Genetic Variant TREX2:p.Glu214Glu (chrX-153444789-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_080701.4(TREX2):c.642G>A(p.Glu214Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000491 in 1,196,533 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 157 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., 7 hem., cov: 25)

Exomes 𝑓: 0.00051 ( 0 hom. 150 hem. )

Consequence

TREX2
NM_080701.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.599

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant X-153444789-C-T is Benign according to our data. Variant chrX-153444789-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2661684.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-153444789-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.599 with no splicing effect.

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.642G>A	p.Glu214Glu	synonymous_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.642G>A	p.Glu214Glu	synonymous_variant	Exon 2 of 2	5	NM_080701.4	ENSP00000359251.2		Q9BQ50-2

Frequencies

GnomAD3 genomes

AF:

0.000318

AC:

AN:

113347

Hom.:

Cov.:

AF XY:

0.000197

AC XY:

AN XY:

35479

show subpopulations

Gnomad AFR

AF:

0.0000640

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000918

Gnomad ASJ

AF:

0.000752

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000314

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000525

Gnomad OTH

AF:

0.000652

GnomAD3 exomes

AF:

0.000336

AC:

AN:

145800

Hom.:

AF XY:

0.000304

AC XY:

AN XY:

46026

show subpopulations

Gnomad AFR exome

AF:

0.000101

Gnomad AMR exome

AF:

0.0000421

Gnomad ASJ exome

AF:

0.000602

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000688

Gnomad OTH exome

AF:

0.000262

GnomAD4 exome

AF:

0.000510

AC:

552

AN:

1083186

Hom.:

Cov.:

AF XY:

0.000424

AC XY:

150

AN XY:

353984

show subpopulations

Gnomad4 AFR exome

AF:

0.000114

Gnomad4 AMR exome

AF:

0.0000614

Gnomad4 ASJ exome

AF:

0.000790

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000779

Gnomad4 NFE exome

AF:

0.000603

Gnomad4 OTH exome

AF:

0.000527

GnomAD4 genome

AF:

0.000318

AC:

AN:

113347

Hom.:

Cov.:

AF XY:

0.000197

AC XY:

AN XY:

35479

show subpopulations

Gnomad4 AFR

AF:

0.0000640

Gnomad4 AMR

AF:

0.0000918

Gnomad4 ASJ

AF:

0.000752

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000314

Gnomad4 NFE

AF:

0.000525

Gnomad4 OTH

AF:

0.000652

Alfa

AF:

0.000912

Hom.:

Bravo

AF:

0.000329

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TREX2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

5.6

DANN

Benign

0.73

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