Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV002511530 | SCV002820922 | uncertain significance | Glanzmann thrombasthenia | 2022-09-20 | reviewed by expert panel | curation | The NM_000419.5(ITGA2B):c.1162G>A (p.Gly388Ser) missense variant has been reported in at least one patient (UPN 4 in PMID: 16879215) with this variant displayed mucocutaneous bleeding and impaired aggregation with all agonists except ristocetin, which is highly specific for Glanzmann thrombasthenia (PP4_moderate). UPN 4 is homozygous for this variant (PM3_supporting; PMID: 16879215). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). The computational predictor REVEL gives a score of 0.855, which is above the ClinGen PD VCEP threshold of >0.7 and predicts a damaging effect on function (PP3). In summary, this variant meets the criteria to be classified as uncertain significance for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PM2_supporting, PM3_supporting, PP4_moderate, PP3. |