Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000003031 | SCV001397477 | likely pathogenic | Glanzmann thrombasthenia | 2023-09-07 | reviewed by expert panel | curation | The NM_000419.5 (ITGA2B):c.1346G>A variant that results in the Gly449Asp amino acid change is reported in one homozygous Glanzmann thrombasthenia patient in the literature (PMID: 7508443; PM3_supporting). The patient had a severe bleeding phenotype, abnormal aggregometry and absent surface expression of GPIIb (PP4_moderate). It is absent in population databases, including gnomADv2.1.1 (PM2_supporting), and is predicted damaging by in-silico tools (REVEL score 0.895; PP3). Experimental evidence shows the variant results in lack of surface expression of the alphaIIb-beta3 complex (PMID: 7508443; PS3_moderate). In summary, based on the available evidence at this time, the Gly449Asp variant is classified as likely pathogenic for autosomal recessive Glanzmann thrombasthenia. GT-specific criteria applied: PM2_Supporting, PP3, PP4_Moderate, PS3_Moderate and PM3_Supporting. |
OMIM | RCV001580161 | SCV000023189 | pathogenic | Glanzmann thrombasthenia 1 | 2021-04-13 | no assertion criteria provided | literature only |