Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV002511552 | SCV002820949 | pathogenic | Glanzmann thrombasthenia | 2022-04-07 | reviewed by expert panel | curation | The NM_000419.5(ITGA2B):c.1096C>T (p.Arg366Ter) nonsense variant in biologically-relevant-exon 12/30 and is predicted to lead to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). At least one patient (Patient CT in PMID: 12083483) with this variant displayed mucocutaneous bleeding and impaired aggregation with all agonists except ristocetin, which is highly specific for Glanzmann thrombasthenia (PP4_moderate). Patient CT of PMID: 12083483 is homozygous for the Arg366Ter nonsense variant (PM3_supporting). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, this variant meets the criteria to be classified as Pathogenic for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PVS1, PP4_moderate, PM2_supporting, PM3_supporting. (VCEP specifications version 2; date of approval 01/18/2022) |