NM_000118.3(ENG):c.992-2A>G AND Hereditary hemorrhagic telangiectasia

Clinical significance:Pathogenic (Last evaluated: Aug 28, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000821165.1

Allele description [Variation Report for NM_000118.3(ENG):c.992-2A>G]

NM_000118.3(ENG):c.992-2A>G

Gene:
ENG:endoglin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
9q34.11
Genomic location:
Preferred name:
NM_000118.3(ENG):c.992-2A>G
HGVS:
  • NC_000009.12:g.127824448T>C
  • NG_009551.1:g.35321A>G
  • NM_000118.3:c.992-2A>G
  • NM_001114753.2:c.992-2A>G
  • NM_001278138.1:c.446-2A>G
  • LRG_589t1:c.992-2A>G
  • LRG_589t2:c.992-2A>G
  • LRG_589:g.35321A>G
  • NC_000009.11:g.130586727T>C
Links:
dbSNP: rs1588580932
NCBI 1000 Genomes Browser:
rs1588580932
Molecular consequence:
  • NM_000118.3:c.992-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001114753.2:c.992-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001278138.1:c.446-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

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
SCV000961912Invitaecriteria provided, single submitter
Pathogenic
(Aug 28, 2018)
germlineclinical testing

PubMed (4)
[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

The physiological role of endoglin in the cardiovascular system.

López-Novoa JM, Bernabeu C.

Am J Physiol Heart Circ Physiol. 2010 Oct;299(4):H959-74. doi: 10.1152/ajpheart.01251.2009. Epub 2010 Jul 23. Review.

PubMed [citation]
PMID:
20656886

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 (4)

Details of each submission

From Invitae, SCV000961912.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change affects an acceptor 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. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with hereditary hemorrhagic telangiectasia (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. Different variants affecting this acceptor dinucleotide (c.992-1G>C and c.992-1G>A) have been observed in affected individuals (PMID: 19270816, 16705692). This suggests that this dinucleotide is important for normal RNA splicing, and that other variants at these positions may also be clinically significant. 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: Oct 7, 2021

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