dbSNP rs1168700579: TBX2:p.Ala64Glu (chr17-61400367-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005994.4(TBX2):c.191C>A(p.Ala64Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000221 in 906,458 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A64V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

TBX2
NM_005994.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.91

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.191C>A	p.Ala64Glu	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.191C>A	p.Ala64Glu	missense	Exon 1 of 7	ENSP00000240328.3	Q13207
TBX2	ENST00000419047.5	TSL:1	n.191C>A		non_coding_transcript_exon	Exon 1 of 7	ENSP00000404781.1	F8WCM9
TBX2	ENST00000964762.1		c.191C>A	p.Ala64Glu	missense	Exon 1 of 8	ENSP00000634821.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000221

AC:

AN:

906458

Hom.:

Cov.:

AF XY:

0.00000470

AC XY:

AN XY:

425298

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

17434

American (AMR)

AF:

0.00

AC:

AN:

3014

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7264

East Asian (EAS)

AF:

0.00

AC:

AN:

9078

South Asian (SAS)

AF:

0.00

AC:

AN:

18088

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7336

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2014

European-Non Finnish (NFE)

AF:

0.00000247

AC:

AN:

810670

Other (OTH)

AF:

0.00

AC:

AN:

31560

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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

0.32

BayesDel_addAF

Uncertain

0.028

BayesDel_noAF

Benign

-0.20

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.24

Eigen

Benign

0.074

Eigen_PC

Benign

0.085

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.33

M_CAP

Pathogenic

0.98

MetaRNN

Uncertain

0.50

MetaSVM

Benign

-0.51

MutationAssessor

Benign

-0.34

PhyloP100

2.9

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.13

REVEL

Uncertain

0.32

Sift

Benign

0.38

Sift4G

Benign

1.0

Polyphen

0.96

Vest4

0.36

MutPred

0.48

Loss of catalytic residue at G59 (P = 0.3669)

MVP

0.52

ClinPred

0.54

GERP RS

3.3

Varity_R

0.13

gMVP

0.48

Mutation Taster

=90/10

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