NM_005994.4:c.201_203dupGGC

Variant names:

• chr17-61400362-C-CGCG
• rs539663160
• NM_005994.4:c.201_203dupGGC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP3 BP6 BS1 BS2

The NM_005994.4(TBX2):​c.201_203dupGGC​(p.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 0.00122 in 1,033,824 control chromosomes in the GnomAD database, including 10 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0054 (7 hom., cov: 32)
  • Exomes 𝑓: 0.00054 (3 hom.)
• Consequence: TBX2 NM_005994.4 disruptive_inframe_insertion
• Clinical Significance: Likely benign no assertion criteria provided B:1
• 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: Benign. The variant received -10 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_005994.4
• BP6: Variant 17-61400362-C-CGCG is Benign according to our data. Variant chr17-61400362-C-CGCG is described in ClinVar as Likely_benign. ClinVar VariationId is 3055119.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00537 (790/147004) while in subpopulation AFR AF = 0.0178 (730/41008). AF 95% confidence interval is 0.0167. There are 7 homozygotes in GnomAd4. There are 382 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 790 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.201_203dupGGC	p.Ala68dup	disruptive_inframe_insertion	Exon 1 of 7	NP_005985.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBX2	ENST00000240328.4	TSL:1 MANE Select	c.201_203dupGGC	p.Ala68dup	disruptive_inframe_insertion	Exon 1 of 7	ENSP00000240328.3	Q13207
	TBX2	ENST00000419047.5	TSL:1	n.201_203dupGGC		non_coding_transcript_exon	Exon 1 of 7	ENSP00000404781.1	F8WCM9
	TBX2	ENST00000964762.1		c.201_203dupGGC	p.Ala68dup	disruptive_inframe_insertion	Exon 1 of 8	ENSP00000634821.1

Frequencies

GnomAD3 genomes AF: 0.00538 AC: 790 AN: 146900 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0179

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00271

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000116

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.000136

Gnomad OTH AF: 0.00346

GnomAD2 exomes AF: 0.000539 AC: 1 AN: 1854 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000628

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000536 AC: 475 AN: 886820 Hom.: 3 Cov.: 30 AF XY: 0.000511 AC XY: 212 AN XY: 415132

African (AFR) AF: 0.0206 AC: 349 AN: 16916

American (AMR) AF: 0.00164 AC: 4 AN: 2438

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 7116

South Asian (SAS) AF: 0.0000561 AC: 1 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: 0.000127 AC: 101 AN: 798122

Other (OTH) AF: 0.000659 AC: 20 AN: 30342

GnomAD4 genome AF: 0.00537 AC: 790 AN: 147004 Hom.: 7 Cov.: 32 AF XY: 0.00534 AC XY: 382 AN XY: 71556

African (AFR) AF: 0.0178 AC: 730 AN: 41008

American (AMR) AF: 0.00270 AC: 40 AN: 14804

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

East Asian (EAS) AF: 0.000197 AC: 1 AN: 5082

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

European-Finnish (FIN) AF: 0.000116 AC: 1 AN: 8648

Middle Eastern (MID) AF: 0.00345 AC: 1 AN: 290

European-Non Finnish (NFE) AF: 0.000136 AC: 9 AN: 66008

Other (OTH) AF: 0.00342 AC: 7 AN: 2044

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	TBX2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

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;