Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV005001341 | SCV005627436 | pathogenic | Hereditary thrombocytopenia and hematologic cancer predisposition syndrome | 2024-11-04 | reviewed by expert panel | curation | NM_001754.5(RUNX1):c.422C>A (p.Ser141Ter) is a nonsense variant which is predicted to undergo nonsense mediated decay in a gene in which loss-of-function is an established mechanism (nonsense c.98-c.916 as per VCEP specifications) (PVS1, PM5_supporting). This variant is completely absent from all population databases 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, PM5_supporting, PM2_supporting. |
| Labcorp Genetics |
RCV003034342 | SCV003330178 | pathogenic | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 | 2024-10-15 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ser141*) in the RUNX1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RUNX1 are known to be pathogenic (PMID: 18723428, 24100448). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RUNX1-related conditions. ClinVar contains an entry for this variant (Variation ID: 2112037). For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV003465901 | SCV004209878 | likely pathogenic | Acute myeloid leukemia | 2022-08-11 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV004725467 | SCV005335877 | likely pathogenic | RUNX1-related disorder | 2024-07-30 | no assertion criteria provided | clinical testing | The RUNX1 c.422C>A variant is predicted to result in premature protein termination (p.Ser141*). This variant has been reported along with 12q deletion in an individual with myelodysplastic syndrome (Table 1 and Table S2: patient #9, Illman et al. 2023. PubMed ID: 36579442). This variant has not been reported in a large population database, indicating this variant is rare. Nonsense variants in RUNX1 are expected to be pathogenic. This variant is interpreted as likely pathogenic. |