NM_001114753.3(ENG):c.689+2T>A AND Hereditary hemorrhagic telangiectasia

Clinical significance:Pathogenic (Last evaluated: Sep 11, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001206775.2

Allele description [Variation Report for NM_001114753.3(ENG):c.689+2T>A]

NM_001114753.3(ENG):c.689+2T>A

Gene:
ENG:endoglin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
9q34.11
Genomic location:
Preferred name:
NM_001114753.3(ENG):c.689+2T>A
HGVS:
  • NC_000009.12:g.127825693A>T
  • NG_009551.1:g.34076T>A
  • NM_000118.3:c.689+2T>A
  • NM_001114753.3:c.689+2T>AMANE SELECT
  • NM_001278138.2:c.143+2T>A
  • LRG_589t1:c.689+2T>A
  • LRG_589:g.34076T>A
  • NC_000009.11:g.130587972A>T
Links:
dbSNP: rs863223535
NCBI 1000 Genomes Browser:
rs863223535
Molecular consequence:
  • NM_000118.3:c.689+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001114753.3:c.689+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001278138.2:c.143+2T>A - 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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001378101Invitaecriteria provided, single submitter
Pathogenic
(Sep 11, 2019)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Molecular screening of ALK1/ACVRL1 and ENG genes in hereditary hemorrhagic telangiectasia in France.

Lesca G, Plauchu H, Coulet F, Lefebvre S, Plessis G, Odent S, Rivière S, Leheup B, Goizet C, Carette MF, Cordier JF, Pinson S, Soubrier F, Calender A, Giraud S; French Rendu-Osler Network..

Hum Mutat. 2004 Apr;23(4):289-99.

PubMed [citation]
PMID:
15024723

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
See all PubMed Citations (6)

Details of each submission

From Invitae, SCV001378101.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This sequence change affects a donor splice site in intron 5 of the ENG gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). Disruption of this splice site has been observed in several individuals affected with hereditary hemorrhagic telangiectasia (PMID: 15024723, Invitae). 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. 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). For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jan 8, 2022

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