Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001580215 | SCV001809848 | likely pathogenic | Glanzmann thrombasthenia | 2024-06-06 | reviewed by expert panel | curation | The NM_000419.5(ITGA2B):c.2029G>A (p.Glu677Lys) missense variant has a highest population minor allele frequency in gnomAD v4.0 of 0.000002625 (2/761904 alleles) in the European (non-Finnish)population, which is lower than the ClinGen PD VCEP threshold (<0.0001; PM2_Supporting). It has been reported in two patients with GT (PMID: 29675921, Patient 439 of the Glanzmann Thrombasthenia Database). GT1 of PMID: 29675921 is compound heterozygous for Glu677Lys and Arg351Ter (classified Pathogenic by the PD-EP SCV001809862.1; PM3_supporting). GT1 of PMID: 29675921 meets the criteria for PP4_strong; including mucocutaneous bleeding, impaired aggregation with all agonists except ristocetin, and <5% expression of αIIbβ3 measured by flow cytometry. ITGA2B and ITGB3 were sequenced across all exons and intron/exon boundaries. In summary, based on the evidence available at this time, the variant is classified as likely pathogenic. GT-specific criteria applied: PM2_supporting, PM3_supporting, and PP4_strong. |