EGFR R521K - GET-Evidence

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

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Curation:
Currentness:

EGFR R521K

(EGFR Arg521Lys)


Short summary

This variant improves tretability and reduces risk to develop CRC colorectal cancer.

Variant evidence
Computational 1

PolyPhen2: Benign, score 0.000
SIFT: Tolerated 0.36
GVGD: GV 70.97; GD 25.51; Class C0
Variant Effect Predictor (Ensembl):
SIFT=tolerated(0.29);
PolyPhen=benign(0);
Condel=deleterious(0.716)
Mutation Tasting Prediction: Polymorphism, P value: 0.999669; protein features (might be) affected (aa 25-645 TOPO_DOM Extracellular gets lost; aa 390-600 REPEAT Approximate gets lost; aa 515-519 STRAND might get lost (downstream of altered splice site)

Functional -
Case/Control 3

See 21896992.

Familial -
 
Clinical importance
Severity -
Treatability 2

improves tretability and reduces risk to develop

See Gonçalves A et al. 2008 (18544172), 21896992.

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

  • A @ chr7:55229255: 20.3% (2189/10758) in EVS
  • A @ chr7:55196748: 12.9% (16/124) in GET-Evidence
  • Frequency shown in summary reports: 20.3% (2189/10758)

Publications
 

Gonçalves A, Esteyries S, Taylor-Smedra B, Lagarde A, Ayadi M, Monges G, Bertucci F, Esterni B, Delpero JR, Turrini O, Lelong B, Viens P, Borg JP, Birnbaum D, Olschwang S, Viret F. A polymorphism of EGFR extracellular domain is associated with progression free-survival in metastatic colorectal cancer patients receiving cetuximab-based treatment. BMC Cancer. 2008 Jun 10;8:169. PubMed PMID: 18544172; PubMed Central PMCID: PMC2432064.

 

Gao LB, Zhou B, Zhang L, Wei YS, Wang YY, Liang WB, Lv ML, Pan XM, Chen YC, Rao L. R497K polymorphism in epidermal growth factor receptor gene is associated with the risk of acute coronary syndrome. BMC Med Genet. 2008 Jul 30;9:74. PubMed PMID: 18664296; PubMed Central PMCID: PMC2515827.

 

Rebaï M, Kallel I, Hamza F, Charfeddine S, Kaffel R, Guermazi F, Rebaï A. Association of EGFR and HER2 polymorphisms with risk and clinical features of thyroid cancer. Genet Test Mol Biomarkers. 2009 Dec;13(6):779-84. PubMed PMID: 19860576.

 

Martinelli M, Ugolini G, Scapoli L, Rivetti S, Lauriola M, Mattei G, Rosati G, Montroni I, Manaresi A, Zattoni D, Taffurelli M, Solmi R. The EGFR R521K polymorphism influences the risk to develop colorectal cancer. Cancer Biomark. 2010-2011;8(2):61-5. doi: 10.3233/DMA-2011-0826. PubMed PMID: 21896992.

 

Genomes
 

 

 

 

 

 

 

 

 

hu43860C - CGI sample GS00253-DNA_A01_200_37
het A @ chr7:55229255

 

 

 

 

 

 

 

 

 

 

hu9385BA - CGI sample GS00253-DNA_E01_200_37
het A @ chr7:55229255

 

 

 

 

 

huE80E3D - CGI sample GS00253-DNA_D01_200_37
het A @ chr7:55229255

 

 

 

GS10851 - var-GS10851-1100-36-ASM
het A @ chr7:55196749

 

GS12004 - var-GS12004-1100-36-ASM
het A @ chr7:55196749

 

GS18555 - var-GS18555-1100-36-ASM
het A @ chr7:55196749

 

GS18942 - var-GS18942-1100-36-ASM
hom A @ chr7:55196749

 

GS18947 - var-GS18947-1100-36-ASM
hom A @ chr7:55196749

 

GS19735 - var-GS19735-1100-36-ASM
het A @ chr7:55196749

 

GS20509 - var-GS20509-1100-36-ASM
het A @ chr7:55196749

 

