chr17-61400362-CGCGGCG-C

Variant names:

• chr17-61400362-CGCGGCG-C
• rs539663160
• NM_005994.4:c.198_203delGGCGGC

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP3

The NM_005994.4(TBX2):​c.198_203delGGCGGC​(p.Ala67_Ala68del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000113 in 886,820 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: TBX2 NM_005994.4 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.91
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP3: Nonframeshift variant in repetitive region in NM_005994.4

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_203delGGCGGC	p.Ala67_Ala68del	disruptive_inframe_deletion	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.198_203delGGCGGC	p.Ala67_Ala68del	disruptive_inframe_deletion	Exon 1 of 7	ENSP00000240328.3	Q13207
	TBX2	ENST00000419047.5	TSL:1	n.198_203delGGCGGC		non_coding_transcript_exon	Exon 1 of 7	ENSP00000404781.1	F8WCM9
	TBX2	ENST00000964762.1		c.198_203delGGCGGC	p.Ala67_Ala68del	disruptive_inframe_deletion	Exon 1 of 8	ENSP00000634821.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000113 AC: 1 AN: 886820 Hom.: 0 AF XY: 0.00000241 AC XY: 1 AN XY: 415132

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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: 0.00 AC: 0 AN: 7114

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5572

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

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

Other (OTH) AF: 0.00 AC: 0 AN: 30342

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.9

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;