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Ensembl / ensembl-vep

The Ensembl Variant Effect Predictor predicts the functional effects of genomic variants
https://www.ensembl.org/vep
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Incorrect pHGVS annotation for variant #1316

Open rosaricla opened 1 year ago

rosaricla commented 1 year ago

Describe the issue

VEP performed incorrect pHGVS annotation for the variant NM_173660.5:c.1124_1127dup (rs606231128) . VEP annotated the variant as NP_775931.3:p.Ala377ProfsTer31 when the correct annotation should be NP_775931.3:p.Ala378Serfs*30

Additional information

Links to the variant with correct annotation:

System

nuno-agostinho commented 1 year ago

Hey @rosaricla, hope you are having a nice day!

Could you please send me the VEP command that returns that output? Did you use shifting arguments (e.g., --shift_genomic)?

Kind regards, Nuno

rosaricla commented 1 year ago

Hi @nuno-agostinho ,

Thank you for checking this out. The VEP command will be the following:

/opt/vep/src/ensembl-vep/vep --cache --offline --force_overwrite --show_ref_allele --numbers --fork 15 --refseq --cache_version 104 --dir_cache /task/in/SNP/VEP/cache/ --dir_plugins /opt/vep/Plugins --fasta /task/in/SNP/VEP/cache/homo_sapiens_refseq/104_GRCh37/Homo_sapiens.GRCh37.75.dna.primary_assembly.fa --assembly GRCh37 -i sample_23456789.vcf -o sample_23456789_VEP_output.tsv --hgvs --hgvsg --symbol

And the output for the variant of interest:

rs606231128 chr4:3494833-3494834 GCCT 285489 NM_173660.5 Transcript frameshift_variant 1190-1191 1120-1121 374 S/SLX agc/aGCCTgc - REF_ALLELE=-;IMPACT=HIGH;STRAND=1;SYMBOL=DOK7;SYMBOL_SOURCE=EntrezGene;GIVEN_REF=-;USED_REF=-;BAM_EDIT=OK;EXON=7/7;HGVSc=NM_173660.5:c.1124_1127dup;HGVSp=NP_775931.3:p.Ala377ProfsTer31;HGVS_OFFSET=7;HGVSg=chr4:g.3494837_3494840dup

Best regards, Rosa

stephan-hutter commented 1 year ago

This sounds like it's related to the HGVS duplication bug I reported here: #712

FlorianErger commented 1 year ago

I am having a possibly related issue with this inframe insertion in a poly-Q stretch:

https://grch37.rest.ensembl.org/vep/human/hgvs/12:g124887095_124887096insCTG?hgvs=1&refseq=1

VEP shifts this variant somehow too far and reports NP_006303.4:p.Pro511_Met512insAla, however this variant is actually https://www.ncbi.nlm.nih.gov/clinvar/variation/1181246/ (NP_006303.4:p.Gln510dup)

likhitha-surapaneni commented 1 month ago

Hi @rosaricla , Hope you are doing well. Are you still facing this issue with release/112?