Variant chr17-61400542-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_005994.4(TBX2):c.366C>A(p.Gly122=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0734 in 1,577,446 control chromosomes in the GnomAD database, including 6,201 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.093 ( 910 hom., cov: 32)

Exomes 𝑓: 0.071 ( 5291 hom. )

Consequence

TBX2
NM_005994.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.903

Variant links:

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 links:

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

TBX2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 17-61400542-C-A is Benign according to our data. Variant chr17-61400542-C-A is described in ClinVar as [Benign]. Clinvar id is 1225829.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.903 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBX2	NM_005994.4 linkuse as main transcript	c.366C>A	p.Gly122=	synonymous_variant	1/7	ENST00000240328.4	NP_005985.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TBX2	ENST00000240328.4 linkuse as main transcript	c.366C>A	p.Gly122=	synonymous_variant	1/7	1	NM_005994.4	ENSP00000240328	P1
TBX2	ENST00000419047.5 linkuse as main transcript	c.366C>A	p.Gly122=	synonymous_variant, NMD_transcript_variant	1/7	1		ENSP00000404781
TBX2-AS1	ENST00000592009.1 linkuse as main transcript	n.41-6795G>T		intron_variant, non_coding_transcript_variant		3
TBX2	ENST00000477081.1 linkuse as main transcript	n.178C>A		non_coding_transcript_exon_variant	1/5	2

Frequencies

GnomAD3 genomes

AF:

0.0928

AC:

14095

AN:

151816

Hom.:

902

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0960

Gnomad AMI

AF:

0.0396

Gnomad AMR

AF:

0.172

Gnomad ASJ

AF:

0.0479

Gnomad EAS

AF:

0.288

Gnomad SAS

AF:

0.124

Gnomad FIN

AF:

0.110

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0569

Gnomad OTH

AF:

0.0899

GnomAD3 exomes

AF:

0.115

AC:

21498

AN:

187362

Hom.:

1812

AF XY:

0.110

AC XY:

11085

AN XY:

100982

show subpopulations

Gnomad AFR exome

AF:

0.0982

Gnomad AMR exome

AF:

0.222

Gnomad ASJ exome

AF:

0.0503

Gnomad EAS exome

AF:

0.293

Gnomad SAS exome

AF:

0.117

Gnomad FIN exome

AF:

0.108

Gnomad NFE exome

AF:

0.0556

Gnomad OTH exome

AF:

0.0931

GnomAD4 exome

AF:

0.0713

AC:

101701

AN:

1425522

Hom.:

5291

Cov.:

AF XY:

0.0725

AC XY:

51140

AN XY:

705512

show subpopulations

Gnomad4 AFR exome

AF:

0.0987

Gnomad4 AMR exome

AF:

0.212

Gnomad4 ASJ exome

AF:

0.0475

Gnomad4 EAS exome

AF:

0.277

Gnomad4 SAS exome

AF:

0.112

Gnomad4 FIN exome

AF:

0.108

Gnomad4 NFE exome

AF:

0.0536

Gnomad4 OTH exome

AF:

0.0810

GnomAD4 genome

AF:

0.0930

AC:

14128

AN:

151924

Hom.:

910

Cov.:

AF XY:

0.0982

AC XY:

7291

AN XY:

74238

show subpopulations

Gnomad4 AFR

AF:

0.0960

Gnomad4 AMR

AF:

0.173

Gnomad4 ASJ

AF:

0.0479

Gnomad4 EAS

AF:

0.289

Gnomad4 SAS

AF:

0.125

Gnomad4 FIN

AF:

0.110

Gnomad4 NFE

AF:

0.0569

Gnomad4 OTH

AF:

0.0890

Alfa

AF:

0.0634

Hom.:

132

Bravo

AF:

0.0981

Asia WGS

AF:

0.168

AC:

575

AN:

3428

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 08, 2019	- -

TBX2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 13, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.94

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over