chr21-34792298-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. BP4PM2_Supporting
This summary comes from the ClinGen Evidence Repository: NM_001754.5(RUNX1):c.1280G>C (p.Arg427Pro) is a missense variant which is completely absent from all population databases with at least 20x coverage for RUNX1 in gnomAD v2.1.1 and v3.1.2 (PM2_supporting). This missense variant has a REVEL score <0.50 (0.499) (BP4). This variant was reported in ClinVar in 2022 by Invitae, but the affected status of the proband is unknown (Variation ID 2089328). 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. LINK:https://erepo.genome.network/evrepo/ui/classification/CA410147522/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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RUNX1 | NM_001754.5 | c.1280G>C | p.Arg427Pro | missense_variant | 9/9 | ENST00000675419.1 | NP_001745.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RUNX1 | ENST00000675419.1 | c.1280G>C | p.Arg427Pro | missense_variant | 9/9 | NM_001754.5 | ENSP00000501943 | A1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome Cov.: 33
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Hereditary thrombocytopenia and hematologic cancer predisposition syndrome Uncertain:1
Uncertain significance, reviewed by expert panel | curation | ClinGen Myeloid Malignancy Variant Curation Expert Panel | Jul 25, 2024 | NM_001754.5(RUNX1):c.1280G>C (p.Arg427Pro) is a missense variant which is completely absent from all population databases with at least 20x coverage for RUNX1 in gnomAD v2.1.1 and v3.1.2 (PM2_supporting). This missense variant has a REVEL score <0.50 (0.499) (BP4). This variant was reported in ClinVar in 2022 by Invitae, but the affected status of the proband is unknown (Variation ID 2089328). 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. - |
Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 24, 2022 | This variant has not been reported in the literature in individuals affected with RUNX1-related conditions. 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. 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 427 of the RUNX1 protein (p.Arg427Pro). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.