Variant 15-90084384-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002168.4(IDH2):c.1272-31A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,597,912 control chromosomes in the GnomAD database, including 56,255 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 12595 hom., cov: 32)

Exomes 𝑓: 0.23 ( 43660 hom. )

Consequence

IDH2
NM_002168.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.904

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 15-90084384-T-C is Benign according to our data. Variant chr15-90084384-T-C is described in ClinVar as [Benign]. Clinvar id is 1260667.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
IDH2	NM_002168.4 linkuse as main transcript	c.1272-31A>G	intron_variant	ENST00000330062.8
IDH2	NM_001289910.1 linkuse as main transcript	c.1116-31A>G	intron_variant
IDH2	NM_001290114.2 linkuse as main transcript	c.882-31A>G	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
IDH2	ENST00000330062.8 linkuse as main transcript	c.1272-31A>G	intron_variant	1	NM_002168.4	P1	P48735-1
IDH2	ENST00000540499.2 linkuse as main transcript	c.1116-31A>G	intron_variant	2			P48735-2
IDH2	ENST00000559482.5 linkuse as main transcript	c.852-31A>G	intron_variant	5
IDH2	ENST00000560061.1 linkuse as main transcript	c.*897-31A>G	intron_variant, NMD_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.354

AC:

53777

AN:

151952

Hom.:

12548

Cov.:

show subpopulations

Gnomad AFR

AF:

0.678

Gnomad AMI

AF:

0.163

Gnomad AMR

AF:

0.296

Gnomad ASJ

AF:

0.195

Gnomad EAS

AF:

0.212

Gnomad SAS

AF:

0.220

Gnomad FIN

AF:

0.234

Gnomad MID

AF:

0.339

Gnomad NFE

AF:

0.220

Gnomad OTH

AF:

0.322

GnomAD3 exomes

AF:

0.259

AC:

61017

AN:

235948

Hom.:

9383

AF XY:

0.250

AC XY:

31879

AN XY:

127632

show subpopulations

Gnomad AFR exome

AF:

0.694

Gnomad AMR exome

AF:

0.260

Gnomad ASJ exome

AF:

0.188

Gnomad EAS exome

AF:

0.226

Gnomad SAS exome

AF:

0.241

Gnomad FIN exome

AF:

0.238

Gnomad NFE exome

AF:

0.218

Gnomad OTH exome

AF:

0.251

GnomAD4 exome

AF:

0.234

AC:

337845

AN:

1445842

Hom.:

43660

Cov.:

AF XY:

0.233

AC XY:

167297

AN XY:

719312

show subpopulations

Gnomad4 AFR exome

AF:

0.701

Gnomad4 AMR exome

AF:

0.266

Gnomad4 ASJ exome

AF:

0.187

Gnomad4 EAS exome

AF:

0.213

Gnomad4 SAS exome

AF:

0.240

Gnomad4 FIN exome

AF:

0.234

Gnomad4 NFE exome

AF:

0.218

Gnomad4 OTH exome

AF:

0.261

GnomAD4 genome

AF:

0.354

AC:

53876

AN:

152070

Hom.:

12595

Cov.:

AF XY:

0.349

AC XY:

25965

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.679

Gnomad4 AMR

AF:

0.296

Gnomad4 ASJ

AF:

0.195

Gnomad4 EAS

AF:

0.212

Gnomad4 SAS

AF:

0.221

Gnomad4 FIN

AF:

0.234

Gnomad4 NFE

AF:

0.220

Gnomad4 OTH

AF:

0.318

Alfa

AF:

0.264

Hom.:

1397

Bravo

AF:

0.374

Asia WGS

AF:

0.230

AC:

801

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.6

DANN

Benign

0.79

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