PKD2 S804N - GET-Evidence


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 -

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



High clinical importance, Uncertain pathogenic

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

Inheritance pattern


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)


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.


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


Other external references

  • GeneTests records for the PKD2 gene
    Polycystic Kidney Disease, Autosomal Dominant
    Polycystic Kidney Disease 2, Autosomal Dominant
  • Score: 0.875 (probably damaging)

Other in silico analyses

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

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Gene search

"GENE" or "GENE A123C":

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