TYK2 A928V - GET-Evidence

Curation:
Currentness:

TYK2 A928V

(TYK2 Ala928Val)


Short summary

Probably benign.

Variant evidence
Computational -1

Polyphen 2 predicts damaging effect

Functional -
Case/Control 3

1.2% allele frequency suggests no severe pathogenic effect for this variant (would have been reported by now).

See Tomasson MH et al. 2008 (18270328).

Familial -
 
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

unknown

Summary of published research, and additional commentary

 

Allele frequency

  • A @ chr19:10464843: 0.6% (63/10758) in EVS
  • A @ chr19:10325842: 0.8% (1/128) in GET-Evidence
  • Frequency shown in summary reports: 0.6% (63/10758)

Publications
 

Tomasson MH, Xiang Z, Walgren R, Zhao Y, Kasai Y, Miner T, Ries RE, Lubman O, Fremont DH, McLellan MD, Payton JE, Westervelt P, DiPersio JF, Link DC, Walter MJ, Graubert TA, Watson M, Baty J, Heath S, Shannon WD, Nagarajan R, Bloomfield CD, Mardis ER, Wilson RK, Ley TJ. Somatic mutations and germline sequence variants in the expressed tyrosine kinase genes of patients with de novo acute myeloid leukemia. Blood. 2008 May 1;111(9):4797-808. Epub 2008 Feb 12. PubMed PMID: 18270328; PubMed Central PMCID: PMC2343607.

This variant (among others) is reported in a study of acute myeloid leukemia cases, no enrichment for the variant was seen in AML cases vs. controls. Controls were /: 172, +/var: 4, var/var:0 and AML cases were /: 183, +/var: 5, and var/var: 0.

These numbers suggest an allele frequency for this variant of 1.2%.

Genomes
 

hu604D39 - CGI sample GS00253-DNA_B02_200_37
het A @ chr19:10464843

 

Other external references
 

    dbSNP
  • rs35018800
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PolyPhen-2
  • Score: 0.999 (probably damaging)
    Web search results (8 hits -- see all)
  • Non-receptor tyrosine-protein kinase TYK2 - Homo sapiens (Human)
    TYK2. Organism. Homo sapiens (Human) [Complete proteome] Taxonomic ... in TYK2 are the cause of protein-tyrosine kinase 2 deficiency (TYK2 deficiency) ...
    www.uniprot.org/uniprot/P29597
  • Blood -- Somatic mutations and germline sequence variants in ...
    TYK2 protein analysis. Parental 2fTGH cells and TYK2-deficient U1A cells were culture in ... TYK2 alleles, U1A cells were transduced with cDNAs encoding wild-type TYK2 and TYK2 ...
    bloodjournal.hematologylibrary.org/cgi/content/full/.../4797
  • Data Mining the Genetics of Leukemia
    Acute Lymphoblastic Leukemia (ALL) is the most common cancer in ... the age of 15. At present, diagnosis, prognosis and treatment decisions are made. based ...
    qspace.library.queensu.ca/bitstream/1974/5390/1/...
  • UniProt: TYK2_HUMAN
    RN [9] RP INVOLVEMENT IN TYK2 DEFICIENCY. RX PubMed=17088085; DOI=10. ... TYK2 are the cause of protein-tyrosine kinase CC 2 deficiency (TYK2 deficiency) ...
    www.genome.jp/dbget-bin/www_bget?uniprot:TYK2_HUMAN
  • Probability KinBase Name ENSEMBL ID
    TYK2. ENSG00000105397. rs35018800. 928. A. V. 3089. C. T. 2. GCG. GTG. kinase. 80. 0.809. ALK ... TYK2. ENSG00000105397. rs34536443. 1104. P. A. 3616. C. G. 1. CCC. GCC. kinase. 92 ...
    bioinformatics.oxfordjournals.org/content/vol0/issue2007/...
  • Somatic mutations and germline sequence variants in the ...
    TYK2 protein analysis. Parental 2fTGH cells and TYK2-deļ¬cient U1A cells were culture in ... transduced with cDNAs encoding wild-type TYK2 and TYK2 alleles ...
    bloodjournal.hematologylibrary.org/cgi/reprint/.../4797.pdf

Other in silico analyses
 

  • NBLOSUM100 score = 2
  • GET-Evidence autoscore = 3

Edit history
 

Gene search

"GENE" or "GENE A123C":

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