chr17-61400286-T-G
Position:
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
NM_005994.4 missense
Scores
9
9
1
Clinical Significance
Conservation
PhyloP100: 6.20
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)
Genome browser will be placed here
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 |
---|---|---|---|---|---|---|---|---|
TBX2 | NM_005994.4 | c.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 |
---|---|---|---|---|---|---|---|---|---|---|
TBX2 | ENST00000240328.4 | c.110T>G | p.Phe37Cys | missense_variant | 1/7 | 1 | NM_005994.4 | ENSP00000240328 | P1 | |
TBX2 | ENST00000419047.5 | c.110T>G | p.Phe37Cys | missense_variant, NMD_transcript_variant | 1/7 | 1 | ENSP00000404781 | |||
TBX2-AS1 | ENST00000592009.1 | n.41-6539A>C | intron_variant, non_coding_transcript_variant | 3 | ||||||
ENST00000585765.1 | upstream_gene_variant | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome Cov.: 32
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 provided | clinical testing | Center for Molecular Medicine, Children’s Hospital of Fudan University | Jul 07, 2020 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Loss of stability (P = 0.105);
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at