dbSNP rs782654526: TREX2:p.Arg140Gln (chrX-153445012-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_080701.4(TREX2):c.419G>A(p.Arg140Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000232 in 1,165,959 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 92 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., 4 hem., cov: 25)

Exomes 𝑓: 0.00024 ( 0 hom. 88 hem. )

Consequence

TREX2
NM_080701.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.49

Publications

1 publications found

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 was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.033571303).

BP6

Variant X-153445012-C-T is Benign according to our data. Variant chrX-153445012-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2568527.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080701.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TREX2	NM_080701.4	MANE Select	c.419G>A	p.Arg140Gln	missense	Exon 2 of 2	NP_542432.2	Q9BQ50-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TREX2	ENST00000370231.3	TSL:5 MANE Select	c.419G>A	p.Arg140Gln	missense	Exon 2 of 2	ENSP00000359251.2	Q9BQ50-2
TREX2	ENST00000334497.7	TSL:1	c.548G>A	p.Arg183Gln	missense	Exon 11 of 11	ENSP00000334993.2	Q9BQ50-1
TREX2	ENST00000370232.4	TSL:1	c.548G>A	p.Arg183Gln	missense	Exon 11 of 11	ENSP00000359252.1	Q9BQ50-1

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

112283

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000226

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:

0.000189

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000284

AC:

AN:

105662

AF XY:

0.0000333

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000758

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000241

AC:

254

AN:

1053676

Hom.:

Cov.:

AF XY:

0.000261

AC XY:

AN XY:

337806

show subpopulations

African (AFR)

AF:

0.000118

AC:

AN:

25416

American (AMR)

AF:

0.00

AC:

AN:

28295

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17920

East Asian (EAS)

AF:

0.0000355

AC:

AN:

28208

South Asian (SAS)

AF:

0.00

AC:

AN:

48800

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36679

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3964

European-Non Finnish (NFE)

AF:

0.000299

AC:

245

AN:

820129

Other (OTH)

AF:

0.000113

AC:

AN:

44265

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000151

AC:

AN:

112283

Hom.:

Cov.:

AF XY:

0.000116

AC XY:

AN XY:

34595

show subpopulations

African (AFR)

AF:

0.000226

AC:

AN:

30906

American (AMR)

AF:

0.00

AC:

AN:

10784

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2646

East Asian (EAS)

AF:

0.00

AC:

AN:

3497

South Asian (SAS)

AF:

0.00

AC:

AN:

2798

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6238

Middle Eastern (MID)

AF:

0.00

AC:

AN:

227

European-Non Finnish (NFE)

AF:

0.000189

AC:

AN:

52996

Other (OTH)

AF:

0.00

AC:

AN:

1520

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.0000982

ExAC

AF:

0.0000839

AC:

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-1.2

CADD

Benign

0.0020

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.049

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.48

M_CAP

Benign

0.0019

MetaRNN

Benign

0.034

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.40

PhyloP100

-5.5

PrimateAI

Benign

0.35

PROVEAN

Benign

1.2

REVEL

Benign

0.013

Sift

Benign

0.58

Sift4G

Benign

0.59

Polyphen

0.0010

Vest4

0.049

MVP

0.048

MPC

0.023

ClinPred

0.051

GERP RS

-9.9

Varity_R

0.054

gMVP

0.090

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over