Variant X-153444824-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_080701.4(TREX2):c.607C>T(p.His203Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000075 in 1,200,056 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 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 (no stars).

Frequency

Genomes: 𝑓 0.0000088 ( 0 hom., 0 hem., cov: 25)

Exomes 𝑓: 0.0000074 ( 0 hom. 4 hem. )

Consequence

TREX2
NM_080701.4 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 1.20

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08718556).

BS2

High Hemizygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TREX2	NM_080701.4 linkuse as main transcript	c.607C>T	p.His203Tyr	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.607C>T	p.His203Tyr	missense_variant	2/2	5	NM_080701.4	ENSP00000359251	P1	Q9BQ50-2

Frequencies

GnomAD3 genomes

AF:

0.00000883

AC:

AN:

113257

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35405

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000395

AC:

AN:

151894

Hom.:

AF XY:

0.0000828

AC XY:

AN XY:

48322

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000332

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000311

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000736

AC:

AN:

1086799

Hom.:

Cov.:

AF XY:

0.0000112

AC XY:

AN XY:

355977

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000168

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000239

Gnomad4 OTH exome

AF:

0.0000219

GnomAD4 genome

AF:

0.00000883

AC:

AN:

113257

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35405

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.0000333

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Intellectual disability

Uncertain:1

Uncertain significance, no assertion criteria provided

case-control

Medical Genetic Institute of Henan Province, Henan Provincial People’s Hospital

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.060

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

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.76

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

M_CAP

Benign

0.0077

MetaRNN

Benign

0.087

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

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

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

MutationTaster

Benign

0.68

D;D;D;D;N;N;N;N

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.19

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

REVEL

Benign

0.12

Sift

Benign

1.0

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

Sift4G

Benign

1.0

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

Polyphen

0.057

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

Vest4

0.23

MutPred

0.52

.;.;Gain of catalytic residue at L241 (P = 0.0578);.;.;Gain of catalytic residue at L241 (P = 0.0578);Gain of catalytic residue at L241 (P = 0.0578);

MVP

0.14

MPC

0.024

ClinPred

0.058

GERP RS

4.9

Varity_R

0.16

gMVP

0.48

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