9-27109166-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_001290077.1(TEK):c.-425A>G variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.00179 in 464,372 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (3 hom.)
• Consequence: TEK NM_001290077.1 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.07

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 9-27109166-A-G is Benign according to our data. Variant chr9-27109166-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 366385.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00313 (477/152284) while in subpopulation AFR AF= 0.00857 (356/41548). AF 95% confidence interval is 0.00783. There are 1 homozygotes in gnomad4. There are 236 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 476 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEK	NM_001290077.1	c.-425A>G		5_prime_UTR_variant	1/22
TEK	NM_001290078.1	c.-425A>G		5_prime_UTR_variant	1/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEK	ENST00000519097.5	c.-425A>G		5_prime_UTR_variant	1/21	2
TEK	ENST00000615002.4	c.-425A>G		5_prime_UTR_variant	1/23	5

Frequencies

GnomAD3 genomes AF: 0.00313 AC: 476 AN: 152166 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00857

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00379

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000588

Gnomad OTH AF: 0.00478

GnomAD4 exome AF: 0.00114 AC: 356 AN: 312088 Hom.: 3 Cov.: 0 AF XY: 0.00106 AC XY: 169 AN XY: 159022

Gnomad4 AFR exome AF: 0.00810

Gnomad4 AMR exome AF: 0.00333

Gnomad4 ASJ exome AF: 0.00140

Gnomad4 EAS exome AF: 0.0000387

Gnomad4 SAS exome AF: 0.0000869

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000773

Gnomad4 OTH exome AF: 0.00346

GnomAD4 genome AF: 0.00313 AC: 477 AN: 152284 Hom.: 1 Cov.: 32 AF XY: 0.00317 AC XY: 236 AN XY: 74456

Gnomad4 AFR AF: 0.00857

Gnomad4 AMR AF: 0.00379

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000588

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00287 Hom.: 1

Bravo AF: 0.00346

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Multiple cutaneous and mucosal venous malformations Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
Cadd	Benign	20
Dann	Benign	0.90

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

Publications

LitVar

Other links and lift over

dbSNP: rs149944814; hg19: chr9-27109164;