Other external references
 

    dbSNP
  • rs2227983
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PharmGKB
  • [Acute coronary syndrome]
    Risk or phenotype-associated allele: A (Lys) allele. Phenotype: Association with increased risk of acute coronary syndrome. Study size: 191 cases and 210 controls. Study population/ethnicity: Chinese acute coronary syndrome patients and age- and sex-matched controls. Significance metric(s): OR = 1.49; p = 0.006. Type of association: GN; CO.
    www.ncbi.nlm.nih.gov/pubmed/18664296
  • [Thyroid Neoplasms]
    Risk or phenotype-associated allele: none. Phenotype: No association with thyroid cancer, or clinicopathological characteristics such as thyroid-stimulating hormone level, off-thyroxin, serum thyroglobulin, tumor histology, metastasis, tumor status, tumor stage, and survival. Study size: 106 cases and 302 controls. Study population/ethnicity: Thyroid cancer patients and healthy individuals. Significance metric(s): not available in abstract. Type of association: CO; GN.
    www.ncbi.nlm.nih.gov/pubmed/19860576
    PolyPhen-2
  • Score: 0 (benign)
    Web search results (104 hits -- see all)
  • CANCER AND IMPORTANT MEDICAL NEWS: EGFR POLYMORPHISM AND SKIN ...
    The common EGFR-R521K genotype (G/G) was significantly associated with increased skin ... revealed an influence of the EGFR-R521K genotype on skin toxicity and ...
    cancerology.blogspot.com/2010/01/egfr-polymorphism-and-sk...
  • BioMed Central | Full text | A polymorphism of EGFR ...
    A polymorphism of EGFR extracellular domain is associated with ... No EGFR mutations were found but a variant of exon 13 (R521K) was observed in 12 patients, ...
    www.biomedcentral.com/1471-2407/8/169
  • A polymorphism of EGFR extracellular domain is associated ...
    A polymorphism of EGFR extracellular domain is associated with progression free ... No EGFR mutations were found but a variant of exon 13 (R521K) was observed in 12 patients, ...
    www.ncbi.nlm.nih.gov/pmc/articles/PMC2432064
  • BMC Cancer
    no EGFR amplification found, but high polysomy was noted in 2 patients, both of ... (Right) curves of patients with EGFR R521K variant and wild-type. ...
    www.biomedcentral.com/content/pdf/1471-2407-8-169.pdf
  • Imen Kallel
    Genetic Polymorphisms in the EGFR (R521K) and Estrogen Receptor (T594T) Genes, EGFR and ErbB-2 Protein Expression, and Breast Cancer Risk in Tunisia ...
    www.hindawi.com/52872736.html
  • BioText Search Engine
    ... in cancer cells with wild-type EGFR or tyrosine kinase domain-mutated EGFR by cetuximab and gefitinib. ... (OS) (Right) curves of patients with EGFR R521K variant and wild-type. ...
    biosearch.berkeley.edu/index.php?q=EGFR&...&sortedby=rel
  • BioPortfolio - clinical biochemistry tests eGFR Na Cr
    clinical biochemistry tests eGFR Na Cr - BioPortfolio ... Genetic Polymorphisms in the EGFR (R521K) and Estrogen Receptor ... To study correlation between clinical ...
    bioportfolio.com/search/clinical_biochemistry_tests_eGFR_...
  • Genetic Alterations in the Tyrosine Kinase Transcriptome of ...
    For epidermal growth factor receptor (EGFR) R521K, a relative overrepresentation of the EGFR K521 allele in cDNAs of normal control samples (55 ...
    cancerres.aacrjournals.org/cgi/content/full/67/23/11368
  • CANCER AND IMPORTANT MEDICAL NEWS: 3/1/2010
    The common EGFR-R521K genotype (G/G) was significantly associated with increased skin ... to show that EGFR mutation predicts benefit with EGFR tyrosine kinase inhibitors (TKIs) ...
    cancerology.blogspot.com/2010_01_03_archive.html
  • Genetic Alterations in the Tyrosine Kinase Transcriptome of ...
    receptor (EGFR) R521K, a relative overrepresentation of the EGFR ... column ) and heterozygous (HE ; light blue column ) carriers of EGFR R521K, ...
    cancerres.aacrjournals.org/cgi/reprint/67/23/11368.pdf

Other in silico analyses
 

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

Edit history
 

Gene search

"GENE" or "GENE A123C":

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