2-74516012-C-T

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

1
8

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]

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
TLX2NM_016170.5 linkc.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
TLX2ENST00000621092.1 linkc.289C>T p.Arg97Cys missense_variant 4/41 ENSP00000482690.1 F1T0F2
TLX2ENST00000233638.8 linkc.678C>T p.Arg226Arg synonymous_variant 3/31 NM_016170.5 ENSP00000233638.6 O43763

Frequencies

GnomAD3 genomes
AF:
0.000651
AC:
99
AN:
152078
Hom.:
1
Cov.:
33
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.:
4
AF XY:
0.00139
AC XY:
95
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.:
7
Cov.:
31
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.:
1
Cov.:
33
AF XY:
0.000779
AC XY:
58
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.:
0
Bravo
AF:
0.000608
ExAC
AF:
0.00129
AC:
137
Asia WGS
AF:
0.00782
AC:
27
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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 23, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.41
T
BayesDel_noAF
Benign
-0.34
CADD
Benign
9.4
DANN
Benign
0.96
DEOGEN2
Benign
0.35
T
FATHMM_MKL
Benign
0.52
D
MetaRNN
Benign
0.0024
T
PrimateAI
Uncertain
0.49
T
Sift4G
Benign
0.13
T
Polyphen
0.12
B
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.

Other links and lift over

dbSNP: rs371068999; hg19: chr2-74743139; API