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NM_001114753.3(ENG):c.1311+2T>C AND Telangiectasia, hereditary hemorrhagic, type 1

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 21, 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:
RCV004594664.1

Allele description [Variation Report for NM_001114753.3(ENG):c.1311+2T>C]

NM_001114753.3(ENG):c.1311+2T>C

Genes:
ENG:endoglin [Gene - OMIM - HGNC]
LOC102723566:uncharacterized LOC102723566 [Gene]
Variant type:
single nucleotide variant
Cytogenetic location:
9q34.11
Genomic location:
Preferred name:
NM_001114753.3(ENG):c.1311+2T>C
HGVS:
  • NC_000009.12:g.127819620A>G
  • NG_009551.1:g.40149T>C
  • NM_000118.4:c.1311+2T>C
  • NM_001114753.3:c.1311+2T>CMANE SELECT
  • NM_001278138.2:c.765+2T>C
  • LRG_589:g.40149T>C
  • NC_000009.11:g.130581899A>G
  • NM_001114753.2:c.1311+2T>C
Molecular consequence:
  • NM_000118.4:c.1311+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001114753.3:c.1311+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001278138.2:c.765+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Telangiectasia, hereditary hemorrhagic, type 1 (HHT1)
Synonyms:
Osler Weber Rendu syndrome type 1
Identifiers:
MONDO: MONDO:0008535; MedGen: C4551861; Orphanet: 774; OMIM: 187300

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV005086792Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Dec 21, 2023) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Novel mutations in ENG and ACVRL1 identified in a series of 200 individuals undergoing clinical genetic testing for hereditary hemorrhagic telangiectasia (HHT): correlation of genotype with phenotype.

Bossler AD, Richards J, George C, Godmilow L, Ganguly A.

Hum Mutat. 2006 Jul;27(7):667-75.

PubMed [citation]
PMID:
16752392

Investigation of endoglin wild-type and missense mutant protein heterodimerisation using fluorescence microscopy based IF, BiFC and FRET analyses.

Förg T, Hafner M, Lux A.

PLoS One. 2014;9(7):e102998. doi: 10.1371/journal.pone.0102998.

PubMed [citation]
PMID:
25080347
PMCID:
PMC4117486
See all PubMed Citations (5)

Details of each submission

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV005086792.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0103 - Dominant negative and loss of function are known mechanisms of disease in this gene and are associated with type 1 hereditary haemorrhagic telangiectasia (MIM#187300). Pathogenic missense variants have been demonstrated to have dominant negative and loss of function effects while premature termination variants are associated with a loss of function mechanism (PMIDs: 2508034, 25312062). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0211 - Canonical splice site variant without proven consequence on splicing (no functional evidence available). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0505 - Abnormal splicing is predicted by in silico tools and affected nucleotide is highly conserved. (SP) 0600 - Variant is predicted to disrupt the Zona pellucida-like domain (DECIPHER). (I) 0701 - Other canonical splice site variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. c.1311+2T>G, c.1311+2T>A, c.1311+1G>A and c.1311+1G>C have been reported as pathogenic by clinical laboratories (ClinVar). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. It has been reported in multiple individuals with hereditary haemorrhagic telangiectasia (PMIDs: 16752392, 34872578). It has also been reported as pathogenic by a clinical laboratory (ClinVar). (SP) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

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

Last Updated: Feb 25, 2025