Variant chrX-153445166-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_080701.4(TREX2):c.265C>T(p.Arg89Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000632 in 1,208,208 control chromosomes in the GnomAD database, including 1 homozygotes. There are 252 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00036 ( 0 hom., 13 hem., cov: 25)

Exomes 𝑓: 0.00066 ( 1 hom. 239 hem. )

Consequence

TREX2
NM_080701.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.764

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01798132).

BS2

High Hemizygotes in GnomAd4 at 13 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TREX2	NM_080701.4 linkuse as main transcript	c.265C>T	p.Arg89Trp	missense_variant	2/2	ENST00000370231.3	NP_542432.2	Q9BQ50-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TREX2	ENST00000370231.3 linkuse as main transcript	c.265C>T	p.Arg89Trp	missense_variant	2/2	5	NM_080701.4	ENSP00000359251.2		Q9BQ50-2

Frequencies

GnomAD3 genomes

AF:

0.000362

AC:

AN:

113225

Hom.:

Cov.:

AF XY:

0.000367

AC XY:

AN XY:

35375

show subpopulations

Gnomad AFR

AF:

0.0000960

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00174

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000488

Gnomad OTH

AF:

0.000653

GnomAD3 exomes

AF:

0.000284

AC:

AN:

169132

Hom.:

AF XY:

0.000427

AC XY:

AN XY:

58526

show subpopulations

Gnomad AFR exome

AF:

0.0000847

Gnomad AMR exome

AF:

0.000150

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00108

Gnomad NFE exome

AF:

0.000352

Gnomad OTH exome

AF:

0.000240

GnomAD4 exome

AF:

0.000659

AC:

722

AN:

1094930

Hom.:

Cov.:

AF XY:

0.000662

AC XY:

239

AN XY:

361166

show subpopulations

Gnomad4 AFR exome

AF:

0.0000759

Gnomad4 AMR exome

AF:

0.000143

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000332

Gnomad4 SAS exome

AF:

0.0000187

Gnomad4 FIN exome

AF:

0.00134

Gnomad4 NFE exome

AF:

0.000756

Gnomad4 OTH exome

AF:

0.000501

GnomAD4 genome

AF:

0.000362

AC:

AN:

113278

Hom.:

Cov.:

AF XY:

0.000367

AC XY:

AN XY:

35438

show subpopulations

Gnomad4 AFR

AF:

0.0000958

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00174

Gnomad4 NFE

AF:

0.000488

Gnomad4 OTH

AF:

0.000645

Alfa

AF:

0.0000961

Hom.:

Bravo

AF:

0.000215

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000346

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.000314

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 14, 2023

The c.265C>T (p.R89W) alteration is located in exon 2 (coding exon 1) of the TREX2 gene. This alteration results from a C to T substitution at nucleotide position 265, causing the arginine (R) at amino acid position 89 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.73

CADD

Benign

7.7

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

.;.;T;.;.;T;T

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.81

T;.;T;.;.;.;.

M_CAP

Benign

0.051

MetaRNN

Benign

0.018

T;T;T;T;T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.1

.;.;L;.;.;L;L

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-2.4

N;N;.;N;N;N;N

REVEL

Benign

0.13

Sift

Uncertain

0.024

D;D;.;D;D;D;D

Sift4G

Benign

0.12

T;T;T;T;T;T;T

Polyphen

1.0

.;.;D;.;.;D;D

Vest4

0.29

MVP

0.15

MPC

0.13

ClinPred

0.058

GERP RS

-0.29

Varity_R

0.22

gMVP

0.44

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