Submissions for variant NM_000419.5(ITGA2B):c.2975_2979del (p.Glu992fs)

dbSNP: rs2048521407

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen	RCV001254667	SCV001809896	pathogenic	Glanzmann thrombasthenia	2022-08-05	reviewed by expert panel	curation	The NM_000419.5(ITGA2B):c.2975_2979del variant (current HGVS nomenclature of c.2971_2975del) that results in the p.Glu992Glyfs*42 frameshift has been reported homozygous (PM3_supporting) in at least one GT proband (P16 in PMID: 34275420) who displayed mucocutaneous bleeding and impaired aggregation with all agonists except ristocetin, which is highly specific for Glanzmann thrombasthenia. Additionally, αIIbβ3 surface expression was reduced to <5%, as measured by flow cytometry (PP4_strong). An additional affected family member (P17) is also homozygous (PP1). The variant alters the critical transmembrane domain (PVS1). The variant is absent from population databases (PM2_supporting). In summary, based on the available evidence at this time, the variant is classified as pathogenic for GT. GT-specific criteria applied: PVS1_Strong, PM2_Supporting, PM3_supporting, PP1, PP4_strong.
Departement d'Immunology Plaquettaire, Institut National de la Transfusion Sanguine	RCV001254667	SCV001430687	pathogenic	Glanzmann thrombasthenia		criteria provided, single submitter	provider interpretation	The variant alters the expression of the platelets fibrinogen receptor alphaIIb beta3