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.
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.
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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