ClinVar Miner

Submissions for variant NM_000419.5(ITGA2B):c.2094+2T>C

dbSNP: rs1555613692
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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 RCV000527479 SCV001809917 pathogenic Glanzmann thrombasthenia 2021-05-07 reviewed by expert panel curation The NM_000419.5(ITGA2B):c.2094+2T>C splice variant is predicted to cause skipping of exon 20, introducing a premature termination codon, and the resulting mRNA product is predicted to undergo nonsense mediated decay, leading to loss of normal protein function. This variant has been observed in homozygosity in one individual reported to have Glanzmann's thrombasthenia (GT), however sufficient phenotype information was not provided to determine if the individual's phenotype is specific for GT. This variant is absent from population databases, including gnomAD. In summary, this variant meets criteria to be classified as pathogenic for GT. GT-specific criteria applied: PVS1, PM2_Supporting, and PM3_supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV000527479 SCV000629597 pathogenic Glanzmann thrombasthenia 2021-05-12 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 20 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). This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with Glanzmann thrombasthenia (Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 458368). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.

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