ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.698del (p.Arg233fs)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel RCV004595740 SCV005088346 pathogenic Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2024-03-26 reviewed by expert panel curation NM_001754.5(RUNX1):c.698del (p.Arg233ProfsTer4) is a variant which is predicted to undergo nonsense mediated decay in a gene in which loss-of-function is an established mechanism (frameshift (-) c.98-c.758 as per VCEP specifications) (PVS1). Transactivation assays demonstrating altered transactivation (<20% of wt, and/or reduced to levels similar to well-established pathogenic variants such as R201Q or R166Q) (17.93%) (PS3_moderate). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting). This variant is a nonsense/frameshift variants that is downstream of c.98 (PM5_Supporting). In summary, this variant meets criteria to be classified as pathogenic. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PVS1, PS3_moderate, PM2_supporting, and PM5_supporting.

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