NM_000020.3(ACVRL1):c.293A>G (p.Asn98Ser) AND Telangiectasia, hereditary hemorrhagic, type 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 9, 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:: RCV000795036.7

Allele description [Variation Report for NM_000020.3(ACVRL1):c.293A>G (p.Asn98Ser)]

NM_000020.3(ACVRL1):c.293A>G (p.Asn98Ser)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

12q13.13

Genomic location:

Preferred name:

NM_000020.3(ACVRL1):c.293A>G (p.Asn98Ser)

HGVS:

NC_000012.12:g.51913330A>G
NG_009549.1:g.10913A>G
NM_000020.3:c.293A>GMANE SELECT
NM_001077401.2:c.293A>G
NP_000011.2:p.Asn98Ser
NP_000011.2:p.Asn98Ser
NP_001070869.1:p.Asn98Ser
LRG_543t1:c.293A>G
LRG_543:g.10913A>G
LRG_543p1:p.Asn98Ser
NC_000012.11:g.52307114A>G
NM_000020.2:c.293A>G

Protein change:

N98S

Links:

dbSNP: rs1085307406

NCBI 1000 Genomes Browser:

rs1085307406

Molecular consequence:

NM_000020.3:c.293A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001077401.2:c.293A>G - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000934476	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 9, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16690726, 18498373, 32503579, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000934476

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 9, 2022)

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: mutation detection, test sensitivity and novel mutations.

Prigoda NL, Savas S, Abdalla SA, Piovesan B, Rushlow D, Vandezande K, Zhang E, Ozcelik H, Gallie BL, Letarte M.

J Med Genet. 2006 Sep;43(9):722-8. Epub 2006 May 11.

PubMed [citation]

PMID:: 16690726
PMCID:: PMC2564570

Detection of a significant association between mutations in the ACVRL1 gene and hepatic involvement in German patients with hereditary haemorrhagic telangiectasia.

Brakensiek K, Frye-Boukhriss H, Mälzer M, Abramowicz M, Bahr MJ, von Beckerath N, Bergmann C, Caselitz M, Holinski-Feder E, Muschke P, Oexle K, Strobl-Wildemann G, Wolff G, El-Harith EA, Stuhrmann M.

Clin Genet. 2008 Aug;74(2):171-7. doi: 10.1111/j.1399-0004.2008.01029.x. Epub 2008 May 21.

PubMed [citation]

PMID:: 18498373

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000934476.4

#	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 replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 98 of the ACVRL1 protein (p.Asn98Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with hereditary hemorrhagic telangiectasia (HHT) (PMID: 16690726, 18498373, 32503579; Invitae). ClinVar contains an entry for this variant (Variation ID: 426011). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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

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