ClinVar Miner

Submissions for variant NM_000419.5(ITGA2B):c.1440-13_1440-1del

dbSNP: rs2048585829
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen RCV001225233 SCV001397483 pathogenic Glanzmann thrombasthenia 2020-09-08 reviewed by expert panel curation The NM_000419.4:c.1440-13_1440-1del variant that deletes 13 bp in intron 14 including the splice acceptor is predicted to use an alternative crytpic splice acceptor site, resulting in a 2-bp deletion of the mRNA inducing a frameshift responsible for a premature stop codon after 105 amino acids. The resulting transcript is predicted to undergo NMD (PMID: 25728920). It is absent in population databases. At least 10 individuals have been reported with the variant in the heterozygous or compound heterozygous state (PMID: 25728920, 22102273, 22394243, 20020534) and the variant was found to segregate in at least two additional family members (PMID: 22394243). In summary, based on the evidence available at this time, the c.1440-13_1440-1del variant is classified "Pathogenic". GT-specific criteria applied: PVS1, PM2_Supporting, PM3_Strong, PP1_Moderate, PP4_Strong.
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology RCV002222678 SCV002500891 uncertain significance Glanzmann thrombasthenia 1 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004738199 SCV005362924 pathogenic ITGA2B-related disorder 2024-09-05 no assertion criteria provided clinical testing The ITGA2B c.1440-13_1440-1del13 variant is predicted to result in a deletion affecting a canonical splice site. This variant was reported in the heterozygous or compound heterozygous state in several individuals with Glanzmann thrombasthenia (see for example the 13bp deletion involving IVS14 in Table 1, aka c.1442-13_1442-1del in Jallu et al 2010. PubMed ID: 20020534), and has been categorized as pathogenic by the ClinGen Platelet Disorders Variant Curation Expert Panel (https://www.ncbi.nlm.nih.gov/clinvar/variation/953002/). This variant has not been reported in a large population database, indicating this variant is rare. This variant is interpreted as pathogenic.

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