ClinVar Miner

Submissions for variant NM_000419.5(ITGA2B):c.800G>A (p.Gly267Glu)

dbSNP: rs2048627164
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen RCV001225247 SCV001397499 likely pathogenic Glanzmann thrombasthenia 2024-04-16 reviewed by expert panel curation The NM_000419.5:c.800G>A (p.Gly267Glu) missense variant has been reported in at least one compound heterozygous patient (PMID: 12083483) with a phenotype highly specific to GT. Patient DRP of PMID: 12083483 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 (PP4_Strong). This patient is compound heterozygous for the variants c.2930del (classified Pathogenic by the Platelet Disorders VCEP) and Gly267Glu (PM3_supporting). It is absent from population databases, including gnomADv4.0.0 (PM2_supporting) and predicted to have a deleterious effect (REVEL score 0.838; PP3). In summary this variant meets criteria to be classified as Likely Pathogenic for GT. GT-specific criteria applied: PM2_Supporting, PM3_Supporting, PP3, and PP4_Strong.
Labcorp Genetics (formerly Invitae), Labcorp RCV001225247 SCV003441987 uncertain significance Glanzmann thrombasthenia 2023-09-20 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies have shown that this missense change affects ITGA2B function (PMID: 18791937). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 953015). This variant is also known as p.Gly236Glu. This missense change has been observed in individual(s) with clinical features of Glanzmann thrombasthenia (PMID: 12083483). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 267 of the ITGA2B protein (p.Gly267Glu).

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