ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000015.9) (NC_000015.10)
  • Haploinsufficiency score: 1
  • Strength of Evidence (disclaimer): Little evidence for dosage pathogenicity

Haploinsufficiency phenotype comments:

This gene is located in the commonly deleted region associated with Prader Willi syndrome (and is imprinted, expressed from the paternal allele). Paternally truncating mutations in MAGEL2 cause Schaaf-Yang syndrome (Fountain et al., 2017, PMID 27195816; Jobling et al., 2018, PMID 29599419). However, it is unclear if the underlying mechanism of mutation is a dominant-negative effect as suggested by Fountain, et al. or if haploinsufficiency plays a role. There are two instances of whole gene deletions outside of the common Prader-Willi deletion. Kanber et al., 2009, PMID 19066619 reported 1 patient with an unbalanced X;15 translocation, resulting in a deletion of MAGEL2 and 2 other genes in a patient with intellectual disability and obesity. Buiting et al., 2014, PMID 24661356 reported a patient with a 3.9Mb deletion including MAGEL2 with hypotonia, mild feeding difficulties, and slight fine/motor delays. For both of these cases, there were other genes involved, thus it is unclear what haploinsufficiency of MAGEL2 contributes to the reported phenotype.

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

Triplosensitivity phenotype comment:

Of note: PMID:18925931 Cai et al. (2008) identified a de novo 120 kb maternally-derived duplication including MKRN3, MAGEL2, and NDN using MLPA probes in monozygotic twins with autism.