Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001580255 | SCV001809899 | likely pathogenic | Glanzmann thrombasthenia | 2024-08-20 | reviewed by expert panel | curation | The ITGA2B missense variant NM_000419.5:c.641T>G replaces the leucine residue with an arginine residue (p.Leu214Arg). This variant has been observed in homozygosity in a proband (Patient B, PMID: 26096001; PM3_supporting) with a phenotype specific for Glanzmann's thrombasthenia (GT), including a history of bleeding and impaired aggregation to at least two agonists, but normal or only mildly reduced agglutination with ristocetin (PP4_Moderate). This variant has not been reported in population databases, including gnomADv4.1.0 (PM2_supporting) and is predicted to be damaging by in silico tools (REVEL score 0.797; PP3). Furthermore, a different missense change at this amino acid residue (ITGA2B c.641T>C (p.Leu214Pro)) is classified as pathogenic by the Platelet Disorders VCEP (PM5). In summary, this variant meets criteria to be classified as likely pathogenic for GT. GT-specific criteria applied: PM2_supporting, PM3_supporting, PM5, PP4_moderate, PP3. |