ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.239A>C (p.Glu80Ala)

gnomAD frequency: 0.00001  dbSNP: rs1313711063
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel RCV003411797 SCV004123157 uncertain significance Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2023-11-13 reviewed by expert panel curation NM_001754.5(RUNX1):c.239A>C (p.Glu80Ala) is a missense mutation. This variant has been seen three times in gnomADv2.1 at a MAF of 0.00001223 (0.001821%, 2/109846 in the European (Non-/finnish) sub-population). It does not meet any population criteria. The computational predictor REVEL gives a score of >0.50 (0.856). There is no predicted splice effect (SpliceAI=0). The variant has not been reported in patients with the RUNX1-defined phenotype. 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: No criteria are met.
Labcorp Genetics (formerly Invitae), Labcorp RCV000814968 SCV000955407 uncertain significance Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2023-02-26 criteria provided, single submitter clinical testing 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. Experimental studies have shown that this missense change does not substantially affect RUNX1 function (PMID: 34166225). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on RUNX1 protein function. ClinVar contains an entry for this variant (Variation ID: 658195). This missense change has been observed in individual(s) with clinical features of RUNX1-related conditions (PMID: 34166225). This variant is present in population databases (no rsID available, gnomAD 0.005%). This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 80 of the RUNX1 protein (p.Glu80Ala).
Baylor Genetics RCV003467474 SCV004209833 uncertain significance Acute myeloid leukemia 2023-10-16 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.