ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000017.10) (NC_000017.11)
Evidence for haploinsufficiency phenotype
PubMed ID Description
15042511 Lammi et al. (2004) identified an Arg656X mutation in the AXIN2 gene (p.R656X) in a Finnish family in which severe permanent tooth agenesis (oligodontia) and colorectal cancer (608615) segregated with dominant inheritance. The p.R656X mutation was present in all 11 patients with oligodontia from a multigeneration family, whereas it was not present in the healthy individuals, thus showing complete segregation with the oligodontia phenotype. Lammi et al. (2004) also identified a de novo frameshift mutation 1994-1995insG (causing a premature stop codon to AXIN2 exon 7) in an 13-year-old boy with severe tooth agenesis. The young age of the patient prevents the confirmation of cancer predisposition.
21416598 Marvin et al. (2011) identified a heterozygous nonsense mutation (c.1989G>A) in the AXIN2 gene in a 3-generation family (4 affected individuals) segregating autosomal dominant oligodontia variably associated with colon or gastric polyps, early-onset colorectal and/or breast cancer, and sparse hair and eyebrows. The mutation was not found in 2 unaffected family members.
28195393 Hansen et al. (2017): A frameshift mutation c.1987dupT, p.Trp663Leufs*44 in gene AXIN2 was identified in patient 112, who was diagnosed with CRC at age 65 and abnormal dentition was reported, consistent with Oligodontia?colorectal cancer syndrome. This variant is not present in ExAC.

Haploinsufficiency phenotype comments:

One more supporting paper: PMID: 27696107, Rohlin et al. (2017) A frameshift mutation c.254delT, p.Leu85Tyrfs*24 in gene AXIN2 was identified in patient (I:55) with late onset CRC, along with a synonymous VUS MSH2 c.1275A > G. oligodonita was not present in this patient. This variant is not present in ExAC.

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