Genetic Variant IDI2:p.Trp144* (chr10-1019770-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_033261.3(IDI2):c.431G>A(p.Trp144*) variant causes a stop gained change. The variant allele was found at a frequency of 0.0657 in 1,613,818 control chromosomes in the GnomAD database, including 3,812 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.058 ( 297 hom., cov: 31)

Exomes 𝑓: 0.067 ( 3515 hom. )

Consequence

IDI2
NM_033261.3 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.87

Variant links:

Genes affected

IDI2 (HGNC:23487): (isopentenyl-diphosphate delta isomerase 2) The protein encoded by this gene catalyzes the conversion of isopentenyl diphosphate to dimethylallyl diphosphate, which is a precursor for the synthesis of cholesterol and other isoprenoids. This gene, which is a product of an ancestral gene duplication event, encodes a protein that may be involved in the aggregation of alpha-synuclein in the cerebral cortex of patients with Lewy body disease. In addition, segmental copy number gains in this locus have been associated with sporadic amyotrophic lateral sclerosis. [provided by RefSeq, Jul 2016]

IDI2 links:

GTPBP4 (HGNC:21535): (GTP binding protein 4) GTP-binding proteins are GTPases and function as molecular switches that can flip between two states: active, when GTP is bound, and inactive, when GDP is bound. 'Active' in this context usually means that the molecule acts as a signal to trigger other events in the cell. When an extracellular ligand binds to a G-protein-linked receptor, the receptor changes its conformation and switches on the trimeric G proteins that associate with it by causing them to eject their GDP and replace it with GTP. The switch is turned off when the G protein hydrolyzes its own bound GTP, converting it back to GDP. But before that occurs, the active protein has an opportunity to diffuse away from the receptor and deliver its message for a prolonged period to its downstream target. [provided by RefSeq, Jul 2008]

GTPBP4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IDI2	NM_033261.3 link	c.431G>A	p.Trp144*	stop_gained	Exon 5 of 5	ENST00000277517.2	NP_150286.1	Q9BXS1
GTPBP4	NM_012341.3 link	c.*2543C>T		3_prime_UTR_variant	Exon 17 of 17	ENST00000360803.9	NP_036473.2	Q9BZE4-1D2CFK9
GTPBP4	XM_047424932.1 link	c.*2543C>T		3_prime_UTR_variant	Exon 17 of 17		XP_047280888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IDI2	ENST00000277517.2 link	c.431G>A	p.Trp144*	stop_gained	Exon 5 of 5	1	NM_033261.3	ENSP00000277517.1		Q9BXS1
GTPBP4	ENST00000360803.9 link	c.*2543C>T		3_prime_UTR_variant	Exon 17 of 17	1	NM_012341.3	ENSP00000354040.4		Q9BZE4-1

Frequencies

GnomAD3 genomes

AF:

0.0582

AC:

8853

AN:

152002

Hom.:

298

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0474

Gnomad AMI

AF:

0.156

Gnomad AMR

AF:

0.0587

Gnomad ASJ

AF:

0.0415

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0164

Gnomad FIN

AF:

0.0434

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.0736

Gnomad OTH

AF:

0.0602

GnomAD3 exomes

AF:

0.0499

AC:

12557

AN:

251484

Hom.:

412

AF XY:

0.0503

AC XY:

6831

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.0431

Gnomad AMR exome

AF:

0.0370

Gnomad ASJ exome

AF:

0.0508

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.0162

Gnomad FIN exome

AF:

0.0436

Gnomad NFE exome

AF:

0.0726

Gnomad OTH exome

AF:

0.0583

GnomAD4 exome

AF:

0.0665

AC:

97203

AN:

1461698

Hom.:

3515

Cov.:

AF XY:

0.0654

AC XY:

47544

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.0462

Gnomad4 AMR exome

AF:

0.0389

Gnomad4 ASJ exome

AF:

0.0483

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0182

Gnomad4 FIN exome

AF:

0.0466

Gnomad4 NFE exome

AF:

0.0761

Gnomad4 OTH exome

AF:

0.0605

GnomAD4 genome

AF:

0.0582

AC:

8858

AN:

152120

Hom.:

297

Cov.:

AF XY:

0.0558

AC XY:

4148

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.0475

Gnomad4 AMR

AF:

0.0586

Gnomad4 ASJ

AF:

0.0415

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0168

Gnomad4 FIN

AF:

0.0434

Gnomad4 NFE

AF:

0.0736

Gnomad4 OTH

AF:

0.0596

Alfa

AF:

0.0712

Hom.:

1053

Bravo

AF:

0.0596

TwinsUK

AF:

0.0717

AC:

266

ALSPAC

AF:

0.0872

AC:

336

ESP6500AA

AF:

0.0474

AC:

209

ESP6500EA

AF:

0.0765

AC:

658

ExAC

AF:

0.0503

AC:

6102

Asia WGS

AF:

0.00693

AC:

AN:

3478

EpiCase

AF:

0.0763

EpiControl

AF:

0.0782

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.16

BayesDel_noAF

Pathogenic

0.53

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.91

Vest4

0.26

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over