Submissions for variant NM_001754.5(RUNX1):c.444C>T (p.Thr148=)

gnomAD frequency: 0.00002  dbSNP: rs773689002

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel	RCV000374908	SCV000965644	likely benign	Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1	2019-07-26	reviewed by expert panel	curation	The NM_001754.4:c.444C>T (p.Thr148=) variant is a synonymous variant that 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 (BP4). In addition, evolutionary conservation prediction algorithms predict the site as not being highly conserved (PhyloP score -4.3832 < 0.1) (BP7). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4, BP7.
Illumina Laboratory Services, Illumina	RCV000374908	SCV000435949	likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000374908	SCV000761123	likely benign	Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1	2024-06-17	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV002258878	SCV002535865	likely benign	Hereditary cancer-predisposing syndrome	2021-04-16	criteria provided, single submitter	curation
PreventionGenetics, part of Exact Sciences	RCV003912429	SCV004730210	likely benign	RUNX1-related disorder	2022-04-04	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).