17-61400404-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005994.4(TBX2):​c.228C>G​(p.His76Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

TBX2
NM_005994.4 missense

Scores

2
7
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.40
Variant links:
Genes affected
TBX2 (HGNC:11597): (T-box transcription factor 2) This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of developmental processes. This gene product is the human homolog of mouse Tbx2, and shares strong sequence similarity with Drosophila omb protein. Expression studies indicate that this gene may have a potential role in tumorigenesis as an immortalizing agent. Transcript heterogeneity due to alternative polyadenylation has been noted for this gene. [provided by RefSeq, Jul 2008]
TBX2-AS1 (HGNC:50355): (TBX2 antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TBX2NM_005994.4 linkc.228C>G p.His76Gln missense_variant Exon 1 of 7 ENST00000240328.4 NP_005985.3 Q13207A0A024QZ86

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TBX2ENST00000240328.4 linkc.228C>G p.His76Gln missense_variant Exon 1 of 7 1 NM_005994.4 ENSP00000240328.3 Q13207
TBX2ENST00000419047.5 linkn.228C>G non_coding_transcript_exon_variant Exon 1 of 7 1 ENSP00000404781.1 F8WCM9
TBX2ENST00000477081.1 linkn.40C>G non_coding_transcript_exon_variant Exon 1 of 5 2
TBX2-AS1ENST00000592009.1 linkn.41-6657G>C intron_variant Intron 1 of 1 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.28
BayesDel_addAF
Uncertain
0.048
T
BayesDel_noAF
Benign
-0.17
CADD
Pathogenic
29
DANN
Benign
0.97
DEOGEN2
Uncertain
0.63
D
Eigen
Uncertain
0.24
Eigen_PC
Benign
0.22
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.83
T
M_CAP
Pathogenic
0.97
D
MetaRNN
Uncertain
0.56
D
MetaSVM
Uncertain
0.027
D
MutationAssessor
Benign
1.8
L
PrimateAI
Pathogenic
0.95
D
PROVEAN
Benign
-1.5
N
REVEL
Uncertain
0.33
Sift
Benign
0.21
T
Sift4G
Benign
0.44
T
Polyphen
1.0
D
Vest4
0.31
MutPred
0.26
Gain of solvent accessibility (P = 0.0837);
MVP
0.66
ClinPred
0.70
D
GERP RS
3.4
Varity_R
0.21
gMVP
0.33

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: rs549885020; hg19: chr17-59477765; API