Genetic Variant TBX2:p.Ala8Pro (chr17-61400198-G-C) – 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.22G>C(p.Ala8Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. A8T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TBX2
NM_005994.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.14

Publications

2 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=0.38398755).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBX2	NM_005994.4 link	c.22G>C	p.Ala8Pro	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
TBX2	ENST00000240328.4 link	c.22G>C	p.Ala8Pro	missense_variant	Exon 1 of 7	1	NM_005994.4	ENSP00000240328.3		Q13207

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000750

AC:

AN:

133360

AF XY:

0.0000128

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000149

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1014632

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

496958

African (AFR)

AF:

0.00

AC:

AN:

19620

American (AMR)

AF:

0.00

AC:

AN:

17918

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11666

East Asian (EAS)

AF:

0.00

AC:

AN:

9228

South Asian (SAS)

AF:

0.00

AC:

AN:

50030

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9488

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2966

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

859422

Other (OTH)

AF:

0.00

AC:

AN:

34294

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Uncertain

0.077

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.40

Eigen

Benign

-0.040

Eigen_PC

Benign

0.014

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.62

M_CAP

Pathogenic

0.96

MetaRNN

Benign

0.38

MetaSVM

Uncertain

-0.051

MutationAssessor

Benign

1.1

PhyloP100

6.1

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-1.1

REVEL

Uncertain

0.37

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.041

Polyphen

0.57

Vest4

0.37

MutPred

0.24

Gain of glycosylation at A8 (P = 0.0338);

MVP

0.36

ClinPred

0.81

GERP RS

3.2

PromoterAI

-0.067

Neutral

(source)

Varity_R

0.56

gMVP

0.61

Mutation Taster

=49/51

disease causing

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over