Genetic Variant TBX2:p.Ala67_Ala68dup (chr17-61400362-C-CGCGGCG) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP3BS2

The NM_005994.4(TBX2):c.198_203dupGGCGGC(p.Ala67_Ala68dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000161 in 1,033,830 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

TBX2
NM_005994.4 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.53

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: Likely_benign. The variant received -5 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_005994.4

BS2

High AC in GnomAd4 at 34 AD gene.

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.198_203dupGGCGGC	p.Ala67_Ala68dup	disruptive_inframe_insertion	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.198_203dupGGCGGC	p.Ala67_Ala68dup	disruptive_inframe_insertion	Exon 1 of 7	ENSP00000240328.3	Q13207
TBX2	ENST00000419047.5	TSL:1	n.198_203dupGGCGGC		non_coding_transcript_exon	Exon 1 of 7	ENSP00000404781.1	F8WCM9
TBX2	ENST00000964762.1		c.198_203dupGGCGGC	p.Ala67_Ala68dup	disruptive_inframe_insertion	Exon 1 of 8	ENSP00000634821.1

Frequencies

GnomAD3 genomes

AF:

0.000231

AC:

AN:

146902

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000636

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000785

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000303

Gnomad OTH

AF:

0.000495

GnomAD4 exome

AF:

0.000149

AC:

132

AN:

886824

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

415134

show subpopulations

African (AFR)

AF:

0.000236

AC:

AN:

16918

American (AMR)

AF:

0.00

AC:

AN:

2438

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

6546

East Asian (EAS)

AF:

0.000141

AC:

AN:

7116

South Asian (SAS)

AF:

0.000168

AC:

AN:

17832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5574

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1934

European-Non Finnish (NFE)

AF:

0.000140

AC:

112

AN:

798124

Other (OTH)

AF:

0.000395

AC:

AN:

30342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

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

AF:

0.000231

AC:

AN:

147006

Hom.:

Cov.:

AF XY:

0.000196

AC XY:

AN XY:

71554

show subpopulations

African (AFR)

AF:

0.000634

AC:

AN:

41010

American (AMR)

AF:

0.00

AC:

AN:

14804

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3392

East Asian (EAS)

AF:

0.000787

AC:

AN:

5082

South Asian (SAS)

AF:

0.000208

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8648

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0000303

AC:

AN:

66008

Other (OTH)

AF:

0.000489

AC:

AN:

2044

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000230

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.5

Mutation Taster

=63/37

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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17-61400362-CGCGGCGGCGGCG-CGCGGCGGCGGCGGCGGCG

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