ClinGen Dosage Sensitivity Curation Page

TRAPPC2

  • Curation Status: Complete

Location Information

Select assembly: (NC_000023.10) (NC_000023.11)
Evidence for haploinsufficiency phenotype
PubMed ID Description
11252002 Matsui et al. 2001: An intragenic deletion including the 5' untranslated region but also the coding sequence for the first methionine through the 25th alanine was found in a Japanese male with X-linked spondyloepiphyseal dysplasia tarda and his carrier mother, but not in his unaffected sister or uncle.
12919139 Shaw et al. 2003: A 1,335bp intragenic deletion (in5/ex6del), was found in a Belgian patient resulting in X-linked spondyloepiphyseal dysplasia tarda.
11349230 Gedeon et al. 2001: Describes the mutations found in 30 unrelated individuals with X-linked sponkyloepiphyseal dysplasia tarda, including multiple nonsense mutations and two exonic deletions (one involving exon 3, and another involving exon 6).

Haploinsufficiency phenotype comments:

Alterations of TRAPPC2 have been associated with X-linked spondyloepiphyseal dysplasia tarda. From GeneReviews: "One report described phenotypically normal females with mild radiologically detectable osteoarthritic changes [Whyte et al 1999]. "

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

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

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.