NM_000459.5(TEK):c.3200+1G>A AND Glaucoma 3, primary congenital, E

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 23, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV004555155.1

Allele description [Variation Report for NM_000459.5(TEK):c.3200+1G>A]

NM_000459.5(TEK):c.3200+1G>A

Gene:

TEK:TEK receptor tyrosine kinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9p21.2

Genomic location:

Preferred name:

NM_000459.5(TEK):c.3200+1G>A

HGVS:

NC_000009.12:g.27220146G>A
NG_011828.1:g.115998G>A
NG_011828.2:g.116007G>A
NM_000459.5:c.3200+1G>AMANE SELECT
NM_001290077.2:c.3071+1G>A
NM_001290078.2:c.2756+1G>A
NM_001375475.1:c.3197+1G>A
NM_001375476.1:c.3068+1G>A
NC_000009.11:g.27220144G>A
NM_000459.4:c.3200+1G>A

Links:

dbSNP: rs2489010435

NCBI 1000 Genomes Browser:

rs2489010435

Molecular consequence:

NM_000459.5:c.3200+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001290077.2:c.3071+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001290078.2:c.2756+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001375475.1:c.3197+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001375476.1:c.3068+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Observations:

Condition(s)

Name:: Glaucoma 3, primary congenital, E (GLC3E)
Identifiers:: MONDO: MONDO:0014998; MedGen: C4310639; OMIM: 617272

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005044068	New York Genome Center - PrenatalSEQ	criteria provided, single submitter (NYGC Assertion Criteria 2020)	Likely pathogenic (Feb 23, 2023)	de novo	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005044068

New York Genome Center - PrenatalSEQ

criteria provided, single submitter

(NYGC Assertion Criteria 2020)

Likely pathogenic
(Feb 23, 2023)

de novo

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	de novo	unknown	1	not provided	not provided	1	not provided	clinical testing

Details of each submission

From New York Genome Center - PrenatalSEQ, SCV005044068.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

Description

The c.3200+1G>A variant in TEK has not previously been reported in the literature or public variant repositories (ClinVar and LOVD), and is absent from population databases (gnomAD v2.1.1 and v3.1.2, TOPMed Freeze 8), suggesting it is not a common benign variant in the populations represented in those databases.The c.3200+1G>A variant in TEK is located in the canonical splice donor site of exon 21 of this 23-exon gene, and is predicted to result in loss of native splice donor site and introduce a cryptic splice donor site 3 bp upstream of the variant (splice AI= 0.94 (DL); 0.37 (DG)), which might result in disruption of open reading frame and incorporation of premature stop codon that is 100 bp upstream of the penultimate exon-intron junction, hence lead to loss-of-function via nonsense mediated decay; however, there are no functional studies to support or refute these predictions. Another downstream canonical splice site variant (c.3300+2delT) was reported in an individual with congenital onset bilateral glaucoma (PMID: 27270174] and downstream loss-of function variants identified in individuals with early onset glaucoma have been deposited in ClinVar [ClinVar IDs= 1687360, 1333465]. Based on available evidence this de novo c.3200+1G>A variant identified in TEK is classified as Likely Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	de novo	unknown	1	not provided	not provided		1	not provided	not provided	not provided

Last Updated: May 16, 2025

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