NM_000020.3(ACVRL1):c.651del (p.Trp217fs) AND Telangiectasia, hereditary hemorrhagic, type 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 4, 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:: RCV002867209.3

Allele description [Variation Report for NM_000020.3(ACVRL1):c.651del (p.Trp217fs)]

NM_000020.3(ACVRL1):c.651del (p.Trp217fs)

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.651del (p.Trp217fs)

HGVS:

NC_000012.12:g.51914464del
NG_009549.1:g.12047del
NM_000020.3:c.651delMANE SELECT
NM_001077401.2:c.651del
NM_001406487.1:c.651delG
NM_001406488.1:c.651delG
NM_001406489.1:c.651delG
NM_001406490.1:c.339delG
NM_001406491.1:c.339delG
NM_001406492.1:c.339delG
NM_001406493.1:c.339delG
NM_001406494.1:c.339delG
NM_001406495.1:c.87delG
NP_000011.2:p.Trp217Cysfs
NP_000011.2:p.Trp217fs
NP_001070869.1:p.Trp217fs
NP_001393416.1:p.Trp217Cysfs
NP_001393417.1:p.Trp217Cysfs
NP_001393418.1:p.Trp217Cysfs
NP_001393419.1:p.Trp113Cysfs
NP_001393420.1:p.Trp113Cysfs
NP_001393421.1:p.Trp113Cysfs
NP_001393422.1:p.Trp113Cysfs
NP_001393423.1:p.Trp113Cysfs
NP_001393424.1:p.Trp29Cysfs
LRG_543t1:c.651del
LRG_543:g.12047del
LRG_543p1:p.Trp217Cysfs
NC_000012.11:g.52308247del
NC_000012.11:g.52308248del
NM_000020.2:c.651delG

Protein change:

W217fs

Molecular consequence:

NM_000020.3:c.651del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001077401.2:c.651del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406487.1:c.651delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406488.1:c.651delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406489.1:c.651delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406490.1:c.339delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406491.1:c.339delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406492.1:c.339delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406493.1:c.339delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406494.1:c.339delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406495.1:c.87delG - 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
SCV003238349	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 4, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 15879500, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003238349

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 4, 2023)

germline

clinical testing

PubMed (2)
[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

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003238349.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Trp217Cysfs*41) 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 variant has not been reported in the literature in individuals affected with ACVRL1-related conditions. ClinVar contains an entry for this variant (Variation ID: 2031436). 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: Sep 29, 2024

ClinVar

Relating variation to medicine