Submissions for variant NM_001754.5(RUNX1):c.1269C>T (p.Arg423=)

gnomAD frequency: 0.00040  dbSNP: rs544247912

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel	RCV000226372	SCV000965631	benign	Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1	2019-08-02	reviewed by expert panel	curation	The MAF for the synonymous variant, NM_001754.4:c.1269C>T (p.Arg423=) is 0.00275 (0.2%, 14/5096 alleles) in the non-Finnish European subpopulation of the ExAC cohort, which is >/= 0.0015 (0.15%) (BA1). This variant is predicted by SSF and MES to lead to an increase in the canonical splice site score or a decrease of the canonical splice site score by no more than 10% AND no putative cryptic splice sites are created (BP4). In summary, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BA1, BP4.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000226372	SCV000287179	benign	Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1	2024-02-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000226372	SCV000435944	benign	Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1	2018-01-12	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.
PreventionGenetics, part of Exact Sciences	RCV000680388	SCV000807759	likely benign	not provided	2017-09-06	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001336401	SCV001529768	uncertain significance	Acute myeloid leukemia	2018-01-17	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Genetic Services Laboratory, University of Chicago	RCV001818590	SCV002067879	benign	not specified	2020-01-13	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV002256139	SCV002535844	benign	Hereditary cancer-predisposing syndrome	2020-07-20	criteria provided, single submitter	curation
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV001336401	SCV004015362	benign	Acute myeloid leukemia	2023-07-07	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000680388	SCV005310045	benign	not provided		criteria provided, single submitter	not provided