PKD2 S804N - GET-Evidence

Curation:
Currentness:

PKD2 S804N

(PKD2 Ser804Asn)


Short summary

Predicted to cause autosomal dominant polycystic kidney disease, but without control allele frequency the report cannot be tested for statistical significance.

Variant evidence
Computational 2

Polyphen 2 and Rossetti et al. predict damaging effect.

Functional -
Case/Control

Without controls from Rossetti et al, cannot assess significance

See Rossetti S et al. 2007 (17582161).

Familial -
 
Clinical importance
Severity 4
Treatability 1
Penetrance 5

GeneTests describes very high penetrance

 

Impact

High clinical importance, Uncertain pathogenic

(The "high clinical importance, uncertain" 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 @ chr4:88989102: 0.3% (28/10758) in EVS
  • A @ chr4:89208125: 0.8% (1/128) in GET-Evidence
  • Frequency shown in summary reports: 0.3% (28/10758)

Publications
 

Rossetti S, Consugar MB, Chapman AB, Torres VE, Guay-Woodford LM, Grantham JJ, Bennett WM, Meyers CM, Walker DL, Bae K, Zhang QJ, Thompson PA, Miller JP, Harris PC; CRISP Consortium. Comprehensive molecular diagnostics in autosomal dominant polycystic kidney disease. J Am Soc Nephrol. 2007 Jul;18(7):2143-60. Epub 2007 Jun 20. PubMed PMID: 17582161.

In analysis of various polycystic kidney disease variants, the authors describe this variant as “likely pathogenic”, classifying it in mutation group C (as opposed to “definite” or “highly likely”).

They report the variant as novel, found once in a screen of 202 families. The number of controls examined, if any, is unknown.

Streets AJ, Needham AJ, Gill SK, Ong AC. Protein kinase D-mediated phosphorylation of polycystin-2 (TRPP2) is essential for its effects on cell growth and calcium channel activity. Mol Biol Cell. 2010 Nov 15;21(22):3853-65. Epub 2010 Sep 29. PubMed PMID: 20881056; PubMed Central PMCID: PMC2982124.

Functional studies determine that this mutation disrupts phosphorylation but uncritically assumes the mutation is pathogenic.

Genomes
 

hu604D39 - CGI sample GS00253-DNA_B02_200_37
het A @ chr4:88989102

 

Other external references
 

    GeneTests
  • GeneTests records for the PKD2 gene
    Polycystic Kidney Disease, Autosomal Dominant
    Polycystic Kidney Disease 2, Autosomal Dominant
    www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/PKD2
    PolyPhen-2
  • Score: 0.875 (probably damaging)

Other in silico analyses
 

  • NBLOSUM100 score = 0
  • GET-Evidence autoscore = 5

Edit history
 

Gene search

"GENE" or "GENE A123C":

Log in