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CYP2D6*10

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Interpretation:
Likely benign; drug response; other​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
6
First in ClinVar:
Apr 4, 2013
Most recent Submission:
May 19, 2020
Last evaluated:
May 1, 2019
Accession:
VCV000016893.7
Variation ID:
16893
Description:
single nucleotide variant
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CYP2D6*10

Allele ID
31932
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
22q13.2
Genomic location
22: 42130692 (GRCh38) GRCh38 UCSC
22: 42526694 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NM_000106.6:c.100C>T MANE Select NP_000097.3:p.Pro34Ser missense
NM_001025161.3:c.100C>T NP_001020332.2:p.Pro34Ser missense
NC_000022.11:g.42130692G>A
... more HGVS
Protein change
P34S
Other names
NM_000106.6(CYP2D6):c.100C>T (p.Pro34Ser)
Canonical SPDI
NC_000022.11:42130691:G:A
Functional consequence
Decreased function
Global minor allele frequency (GMAF)
0.23802 (A)

Allele frequency
Trans-Omics for Precision Medicine (TOPMed) 0.19196
1000 Genomes Project 0.23802
The Genome Aggregation Database (gnomAD), exomes 0.20875
The Genome Aggregation Database (gnomAD) 0.18675
The Genome Aggregation Database (gnomAD) 0.19180
Exome Aggregation Consortium (ExAC) 0.24669
Links
ClinGen: CA126956
Genetic Testing Registry (GTR): GTR000562560
UniProtKB: P10635#VAR_008336
OMIM: 124030.0005
dbSNP: rs1065852
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely benign 1 criteria provided, single submitter Mar 9, 2018 RCV000603460.1
other 1 criteria provided, single submitter Aug 6, 2018 RCV000734607.3
drug response 1 criteria provided, single submitter May 1, 2019 RCV001030444.2
drug response 1 criteria provided, single submitter May 1, 2019 RCV001093717.2
drug response 1 no assertion criteria provided May 18, 2015 RCV000018389.23
drug response 1 no assertion criteria provided Apr 28, 2018 RCV001029560.2
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
CYP2D6 - - GRCh38
GRCh38
GRCh38
GRCh38
GRCh38
GRCh38
GRCh37
216 307

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter More information
Likely benign
(Mar 09, 2018)
criteria provided, single submitter
Method: clinical testing
not specified
Affected status: yes
Allele origin: germline
GeneDx
Accession: SCV000730663.1
First in ClinVar: Apr 09, 2018
Last updated: Apr 09, 2018
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
other
(Aug 06, 2018)
criteria provided, single submitter
Method: clinical testing
not provided
Affected status: unknown
Allele origin: germline
Eurofins NTD LLC (GA)
Accession: SCV000862761.1
First in ClinVar: Dec 16, 2018
Last updated: Dec 16, 2018
Other databases
http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CYP2D6
Sex: mixed
drug response
(May 01, 2019)
criteria provided, single submitter
Method: curation
Deutetrabenazine response
Drug used for Chorea , Huntington disease , and Tardive dyskinesia
Affected status: unknown
Allele origin: germline
Medical Genetics Summaries
Accession: SCV001193762.1
First in ClinVar: Apr 06, 2020
Last updated: Apr 06, 2020
Publications:
PubMed (7)
Other databases
https://dailymed.nlm.nih.gov/dai… https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7ea3c60a-45c7-44cc-afc2-d87fa53993c0
Comment:
CYP2D6*10 has decreased function: individuals with one decreased function and one no function allele (e.g., *4/*10) are intermediate metabolizers; individuals with two decreased function alleles … (more)
drug response
(May 01, 2019)
criteria provided, single submitter
Method: curation
Tamoxifen response
Drug used for Breast cancer
Affected status: unknown
Allele origin: germline
Medical Genetics Summaries
Accession: SCV001250912.1
First in ClinVar: May 19, 2020
Last updated: May 19, 2020
Publications:
PubMed (30)
Other databases
https://dailymed.nlm.nih.gov/dai… https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7ee3d3d2-85d1-4018-8e70-5ed8a64ae1f0
Comment:
CYP2D6*10 has decreased function: individuals with one decreased function and one no function allele (e.g., *4/*10) are intermediate metabolizers; individuals with two decreased function alleles … (more)
drug response
(May 18, 2015)
no assertion criteria provided
Method: literature only
DEBRISOQUINE, POOR METABOLISM OF
Affected status: not provided
Allele origin: germline
OMIM
Accession: SCV000038671.1
First in ClinVar: Apr 04, 2013
Last updated: Apr 04, 2013
Publications:
PubMed (2)
PubMed: 221162112051754
Comment on evidence:
This allelic variant is also known as CYP2D6*10 or CYP2D6(J) or CYP2D6(Ch1, Ch2). Kagimoto et al. (1990) identified a 188C-T transition in exon 1 of … (more)
drug response
(Apr 28, 2018)
no assertion criteria provided
Method: research
Tramadol response
Affected status: yes
Allele origin: somatic
Bruce Budowle Laboratory,University of North Texas Health Science Center
Accession: SCV001192346.1
First in ClinVar: Mar 29, 2020
Last updated: Mar 29, 2020
Number of individuals with the variant: 32

