ClinVar Miner

Submissions for variant NM_000212.3(ITGB3):c.921C>A (p.Tyr307Ter)

dbSNP: rs2143099209
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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 RCV001803442 SCV002047594 pathogenic Glanzmann thrombasthenia 2021-07-14 reviewed by expert panel curation The ITGB3 nonsense variant NM_000212.3:c.921C>A (p.Tyr307Ter) introduces a premature termination codon in exon 6 of 15 total exons 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 three individuals with a phenotype specific for Glanzmann's thrombasthenia (GT) and haplotype analysis suggests a founder effect (GT21, GT25, GT55, PMID: 16463284). Furthermore, this variant is absent from population databases. In summary, this variant meets criteria to be classified as pathogenic for GT. GT-specific criteria applied: PVS1, PM2_Supporting, PM3, PP4_Moderate.
Neuberg Centre For Genomic Medicine, NCGM RCV004728822 SCV005329357 pathogenic Glanzmann thrombasthenia 2 2023-05-20 criteria provided, single submitter clinical testing The observed stop gained variant c.921C>A (p.Tyr307Ter) in the ITGB3 gene has been reported previously in individuals affected with Glanzmann's thrombasthenia (GT) and haplotype analysis suggests a founder effect (Peretz H, et al., 2006). This variant is absent in the gnomAD Exomes. It is submitted to ClinVar as Pathogenic. Computational evidence (MutationTaster - Disease causing) predicts damaging effect on protein structure and function for this variant. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Pathogenic.

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