rs2270114

Positions:

• chr17-61401415-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005994.4(TBX2):​c.396-269G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 152,108 control chromosomes in the GnomAD database, including 25,801 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 0.54 (25801 hom., cov: 32)
• Consequence: TBX2 NM_005994.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.14

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBX2	NM_005994.4	c.396-269G>C		intron_variant		ENST00000240328.4	NP_005985.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBX2	ENST00000240328.4	c.396-269G>C		intron_variant		1	NM_005994.4	ENSP00000240328.3
TBX2	ENST00000419047.5	n.396-291G>C		intron_variant		1		ENSP00000404781.1
TBX2	ENST00000477081.1	n.208-269G>C		intron_variant		2
TBX2-AS1	ENST00000592009.1	n.41-7668C>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81913 AN: 151990 Hom.: 25800 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.724

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.722

Gnomad OTH AF: 0.567

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.539 AC: 81918 AN: 152108 Hom.: 25801 Cov.: 32 AF XY: 0.537 AC XY: 39937 AN XY: 74346

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.469

Gnomad4 ASJ AF: 0.699

Gnomad4 EAS AF: 0.351

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.724

Gnomad4 NFE AF: 0.722

Gnomad4 OTH AF: 0.567

Alfa AF: 0.630 Hom.: 4073

Bravo AF: 0.505

Asia WGS AF: 0.410 AC: 1429 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	12
DANN	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2270114; hg19: chr17-59478776;