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17-61400542-C-A

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

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.903 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
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 UniProt
TBX2NM_005994.4 linkuse as main transcriptc.366C>A p.Gly122= synonymous_variant 1/7 ENST00000240328.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TBX2ENST00000240328.4 linkuse as main transcriptc.366C>A p.Gly122= synonymous_variant 1/71 NM_005994.4 P1
TBX2ENST00000419047.5 linkuse as main transcriptc.366C>A p.Gly122= synonymous_variant, NMD_transcript_variant 1/71
TBX2-AS1ENST00000592009.1 linkuse as main transcriptn.41-6795G>T intron_variant, non_coding_transcript_variant 3
TBX2ENST00000477081.1 linkuse as main transcriptn.178C>A non_coding_transcript_exon_variant 1/52

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0928
AC:
14095
AN:
151816
Hom.:
902
Cov.:
32
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.:
34
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0930
AC:
14128
AN:
151924
Hom.:
910
Cov.:
32
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:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxFeb 08, 2019- -
TBX2-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesAug 13, 2019This 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
14
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.

Other links and lift over

dbSNP: rs75743672; hg19: chr17-59477903; COSMIC: COSV53598652; COSMIC: COSV53598652; API