ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.351+4C>T

dbSNP: rs1229295922
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel RCV005001182 SCV005627430 likely benign Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2024-11-04 reviewed by expert panel curation NM_001754.5(RUNX1):c.351+4C>T is an intronic variant which has a SpliceAI score ≤ 0.20 (0.01) (BP4). This variant has a SpliceAI score ≤ 0.20 (0.01) and evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score ≤ 2.0 (0.53) (BP7). 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 likely benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4, BP7, PM2_supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV001238719 SCV001411547 uncertain significance Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2019-11-06 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency). 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. Nucleotide substitutions within 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, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with RUNX1-related conditions. 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, but it affects a nucleotide within the consensus splice site of the intron.

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