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NM_000020.3(ACVRL1):c.1347del (p.Thr450fs) AND Telangiectasia, hereditary hemorrhagic, type 2

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 18, 2021
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:
RCV001874813.4

Allele description [Variation Report for NM_000020.3(ACVRL1):c.1347del (p.Thr450fs)]

NM_000020.3(ACVRL1):c.1347del (p.Thr450fs)

Gene:
ACVRL1:activin A receptor like type 1 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
12q13.13
Genomic location:
Preferred name:
NM_000020.3(ACVRL1):c.1347del (p.Thr450fs)
HGVS:
  • NC_000012.12:g.51919085del
  • NG_009549.1:g.16668del
  • NM_000020.3:c.1347delMANE SELECT
  • NM_001077401.2:c.1347del
  • NP_000011.2:p.Thr450fs
  • NP_001070869.1:p.Thr450fs
  • LRG_543t1:c.1347del
  • LRG_543:g.16668del
  • NC_000012.11:g.52312865del
  • NC_000012.11:g.52312869del
  • NM_000020.2:c.1347delC
Protein change:
T450fs
Links:
dbSNP: rs1940908396
NCBI 1000 Genomes Browser:
rs1940908396
Molecular consequence:
  • NM_000020.3:c.1347del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001077401.2:c.1347del - frameshift variant - [Sequence Ontology: SO:0001589]

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002144432Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Sep 18, 2021) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Clinical and molecular genetic features of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia.

Trembath RC, Thomson JR, Machado RD, Morgan NV, Atkinson C, Winship I, Simonneau G, Galie N, Loyd JE, Humbert M, Nichols WC, Morrell NW, Berg J, Manes A, McGaughran J, Pauciulo M, Wheeler L.

N Engl J Med. 2001 Aug 2;345(5):325-34.

PubMed [citation]
PMID:
11484689

DHPLC-based mutation analysis of ENG and ALK-1 genes in HHT Italian population.

Lenato GM, Lastella P, Di Giacomo MC, Resta N, Suppressa P, Pasculli G, Sabbà C, Guanti G.

Hum Mutat. 2006 Feb;27(2):213-4.

PubMed [citation]
PMID:
16429404
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002144432.3

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the ACVRL1 protein in which other variant(s) (p.Gln490*) have been determined to be pathogenic (PMID: 11484689, 16429404, 24603890). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with ACVRL1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Thr450Profs*15) in the ACVRL1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 54 amino acid(s) of the ACVRL1 protein.

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

Last Updated: Sep 29, 2024