NA17280

NA17280 DNA from LCL

Description:

HUMAN VARIATION PANEL - WHITE PANEL OF 100 (SET 1)
HUMAN VARIATION PANEL - WHITE PANEL OF 200
CYTOCHROME P450, SUBFAMILY IIC, POLYPEPTIDE 19; CYP2C19
CYTOCHROME P450, SUBFAMILY IID, POLYPEPTIDE 6; CYP2D6

Affected:

No

Sex:

Male

Age:

No Data

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Human Variation
Pharmacogenetics
GeT-RM Samples
dbGaP

Alternate IDs

GM08036 [HUMAN VARIATION PANEL - WHITE PANEL OF 100 (SET 1)]

Quantity

25 µg

Quantitation Method

Please see our FAQ

Biopsy Source

Peripheral vein

Cell Type

B-Lymphocyte

Tissue Type

Blood

Transformant

Epstein-Barr Virus

Sample Source

DNA from LCL

Species

Homo sapiens

Common Name

Human

Remarks

Donor subject is heterozygous for a T>C change at nucleotide 358 (358T>C) in exon 3 of the CYP2C19 gene (CYP2C19*8) which results in a substitution of an arginine for tryptophan at codon 120 [Trp120Arg (W120R)] and donor subject is also a compound heterozygote with respect to CYP2D6: one allele has a variant CYP2D6 gene (CYP2D6*2) which contains two amino acid substitutions: a C>T transition at nucleotide 2938 in exon 6 resulting in an arg296-to-cys [Arg296Cys (R296C)] and a G>C transversion at nucleotide 4268 in exon 9 resulting in a ser486-to-thr [Ser486Thr (S486T)]; a second allele has a 1 bp deletion at nucleotide 2637 (2637delA) in exon 5 (CYP2D6*3)

Characterizations

Pharmacogenomics Panel

For pharmacogenetic variants please click here: GeT-RM PGx Search

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by LINE assay

Gene

CYP2C19

Chromosomal Location

10q23.33

Allelic Variant 1

W120R; MEPHENYTOIN 4-HYDROXYLASE POOR METABOLIZER

Identified Mutation

TRP120ARG

Gene

CYP2D6

Chromosomal Location

22q13.1

Allelic Variant 1

124030.0006; DEBRISOQUINE, POOR METABOLISM OF

Identified Mutation

1-BP DEL, 2549A; This allelic variant is also known as CYP2D6*3 or CYP2D6(A). Marez et al. (Pharmacogenetics 7: 193-202, 1997) identified a 1-bp deletion (2637A) in exon 5 of the CYP2D6 gene in a group of individuals with the poor metabolizer phenotype (608902).

Gene

CYP2D6

Chromosomal Location

22q13.1

Allelic Variant 2

124030.0007; DEBRISOQUINE, ULTRARAPID METABOLISM OF

Identified Mutation

ARG296CYS AND SER486THR; This allelic variant is also known as CYP2D6*2 or CYP2D6L. In a family in which 2 sibs and their father had MRs of less that 0.02 (ultrarapid phenotype, see 608902), Johansson et al. (Proc Nat Acad Sci 90:11825-11829, 1993) found 12 extra copies of the CYP2D6 gene inherited in an autosomal dominant pattern; in a second family in which 2 sibs had MRs of less than 0.1, the authors found 2 extra copies of the CYP2D6 gene. All affected individuals had a variant CYP2D6 gene, termed CYP2D6L, which contained 2 amino acid substitutions: a 2938C-T transition in exon 6, resulting in an arg296-to-cys (R296C), and a 4268G-to-C transversion in exon 9, resulting in a resulting in a ser486-to-thr (S486T) substitution. The MR of individuals with 1 copy of the CYP2D6L gene did not differ from those with the wildtype gene, but there was a correlation between decreased MR and increased copies of the CYP2D6L gene.

