ARPC1B was first reported in relation to autosomal recessive Platelet abnormalities with eosinophilia and immune-mediated inflammatory disease in 2017 by Kahr et al. (PMID: 28368018). At least 10 loss of function (indel, deletions, duplications, nonsense) and missense variants have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data and experimental data.
Summary of Case Level Data: 12 POINTS Variants in this gene have been reported in at least 10 probands in 4 publications (PMIDs 30254128, 28368018, 27965109, 29127144). Variants in this gene segregated with disease in 2 additional family members. More evidence is available in the literature (PMID: 30771411), but the maximum score for genetic evidence and/or experimental evidence (12 pts.) has been reached.
The mechanism for disease is expected to be homozygous loss of function (PMID: 28368018).
Summary of Experimental Data: 2 POINTS
This gene-disease association is supported by animal models and in vitro functional assays (PMIDs 30254128, 28368018, 27965109, 29127144). However,
In summary, the ARPC1B-autosomal recessive Platelet abnormalities with eosinophilia and immune-mediated inflammatory disease gene-disease relationship is definitive. 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 Hemostasis/Thrombosis GCEP on July 22, 2020. (SOP Version 7)
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