ClinVar Miner

Submissions for variant NM_000419.5(ITGA2B):c.571T>G (p.Phe191Val)

dbSNP: rs2048639566
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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 RCV001290465 SCV001478501 likely pathogenic Glanzmann thrombasthenia 2023-11-02 reviewed by expert panel curation The NM_000419.5(ITGA2B):c.571T>G (p.Phe191Val) variant has been reported in at least 1 compound heterozygous GT proband (PMID:25728920) with a phenotype highly specific to Glanzmann thrombasthenia with mucocutaneous bleeding, impaired aggregation with all agonists except ristocetin, and reduced surface expression of αIIbβ3 measured by flow cytometry (PP4_Strong). It is absent from population databases, including gnomADv2.1.1 (PM2_supporting). Splicing predictors, HSF and SpliceAI, agree that there is activation of a cryptic donor site with potential alteration of splicing. This was confirmed by minigene study in PMID: 20020534; sequencing revealed the most common transcript contained a 4-bp deletion that introduced a frameshift and a premature stop codon in exon 7 of 30 (PM4). In summary, this variant meets criteria to be classified as likely pathogenic for GT. GT-specific criteria applied: PM2_Supporting, PM4, and PP4_Strong.

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