ClinVar Miner

Submissions for variant NM_000419.5(ITGA2B):c.2333A>C (p.Gln778Pro)

gnomAD frequency: 0.00001  dbSNP: rs74475415
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen RCV000490428 SCV001397557 pathogenic Glanzmann thrombasthenia 2020-09-08 reviewed by expert panel curation The NM_000419.4:c.2333A>C variant that results in the p.Gln778Pro amino acid change is reported in at least 5 homozygous and 6 compound heterozygous probands in the literature (PMID: 9722314, 22190468, 9763559, 29675921, 32237906). At least 5 variants in trans with Gln778Pro have been curated and evaluated for PM3 scoring. The variant is reported at frequency <0.0001 in the combined gnomAD v3 and v2.1.1 datasets. In summary, based on the available evidence at this time, the Gln778Pro variant is classified as pathogenic. GT-specific criteria applied: PM2_Supporting, PM3_Strong, PP4_Strong.
Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center RCV000490428 SCV000267365 likely pathogenic Glanzmann thrombasthenia 2016-03-18 criteria provided, single submitter reference population
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology RCV002254157 SCV002525463 pathogenic Glanzmann thrombasthenia 1 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004547508 SCV004105555 pathogenic ITGA2B-related disorder 2023-07-29 criteria provided, single submitter clinical testing The ITGA2B c.2333A>C variant is predicted to result in the amino acid substitution p.Gln778Pro. This variant is also known as p.Gln747Pro in the literature. This variant was reported in the homozygous and compound heterozygous states in individuals with Glanzmann thrombasthenia (Ambo et al. 1998. PubMed ID: 9722314; Park et al. 2012. PubMed ID: 22190468; Bastida et al. 2018. PubMed ID: 28983057; Zhou et al. 2018. PubMed ID: 29675921). Functional studies showed that this variant impairs surface expression and endoproteolytic cleavage (Ambo et al. 1998. PubMed ID: 9722314; Tadokoro et al. 1998. PubMed ID: 9763559). This variant is reported in 0.011% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-42453691-T-G) and is classified as pathogenic by ClinGen Platelet Disorders Variant Curation Expert Panel (https://www.ncbi.nlm.nih.gov/clinvar/variation/225393/). This variant is interpreted as pathogenic.

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