DYNC2I1 was first reported in relation to autosomal recessive short-rib thoracic dysplasia 8 with or without polydactyly (SRTD8) in 2013 ( McInerney-Leo et al., PMID: 23910462). SRTD8 efers to a group of autosomal recessive skeletal ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. Five missense, two nonsense, one frameshift, and one duplication that have been reported in seven probands in four publications (PMIDs: 23910462, 26874042, 29068549, 36381051) are included in this curation. The mechanism of pathogenicity at this time is unknown. This gene-disease relationship is also supported by functional alteration of patient cells, protein-protein interactions, and animal models (PMIDs: 23910462, 29742051, 34739033, 37228654). In summary, there is definitive evidence supporting the relationship between DYNC2I1 and autosomal recessive short-rib thoracic dysplasia 8 with or without polydactyly. 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 Skeletal Disorders GCEP on the meeting date September 4th, 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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