Variant X-153445174-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.257C>T(p.Ala86Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000389 in 1,208,399 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 13 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000071 ( 0 hom., 2 hem., cov: 24)

Exomes 𝑓: 0.000036 ( 0 hom. 11 hem. )

Consequence

TREX2
NM_080701.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.401

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=0.045274943).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TREX2	NM_080701.4 linkuse as main transcript	c.257C>T	p.Ala86Val	missense_variant	2/2	ENST00000370231.3	NP_542432.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TREX2	ENST00000370231.3 linkuse as main transcript	c.257C>T	p.Ala86Val	missense_variant	2/2	5	NM_080701.4	ENSP00000359251	P1	Q9BQ50-2

Frequencies

GnomAD3 genomes

AF:

0.0000706

AC:

AN:

113236

Hom.:

Cov.:

AF XY:

0.0000565

AC XY:

AN XY:

35388

show subpopulations

Gnomad AFR

AF:

0.0000320

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000277

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000707

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000375

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000820

AC:

AN:

170701

Hom.:

AF XY:

0.0000334

AC XY:

AN XY:

59851

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.000279

Gnomad FIN exome

AF:

0.0000671

Gnomad NFE exome

AF:

0.0000267

Gnomad OTH exome

AF:

0.000237

GnomAD4 exome

AF:

0.0000356

AC:

AN:

1095117

Hom.:

Cov.:

AF XY:

0.0000304

AC XY:

AN XY:

361291

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000143

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000332

Gnomad4 SAS exome

AF:

0.000224

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000119

Gnomad4 OTH exome

AF:

0.0000435

GnomAD4 genome

AF:

0.0000706

AC:

AN:

113282

Hom.:

Cov.:

AF XY:

0.0000564

AC XY:

AN XY:

35444

show subpopulations

Gnomad4 AFR

AF:

0.0000319

Gnomad4 AMR

AF:

0.000276

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000709

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000375

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000907

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000298

AC:

ExAC

AF:

0.0000578

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

Oct 12, 2021

The c.257C>T (p.A86V) 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 257, causing the alanine (A) at amino acid position 86 to be replaced by a valine (V). 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

0.078

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-1.1

CADD

Benign

1.2

DANN

Benign

0.92

DEOGEN2

Benign

0.19

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

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.34

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

M_CAP

Benign

0.0045

MetaRNN

Benign

0.045

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

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

MutationTaster

Benign

1.0

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

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.4

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

REVEL

Benign

0.026

Sift

Benign

0.26

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

Sift4G

Benign

0.28

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

Polyphen

0.0040

.;.;B;.;.;B;B

Vest4

0.036

MVP

0.31

MPC

0.022

ClinPred

0.013

GERP RS

-0.0010

Varity_R

0.098

gMVP

0.17

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