ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.97+1G>A

gnomAD frequency: 0.00001  dbSNP: rs375131372
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 RCV004692676 SCV005196410 uncertain significance Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2024-08-01 reviewed by expert panel curation NM_001754.5(RUNX1):c.97+1G>A is a splice donor variant which is only predicted to affect isoform c. This variant is present in three alleles (European Non-Finnish), 0.002656% in gnomAD v2.1.1, and is absent in gnomAD v3.1.2 (mean depth coverage 30x). This variant has been reported in two probands meeting at least one of the RUNX1-phenotypic criteria (PS4_Moderate; PMID: 33075818). In summary, this variant meets the criteria to be classified as a variant of unknown significance. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PS4_Moderate.
Labcorp Genetics (formerly Invitae), Labcorp RCV001378678 SCV001576301 uncertain significance Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2023-09-11 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 1067421). Disruption of this splice site has been observed in individual(s) with acute myeloid leukemia (PMID: 33075818). This variant is present in population databases (rs375131372, gnomAD 0.002%). This sequence change affects a donor splice site in intron 3 of the RUNX1 gene. However, it is currently unclear if variants that occur in this region of the gene cause disease.

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.