9-27109315-T-TG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000459.5(TEK):c.-275dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 571,032 control chromosomes in the GnomAD database, including 10,134 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1794 hom., cov: 31)
  • Exomes 𝑓: 0.11 (8340 hom.)
• Consequence: TEK NM_000459.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.81

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 9-27109315-T-TG is Benign according to our data. Variant chr9-27109315-T-TG is described in ClinVar as [Benign]. Clinvar id is 366388.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEK	NM_000459.5	c.-275dup		5_prime_UTR_variant	1/23	ENST00000380036.10
TEK	NM_001290077.1	c.-275dup		5_prime_UTR_variant	1/22
TEK	NM_001290078.1	c.-275dup		5_prime_UTR_variant	1/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEK	ENST00000380036.10	c.-275dup		5_prime_UTR_variant	1/23	1	NM_000459.5	P1
TEK	ENST00000519097.5	c.-275dup		5_prime_UTR_variant	1/21	2
TEK	ENST00000615002.4	c.-275dup		5_prime_UTR_variant	1/23	5

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15960 AN: 152060 Hom.: 1782 Cov.: 31

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.0214

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0449

Gnomad OTH AF: 0.0880

GnomAD4 exome AF: 0.113 AC: 47298 AN: 418854 Hom.: 8340 Cov.: 0 AF XY: 0.114 AC XY: 24887 AN XY: 218788

Gnomad4 AFR exome AF: 0.122

Gnomad4 AMR exome AF: 0.192

Gnomad4 ASJ exome AF: 0.0196

Gnomad4 EAS exome AF: 0.668

Gnomad4 SAS exome AF: 0.157

Gnomad4 FIN exome AF: 0.0969

Gnomad4 NFE exome AF: 0.0454

Gnomad4 OTH exome AF: 0.0984

GnomAD4 genome AF: 0.105 AC: 15997 AN: 152178 Hom.: 1794 Cov.: 31 AF XY: 0.113 AC XY: 8433 AN XY: 74396

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.0214

Gnomad4 EAS AF: 0.615

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.0449

Gnomad4 OTH AF: 0.0946

Alfa AF: 0.0686 Hom.: 84

Bravo AF: 0.113

Asia WGS AF: 0.358 AC: 1241 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Multiple cutaneous and mucosal venous malformations Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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

Other links and lift over

dbSNP: rs3837240; hg19: chr9-27109313;