Functional evidence

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Functional consequence Method Result Submitter Supporting information
Decreased function
Medical Genetics Summaries
Accession: SCV001193762.1
Submitted: (Nov 07, 2019)
Evidence details
Publications
PubMed (7)
Other databases
https://dailymed.nlm.nih.gov/dai…
Decreased function
Medical Genetics Summaries
Accession: SCV001250912.1
Submitted: (Mar 06, 2020)
Evidence details
Publications
PubMed (30)
Other databases
https://dailymed.nlm.nih.gov/dai…

Citations for this variant

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Title Author Journal Year Link
Deutetrabenazine Therapy and <i>CYP2D6</i> Genotype Dean L - 2019 PMID: 31046213
Tamoxifen Pharmacogenetics and Metabolism: Results From the Prospective CYPTAM Study. Sanchez-Spitman A Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2019 PMID: 30676859
Tamoxifen Therapy and <i>CYP2D6</i> Genotype Dean L - 2019 PMID: 28520357
Tamoxifen and CYP2D6: A Controversy in Pharmacogenetics. Cronin-Fenton DP Advances in pharmacology (San Diego, Calif.) 2018 PMID: 29801584
Review of deutetrabenazine: a novel treatment for chorea associated with Huntington's disease. Dean M Drug design, development and therapy 2018 PMID: 29497277
Tamoxifen Metabolism and Efficacy in Breast Cancer: A Prospective Multicenter Trial. Neven P Clinical cancer research : an official journal of the American Association for Cancer Research 2018 PMID: 29459457
Tardive dyskinesia: Out of the shadows. Hauser RA Journal of the neurological sciences 2018 PMID: 29449008
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and Tamoxifen Therapy. Goetz MP Clinical pharmacology and therapeutics 2018 PMID: 29385237
Impact of CYP2D6 polymorphisms on endoxifen concentrations and breast cancer outcomes. Hwang GS The pharmacogenomics journal 2018 PMID: 28762370
Serum concentrations of active tamoxifen metabolites predict long-term survival in adjuvantly treated breast cancer patients. Helland T Breast cancer research : BCR 2017 PMID: 29183390
Impact of ABCB1 and CYP2D6 polymorphisms on tamoxifen treatment outcomes and adverse events in breast cancer patients. Argalacsova S Journal of B.U.ON. : official journal of the Balkan Union of Oncology 2017 PMID: 29135105
Improved Prediction of Endoxifen Metabolism by CYP2D6 Genotype in Breast Cancer Patients Treated with Tamoxifen. Schroth W Frontiers in pharmacology 2017 PMID: 28955222
CYP2D6 genotype is not associated with survival in breast cancer patients treated with tamoxifen: results from a population-based study. Hertz DL Breast cancer research and treatment 2017 PMID: 28730340
Don't think twice it's all right: tamoxifen and CYP2D6 genotyping in the treatment of breast cancer patients. Damkier P Pharmacogenomics 2017 PMID: 28592184
Indirect tolerability comparison of Deutetrabenazine and Tetrabenazine for Huntington disease. Claassen DO Journal of clinical movement disorders 2017 PMID: 28265459
Cytochrome P-450 2D6 (CYP2D6) Genotype and Breast Cancer Recurrence in Tamoxifen-Treated Patients: Evaluating the Importance of Loss of Heterozygosity. Ahern TP American journal of epidemiology 2017 PMID: 27988492
Significant Effect of Polymorphisms in <i>CYP2D6</i> on Response to Tamoxifen Therapy for Breast Cancer: A Prospective Multicenter Study. Zembutsu H Clinical cancer research : an official journal of the American Association for Cancer Research 2017 PMID: 27797974
Should CYP2D6 be genotyped when treating with tamoxifen? Del Re M Pharmacogenomics 2016 PMID: 27883289
Dopamine depleters in the treatment of hyperkinetic movement disorders. Jankovic J Expert opinion on pharmacotherapy 2016 PMID: 27819145
Providing Balance in ASCO Clinical Practice Guidelines: CYP2D6 Genotyping and Tamoxifen Efficacy. Goetz MP Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2016 PMID: 27551126
