Submissions for variant NM_000419.5(ITGA2B):c.558C>G (p.Tyr186Ter)

dbSNP: rs1416238665

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen	RCV001580241	SCV001809880	likely pathogenic	Glanzmann thrombasthenia	2024-02-20	reviewed by expert panel	curation	The ITGA2B nonsense variant NM_000419.5:c.558C>G (p.Tyr186Ter) is expected to introduce a premature termination codon, in exon 4 of 30, and the resulting mRNA product is predicted to undergo nonsense mediated decay, leading to loss of normal protein function (PVS1). This variant has been observed in heterozygosity in an individual suspected to have Glanzmann's thrombasthenia (GT) (GT-63 in PMID: 30792900), however sufficient information to confirm if the individual's phenotype is specific for GT was not provided and a second ITGA2B variant was not identified. This variant is absent from population databases, including gnomADv4.0 (PM2_supporting). In summary, this variant meets criteria to be classified as likely pathogenic for GT. GT-specific criteria applied: PVS1, PM2_supporting.
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV003989698	SCV004807970	pathogenic	Glanzmann thrombasthenia 1	2024-03-29	criteria provided, single submitter	clinical testing