The GRIN2A gene has been associated with autosomal dominant complex neurodevelopmental disorder. This disease association was made using case-level data and experimental data. At least 10 variants (missense, frameshift, truncating, deletion, and de novo) were curated from two publications (23933819, 50890276). More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. This gene-disease association is supported by non-patient cells functional alteration and non-human model systems (27839871, 7816096). Additional experimental evidence exists, but was not reviewed in this curation (31158310, 30146685 [additional mouse models], 26312887 [variant expression in cultured neurons]). A treatment paper with N=1 was also reviewed (24839611), but did not qualify as a true genetic rescue; however, it does highlight the potential to translate functional data to targeted treatment. In summary, GRIN2A is definitively associated with autosomal dominant complex neurodevelopmental disorder. 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 Epilepsy Gene Curation Expert Panel on 7/16/19 (SOP Version 6).
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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