ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.101C>A (p.Ala34Asp)

dbSNP: rs2058006183
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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 RCV004774568 SCV005382814 uncertain significance Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2024-10-29 reviewed by expert panel curation NM_001754.5(RUNX1):c.101C>A (p.Ala34Asp) is a missense variant which has a REVEL score of 0.456, which is less than 0.50, and a SpliceAI score of ≤ 0.20. This variant is completely absent from gnomAD v2.1.1 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: PM2_supporting, BP4.
Labcorp Genetics (formerly Invitae), Labcorp RCV001970503 SCV002255798 uncertain significance Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2021-01-11 criteria provided, single submitter clinical testing This sequence change replaces alanine with aspartic acid at codon 34 of the RUNX1 protein (p.Ala34Asp). The alanine residue is weakly conserved and there is a moderate physicochemical difference between alanine and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with RUNX1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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.

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