Page 288 - Personalised medicine of fluoropyrimidines using DPYD pharmacogenetics Carin Lunenburg

Chapter 11
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Table 4. MAF per database
Three databases (GoNL, 1000Genomes, and exome trios LUMC) containing phased data were checked for four DPYD variants. Two large online databases (ExAC and gnomAD) were checked to identify the MAFs of the individual DPYD variants. For each DPYD variant, the genotype distribution and MAF are shown.
databases
HW/HE/HM
MAF
GoNL
1000 Genomes Exome Trios LUMC ExAC
gnomAD
489/7/0 0.7% 405/2/0 0.2% 946/15/0 0.8% 60,627/624/5 0.5% 138,489/1,586/10 0.6%
494/2/0 0.2% 406/1/0 0.1% 946/0/0 0.00% 60,320/42/0 0.03% 138,166/83/0 0.03%
475/21/0 389/18/0 946/46/0 60,652/1,808/27 138,407/3,841/39
2.1% 2.2% 2.3% 1.5% 1.4%
490/6/0 0.6% 403/4/0 0.5% 946/2/0 0.1% 60,687/317/1 0.3% 138,478/792/1 0.3%
variants
DPYD*2A (rs3918290) HW/HE/HM MAF
DPYD*13 (rs55886062) HW/HE/HM MAF
c.1236G>A (rs56038477)
c.2846A>T (rs67376798) HW/HE/HM MAF
Abbreviations: MAF: minor allele frequency; HW: homozygous wild-type; HE: heterozygous carrier; HM: homozygous carrier; GoNL: Genome of the Netherlands; ExAC: Exome Aggregation Consortium; gnomAD: Genome Aggregation Database.
Table 5. Calculated frequency for compound heterozygous DPYD patients
Using the average MAFs of the ExAC and gnomAD databases (for DPYD*2A, DPYD*13, c.1236G>A, and c.2846A>T, these are 0.55%, 0.03%, 1.43%, and 0.27% respectively), possible combinations for two out of four currently genotyped DPYD variants are shown.
Combination of DPYD variants DPYD*2A + DPYD*13 DPYD*2A + c.1236G>A DPYD*2A + c.2846A>T DPYD*13 + c.1236G>A DPYD*13 + c.2846A>T c.1236G>A + c.2846A>T
Calculated frequency
Abbreviations: MAF: minor allele frequency; ExAC: Exome Aggregation Consortium; gnomAD: Genome Aggregation Database.
0.0002% 0.008% 0.001% 0.0005% 0.0001% 0.004%