NM_000020.2(ACVRL1):c.1336C>T (p.Gln446Ter) AND Telangiectasia, hereditary hemorrhagic, type 2

Clinical significance:Pathogenic (Last evaluated: Jul 24, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000531463.1

Allele description [Variation Report for NM_000020.2(ACVRL1):c.1336C>T (p.Gln446Ter)]

NM_000020.2(ACVRL1):c.1336C>T (p.Gln446Ter)

Gene:
ACVRL1:activin A receptor like type 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12q13.13
Genomic location:
Preferred name:
NM_000020.2(ACVRL1):c.1336C>T (p.Gln446Ter)
HGVS:
  • NC_000012.12:g.51919074C>T
  • NG_009549.1:g.16657C>T
  • NM_000020.2:c.1336C>T
  • NM_001077401.2:c.1336C>T
  • NP_000011.2:p.Gln446Ter
  • NP_001070869.1:p.Gln446Ter
  • LRG_543t1:c.1336C>T
  • LRG_543:g.16657C>T
  • LRG_543p1:p.Gln446Ter
  • NC_000012.11:g.52312858C>T
Protein change:
Q446*
Links:
dbSNP: rs1064794217
NCBI 1000 Genomes Browser:
rs1064794217
Molecular consequence:
  • NM_000020.2:c.1336C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001077401.2:c.1336C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Telangiectasia, hereditary hemorrhagic, type 2 (HHT2)
Synonyms:
Telangiectasia, hereditary hemorrhagic, type II; Osler Weber Rendu syndrome type 2
Identifiers:
MONDO: MONDO:0010880; MedGen: C1838163; Orphanet: 774; OMIM: 600376

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000639392Invitaecriteria provided, single submitter
Pathogenic
(Jul 24, 2017)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000639392.1

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

Description

This sequence change results in a premature translational stop signal in the ACVRL1 gene (p.Gln446*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 58 amino acids of the ACVRL1 protein. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with hemorrhagic telangiectasia (PMID: 21158752). ClinVar contains an entry for this variant (Variation ID: 419979). A different truncation downstream of this variant (p.Arg479*) has been determined to be pathogenic (PMID: 15024723, 15065824, 15517393, 15712271, 16429404, 16540754, 18673552, 21158752, 23722869). This suggests that deletion of this region of the ACVRL1 protein is causative of disease. 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

Support Center