Variant 2-74516012-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000621092.1(TLX2):c.289C>T(p.Arg97Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000326 in 1,522,418 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00066 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00029 ( 7 hom. )

Consequence

TLX2
ENST00000621092.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.474

Variant links:

Genes affected

TLX2 (HGNC:5057): (T cell leukemia homeobox 2) This gene is a member of an orphan homeobox-containing transcription factor family. Studies of the mouse ortholog have shown that the encoded protein is crucial for the development of the enteric nervous system; in humans, loss-of-function may play a role in tumorigenesis of gastrointestinal stromal tumors. [provided by RefSeq, May 2010]

TLX2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024291873).

BP6

Variant 2-74516012-C-T is Benign according to our data. Variant chr2-74516012-C-T is described in ClinVar as [Benign]. Clinvar id is 716444.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLX2	NM_016170.5 link	c.678C>T	p.Arg226Arg	synonymous_variant	3/3	ENST00000233638.8	NP_057254.1	O43763

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLX2	ENST00000621092.1 link	c.289C>T	p.Arg97Cys	missense_variant	4/4	1		ENSP00000482690.1		F1T0F2
TLX2	ENST00000233638.8 link	c.678C>T	p.Arg226Arg	synonymous_variant	3/3	1	NM_016170.5	ENSP00000233638.6		O43763

Frequencies

GnomAD3 genomes

AF:

0.000651

AC:

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0158

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00175

AC:

213

AN:

121884

Hom.:

AF XY:

0.00139

AC XY:

AN XY:

68588

show subpopulations

Gnomad AFR exome

AF:

0.000565

Gnomad AMR exome

AF:

0.0000477

Gnomad ASJ exome

AF:

0.000331

Gnomad EAS exome

AF:

0.0243

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000878

GnomAD4 exome

AF:

0.000289

AC:

396

AN:

1370232

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

164

AN XY:

677076

show subpopulations

Gnomad4 AFR exome

AF:

0.000247

Gnomad4 AMR exome

AF:

0.0000307

Gnomad4 ASJ exome

AF:

0.0000865

Gnomad4 EAS exome

AF:

0.00775

Gnomad4 SAS exome

AF:

0.000105

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000465

Gnomad4 OTH exome

AF:

0.00197

GnomAD4 genome

AF:

0.000664

AC:

101

AN:

152186

Hom.:

Cov.:

AF XY:

0.000779

AC XY:

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0163

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.0000461

Hom.:

Bravo

AF:

0.000608

ExAC

AF:

0.00129

AC:

137

Asia WGS

AF:

0.00782

AC:

AN:

3468

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.34

CADD

Benign

9.4

DANN

Benign

0.96

DEOGEN2

Benign

0.35

FATHMM_MKL

Benign

0.52

MetaRNN

Benign

0.0024

PrimateAI

Uncertain

0.49

Sift4G

Benign

0.13

Polyphen

0.12

Vest4

0.16

MVP

0.56

GERP RS

0.61

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