ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.999dup (p.Arg334fs)

dbSNP: rs2145878129
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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 RCV004692766 SCV005196561 likely pathogenic Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2024-08-01 reviewed by expert panel curation NM_001754.5(RUNX1):c.999dup (p.Arg334fs) is a frameshift variant in exon 8 which is predicted to not undergo nonsense-mediated mRNA decay (PVS1_strong). It 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 likely pathogenic. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PVS1_strong, PM2_supporting, PM5_supporting.
Genetic Services Laboratory, University of Chicago RCV001817928 SCV002067411 likely pathogenic not provided 2020-02-24 criteria provided, single submitter clinical testing DNA sequence analysis of the RUNX1 gene demonstrated a 1 base pair duplication in exon 9, c.999dup. The c.999dup sequence change has not been described in population databases (gnomAD, ExAC). This sequence change is predicted to result in a frameshift leading to the formation of a premature stop codon 265 amino acids downstream of the duplication, p.Arg334Alafs*266. While this duplication has not previously been described in the literature, other frameshift duplications in the RUNX1 gene have been described in patients with RUNX1-related disorders (PMIDs: 19357396, 28181366).

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