rs2270114

Variant names:

• chr17-61401415-G-C
• rs2270114
• NM_005994.4:c.396-269G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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 -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 rank	MANE	Protein	UniProt
TBX2	NM_005994.4	c.396-269G>C		intron_variant	Intron 1 of 6	ENST00000240328.4	NP_005985.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBX2	ENST00000240328.4	c.396-269G>C		intron_variant	Intron 1 of 6	1	NM_005994.4	ENSP00000240328.3

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

African (AFR) AF: 0.223 AC: 9262 AN: 41508

American (AMR) AF: 0.469 AC: 7167 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.699 AC: 2424 AN: 3470

East Asian (EAS) AF: 0.351 AC: 1815 AN: 5168

South Asian (SAS) AF: 0.505 AC: 2432 AN: 4816

European-Finnish (FIN) AF: 0.724 AC: 7649 AN: 10568

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.722 AC: 49089 AN: 67980

Other (OTH) AF: 0.567 AC: 1199 AN: 2114

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
PhyloP100		2.1
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2270114; hg19: chr17-59478776;