ClinVar Miner

Submissions for variant NM_000419.5(ITGA2B):c.175del (p.Asp59fs)

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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 RCV003222561 SCV003915977 pathogenic Glanzmann thrombasthenia 2023-02-23 reviewed by expert panel curation NM_000419.5(ITGA2B):c.175del (p.Asp59ThrfsTer?) is a frameshift variant that causes a premature stop codon at exon 3 and is predicted to undergo nonsense mediated decay (PVS1). At least one patient homozygous for this variant displayed mucocutaneous bleeding and impaired aggregation with all agonists except ristocetin, which is highly specific for Glanzmann thrombasthenia (PMID:28078347; PP4_moderate, PM3_supporting). Additionally, αIIbβ3 surface expression was reduced to 3.8%, as measured by flow cytometry. The variant was not found in gnomAD v2.1.1 (PM2_supporting). In summary, this variant meets the criteria to be classified as Pathogenic for autosomal recessive Glanzmann thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PSV1, PM2_supporting, PM3_supporting, PP4_moderate (PD VCEP specifications version 2.1).

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