NM_005994.4:c.21G>C

Variant names:

• chr17-61400197-G-C
• rs1219858842
• NM_005994.4:c.21G>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_005994.4(TBX2):​c.21G>C​(p.Ala7Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TBX2 NM_005994.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.377
• 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 17-61400197-G-C is Benign according to our data. Variant chr17-61400197-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2647997.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.377 with no splicing effect.

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.21G>C	p.Ala7Ala	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.21G>C	p.Ala7Ala	synonymous	Exon 1 of 7	ENSP00000240328.3	Q13207
	TBX2	ENST00000419047.5	TSL:1	n.21G>C		non_coding_transcript_exon	Exon 1 of 7	ENSP00000404781.1	F8WCM9
	TBX2	ENST00000964762.1		c.21G>C	p.Ala7Ala	synonymous	Exon 1 of 8	ENSP00000634821.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1013106 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 496074

African (AFR) AF: 0.00 AC: 0 AN: 19572

American (AMR) AF: 0.00 AC: 0 AN: 17774

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11604

East Asian (EAS) AF: 0.00 AC: 0 AN: 9150

South Asian (SAS) AF: 0.00 AC: 0 AN: 49806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9356

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2942

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 858662

Other (OTH) AF: 0.00 AC: 0 AN: 34240

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	13
DANN	Benign	0.85
PhyloP100		0.38
PromoterAI		-0.0016	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=99/1	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: rs1219858842; hg19: chr17-59477558;