ClinVar Miner

Submissions for variant NM_000419.5(ITGA2B):c.416C>T (p.Ala139Val)

dbSNP: rs2143489510
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen RCV001580238 SCV001809875 likely pathogenic Glanzmann thrombasthenia 2024-08-20 reviewed by expert panel curation The ITGA2B missense variant NM_000419.5:c.416C>T replaces the alanine residue with a valine residue (p.Ala139Val). This variant is absent from population databases including gnomADv4.1.0 (PM2_supporting), but has been observed in homozygosity in two individuals suspected to have Glanzmann's thrombasthenia (GT) (Patient PF in PMID: 12083483; GT22 in PMID: 16463284) (PM3). At least one of these individuals (Patient PF in PMID: 12083483) has a phenotype specific for GT (PP4_strong); bleeding phenotype strongly indicative of Glanzmann's thrombasthenia; impaired aggregation to at least two agonists, but normal or only mildly reduced agglutination with ristocetin; <10% expression of GPIIb/IIIa; direct sequencing of all coding regions and intron/exon boundaries of ITGA2B and ITGB3. The variant is predicted by in silico tools to be damaging to protein function (REVEL score 0.794; PP3). In summary, this variant meets criteria to be classified as likely pathogenic for GT. GT-specific criteria applied: PM2_supporting, PM3, PP3, PP4_strong.

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