Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001225281 | SCV001397551 | likely pathogenic | Glanzmann thrombasthenia | 2023-05-16 | reviewed by expert panel | curation | The NM_000419.5(ITGA2B):c.460_462del deletion variant results in the in-frame deletion of Glu154 (PM4). It has been observed, in the homozygous state, in at least one case (PMID: 29675921; PM3_supporting) meeting the clinical and laboratory criteria of Glanzmann thrombasthenia, including mucocutaneous bleeding, impaired aggregation with all agonists except ristocetin, and reduced surface expression of αIIbβ3 measured by flow cytometry (PP4_strong). This variant occurs at an extremely low frequency with an overall allele frequency from gnomAD of 0.000004017 and MAF of 0.000008870 in the non-Finnish European population (PM2_supporting). In summary, this variant meets the criteria to be classified as Likely Pathogenic for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PP4_strong, PM2_supporting, PM3_supporting, PM4, PP4_strong. (VCEP specifications version 2). |