rs2273720

Variant names:

• chr9-27209471-A-C
• rs2273720
• NM_000459.5:c.2686+240A>C

Your query was ambiguous. Multiple possible variants found:

• chr9-27209471-A-C
• chr9-27209471-A-G
• chr9-27209471-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000459.5(TEK):​c.2686+240A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0358 in 152,202 control chromosomes in the GnomAD database, including 129 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.036 (129 hom., cov: 32)
• Consequence: TEK NM_000459.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00900
• Publications: 11 publications found

Genes affected

TEK (HGNC:11724): (TEK receptor tyrosine kinase) This gene encodes a receptor that belongs to the protein tyrosine kinase Tie2 family. The encoded protein possesses a unique extracellular region that contains two immunoglobulin-like domains, three epidermal growth factor (EGF)-like domains and three fibronectin type III repeats. The ligand angiopoietin-1 binds to this receptor and mediates a signaling pathway that functions in embryonic vascular development. Mutations in this gene are associated with inherited venous malformations of the skin and mucous membranes. Alternative splicing results in multiple transcript variants. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Feb 2014]

TEK Gene-Disease associations (from GenCC):

• multiple cutaneous and mucosal venous malformations

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
• primary congenital glaucoma

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• TEK-related primary glaucoma

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• glaucoma 3, primary congenital, E

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
• congenital glaucoma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0564 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000459.5. 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
	TEK	NM_000459.5	MANE Select	c.2686+240A>C		intron	N/A	NP_000450.3	Q02763-1
	TEK	NM_001375475.1		c.2683+240A>C		intron	N/A	NP_001362404.1
	TEK	NM_001290077.2		c.2557+240A>C		intron	N/A	NP_001277006.2	Q02763-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEK	ENST00000380036.10	TSL:1 MANE Select	c.2686+240A>C		intron	N/A	ENSP00000369375.4	Q02763-1
	TEK	ENST00000923267.1		c.2725+240A>C		intron	N/A	ENSP00000593326.1
	TEK	ENST00000856712.1		c.2683+240A>C		intron	N/A	ENSP00000526771.1

Frequencies

GnomAD3 genomes AF: 0.0359 AC: 5456 AN: 152084 Hom.: 129 Cov.: 32

Gnomad AFR AF: 0.00932

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.0387

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.0505

Gnomad SAS AF: 0.0628

Gnomad FIN AF: 0.0139

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0476

Gnomad OTH AF: 0.0421

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0358 AC: 5454 AN: 152202 Hom.: 129 Cov.: 32 AF XY: 0.0352 AC XY: 2622 AN XY: 74406

African (AFR) AF: 0.00930 AC: 386 AN: 41526

American (AMR) AF: 0.0386 AC: 590 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 351 AN: 3470

East Asian (EAS) AF: 0.0506 AC: 262 AN: 5176

South Asian (SAS) AF: 0.0622 AC: 300 AN: 4820

European-Finnish (FIN) AF: 0.0139 AC: 147 AN: 10608

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0476 AC: 3238 AN: 68006

Other (OTH) AF: 0.0417 AC: 88 AN: 2112

Alfa AF: 0.0459 Hom.: 307

Bravo AF: 0.0362

Asia WGS AF: 0.0380 AC: 132 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.0
DANN	Benign	0.45
PhyloP100		0.0090
Mutation Taster		=100/0	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: rs2273720; hg19: chr9-27209469;