chr17-61400362-C-CGCGGCGGCG

Variant names:

• chr17-61400362-C-CGCGGCGGCG
• rs539663160
• NM_005994.4:c.195_203dupGGCGGCGGC

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP3 BS2_Supporting

The NM_005994.4(TBX2):​c.195_203dupGGCGGCGGC​(p.Ala66_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 0.0000058 in 1,033,728 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 0.0000068 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000056 (0 hom.)
• Consequence: TBX2 NM_005994.4 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53
• Publications: 0 publications found

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)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_005994.4
• BS2: High AC in GnomAdExome4 at 5 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBX2	NM_005994.4	c.195_203dupGGCGGCGGC	p.Ala66_Ala68dup	disruptive_inframe_insertion	Exon 1 of 7	ENST00000240328.4	NP_005985.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBX2	ENST00000240328.4	c.195_203dupGGCGGCGGC	p.Ala66_Ala68dup	disruptive_inframe_insertion	Exon 1 of 7	1	NM_005994.4	ENSP00000240328.3

Frequencies

GnomAD3 genomes AF: 0.00000681 AC: 1 AN: 146904 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000564 AC: 5 AN: 886824 Hom.: 0 Cov.: 30 AF XY: 0.00000482 AC XY: 2 AN XY: 415134

African (AFR) AF: 0.00 AC: 0 AN: 16918

American (AMR) AF: 0.00 AC: 0 AN: 2438

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6546

East Asian (EAS) AF: 0.000422 AC: 3 AN: 7116

South Asian (SAS) AF: 0.00 AC: 0 AN: 17832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1934

European-Non Finnish (NFE) AF: 0.00000125 AC: 1 AN: 798124

Other (OTH) AF: 0.0000330 AC: 1 AN: 30342

GnomAD4 genome AF: 0.00000681 AC: 1 AN: 146904 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 71442

African (AFR) AF: 0.00 AC: 0 AN: 40896

American (AMR) AF: 0.00 AC: 0 AN: 14784

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3392

East Asian (EAS) AF: 0.000196 AC: 1 AN: 5098

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8648

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66018

Other (OTH) AF: 0.00 AC: 0 AN: 2022

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5
Mutation Taster		=63/37	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs539663160; hg19: chr17-59477723;