ClinVar Miner

Submissions for variant NM_000419.5(ITGA2B):c.48G>A (p.Trp16Ter)

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 RCV002511531 SCV002820923 likely pathogenic Glanzmann thrombasthenia 2022-09-20 reviewed by expert panel curation The NM_000419.5(ITGA2B):c.48G>A (p.Trp16Ter) variant in exon 1 is a nonsense variant in biologically-relevant-exon 1/30. Premature termination codons within exon 1/ first 100 nucleotides may not cause NMD and instead may lead to translation re-initiation (PMID: 27618451). Therefore, PVS1 is downgraded to PVS1_Moderate. At least one patient (UPN 1 in PMID: 16879215) with this variant displayed mucocutaneous bleeding and impaired aggregation with all agonists except ristocetin, which is highly specific for Glanzmann thrombasthenia (PP4_moderate). Additionally, αIIbβ3 surface expression was reduced to 5.6%, as measured by flow cytometry. UPN 1 is homozygous for this variant (PM3_supporting; PMID: 16879215). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, this variant meets the criteria to be classified as likely pathogenic for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PVS1_moderate, 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.