rs267606870
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PM5PP3_Strong
The NM_002168.4(IDH2):c.418C>T(p.Arg140Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R140G) has been classified as Pathogenic.
Frequency
Consequence
NM_002168.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IDH2 | NM_002168.4 | c.418C>T | p.Arg140Trp | missense_variant | 4/11 | ENST00000330062.8 | |
IDH2 | NM_001289910.1 | c.262C>T | p.Arg88Trp | missense_variant | 4/11 | ||
IDH2 | NM_001290114.2 | c.28C>T | p.Arg10Trp | missense_variant | 2/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IDH2 | ENST00000330062.8 | c.418C>T | p.Arg140Trp | missense_variant | 4/11 | 1 | NM_002168.4 | P1 | |
IDH2 | ENST00000540499.2 | c.262C>T | p.Arg88Trp | missense_variant | 4/11 | 2 | |||
IDH2 | ENST00000559482.5 | c.208-201C>T | intron_variant | 5 | |||||
IDH2 | ENST00000560061.1 | c.*43C>T | 3_prime_UTR_variant, NMD_transcript_variant | 2/9 | 2 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461864Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727234
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Myelodysplastic syndrome Pathogenic:1
Likely pathogenic, no assertion criteria provided | literature only | Database of Curated Mutations (DoCM) | May 31, 2016 | - - |
Multiple myeloma Pathogenic:1
Likely pathogenic, no assertion criteria provided | literature only | Database of Curated Mutations (DoCM) | May 31, 2016 | - - |
Neoplasm of the large intestine Pathogenic:1
Likely pathogenic, no assertion criteria provided | literature only | Database of Curated Mutations (DoCM) | May 31, 2016 | - - |
Squamous cell carcinoma of the head and neck Pathogenic:1
Likely pathogenic, no assertion criteria provided | literature only | Database of Curated Mutations (DoCM) | May 31, 2016 | - - |
Acute myeloid leukemia Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | Database of Curated Mutations (DoCM) | May 31, 2016 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 25, 2023 | Has not been previously published as pathogenic or benign germline variant to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 32629801, 26331834, 31604779, 20929327, 27904446, 30577887) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at