Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001803418 | SCV002047569 | uncertain significance | Glanzmann thrombasthenia | 2024-09-05 | reviewed by expert panel | curation | The ITGA2B missense variant NM_000419.5:c.1520C>G replaces the proline residue with an arginine residue (p.Pro507Arg). This variant has been observed in homozygosity (PM3_supporting) in one individual with a phenotype specific for Glanzmann's thrombasthenia (GT) (GT43, PMID: 16463284). All requirements for PP4_moderate are met (GT43 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 gnomADv4.1.0 (PM2_supporting). The in silico meta-predictor REVEL score for this variant is 0.224, below the VCEP-established threshold of <0.25 and suggestive of no damaging effect on protein function (BP4). In summary, this variant is of uncertain significance and lacks sufficient evidence to be classified as pathogenic or benign for GT. GT-specific criteria applied: PP4_Moderate, PM2_Supporting, PM3_Supporting, and BP4. |