ClinVar

Description

Variant summary: ITGA2B c.3092delT (p.Leu1031ArgfsX70+) causes a frameshift which results in an extension of the protein. This variant results in the addition of 90 amino acids to the ITGA2B protein, beyond the cytoplasmic domain. The variant was absent in 251356 control chromosomes. c.3092delT has been reported in the literature in at-least two individuals affected with Glanzmann thrombasthenia, in each case, it was at a compound heterozygous along with a different pathogenic missense (example, Sandrock-Lang_2015, Sharma_2021). These data indicate that the variant may be associated with disease. Additionally, a similar extension variant c.3091delC variant causes a frameshift Leu1031TrpfsTer97 and subsequent stop loss, also adds 90 amino acids to the ITGA2B protein, and was evaluated Likely Pathogenic per ClinGen Platelet Disorders Variant Curation Expert Panel (ClinVar ID 1879040). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 25373348, 34267460). ClinVar contains an entry for this variant (Variation ID: 1691488). Based on the evidence outlined above, the variant was classified as likely pathogenic.