rs2286524

Variant names:

• chr17-61399531-C-T
• rs2286524
• ENST00000589814.6:n.49G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000590421.2(TBX2-AS1):​n.76G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0926 in 152,298 control chromosomes in the GnomAD database, including 906 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.093 (906 hom., cov: 33)
  • Exomes 𝑓: 0.048 (0 hom.)
• Consequence: TBX2-AS1 ENST00000590421.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 4 publications found

Genes affected

TBX2-AS1 (HGNC:50355): (TBX2 antisense RNA 1)

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 Gene-Disease associations (from GenCC):

• vertebral anomalies and variable endocrine and T-cell dysfunction

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000590421.2. 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-AS1	NR_125749.1		n.76G>A		non_coding_transcript_exon	Exon 1 of 2
	TBX2-AS1	NR_125750.1		n.76G>A		non_coding_transcript_exon	Exon 1 of 3
	TBX2-AS1	NR_125751.1		n.76G>A		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBX2-AS1	ENST00000589814.6	TSL:3	n.49G>A		non_coding_transcript_exon	Exon 1 of 3
	TBX2-AS1	ENST00000590421.2	TSL:2	n.76G>A		non_coding_transcript_exon	Exon 1 of 2
	TBX2-AS1	ENST00000591313.8	TSL:2	n.79G>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0924 AC: 14053 AN: 152066 Hom.: 897 Cov.: 33

Gnomad AFR AF: 0.0946

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.0478

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.0637

Gnomad NFE AF: 0.0567

Gnomad OTH AF: 0.0898

GnomAD4 exome AF: 0.0484 AC: 6 AN: 124 Hom.: 0 Cov.: 0 AF XY: 0.0510 AC XY: 5 AN XY: 98

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0431 AC: 5 AN: 116

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.0926 AC: 14092 AN: 152174 Hom.: 906 Cov.: 33 AF XY: 0.0979 AC XY: 7284 AN XY: 74386

African (AFR) AF: 0.0948 AC: 3937 AN: 41538

American (AMR) AF: 0.173 AC: 2639 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0478 AC: 166 AN: 3470

East Asian (EAS) AF: 0.290 AC: 1485 AN: 5124

South Asian (SAS) AF: 0.125 AC: 603 AN: 4834

European-Finnish (FIN) AF: 0.109 AC: 1161 AN: 10604

Middle Eastern (MID) AF: 0.0685 AC: 20 AN: 292

European-Non Finnish (NFE) AF: 0.0567 AC: 3857 AN: 67992

Other (OTH) AF: 0.0888 AC: 188 AN: 2116

Alfa AF: 0.0721 Hom.: 62

Bravo AF: 0.0978

Asia WGS AF: 0.178 AC: 616 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	13
DANN	Benign	0.96
PhyloP100		-1.2
PromoterAI		-0.0062	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

Splicing

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

Other links and lift over

dbSNP: rs2286524; hg19: chr17-59476892; COSMIC: COSV107270566;