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

gnomAD frequency: 0.00072  dbSNP: rs143947839

Total submissions: 6

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.
Invitae	RCV000464138	SCV000560760	benign	Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1	2023-12-15	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
PreventionGenetics, part of Exact Sciences	RCV003925365	SCV004752821	likely benign	RUNX1-related disorder	2019-07-02	criteria provided, single submitter	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).