ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000015.9) (NC_000015.10)
  • Haploinsufficiency score: 2
  • Strength of Evidence (disclaimer): Some evidence for dosage pathogenicity
Evidence for haploinsufficiency phenotype
PubMed ID Description
20425846 Crowley, et al. (2010) report a male infant born with cleft palate, ventricular septal defect, and bilateral hearing loss who had a de novo mosaic 123 kilobase deletion of exon 9 on the MEIS2 gene. This deletion was predicted to result in a frameshift and truncated protein. The deletion was estimated to be present in about 40% of cells.
24678003 Johansson, et al. (2014) report three siblings and their mother who had cleft palate, delayed motor skills, and intellectual disability. They were all found to carry a 58 kilobase intragenic tandem duplication which leads to a frameshift. The duplication occurred de novo in the mother. The authors also report individuals from four other families with deletions ranging from 0.6-4.8 Mb that include MEIS2. All of these individuals had cleft palate, all but one had intellectual disability and delayed motor skills, one had a cleft lip, and three had ventricular septal defects.

Haploinsufficiency phenotype comments:

The evidence for haploinsufficiency of MEIS2 is considered to be emerging at this time. Current evidence includes two focal MEIS2 alterations, predicted to result in a loss of function for this gene, as well as several non-focal deletions (1.6-5.6 Mb) encompassing MEIS2 and additional genes that have been identified in patients with similar clinical findings, including intellectual disability, delayed motor development, orofacial clefting and/or cardiac malformations (PMIDs:17163532, 18458017, 21504564).

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