Submissions for variant NM_000419.5(ITGA2B):c.1063G>A (p.Glu355Lys)

gnomAD frequency: 0.00001  dbSNP: rs137852910

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen	RCV001580264	SCV001809928	pathogenic	Glanzmann thrombasthenia	2021-02-10	reviewed by expert panel	curation	The NM_000419.5(ITGA2B):c.1063G>A (p.Glu355Lys) missense variant has been reported in several patients (PMIDs: 11122161, 9722314, 9215749, 22250950, 9734640) with a phenotype highly specific to GT. It is occurs at a very low allele frequency of 0.00001978 (2/101,102 alleles) in the non-Finnish European gnomAD population. The variant is predicted to have a deleterious effect (REVEL score 0.793). The functional impact has been assessed by transfection in CHO cells, showing lack of αIIbβ3 surface expression with the Glu355Lys mutant (PMIDs: 11122161, 12362239). In summary this variant meets criteria to be classified as Pathogenic for GT. GT-specific criteria applied: PS3, PM2_Supporting, PM3, PP3, and PP4_Moderate.
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	RCV000003033	SCV002569920	pathogenic	Glanzmann thrombasthenia 1		criteria provided, single submitter	clinical testing
OMIM	RCV000003033	SCV000023191	pathogenic	Glanzmann thrombasthenia 1	1998-09-01	no assertion criteria provided	literature only