ClinGen Dosage Sensitivity Curation Page

NOTCH2

  • Curation Status: Complete

Location Information

Select assembly: (NC_000001.10) (NC_000001.11)

Haploinsufficiency phenotype comments:

Though variantion in NOTCH2 has been associated with Alagile syndrome 2, the mechanism by which this occurs is unclear. Kamath et al. (2012) (PMID:22209762) note that two reported nonsense variants have been shown to result in mRNAs escaping nonsense-mediated decay, suggesting a mechanism other than haploinsufficiency. Specific gain of function mutations in NOTCH2 (resulting in signalling persistance) are associated with Hajdu-Cheney syndrome (OMIM#102500). It is important to note that many of the gain of function mutations resulting in Hajdu-Cheney are actually truncating mutations.

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

Triplosensitivity phenotype comment:

While specific gain of function mutations in NOTCH2 (resulting in signalling persistance) are associated with Hajdu-Cheney syndrome (OMIM#102500), single copy gains have not yet been reported in the literature. It is unclear at the time of this review if NOTCH2 is subject to triplosensitivity.