Variant chrX-153445234-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_080701.4(TREX2):c.197C>T(p.Pro66Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000233 in 1,201,794 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 1 hem., cov: 24)

Exomes 𝑓: 0.000023 ( 0 hom. 6 hem. )

Consequence

TREX2
NM_080701.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.67

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 -2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.86

BS2

High Hemizygotes in GnomAdExome4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TREX2	NM_080701.4 linkuse as main transcript	c.197C>T	p.Pro66Leu	missense_variant	2/2	ENST00000370231.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TREX2	ENST00000370231.3 linkuse as main transcript	c.197C>T	p.Pro66Leu	missense_variant	2/2	5	NM_080701.4	P1	Q9BQ50-2

Frequencies

GnomAD3 genomes

AF:

0.0000267

AC:

AN:

112512

Hom.:

Cov.:

AF XY:

0.0000288

AC XY:

AN XY:

34674

show subpopulations

Gnomad AFR

AF:

0.0000645

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000931

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000407

AC:

AN:

171906

Hom.:

AF XY:

0.0000340

AC XY:

AN XY:

58828

show subpopulations

Gnomad AFR exome

AF:

0.0000782

Gnomad AMR exome

AF:

0.000191

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:

0.0000131

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000230

AC:

AN:

1089230

Hom.:

Cov.:

AF XY:

0.0000169

AC XY:

AN XY:

356030

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000145

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000189

Gnomad4 FIN exome

AF:

0.0000499

Gnomad4 NFE exome

AF:

0.0000167

Gnomad4 OTH exome

AF:

0.0000657

GnomAD4 genome

AF:

0.0000267

AC:

AN:

112564

Hom.:

Cov.:

AF XY:

0.0000288

AC XY:

AN XY:

34736

show subpopulations

Gnomad4 AFR

AF:

0.0000644

Gnomad4 AMR

AF:

0.0000930

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000491

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

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

Jul 15, 2021

The c.197C>T (p.P66L) 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 197, causing the proline (P) at amino acid position 66 to be replaced by a leucine (L). 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

Uncertain

0.49

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Pathogenic

0.40

CADD

Benign

DANN

Uncertain

1.0

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.82

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

M_CAP

Uncertain

0.27

MetaRNN

Pathogenic

0.86

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

MetaSVM

Uncertain

0.47

MutationTaster

Benign

1.0

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

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-9.8

D;D;.;D;D;D;D

REVEL

Pathogenic

0.79

Sift

Pathogenic

0.0

D;D;.;D;D;D;D

Sift4G

Pathogenic

0.0

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

Polyphen

1.0

.;.;D;.;.;D;D

Vest4

0.44

MVP

0.41

MPC

0.18

ClinPred

1.0

GERP RS

5.0

Varity_R

0.86

gMVP

0.71

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