rs2060259013

Variant names:

• chr17-61400349-C-A
• rs2060259013
• NM_005994.4:c.173C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-61400349-C-A
• chr17-61400349-C-T

Variant summary

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

The NM_005994.4(TBX2):​c.173C>A​(p.Ala58Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000116 in 861,068 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: TBX2 NM_005994.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.06
• 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.173C>A	p.Ala58Glu	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.173C>A	p.Ala58Glu	missense	Exon 1 of 7	ENSP00000240328.3	Q13207
	TBX2	ENST00000419047.5	TSL:1	n.173C>A		non_coding_transcript_exon	Exon 1 of 7	ENSP00000404781.1	F8WCM9
	TBX2	ENST00000964762.1		c.173C>A	p.Ala58Glu	missense	Exon 1 of 8	ENSP00000634821.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000116 AC: 1 AN: 861068 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 401374

African (AFR) AF: 0.00 AC: 0 AN: 16282

American (AMR) AF: 0.00 AC: 0 AN: 1756

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5712

East Asian (EAS) AF: 0.00 AC: 0 AN: 4776

South Asian (SAS) AF: 0.00 AC: 0 AN: 17594

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2726

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1784

European-Non Finnish (NFE) AF: 0.00000128 AC: 1 AN: 781686

Other (OTH) AF: 0.00 AC: 0 AN: 28752

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

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	Uncertain	0.37
BayesDel_addAF	Uncertain	0.051	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	T
Eigen	Benign	0.18
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.69	T
M_CAP	Pathogenic	0.94	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Uncertain	0.18	D
MutationAssessor	Benign	1.6	L
PhyloP100		1.1
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-1.0	N
REVEL	Uncertain	0.36
Sift	Benign	0.13	T
Sift4G	Benign	0.37	T
Polyphen		0.99	D
Vest4		0.34
MutPred		0.25		Gain of helix (P = 0.2059)
MVP		0.61
ClinPred		0.94	D
GERP RS		3.6
Varity_R		0.21
gMVP		0.67
Mutation Taster		=59/41	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: rs2060259013; hg19: chr17-59477710;