Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000778499 | SCV001809903 | pathogenic | Glanzmann thrombasthenia | 2021-03-05 | reviewed by expert panel | curation | NM_000419.5(ITGA2B):c.1357C>T (p.Arg453Ter) is a nonsense variant located on exon 13, predicted to result in NMD. It is absent from all large population cohorts (gnomAD). This variant has been reported to occur in homozygous state in one proband (PMID: 25728920). This variant meets GT specific criteria for PVS1, PM2_supporting, and PM3_supporting and is therefore classified as Pathogenic. |
Illumina Laboratory Services, |
RCV000778499 | SCV000914769 | uncertain significance | Glanzmann thrombasthenia | 2019-01-10 | criteria provided, single submitter | clinical testing | The ITGA2B c.1357C>T (p.Arg453Ter) variant is a stop-gained variant that has been reported in a homozygous state in one individual with Glanzmann thombasthenia who showed mucocutaneous bleeding with transfusions (Nurden et al. 2015; Nurden et al. 2018). This variant is not reported in the 1000 Genomes Project, Exome Sequencing Project, Exome Aggregation Consortium, or Genome Aggregation Database despite its location in a region of good sequencing coverage. It is therefore presumed to be rare. The evidence for this variant is limited. Based on the potential impact of stop-gained variants and the supporting evidence, the p.Arg453Ter variant is classified as of uncertain significance suspicious for pathogenicity for thrombasthenia of Glanzmann and Naegeli. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |