ClinVar

Description

Variant summary: HBB c.8delA (p.His3LeufsX2) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251090 control chromosomes. c.8delA has been reported in the literature in the mother of a deceased thalassemic child who presented at age 6 months, and survived until 11 months, with two transfusions occurring within that period (Nagar_2015). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.