Submissions for variant NM_001754.5(RUNX1):c.654C>T (p.Ser218=)

gnomAD frequency: 0.00063  dbSNP: rs145230602

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel	RCV000230532	SCV000965630	likely benign	Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1	2019-08-02	reviewed by expert panel	curation	The MAF of the synonymous variant, NM_001754.4:c.654C>T (p.Ser218=), is 0.00105 (0.1%, 36/34418 alleles) in the Latino subpopulation of the gnomAD cohort, which is between 0.00015 (0.015%) and 0.0015 (0.15%) (BS1). This synonymous 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 likely benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BS1, BP4.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000230532	SCV000287189	benign	Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1	2024-01-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000230532	SCV000435947	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.
PreventionGenetics, part of Exact Sciences	RCV000680430	SCV000807801	likely benign	not provided	2018-04-05	criteria provided, single submitter	clinical testing
GeneDx	RCV000680430	SCV001767905	likely benign	not provided	2021-04-30	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 27106701)
Sema4, Sema4	RCV002257544	SCV002535873	benign	Hereditary cancer-predisposing syndrome	2020-11-28	criteria provided, single submitter	curation
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV003316254	SCV004015360	benign	Acute myeloid leukemia	2023-07-07	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000680430	SCV005206251	likely benign	not provided		criteria provided, single submitter	not provided