JARID2 was first reported in relation to autosomal dominant developmental delay with variable intellectual disability and dysmorphic facies in 2021 (Verberne et al., PMID: 33077894). Phenotypic features reported in affected individuals include developmental delay, intellectual disability, autism spectrum disorders (ASD), behavioral abnormalities and dysmorphic features including high anterior hairline, deep-set eyes, full lips, broad forehead, bulbous nasal tip, and depressed nasal bridge.
Twenty-three variants (nonsense, frameshift and exon deletion variants) that have been reported in 23 probands in 3 publications (PMIDs: 33077894, 35887345, 35533077) are included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The mechanism of pathogenicity is reported to be loss of function that disrupts genome wide methylation as demonstrated by an abnormal methylation signature pattern in probands with JARID2 pathogenic variants (PMID: 35887345).
In summary, there is definitive evidence to support the relationship between JARID2 and autosomal dominant developmental delay with variable intellectual disability and dysmorphic facies. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on February 6, 2024 (SOP Version 10).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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