ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.97G>A (p.Asp33Asn)

dbSNP: rs781761402
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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 RCV004735542 SCV005367723 uncertain significance Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2024-09-25 reviewed by expert panel curation NM_001754.5(RUNX1):c.97G>A (p.Asp33Asn) is a missense variant has a SpliceAI score ≥ 0.38 (Acceptor Loss: 0.68; Donor Loss: 0.76) and is predicted to impact splicing (PP3). 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: PP3.
Labcorp Genetics (formerly Invitae), Labcorp RCV000475097 SCV000550154 uncertain significance Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2023-06-02 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 409811). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown this missense change is associated with skipping of exon 3, but one or more of the resulting mRNA isoform(s) may be naturally occurring (Invitae). 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 missense change has been observed in individual(s) with clinical features of thrombocytopenia (PMID: 32208489). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 33 of the RUNX1 protein (p.Asp33Asn). This variant also falls at the last nucleotide of exon 3, which is part of the consensus splice site for this exon. This variant is present in population databases (rs781761402, gnomAD 0.003%).

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