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NM_000020.3(ACVRL1):c.269G>A (p.Cys90Tyr) AND Cardiovascular phenotype

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 14, 2020
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:
RCV002426928.2

Allele description [Variation Report for NM_000020.3(ACVRL1):c.269G>A (p.Cys90Tyr)]

NM_000020.3(ACVRL1):c.269G>A (p.Cys90Tyr)

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.269G>A (p.Cys90Tyr)
Other names:
p.C90Y:TGC>TAC
HGVS:
  • NC_000012.12:g.51913306G>A
  • NG_009549.1:g.10889G>A
  • NM_000020.3:c.269G>AMANE SELECT
  • NM_001077401.2:c.269G>A
  • NP_000011.2:p.Cys90Tyr
  • NP_000011.2:p.Cys90Tyr
  • NP_001070869.1:p.Cys90Tyr
  • LRG_543t1:c.269G>A
  • LRG_543:g.10889G>A
  • LRG_543p1:p.Cys90Tyr
  • NC_000012.11:g.52307090G>A
  • NM_000020.2:c.269G>A
Protein change:
C90Y
Links:
dbSNP: rs863223410
NCBI 1000 Genomes Browser:
rs863223410
Molecular consequence:
  • NM_000020.3:c.269G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001077401.2:c.269G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002742727Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Aug 14, 2020) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

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

Citations

PubMed

Distribution of ENG and ACVRL1 (ALK1) mutations in French HHT patients.

Lesca G, Burnichon N, Raux G, Tosi M, Pinson S, Marion MJ, Babin E, Gilbert-Dussardier B, Rivière S, Goizet C, Faivre L, Plauchu H, Frébourg T, Calender A, Giraud S; French Rendu-Osler Network..

Hum Mutat. 2006 Jun;27(6):598.

PubMed [citation]
PMID:
16705692

Clinical and analytical sensitivities in hereditary hemorrhagic telangiectasia testing and a report of de novo mutations.

Gedge F, McDonald J, Phansalkar A, Chou LS, Calderon F, Mao R, Lyon E, Bayrak-Toydemir P.

J Mol Diagn. 2007 Apr;9(2):258-65.

PubMed [citation]
PMID:
17384219
PMCID:
PMC1867450
See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV002742727.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

The p.C90Y pathogenic mutation (also known as c.269G>A), located in coding exon 2 of the ACVRL1 gene, results from a G to A substitution at nucleotide position 269. The cysteine at codon 90 is replaced by tyrosine, an amino acid with highly dissimilar properties. This mutation was identified in two individuals with a clinical diagnosis of hereditary hemorrhagic telangiectasia (Lesca G et al. Hum. Mutat., 2006 Jun;27:598; Gedge F et al. J Mol Diagn, 2007 Apr;9:258-65). Based on internal structural analysis, p.C90Y results in loss of a clinically relevant disulfide motif (Townson SA et al. J. Biol. Chem., 2012 Aug;287:27313-25). Two other alterations at the same codon, p.C90W (c.270C>G) and p.C90F (c.269G>T), have been described in individuals with suspected or confirmed HHT (Komiyama M et al. J. Hum. Genet., 2014 Jan;59:37-41; Goulielmos GN et al. IJNTR, 2016 Feb;2(1):32-6). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. 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: May 1, 2024