Submissions for variant NM_001754.5(RUNX1):c.806-15T>C

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel	RCV004595685	SCV005088261	likely benign	Hereditary thrombocytopenia and hematologic cancer predisposition syndrome	2024-07-11	reviewed by expert panel	curation	NM_001754.5:c.806-15T>C is an intronic variant occurring in intron 7. This variant is completely absent from all population databases, including gnomAD v2.1.1 and v3.1.2, which have coverage of at least 20x for the RUNX1 gene at this position (PM2_supporting). Additionally, the variant has SpliceAI ∆ scores of ≤ 0.20, with a prediction of 0.04 for the loss of the acceptor splice site and of 0.03 for the loss of the donor splice site, thus indicating a low likelihood of altering splicing (BP4). Evolutionary conservation algorithms also suggest that the site is not conserved, as indicated by a PhyloPway score of 0.647, which is below the threshold of 2.0 (BP7). Furthermore, there is no known previous report of this variant to our knowledge. In summary, this variant meets the criteria to be classified as likely benign according to ACMG/AMP criteria, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PM2_supporting, BP4, BP7 PM2_supporting.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003088017	SCV003477319	likely benign	Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1	2023-11-10	criteria provided, single submitter	clinical testing