ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.956G>A (p.Ser319Asn)

dbSNP: rs2145907184
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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 RCV004699517 SCV005205672 likely benign Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2024-08-28 reviewed by expert panel curation NM_001754.5(RUNX1):c.956G>A (p.Ser319Asn) is a missense variant which has been demonstrated to have normal transactivation (80-115% of wt) in transactivation assays (BS3_supporting; PMID: 34166225). This missense variant has a REVEL score < 0.50 (0.127) and a SpliceAI score ≤ 0.20 (0.01) (BP4). 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 benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BS3_supporting, BP4, PM2_supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV001899527 SCV002139065 uncertain significance Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2022-12-14 criteria provided, single submitter clinical testing Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RUNX1 protein function. ClinVar contains an entry for this variant (Variation ID: 1371213). This missense change has been observed in individual(s) with acute lymphoblastic leukemia (PMID: 34166225). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 319 of the RUNX1 protein (p.Ser319Asn). 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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