PGx Allele Definitions and PGx Guidelines
PGx Allele Definitions and PGx Guidelines
DRAGEN Array star allele calling leverages the star allele definitions provided by PharmVar and PharmGKB. DRAGEN Array star allele phenotype annotation, using the “star-allele annotate” command, is achieved through direct lookup into public PGx guidelines CPIC or DPWG, which is selected by the user when running DRAGEN Array.
See table below for details of the data sources.
| Data Source | Version | URL |
|---|---|---|
PharmVar | 6.1 | https://www.pharmvar.org |
PharmGKB | Snapshot-2024.05.16 | https://www.pharmgkb.org/ |
UGT Alleles Nomenclature | 2010.12.21 | https://www.pharmacogenomics.pha.ulaval.ca/ugt-alleles-nomenclature/ |
Human Cytochrome P450 (CYP) Allele Nomenclature Database Legacy Content | July 2024 | https://www.pharmvar.org/htdocs/archive/index_original.htm |
CPIC guidelines | 1.38.0 | https://cpicpgx.org/guidelines/ https://github.com/cpicpgx/cpic-data/ |
DPWG guidelines | June 2023 | https://www.pharmgkb.org/page/dpwgMapping |
DRAGEN Array “star-allele annotate” command provides both metabolizer status and activity score annotations for genes covered by the CPIC and DPWG guidelines.
Specifically, CPIC metabolizer/phenotype annotations are supported for CACNA1S, CYP2B6, CYP2C19, CYP2C9, CYP2D6, CYP3A5, DPYD, G6PD, MT-RNR1, NUDT15, RYR1, SLCO1B1, TPMT, UGT1A1, CFTR, IFNL3/IFNL4 and VKORC1, among them activity scores are supported for CYP2C9, CYP2D6, and DPYD. DPWG metabolizer/phenotype annotations are supported for CYP1A2, CYP2B6, CYP2C19, CYP2C9, CYP2D6, CYP3A4, CYP3A5, DPYD, NUDT15, SLCO1B1, TPMT, UGT1A1, VKORC1 and F5, among them activity scores are supported for CYP2D6 and DPYD.
Extended Multi-allelic variants based on the designs in the supported PGx products
DRAGEN Array PGx extends any single allele variant definitions obtained from PharmVar or PharmGKB that have multiple alleles in Illumina's product files to include all alleles of the Multi Allelic Variant (MAV). The table below shows the MAVs that were extended in the DRAGEN Array Database to cover all alleles for that MAV that are in the product files. Allele Name describes the allele that was added to the database.
| Gene Symbol | Allele Name | Hgvs |
|---|---|---|
CACNA1S.rs1800559 | rs1800559.C>A | NC_000001.11:g.201060815C>A |
CFTR.rs113993958 | rs113993958.G>A | NC_000007.14:g.117530953G>A |
CFTR.rs113993958 | rs113993958.G>T | NC_000007.14:g.117530953G>T |
CFTR.rs11971167 | rs11971167.G>T | NC_000007.14:g.117642528G>T |
CFTR.rs121908755 | rs121908755.G>T | NC_000007.14:g.117587800G>T |
CFTR.rs121909005 | rs121909005.T>C | NC_000007.14:g.117587801T>C |
CFTR.rs121909020 | rs121909020.G>C | NC_000007.14:g.117611640G>C |
CFTR.rs150212784 | rs150212784.T>C | NC_000007.14:g.117611595T>C |
CFTR.rs193922525 | rs193922525.G>C | NC_000007.14:g.117664770G>C |
CFTR.rs267606723 | rs267606723.G>T | NC_000007.14:g.117642451G>T |
CFTR.rs397508288 | rs397508288.A>C | NC_000007.14:g.117590409A>C |
CFTR.rs397508759 | rs397508759.G>T | NC_000007.14:g.117534363G>T |
CFTR.rs74551128 | rs74551128.C>T | NC_000007.14:g.117548795C>T |
CFTR.rs75039782 | rs75039782.C>G | NC_000007.14:g.117639961C>G |
CFTR.rs77834169 | rs77834169.C>A | NC_000007.14:g.117530974C>A |
CFTR.rs77834169 | rs77834169.C>G | NC_000007.14:g.117530974C>G |
