ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.792G>C (p.Gln264His)

dbSNP: rs2057110893
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel RCV004692603 SCV005196413 uncertain significance Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2024-08-01 reviewed by expert panel curation NM_001754.5(RUNX1):c.792G>C (p.Gln264His) is a missense variant which is absent from gnomAD v2 and v3 (PM2_Supporting) and has only been reported in a patient with oligopolyposis (PMID: 31942411). The computational predictor REVEL gives a score of 0.392, which is below the threshold of 0.50, and the splice site predictor SpliceAI indicated that the variant has no impact on splicing, evidence that does not predict a damaging effect on RUNX1 function (BP4). In summary, this variant meets the criteria to be classified as a VUS for autosomal dominant hereditary thrombocytopenia and hematologic cancer predisposition syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy VCEP: PM2_Supporting and BP4.
Labcorp Genetics (formerly Invitae), Labcorp RCV001344575 SCV001538635 uncertain significance Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2022-05-26 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 1040855). This variant has not been reported in the literature in individuals affected with RUNX1-related conditions. This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 264 of the RUNX1 protein (p.Gln264His).

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.