Targeted next generation sequencing as a tool for precision medicine

Gulilat, Markus; Lamb, Tyler; Teft, Wendy A.; Wang, Jian; Dron, Jacqueline S.; Robinson, John F.; Tirona, Rommel G.; Hegele, Robert A.; Kim, Richard B.; Schwarz, Ute I.

doi:10.1186/s12920-019-0527-2

BMC Medical Genomics

Table 2 Concordance rate (%) between PGxSeq sequencing data compared to TaqMan-derived genotypes for clinically important SNVs as defined by PharmGKB

From: Targeted next generation sequencing as a tool for precision medicine

PharmGKB	Gene	Allele	Nucleotide change	Effect	dbSNP	Allele frequency			TaqMan			Concordanceª	FP	FN
Level of evidence					150	Study	1000G	ExAC	Patients genotyped (N)			(%)	(%)	(%)
Level of evidence					150	(n = 235)	EUR	EUR	WT	HET	HOM	(%)	(%)	(%)
1A	CYP2C19	*17	C > T	promoter	rs12248560	0.23	0.23	NR	23	11	1	100	0	0
1A	CYP2C19	*2	G > A	p.P227P	rs4244285	0.14	0.15	0.15	25	11	0	100	0	0
1A	CYP2C19	*3	G > A	p.Y212X	rs4986893	ND	0	1.80E-04	50	0	0	100	0	NA
1A	CYP2C9	*2	C > T	p.R144C	rs1799853	0.13	0.12	0.13	72	23	3	100	0	0
1A	CYP2C9	*3	A > C	p.I359L	rs1057910	0.06	0.06	0.07	87	13	0	100	0	0
1A	CYP2D6	*10	C > T	p.P34P	rs1065852	0.21	0.2	0.25	30	19	3	98.1	0	1.9
1A	CYP2D6	*4	G > A	splice	rs3892097	0.19	0.19	0.17	52	26	6	100	0	0
1A	CYP2D6	*3A	A > del	p.R208fs	rs35742686	0.03	0.02	0.02	50	2	0	100	0	0
1A	CYP2D6	*41	G > A	intronic	rs28371725	0.12	0.09	0.09	38	14	0	100	0	0
1A	CYP3A5	*3	A > G	splice	rs776746	0.93	0.95	NR	1	9	27	100	0	0
1A	CYP4F2	*3	C > T	p.V433 M	rs2108622	0.30	0.27	0.29	23	17	0	100	0	0
1A	DPYD	*13	T > G	p.I560S	rs55886062	2.1E-03	1.3E-03	6.18E-04	97	1	0	100	0	0
1A	DPYD	*2A	G > A	splice	rs3918290	0.02	0.01	0.01	100	1	0	100	0	0
1A	DPYD		A > T	p.D949V	rs67376798	0.02	2.2E-03	4.09E-03	80	8	0	98.9	0	1.1
1A	SLCO1B1	*5	T > C	p.V174A	rs4149056	0.18	0.17	0.16	67	31	4	100	0	0
1A	TPMT	*2	G > C	p.A80P	rs1800462	2.1E-03	6.00E-03	1.97E-03	51	1	0	100	0	0
1A	TPMT	*3B	G > A	p.A154T	rs1800460	0.04	0.03	0.04	41	10	0	100	0	0
1A	TPMT	*4	G > A	splice	rs1800584	ND	NR	3.01E-05	51	0	0	100	0	NA
1A	TPMT	*3C	A > G	p.Y240C	rs1142345	0.04	0.03	0.04	41	10	0	100	0	0
1A	UGT1A1	*28	(TA)₆ > (TA)₇	promoter	rs3064744	0.32	0.29	NR	36	40	5	100	0	0
1A	VKORC1		G > A	intergenic	rs9923231	0.40	0.40	NR	19	15	6	100	0	0
1B	CYP2B6	*9	G > T	p.Q172H	rs3745274	0.21	0.23	0.24	22	9	0	100	0	0
2A	ABCB1		C > T	p.I1145I	rs1045642	0.48	0.47	0.47	18	61	26	100	0	0
2A	CYP2D6	*9	AAG > del	p.K281del	rs5030656	0.02	0.02	0.03	48	4	0	100	0	0
2A	SLCO1B1	*1B	A > G	p.N130D	rs2306283	0.41	0.40	0.41	40	46	15	100	0	0
2B	ABCG2		C > A	p.Q141K	rs2231142	0.12	0.10	0.10	87	20	1	100	0	0
3	ABCC2		G > A	p.V417I	rs2273697	0.19	0.20	0.20	45	19	4	100	0	0
3	ABCG2		G > A	p.V12 M	rs2231137	0.04	0.06	0.05	81	9	0	100	0	0
3	CYP2B6		C > T	p.R487C	rs3211371	0.12	0.10	0.12	23	8	0	100	0	0
3	CYP3A4	*22	C > T	intronic	rs35599367	0.05	0.05	NR	36	8	0	100	0	0
3	DPYD	HapB3	G > A	p.E412E	rs56038477	0.03	0.02	0.02	73	11	0	100	0	0
3	SLCO2B1		G > A	p.R290Q	rs12422149	0.06	0.10	0.11	62	6	0	100	0	0

ª Percentage of total tested DNA samples with NGS-determined genotypes concordant with TaqMan results. False positive was defined as TaqMan determined “homozygous wildtype” and NGS determined “variant carrier”. False negative was defined as TaqMan determined “variant carrier” and NGS determined “homozygous wildtype”. PharmGKB definition for levels of evidence can be found at https://www.pharmgkb.org/page/clinAnnLevels. Nucleotide change presented as the change on the coding strand. Abbreviations: dbSNP 150 Single Nucleotide Polymorphism database build 150, ExAC Exome Aggregation Consortium European dataset, FP false positive, FN false negative, HET heterozygous genotype, HOM homozygous genotype, ND not detected in our patient database, NA not applicable as no variant carriers were found, NR, not reported in, 1000G EUR, or ExAC database, 1000G EUR 1000 Genomes Project European dataset, PharmGKB Pharmacogenomics Knowledge Base

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ISSN: 1755-8794

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