Submission Details

The ADNP gene is located on chromosome 20 at 20q13.13 and encodes the activity dependent neuroprotector homeobox protein, which regulates gene expression via chromatin remodeling. ADNP was first reported in relation to autosomal dominant ADNP-related multiple congenital anomalies-intellectual disability-autism spectrum disorder in 2014 (24531329: Helsmoortel et al. 2014). Evidence supporting this gene-disease relationship includes case-level data and experimental data. At least five unique de novo loss-of-function variants have been reported in probands from three publications (24531329: Helsmoortel et al. 2014; 25057125: Pescosolido et al. 2014; 31029150: Bend et al. 2019). More evidence is available in the literature, but the maximum score for genetic evidence has been reached. This gene-disease relationship is supported by protein interaction with SWI/SNF chromatin remodelling complex subunits, dysregulated gene expression in ADNP knockout mouse embryos, and a heterozygous knockout mouse model that shows strong phenotypic overlap with human patients (17878164: Mandel & Gozes 2007; 17222401: Mandel et al. 2007; 30106381: Hacohen-Kleiman et al. 2018). In summary, ADNP is definitively associated with autosomal dominant ADNP-related multiple congenital anomalies-intellectual disability-autism spectrum disorder. This has been repeatedly demonstrated in both the research and clinical diagnostic settings and has been upheld over time.

PubMed IDs:

24531329 25057125 31029150 17878164 17222401

Assertion Criteria:

Click here to view assertion criteria

https://www.clinicalgenome.org/site/assets/files/3975/gene-disease_validity_standard_operating_procedures_version_7-1.pdf

Submitter Submitted Date:

10/15/2020

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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