CASP10 V410I - GET-Evidence

Curation:
Currentness:

CASP10 V410I

(CASP10 Val410Ile)


Short summary

Reported to have a protective effect on breast cancer. If the lifetime risk of breast cancer is 12%, women with this variant may have a lower risk of 8-9% (30% less than average).

Variant evidence
Computational 1

Polyphen 2 supports functional effect

Functional -
Case/Control 4

p=.004

Familial
 
Clinical importance
Severity 3

Breast cancer

Treatability 3

Screening and surgery reduce mortality

Penetrance 2

See Frank B et al. 2006 (16251207).

 

Impact

Low clinical importance, Likely protective

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

Inheritance pattern

dominant

Summary of published research, and additional commentary

 

Allele frequency

  • A @ chr2:202074098: 4.7% (510/10758) in EVS
  • A @ chr2:201782342: 2.3% (3/128) in GET-Evidence
  • Frequency shown in summary reports: 4.7% (510/10758)

Publications
 

Wang J, Zheng L, Lobito A, Chan FK, Dale J, Sneller M, Yao X, Puck JM, Straus SE, Lenardo MJ. Inherited human Caspase 10 mutations underlie defective lymphocyte and dendritic cell apoptosis in autoimmune lymphoproliferative syndrome type II. Cell. 1999 Jul 9;98(1):47-58. PubMed PMID: 10412980.

The variant was found in a homozygous state in a male with Autoimmune lymphoproliferative syndrome type II. Onset was at 11 months. Both parents were heterozygous for the mutation which was not seen in 440 alleles, 200 of which were matched to the probands Ashkenazi Jewish ethnicity. Two families are described in the paper and are numbered “11” and “36”; a best case scenario assumes a total of 36 families screened, giving case/control data: case+: 1, case-: 35, control+: 0, control-: 220 — this is not significant.

Based on allele frequency data and on the later report from Frank et al., which has several homozygous controls, the hypothesis from this paper must be incorrect.

Frank B, Hemminki K, Wappenschmidt B, Meindl A, Klaes R, Schmutzler RK, Bugert P, Untch M, Bartram CR, Burwinkel B. Association of the CASP10 V410I variant with reduced familial breast cancer risk and interaction with the CASP8 D302H variant. Carcinogenesis. 2006 Mar;27(3):606-9. Epub 2005 Oct 26. PubMed PMID: 16251207.

This case/control study investigates the association of this polymorphism and the D302H with breast cancer.

controls — wt/wt: 456, wt/var: 85, var/var: 6
cases — wt/wt: 455, wt/var: 55, var/var: 1

Using Cochran-Armitage trend test, p=0.0039. Assuming a 12% lifetime risk of developing breast cancer, we estimate the risk associated with the variant is 3-4% lower (~8-9% instead of 12%).

Genomes
 

hu011C57 - CGI sample GS01669-DNA_B05 from PGP sample 86486261
het A @ chr2:202074098

 

hu0D879F - CGI sample GS00253-DNA_G01_200_37
het A @ chr2:202074098

 

hu241DEA - CGI sample GS01175-DNA_D05 from PGP sample 1205491
het A @ chr2:202074098

 

hu342A08 - CGI sample GS01175-DNA_B05 from PGP sample 83494370
het A @ chr2:202074098

 

hu4CA5B9 - CGI sample GS01669-DNA_B03 from PGP sample 14427241
het A @ chr2:202074098

 

hu8229AE - CGI sample GS01173-DNA_A07 from PGP sample 96240009
hom A @ chr2:202074098

 

huA0E089 - CGI sample GS01175-DNA_B04 from PGP sample 88590671
het A @ chr2:202074098

 

huB1FD55 - CGI sample GS01173-DNA_B07 from PGP sample 61499538
het A @ chr2:202074098

 

Other external references
 

    dbSNP
  • rs13010627
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    GeneTests
  • GeneTests records for the CASP10 gene
    Autoimmune Lymphoproliferative Syndrome
    CASP10-Related Autoimmune Lymphoproliferative Syndrome
    www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/CASP10
    PolyPhen-2
  • Score: 0.874 (probably damaging)
    Web search results (112 hits -- see all)
  • Association of the CASP10 V410I variant with reduced familial ...
    CASP10 V410I is associated with a reduced familial BC risk ... CASP10 V410I is located five amino. acids upstream of this cleavage site as well as seven ...
    carcin.oxfordjournals.org/cgi/reprint/27/3/606.pdf
  • Association of the CASP10 V410I variant with reduced familial ...
    CASP10 V410I is associated with a reduced familial BC risk ... CASP10 V410I is located five amino acids upstream of this cleavage site as well as seven amino acids ...
    carcin.oxfordjournals.org/cgi/content/full/27/3/606
  • WikiGenes - CASP10 - caspase 10, apoptosis-related cysteine...
    The world's first wiki where authorship really matters. Due credit and reputation for ... Association of the CASP10 V410I variant with reduced familial breast cancer risk and ...
    www.wikigenes.org/e/gene/e/843.html
  • Wappenschmidt, B (Barbara)
    Association of the CASP10 V410I variant with reduced familial breast cancer risk and interaction with the CASP8 D302H variant. Association of ...
    lib.bioinfo.pl/auid:82492
  • Frank, B (Bernd)
    Frank, B (Bernd) :: The effects of proprioceptive stimulation on cognitive processes in ... Association of the CASP10 V410I variant with reduced familial breast cancer risk and ...
    lib.bioinfo.pl/auid:82487
  • CiteULike: Association of the CASP10 V410I variant with ...
    Association of the CASP10 V410I variant with reduced familial breast cancer risk and interaction with the CASP8 D302H variant Export Find Similar ...
    www.citeulike.org/article/526197
  • Re: Association of a Common Variant of the CASP8 Gene With ...
    JNCI Journal of the National Cancer Institute 2005 97(13):1012; doi:10.1093/jnci/dji178 ... Association of the CASP10 V410I variant with reduced familial breast cancer risk and ...
    jnci.oxfordjournals.org/cgi/content/short/97/13/1012
  • Institut f├╝r Humangenetik: Liste 2005 - Universit├Ątsklinikum ...
    DNA polymorphisms of the prion doppel gene region in four different German cattle breeds and cows tested ... Association of the CASP10 V410I variant with familial breast cancer ...
    www.klinikum.uni-heidelberg.de/index.php?6792&type=1&L=0
  • Caspase-10 Sensitizes Breast Carcinoma Cells to TRAIL-Induced ...
    Alert me when this article is cited. Alert me if a correction is ... Association of the CASP10 V410I variant with reduced familial breast cancer risk and ...
    mcb.asm.org/cgi/content/short/25/7/2808
  • T1DBase - CASP10 Gene Overview
    Below is the interaction network for CASP10. To modify the display, click on an ... Association of the CASP10 V410I variant with reduced familial breast cancer risk and ...
    www.t1dbase.org/page/GeneOverview/display/?gene_id=843

Other in silico analyses
 

  • NBLOSUM100 score = –4
  • GET-Evidence autoscore = 5

Edit history
 

Gene search

"GENE" or "GENE A123C":

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