ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.508+4C>A

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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 RCV005245542 SCV005894757 likely benign Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2024-06-24 reviewed by expert panel curation The NM_001754.5(RUNX1):c.508+4C>A is a variant is located in Intron 5. It affects a nucleotide within the consensus splice site. However, splice prediction algorithms do not predict an effect on splicing (BP4). This variant is present at a MAF of 0.00006 (0.006%, 1/16256 alleles) in the African/African American population of gnomADv2.1.1. The nucleotide is not highly conserved with a phyloP score of -2.61. In summary, this variant meets the criteria to be classified as Likely Benign for autosomal dominant hereditary thrombocytopenia and hematologic cancer predisposition syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy VCEP: BP4, BP7.
Labcorp Genetics (formerly Invitae), Labcorp RCV002585092 SCV003489337 uncertain significance Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2022-05-11 criteria provided, single submitter clinical testing This sequence change falls in intron 5 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. 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. 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. This variant has not been reported in the literature in individuals affected with RUNX1-related conditions. This variant is present in population databases (rs770788424, gnomAD 0.007%).

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