ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000020.10) (NC_000020.11)
Evidence for haploinsufficiency phenotype
PubMed ID Description
12567410 Savarirayan et al. (2003) identified a heterozygous 1-bp insertion in the GDF5 gene, 206insG, in 8 members of 3 unrelated families with type C brachydactyly. This mutation results in a frameshift and premature termination 25 amino acids downstream. The change was not detected in 100 control alleles.
9288091 Polinkovsky et al. (1997) identified a heterozygous C-to-T transition at nucleotide 901 of the GDF5 mRNA coding sequence in affected members of a family with brachydactyly type C. The mutation results in a R301X substitution.
18283415 Yang et al (2008) identified a T-to-G transversion in GDF5 in a 4 generation family with brachydactyly type C. The mutation was not detected in unaffected family members or 50 controls. The mutation results in a Y487X substitution that is predicted to truncate the precursor polypeptide by 15 amino acids.

Haploinsufficiency phenotype comments:

The loss evidence listed above and the haploinsufficiency score is based only on the phenotype of brachydactyly type C; however, please note that mutations of GDF5 are associated with additional phenotypes (see OMIM IDs 201250, 112600, 200700, 228900, 610017, 185800, 612400).

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