Phenotypic Data

Remarks

Publications

Charnaud S, Munro JE, Semenec L, Mazhari R, Brewster J, Bourke C, Ruybal-Pesántez S, James R, Lautu-Gumal D, Karunajeewa H, Mueller I, Bahlo M, PacBio long-read amplicon sequencing enables scalable high-resolution population allele typing of the complex CYP2D6 locus Communications biology5:168 2021

PubMed ID: 35217695

Moon MH, Hong SR, Shin KJ, Sequence Variations of 31 ?-Chromosomal Short Tandem Repeats Analyzed by Massively Parallel Sequencing in Three US Population Groups and Korean Population Journal of Korean medical science37:e40 2021

PubMed ID: 35166077

Pratt VM, Turner A, Broeckel U, Dawson DB, Gaedigk A, Lynnes TC, Medeiros EB, Moyer AM, Requesens D, Ventrini F, Kalman LV, Characterization of Reference Materials for CYP2C9, CYP2C19, VKORC1, CYP2C Cluster Variant, GGCX, and Other Pharmacogenetic Alleles with an Association for Molecular Pathology (AMP) Pharmacogenetics Working Group Tier 2 Status - A GeT-RM Collaborative Project The Journal of molecular diagnostics : JMD37:e40 2021

PubMed ID: 34020041

Botton MR, Yang Y, Scott ER, Desnick RJ, Scott SA, Phased Haplotype Resolution of the Genes11:e40 2020

PubMed ID: 33198140

Kwon YL, Kim BM, Lee EY, Shin KJ, Massively parallel sequencing of 25 autosomal STRs including SE33 in four population groups for forensic applications Scientific reports11:4701 2020

PubMed ID: 33633141

Scott SA, Scott ER, Seki Y, Chen AJ, Wallsten R, Owusu Obeng A, Botton MR, Cody N, Shi H, Zhao G, Brake P, Nicoletti P, Yang Y, Delio M, Shi L, Kornreich R, Schadt EE, Edelmann L, Development and Analytical Validation of a 29 Gene Clinical Pharmacogenetic Genotyping Panel: Multi-Ethnic Allele and Copy Number Variant Detection Clinical and translational science14:204-213 2020

PubMed ID: 32931151

Swart M, Stansberry WM, Pratt VM, Medeiros EB, Kiel PJ, Shen F, Schneider BP, Skaar TC, Analytical Validation of Variants to Aid in Genotype-Guided Therapy for Oncology The Journal of molecular diagnostics : JMD21:491-502 2018

PubMed ID: 30794985

Yousaf R, Ahmed ZM, Giese AP, Morell RJ, Lagziel A, Dabdoub A, Wilcox ER, Riazuddin S, Friedman TB, Riazuddin S, Modifier variant of METTL13 suppresses human GAB1-associated profound deafness The Journal of clinical investigation21:491-502 2018

PubMed ID: 29408807

Lee CC, McMillin GA, Babic N, Melis R, Yeo KT, Evaluation of a CYP2C19 genotype panel on the GenMark eSensor® platform and the comparison to the Autogenomics Infiniti™ and Luminex CYP2C19 panels Clinica chimica acta; international journal of clinical chemistry412(11-12):133-7 2010

PubMed ID: 21385571

Pratt VM, Zehnbauer B, Wilson JA, Baak R, Babic N, Bettinotti M, Buller A, Butz K, Campbell M, Civalier C, El-Badry A, Farkas DH, Lyon E, Mandal S, McKinney J, Muralidharan K, Noll L, Sander T, Shabbeer J, Smith C, Telatar M, Toji L, Vairavan A, Vance C, Weck KE, Wu AH, Yeo KT, Zeller M, and Kalman L., Characterization of 107 Genomic DNA Reference Materials for CYP2D6, CYP2C19, CYP2C9, VKORC1, and UGT1A1 J Mol Diagn12(6):835-46 2010

PubMed ID: 20889555

Marini NJ, Gin J, Ziegle J, Keho KH, Ginzinger D, Gilbert DA, Rine J, The prevalence of folate-remedial MTHFR enzyme variants in humans Proceedings of the National Academy of Sciences of the United States of America12(6):835-46 2008

PubMed ID: 18523009

Mohler PJ, Le Scouarnec S, Denjoy I, Lowe JS, Guicheney P, Caron L, Driskell IM, Schott JJ, Norris K, Leenhardt A, Kim RB, Escande D, Roden DM, Defining the cellular phenotype of "ankyrin-B syndrome" variants: human ANK2 variants associated with clinical phenotypes display a spectrum of activities in cardiomyocytes Circulation115:432-41 2007

PubMed ID: 17242276

Melis, R., Lyon, E., and McMillin, G.A., Determination of CYP2D6, CYP2C9 and CYP2C19 genotypes with Tag-It mutation detection assays Expert Rev Mol Diagn6(6):811-20 2006

PubMed ID: 17140368