Effect of Deutetrabenazine on Chorea Among Patients With Huntington Disease: A Randomized Clinical Trial. Huntington Study Group. JAMA 2016 PMID: 27380342
Deutetrabenazine for Treatment of Chorea in Huntington Disease. Geschwind MD JAMA 2016 PMID: 27380339
One step at a time: CYP2D6 guided tamoxifen treatment awaits convincing evidence of clinical validity. Hertz DL Pharmacogenomics 2016 PMID: 27249031
Tamoxifen Dose Escalation in Patients With Diminished CYP2D6 Activity Normalizes Endoxifen Concentrations Without Increasing Toxicity. Hertz DL The oncologist 2016 PMID: 27226358
Pharmacogenetics of CYP2D6 and tamoxifen therapy: Light at the end of the tunnel? Del Re M Pharmacological research 2016 PMID: 27060675
Tamoxifen metabolism predicts drug concentrations and outcome in premenopausal patients with early breast cancer. Saladores P The pharmacogenomics journal 2015 PMID: 25091503
Population pharmacokinetic modelling to assess the impact of CYP2D6 and CYP3A metabolic phenotypes on the pharmacokinetics of tamoxifen and endoxifen. ter Heine R British journal of clinical pharmacology 2014 PMID: 24697814
Association between CYP2D6 genotypes and the clinical outcomes of adjuvant tamoxifen for breast cancer: a meta-analysis. Jung JA Pharmacogenomics 2014 PMID: 24329190
CYP2D6 genotype and adjuvant tamoxifen: meta-analysis of heterogeneous study populations. Province MA Clinical pharmacology and therapeutics 2014 PMID: 24060820
Prediction of tamoxifen outcome by genetic variation of CYP2D6 in post-menopausal women with early breast cancer. Brauch H British journal of clinical pharmacology 2014 PMID: 24033728
CYP2D6 genotype and tamoxifen activity: understanding interstudy variability in methodological quality. Ratain MJ Clinical pharmacology and therapeutics 2013 PMID: 23872831
CYP2D6 genotype and tamoxifen response in postmenopausal women with endocrine-responsive breast cancer: the breast international group 1-98 trial. Regan MM Journal of the National Cancer Institute 2012 PMID: 22395644
CYP2D6 and UGT2B7 genotype and risk of recurrence in tamoxifen-treated breast cancer patients. Rae JM Journal of the National Cancer Institute 2012 PMID: 22395643
The tamoxifen metabolite norendoxifen is a potent and selective inhibitor of aromatase (CYP19) and a potential lead compound for novel therapeutic agents. Lu WJ Breast cancer research and treatment 2012 PMID: 21814747
Association between CYP2D6 polymorphisms and outcomes among women with early stage breast cancer treated with tamoxifen. Schroth W JAMA 2009 PMID: 19809024
Clinical implications of CYP2D6 genotypes predictive of tamoxifen pharmacokinetics in metastatic breast cancer. Lim HS Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2007 PMID: 17761971
Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. Desta Z The Journal of pharmacology and experimental therapeutics 2004 PMID: 15159443
CYP2D6.10 present in human liver microsomes shows low catalytic activity and thermal stability. Nakamura K Biochemical and biophysical research communications 2002 PMID: 12051754
Multiple mutations of the human cytochrome P450IID6 gene (CYP2D6) in poor metabolizers of debrisoquine. Study of the functional significance of individual mutations by expression of chimeric genes. Kagimoto M The Journal of biological chemistry 1990 PMID: 2211621
DailyMed Drug Label, AUSTEDO- deutetrabenazine tablet, coated, deutetrabenazine kit, 2021 - - - -
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CYP2D6 - - - -
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7ea3c60a-45c7-44cc-afc2-d87fa53993c0 - - - -
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7ee3d3d2-85d1-4018-8e70-5ed8a64ae1f0 - - - -

Text-mined citations for rs1065852...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jun 24, 2022