ireneisdoomed
commented
7 months ago The above proposal was implemented by @apriltuesday and now this is correctly linking to CFTR
-RECORD 0----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
datasourceId | pharmgkb
datasourceVersion | 2024-01-05
datatypeId | clinical_annotation
directionality | NULL
drugFromSource | ivacaftor
drugFromSourceId | CHEBI_66901
evidenceLevel | 1A
genotype | GG
genotypeAnnotationText | Patients with the rs75527207 GG genotype (do not have a copy of the CFTR G551D variant) and cystic fibrosis have an unknown response to ivacaftor treatment, as response may depend on the presence of other CFTR variants. FDA-approved drug labeling information and CPIC guidelines indicate use of ivacaftor in cystic fibrosis patients with at least one copy of a list of 33 CFTR genetic variants, including G551D. Other genetic and clinical factors may also influence response to ivacaftor.
genotypeId | 7_117587806_G_G,G
haplotypeFromSourceId | NULL
haplotypeId | NULL
literature | [21083385, 22047557, 23590265, 23757361, 23891399, 24066763, 27745802, 27773592, 25682022, 28651844, 28711222, 25311995, 28611235, 26135562, 25171465, 25755212, 26568242, 25473543, 25145599, 23628510, 25049054, 22942289, 19846789, 22293084, 23757359, 23313410, 24461666, 27158673]
pgxCategory | efficacy
phenotypeFromSourceId | MONDO_0009061
phenotypeText | Cystic Fibrosis
studyId | 981755803
targetFromSourceId | ENSG00000001626
variantFunctionalConsequenceId | SO_0002073
variantRsId | rs75527207
Describe the bug The PGx annotations for rs75527207 (7_117587806_G_G,G) in PharmGKB are not correctly linking to the CFTR gene. This issue arises because we query VEP with genotypes that only consist of reference alleles. VEP does not recognise these as variants and thus fails to return the associated gene.
Observed behaviour When querying VEP with the genotype information for rs75527207, which contains only reference alleles, VEP does not identify a variant. Consequently, no gene annotation is provided, and our evidence does not link to the CFTR gene as expected.
Expected behaviour Our PGx dataset should correctly link rs75527207 to the CFTR gene, even when the genotype comprises only reference alleles. For these situations, the gene won't be provided by VEP, but by PharmGKB directly. As functional annotation for the genotype we will show
no_sequence_alterationfor all ref/ref genotypes.This implementation has been done by the EVA team, and is expected in the next submission. No action on our side, just to make sure this is fixed for the next release.