Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001803447 | SCV002047600 | uncertain significance | Glanzmann thrombasthenia | 2021-12-21 | reviewed by expert panel | curation | TheNM_000419.5(ITGA2B):c.1742C>A (p.Ala581Asp) missense variant has been reported in at least one patient (Patient PL in PMID:12083483) who displayed mucocutaneous bleeding and impaired aggregation with all agonists except ristocetin, which is highly specific for Glanzmann thrombasthenia. Additionally, αIIbβ3 surface expression was reduced to 0.3-1.4% of normal, as measured by flow cytometry. ITGA2B and ITGB3 were sequenced across all exons and intron/exon boundaries (PP4_strong). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, this variant meets the criteria to be classified as uncertain significance for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PP4_strong, PM2_supporting. (VCEP specifications version 2; date of approval 12/21/2021) |