rs150943639
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BS1BS2
The NM_002168.4(IDH2):c.327G>A(p.Val109=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00375 in 1,614,162 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0024 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0039 ( 13 hom. )
Consequence
IDH2
NM_002168.4 synonymous
NM_002168.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.153
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 -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.28).
BP6
?
Variant 15-90090525-C-T is Benign according to our data. Variant chr15-90090525-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 158665.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Likely_benign=1, Uncertain_significance=1}. Variant chr15-90090525-C-T is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-0.153 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00243 (370/152340) while in subpopulation NFE AF= 0.00398 (271/68020). AF 95% confidence interval is 0.00359. There are 0 homozygotes in gnomad4. There are 170 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High AC in GnomAd at 371 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IDH2 | NM_002168.4 | c.327G>A | p.Val109= | synonymous_variant | 3/11 | ENST00000330062.8 | |
IDH2 | NM_001289910.1 | c.171G>A | p.Val57= | synonymous_variant | 3/11 | ||
IDH2 | NM_001290114.2 | c.-17-1778G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IDH2 | ENST00000330062.8 | c.327G>A | p.Val109= | synonymous_variant | 3/11 | 1 | NM_002168.4 | P1 | |
IDH2 | ENST00000540499.2 | c.171G>A | p.Val57= | synonymous_variant | 3/11 | 2 | |||
IDH2 | ENST00000559482.5 | c.207+1028G>A | intron_variant | 5 | |||||
IDH2 | ENST00000560061.1 | c.116-1778G>A | intron_variant, NMD_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00244 AC: 371AN: 152222Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00247 AC: 621AN: 251372Hom.: 0 AF XY: 0.00243 AC XY: 330AN XY: 135884
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GnomAD4 exome AF: 0.00388 AC: 5679AN: 1461822Hom.: 13 Cov.: 32 AF XY: 0.00362 AC XY: 2633AN XY: 727202
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 16, 2014 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Sep 01, 2023 | IDH2: BP4, BP7 - |
D-2-hydroxyglutaric aciduria 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
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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