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

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 28, 2015
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:: RCV002438191.2

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:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002752450	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Oct 28, 2015)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 16690726, 18498373 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002752450

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Oct 28, 2015)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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

Details of each submission

From Ambry Genetics, SCV002752450.2

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

Description

The p.N98S variant (also known as c.293A>G), located in coding exon 2 of the ACVRL1 gene, results from an A to G substitution at nucleotide position 293. The asparagine at codon 98 is replaced by serine, an amino acid with highly similar properties. There have been two independent reports of individuals heterozygous for this alteration: one presented with telangiectases and severe hepatic arteriovenous malformations (HAVMs) (Prigoda NL et al, J. Med. Genet. 2006 Sep; 43(9):722-8) and the other with focal nodular hyperplasia and typical HAVMs (Brakensiek K et al, Clin. Genet. 2008 Aug; 74(2):171-7). Although both were reported to have hereditary hemorrhagic telangiectasia (HHT), insufficient information was provided in the primary reports to confirm a definite diagnosis based on Curacoa’s diagnostic criteria. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6500 samples (13000 alleles) with coverage at this position. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.

#	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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