ClinVar Miner

Submissions for variant NM_000419.5(ITGA2B):c.1639C>T (p.Arg547Cys)

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
Neuberg Centre For Genomic Medicine, NCGM RCV003448771 SCV004176475 uncertain significance Platelet-type bleeding disorder 16 2023-03-01 criteria provided, single submitter clinical testing The missense variant c.1639C>T(p.Arg547Cys) in ITGA2B gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The variant has 0.003% allele frequency in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. The amino acid Arginine at position 547 is changed to a Cysteine changing protein sequence and it might alter its composition and physico-chemical properties. The variant is predicted to be damaging by SIFT. The amino acid change p.Arg547Cys in ITGA2B is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV003500852 SCV004253878 uncertain significance Glanzmann thrombasthenia 2023-05-03 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 547 of the ITGA2B protein (p.Arg547Cys). This variant is present in population databases (rs372316950, gnomAD 0.005%). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ITGA2B protein function. This variant has not been reported in the literature in individuals affected with ITGA2B-related conditions.

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.