ClinVar Miner

Submissions for variant NM_000419.5(ITGA2B):c.1999dup (p.Asp667fs)

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 RCV002511527 SCV002820918 pathogenic Glanzmann thrombasthenia 2022-09-20 reviewed by expert panel curation The NM_000419.5(ITGA2B):c.1999dup (p.Asp667GlyfsTer11) frameshift variant in exon 20 is predicted to cause a premature stop codon in biologically-relevant-exon 21/30 and is predicted to lead to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). It has been reported homozygous (PM3_supporting) in at least one GT proband (case 12 in PMID: 32089034) who displayed mucocutaneous bleeding and impaired aggregation with all agonists except ristocetin, which is highly specific for Glanzmann thrombasthenia. Additionally, αIIbβ3 surface expression was 0.2-4%, as measured by flow cytometry (PP4_moderate). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, based on the available evidence at this time, the variant is classified as pathogenic for GT. GT-specific criteria applied: PVS1, PM2_supporting, PM3_supporting, PP4_moderate.

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.