rs11540478
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_002168.4(IDH2):c.1050C>T(p.Thr350=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0156 in 1,551,798 control chromosomes in the GnomAD database, including 1,600 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.052 ( 520 hom., cov: 32)
Exomes 𝑓: 0.012 ( 1080 hom. )
Consequence
IDH2
NM_002168.4 synonymous
NM_002168.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -5.17
Genes affected
IDH2 (HGNC:5383): (isocitrate dehydrogenase (NADP(+)) 2) Isocitrate dehydrogenases catalyze the oxidative decarboxylation of isocitrate to 2-oxoglutarate. These enzymes belong to two distinct subclasses, one of which utilizes NAD(+) as the electron acceptor and the other NADP(+). Five isocitrate dehydrogenases have been reported: three NAD(+)-dependent isocitrate dehydrogenases, which localize to the mitochondrial matrix, and two NADP(+)-dependent isocitrate dehydrogenases, one of which is mitochondrial and the other predominantly cytosolic. Each NADP(+)-dependent isozyme is a homodimer. The protein encoded by this gene is the NADP(+)-dependent isocitrate dehydrogenase found in the mitochondria. It plays a role in intermediary metabolism and energy production. This protein may tightly associate or interact with the pyruvate dehydrogenase complex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
?
Variant 15-90085305-G-A is Benign according to our data. Variant chr15-90085305-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 158663.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-90085305-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-5.17 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IDH2 | NM_002168.4 | c.1050C>T | p.Thr350= | synonymous_variant | 8/11 | ENST00000330062.8 | |
IDH2 | NM_001289910.1 | c.894C>T | p.Thr298= | synonymous_variant | 8/11 | ||
IDH2 | NM_001290114.2 | c.660C>T | p.Thr220= | synonymous_variant | 6/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IDH2 | ENST00000330062.8 | c.1050C>T | p.Thr350= | synonymous_variant | 8/11 | 1 | NM_002168.4 | P1 | |
IDH2 | ENST00000540499.2 | c.894C>T | p.Thr298= | synonymous_variant | 8/11 | 2 | |||
IDH2 | ENST00000559482.5 | c.723C>T | p.Thr241= | synonymous_variant | 6/8 | 5 | |||
IDH2 | ENST00000560061.1 | c.*675C>T | 3_prime_UTR_variant, NMD_transcript_variant | 6/9 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0519 AC: 7880AN: 151976Hom.: 519 Cov.: 32
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GnomAD3 exomes AF: 0.0352 AC: 5524AN: 156770Hom.: 375 AF XY: 0.0291 AC XY: 2404AN XY: 82632
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GnomAD4 exome AF: 0.0116 AC: 16254AN: 1399704Hom.: 1080 Cov.: 32 AF XY: 0.0107 AC XY: 7401AN XY: 690512
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GnomAD4 genome ? AF: 0.0519 AC: 7889AN: 152094Hom.: 520 Cov.: 32 AF XY: 0.0517 AC XY: 3846AN XY: 74348
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 04, 2021 | This variant is associated with the following publications: (PMID: 27649069) - |
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Mar 16, 2016 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Oct 31, 2013 | - - |
D-2-hydroxyglutaric aciduria 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at