Variant X-153445205-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_080701.4(TREX2):c.226G>A(p.Glu76Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000457 in 1,093,804 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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: not found (cov: 25)

Exomes 𝑓: 0.0000046 ( 0 hom. 1 hem. )

Consequence

TREX2
NM_080701.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.78

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15666354).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TREX2	NM_080701.4 link	c.226G>A	p.Glu76Lys	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 link	c.226G>A	p.Glu76Lys	missense_variant	2/2	5	NM_080701.4	ENSP00000359251.2		Q9BQ50-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000172

AC:

AN:

174019

Hom.:

AF XY:

0.0000163

AC XY:

AN XY:

61473

show subpopulations

Gnomad AFR exome

AF:

0.0000803

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000260

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000457

AC:

AN:

1093804

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

359796

show subpopulations

Gnomad4 AFR exome

AF:

0.0000380

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000332

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000357

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

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

Nov 07, 2022

The c.226G>A (p.E76K) alteration is located in exon 2 (coding exon 1) of the TREX2 gene. This alteration results from a G to A substitution at nucleotide position 226, causing the glutamic acid (E) at amino acid position 76 to be replaced by a lysine (K). 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

0.13

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

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

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.78

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

M_CAP

Benign

0.014

MetaRNN

Benign

0.16

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.92

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

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.2

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

REVEL

Benign

0.067

Sift

Benign

0.29

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

Sift4G

Benign

0.50

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

Polyphen

0.29

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

Vest4

0.29

MutPred

0.47

.;.;Gain of ubiquitination at E119 (P = 0.0219);.;.;Gain of ubiquitination at E119 (P = 0.0219);Gain of ubiquitination at E119 (P = 0.0219);

MVP

0.28

MPC

0.031

ClinPred

0.11

GERP RS

4.1

Varity_R

0.33

gMVP

0.31

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