ClinVar Miner

Submissions for variant NM_000419.5(ITGA2B):c.2602-2A>G

dbSNP: rs2143436505
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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 RCV001580239 SCV001809877 likely pathogenic Glanzmann thrombasthenia 2023-09-07 reviewed by expert panel curation The NM_000419.5(ITGA2B):c.2602-2A>G variant disrupts the canonical splice acceptor site in intron 25 and is predicted to result in skipping of exon 26, removing 3.9% of the protein (PVS1_moderate). The variant is absent from population database, including gnomADv2.1.1 (PM2_supporting). It is reported in one compound heterozygous individual with the c.2602-3C>A and Thr281Ile (PMID: 25373348). GT16 of PMID: 25373348 meets bleeding phenotype, aggregometry criteria, integrin expression is reported to be <5% reduced by flow cytometry, and all exons of ITGA2B and ITGB3 genes as well as surrounding intron regions were sequenced (PP4_strong). In summary, based on evidence at this time the variant is classified as likely pathogenic for GT. GT-specific criteria applied: PVS1_Moderate, PP4_Strong, PM2_Supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV001580239 SCV004298231 likely pathogenic Glanzmann thrombasthenia 2023-01-25 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 1210193). This variant has not been reported in the literature in individuals affected with ITGA2B-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 25 of the ITGA2B gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ITGA2B are known to be pathogenic (PMID: 21917754).

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