Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV003448388 | SCV004176276 | pathogenic | Hereditary thrombocytopenia and hematologic cancer predisposition syndrome | 2023-12-09 | reviewed by expert panel | curation | The c.351+1G>T variant is a canonical splice site variant predicted to disrupt exon 4 donor splice site recognition. The c.351+1G>T variant is a canonical splice site variant predicted to disrupt exon 4 donor splice site recognition. According to SpliceAI prediction, the donor loss is 0.99 at -1 bp. This variant is expected to result in exon 4 skipping, leading to a frameshift (PVS1). This variant has been reported in 2 probands (#17, and #44.2), both meeting at least one of the RUNX1-phenotypic criteria (PS4_Moderate; PMID: 24100448 and 32935436). This variant is completely absent from all population databases (gnomAD v2.1.1, v3.1.2, and gnomAD v4.0.0) with at least 20x coverage for RUNX1 (PM2_supporting). In summary, this variant meets criteria to be classified as pathogenic. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PVS1, PS4_moderate, PM2_supporting. |
Birmingham Platelet Group; University of Birmingham | RCV001270534 | SCV001450833 | pathogenic | Abnormal bleeding; Thrombocytopenia | 2020-05-01 | no assertion criteria provided | research |