rs1044261

Variant names:

• chr10-1019770-C-T
• rs1044261
• NM_033261.3:c.431G>A

Variant summary

Our verdict is Benign. The variant received -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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.87
• Publications: 41 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0719 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033261.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IDI2	NM_033261.3	MANE Select	c.431G>A	p.Trp144*	stop_gained	Exon 5 of 5	NP_150286.1
	GTPBP4	NM_012341.3	MANE Select	c.*2543C>T		3_prime_UTR	Exon 17 of 17	NP_036473.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IDI2	ENST00000277517.2	TSL:1 MANE Select	c.431G>A	p.Trp144*	stop_gained	Exon 5 of 5	ENSP00000277517.1
	GTPBP4	ENST00000360803.9	TSL:1 MANE Select	c.*2543C>T		3_prime_UTR	Exon 17 of 17	ENSP00000354040.4

Frequencies

GnomAD3 genomes AF: 0.0582 AC: 8853 AN: 152002 Hom.: 298 Cov.: 31

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

GnomAD2 exomes AF: 0.0499 AC: 12557 AN: 251484 AF XY: 0.0503

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 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.: 32 AF XY: 0.0654 AC XY: 47544 AN XY: 727172

African (AFR) AF: 0.0462 AC: 1548 AN: 33478

American (AMR) AF: 0.0389 AC: 1740 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0483 AC: 1262 AN: 26136

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39700

South Asian (SAS) AF: 0.0182 AC: 1571 AN: 86258

European-Finnish (FIN) AF: 0.0466 AC: 2490 AN: 53420

Middle Eastern (MID) AF: 0.0650 AC: 375 AN: 5768

European-Non Finnish (NFE) AF: 0.0761 AC: 84556 AN: 1111828

Other (OTH) AF: 0.0605 AC: 3655 AN: 60386

GnomAD4 genome AF: 0.0582 AC: 8858 AN: 152120 Hom.: 297 Cov.: 31 AF XY: 0.0558 AC XY: 4148 AN XY: 74334

African (AFR) AF: 0.0475 AC: 1970 AN: 41514

American (AMR) AF: 0.0586 AC: 895 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0415 AC: 144 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.0168 AC: 81 AN: 4820

European-Finnish (FIN) AF: 0.0434 AC: 459 AN: 10564

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0736 AC: 5004 AN: 68008

Other (OTH) AF: 0.0596 AC: 126 AN: 2114

Alfa AF: 0.0691 Hom.: 1344

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: 24 AN: 3478

EpiCase AF: 0.0763

EpiControl AF: 0.0782

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Pathogenic	0.53
CADD	Pathogenic	36
DANN	Uncertain	0.99
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.91	D
PhyloP100		4.9
Vest4		0.26
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=132/68	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1044261; hg19: chr10-1065710;