Submissions for variant NM_001754.5(RUNX1):c.927C>T (p.Gly309=)

gnomAD frequency: 0.01119  dbSNP: rs59802347

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel	RCV001290706	SCV001478843	benign	Hereditary thrombocytopenia and hematologic cancer predisposition syndrome	2021-01-12	reviewed by expert panel	curation	This synonymous variant is present in gnomAD (v2 and v3) at an allele frequency >0.15% with at least 5 alleles in any general continental population (BA1); in addition, the variant was found in homozygosity in the population database (BP2). Although the variant is predicted by SSF and MES to create a putative cryptic donor splice site at c.925 (insignificant prediction by SpliceAI), evolutionary conservation prediction algorithms predict the site as being weakly conserved (PhyloP score: 1.25 > 0.1 [-14.1;6.4]), and the variant is not the reference nucleotide in one primate and/or three mammal species, SSF and MES predict either an increase in the canonical splice site score or a decrease of the canonical splice site score by no more than 10%. In summary, the clinical significance of this variant is benign. ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BA1 and BP2.
Invitae	RCV000228598	SCV000287194	benign	Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1	2024-01-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000228598	SCV000435946	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	RCV003891807	SCV000807807	benign	RUNX1-related disorder	2023-01-10	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).
GeneDx	RCV000680436	SCV001781123	likely benign	not provided	2021-06-02	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV003316255	SCV004015352	benign	Acute myeloid leukemia	2023-07-07	criteria provided, single submitter	clinical testing