Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
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Clin |
RCV001290469 | SCV001478505 | likely pathogenic | Glanzmann thrombasthenia | 2023-12-19 | reviewed by expert panel | curation | The NM_000212.3(ITGB3):c.760C>A (p.Gln254Lys) missense variant is reported in at least 1 compound heterozygous GT proband as well as one additional affected family member (PMID: 31088191; PP1_supporting), with the likely pathogenic variant Cys549Ser (PM3). Proband 2 of PMID: 31088191 was a 6-year-old girl diagnosed with recurrent hematemesis at age 2. Platelet aggregation was absent or defective upon stimulation with physiological stimuli like AA and ADP, but platelets agglutinated near normal in response to ristocetin. Flow cytometric studies found reduced expression of αIIbβ3. Together this is highly specific for Glanzmann thrombasthenia (PP4_Moderate) It is absent from all population databases, including gnomAD (PM2_Supporting) and is predicted damaging by in-silico tools (REVEL score of 0.972; PP3). In summary, this variant meets criteria to be classified as Likely Pathogenic for GT. GT-specific criteria applied: PM2_Supporting, PM3, PP1, PP3, and PP4_Moderate. |