17-61406405-C-T

Variant names:

• chr17-61406405-C-T
• rs8068318
• NM_005994.4:c.1686+569C>T

Variant summary

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

The NM_005994.4(TBX2):​c.1686+569C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 152,088 control chromosomes in the GnomAD database, including 26,509 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 0.56 (26484 hom., cov: 31)
  • Exomes 𝑓: 0.74 (25 hom.)
• Consequence: TBX2 NM_005994.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.304

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• 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.1686+569C>T		intron_variant	Intron 6 of 6	ENST00000240328.4	NP_005985.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBX2	ENST00000240328.4	c.1686+569C>T		intron_variant	Intron 6 of 6	1	NM_005994.4	ENSP00000240328.3
TBX2	ENST00000419047.5	n.*1223+569C>T		intron_variant	Intron 6 of 6	1		ENSP00000404781.1
TBX2	ENST00000477081.1	n.2499C>T		non_coding_transcript_exon_variant	Exon 5 of 5	2
TBX2-AS1	ENST00000592009.1	n.40+5111G>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84411 AN: 151884 Hom.: 26484 Cov.: 31

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.524

Gnomad FIN AF: 0.724

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.722

Gnomad OTH AF: 0.582

GnomAD4 exome AF: 0.744 AC: 64 AN: 86 Hom.: 25 Cov.: 0 AF XY: 0.774 AC XY: 48 AN XY: 62

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.833

Gnomad4 NFE exome AF: 0.766

Gnomad4 OTH exome AF: 0.667

GnomAD4 genome AF: 0.555 AC: 84419 AN: 152002 Hom.: 26484 Cov.: 31 AF XY: 0.553 AC XY: 41089 AN XY: 74290

Gnomad4 AFR AF: 0.278

Gnomad4 AMR AF: 0.476

Gnomad4 ASJ AF: 0.699

Gnomad4 EAS AF: 0.355

Gnomad4 SAS AF: 0.523

Gnomad4 FIN AF: 0.724

Gnomad4 NFE AF: 0.722

Gnomad4 OTH AF: 0.581

Alfa AF: 0.674 Hom.: 48068

Bravo AF: 0.524

Asia WGS AF: 0.423 AC: 1476 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.2
DANN	Benign	0.64

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: rs8068318; hg19: chr17-59483766;