Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV002511535 | SCV002820930 | likely pathogenic | Glanzmann thrombasthenia | 2022-08-05 | reviewed by expert panel | curation | The NM_000419.5(ITGA2B):c.1563T>A (p.Cys521Ter) nonsense variant in exon 16/30 is predicted to lead to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). This variant has been observed in heterozygosity in an individual with a laboratory phenotype (platelet aggregation and surface expression) consistent with Glanzmann's thrombasthenia (GT), however a second ITGA2B variant was not identified and sufficient bleeding phenotype information to confirm if the individual's phenotype is specific for GT was not provided. This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary this variant meets 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: PVS1, PM2_supporting. (VCEP specifications version 2.1) |