dbSNP rs1048308922: TBX2:p.Pro55Gln (chr17-61400340-C-A) – 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.164C>A(p.Pro55Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000002 in 1,000,292 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. P55S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000068 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000012 ( 0 hom. )

Consequence

TBX2
NM_005994.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.38

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:

Genome browser will be placed here

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=0.27443993).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBX2	NM_005994.4 link	c.164C>A	p.Pro55Gln	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.164C>A	p.Pro55Gln	missense_variant	Exon 1 of 7	1	NM_005994.4	ENSP00000240328.3		Q13207

Frequencies

GnomAD3 genomes

AF:

0.00000682

AC:

AN:

146656

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000152

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000117

AC:

AN:

853636

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

397192

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

16110

American (AMR)

AF:

0.00

AC:

AN:

1562

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5530

East Asian (EAS)

AF:

0.00

AC:

AN:

4380

South Asian (SAS)

AF:

0.00

AC:

AN:

17522

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1926

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1794

European-Non Finnish (NFE)

AF:

0.00000129

AC:

AN:

776540

Other (OTH)

AF:

0.00

AC:

AN:

28272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000682

AC:

AN:

146656

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

71316

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40908

American (AMR)

AF:

0.00

AC:

AN:

14764

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3394

East Asian (EAS)

AF:

0.00

AC:

AN:

5118

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8478

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000152

AC:

AN:

65924

Other (OTH)

AF:

0.00

AC:

AN:

2016

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

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.050

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.25

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.82

M_CAP

Pathogenic

0.90

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.57

MutationAssessor

Benign

0.34

PhyloP100

4.4

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

1.7

REVEL

Benign

0.23

Sift

Benign

0.37

Sift4G

Benign

0.59

Polyphen

0.87

Vest4

0.20

MutPred

0.27

Loss of glycosylation at P55 (P = 0.0381);

MVP

0.40

ClinPred

0.69

GERP RS

2.3

PromoterAI

0.035

Neutral

(source)

Varity_R

0.069

gMVP

0.29

Mutation Taster

=98/2

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.

rs1048308922

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over