NM_000020.3(ACVRL1):c.154_169del (p.Thr52fs) AND Telangiectasia, hereditary hemorrhagic, type 2

Germline classification:: Pathogenic (1 submission)
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:: RCV004720190.1

Allele description [Variation Report for NM_000020.3(ACVRL1):c.154_169del (p.Thr52fs)]

NM_000020.3(ACVRL1):c.154_169del (p.Thr52fs)

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.154_169del (p.Thr52fs)

HGVS:

NC_000012.12:g.51913191_51913206del
NG_009549.1:g.10774_10789del
NM_000020.3:c.154_169delMANE SELECT
NM_001077401.2:c.154_169del
NM_001406487.1:c.154_169del
NM_001406488.1:c.154_169del
NM_001406489.1:c.154_169del
NM_001406490.1:c.154_169del
NM_001406491.1:c.154_169del
NM_001406492.1:c.154_169del
NM_001406493.1:c.154_169del
NM_001406494.1:c.154_169del
NM_001406495.1:c.61+656_61+671del
NP_000011.2:p.Thr52Glyfs
NP_000011.2:p.Thr52fs
NP_001070869.1:p.Thr52fs
NP_001393416.1:p.Thr52fs
NP_001393417.1:p.Thr52fs
NP_001393418.1:p.Thr52fs
NP_001393419.1:p.Thr52fs
NP_001393420.1:p.Thr52fs
NP_001393421.1:p.Thr52fs
NP_001393422.1:p.Thr52fs
NP_001393423.1:p.Thr52fs
LRG_543t1:c.154_169del16
LRG_543:g.10774_10789del
LRG_543p1:p.Thr52Glyfs
NC_000012.11:g.52306975_52306990del
NM_000020.2:c.154_169del16

Protein change:

T52fs

Molecular consequence:

NM_000020.3:c.154_169del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001077401.2:c.154_169del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406487.1:c.154_169del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406488.1:c.154_169del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406489.1:c.154_169del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406490.1:c.154_169del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406491.1:c.154_169del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406492.1:c.154_169del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406493.1:c.154_169del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406494.1:c.154_169del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406495.1:c.61+656_61+671del - intron variant - [Sequence Ontology: SO:0001627]

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
SCV005326318	Seattle Children's Hospital Molecular Genetics Laboratory, Seattle Children's Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005326318

Seattle Children's Hospital Molecular Genetics Laboratory, Seattle Children's Hospital

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Seattle Children's Hospital Molecular Genetics Laboratory, Seattle Children's Hospital, SCV005326318.1

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

Description

The ACVRL1 p.Thr52Glyfs*65 variant substitutes a threonine at amino acid position 52 with a glycine, followed by a premature termination codon after 65 residues. This is predicted to result in loss-of-function of the ACVRL1 protein. While this variant is absent from the medical literature and patient databases, loss-of-function of ACVRL1 is an established mechanism of disease in hereditary hemorrhagic telangiectasia (HHT, MIM: 600376). The p.Thr52Gly*65 variant is absent from large population studies (gnomAD v2.1.1).

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

Last Updated: Oct 8, 2024

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