HBA2 was first reported in relation to autosomal dominant erythrocytosis 7 in 1980 (Honig et al. 1980; PMID: 7213661). Erythrocytosis 7 is a disorder of the blood characterized by a high concentration of erythrocytes in the blood and an increased oxygen affinity of hemoglobin. Per criteria outlined by the ClinGen Lumping & Splitting Working Group, we found differences in molecular mechanisms, inheritance pattern, and phenotypic variability in erythrocytosis 7 relative to other disease entities associated with HBA2. Therefore, the following disease entities have been split into multiple curations: AD erythrocytosis, AD and AR alpha-thalassemia, unstable hemoglobin disease, and methemoglobinemia. This curation addresses only AD erythrocytosis. This curation includes at least 10 missense variants reported in 10 probands with AD erythrocytosis in 10 publications (PMIDs: 7213661, 1634363, 1634355, 11186265, 18818920, 19205974, 22959973, 25818820, 27240426, 33217156). This gene disease association is also supported by experimental evidence including expression, biochemical function, and protein-protein interactions (PMIDs: 11747442, 6644819). In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the ClinGen General Gene Curation Expert Panel on 10/25/2023 (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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