chr17-61400362-C-CGCGGCG

Variant names:

• chr17-61400362-C-CGCGGCG
• rs539663160
• NM_005994.4:c.198_203dupGGCGGC

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP3 BS2

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
• 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 -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
TBX2	NM_005994.4	c.198_203dupGGCGGC	p.Ala67_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.198_203dupGGCGGC	p.Ala67_Ala68dup	disruptive_inframe_insertion	Exon 1 of 7	1	NM_005994.4	ENSP00000240328.3

Frequencies

GnomAD3 genomes AF: 0.000231 AC: 34 AN: 146902 Hom.: 0 Cov.: 32

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

African (AFR) AF: 0.000236 AC: 4 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: 0.000141 AC: 1 AN: 7116

South Asian (SAS) AF: 0.000168 AC: 3 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: 0.000140 AC: 112 AN: 798124

Other (OTH) AF: 0.000395 AC: 12 AN: 30342

GnomAD4 genome AF: 0.000231 AC: 34 AN: 147006 Hom.: 0 Cov.: 32 AF XY: 0.000196 AC XY: 14 AN XY: 71554

African (AFR) AF: 0.000634 AC: 26 AN: 41010

American (AMR) AF: 0.00 AC: 0 AN: 14804

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

East Asian (EAS) AF: 0.000787 AC: 4 AN: 5082

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4816

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.0000303 AC: 2 AN: 66008

Other (OTH) AF: 0.000489 AC: 1 AN: 2044

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000230

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;