Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV000003036 | SCV001397553 | uncertain significance | Glanzmann thrombasthenia | 2023-03-16 | reviewed by expert panel | curation | The c.2870C>T; p.Ser957Leu variant has been reported, in the homozygous state, in at least one proband (PMID: 20020534). It is absent from population databases ExAC and gnomAD. The Ser957Leu mutant complex was expressed in COS-7 cells and, in three replicates, expression of the complex (% positive cells) was assessed by flow cytometry, using antibodies to alpha-IIb, beta-3 or the complex, finding approximately 19% positive cells for the αIIbβ3 complex compared to WT. In summary, this variant meets criteria to be classified as uncertain significance for GT. GT-specific criteria applied: PS3_supporting, PM2_Supporting and PM3_Supporting. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004689406 | SCV005185306 | uncertain significance | not specified | 2024-05-09 | criteria provided, single submitter | clinical testing | Variant summary: ITGA2B c.2870C>T (p.Ser957Leu) results in a non-conservative amino acid change located in the Integrin alpha, third immunoglobulin-like domain (IPR048286) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250924 control chromosomes. c.2870C>T has been reported in the literature in homozygous state in one individual affected with Glanzmann thrombasthenia 1 (Jallu_2010). 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 (approximately 33% of WT) "alpha IIb beta3" Fibrinogen receptor complex expression at the surface of Cos-7 cells that correlated with 10% beta3 expression at the surface of patient platelets (Jallu_2010). The following publications have been ascertained in the context of this evaluation (PMID: 20020534). ClinVar contains an entry for this variant (Variation ID: 2902). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |
| OMIM | RCV001580158 | SCV000023194 | pathogenic | Glanzmann thrombasthenia 1 | 2010-03-01 | no assertion criteria provided | literature only |