NM_000020.3(ACVRL1):c.1008_1009del (p.Leu337fs) AND Telangiectasia, hereditary hemorrhagic, type 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 18, 2024
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:: RCV003510752.1

Allele description [Variation Report for NM_000020.3(ACVRL1):c.1008_1009del (p.Leu337fs)]

NM_000020.3(ACVRL1):c.1008_1009del (p.Leu337fs)

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.1008_1009del (p.Leu337fs)

HGVS:

NC_000012.12:g.51915460_51915461del
NG_009549.1:g.13043_13044del
NG_125718.1:g.759_760del
NM_000020.3:c.1008_1009delMANE SELECT
NM_001077401.2:c.1008_1009del
NM_001406487.1:c.1008_1009del
NM_001406488.1:c.1008_1009del
NM_001406489.1:c.1008_1009del
NM_001406490.1:c.696_697del
NM_001406491.1:c.696_697del
NM_001406492.1:c.696_697del
NM_001406493.1:c.696_697del
NM_001406494.1:c.696_697del
NM_001406495.1:c.444_445del
NP_000011.2:p.Leu337Glyfs
NP_000011.2:p.Leu337fs
NP_001070869.1:p.Leu337fs
NP_001393416.1:p.Leu337fs
NP_001393417.1:p.Leu337fs
NP_001393418.1:p.Leu337fs
NP_001393419.1:p.Leu233fs
NP_001393420.1:p.Leu233fs
NP_001393421.1:p.Leu233fs
NP_001393422.1:p.Leu233fs
NP_001393423.1:p.Leu233fs
NP_001393424.1:p.Leu149fs
LRG_543t1:c.1008_1009del
LRG_543:g.13043_13044del
LRG_543p1:p.Leu337Glyfs
NC_000012.11:g.52309244_52309245del
NM_000020.2:c.1008_1009delGC

Protein change:

L149fs

Molecular consequence:

NM_000020.3:c.1008_1009del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001077401.2:c.1008_1009del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406487.1:c.1008_1009del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406488.1:c.1008_1009del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406489.1:c.1008_1009del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406490.1:c.696_697del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406491.1:c.696_697del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406492.1:c.696_697del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406493.1:c.696_697del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406494.1:c.696_697del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406495.1:c.444_445del - 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
SCV004261161	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 18, 2024)	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

SCV004261161

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 18, 2024)

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV004261161.1

#	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.Leu337Glyfs*54) 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. 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: Feb 20, 2024

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