rs141205509

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_080701.4(TREX2):c.541C>T(p.Arg181Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000354 in 1,203,625 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 132 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., 7 hem., cov: 25)

Exomes 𝑓: 0.00036 ( 0 hom. 125 hem. )

Consequence

TREX2
NM_080701.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.112

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0042400956).

BP6

Variant X-153444890-G-A is Benign according to our data. Variant chrX-153444890-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2365083.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}. Variant chrX-153444890-G-A is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TREX2	NM_080701.4 link	c.541C>T	p.Arg181Trp	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.541C>T	p.Arg181Trp	missense_variant	Exon 2 of 2	5	NM_080701.4	ENSP00000359251.2		Q9BQ50-2

Frequencies

GnomAD3 genomes

AF:

0.000283

AC:

AN:

113067

Hom.:

Cov.:

AF XY:

0.000199

AC XY:

AN XY:

35225

show subpopulations

Gnomad AFR

AF:

0.0000320

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00101

Gnomad ASJ

AF:

0.00453

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000939

Gnomad OTH

AF:

0.00197

GnomAD3 exomes

AF:

0.000568

AC:

AN:

158578

Hom.:

AF XY:

0.000493

AC XY:

AN XY:

52706

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000660

Gnomad ASJ exome

AF:

0.00722

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000736

Gnomad NFE exome

AF:

0.000295

Gnomad OTH exome

AF:

0.000499

GnomAD4 exome

AF:

0.000361

AC:

394

AN:

1090558

Hom.:

Cov.:

AF XY:

0.000349

AC XY:

125

AN XY:

358152

show subpopulations

Gnomad4 AFR exome

AF:

0.0000380

Gnomad4 AMR exome

AF:

0.000669

Gnomad4 ASJ exome

AF:

0.00819

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000257

Gnomad4 NFE exome

AF:

0.000211

Gnomad4 OTH exome

AF:

0.000764

GnomAD4 genome

AF:

0.000283

AC:

AN:

113067

Hom.:

Cov.:

AF XY:

0.000199

AC XY:

AN XY:

35225

show subpopulations

Gnomad4 AFR

AF:

0.0000320

Gnomad4 AMR

AF:

0.00101

Gnomad4 ASJ

AF:

0.00453

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000939

Gnomad4 OTH

AF:

0.00197

Alfa

AF:

0.000736

Hom.:

Bravo

AF:

0.000559

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000692

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00179

AC:

ExAC

AF:

0.000509

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 20, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.541C>T (p.R181W) 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 541, causing the arginine (R) at amino acid position 181 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TREX2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

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

FATHMM_MKL

Benign

0.073

LIST_S2

Benign

0.68

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

M_CAP

Benign

0.023

MetaRNN

Benign

0.0042

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

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

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.53

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

REVEL

Benign

0.059

Sift

Benign

0.17

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

Sift4G

Uncertain

0.037

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

Polyphen

0.94

.;.;P;.;.;P;P

Vest4

0.12

MVP

0.28

MPC

0.056

ClinPred

0.043

GERP RS

1.6

Varity_R

0.23

gMVP

0.34

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