Submissions for variant NM_001754.5(RUNX1):c.830del (p.Pro277fs)

dbSNP: rs2145909826

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel	RCV004692761	SCV005196565	pathogenic	Hereditary thrombocytopenia and hematologic cancer predisposition syndrome	2024-08-01	reviewed by expert panel	curation	NM_001754.5(RUNX1):c.830del (p.Pro277fs) is a frameshift variant predicted to undergo NMD (PVS1 CNV tree). This variant is downstream of c.98 (PM5_Supporting). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting). In summary, this variant meets criteria to be classified as pathogenic. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PVS1, PM2_supporting, PM5_supporting.
Genetic Services Laboratory, University of Chicago	RCV001822642	SCV002071803	likely pathogenic	not provided	2021-07-28	criteria provided, single submitter	clinical testing	DNA sequence analysis of the RUNX1 gene demonstrated a single base pair deletion in exon 9 RUNX1 c.830del. This sequence change results in an amino acid frameshift and creates a premature stop codon 33 amino acids downstream of the change, p.Pro277Hisfs*34. This sequence change is predicted to result in an abnormal transcript, which may be degraded, or may lead to the production of a truncated RUNX1 protein with potentially abnormal function. While this deletion has not previously been described in the literature, several other frameshift and truncating variants downstream of this position have been described in individuals with RUNX1-related disorders. This sequence change is likely causative of this individual's phenotype; however functional studies have not been performed to prove this conclusively.