chr21-34792191-G-T
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001754.5(RUNX1):c.1387C>A(p.Pro463Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000722 in 1,385,328 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P463L) has been classified as Uncertain significance.
Frequency
Consequence
NM_001754.5 missense
Scores
Clinical Significance
Conservation
Publications
- hereditary thrombocytopenia and hematologic cancer predisposition syndromeInheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
- hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)
- acute myeloid leukemiaInheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
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ACMG classification
Our verdict: Uncertain_significance. The variant received 4 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD2 exomes AF: 0.00000718 AC: 1AN: 139258 AF XY: 0.0000132 show subpopulations
GnomAD4 exome AF: 7.22e-7 AC: 1AN: 1385328Hom.: 0 Cov.: 33 AF XY: 0.00000146 AC XY: 1AN XY: 684330 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
Age Distribution
GnomAD4 genome Cov.: 31
ClinVar
Not reported inComputational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at