ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000019.9) (NC_000019.10)
  • Haploinsufficiency score: 1
  • Strength of Evidence (disclaimer): Little evidence for dosage pathogenicity
Evidence for haploinsufficiency phenotype
PubMed ID Description
Nowaczyk et al. (2014) report a patient with a de novo ~60 kb deletion that encompasses at least 6 exons (2-7) of MAP2K2. The authors also report 8 other individuals with non-focal deletions (0.39-1.93 Mb) that encompass part or all of MAP2K2, as well as additional genes. The patient with the focal deletion presented with failure to thrive, intellectual disability, developmental delay, craniofacial abnormalities, gastrointestinal anomalies, cardiac anomalies, hypotonia, and other dysmorphic features. Patients with non-focal deletions were also found to have these phenotypic abnormalities, and in addition were found to present with sleep apnea and additional dysmorphic features.

Haploinsufficiency phenotype comments:

At this time there is a limited evidence to support the haploinsufficiency of MAP2K2. Current evidence includes a single patient with a focal deletion of MAP2K2 as well as several patients with non-focal deletions (0.39-1.98Mb) that encompass MAP2K2 and additional genes. Patients with deletions encompassing MAP2K2 were found to have similar clinical findings, including failure to thrive, craniofacial anomalies, intellectual disability, developmental delay, speech delay, gastrointestinal anomalies, hypotonia, sleep apnea, cardiac anomalies, and other dysmorphic features (PMIDs: 23379592, 23610052, and 21108400). Missense mutations in MAP2K2 have also been associated with Cardio-facio-cutaneous syndrome (OMIM: 615280); however, these mutations are thought to result in a gain-of-function.

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