Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV002254793 | SCV002525882 | likely pathogenic | Glanzmann thrombasthenia | 2022-04-19 | reviewed by expert panel | curation | The missense variant NM_000419.5(ITGA2B):c.2437C>A (p.His813Asn) has been reported in at least one patient (PMID: 17488698) with mucocutaneous bleeding and impaired aggregation with all agonists except ristocetin, which is highly specific for Glanzmann thrombasthenia. Additionally, alphaIIbbeta3 surface expression was reduced to 4.5%, as measured by flow cytometry (PP4_strong). The patient is compound heterozygous for in trans variants c.1771dup (classified Pathogenic by the PD-EP) and His813Asn (PM3). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary this variant meets 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: PP4_strong, PM2_supporting, PM3 (VCEP specifications version 2.1). |