Genetic Variant TBX2:p.Ala58Val (chr17-61400349-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_005994.4(TBX2):c.173C>T(p.Ala58Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000116 in 861,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A58E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000012 ( 0 hom. )

Consequence

TBX2
NM_005994.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.06

Publications

0 publications found

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 links:

TBX2-AS1 (HGNC:50355): (TBX2 antisense RNA 1)

TBX2-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3774511).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005994.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBX2	NM_005994.4	MANE Select	c.173C>T	p.Ala58Val	missense	Exon 1 of 7	NP_005985.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TBX2	ENST00000240328.4	TSL:1 MANE Select	c.173C>T	p.Ala58Val	missense	Exon 1 of 7	ENSP00000240328.3	Q13207
TBX2	ENST00000419047.5	TSL:1	n.173C>T		non_coding_transcript_exon	Exon 1 of 7	ENSP00000404781.1	F8WCM9
TBX2	ENST00000964762.1		c.173C>T	p.Ala58Val	missense	Exon 1 of 8	ENSP00000634821.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000116

AC:

AN:

861068

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

401374

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

16282

American (AMR)

AF:

0.00

AC:

AN:

1756

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5712

East Asian (EAS)

AF:

0.00

AC:

AN:

4776

South Asian (SAS)

AF:

0.00

AC:

AN:

17594

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2726

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1784

European-Non Finnish (NFE)

AF:

0.00000128

AC:

AN:

781686

Other (OTH)

AF:

0.00

AC:

AN:

28752

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.0035

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

Eigen

Benign

0.040

Eigen_PC

Benign

0.048

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.77

M_CAP

Pathogenic

0.93

MetaRNN

Benign

0.38

MetaSVM

Uncertain

-0.042

MutationAssessor

Benign

1.6

PhyloP100

1.1

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

0.82

REVEL

Benign

0.26

Sift

Benign

0.71

Sift4G

Benign

0.58

Polyphen

0.98

Vest4

0.17

MutPred

0.32

Loss of glycosylation at P55 (P = 0.1582)

MVP

0.61

ClinPred

0.91

GERP RS

3.6

Varity_R

0.083

gMVP

0.46

Mutation Taster

=66/34

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over