ClinVar Miner

Submissions for variant NM_000419.5(ITGA2B):c.1769G>A (p.Arg590Gln)

gnomAD frequency: 0.00002  dbSNP: rs747930676
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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 RCV001580252 SCV001809895 uncertain significance Glanzmann thrombasthenia 2024-08-20 reviewed by expert panel curation The NM_000419.5(ITGA2B):c.1769G>A (p.Arg590Gln) has been reported in one patient with suspected type 3 GT (PMID: 29675921). GT39 of PMID: 29675921 meets the criteria for PP4_moderate; including mucocutaneous bleeding, and impaired aggregation with all agonists except ristocetin. There was reduced function of αIIbβ3 measured by flow cytometry, however 43% PAC-1 binding was not considered sufficient to meet PP4_strong. GT39 is compound heterozygous for Cys857Phe (classified as VUS b the PD VCEP; SCV001809850.1) and Arg590Gln. Based on the evidence available at this time, the variant is classified as uncertain significance. GT-specific criteria applied: PP4_moderate.
Labcorp Genetics (formerly Invitae), Labcorp RCV001580252 SCV005735235 uncertain significance Glanzmann thrombasthenia 2024-08-20 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 590 of the ITGA2B protein (p.Arg590Gln). This variant is present in population databases (rs747930676, gnomAD 0.02%). This missense change has been observed in individual(s) with Glanzmann's thrombasthenia (PMID: 29675921). ClinVar contains an entry for this variant (Variation ID: 1210202). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt ITGA2B protein function with a negative predictive value of 80%. 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.

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