RASGRP2 was first reported in relation to autosomal recessive platelet-type bleeding disorder 18 in 2014 (Canault et al., PMID: 24958846). At least 20 unique variants (including mostly missense, as well as nonsense, and a few splicing and frameshift variants) have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data and experimental data. Variants in this gene have been reported in at least 13 probands in 5 publications (PMIDs: 24958846, 27235135, 28637664, 27663674, 28762304). Variants in this gene segregated with disease in 5 additional family members. 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 the protein function in integrin activation, functional alteration and rescue in patient cells, and mouse models (including a knockout mouse and a humanized knock-in partial rescue). In summary, RASGRP2 is definitively associated with autosomal recessive platelet-type bleeding disorder 18. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. Of note, this gene was previously implicated to be associated with leukocyte adhesion deficiency-3 (LAD3) (PMID:17576779), however it was later shown (PMIDs:19064721, 19234463, and 19234460) to not be the case and LAD3 is associated with defects in the FERMT3 gene.
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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