DSPP R68W - GET-Evidence

Curation:
Currentness:

DSPP R68W

(DSPP Arg68Trp)


Short summary

Probably benign. One report linked this to causing dentinogenesis Imperfecta type II in a large Swedish family, but subsequent publications have observed this is a common variant and conclude it is a nonpathogenic polymorphism.

Variant evidence
Computational -1

BLOSUM100 predicts disruptive effect, other variants in the gene associated with disease. Polyphen 2 score unavailable.

Functional -
Case/Control 3

Frequency of this variant allele supports no significant pathogenic effect

See Acevedo AC et al. 2009 (18797159), unpublished research (below).

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

  • T @ chr4:88533540: 14.3% (1413/9878) in EVS
  • T @ chr4:88752563: 17.2% (22/128) in GET-Evidence
  • Frequency shown in summary reports: 14.3% (1413/9878)

Publications
 

Malmgren B, Lindskog S, Elgadi A, Norgren S. Clinical, histopathologic, and genetic investigation in two large families with dentinogenesis imperfecta type II. Hum Genet. 2004 Apr;114(5):491-8. Epub 2004 Feb 3. PubMed PMID: 14758537.

This variant was found segregating with Dentinogenesis Imperfecta type II in a large Swedish family. 6/14 affected and 10/56 unaffected were genotyped and the variant was shown to segregate with disease. LOD score is not reported, we calculate it to be 3.6. Controls are not reported.

Kim JW, Simmer JP. Hereditary dentin defects. J Dent Res. 2007 May;86(5):392-9. Review. PubMed PMID: 17452557.

Review article. Other variants in DSPP covered that have been reported to cause the disease.

Acevedo AC, Santos LJ, Paula LM, Dong J, MacDougall M. Phenotype characterization and DSPP mutational analysis of three Brazilian dentinogenesis imperfecta type II families. Cells Tissues Organs. 2009;189(1-4):230-6. Epub 2008 Sep 16. PubMed PMID: 18797159; PubMed Central PMCID: PMC2824200.

Cites Holappa et al. 2006, Hart and Hart 2007, and dbSNP data as showing allele frequencies of 6-16%, concluding “Collectively, these findings and the data present in our study suggest that this variation is a polymorphism and not a mutation associated with the pathogenesis of DGI-II.”

Genomes
 

 

 

hu604D39 - CGI sample GS00253-DNA_B02_200_37
het T @ chr4:88533540

 

 

huE80E3D - CGI sample GS00253-DNA_D01_200_37
het T @ chr4:88533540

 

GS18501 - var-GS18501-1100-36-ASM
hom T @ chr4:88752564

 

GS18502 - var-GS18502-1100-36-ASM
het T @ chr4:88752564

 

GS18504 - var-GS18504-1100-36-ASM
het T @ chr4:88752564

 

GS18508 - var-GS18508-1100-36-ASM
het T @ chr4:88752564

 

GS19025 - var-GS19025-1100-36-ASM
het T @ chr4:88752564

 

GS19026 - var-GS19026-1100-36-ASM
het T @ chr4:88752564

 

GS19129 - var-GS19129-1100-36-ASM
hom T @ chr4:88752564

 

GS19239 - var-GS19239-1100-36-ASM
het T @ chr4:88752564

 

GS19240 - var-GS19240-1100-36-ASM
het T @ chr4:88752564

 

GS19701 - var-GS19701-1100-36-ASM
het T @ chr4:88752564

 

GS19703 - var-GS19703-1100-36-ASM
het T @ chr4:88752564

 

GS19834 - var-GS19834-1100-36-ASM
het T @ chr4:88752564

 

GS21767 - var-GS21767-1100-36-ASM
het T @ chr4:88752564

 

Other external references
 

    dbSNP
  • rs36094464
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi

Other in silico analyses
 

  • NBLOSUM100 score = 7
  • GET-Evidence autoscore = 2

Edit history
 

Gene search

"GENE" or "GENE A123C":

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