chr9-27202872-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000459.5(TEK):c.1962A>G(p.Ser654Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 1,613,684 control chromosomes in the GnomAD database, including 185,217 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16319 hom., cov: 32)

Exomes 𝑓: 0.48 ( 168898 hom. )

Consequence

TEK
NM_000459.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -3.62

Publications

36 publications found

Variant links:

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

TEK links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 9-27202872-A-G is Benign according to our data. Variant chr9-27202872-A-G is described in ClinVar as Benign. ClinVar VariationId is 366434.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.62 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEK	NM_000459.5 link	c.1962A>G	p.Ser654Ser	synonymous_variant	Exon 13 of 23	ENST00000380036.10	NP_000450.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEK	ENST00000380036.10 link	c.1962A>G	p.Ser654Ser	synonymous_variant	Exon 13 of 23	1	NM_000459.5	ENSP00000369375.4

Frequencies

GnomAD3 genomes

AF:

0.456

AC:

69340

AN:

151942

Hom.:

16313

Cov.:

show subpopulations

Gnomad AFR

AF:

0.366

Gnomad AMI

AF:

0.501

Gnomad AMR

AF:

0.486

Gnomad ASJ

AF:

0.372

Gnomad EAS

AF:

0.402

Gnomad SAS

AF:

0.378

Gnomad FIN

AF:

0.642

Gnomad MID

AF:

0.399

Gnomad NFE

AF:

0.490

Gnomad OTH

AF:

0.432

GnomAD2 exomes

AF:

0.471

AC:

118122

AN:

251000

AF XY:

0.466

show subpopulations

Gnomad AFR exome

AF:

0.361

Gnomad AMR exome

AF:

0.532

Gnomad ASJ exome

AF:

0.386

Gnomad EAS exome

AF:

0.393

Gnomad FIN exome

AF:

0.627

Gnomad NFE exome

AF:

0.482

Gnomad OTH exome

AF:

0.469

GnomAD4 exome

AF:

0.477

AC:

697869

AN:

1461624

Hom.:

168898

Cov.:

AF XY:

0.475

AC XY:

345034

AN XY:

727118

show subpopulations

African (AFR)

AF:

0.359

AC:

12025

AN:

33470

American (AMR)

AF:

0.523

AC:

23379

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.391

AC:

10204

AN:

26130

East Asian (EAS)

AF:

0.384

AC:

15253

AN:

39694

South Asian (SAS)

AF:

0.380

AC:

32761

AN:

86254

European-Finnish (FIN)

AF:

0.622

AC:

33241

AN:

53412

Middle Eastern (MID)

AF:

0.391

AC:

2253

AN:

5768

European-Non Finnish (NFE)

AF:

0.486

AC:

540671

AN:

1111790

Other (OTH)

AF:

0.465

AC:

28082

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

21620

43241

64861

86482

108102

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15806

31612

47418

63224

79030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.456

AC:

69357

AN:

152060

Hom.:

16319

Cov.:

AF XY:

0.462

AC XY:

34350

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.366

AC:

15169

AN:

41456

American (AMR)

AF:

0.486

AC:

7426

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.372

AC:

1290

AN:

3468

East Asian (EAS)

AF:

0.402

AC:

2082

AN:

5176

South Asian (SAS)

AF:

0.379

AC:

1824

AN:

4816

European-Finnish (FIN)

AF:

0.642

AC:

6796

AN:

10580

Middle Eastern (MID)

AF:

0.381

AC:

112

AN:

294

European-Non Finnish (NFE)

AF:

0.490

AC:

33299

AN:

67976

Other (OTH)

AF:

0.429

AC:

903

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1909

3819

5728

7638

9547

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

634

1268

1902

2536

3170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.463

Hom.:

30018

Bravo

AF:

0.442

Asia WGS

AF:

0.425

AC:

1480

AN:

3478

EpiCase

AF:

0.464

EpiControl

AF:

0.462

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Multiple cutaneous and mucosal venous malformations

Benign:3

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Sep 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Glaucoma 3, primary congenital, E

Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.36

(source)

DANN

Benign

0.58

PhyloP100

-3.6

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over