chr15-90084269-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_002168.4(IDH2):​c.1356G>A​(p.Gln452=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Consequence

IDH2
NM_002168.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.532
Variant links:
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 Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
Variant 15-90084269-C-T is Benign according to our data. Variant chr15-90084269-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1582248.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.532 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IDH2NM_002168.4 linkuse as main transcriptc.1356G>A p.Gln452= synonymous_variant 11/11 ENST00000330062.8
IDH2NM_001289910.1 linkuse as main transcriptc.1200G>A p.Gln400= synonymous_variant 11/11
IDH2NM_001290114.2 linkuse as main transcriptc.966G>A p.Gln322= synonymous_variant 9/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IDH2ENST00000330062.8 linkuse as main transcriptc.1356G>A p.Gln452= synonymous_variant 11/111 NM_002168.4 P1P48735-1
IDH2ENST00000540499.2 linkuse as main transcriptc.1200G>A p.Gln400= synonymous_variant 11/112 P48735-2
IDH2ENST00000559482.5 linkuse as main transcriptc.936G>A p.Gln312= synonymous_variant 8/85
IDH2ENST00000560061.1 linkuse as main transcriptc.*981G>A 3_prime_UTR_variant, NMD_transcript_variant 9/92

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

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 submitterclinical testingInvitaeJul 19, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.46
CADD
Benign
8.8
DANN
Benign
0.83

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-90627501; API