Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV002254800 | SCV002525889 | uncertain significance | Glanzmann thrombasthenia | 2024-04-16 | reviewed by expert panel | curation | The ITGA2B missense variant NM_000419.5:c.1139G>T replaces the glycine residue with a valine residue (p.Gly380Val). This variant has been observed in homozygosity in one individual with a phenotype specific for Glanzmann's thrombasthenia (GT) (GT28, PMID: 16463284; PM3_supporting). All requirements for PP4_Moderate are met (GT28 in PMID: 16463284): history of bleeding and impaired aggregation to at least two agonists, but normal or only mildly reduced agglutination with ristocetin. This variant is absent from gnomADv4.0 (PM2_supporting) and the in silico meta-predictor REVEL score for this variant is 0.853, exceeding the VCEP-established threshold of ≥0.7 and suggestive of a damaging effect on protein function (PP3). Another missense change at this amino acid codon has been observed (c.1139G>A (p.Gly380Asp), Patient GM in PMID: 12083483) and classified as uncertain significance by the Platelet Disorders VCEP. In summary, this variant meets criteria to be classified as uncertain significance for GT. GT-specific criteria applied: PP4_moderate, PM2_supporting, PM3_supporting, and PP3. |