ClinVar Miner

Submissions for variant NM_000419.5(ITGA2B):c.257T>C (p.Leu86Pro)

dbSNP: rs1052533574
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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 RCV001225273 SCV001397540 pathogenic Glanzmann thrombasthenia 2020-09-08 reviewed by expert panel curation The ITGA2B missense variant c.257T>C (p.Leu86Pro), is demonstrated to cause reduced integrin surface expression in transfection experiments in COS7 cells (PMID: 12181054). The variant is absent from population databases. It has a REVEL score >0.7 (0.859). At least 2 compound heterozygous probands are reported in the literature (PMID: 12181054, 25728920). One proband has the pathogenic c.1440-13_1440-1del variant (assessed by Platelet Disorders VCEP) in trans (without phase confirmation). In summary, based on the available evidence at this time, the Leu86Pro variant is classified "Pathogenic". GT-specific criteria applied: PS3_Moderate, PM2_Supporting, PM3, PP3, PP4_Strong.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004782674 SCV005395424 likely pathogenic Glanzmann thrombasthenia 1 2024-09-18 criteria provided, single submitter clinical testing Variant summary: ITGA2B c.257T>C (p.Leu86Pro) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 243976 control chromosomes. c.257T>C has been reported in the literature in individuals affected with Glanzmann thrombasthenia 1 (Nurden_2015, Tanaka_2002). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in reduced integrin complex surface expression (Tanaka_2002). The following publications have been ascertained in the context of this evaluation (PMID: 25728920, 37647632, 12181054). ClinVar contains an entry for this variant (Variation ID: 953037). Based on the evidence outlined above, the variant was classified as likely pathogenic.

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