2-74514864-G-C
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_016170.5(TLX2):āc.58G>Cā(p.Gly20Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000396 in 1,613,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.00021 ( 0 hom., cov: 33)
Exomes š: 0.00042 ( 0 hom. )
Consequence
TLX2
NM_016170.5 missense
NM_016170.5 missense
Scores
12
6
1
Clinical Significance
Conservation
PhyloP100: 7.92
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.873
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TLX2 | NM_016170.5 | c.58G>C | p.Gly20Arg | missense_variant | 1/3 | ENST00000233638.8 | NP_057254.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TLX2 | ENST00000233638.8 | c.58G>C | p.Gly20Arg | missense_variant | 1/3 | 1 | NM_016170.5 | ENSP00000233638.6 | ||
TLX2 | ENST00000621092.1 | c.11+630G>C | intron_variant | 1 | ENSP00000482690.1 | |||||
TLX2 | ENST00000497238.1 | n.522-158G>C | intron_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.000210 AC: 32AN: 152214Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000129 AC: 32AN: 248146Hom.: 0 AF XY: 0.000141 AC XY: 19AN XY: 135050
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GnomAD4 exome AF: 0.000416 AC: 607AN: 1460736Hom.: 0 Cov.: 34 AF XY: 0.000356 AC XY: 259AN XY: 726738
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GnomAD4 genome AF: 0.000210 AC: 32AN: 152330Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11AN XY: 74496
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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 | May 31, 2023 | The c.58G>C (p.G20R) alteration is located in exon 1 (coding exon 1) of the TLX2 gene. This alteration results from a G to C substitution at nucleotide position 58, causing the glycine (G) at amino acid position 20 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Pathogenic
D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at