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
29698805 Gazdagh et al (2018) - DDD/Decipher paper, exomes (WES) and CMA. 5 unrelated individuals with de novo truncating mutations in the ARID2 gene. 1 individual with de novo deletion of 5' end of ARID2 gene. (1 additional individual with a larger deletion that includes ARID2). All cases had features similar to Coffin-Siris syndrome (although hypertrichosis and hypoplasia of the fifth finger nail and distal phalanx do not appear to be common in these patients, toenail hypoplasia and the presence of Wormian bones was common).
26238514 Shang et al (2015) - exomes (WES). 3 independent LOF de novo variants in ARID2. (1 additional LOF but inheritance unknown). All patients have intellectual disability and share other characteristics including attention deficit hyperactivity disorder, short stature, dysmorphic features and Wormian bones.
28124119 Bramswig et al (2017) - exomes (WES) 2 individuals with de novo ARID2 frameshift variants. Both had Coffin-Siris type phenotpyes (intellectual disability, coarsening of facial features, other recognizable facial dysmorphisms and hypoplasia of the fifth toenails).

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.