Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV002264703 | SCV002546386 | uncertain significance | Hereditary thrombocytopenia and hematologic cancer predisposition syndrome | 2021-06-22 | reviewed by expert panel | curation | The NM_001754.5(RUNX1):c.649G>A (p.Gly217Arg) variant is reported in gnomAD v3.1 at an MAF of 0.0001064 (0.01%, 7/65790 alleles) in the non-Finish European subpopulation, which does not meet the thresholds for BA1 (≥0.0015) or BS1 (0.00015-0.0015). This variant has been reported in one proband meeting at least one of the RUNX1-phenotypic criteria (PMID: 29365323); however, PS4 cannot be applied as 9 alleles overall are noted in gnomAD. This missense variant has a REVEL score of 0.624, which does not meet the threshold for PP3 (>0.75) or BP4 (<0.15). In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: none. |
Genetic Services Laboratory, |
RCV000501810 | SCV000596878 | uncertain significance | not specified | 2017-02-16 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000694237 | SCV000822672 | uncertain significance | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 | 2023-09-15 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 217 of the RUNX1 protein (p.Gly217Arg). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RUNX1 protein function. ClinVar contains an entry for this variant (Variation ID: 436614). This variant is also known as Gly190Arg. This missense change has been observed in individual(s) with familial platelet disorder with B-cell precursor acute lymphoblastic leukemia and/or hereditary hematopoietic malignancies (PMID: 20880108, 29365323). This variant is present in population databases (rs749004431, gnomAD 0.008%). |
Fulgent Genetics, |
RCV000765505 | SCV000896808 | uncertain significance | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1; Acute myeloid leukemia | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Gene |
RCV002473028 | SCV002770245 | uncertain significance | not provided | 2023-04-04 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in individuals with multiple myeloma, acute myeloid leukemia, and chronic myelogenous leukemia (Yamamoto et al., 2013; Drazer et al., 2018); Published functional studies demonstrate association with a cellular growth advantage (Yamamoto et al., 2013); This variant is associated with the following publications: (PMID: 20880108, 24098673, 28277065, 29365323) |
Baylor Genetics | RCV003470632 | SCV004209829 | uncertain significance | Acute myeloid leukemia | 2023-10-26 | criteria provided, single submitter | clinical testing |