ClinVar Miner

Submissions for variant NM_000419.5(ITGA2B):c.1878G>C (p.Gln626His) (rs80277041)

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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 RCV000003037 SCV001397555 likely pathogenic Glanzmann thrombasthenia 2020-06-15 reviewed by expert panel curation The c.1878G>C; p.Gln626His splicing variant has been reported in at least 5 GT probands (PMIDs: 20020534, 22513797, 25728920, 21113249, 29474205) and co-segregated in one additional affected family member (PMID: 22513797). It is absent from ExAC and gnomAD. Flow cytometric studies of the mutant protein expressed in COS-7 cells showed that the mutation did not prevent expression of the GPIIb/IIIa complex on the cell surface (PMID: 20020534). However, the mutation was found to result in a splice site error, skipping of exon 18, which could explain the absence of mRNA in the patients (PMID: 20020534). Splicing predictors, HSF and MaxEntScan, agree that there is alteration to the WT donor site, most likely affecting splicing. In summary, this variant meets criteria to be classified as likely pathogenic for GT. GT-specific criteria applied: PM2_Supporting, PM3, PM4, PP3, PP4_Moderate, and PP1.
OMIM RCV000003037 SCV000023195 pathogenic Glanzmann thrombasthenia 2010-03-01 no assertion criteria provided literature only

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