NM_000020.3(ACVRL1):c.145dup (p.Ala49fs) AND Telangiectasia, hereditary hemorrhagic, type 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 11, 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:: RCV000459586.8

Allele description [Variation Report for NM_000020.3(ACVRL1):c.145dup (p.Ala49fs)]

NM_000020.3(ACVRL1):c.145dup (p.Ala49fs)

Gene:

ACVRL1:activin A receptor like type 1 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

12q13.13

Genomic location:

Preferred name:

NM_000020.3(ACVRL1):c.145dup (p.Ala49fs)

HGVS:

NC_000012.12:g.51913182dup
NG_009549.1:g.10765dup
NM_000020.3:c.145dupMANE SELECT
NM_001077401.2:c.145dup
NP_000011.2:p.Ala49fs
NP_000011.2:p.Ala49fs
NP_001070869.1:p.Ala49fs
LRG_543t1:c.145dup
LRG_543:g.10765dup
LRG_543p1:p.Ala49fs
NC_000012.11:g.52306960_52306961insG
NC_000012.11:g.52306966dup
NM_000020.2:c.145dup
NM_000020.2:c.145dupG
NM_001077401.1:c.145dupG
p.A49Gfs*120

Protein change:

A49fs

Links:

dbSNP: rs863223415

NCBI 1000 Genomes Browser:

rs863223415

Molecular consequence:

NM_000020.3:c.145dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001077401.2:c.145dup - 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

Recent activity

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Homo sapiens FERM domain containing 8 (FRMD8), transcript variant 1, mRNA
Homo sapiens FERM domain containing 8 (FRMD8), transcript variant 1, mRNA
gi|1519315772|ref|NM_031904.5|

Nucleotide
Homo sapiens Jrk helix-turn-helix protein (JRK), transcript variant 1, mRNA
Homo sapiens Jrk helix-turn-helix protein (JRK), transcript variant 1, mRNA
gi|1705442040|ref|NM_003724.4|

Nucleotide
glycoside hydrolase family 2 protein [Blautia pseudococcoides]
glycoside hydrolase family 2 protein [Blautia pseudococcoides]
gi|1957933713|gnl|PRJNA680355|I5Q86 5|gb|QQQ93614.1|

Protein
transcription factor, Fur family [synthetic bacterium JCVI-Syn3.0]
transcription factor, Fur family [synthetic bacterium JCVI-Syn3.0]
gi|1015828636|gb|AMW76581.1||gnl|PR 2950|JCVISYN3_0620

Protein
FS400464 normalized full-length tobacco cDNA library Nicotiana tabacum cDNA clon...
FS400464 normalized full-length tobacco cDNA library Nicotiana tabacum cDNA clone TBK01A01NGRL0077_4_C06 5', mRNA sequence
gi|254604633|gnl|dbEST|66633142|dbj 0464.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000552418	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 11, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 15879500, 10694922, 12114496, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000552418

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 11, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

Novel missense and frameshift mutations in the activin receptor-like kinase-1 gene in hereditary hemorrhagic telangiectasia. Mutations in brief no. 164. Online.

Klaus DJ, Gallione CJ, Anthony K, Yeh EY, Yu J, Lux A, Johnson DW, Marchuk DA.

Hum Mutat. 1998;12(2):137.

PubMed [citation]

PMID:: 10694922

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000552418.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Ala49Glyfs*120) in the ACVRL1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ACVRL1 are known to be pathogenic (PMID: 15879500). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with hereditary hemorrhagic telangiectasia (HHT) (PMID: 10694922, 12114496). ClinVar contains an entry for this variant (Variation ID: 212805). For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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