ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000001.10) (NC_000001.11)
  • Haploinsufficiency score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Haploinsufficiency phenotype comments:

Variants in MFN2 have been associated with Charcot-Marie-Tooth disease Type 2A and hereditary motor and sensory neuropathy type VI. Per GeneReviews (, the mechanism of disease is currently unknown. Most of the known pathogenic variants associated with these conditions are missense, though a few frameshift and nonsense variants have been reported. For example, Verhoeven et al. (2006) (PMID:16714318) reported two nonsense variants (one of which was observed in two unrelated individuals) and one small in-frame deletion. Of note, the nonsense variant observed in two different individuals was in the last exon of the gene. Additionally, there have been reports of CMT Type 2A being inherited in an autosomal recessive manner, with individuals having one nonsense or exonic deletion and one known pathogenic missense variant in trans (see PMIDs 26114802, 26306937). In Piscosquito et al. 2015 (PMID: 26306937), the authors propose that haploinsufficiency of MFN2 alone is not sufficient to cause disease, but may contribute to disease when inherited with another functionally altered MFN2 allele.

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