Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV003222577 | SCV003916005 | likely pathogenic | Glanzmann thrombasthenia | 2023-04-06 | reviewed by expert panel | curation | NM_000212.3(ITGB3):c.887_901del (p.Asp296_His300del) is an in frame deletion variant predicted to remove 5 amino acid residues (PM4). At least one patient (Patient GT41 in PMID:19691478) who was homozygous for this variant displayed mucocutaneous bleeding and impaired aggregation with all agonists except ristocetin, which is highly specific for Glanzmann thrombasthenia (PP4_moderate, PM3_supporting). The highest population minor allele frequency in gnomAD v2.1.1 is 0.00003266 (1/30616alleles) in the South Asian population, which meets criteria for PM2_supporting. In summary, this variant meets the criteria to be classified as likely pathogenic for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PM2_Supporting, PM4, PP4_moderate, and PM3_supporting. (VCEP specifications version 2; date of approval 04/06/2023) |