rs1555899813
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM5_SupportingPVS1PM2_SupportingPS4_Supporting
This summary comes from the ClinGen Evidence Repository: The NM_001754.4:c.215_216dup (p.Ser73Glyfs) variant is a frameshift variant that is predicted to introduce a premature stop codon and expected to result in nonsense-mediated mRNA decay (PVS1). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). This variant is a nonsense/frameshift variants that is downstream of c.98 (PM5_Supporting). This variant has been reported in one proband meeting at least one of the RUNX1-phenotypic criteria (PS4_ Supporting; SCV000638134.1). In summary, this variant meets criteria to be classified as pathogenic. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PVS1, PM2_supporting, PS4_Supporting, PM5_supporting. LINK:https://erepo.genome.network/evrepo/ui/classification/CA658656806/MONDO:0011071/008
Frequency
Consequence
NM_001754.5 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RUNX1 | NM_001754.5 | c.216_217insGG | p.Ser73GlyfsTer50 | frameshift_variant | 4/9 | ENST00000675419.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RUNX1 | ENST00000675419.1 | c.216_217insGG | p.Ser73GlyfsTer50 | frameshift_variant | 4/9 | NM_001754.5 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 35
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Hereditary thrombocytopenia and hematologic cancer predisposition syndrome Pathogenic:1
Pathogenic, reviewed by expert panel | curation | ClinGen Myeloid Malignancy Variant Curation Expert Panel | Mar 26, 2024 | The NM_001754.4:c.215_216dup (p.Ser73Glyfs) variant is a frameshift variant that is predicted to introduce a premature stop codon and expected to result in nonsense-mediated mRNA decay (PVS1). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). This variant is a nonsense/frameshift variants that is downstream of c.98 (PM5_Supporting). This variant has been reported in one proband meeting at least one of the RUNX1-phenotypic criteria (PS4_ Supporting; SCV000638134.1). In summary, this variant meets criteria to be classified as pathogenic. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PVS1, PM2_supporting, PS4_Supporting, PM5_supporting. - |
Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | May 09, 2019 | This sequence change creates a premature translational stop signal (p.Ser73Glyfs*50) in the RUNX1 gene. It is expected to result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in RUNX1 are known to be pathogenic (PMID: 18723428, 24100448). This variant has not been reported in the literature in individuals with RUNX1-related disease. ClinVar contains an entry for this variant (Variation ID: 463988). This variant is not present in population databases (ExAC no frequency). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at