rs757195340

Variant names:

• chr17-61400328-C-A
• rs757195340
• NM_005994.4:c.152C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005994.4(TBX2):​c.152C>A​(p.Pro51Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000196 in 1,019,856 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000068 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: TBX2 NM_005994.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.66
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.152C>A	p.Pro51Gln	missense	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.152C>A	p.Pro51Gln	missense	Exon 1 of 7	ENSP00000240328.3	Q13207
	TBX2	ENST00000419047.5	TSL:1	n.152C>A		non_coding_transcript_exon	Exon 1 of 7	ENSP00000404781.1	F8WCM9
	TBX2	ENST00000964762.1		c.152C>A	p.Pro51Gln	missense	Exon 1 of 8	ENSP00000634821.1

Frequencies

GnomAD3 genomes AF: 0.00000682 AC: 1 AN: 146646 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 9476 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000115 AC: 1 AN: 873210 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 409964

African (AFR) AF: 0.0000601 AC: 1 AN: 16628

American (AMR) AF: 0.00 AC: 0 AN: 4284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6594

East Asian (EAS) AF: 0.00 AC: 0 AN: 4416

South Asian (SAS) AF: 0.00 AC: 0 AN: 22650

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2240

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1952

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 785344

Other (OTH) AF: 0.00 AC: 0 AN: 29102

GnomAD4 genome AF: 0.00000682 AC: 1 AN: 146646 Hom.: 0 Cov.: 32 AF XY: 0.0000140 AC XY: 1 AN XY: 71320

African (AFR) AF: 0.0000244 AC: 1 AN: 40918

American (AMR) AF: 0.00 AC: 0 AN: 14760

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3392

East Asian (EAS) AF: 0.00 AC: 0 AN: 5126

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8424

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65948

Other (OTH) AF: 0.00 AC: 0 AN: 2022

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000348 AC: 2

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	27
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.69	D
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.67	T
M_CAP	Pathogenic	0.91	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Uncertain	0.52	D
MutationAssessor	Benign	1.9	L
PhyloP100		4.7
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.49
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.090	T
Polyphen		1.0	D
Vest4		0.34
MutPred		0.24		Gain of helix (P = 0.0093)
MVP		0.22
ClinPred		0.97	D
GERP RS		3.3
PromoterAI		-0.047	Neutral
Varity_R		0.41
gMVP		0.66
Mutation Taster		=71/29	polymorphism

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: rs757195340; hg19: chr17-59477689;