CDA K27Q - GET-Evidence

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

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Curation:
Currentness:

CDA K27Q

(CDA Lys27Gln)


Short summary

 

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 @ chr1:20915701: 26.2% (2817/10758) in EVS
  • C @ chr1:20788287: 19.2% (23/120) in GET-Evidence
  • Frequency shown in summary reports: 26.2% (2817/10758)

Publications
 

Fukunaga AK, Marsh S, Murry DJ, Hurley TD, McLeod HL. Identification and analysis of single-nucleotide polymorphisms in the gemcitabine pharmacologic pathway. Pharmacogenomics J. 2004;4(5):307-14. PubMed PMID: 15224082.

 

Sugiyama E, Kaniwa N, Kim SR, Kikura-Hanajiri R, Hasegawa R, Maekawa K, Saito Y, Ozawa S, Sawada J, Kamatani N, Furuse J, Ishii H, Yoshida T, Ueno H, Okusaka T, Saijo N. Pharmacokinetics of gemcitabine in Japanese cancer patients: the impact of a cytidine deaminase polymorphism. J Clin Oncol. 2007 Jan 1;25(1):32-42. PubMed PMID: 17194903.

 

Mahlknecht U, Dransfeld CL, Bulut N, Kramer M, Thiede C, Ehninger G, Schaich M. SNP analyses in cytarabine metabolizing enzymes in AML patients and their impact on treatment response and patient survival: identification of CDA SNP C-451T as an independent prognostic parameter for survival. Leukemia. 2009 Oct;23(10):1929-32. Epub 2009 May 21. PubMed PMID: 19458626.

 

Genomes
 

 

hu034DB1 - CGI sample GS00253-DNA_A02_200_37
het C @ chr1:20915701

 

hu0D879F - CGI sample GS00253-DNA_G01_200_37
het C @ chr1:20915701

 

 

 

 

 

 

 

 

 

 

 

 

hu9385BA - CGI sample GS00253-DNA_E01_200_37
het C @ chr1:20915701

 

 

 

 

huAE6220 - CGI sample GS00253-DNA_H01_200_37
het C @ chr1:20915701

 

 

 

huBEDA0B - CGI sample GS00253-DNA_C01_200_37
het C @ chr1:20915701

 

huC30901 - CGI sample GS00253-DNA_B01_200_37
het C @ chr1:20915701

 

 

 

GS06994 - var-GS06994-1100-36-ASM
het C @ chr1:20788288

 

GS12004 - var-GS12004-1100-36-ASM
het C @ chr1:20788288

 

GS18526 - var-GS18526-1100-36-ASM
het C @ chr1:20788288

 

GS18942 - var-GS18942-1100-36-ASM
het C @ chr1:20788288

 

GS19649 - var-GS19649-1100-36-ASM
hom C @ chr1:20788288

 

GS19670 - var-GS19670-1100-36-ASM
het C @ chr1:20788288

 

GS19703 - var-GS19703-1100-36-ASM
het C @ chr1:20788288

 

GS19735 - var-GS19735-1100-36-ASM
het C @ chr1:20788288

 

GS20509 - var-GS20509-1100-36-ASM
het C @ chr1:20788288

 

NA12878

 

Other external references
 

    dbSNP
  • rs2072671
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PharmGKB
  • [gemcitabine]
    Risk or phenotype-associated allele: None. Phenotype: Variants identified in a screen of 13 genes involved in the gemcitabine drug metabolic pathway. For the non-synonymous CDA:79A>C (K27Q) SNP, the C allele (27Gln) was at frequency 0.36 and 0.04 in Europeans and Africans, respectively. There was a significant difference between ethnic groups in genotype frequency distribution (p < 0.001) Study size: 180. Study population/ethnicity: Healthy, unrelated blood donors of European (n = 95) and African (n = 85) descent. Significance metric(s): p < 0.001. Type of association: GN.
    www.ncbi.nlm.nih.gov/pubmed/15224082
  • [Drug Toxicity; Leukemia, Myeloid, Acute]
    [cytarabine; daunorubicin]
    Risk or phenotype-associated allele: wildtype AA genotype. Phenotype: The wildtype homozygous genotype of rs2072671 (c.79AA, p.27Lys/Lys) and AA gentoype at promoter position -92 (SNP4) had lower incidences for grade III/IV liver toxicity when compared with the respective variant heterozygous and variant homozygous genotypes (13 vs 21 vs 23%) (p = 0.03). Study size: 360. Study population/ethnicity: AML patients. /Caucasian Germans. Significance metric(s): Type of association: GN; CO; TOX; ADR
    www.ncbi.nlm.nih.gov/pubmed/19458626
  • [Drug Toxicity; Lung Neoplasms; Mesothelioma; Neutropenia; Pancreatic Neoplasms]
    [carboplatin; cisplatin; fluorouracil; gemcitabine]
    Risk or phenotype-associated allele: CDA*3 and CDA*2 haplotypic alleles (defined by combined SNPs: rs2072671 c.79A p.Lys27, and rs60369023 c.208G p.Ala70) Phenotype: The CDA*3 haplotype (c.79A, p.Lys27/ c.208A, p.Thr70) was associated with increased incidences of grade 3 or higher neutropenia, and decreased clearance of gemcitabine ( p = 0.0017, n = 177) in the patients receiving gemcitabine with fluorouracil (p = 0.029, n = 14), cisplatin (p = 0.030, n = 30), or carboplatin (p = 0.033, n = 16). The CDA*2 haplotype (c.79C, p.Gln27/ c.208G, p.Ala70) showed no significant effect on gemcitabine pharmacokinetics. Study size: subsets of 256. Study population/ethnicity: Patients with pancreatic, lung or mesothelium carcinoma. /Japanese Significance metric(s): p less than 0.03. Type of association: PK; CO; TOX; ADR
    www.ncbi.nlm.nih.gov/pubmed/17194903
    PolyPhen-2
  • Score: 0 (benign)

Other in silico analyses
 

  • NBLOSUM100 score = –2
  • GET-Evidence autoscore = 1

Edit history
 

Gene search

"GENE" or "GENE A123C":

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