CFTR.rs77932196 | rs77932196.G>C | NC_000007.14:g.117540270G>C |
CFTR.rs77932196 | rs77932196.G>T | NC_000007.14:g.117540270G>T |
CFTR.rs78655421 | rs78655421.G>C | NC_000007.14:g.117530975G>C |
CFTR.rs78655421 | rs78655421.G>T | NC_000007.14:g.117530975G>T |
COMT.rs13306278 | rs13306278.C>G | NC_000022.11:g.19941504C>G |
DPYD.rs114096998 | rs114096998.2.G>C | NC_000001.11:g.97078987G>C |
DPYD.rs140602333 | rs140602333.G>T | NC_000001.11:g.97573919G>T |
DPYD.rs142619737 | rs142619737.C>G | NC_000001.11:g.97515851C>G |
DPYD.rs143154602 | rs143154602.G>T | NC_000001.11:g.97593289G>T |
DPYD.rs145548112 | rs145548112.C>A | NC_000001.11:g.97306195C>A |
DPYD.rs190951787 | rs190951787.G>T | NC_000001.11:g.97515889G>T |
DPYD.rs200687447 | rs200687447.2.C>A | NC_000001.11:g.97193209C>A |
DPYD.rs3918289 | rs3918289.G>A | NC_000001.11:g.97450059G>A |
DPYD.rs3918290 | rs3918290.C>G | NC_000001.11:g.97450058C>G |
DPYD.rs6670886 | rs6670886.C>A | NC_000001.11:g.97699506C>A |
DPYD.rs72549304 | rs72549304.G>C | NC_000001.11:g.97549609G>C |
DPYD.rs72549304 | rs72549304.G>T | NC_000001.11:g.97549609G>T |
DPYD.rs748620513 | rs748620513.C>A | NC_000001.11:g.97573799C>A |
DPYD.rs748639205 | rs748639205.A>G | NC_000001.11:g.97082415A>G |
DPYD.rs760663364 | rs760663364.G>C | NC_000001.11:g.97515928G>C |
DPYD.rs777425216 | rs777425216.C>A | NC_000001.11:g.97515815C>A |
RYR1.38499667G>A | NC_000019.10:g.38499667G>T | NC_000019.10:g.38499667G>T |
RYR1.rs118192116 | rs118192116.C>T | NC_000019.10:g.38451850C>T |
RYR1.rs118192151 | rs118192151.G>C | NC_000019.10:g.38584974G>C |
RYR1.rs118204423 | rs118204423.G>A | NC_000019.10:g.38457539G>A |
RYR1.rs142474192 | rs142474192.G>T | NC_000019.10:g.38443790G>T |
RYR1.rs143988412 | rs143988412.A>G | NC_000019.10:g.38580066A>G |
RYR1.rs1801086 | rs1801086.G>T | NC_000019.10:g.38446710G>T |
RYR1.rs186983396 | rs186983396.C>G | NC_000019.10:g.38442434C>G |
RYR1.rs193922762 | rs193922762.C>A | NC_000019.10:g.38448673C>A |
RYR1.rs193922767 | rs193922767.G>A | NC_000019.10:g.38452996G>A |
RYR1.rs193922772 | rs193922772.G>A | NC_000019.10:g.38457546G>A |
RYR1.rs193922826 | rs193922826.C>G | NC_000019.10:g.38504319C>G |
RYR1.rs193922838 | rs193922838.G>A | NC_000019.10:g.38529036G>A |
RYR1.rs193922842 | rs193922842.C>T | NC_000019.10:g.38543821C>T |
RYR1.rs370634440 | rs370634440.G>T | NC_000019.10:g.38463499G>T |
Exceptions to Star Allele Definitions
G6PD
With the changes of reference genomes, the definition for a star allele sometimes need to be updated accordingly.
Mediterranean Haplotype and Mediterranean, Dallas, Panama, Sassari, Cagliari, Birmingham are defined by two variants rs5030868 and rs2230037. In genome build GRCh37, Mediterranean Haplotype is defined by rs2230037 G>A and rs5030868 G>A, and Mediterranean, Dallas, Panama, Sassari, Cagliari, Birmingham is defined by rs5030868 G>A, with rs2230037 reference allele G.
In genome build GRCh38, Mediterranean Haplotype is defined by rs5030868 G>A, with rs2230037 reference allele A, and Mediterranean, Dallas, Panama, Sassari, Cagliari, Birmingham is defined by rs2230037 A>G and rs5030868 G>A.
Variant rs2230037 is ignored in all other G6PD alleles except in the two Mediterranean alleles.
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