ClinGen Dosage Sensitivity Curation Page

AFF2

  • Curation Status: Complete

Location Information

Select assembly: (NC_000023.10) (NC_000023.11)
Evidence for haploinsufficiency phenotype
PubMed ID Description
22065534 Sahoo (2011): Report of two male patients with focal deletions involving AFF2 who had features consistent with FRAXE syndrome. Patient 1 had a maternally-inherited deletion resulting in loss of exons 2-4. Maternal phenotype is not reported. Patient 2 had a deletion resulting is loss of exons 1-3 and the 343 kb region upstream of AFF2, inheritance was not known. Patient 2 also had a 358 kb duplication at 1q21.1 that overlapped the TAR syndrome critical region.
21739600 Stettner (2011): Report of two brothers with features consistent with FRAXE syndrome who had a maternally-inherited deletion in AFF2 resulting in loss of exon 3. The mother was phenotypically normal and an affected maternal uncle was also found to carry the deletion.
8673085 Gecz (1996): Characterization of a deletion found in a boy with features consistent with FRAXE syndrome that had been reported previously (PMID: 7536393). The deletion was 982 kb and resulted in loss of exons 2 and 3 and a premature truncation. It was maternally-inherited.

Haploinsufficiency phenotype comments:

Additional publications implicating loss of AFF2 with FRAXE syndrome due to deletion or hypermethylation include PMID: 17343270 and 11246464. The potential phenotypic spectrum seen in female carriers is not fully understood.

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.