ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.186C>G (p.Asp62Glu)

dbSNP: rs886450546
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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 RCV005001208 SCV005627409 uncertain significance Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2025-01-15 reviewed by expert panel curation NM_001754.5(RUNX1):c.186C>G (p.Asp62Glu) is a missense variant which has a REVEL score < 0.50 (0.31) and a SpliceAI score ≤ 0.20 (0.02) (BP4). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting). In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4, PM2_supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV001343202 SCV001537166 uncertain significance Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2020-03-12 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamic acid amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. This variant has not been reported in the literature in individuals with RUNX1-related conditions. This sequence change replaces aspartic acid with glutamic acid at codon 62 of the RUNX1 protein (p.Asp62Glu). The aspartic acid residue is weakly conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. This variant is not present in population databases (ExAC no frequency).

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