ClinGen Dosage Sensitivity Curation Page

GDF2

  • Curation Status: Complete

Location Information

Select assembly: (NC_000010.10) (NC_000010.11)
  • Haploinsufficiency score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Haploinsufficiency phenotype comments:

Variants in GDF2 have been associated with hereditary hemorrhagic telangiectasia (HHT) type 5 (OMIM:615506). At the time of this review, four missense variants have been reported in individuals with phenotypic features overlapping those of HHT (PMID:23972370 and PMID: 27081547), including one that the authors deemed of "uncertain significance" (PMID: 27081547). Wooderchak-Donahue et al. performed functional analyses on three of the variants, determining that they "negatively affect protein processing and/or function," though it remains unclear whether or not this is through a loss of function mechanism (PMID:23972370). No loss-of-function variants or focal deletions of this gene have been reported at this time. Of note, other HHT-causing genes in the TGFbeta-signaling pathway (ENG, ACVRL1, SMAD4) are known to cause disease through loss of function mechanisms.

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