ClinGen Dosage Sensitivity Curation Page


Curation Status: Complete

Gene Information

Location Information

Evidence for Loss Phenotypes

Evidence for loss of function phenotype
PubMed ID Description
23064416 Pohler et al 2012: 18 families with autosomal dominant punctate palmoplantar keratoderma were shown to have loss of function mutations (variety of nonsense, frameshift and splicing mutations) in AAGAB. The skin findings were variable, with both mild and severe manifestations and onset in the first or second decade of life. Authors of this paper state that anecdotal association of AAGAB mutations with neoplasia has not been proven and may be coincidental.
23000146 Giel et al 2012: 2 novel nonsense mutations described in 3 independent pedigrees segregating autosomal dominant punctate palmoplantar keratoderma. Both intra- and inter-familial phenotypic heterogeneity was described.

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.