rs766206710
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. BP4PM2
This summary comes from the ClinGen Evidence Repository: This synonymous variant is predicted by SSF and MES to lead to either an increase in the canonical splice site score or a decrease of the canonical splice site score by no more than 10% and no putative cryptic splice sites are created (BP4). However, evolutionary conservation prediction algorithms predict the site as being weakly conserved (PhyloP score: 0.77 < 0.1 [-14.1;6.4]) and the variant is not the reference nucleotide in one primate and/or three mammal species. In addition, this variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2). In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4 and PM2. LINK:https://erepo.genome.network/evrepo/ui/classification/CA512318955/MONDO:0011071/008
Frequency
Consequence
NM_001754.5 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RUNX1 | NM_001754.5 | c.165G>A | p.Ala55= | synonymous_variant | 4/9 | ENST00000675419.1 | NP_001745.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RUNX1 | ENST00000675419.1 | c.165G>A | p.Ala55= | synonymous_variant | 4/9 | NM_001754.5 | ENSP00000501943 | A1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 6.90e-7 AC: 1AN: 1449128Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0AN XY: 721240
GnomAD4 genome Cov.: 32
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 | Apr 10, 2020 | This synonymous variant is predicted by SSF and MES to lead to either an increase in the canonical splice site score or a decrease of the canonical splice site score by no more than 10% and no putative cryptic splice sites are created (BP4). However, evolutionary conservation prediction algorithms predict the site as being weakly conserved (PhyloP score: 0.77 < 0.1 [-14.1;6.4]) and the variant is not the reference nucleotide in one primate and/or three mammal species. In addition, this variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2). In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4 and PM2. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 19, 2017 | - - |
Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 10, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at