rs1555877071
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP3BS2_Supporting
The NM_005994.4(TBX2):c.914G>A(p.Arg305His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000035 in 1,429,056 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 (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000035 ( 0 hom. )
Consequence
TBX2
NM_005994.4 missense
NM_005994.4 missense
Scores
4
12
3
Clinical Significance
Conservation
PhyloP100: 7.42
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]
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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;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.797
BS2
High AC in GnomAdExome4 at 5 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TBX2 | NM_005994.4 | c.914G>A | p.Arg305His | missense_variant | 5/7 | ENST00000240328.4 | NP_005985.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TBX2 | ENST00000240328.4 | c.914G>A | p.Arg305His | missense_variant | 5/7 | 1 | NM_005994.4 | ENSP00000240328.3 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 0.00000350 AC: 5AN: 1429056Hom.: 0 Cov.: 31 AF XY: 0.00000424 AC XY: 3AN XY: 707084
GnomAD4 exome
AF:
AC:
5
AN:
1429056
Hom.:
Cov.:
31
AF XY:
AC XY:
3
AN XY:
707084
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Pathogenic:1Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Vertebral anomalies and variable endocrine and T-cell dysfunction Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 06, 2018 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 10, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Benign
L
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
T
Polyphen
D
Vest4
MutPred
Loss of MoRF binding (P = 0.0174);
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