ClinVar Miner

Submissions for variant NM_000419.5(ITGA2B):c.1946+1G>A (rs746091910)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Platelet Disorders Variant Curation Expert Panel,ClinGen RCV000689591 SCV001397586 pathogenic Glanzmann thrombasthenia 2020-09-06 reviewed by expert panel curation The splicing variant, c.1946+1G>A, has been observed in at least one compound heterozygous patient in the literature with a phenotype highly specific to GT (PMID: 15099289). The canonical IVS19+1 donor splice site is lost, which is expected to result in skipping of exon 19 causing a reading frame shift with 10 new amino acids followed by a stop codon that leads to NMD. The variant is absent form ExAC, gnomAD, and 1000 Genomes. In summary, this variant meets criteria to be classified as Pathogenic for GT. GT-specific criteria applied: PVS1, PM2_Supporting, PP4_Moderate.
Invitae RCV000689591 SCV000817248 likely pathogenic Glanzmann thrombasthenia 2017-11-30 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 19 of the ITGA2B gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs746091910, ExAC 0.07%). This variant has been reported in a child affected with Glanzmann’s thrombasthenia (PMID: 15099289). 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. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ITGA2B are known to be pathogenic (PMID: 21917754). 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.