NM_000020.3(ACVRL1):c.877del (p.Thr293fs) AND Telangiectasia, hereditary hemorrhagic, type 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 20, 2022
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:: RCV002735848.3

Allele description [Variation Report for NM_000020.3(ACVRL1):c.877del (p.Thr293fs)]

NM_000020.3(ACVRL1):c.877del (p.Thr293fs)

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.877del (p.Thr293fs)

HGVS:

NC_000012.12:g.51915329del
NG_009549.1:g.12912del
NG_125718.1:g.628del
NM_000020.3:c.877delMANE SELECT
NM_001077401.2:c.877del
NM_001406487.1:c.877delA
NM_001406488.1:c.877delA
NM_001406489.1:c.877delA
NM_001406490.1:c.565delA
NM_001406491.1:c.565delA
NM_001406492.1:c.565delA
NM_001406493.1:c.565delA
NM_001406494.1:c.565delA
NM_001406495.1:c.313delA
NP_000011.2:p.Thr293Argfs
NP_000011.2:p.Thr293fs
NP_001070869.1:p.Thr293fs
NP_001393416.1:p.Thr293Argfs
NP_001393417.1:p.Thr293Argfs
NP_001393418.1:p.Thr293Argfs
NP_001393419.1:p.Thr189Argfs
NP_001393420.1:p.Thr189Argfs
NP_001393421.1:p.Thr189Argfs
NP_001393422.1:p.Thr189Argfs
NP_001393423.1:p.Thr189Argfs
NP_001393424.1:p.Thr105Argfs
LRG_543t1:c.877del
LRG_543:g.12912del
LRG_543p1:p.Thr293Argfs
NC_000012.11:g.52309113del
NM_000020.2:c.877delA

Protein change:

T293fs

Molecular consequence:

NM_000020.3:c.877del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001077401.2:c.877del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406487.1:c.877delA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406488.1:c.877delA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406489.1:c.877delA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406490.1:c.565delA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406491.1:c.565delA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406492.1:c.565delA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406493.1:c.565delA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406494.1:c.565delA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406495.1:c.313delA - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003013558	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 20, 2022)	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

SCV003013558

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 20, 2022)

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, SCV003013558.2

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with ACVRL1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Thr293Argfs*8) 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).

#	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

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