chr17-61400362-C-CGCGGCG

Variant summary

Our verdict is Likely benign. Variant got -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
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-AS1 (HGNC:50355): (TBX2 antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP3
Nonframeshift variant in repetitive region in NM_005994.4
BS2
High AC in GnomAd4 at 34 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TBX2NM_005994.4 linkc.198_203dupGGCGGC p.Ala67_Ala68dup disruptive_inframe_insertion Exon 1 of 7 ENST00000240328.4 NP_005985.3 Q13207A0A024QZ86

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TBX2ENST00000240328.4 linkc.198_203dupGGCGGC p.Ala67_Ala68dup disruptive_inframe_insertion Exon 1 of 7 1 NM_005994.4 ENSP00000240328.3 Q13207

Frequencies

GnomAD3 genomes
AF:
0.000231
AC:
34
AN:
146902
Hom.:
0
Cov.:
32
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.:
0
Cov.:
30
AF XY:
0.000161
AC XY:
67
AN XY:
415134
show subpopulations
Gnomad4 AFR exome
AF:
0.000236
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000141
Gnomad4 SAS exome
AF:
0.000168
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000140
Gnomad4 OTH exome
AF:
0.000395
GnomAD4 genome
AF:
0.000231
AC:
34
AN:
147006
Hom.:
0
Cov.:
32
AF XY:
0.000196
AC XY:
14
AN XY:
71554
show subpopulations
Gnomad4 AFR
AF:
0.000634
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000787
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000303
Gnomad4 OTH
AF:
0.000489
Bravo
AF:
0.000230

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs539663160; hg19: chr17-59477723; API