rs639225

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000459.5(TEK):c.1962A>G(p.Ser654=) 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:7

Conservation

PhyloP100: -3.62

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 366434.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-27202872-A-G is described in Lovd as [Benign].

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/exons	MANE	UniProt
TEK	NM_000459.5 linkuse as main transcript	c.1962A>G	p.Ser654=	synonymous_variant	13/23	ENST00000380036.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEK	ENST00000380036.10 linkuse as main transcript	c.1962A>G	p.Ser654=	synonymous_variant	13/23	1	NM_000459.5	P1	Q02763-1

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

GnomAD3 exomes

AF:

0.471

AC:

118122

AN:

251000

Hom.:

28732

AF XY:

0.466

AC XY:

63156

AN XY:

135644

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 SAS exome

AF:

0.382

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

Gnomad4 AFR exome

AF:

0.359

Gnomad4 AMR exome

AF:

0.523

Gnomad4 ASJ exome

AF:

0.391

Gnomad4 EAS exome

AF:

0.384

Gnomad4 SAS exome

AF:

0.380

Gnomad4 FIN exome

AF:

0.622

Gnomad4 NFE exome

AF:

0.486

Gnomad4 OTH exome

AF:

0.465

GnomAD4 genome

AF:

0.456

AC:

69357

AN:

152060

Hom.:

16319

Cov.:

AF XY:

0.462

AC XY:

34350

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.366

Gnomad4 AMR

AF:

0.486

Gnomad4 ASJ

AF:

0.372

Gnomad4 EAS

AF:

0.402

Gnomad4 SAS

AF:

0.379

Gnomad4 FIN

AF:

0.642

Gnomad4 NFE

AF:

0.490

Gnomad4 OTH

AF:

0.429

Alfa

AF:

0.466

Hom.:

22347

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:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Multiple cutaneous and mucosal venous malformations

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

Clinical Genetics, Academic Medical Center

- -

Glaucoma 3, primary congenital, E

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.36

DANN

Benign

0.58

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over