EDNRB Y293Shift - GET-Evidence

Curation:
Currentness:

EDNRB Y293Shift

(EDNRB 293delYinsShift)


Short summary

Reported as “EDNRB, 1-BP INS, 878T” in OMIM, this frameshift variant has been reported to cause increased susceptibility to Hirschsprung’s disease (partial lack of nerves in the bowel, potentially leading to severe constipation and digestive issues). It may also be associated with Waardenburg syndrome type 4 in a recessive or incomplete-dominance manner.

Variant evidence
Computational 3

Frameshift predicted to be severely disruptive.

Functional -
Case/Control

Reported data is insufficient to evaluate statistical significance.

See Kusafuka T et al. 1996 (8852658).

Familial -
 
Clinical importance
Severity 4
Treatability 3
Penetrance 3

Penetrance unclear. Puffenberger et al report that heterozygotes for W276C in the Mennonite population have a penetrance of around 20% for Hirschsprung’s disease.

 

Impact

Moderate clinical importance, Uncertain pathogenic

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

Inheritance pattern

other

Summary of published research, and additional commentary

Puffenberger et al. 1994 “A missense mutation of the endothelin-B receptor gene in multigenic Hirschsprung’s disease.” http://www.ncbi.nlm.nih.gov/pubmed/8001158

Allele frequency

  • None available.

Publications
 

Kusafuka T, Wang Y, Puri P. Novel mutations of the endothelin-B receptor gene in isolated patients with Hirschsprung's disease. Hum Mol Genet. 1996 Mar;5(3):347-9. PubMed PMID: 8852658.

This variant is reported here as an insertion of T at nucleotide 878. This variant was seen heterozygously in one of two patents with Hirschsprung’s disease that were examined.

Genomes
 

Other external references
 

    GeneTests
  • GeneTests records for the EDNRB gene
    Hirschsprung Disease
    Waardenburg Syndrome Type IV
    EDNRB-Related Hirschsprung Disease
    www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/EDNRB

Other in silico analyses
 

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

Edit history
 

Gene search

"GENE" or "GENE A123C":

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