ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.167T>C (p.Leu56Ser)

gnomAD frequency: 0.01206  dbSNP: rs111527738
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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel RCV000226755 SCV000965641 benign Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2019-07-26 reviewed by expert panel curation The NM_001754.4:c.167T>C (p.Leu56Ser) variant has a MAF of 0.03259 (3.259%, 518/15,894 alleles) in the South Asian subpopulation of the ExAC cohort that is >/= 0.0015 (0.15%) (BA1). This variant is detected in homozygous state (56) in gnomAD population database (BP2). Transactivation assays demonstrating normal transactivation (80-115% of wt) and data from secondary assays demonstrate normal DNA binding, CBF-beta binding and sub-cellular localization (BS3; PMID: 23817177). Two patients reported in PMID:29365323 with AML. But PS4 can not apply in combined with BA1. In summary, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BA1, BS3, BP2.
Invitae RCV000226755 SCV000287182 benign Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2024-02-01 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003891806 SCV000308031 benign RUNX1-related disorder 2019-10-22 criteria provided, single submitter clinical testing This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Illumina Laboratory Services, Illumina RCV000226755 SCV000435952 benign Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000226755 SCV000743126 benign Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2015-01-08 criteria provided, single submitter clinical testing
GeneDx RCV000680395 SCV001753940 benign not provided 2019-07-12 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 31385734, 31289210, 11921279, 21343560, 27106701, 22753902, 28386644)
Sema4, Sema4 RCV002256141 SCV002535853 benign Hereditary cancer-predisposing syndrome 2020-10-21 criteria provided, single submitter curation
CeGaT Center for Human Genetics Tuebingen RCV000680395 SCV003916330 benign not provided 2023-03-01 criteria provided, single submitter clinical testing RUNX1: PP3, BS1, BS2
KCCC/NGS Laboratory, Kuwait Cancer Control Center RCV002277588 SCV004015357 benign Acute myeloid leukemia 2023-07-07 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000226755 SCV000745582 benign Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2015-05-08 no assertion criteria provided clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000680395 SCV001798345 likely benign not provided no assertion criteria provided clinical testing
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology RCV000226755 SCV002515757 uncertain significance Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 no assertion criteria provided research
Nadeem Sheikh Lab, University of the Punjab RCV002277588 SCV002564649 likely pathogenic Acute myeloid leukemia no assertion criteria provided clinical testing

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