Variant chrX-153445172-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PVS1_StrongBS2

The NM_080701.4(TREX2):c.259C>T(p.Arg87Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00076 in 1,208,420 control chromosomes in the GnomAD database, including 4 homozygotes. There are 257 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0041 ( 2 hom., 137 hem., cov: 24)

Exomes 𝑓: 0.00042 ( 2 hom. 120 hem. )

Consequence

TREX2
NM_080701.4 stop_gained

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.265

Variant links:

Genes affected

TREX2 (HGNC:12270): (three prime repair exonuclease 2) This gene encodes a nuclear protein with 3' to 5' exonuclease activity. The encoded protein participates in double-stranded DNA break repair, and may interact with DNA polymerase delta. [provided by RefSeq, Nov 2012]

TREX2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.636 CDS is truncated, and there are 0 pathogenic variants in the truncated region.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TREX2	NM_080701.4 linkuse as main transcript	c.259C>T	p.Arg87Ter	stop_gained	2/2	ENST00000370231.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TREX2	ENST00000370231.3 linkuse as main transcript	c.259C>T	p.Arg87Ter	stop_gained	2/2	5	NM_080701.4	P1	Q9BQ50-2

Frequencies

GnomAD3 genomes

AF:

0.00407

AC:

461

AN:

113150

Hom.:

Cov.:

AF XY:

0.00382

AC XY:

135

AN XY:

35308

show subpopulations

Gnomad AFR

AF:

0.0138

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00194

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000355

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000750

Gnomad OTH

AF:

0.00260

GnomAD3 exomes

AF:

0.00114

AC:

195

AN:

170385

Hom.:

AF XY:

0.000722

AC XY:

AN XY:

59561

show subpopulations

Gnomad AFR exome

AF:

0.0135

Gnomad AMR exome

AF:

0.00105

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000536

Gnomad OTH exome

AF:

0.000713

GnomAD4 exome

AF:

0.000415

AC:

455

AN:

1095218

Hom.:

Cov.:

AF XY:

0.000332

AC XY:

120

AN XY:

361376

show subpopulations

Gnomad4 AFR exome

AF:

0.0132

Gnomad4 AMR exome

AF:

0.00123

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000559

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000250

Gnomad4 OTH exome

AF:

0.000805

GnomAD4 genome

AF:

0.00410

AC:

464

AN:

113202

Hom.:

Cov.:

AF XY:

0.00387

AC XY:

137

AN XY:

35370

show subpopulations

Gnomad4 AFR

AF:

0.0139

Gnomad4 AMR

AF:

0.00194

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000356

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000751

Gnomad4 OTH

AF:

0.00257

Alfa

AF:

0.000805

Hom.:

Bravo

AF:

0.00468

ESP6500AA

AF:

0.0159

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00126

AC:

153

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Abnormality of neuronal migration

Benign:1

Benign, no assertion criteria provided

clinical testing

Génétique et pathophysiologie de maladies neurodéveloppementales et épileptogènes, Institut de génétique et de biologie moléculaire et cellulaire

Oct 31, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.019

BayesDel_noAF

Pathogenic

0.21

CADD

Pathogenic

DANN

Uncertain

0.99

FATHMM_MKL

Benign

0.066

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D

Vest4

0.80

GERP RS

0.41

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