rs11540478

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.Thr350Thr) 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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -5.17

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]

IDH2 links:

Genome browser will be placed here

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 rank	MANE	Protein	UniProt
IDH2	NM_002168.4 link	c.1050C>T	p.Thr350Thr	synonymous_variant	Exon 8 of 11	ENST00000330062.8	NP_002159.2	P48735-1
IDH2	NM_001289910.1 link	c.894C>T	p.Thr298Thr	synonymous_variant	Exon 8 of 11		NP_001276839.1	P48735-2
IDH2	NM_001290114.2 link	c.660C>T	p.Thr220Thr	synonymous_variant	Exon 6 of 9		NP_001277043.1	P48735B4DSZ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IDH2	ENST00000330062.8 link	c.1050C>T	p.Thr350Thr	synonymous_variant	Exon 8 of 11	1	NM_002168.4	ENSP00000331897.4		P48735-1

Frequencies

GnomAD3 genomes

AF:

0.0519

AC:

7880

AN:

151976

Hom.:

519

Cov.:

show subpopulations

Gnomad AFR

AF:

0.145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0504

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.176

Gnomad SAS

AF:

0.00519

Gnomad FIN

AF:

0.000942

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00110

Gnomad OTH

AF:

0.0407

GnomAD3 exomes

AF:

0.0352

AC:

5524

AN:

156770

Hom.:

375

AF XY:

0.0291

AC XY:

2404

AN XY:

82632

show subpopulations

Gnomad AFR exome

AF:

0.153

Gnomad AMR exome

AF:

0.0737

Gnomad ASJ exome

AF:

0.000353

Gnomad EAS exome

AF:

0.184

Gnomad SAS exome

AF:

0.00257

Gnomad FIN exome

AF:

0.000529

Gnomad NFE exome

AF:

0.00135

Gnomad OTH exome

AF:

0.0242

GnomAD4 exome

AF:

0.0116

AC:

16254

AN:

1399704

Hom.:

1080

Cov.:

AF XY:

0.0107

AC XY:

7401

AN XY:

690512

show subpopulations

Gnomad4 AFR exome

AF:

0.150

Gnomad4 AMR exome

AF:

0.0718

Gnomad4 ASJ exome

AF:

0.000477

Gnomad4 EAS exome

AF:

0.172

Gnomad4 SAS exome

AF:

0.00347

Gnomad4 FIN exome

AF:

0.000571

Gnomad4 NFE exome

AF:

0.000896

Gnomad4 OTH exome

AF:

0.0254

GnomAD4 genome

AF:

0.0519

AC:

7889

AN:

152094

Hom.:

520

Cov.:

AF XY:

0.0517

AC XY:

3846

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.145

Gnomad4 AMR

AF:

0.0504

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.175

Gnomad4 SAS

AF:

0.00519

Gnomad4 FIN

AF:

0.000942

Gnomad4 NFE

AF:

0.00110

Gnomad4 OTH

AF:

0.0402

Alfa

AF:

0.0149

Hom.:

166

Bravo

AF:

0.0626

Asia WGS

AF:

0.0800

AC:

277

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 27649069) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 16, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not specified

Benign:1

Oct 31, 2013

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

D-2-hydroxyglutaric aciduria 2

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.089

DANN

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over