Genetic Variant TBX2:c.1686+569C>T (chr17-61406405-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005994.4(TBX2):c.1686+569C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 152,088 control chromosomes in the GnomAD database, including 26,509 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.56 ( 26484 hom., cov: 31)

Exomes 𝑓: 0.74 ( 25 hom. )

Consequence

TBX2
NM_005994.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.304

Publications

50 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

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.1686+569C>T		intron	N/A	NP_005985.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TBX2	ENST00000240328.4	TSL:1 MANE Select	c.1686+569C>T	intron	N/A	ENSP00000240328.3	Q13207
TBX2	ENST00000419047.5	TSL:1	n.*1223+569C>T	intron	N/A	ENSP00000404781.1	F8WCM9
TBX2	ENST00000964762.1		c.1746+569C>T	intron	N/A	ENSP00000634821.1

Frequencies

GnomAD3 genomes

AF:

0.556

AC:

84411

AN:

151884

Hom.:

26484

Cov.:

show subpopulations

Gnomad AFR

AF:

0.278

Gnomad AMI

AF:

0.768

Gnomad AMR

AF:

0.477

Gnomad ASJ

AF:

0.699

Gnomad EAS

AF:

0.354

Gnomad SAS

AF:

0.524

Gnomad FIN

AF:

0.724

Gnomad MID

AF:

0.623

Gnomad NFE

AF:

0.722

Gnomad OTH

AF:

0.582

GnomAD4 exome

AF:

0.744

AC:

AN:

Hom.:

Cov.:

AF XY:

0.774

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.833

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.766

AC:

AN:

Other (OTH)

AF:

0.667

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.564

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

AF:

0.555

AC:

84419

AN:

152002

Hom.:

26484

Cov.:

AF XY:

0.553

AC XY:

41089

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.278

AC:

11512

AN:

41440

American (AMR)

AF:

0.476

AC:

7278

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.699

AC:

2426

AN:

3472

East Asian (EAS)

AF:

0.355

AC:

1833

AN:

5164

South Asian (SAS)

AF:

0.523

AC:

2518

AN:

4814

European-Finnish (FIN)

AF:

0.724

AC:

7645

AN:

10558

Middle Eastern (MID)

AF:

0.626

AC:

184

AN:

294

European-Non Finnish (NFE)

AF:

0.722

AC:

49095

AN:

67962

Other (OTH)

AF:

0.581

AC:

1229

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1646

3293

4939

6586

8232

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

704

1408

2112

2816

3520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.651

Hom.:

110297

Bravo

AF:

0.524

Asia WGS

AF:

0.423

AC:

1476

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

9.2

(source)

DANN

Benign

0.64

PhyloP100

0.30

Mutation Taster

=100/0

polymorphism (auto)

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over