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CYP2D6*6

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Interpretation:
Likely benign; drug response; other​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
5
First in ClinVar:
Apr 4, 2013
Most recent Submission:
May 19, 2020
Last evaluated:
May 1, 2019
Accession:
VCV000016891.9
Variation ID:
16891
Description:
1bp deletion
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CYP2D6*6

Allele ID
31930
Variant type
Deletion
Variant length
1 bp
Cytogenetic location
22q13.2
Genomic location
22: 42129084 (GRCh38) GRCh38 UCSC
22: 42525086 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NM_000106.6:c.454del MANE Select NP_000097.3:p.Trp152fs frameshift
NM_000106.5:c.454delT
NM_001025161.3:c.353-140del
... more HGVS
Protein change
W152fs
Other names
NM_000106.5(CYP2D6):c.454delT (p.Trp152Glyfs)
CYP2D6T
1707delT
Canonical SPDI
NC_000022.11:42129083:A:
Functional consequence
No function
Global minor allele frequency (GMAF)
0.00479 ()

Allele frequency
Trans-Omics for Precision Medicine (TOPMed) 0.00711
Trans-Omics for Precision Medicine (TOPMed) 0.00718
The Genome Aggregation Database (gnomAD) 0.00908
1000 Genomes Project 0.00479
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00665
The Genome Aggregation Database (gnomAD), exomes 0.00792
Exome Aggregation Consortium (ExAC) 0.00793
The Genome Aggregation Database (gnomAD) 0.00883
Links
ClinGen: CA126953
Genetic Testing Registry (GTR): GTR000562560
OMIM: 124030.0003
dbSNP: rs5030655
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely benign; other 2 criteria provided, multiple submitters, no conflicts Aug 6, 2018 RCV000734613.5
drug response 1 criteria provided, single submitter May 1, 2019 RCV001030443.2
drug response 1 criteria provided, single submitter May 1, 2019 RCV001093716.2
drug response 1 no assertion criteria provided Jun 1, 1994 RCV000018387.28
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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
other
(Aug 06, 2018)
criteria provided, single submitter
Method: clinical testing
not provided
Affected status: unknown
Allele origin: germline
Eurofins NTD LLC (GA)
Accession: SCV000862767.1
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: SCV001193761.1
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:
Individuals who do not have any fully functional alleles are either intermediate metabolizers (one decreased function and one no function allele, e.g., *6/*41) or poor … (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: SCV001250911.1
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:
Individuals who do not have any fully functional alleles are either intermediate metabolizers (one decreased function and one no function allele, e.g., *4/*41) or poor … (more)
Likely benign
(Mar 14, 2018)
criteria provided, single submitter
Method: clinical testing
Not Provided
Affected status: yes
Allele origin: germline
GeneDx
Accession: SCV000977563.2
First in ClinVar: Aug 26, 2019
Last updated: Aug 26, 2019
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)
drug response
(Jun 01, 1994)
no assertion criteria provided
Method: literature only
DEBRISOQUINE, POOR METABOLISM OF
Affected status: not provided
Allele origin: germline
OMIM
Accession: SCV000038669.1
First in ClinVar: Apr 04, 2013
Last updated: Apr 04, 2013
Publications:
PubMed (1)
PubMed: 7951238
Comment on evidence:
This allelic variant is also known as CYP2D6*6 or CYP2D6(T). In individuals with the PM phenotype (608902), Saxena et al. (1994) identified a single base … (more)

Functional evidence

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Functional consequence Method Result Submitter Supporting information
No function
Medical Genetics Summaries
Accession: SCV001193761.1
Submitted: (Nov 07, 2019)
Evidence details
Publications
PubMed (7)
Other databases
https://dailymed.nlm.nih.gov/dai…
No function
Medical Genetics Summaries
Accession: SCV001250911.1
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
Identification of a new variant CYP2D6 allele with a single base deletion in exon 3 and its association with the poor metabolizer phenotype. Saxena R Human molecular genetics 1994 PMID: 7951238
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 rs5030655...

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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 Apr 24, 2022