AURKA F31I - GET-Evidence

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

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Curation:
Currentness:

AURKA F31I

(AURKA Phe31Ile)


Short summary

The AURKA (STK15) 91T->A variant is preferentially amplified and linked to the degree of aneuploidy in colon tumors. The variant is a low-penetrance cancer susceptibility allele associated with multiple cancer types.

Variant evidence
Computational -
Functional -
Case/Control 4

Report OR of 1.4 for 91A homozygotes (95% CI of 1.22—1.59, P-value < 0.001) and 1.10 for heterozygotes (95% CI 1.03—1.18, P-value = 0.006).

See Ewart-Toland A et al. 2005 (15802297).

Familial -
 
Clinical importance
Severity -
Treatability -
Penetrance -
 

Impact

Insufficiently evaluated pathogenic

(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

  • T @ chr20:54961541: 18.8% (2018/10758) in EVS
  • T @ chr20:54394947: 23.4% (30/128) in GET-Evidence
  • Frequency shown in summary reports: 18.8% (2018/10758)

Publications
 

Ewart-Toland A, Briassouli P, de Koning JP, Mao JH, Yuan J, Chan F, MacCarthy-Morrogh L, Ponder BA, Nagase H, Burn J, Ball S, Almeida M, Linardopoulos S, Balmain A. Identification of Stk6/STK15 as a candidate low-penetrance tumor-susceptibility gene in mouse and human. Nat Genet. 2003 Aug;34(4):403-12. PubMed PMID: 12881723.

Based on mouse studies, AURKA (STK15) was identified as a candidate skin tumor susceptibility gene. STK15 is frequently amplified in human colon cancers and other tumor types. The authors identified the STK15 91T->A variant and showed “statistically significant allele-specific amplification of the 91A allele (P = 0.018, chi squared test), providing additional evidence for the role of this allele in human cancer”. Individuals with even one copy of the 91A allele develop tumors with a higher degree of aneuploidy than homozygous 91T individuals.

Ewart-Toland A, Dai Q, Gao YT, Nagase H, Dunlop MG, Farrington SM, Barnetson RA, Anton-Culver H, Peel D, Ziogas A, Lin D, Miao X, Sun T, Ostrander EA, Stanford JL, Langlois M, Chan JM, Yuan J, Harris CC, Bowman ED, Clayman GL, Lippman SM, Lee JJ, Zheng W, Balmain A. Aurora-A/STK15 T+91A is a general low penetrance cancer susceptibility gene: a meta-analysis of multiple cancer types. Carcinogenesis. 2005 Aug;26(8):1368-73. Epub 2005 Mar 31. PubMed PMID: 15802297.

Meta-analysis confirmed that the 91A polymorphism is a low-penetrance cancer susceptibility allele in several cancer types, with greater risk for the 91A homozygotes. When the results were combined in a meta-analysis, the authors “found an OR of 1.4 for the T+91A homozygotes (95% CI of 1.22—1.59, P-value < 0.001)” and a “modest but significant increase in risk in the T+91A heterozygotes (OR = 1.10, 95% CI 1.03—1.18, P-value = 0.006)”.

Genomes
 

hu025CEA - CGI sample GS01669-DNA_D02 from PGP sample 27316983
het T @ chr20:54961541

 

hu034DB1 - CGI sample GS00253-DNA_A02_200_37
het T @ chr20:54961541

 

hu2DBF2D - CGI sample GS01173-DNA_G02 from PGP sample 67180598
het T @ chr20:54961541

 

hu38168C - CGI sample GS01173-DNA_H06 from PGP sample 91708424
hom T @ chr20:54961541

 

 

hu3CAB43 - CGI sample GS01175-DNA_D03 from PGP sample 27486199
het T @ chr20:54961541

 

hu4CA5B9 - CGI sample GS01669-DNA_B03 from PGP sample 14427241
het T @ chr20:54961541

 

hu92C40A - CGI sample GS01175-DNA_G03 from PGP sample 92527586
het T @ chr20:54961541

 

hu92FD55 - CGI sample GS01669-DNA_A04 from PGP sample 08188426
hom T @ chr20:54961541

 

huAE4A11 - CGI sample GS01669-DNA_F02 from PGP sample 40767107
het T @ chr20:54961541

 

huD37D14 - CGI sample GS01175-DNA_A04 from PGP sample 13272228
het T @ chr20:54961541

 

huD81F3D - CGI sample GS01173-DNA_D06 from PGP sample 69488604
hom T @ chr20:54961541

 

GS18501 - var-GS18501-1100-36-ASM
het T @ chr20:54394948

 

GS18505 - var-GS18505-1100-36-ASM
het T @ chr20:54394948

 

GS18517 - var-GS18517-1100-36-ASM
het T @ chr20:54394948

 

GS18526 - var-GS18526-1100-36-ASM
het T @ chr20:54394948

 

GS18537 - var-GS18537-1100-36-ASM
hom T @ chr20:54394948

 

GS18555 - var-GS18555-1100-36-ASM
hom T @ chr20:54394948

 

GS18940 - var-GS18940-1100-36-ASM
hom T @ chr20:54394948

 

GS18942 - var-GS18942-1100-36-ASM
het T @ chr20:54394948

 

GS18947 - var-GS18947-1100-36-ASM
hom T @ chr20:54394948

 

GS18956 - var-GS18956-1100-36-ASM
het T @ chr20:54394948

 

GS19020 - var-GS19020-1100-36-ASM
het T @ chr20:54394948

 

GS19025 - var-GS19025-1100-36-ASM
het T @ chr20:54394948

 

GS19129 - var-GS19129-1100-36-ASM
het T @ chr20:54394948

 

GS19238 - var-GS19238-1100-36-ASM
hom T @ chr20:54394948

 

GS19240 - var-GS19240-1100-36-ASM
het T @ chr20:54394948

 

GS19704 - var-GS19704-1100-36-ASM
het T @ chr20:54394948

 

GS19735 - var-GS19735-1100-36-ASM
het T @ chr20:54394948

 

GS19834 - var-GS19834-1100-36-ASM
het T @ chr20:54394948

 

GS20509 - var-GS20509-1100-36-ASM
het T @ chr20:54394948

 

GS21767 - var-GS21767-1100-36-ASM
hom T @ chr20:54394948

 

Other external references
 

    dbSNP
  • rs2273535
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi

Other in silico analyses
 

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

Edit history
 

Gene search

"GENE" or "GENE A123C":

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