Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001580218 | SCV001809851 | likely pathogenic | Glanzmann thrombasthenia | 2024-09-05 | reviewed by expert panel | curation | The c.614+1G>T variant on ITGB3 gene is a canonical splice donor variant that has been reported previously in the context of Glanzmann Thrombasthenia (PMID: 25728920). It is predicted to cause a disruption of the canonical donor splice site in intron 4, this is expected to cause a frameshift with premature stop at codon 122 (exon 5 of 15), therefore NMD would be expected. (PVS1). It is absent from all major population cohorts in gnomADv4.1 (PM2_supporting). This variant has been reported in homozygosity in two symptomatic siblings who meet diagnostic criteria for GT phenotype (PMID: 25728920). However, the siblings are homozygous for both c.614+1G>T and Arg228His and while this splice variant is Likely Pathogenic an impact of the missense variant can not be excluded so this case has not been considered in the classification of this variant. This variant meets GT-specific criteria for PVS1 and PM2_supporting and is therefore classified as Likely Pathogenic. |