations with cpsr-summarise
• cpsr-gene-annotate - WARNING - Picked VEP block for 1_36066715_T_C does not match virtual panel target genes - considering alternative consequences
• cpsr-gene-annotate - WARNING - Picked VEP block for 1_45785983_CTTTTTTT_C does not match virtual panel target genes - considering alternative consequences
• cpsr-gene-annotate - INFO - NO VEP BLOCK FOUND

Can you please assist? Thank you so much.

[sigven]

Hi,

Thanks for reaching out:) Is this hg38? Can you show me the full command you are using? panel id etc?

best, Sigve

[ShimaaSherif]

Hi Sigve, thank you for the fast response.

Yes; grch38, here is the command:

docker run -it --rm -v /Path/:/PCGR --name Sample.ID sigven/pcgr:2.0.3 bash cpsr --input_vcf /Path/Sample.ID.germline.filtered.vcf.gz --output_dir /Path --genome_assembly grch38 --sample_id Sample.ID --refdata_dir /PCGR/PCGR/data2.0.3/ --vep_dir /PCGR/PCGR/data2.0.3/data/grch38/.vep --panel_id 42 --secondary_findings --gwas_findings --ignore_noncoding --pop_gnomad global --maf_upper_threshold 0.01 --classify_all --force_overwrite

Note: The PCGR v.2.03 (somatic variant) is working perfectly fine.

[sigven]

Hi,

I've looked into the case. And as specified in the output, it's not an error, it's a warning. Basically, it has to deal with variants in your input that overlap with the GWAS track (option --gwas_findings, i.e. common variants associated with cancer from genome-wide association-studies). What happens is that some of your input variants overlap GWAS variants at the exact chromosomal position (e.g. 1 36066715 T), but not at the allelic level (the risk allele at that position is A, and not C). So such variants makes CPSR somewhat "confused", it's not a variant that overlaps a GWAS variant (exactly), and not a variant that overlaps with the virtual gene panel, only a variant that matches the GWAS loci by position, hence the warning:) Does that make sense ?

I suspect that such cases may have very well happened in previous versions (e.g. 1.0.2), only that the then, the warning was not made explicit to the user.

best, Sigve

[sigven]

Closing this issue for now. The warning you encountered is a bit confusing, and I will try to remove this in a future release, but as stated above, it's not an error.

BTW: just released 2.1.0 over the weekend. Fresh data, re-calibration of classification thresholds.

best, Sigve