DPYD I543V - GET-Evidence

Note: This variant has not been sufficiently evaluated by a GET-Evidence editor.

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DPYD I543V

(DPYD Ile543Val)


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Short summary

Increase incidence of nausea with fluoruracil.

Variant evidence
Computational -
Functional -
Case/Control -
Familial -
 
Clinical importance
Severity -
Treatability -
Penetrance -
 

Impact

Insufficiently evaluated pharmacogenetic

(The "insufficiently evaluated" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

unknown

Summary of published research, and additional commentary

 

Allele frequency

  • C @ chr1:97981395: 18.5% (1988/10758) in EVS
  • C @ chr1:97753982: 17.7% (22/124) in GET-Evidence
  • Frequency shown in summary reports: 18.5% (1988/10758)

Publications
 

Kleibl Z, Fidlerova J, Kleiblova P, Kormunda S, Bilek M, Bouskova K, Sevcik J, Novotny J. Influence of dihydropyrimidine dehydrogenase gene (DPYD) coding sequence variants on the development of fluoropyrimidine-related toxicity in patients with high-grade toxicity and patients with excellent tolerance of fluoropyrimidine-based chemotherapy. Neoplasma. 2009;56(4):303-16. PubMed PMID: 19473056.

 

Genomes
 

hu034DB1 - CGI sample GS00253-DNA_A02_200_37
het C @ chr1:97981395

 

 

 

 

Added in this revision:

 

 

 

 

 

 

huAE6220 - CGI sample GS00253-DNA_H01_200_37
het C @ chr1:97981395

 

 

 

GS07357 - var-GS07357-1100-36-ASM
het C @ chr1:97753983

 

GS18504 - var-GS18504-1100-36-ASM
het C @ chr1:97753983

 

GS18505 - var-GS18505-1100-36-ASM
het C @ chr1:97753983

 

GS18558 - var-GS18558-1100-36-ASM
hom C @ chr1:97753983

 

GS19020 - var-GS19020-1100-36-ASM
het C @ chr1:97753983

 

GS19025 - var-GS19025-1100-36-ASM
hom C @ chr1:97753983

 

GS19026 - var-GS19026-1100-36-ASM
hom C @ chr1:97753983

 

GS19649 - var-GS19649-1100-36-ASM
het C @ chr1:97753983

 

GS19704 - var-GS19704-1100-36-ASM
het C @ chr1:97753983

 

Other external references
 

    dbSNP
  • rs1801159
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PharmGKB
  • [Nausea; Vomiting]
    [fluorouracil]
    The G allele of this SNP is associated with increased incidence of medium-severe nausea or vomiting, and with reduced leukocyte counts in gastric carcinoma and colon carcinoma patients treated with 5-fluorouracil. The elimination constant (Ke) for 5-fluorouracil was significantly lower in patients homozygous for the G allele.
    www.ncbi.nlm.nih.gov/pubmed/17848752; PubMed ID:9918128
    PolyPhen-2
  • Score: 0 (benign)
    Web search results (34 hits -- see all)
  • DPYD [PharmGKB]
    Decreased DPYD activity is associated with a >four-fold risk of severe or fatal ... DPYD*5, DPYD:I543V, DPYD:A1627G. Related Drugs: fluorouracil. Related ...
    www.pharmgkb.org/do/serve?objId=PA145&objCls=Gene
  • Detailed Analysis of Five Mutations in Dihydropyrimidine ...
    dehydrogenase gene (DPYD): one novel mutation, c.775A>G (K259E); four known missense. mutations, c.85T>C (C29R), c.496A>G (M166V), c.1601G>A (S534N), c.1627A>G (I543V) ...
    interscience.wiley.com/homepages/38515/pdf/mutation/672.pdf
  • Use of Pyrosequencing to Detect Clinically Relevant ...
    At least 13 variant alleles of the DPYD gene have been described (13) ... DPYD*2B includes the exon 14 splice SNP and A1627G in exon 13 (I543V), but it is extremely rare in the ...
    www.clinchem.org/cgi/content/full/49/10/1661
  • Hypermethylation of the DPYD promoter region is not a major ...
    Recently, hypermethylation of the DPYD promoter region has been ... No evidence of DPYD promoter methylation was observed in any of the investigated ...
    www.jeccr.com/content/xml/1756-9966-27-54.xml
  • Pharmacogenetic and clinical aspects of dihydropyrimidine ...
    Alert me when this article is cited. Alert me if a correction is ... mutations have been identified in DPYD, including one splice-site mutation ...
    acb.rsmjournals.com/cgi/content/abstract/40/1/41
  • Zhiling Yu, PhD* John T. Mondick, PhD Elke H. Krekels, MSc ...
    I543V. DPYD*6: G2194A. V732I. DPYD*2A. G>A. intron 14 splice site: "exon 14 skipping" NH. 2 ... Limited Effect of DPYD and TYMS Polymorphisms - Sensitivity and ...
    ascpt.org/.../Late_Breaking_Oral_Session_LBIIA.pdf
  • Mutational analysis of the dihydropyrimidine dehydrogenase ...
    Mutational analysis of the dihydropyrimidine dehydrogenase [DPYD] gene in 125 patients treated with fluoropyrimidine-containing regimens. - ASCO - The American ...
    asco.org/ASCOv2/Meetings/Abstracts?...
  • Lethal 5-fluorouracil toxicity associated with a novel ...
    Analysis of DPYD for the presence of mutations showed that the ... for two other mutations 1627AG (I543V) and 85TC (C29R), which have been suggested to be common polymorphisms. ...
    annonc.oxfordjournals.org/cgi/content/full/14/2/341-a
  • Dihydropyrimidine Dehydrogenase Defi ciency: Impact of ...
    This fi gure locates the sequence variations identifi ed in the coding and noncoding regions of the DPYD gene. ... DPYD*2A (IVS14+1G>A) in intron 14 and DPYD*5 (1627A>G; I543V) in ...
    clinicaladvances.com/article_pdfs/ho-article-200408-lee.pdf
  • 1661
    DPYD*2A is the result of a G-to-A transition in a splice. donor site that causes skipping of exon 14 (9 ) ... (I543V), but it is extremely rare in the general population. DPYD*5 ...
    www.clinchem.org/cgi/reprint/49/10/1661.pdf

Other in silico analyses
 

  • NBLOSUM100 score = –4
  • GET-Evidence autoscore = 3

Edit history
 

Gene search

"GENE" or "GENE A123C":

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