2-208248468-G-A

Position:

chr2-208248468-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005896.4(IDH1):c.315C>T(p.Gly105=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0552 in 1,613,868 control chromosomes in the GnomAD database, including 2,834 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G105G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.067 ( 442 hom., cov: 32)

Exomes 𝑓: 0.054 ( 2392 hom. )

Consequence

IDH1
NM_005896.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.35

Variant links:

Genes affected

IDH1 (HGNC:5382): (isocitrate dehydrogenase (NADP(+)) 1) 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 cytoplasm and peroxisomes. It contains the PTS-1 peroxisomal targeting signal sequence. The presence of this enzyme in peroxisomes suggests roles in the regeneration of NADPH for intraperoxisomal reductions, such as the conversion of 2, 4-dienoyl-CoAs to 3-enoyl-CoAs, as well as in peroxisomal reactions that consume 2-oxoglutarate, namely the alpha-hydroxylation of phytanic acid. The cytoplasmic enzyme serves a significant role in cytoplasmic NADPH production. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Sep 2013]

IDH1 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=-0.5).

BP6

Variant 2-208248468-G-A is Benign according to our data. Variant chr2-208248468-G-A is described in ClinVar as [Benign]. Clinvar id is 402961.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.35 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
IDH1	NM_005896.4 linkuse as main transcript	c.315C>T	p.Gly105=	synonymous_variant	4/10	ENST00000345146.7
IDH1	NM_001282386.1 linkuse as main transcript	c.315C>T	p.Gly105=	synonymous_variant	4/10
IDH1	NM_001282387.1 linkuse as main transcript	c.315C>T	p.Gly105=	synonymous_variant	4/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IDH1	ENST00000345146.7 linkuse as main transcript	c.315C>T	p.Gly105=	synonymous_variant	4/10	1	NM_005896.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0665

AC:

10107

AN:

152062

Hom.:

441

Cov.:

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0600

Gnomad ASJ

AF:

0.0930

Gnomad EAS

AF:

0.0100

Gnomad SAS

AF:

0.0415

Gnomad FIN

AF:

0.0235

Gnomad MID

AF:

0.0478

Gnomad NFE

AF:

0.0568

Gnomad OTH

AF:

0.0656

GnomAD3 exomes

AF:

0.0506

AC:

12716

AN:

251452

Hom.:

418

AF XY:

0.0506

AC XY:

6881

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.104

Gnomad AMR exome

AF:

0.0377

Gnomad ASJ exome

AF:

0.0870

Gnomad EAS exome

AF:

0.00674

Gnomad SAS exome

AF:

0.0513

Gnomad FIN exome

AF:

0.0241

Gnomad NFE exome

AF:

0.0552

Gnomad OTH exome

AF:

0.0582

GnomAD4 exome

AF:

0.0540

AC:

78889

AN:

1461688

Hom.:

2392

Cov.:

AF XY:

0.0537

AC XY:

39059

AN XY:

727140

show subpopulations

Gnomad4 AFR exome

AF:

0.106

Gnomad4 AMR exome

AF:

0.0390

Gnomad4 ASJ exome

AF:

0.0822

Gnomad4 EAS exome

AF:

0.0119

Gnomad4 SAS exome

AF:

0.0484

Gnomad4 FIN exome

AF:

0.0277

Gnomad4 NFE exome

AF:

0.0551

Gnomad4 OTH exome

AF:

0.0619

GnomAD4 genome

AF:

0.0665

AC:

10120

AN:

152180

Hom.:

442

Cov.:

AF XY:

0.0648

AC XY:

4819

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.105

Gnomad4 AMR

AF:

0.0600

Gnomad4 ASJ

AF:

0.0930

Gnomad4 EAS

AF:

0.0101

Gnomad4 SAS

AF:

0.0411

Gnomad4 FIN

AF:

0.0235

Gnomad4 NFE

AF:

0.0568

Gnomad4 OTH

AF:

0.0649

Alfa

AF:

0.0639

Hom.:

156

Bravo

AF:

0.0693

Asia WGS

AF:

0.0480

AC:

167

AN:

3478

EpiCase

AF:

0.0579

EpiControl

AF:

0.0603

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

9.8

DANN

Benign

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

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