ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000012.11) (NC_000012.12)
Evidence for haploinsufficiency phenotype
PubMed ID Description
24741995 Behlouli et al. 2014 studied a consanguineous Algerian family with 2 affecteds having congenital sensorineural hearing loss. GJB2, OTOF and MYO15A were excluded as the cause of hearing loss. Whole exome sequencing was performed and revealed a homozygous nonsense c.88C>T, p.Gln30X variant in the EPS8 gene. The variant was not present in 120 Algerian controls. Evidence for pathogenicity of this variant came from Manor et al. 2011 and Zambini et al. 2011 mice models.
27344577 Yan et al. 2016 studied 342 GJB2 variant-negative families and found a family of Tunisian decent with prelingual hearing loss and a homozygous c.115delA p.Thr39GlnfsX32 variant in EPS8.

Haploinsufficiency phenotype comments:

Only two variants, both loss of function and both homozygous, have been reported in the EPS8 gene (Yan et al. 2016, Behlouli et al. 2014). The overall evidence that EPS8, when altered, causes autosomal recessive nonsyndromic hearing loss has been Expert reviewed as Moderate by the ClinGen Hearing Loss Gene Curation Working Group. Based on the lack of autosomal dominant loss of function variants reported in this gene, it receives a haploinsufficiency score of 30: Gene associated with autosomal recessive phenotype.

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity