Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001803410 | SCV002047560 | likely pathogenic | Glanzmann thrombasthenia | 2021-11-04 | reviewed by expert panel | curation | The NM_000419.5(ITGA2B):c.620C>T (p.Thr207Ile) missense variant has been reported in at least one Glanzmann thrombasthenia patient (PMIDs: 21113249, 15543332). Patient OK displayed mucocutaneous bleeding and impaired aggregation with all agonists except ristocetin, which is highly specific for Glanzmann thrombasthenia . Additionally, αIIbβ3 surface expression was reduced to 4%, as measured by flow cytometry, and there was<1% binding to PAC-1. (PP4_strong). Patient OK is homozygous for this variant (PM3_Supporting). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). The computational predictor REVEL gives a score of 0.729 (PP3). 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, PM3_supporting, PM2_supporitng, PP3. (VCEP specifications version 2; date of approval 11/04/2021) |