Submissions for variant NM_001754.5(RUNX1):c.1272G>C (p.Ser424=)

dbSNP: rs1459260782

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel	RCV004595548	SCV005088280	likely benign	Hereditary thrombocytopenia and hematologic cancer predisposition syndrome	2024-07-11	reviewed by expert panel	curation	NM_001754.5(RUNX1): c.1272G>C (p.Ser424=) is a synonymous variant. Evolutionary conservation algorithms predict the site as not being conserved (PhyloP -2.00124 < 2.0), meeting BP7. Since it is synonymous, no REVEL score is applicable, and SpliceAI score is ≤ 0.20 (0.00), meeting BP4. In summary, this variant meets the criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4, BP7.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000918003	SCV001063299	likely benign	Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1	2025-01-31	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV002256599	SCV002535847	likely benign	Hereditary cancer-predisposing syndrome	2021-05-12	criteria provided, single submitter	curation
Fulgent Genetics, Fulgent Genetics	RCV002505358	SCV002801814	likely benign	Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1; Acute myeloid leukemia	2022-02-16	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV004704321	SCV005206246	likely benign	not provided		criteria provided, single submitter	not provided
Ambry Genetics	RCV004958279	SCV005495299	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	RCV003978019	SCV004786587	likely benign	RUNX1-related disorder	2024-05-01	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).