NM_000020.3(ACVRL1):c.1411T>G (p.Cys471Gly) AND Telangiectasia, hereditary hemorrhagic, type 2

Clinical significance:Uncertain significance (Last evaluated: Feb 18, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001313821.1

Allele description [Variation Report for NM_000020.3(ACVRL1):c.1411T>G (p.Cys471Gly)]

NM_000020.3(ACVRL1):c.1411T>G (p.Cys471Gly)

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.1411T>G (p.Cys471Gly)
HGVS:
  • NC_000012.12:g.51920792T>G
  • NG_009549.1:g.18375T>G
  • NM_000020.3:c.1411T>GMANE SELECT
  • NM_001077401.2:c.1411T>G
  • NP_000011.2:p.Cys471Gly
  • NP_001070869.1:p.Cys471Gly
  • LRG_543:g.18375T>G
  • NC_000012.11:g.52314576T>G
Protein change:
C471G
Molecular consequence:
  • NM_000020.3:c.1411T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001077401.2:c.1411T>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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001504328Invitaecriteria provided, single submitter
Uncertain significance
(Feb 18, 2020)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV001504328.1

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

Description

This sequence change replaces cysteine with glycine at codon 471 of the ACVRL1 protein (p.Cys471Gly). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ACVRL1-related conditions. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Oct 7, 2021

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