ClinVar Miner

Submissions for variant NM_000212.3(ITGB3):c.1094A>G (p.Asn365Ser)

dbSNP: rs2143107081
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen RCV001580232 SCV001809869 likely pathogenic Glanzmann thrombasthenia 2024-09-05 reviewed by expert panel curation The p.Asn365Ser missense variant on ITGB3 gene has been previously reported in the context of Glanzmann thrombasthenia. The highest population minor allele frequency in gnomAD v4.1 is 0.000001695 (2/1179950 alleles) in the European non-Finnish population, which is lower than the ClinGen PD VCEP threshold (<0.0001; PM2_Supporting). This variant has been reported to occur in compound heterozygous state with a pathogenic frameshift variant (p.Gln508Serfs*) in one proband (PM3_supporting) who meets the PD-VCEP criteria for the GT phenotype (PMID: 25728920). The patient presented with significant mucocutaneous bleeding. Platelet aggregometry demonstrated absence of platelet aggregation with 3 platelet agonists and normal aggregation with ristocetin. Surface expression of αIIbβ3 was demonstrated to be reduced (<5%) by flowcytometry (PMID: 25728920); PP4_strong). Multiple in silico tools predict this variant to be deleterious (REVEL score = 0.94). This variant meets GT specific criteria for PP4_Strong, PM3_supporting, PP3 and PM2_supporting and is therefore classified as Likely Pathogenic.

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