chr15-90084266-C-T
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2
The NM_002168.4(IDH2):c.1359G>A(p.Ter453=) variant causes a stop retained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,613,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000036 ( 0 hom. )
Consequence
IDH2
NM_002168.4 stop_retained
NM_002168.4 stop_retained
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.01
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 -9 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
Variant 15-90084266-C-T is Benign according to our data. Variant chr15-90084266-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2918612.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=1.01 with no splicing effect.
BS2
High AC in GnomAdExome4 at 52 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IDH2 | NM_002168.4 | c.1359G>A | p.Ter453= | stop_retained_variant | 11/11 | ENST00000330062.8 | |
IDH2 | NM_001289910.1 | c.1203G>A | p.Ter401= | stop_retained_variant | 11/11 | ||
IDH2 | NM_001290114.2 | c.969G>A | p.Ter323= | stop_retained_variant | 9/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IDH2 | ENST00000330062.8 | c.1359G>A | p.Ter453= | stop_retained_variant | 11/11 | 1 | NM_002168.4 | P1 | |
IDH2 | ENST00000540499.2 | c.1203G>A | p.Ter401= | stop_retained_variant | 11/11 | 2 | |||
IDH2 | ENST00000559482.5 | c.939G>A | p.Ter313= | stop_retained_variant | 8/8 | 5 | |||
IDH2 | ENST00000560061.1 | c.*984G>A | 3_prime_UTR_variant, NMD_transcript_variant | 9/9 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152226Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000279 AC: 7AN: 250494Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135518
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GnomAD4 exome AF: 0.0000356 AC: 52AN: 1461436Hom.: 0 Cov.: 30 AF XY: 0.0000371 AC XY: 27AN XY: 727036
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152226Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74358
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
D-2-hydroxyglutaric aciduria 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 10, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at