TANC2 was first reported in relation to autosomal dominant Intellectual developmental disorder with autistic features and language delay, with or without seizures in 2019 (Guo et al., PMID: 31616000). The mechanism for the disease is haploinsufficiency and more than 20 unique loss-of-function variants have been reported in humans. Most variants occurred de novo, but some individuals inherited the variant from an affected parent. Variants in this gene have been reported in over 20 probands from a total of 3 publications, reaching the maximum score for genetic evidence (Guo et al. 2019, PMID: 31616000; Tian et al., 2019, PMID: 34861844; Tassano et al., 2020, PMID: 33160097). In addition to the case-level data, this gene-disease association is supported by experimental evidence, including animal models, protein interaction assays, and in vitro functional assays.
In summary, there is definitive evidence to support the relationship between TANC2 and autosomal dominant Intellectual developmental disorder with autistic features and language delay, with or without seizures. This classification was approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on September 7th, 2022 (SOP Version 9).
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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