NM_000118.3(ENG):c.736del (p.Asp246fs) AND not provided

Clinical significance:Pathogenic (Last evaluated: Sep 18, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000522835.1

Allele description [Variation Report for NM_000118.3(ENG):c.736del (p.Asp246fs)]

NM_000118.3(ENG):c.736del (p.Asp246fs)

Gene:
ENG:endoglin [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
9q34.11
Genomic location:
Preferred name:
NM_000118.3(ENG):c.736del (p.Asp246fs)
HGVS:
  • NC_000009.12:g.127825314del
  • NG_009551.1:g.34458del
  • NM_000118.3:c.736del
  • NM_001114753.2:c.736del
  • NM_001278138.1:c.190del
  • NP_000109.1:p.Asp246fs
  • NP_001108225.1:p.Asp246fs
  • NP_001265067.1:p.Asp64fs
  • LRG_589t1:c.736del
  • LRG_589t2:c.736del
  • LRG_589:g.34458del
  • LRG_589p1:p.Asp246fs
  • LRG_589p2:p.Asp246fs
  • NC_000009.11:g.130587593del
  • NM_000118.2:c.736delG
  • NM_000118.3:c.736delG
Protein change:
D246fs
Links:
dbSNP: rs1554810249
NCBI 1000 Genomes Browser:
rs1554810249
Molecular consequence:
  • NM_000118.3:c.736del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001114753.2:c.736del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001278138.1:c.190del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000617304GeneDxcriteria provided, single submitter
Pathogenic
(Sep 18, 2017)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000617304.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The c.736delG pathogenic variant in the ENG gene has previously been reported in a patient with epistaxis, telangiectases, and a pulmonary arteriovenous malformation (Cymerman et al., 2003). This variant has also been reported in another unrelated patient who met Curacao criteria for a diagnosis of HHT (reported as c.733delG due to use of alternative nomenclature) (Letteboer et al., 2005). The 736delG variant causes a shift in reading frame starting at codon aspartic acid 246, changing it to an isoleucine, and creating a premature stop codon at position 113 of the new reading frame, denoted p.Asp246IlefsX113. This pathogenic variant is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. Other downstream frameshift variants in the ENG gene have been reported in Human Gene Mutation Database in association with HHT (Stenson et al., 2014), indicating that loss of function is a mechanism of disease for this gene. Furthermore, the c.736delG variant has not been observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server).

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

Last Updated: Apr 12, 2021

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