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
25296922 Smith et al. (2015): Case report of 10 year old boy with specific language impairment. Patient has a 159Kb deletion that includes ATP2C2 as well as a second gene, TLDC1. The deletion was found to be de novo. ATP2C2 is a candidate gene for specific language impairment based on GWAS studies [PMID: 19646677]. The authors propose a neurobiological role of the ATP2C2 gene in specific language impairment through effects on the development of phonologic short-term memory.

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.