Submissions for variant NM_001754.5(RUNX1):c.1086G>C (p.Ser362=)

gnomAD frequency: 0.00072  dbSNP: rs143947839

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel	RCV000464138	SCV001244328	benign	Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1	2020-01-13	reviewed by expert panel	curation	This synonymous variant has a MAF of 0.002828 (0.2828%, 61/21570, 43140 alleles) in the African (gnomAD) cohort is =/> 0.0015 (0.15%) (BA1). It is predicted by SSF and MES to lead to either 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; in addition, evolutionary conservation prediction algorithms predict the site as not being highly conserved (PhyloP score -0.12 < 0.1 [-14.1;6.4]) (BP4+BP7). 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, BP4, and BP7.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000464138	SCV000560760	benign	Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1	2025-01-21	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV001821362	SCV002071693	likely benign	not specified	2017-11-20	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV002256309	SCV002535839	benign	Hereditary cancer-predisposing syndrome	2020-12-07	criteria provided, single submitter	curation
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV003316617	SCV004015359	benign	Acute myeloid leukemia	2023-07-07	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV004717635	SCV005310046	benign	not provided		criteria provided, single submitter	not provided
Ambry Genetics	RCV004955529	SCV005495284	likely benign	Inborn genetic diseases	2024-08-21	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000464138	SCV005881281	benign	Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1	2025-02-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003925365	SCV004752821	likely benign	RUNX1-related disorder	2019-07-02	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).