ClinVar Miner

Submissions for variant NM_000419.5(ITGA2B):c.1973del (p.Ala658fs)

dbSNP: rs1598378490
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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 RCV004577531 SCV005061684 likely pathogenic Glanzmann thrombasthenia 2024-05-02 reviewed by expert panel curation The frameshift variant NM_000419.5(ITGA2B):c.1973del (p.Ala658GlufsTer?) has been reported in one individual with a disorder of platelet function, (TGP0048 in PMID:31064749). Communication with the authors confirmed a diagnosis of Glanzmann thrombasthenia. The patient had impaired platelet aggregation and prolonged bleeding after dental extraction. This individual, TGP0048, is compound heterozygous for this frameshift variant and a variant of uncertain significance (NM_000419.5(ITGA2B):c.188+5G>T). The c.1973del frameshift variant causes a premature stop codon in exon 20/30, which is predicted to undergo nonsense mediated decay in a disease that is loss of function (PVS1). The highest population minor allele frequency in gnomAD v4.0.0 is 0.00006335 (1/15786 alleles) in the African/African American population, which is lower than the ClinGen PD VCEP threshold (<0.0001; PM2_Supporting). In summary, this variant meets the criteria to be classified as Likely Pathogenic for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PVS1 and PM2_supporting (VCEP specifications version 2.1.0).
NIHR Bioresource Rare Diseases, University of Cambridge RCV000851728 SCV000899581 likely pathogenic Abnormal platelet aggregation 2019-02-01 criteria provided, single submitter research

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