Submissions for variant NM_000419.5(ITGA2B):c.476G>T (p.Gly159Val)

dbSNP: rs2048641442

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen	RCV001254663	SCV002820925	likely pathogenic	Glanzmann thrombasthenia	2022-08-05	reviewed by expert panel	curation	The missense variant NM_000419.5(ITGA2B):c.476G>T (p.Gly159Val) has been reported in at least one patient (P2 in PMID: 34275420) with mucocutaneous bleeding and impaired aggregation with all agonists except ristocetin, which is highly specific for Glanzmann thrombasthenia (PP4_moderate). The patient is homozygous for Gly159Val (PM3_supporting). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). The computational predictor REVEL gives a score of 0.751, which is above the ClinGen PD VCEP threshold of >0.7 and predicts a damaging effect on function (PP3) and is is absent from gnomAD v2.1.1 (PM2_Supporting). Another missense variant c.475G>A (p.Gly159Ser) [PMID: 16359515] in the same codon has been classified Likely Pathogenic for Glanzmann thrombasthenia by the ClinGen PD VCEP (PM5_supporting). In summary this variant meets criteria to be classified as Likely Pathogenic for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PP3, PP4_moderate, PM2_supporting, PM3_supporting, PM5_supporting (VCEP specifications version 2.1).
Departement d'Immunology Plaquettaire, Institut National de la Transfusion Sanguine	RCV001254663	SCV001430682	uncertain significance	Glanzmann thrombasthenia		criteria provided, single submitter	provider interpretation	The variant alters the expression of the platelets fibrinogen receptor alphaIIb beta3