chr17-61400286-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3PP5

The NM_005994.4(TBX2):​c.110T>G​(p.Phe37Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

TBX2
NM_005994.4 missense

Scores

9
9
1

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 6.20
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 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.821
PP5
Variant 17-61400286-T-G is Pathogenic according to our data. Variant chr17-61400286-T-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 978728.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TBX2NM_005994.4 linkuse as main transcriptc.110T>G p.Phe37Cys missense_variant 1/7 ENST00000240328.4 NP_005985.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TBX2ENST00000240328.4 linkuse as main transcriptc.110T>G p.Phe37Cys missense_variant 1/71 NM_005994.4 ENSP00000240328 P1
TBX2ENST00000419047.5 linkuse as main transcriptc.110T>G p.Phe37Cys missense_variant, NMD_transcript_variant 1/71 ENSP00000404781
TBX2-AS1ENST00000592009.1 linkuse as main transcriptn.41-6539A>C intron_variant, non_coding_transcript_variant 3
ENST00000585765.1 linkuse as main transcript upstream_gene_variant 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Vertebral anomalies and variable endocrine and T-cell dysfunction Pathogenic:1
Likely pathogenic, no assertion criteria providedclinical testingCenter for Molecular Medicine, Children’s Hospital of Fudan UniversityJul 07, 2020- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.62
BayesDel_addAF
Pathogenic
0.23
D
BayesDel_noAF
Uncertain
0.090
CADD
Pathogenic
30
DANN
Uncertain
0.99
DEOGEN2
Pathogenic
0.83
D
Eigen
Uncertain
0.51
Eigen_PC
Uncertain
0.43
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Pathogenic
0.97
D
M_CAP
Pathogenic
0.81
D
MetaRNN
Pathogenic
0.82
D
MetaSVM
Uncertain
0.55
D
MutationAssessor
Uncertain
2.3
M
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.95
D
PROVEAN
Uncertain
-4.1
D
REVEL
Pathogenic
0.68
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.042
D
Polyphen
1.0
D
Vest4
0.69
MutPred
0.25
Loss of stability (P = 0.105);
MVP
0.64
ClinPred
1.0
D
GERP RS
3.6
Varity_R
0.80
gMVP
0.80

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: rs2060258573; hg19: chr17-59477647; API