NM_001114753.3(ENG):c.991+2T>G AND Hereditary hemorrhagic telangiectasia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 14, 2021
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:: RCV000820521.9

Allele description [Variation Report for NM_001114753.3(ENG):c.991+2T>G]

NM_001114753.3(ENG):c.991+2T>G

Gene:

ENG:endoglin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q34.11

Genomic location:

Preferred name:

NM_001114753.3(ENG):c.991+2T>G

HGVS:

NC_000009.12:g.127824798A>C
NG_009551.1:g.34971T>G
NM_000118.4:c.991+2T>G
NM_001114753.3:c.991+2T>GMANE SELECT
NM_001278138.2:c.445+2T>G
NM_001406715.1:c.991+2T>G
LRG_589t1:c.991+2T>G
LRG_589:g.34971T>G
NC_000009.11:g.130587077A>C
NM_000118.3:c.991+2T>G

Links:

dbSNP: rs1564455554

NCBI 1000 Genomes Browser:

rs1564455554

Molecular consequence:

NM_000118.4:c.991+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001114753.3:c.991+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001278138.2:c.445+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406715.1:c.991+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Hereditary hemorrhagic telangiectasia (HHT)
Synonyms:: Osler Weber Rendu syndrome; ORW disease; Osler-Rendu-Weber disease; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0019180; MedGen: C0039445; OMIM: PS187300

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000961237	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 14, 2021)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 16199547, 15879500, 20656886, 22385575, 16752392, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000961237

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 14, 2021)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

Hereditary haemorrhagic telangiectasia: current views on genetics and mechanisms of disease.

Abdalla SA, Letarte M.

J Med Genet. 2006 Feb;43(2):97-110. Epub 2005 May 6. Review.

PubMed [citation]

PMID:: 15879500
PMCID:: PMC2603035

See all PubMed Citations (6)

Details of each submission

From Invitae, SCV000961237.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

For these reasons, this variant has been classified as Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ENG are known to be pathogenic (PMID: 15879500, 20656886, 22385575). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has been observed in individuals affected with¬†hereditary hemorrhagic telangiectasia¬†(PMID: 16752392, Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 7 of the ENG gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.

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

Last Updated: Feb 20, 2024

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