Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001803412 | SCV002047562 | pathogenic | Glanzmann thrombasthenia | 2021-11-04 | reviewed by expert panel | curation | The NM_000419.5(ITGA2B):c.2444_2445del (p.Tyr815Ter) variant in exon 24 of ITGA2B is a frameshift variant predicted to cause an immediate premature stop codon in biologically-relevant-exon 24/30 and is predicted to lead to nonsense mediated decay (PVS1). GT16 of PMID: 32237906 displayed mucocutaneous bleeding and impaired aggregation with all agonists except ristocetin, which is highly specific for Glanzmann thrombasthenia (PP4_moderate).Additionally, αIIb surface expression was reduced to 0.1%, as measured by flow cytometry. GT16 (PMID: 32237906) is compound heterozygous for c.2444_2445del and Arg977Ter (classified Pathogenic by the PD-VCEP; PM3_supporting). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, this variant meets the criteria to be classified as Pathogenic for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PVS1, PP4_moderate, PM2_supporting, PM3_supporting. (VCEP specifications version 2; date of approval 11/04/2021) |