STAG1 was first reported in relation to autosomal dominant intellectual disability with syndromic features in 2017 (Lehalle et al., PMID: 28119487). Phenotypes reported with STAG1 variants most frequently include intellectual disability, autism, seizures, hypotonia, hyperlaxity, and dysmorphic features. Considering the additional features that present with intellectual disability, variants in this gene have been curated for disease assertion “complex neurodevelopmental disorder”.
Fourteen variants (missense and frameshift) in 14 probands, reported in three publications (PMIDs: 30158690, 34440290, 28119487) 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 believed to be haploinsufficiency (PMID: 28119487). No experimental evidence currently supports this gene-disease relationship. While one knockout mouse model has been reported, it was not scored as evidence due to insufficient face validity regarding the human phenotype (PMID: 22415365).
In summary, there is definitive evidence to support the relationship between STAG1 and autosomal dominant complex neurodevelopmental disorder. This classification was approved by the ClinGen Intellectual Disability and Autism GCEP on September 20, 2022 (SOP 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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