Submission Details

Autosomal dominant

03/06/2020

The ARID2 gene is located on chromosome 12 at 12q12 and encodes the AT-rich interaction domain 2 protein, which is subunit of the SWI/SNF chromatin remodeling complex (PBAF). The PBAF complex facilitates transcriptional activation and repression of select genes by chromatin remodeling. ARID2 was first reported in relation to autosomal dominant, Coffin-Siris syndrome in 2015 (26238514: Shang et al. 2015). At least six unique loss-of-function variants have been reported. Evidence supporting this gene-disease relationship includes case-level data and experimental data. De novo variants in this gene have been reported in at least six probands from four publications (26238514: Shang et al. 2015; 28124119: Bramswig et al. 2017; 29698805: Gazdagh et al. 2018; 30838730: Khazanchi et al. 2019). More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The mechanism for disease is consistent with haploinsufficiency. This gene-disease relationship is supported by expression studies that demonstrate ubiquitous expression of ARDI2 throughout the developing spinal cord, brain and other embryonic tissues such as heart and liver in mouse, and biochemical function (26238514: Shang et al. 2015). Additionally, ARID2 is one of the three ARID proteins in SWI/ SNF complex, which is divided into BAF and PBA complex. The BAF complex is important in human brain development and five subunits of the BAF complex are associated with neurobehavioral disorders. In summary, there is strong evidence to support the relationship between ARID2 and Coffin-Siris syndrome, autosomal dominant. Additional experimental evidence is needed to reach a definitive classification.

26238514 28124119 29698805 30838730