rs769213771
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PM2_SupportingBP4
This summary comes from the ClinGen Evidence Repository: NM_001754.5(RUNX1):c.182C>G (p.Pro61Arg) is a missense variant which is absent from gnomAD v2.1.1 and v3.1.2 (PM2_supporting). This variant has a REVEL score < 0.50 (0.316), and a SpliceAI score ≤ 0.20 (0.0) (BP4). 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. LINK:https://erepo.genome.network/evrepo/ui/classification/CA410203987/MONDO:0011071/008
Frequency
Consequence
NM_001754.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RUNX1 | NM_001754.5 | c.182C>G | p.Pro61Arg | missense_variant | 4/9 | ENST00000675419.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RUNX1 | ENST00000675419.1 | c.182C>G | p.Pro61Arg | missense_variant | 4/9 | NM_001754.5 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.90e-7 AC: 1AN: 1450018Hom.: 0 Cov.: 35 AF XY: 0.00000139 AC XY: 1AN XY: 721306
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 07, 2022 | This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 61 of the RUNX1 protein (p.Pro61Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RUNX1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.