ClinVar Miner

Submissions for variant NM_000419.5(ITGA2B):c.647C>T (p.Ala216Val)

dbSNP: rs2143485154
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen RCV001580219 SCV001809852 likely pathogenic Glanzmann thrombasthenia 2024-09-05 reviewed by expert panel curation The NM_000419.5(ITGA2B):c.647C>T (p.Ala216Val) missense variant has been previously reported in the context of Glanzmann thrombasthenia. One individual (GT55) with the p.Ala216Val missense variant in homozygous state (PM3_supporting) presented with significant mucocutaneous bleeding. Platelet aggregometry demonstrated absence of platelet aggregation with 3 platelet agonists and normal aggregation with ristocetin. Surface expression of αIIbβ3 was demonstrated to be reduced (11-22%) by flowcytometry. Sanger sequencing ensured coverage of exons and splice sites of the ITGA2B and ITGB3 genes as well as untranslated regions (PMID:25728920; PP4_strong). This variant is absent from all continental populations in gnomAD v4.1.0 (PM2_Supporting). Multiple in silico tools predict this variant to be deleterious (REVEL score = 0.85; PP3). This variant meets criteria for PP4_strong, PM2_supporting, PM3_supporting and PP3 and is classified as Likely pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.