ClinVar Miner

Submissions for variant NM_000419.5(ITGA2B):c.337C>T (p.Gln113Ter)

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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 RCV002511149 SCV002820936 pathogenic Glanzmann thrombasthenia 2022-04-07 reviewed by expert panel curation The NM_000419.5(ITGA2B):c.337C>T (p.Gln113Ter) variant in exon 3/30 is a nonsense variant predicted to lead to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). At least one patient (reported via personal communication with Dr. Jose Rivera, Servicio de Hematolog_x0019_ıa y Oncolog_x0019_ıa Me_x0019_dica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonacio_x0019_n, Universidad de Murcia) with this variant (in combination with c.2150T>C (p.Leu717Pro)) displayed mucocutaneous bleeding and impaired aggregation with all agonists except ristocetin, which is highly specific for Glanzmann thrombasthenia. Additionally, αIIbβ3 surface expression was absent, as measured by flow cytometry and Western blot, and ITGA2B and ITGB3 were sequenced across all exons and intron/exon boundaries (PP4_Strong). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary this variant meets 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: PVS1, PP4_Strong, PM2_Supporting. (VCEP specifications version 2; date of approval 03/15/2022)
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology RCV002281026 SCV002569354 uncertain significance Glanzmann thrombasthenia 1 criteria provided, single submitter clinical testing

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