Submissions for variant NM_000419.5(ITGA2B):c.886G>A (p.Gly296Arg)

dbSNP: rs753264426

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen	RCV001225276	SCV001397544	likely pathogenic	Glanzmann thrombasthenia	2023-11-02	reviewed by expert panel	curation	The NM_000419.5(ITGA2B):c.886G>A (p.Gly296Arg) variant has been reported in two compound heterozygous individual with the pathogenic Gln228Ter and likely pathogenic Glu145del variants, phase unknown (PMID: 16463284, PMID: 29675921; PM3_supporting). Patient GT32 of PMID: 29675921 meets the criteria for PP4_Strong; including mucocutaneous bleeding, impaired aggregation with all agonists except ristocetin, and reduced surface expression of αIIbβ3 measured by flow cytometry. ITGA2B and ITGB3 were sequenced across all exons and intron/exon boundaries. The prevalence in gnomAD is 1/18334 which is less than 1/10,000; therefore, PM2_supporting is met. In summary, the variant is classified as likely pathogenic for Glanzmann thrombasthenia. GT-specific criteria applied: PM2_Supporting, PP4_Strong, PM3_Supporting.
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	RCV002245885	SCV002515501	uncertain significance	Glanzmann thrombasthenia 1		no assertion criteria provided	research