ClinGen Dosage Sensitivity Curation Page

EXT2

Curation Status: Complete

Gene Information

Location Information

Evidence for Loss Phenotypes

Evidence for loss of function phenotype
PubMed ID Description
29529714 In 2018, Santos et al. used Sanger sequencing and Multiplex ligation-dependent probe amplification (MLPA) on 153 Brazilian patients in 114 families with multiple osteochondromas (MO) to identify variants in EXT1 and EXT2. The authors identified variants in EXT2 in 53 of the 114 unrelated individuals with MO. 17 of these variants were unique. Of these variants, 6 were frameshifts, 1 was a missense variant, 3 were nonsense, 6 were splice site variants, and 1 was a large deletion.
30334991 In 2018, Li et al. used Sanger sequencing and Multiplex ligation-dependent probe amplification (MLPA) on unrelated individuals from 73 families with hereditary multiple osteochondroma (HMO) to identify variants in EXT1 and EXT2. Analysis identified 25 unique variants in EXT2 in 29 families. Of these, 4 were frameshifts, 13 were nonsense variants, 4 were splice site variants, and 1 was a large deletion.
28690282 In 2017, Guo et al. used targeted next-generation sequencing (t-NGS) and Sanger sequencing on 10 patients with multiple osteochondromas (MO) to identify potential variants in EXT1 and EXT2. The authors identified 3 variants in EXT2. Of these, 1 was a splice site variant and 2 were nonsense variants.

Evidence for Triplosenstive Phenotype

NOTE:The loss of function score should be used to evaluate deletions, and the triplosensitivity score should be used to evaluated duplications. CNVs encompassing more than one gene must be evaluated in their totality (e.g. overall size, gain vs. loss, presence of other genes, etc). The rating of a single gene within the CNV should not necessarily be the only criteria by which one defines a clinical interpretation. Individual interpretations must take into account the phenotype described for the patient as well as issues of penetrance and expressivity of the disorder. ACMG has published guidelines for the characterization of postnatal CNVs, and these recommendations should be utilized (Genet Med (2011)13: 680-685). Exceptions to these interpretive correlations will occur, and clinical judgment should always be exercised.