rs75743672

Variant names:

• chr17-61400542-C-A
• rs75743672
• NM_005994.4:c.366C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-61400542-C-A
• chr17-61400542-C-T
• chr17-61400542-C-G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_005994.4(TBX2):​c.366C>A​(p.Gly122Gly) 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 (★★). Synonymous variant affecting the same amino acid position (i.e. G122G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.093 (910 hom., cov: 32)
  • Exomes 𝑓: 0.071 (5291 hom.)
• Consequence: TBX2 NM_005994.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.903
• Publications: 11 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 -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005994.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBX2	NM_005994.4	MANE Select	c.366C>A	p.Gly122Gly	synonymous	Exon 1 of 7	NP_005985.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBX2	ENST00000240328.4	TSL:1 MANE Select	c.366C>A	p.Gly122Gly	synonymous	Exon 1 of 7	ENSP00000240328.3	Q13207
	TBX2	ENST00000419047.5	TSL:1	n.366C>A		non_coding_transcript_exon	Exon 1 of 7	ENSP00000404781.1	F8WCM9
	TBX2	ENST00000964762.1		c.366C>A	p.Gly122Gly	synonymous	Exon 1 of 8	ENSP00000634821.1

Frequencies

GnomAD3 genomes AF: 0.0928 AC: 14095 AN: 151816 Hom.: 902 Cov.: 32

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

GnomAD2 exomes AF: 0.115 AC: 21498 AN: 187362 AF XY: 0.110

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 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

African (AFR) AF: 0.0987 AC: 3253 AN: 32956

American (AMR) AF: 0.212 AC: 8277 AN: 39066

Ashkenazi Jewish (ASJ) AF: 0.0475 AC: 1208 AN: 25416

East Asian (EAS) AF: 0.277 AC: 10623 AN: 38410

South Asian (SAS) AF: 0.112 AC: 9125 AN: 81344

European-Finnish (FIN) AF: 0.108 AC: 5337 AN: 49520

Middle Eastern (MID) AF: 0.0860 AC: 476 AN: 5538

European-Non Finnish (NFE) AF: 0.0536 AC: 58619 AN: 1094230

Other (OTH) AF: 0.0810 AC: 4783 AN: 59042

GnomAD4 genome AF: 0.0930 AC: 14128 AN: 151924 Hom.: 910 Cov.: 32 AF XY: 0.0982 AC XY: 7291 AN XY: 74238

African (AFR) AF: 0.0960 AC: 3984 AN: 41496

American (AMR) AF: 0.173 AC: 2647 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0479 AC: 166 AN: 3464

East Asian (EAS) AF: 0.289 AC: 1466 AN: 5080

South Asian (SAS) AF: 0.125 AC: 602 AN: 4820

European-Finnish (FIN) AF: 0.110 AC: 1159 AN: 10570

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0569 AC: 3861 AN: 67898

Other (OTH) AF: 0.0890 AC: 187 AN: 2102

Alfa AF: 0.0720 Hom.: 275

Bravo AF: 0.0981

Asia WGS AF: 0.168 AC: 575 AN: 3428

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	TBX2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	14
DANN	Benign	0.94
PhyloP100		0.90
Mutation Taster		=100/0	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: rs75743672; hg19: chr17-59477903; COSMIC: COSV53598652; COSMIC: COSV53598652;