Genetic Variant NM_016170.5:c.100G>C (chr2-74514906-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016170.5(TLX2):c.100G>C(p.Gly34Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,610,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

TLX2
NM_016170.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.181

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18524262).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016170.5. 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
	TLX2	NM_016170.5	MANE Select	c.100G>C	p.Gly34Arg	missense	Exon 1 of 3	NP_057254.1	O43763

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TLX2	ENST00000233638.8	TSL:1 MANE Select	c.100G>C	p.Gly34Arg	missense	Exon 1 of 3	ENSP00000233638.6	O43763
TLX2	ENST00000621092.1	TSL:1	c.11+672G>C		intron	N/A	ENSP00000482690.1	F1T0F2
TLX2	ENST00000497238.1	TSL:5	n.522-116G>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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

GnomAD2 exomes

AF:

0.00000414

AC:

AN:

241448

AF XY:

0.00

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:

0.00000926

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1458714

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725686

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33106

American (AMR)

AF:

0.0000674

AC:

AN:

44522

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26024

East Asian (EAS)

AF:

0.00

AC:

AN:

39536

South Asian (SAS)

AF:

0.00

AC:

AN:

86020

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52548

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1110950

Other (OTH)

AF:

0.00

AC:

AN:

60250

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41474

American (AMR)

AF:

0.0000654

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000227

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

0.18

BayesDel_addAF

Benign

-0.040

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Uncertain

0.43

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.55

M_CAP

Pathogenic

0.72

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.78

MutationAssessor

Benign

2.0

PhyloP100

0.18

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.41

REVEL

Benign

0.28

Sift

Benign

0.68

Sift4G

Benign

0.52

Polyphen

0.0

Vest4

0.23

MutPred

0.39

Gain of sheet (P = 0.0221)

MVP

0.71

MPC

1.3

ClinPred

0.043

GERP RS

-2.4

PromoterAI

-0.12

Neutral

(source)

Varity_R

0.049

gMVP

0.51

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over