Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV004577679 | SCV005061668 | likely pathogenic | Glanzmann thrombasthenia | 2024-03-07 | reviewed by expert panel | curation | The NM_000212.3(ITGB3):c.428T>C (p.Leu143Ser) missense variant is absent from gnomADv4.0.0 (PM2_supporting) and has a REVEL score of 0.973, above the >.0.7 threshold in support of a deleterious effect (PP3). Another missense variant NM_000212.3(ITGB3):c.428T>G (p.Leu143Trp) in the same codon has been classified as likely pathogenic for Glanzmann thrombasthenia by the ClinGen PD VCEP (PM5_supporting). It has been reported once, homozygous in Patient 15 of PMID: 36672149 has history of bleeding and impaired aggregation to at least two agonists, but normal agglutination with ristocetin (PM3_supporting; PP4_Moderate). In summary, this variant meets criteria to be classified as likely pathogenic for autosomal recessive Glanzmann thrombasthenia. GT-specific criteria applied: PM2_supporting, PP3, PM5_supporting, PM3_supporting, PP4_Moderate. |