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NM_000020.3(ACVRL1):c.1415G>A (p.Trp472Ter) AND Cardiovascular phenotype

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 3, 2023
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:
RCV002388766.2

Allele description [Variation Report for NM_000020.3(ACVRL1):c.1415G>A (p.Trp472Ter)]

NM_000020.3(ACVRL1):c.1415G>A (p.Trp472Ter)

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.1415G>A (p.Trp472Ter)
Other names:
p.Trp472*
HGVS:
  • NC_000012.12:g.51920796G>A
  • NG_009549.1:g.18379G>A
  • NM_000020.2:c.1415G>A
  • NM_000020.3:c.1415G>AMANE SELECT
  • NM_001077401.2:c.1415G>A
  • NP_000011.2:p.Trp472Ter
  • NP_001070869.1:p.Trp472Ter
  • LRG_543:g.18379G>A
  • NC_000012.11:g.52314580G>A
Protein change:
W472*
Links:
dbSNP: rs1555154144
NCBI 1000 Genomes Browser:
rs1555154144
Molecular consequence:
  • NM_000020.3:c.1415G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001077401.2:c.1415G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002696550Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Nov 3, 2023) 		germlineclinical testing

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From Ambry Genetics, SCV002696550.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The p.W472* pathogenic mutation (also known as c.1415G>A), located in coding exon 9 of the ACVRL1 gene, results from a G to A substitution at nucleotide position 1415. This changes the amino acid from a tryptophan to a stop codon within coding exon 9. This alteration occurs at the 3' terminus of theACVRL1 gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 6.3% of the protein. However, premature stop codons are typically deleterious in nature, and the impacted region is critical for protein function (Ambry internal data). This mutation has been observed in at least one individual with clinical features of hereditary hemorrhagic telangiectasia (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024