ClinVar

Description

Variant summary: HBA2 c.77G>A (p.Gly26Asp), also referred to as Hb Cibeles, results in a non-conservative amino acid change located in the globin domain (IPR000971) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 53842 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.77G>A has been reported in the literature in at least two heterozygous individuals with mild/moderate microcytic hypochromic anemia with normal Hb A2 levels (e.g. de la Fuente-Gonzalo_2014, Farashi_2015). These reports do not provide unequivocal conclusions about association of the variant with Alpha Thalassemia. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported, although it has been suggested that this variant is unstable as it was not detected by electrophoretic or chromatographic methods (de la Fuente-Gonzalo_2014). The following publications have been ascertained in the context of this evaluation (PMID: 26329872, 25212678). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.