Submissions for variant NM_001754.5(RUNX1):c.351+3A>G

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel	RCV004695259	SCV005196419	uncertain significance	Hereditary thrombocytopenia and hematologic cancer predisposition syndrome	2024-08-01	reviewed by expert panel	curation	NM_001754.5(RUNX1):c.351+3A>G is an intronic variant which is completely absent from all population databases with at least 20x coverage for RUNX1 in gnomAD v2.1.1 and v3.1.2 (PM2_supporting). This intronic variant has a SpliceAI score ≤ 0.20 (0.02) (BP4). In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PM2_supporting, BP4.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002863702	SCV003232599	uncertain significance	Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1	2022-09-05	criteria provided, single submitter	clinical testing	This sequence change falls in intron 4 of the RUNX1 gene. It does not directly change the encoded amino acid sequence of the RUNX1 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RUNX1-related conditions. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.