Submissions for variant NM_001754.5(RUNX1):c.1142_1145dup (p.Pro383fs)

dbSNP: rs2145876252

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel	RCV004699486	SCV005205692	likely pathogenic	Hereditary thrombocytopenia and hematologic cancer predisposition syndrome	2024-09-10	reviewed by expert panel	curation	NM_001754.5(RUNX1):c.1142_1145dup (p.Pro383AlafsTer?) is a duplication variant that results in a frameshift in the last exon. This variant is located downstream of c.98 in transcript NM_001754.4 (PM5_Supporting), is not expected to undergo nonsense-mediated decay, and the resulting frameshift affects positions c.759-c.1440 as per VCEP specifications, which is critical for protein function (PVS1_Strong). It is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). In summary, this variant meets the criteria to be classified as likely pathogenic for hereditary thrombocytopenia and hematologic cancer predisposition syndrome based on the ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PVS1_strong, PM2_supporting, PM5_supporting.
Genetic Services Laboratory, University of Chicago	RCV001817935	SCV002067434	uncertain significance	not specified	2020-01-07	criteria provided, single submitter	clinical testing