dbSNP rs782760279: TREX2:p.Arg152Trp (chrX-153444977-G-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_080701.4(TREX2):c.454C>T(p.Arg152Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000195 in 1,177,644 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 0 hem., cov: 25)

Exomes 𝑓: 0.000019 ( 0 hom. 8 hem. )

Consequence

TREX2
NM_080701.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0990

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 Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.4097389).

BS2

High Hemizygotes in GnomAdExome4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TREX2	NM_080701.4 link	c.454C>T	p.Arg152Trp	missense_variant	Exon 2 of 2	ENST00000370231.3	NP_542432.2	Q9BQ50-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TREX2	ENST00000370231.3 link	c.454C>T	p.Arg152Trp	missense_variant	Exon 2 of 2	5	NM_080701.4	ENSP00000359251.2		Q9BQ50-2

Frequencies

GnomAD3 genomes

AF:

0.0000266

AC:

AN:

112734

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34934

show subpopulations

Gnomad AFR

AF:

0.0000644

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000924

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000515

AC:

AN:

116544

Hom.:

AF XY:

0.0000279

AC XY:

AN XY:

35858

show subpopulations

Gnomad AFR exome

AF:

0.000293

Gnomad AMR exome

AF:

0.0000965

Gnomad ASJ exome

AF:

0.000171

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000706

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000188

AC:

AN:

1064910

Hom.:

Cov.:

AF XY:

0.0000232

AC XY:

AN XY:

344240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000101

Gnomad4 ASJ exome

AF:

0.0000539

Gnomad4 EAS exome

AF:

0.0000348

Gnomad4 SAS exome

AF:

0.0000989

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000109

Gnomad4 OTH exome

AF:

0.0000223

GnomAD4 genome

AF:

0.0000266

AC:

AN:

112734

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34934

show subpopulations

Gnomad4 AFR

AF:

0.0000644

Gnomad4 AMR

AF:

0.0000924

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

ExAC

AF:

0.0000461

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.454C>T (p.R152W) 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 454, causing the arginine (R) at amino acid position 152 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

0.21

BayesDel_addAF

Uncertain

0.066

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.53

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

FATHMM_MKL

Benign

0.60

LIST_S2

Uncertain

0.86

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

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.41

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

MetaSVM

Benign

-0.63

MutationAssessor

Pathogenic

3.3

.;.;M;.;.;M;M

PrimateAI

Uncertain

0.60

PROVEAN

Pathogenic

-5.5

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

REVEL

Benign

0.26

Sift

Uncertain

0.0010

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

Sift4G

Uncertain

0.0020

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

Polyphen

1.0

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

Vest4

0.53

MVP

0.42

MPC

0.17

ClinPred

0.72

GERP RS

3.0

Varity_R

0.33

gMVP

0.58

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