Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001225246 | SCV001397498 | likely pathogenic | Glanzmann thrombasthenia | 2021-03-05 | reviewed by expert panel | curation | The NM_000419.4:c.527C>A (p.Pro176His) missense variant was identified from an individual in The National Heart, Lung and Blood Institute Exome Sequencing Project (ESP) whose full genotype and phenotype were not reported. It occurs at an extremely low frequency of 0.000008248 in the African population of gnomAD. It is predicted to have a deleterious effect (REVEL score of 0.913) which was confirmed by functional studies showing virtually no mature GPIIb protein in transfected HEK293 cells (PMID: 25827233). This variant occurs at the same residue as the pathogenic variant Pro176Ala. In summary, this variant meets criteria to be classified as Likely Pathogenic for GT. GT specific criteria used: PS3_moderate, PM2_Supporting, PM5, PP3. |