TERT A279T - GET-Evidence

Curation:
Currentness:

TERT A279T

(TERT Ala279Thr)


Short summary

Reported as a rare but probably nonpathogenic polymorphism occurring in controls as well as patients. Other defects in this gene are associated with telomere shortening which may cause aplastic anemia or dyskeratosis congenita.

Variant evidence
Computational

Polyphen 2 predicts “possibly damaging” (ambiguous result)

Functional -
Case/Control 3

Same allele frequency in patients and controls

See Yamaguchi H et al. 2005 (15814878).

Familial

No familial data

 
Clinical importance
Severity -
Treatability -
Penetrance -
 

Impact

Low clinical importance, Uncertain benign

(The "low clinical importance, uncertain" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

undefined

Summary of published research, and additional commentary

 

Allele frequency

  • T @ chr5:1294166: 2.0% (214/10698) in EVS
  • Frequency shown in summary reports: 2.0% (214/10698)

Publications
 

Yamaguchi H, Calado RT, Ly H, Kajigaya S, Baerlocher GM, Chanock SJ, Lansdorp PM, Young NS. Mutations in TERT, the gene for telomerase reverse transcriptase, in aplastic anemia. N Engl J Med. 2005 Apr 7;352(14):1413-24. PubMed PMID: 15814878.

This study looked for mutations that may be associated with short telomeres, causing aplastic anemia. This particular variant was seen in both patients (6 in 200) and controls (10 in 528); the authors classify it as a nonpathogenic polymorphism.

Du HY, Pumbo E, Ivanovich J, An P, Maziarz RT, Reiss UM, Chirnomas D, Shimamura A, Vlachos A, Lipton JM, Goyal RK, Goldman F, Wilson DB, Mason PJ, Bessler M. TERC and TERT gene mutations in patients with bone marrow failure and the significance of telomere length measurements. Blood. 2009 Jan 8;113(2):309-16. Epub 2008 Oct 17. PubMed PMID: 18931339; PubMed Central PMCID: PMC2615648.

Because other studies report the A279T variant present in controls at a similar level, these authors concluded it is a rare single nucleotide polymorphisms unlikely to cause or contribute to the disease they were studying (bone marrow failure due to shortened telomeres).

Genomes
 

huC30901 - CGI sample GS00253-DNA_B01_200_37
het T @ chr5:1294166

 

Other external references
 

    dbSNP
  • rs61748181
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    GeneTests
  • GeneTests records for the TERT gene
    Idiopathic pulmonary fibrosis
    Aplastic Anemia
    Dyskeratosis Congenita
    Familial Pulmonary Fibrosis
    TERT-Related Dyskeratosis Congenita
    www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/TERT
    PolyPhen-2
  • Score: 0.778 (possibly damaging)
    Web search results (8 hits -- see all)
  • Blood -- TERC and TERT gene mutations in patients with bone ...
    TERC and TERT gene mutations in patients with bone marrow failure and the significance of ... and the G835A (A279T) or C1234T (H412Y) TERT gene variants, in ...
    bloodjournal.hematologylibrary.org/cgi/content/full/113/...
  • Blood -- Functional characterization of natural telomerase ...
    ... are indicated in black, whereas the A279T variant that has also been identified in ... reverse transcriptase component of telomerase (TERT) in patients with bone marrow failure. ...
    bloodjournal.hematologylibrary.org/cgi/content/full/109/...
  • Catalogue of Somatic Mutations in Cancer
    p.A279T. c.835G>A. Confirmed somatic variant. Homozygous. 753582. MMP3. p.A342A. c.1026C>T ... TERT. p.V299L. c.895G>T. Confirmed somatic variant. Heterozygous. 753582 ...
    sanger.ac.uk/perl/genetics/CGP/...?action=sample&id=753582
  • Cancer Genome Project Data
    p.A279T. c.835G>A. Confirmed somatic variant. Homozygous. 753582. MMP3. p.A342A. c.1026C>T ... TERT. p.V299L. c.895G>T. Confirmed somatic variant. Heterozygous. 753582 ...
    sanger.ac.uk/perl/genetics/CGP/cgp_viewer?action=sample&...
  • Paper: High Prevalence of TERT Mutations in Chronic ...
    3126 High Prevalence of TERT Mutations in Chronic Lymphocytic Leukemia ... the 80 CLL patients carried the A279T TERT variant but this allele was also present in ...
    ash.confex.com/ash/2008/webprogram/Paper11162.html

Other in silico analyses
 

  • NBLOSUM100 score = 1
  • GET-Evidence autoscore = 4

Edit history
 

Gene search

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