Submissions for variant NM_001754.5(RUNX1):c.1260C>G (p.Gly420=)

dbSNP: rs2145874515

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel	RCV003408156	SCV004123214	likely benign	Hereditary thrombocytopenia and hematologic cancer predisposition syndrome	2023-11-13	reviewed by expert panel	curation	The c.1260C>G (p.Gly420=) variant is a synonymous (silent) variant that is not predicted by SpliceAI to impact splicing (BP4); in addition, an evolutionary conservation algorithm predicts the site as being non-conserved (PhyloP score = -1.00262 in GRCh38) (BP7). The variant also has not been reported in relevant cases or the literature. In summary, this variant meets the criteria to be classified as likely benign for hereditary thrombocytopenia and hematologic cancer predisposition syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy VCEP: BP4 and BP7.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002178562	SCV002474628	likely benign	Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1	2024-09-06	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV004703244	SCV005206249	likely benign	not provided		criteria provided, single submitter	not provided
CeGaT Center for Human Genetics Tuebingen	RCV004703244	SCV005436306	likely benign	not provided	2024-10-01	criteria provided, single submitter	clinical testing	RUNX1: BP4, BP7
Ambry Genetics	RCV004965800	SCV005495303	likely benign	Inborn genetic diseases	2024-11-28	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.
PreventionGenetics, part of Exact Sciences	RCV003903581	SCV004721515	likely benign	RUNX1-related disorder	2021-10-26	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).