dbSNP rs369445642: IDH2:p.Val8Gly (chr15-90102368-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002168.4(IDH2):c.23T>G(p.Val8Gly) variant causes a missense 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V8A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

IDH2
NM_002168.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0680

Publications

0 publications found

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:

IDH2-DT (HGNC:53154): (IDH2 divergent transcript)

IDH2-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14733687).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002168.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
IDH2	NM_002168.4	MANE Select	c.23T>G	p.Val8Gly	missense	Exon 1 of 11	NP_002159.2
IDH2-DT	NR_149130.1		n.237A>C		non_coding_transcript_exon	Exon 1 of 3
IDH2	NM_001290114.2		c.-110T>G		5_prime_UTR	Exon 1 of 9	NP_001277043.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
IDH2	ENST00000330062.8	TSL:1 MANE Select	c.23T>G	p.Val8Gly	missense	Exon 1 of 11	ENSP00000331897.4
IDH2	ENST00000559482.5	TSL:5	c.23T>G	p.Val8Gly	missense	Exon 1 of 8	ENSP00000453016.1
IDH2	ENST00000560061.1	TSL:2	n.23T>G		non_coding_transcript_exon	Exon 1 of 9	ENSP00000453254.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1214090

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

595936

African (AFR)

AF:

0.00

AC:

AN:

25324

American (AMR)

AF:

0.00

AC:

AN:

23166

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20196

East Asian (EAS)

AF:

0.00

AC:

AN:

26130

South Asian (SAS)

AF:

0.00

AC:

AN:

57900

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28104

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4112

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

981042

Other (OTH)

AF:

0.00

AC:

AN:

48116

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.0052

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.18

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.66

M_CAP

Pathogenic

0.81

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

PhyloP100

-0.068

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

0.85

REVEL

Benign

0.16

Sift

Benign

0.32

Sift4G

Benign

0.48

Polyphen

0.099

Vest4

0.29

MutPred

0.35

Gain of disorder (P = 0.0158)

MVP

0.55

MPC

0.70

ClinPred

0.072

GERP RS

0.98

PromoterAI

-0.047

Neutral

(source)

Varity_R

0.045

gMVP

0.43

Mutation Taster

=85/15

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over