NM_000020.2(ACVRL1):c.992T>C (p.Phe331Ser) AND Telangiectasia, hereditary hemorrhagic, type 2

Clinical significance:Uncertain significance (Last evaluated: Apr 12, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000538925.1

Allele description [Variation Report for NM_000020.2(ACVRL1):c.992T>C (p.Phe331Ser)]

NM_000020.2(ACVRL1):c.992T>C (p.Phe331Ser)

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_000020.2(ACVRL1):c.992T>C (p.Phe331Ser)
HGVS:
  • NC_000012.12:g.51915444T>C
  • NG_009549.1:g.13027T>C
  • NM_000020.2:c.992T>C
  • NM_001077401.2:c.992T>C
  • NP_000011.2:p.Phe331Ser
  • NP_001070869.1:p.Phe331Ser
  • LRG_543t1:c.992T>C
  • LRG_543:g.13027T>C
  • LRG_543p1:p.Phe331Ser
  • NC_000012.11:g.52309228T>C
Protein change:
F331S
Links:
dbSNP: rs1166311240
NCBI 1000 Genomes Browser:
rs1166311240
Molecular consequence:
  • NM_000020.2:c.992T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001077401.2:c.992T>C - 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
SCV000639413Invitaecriteria provided, single submitter
Uncertain significance
(Apr 12, 2017)
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, SCV000639413.1

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

Description

This sequence change replaces phenylalanine with serine at codon 331 of the ACVRL1 protein (p.Phe331Ser). The phenylalanine residue is weakly conserved and there is a large physicochemical difference between phenylalanine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in one individual affected with hereditary hemorrhagic telangiectasia (HHT) (PMID: 16752392). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C55"). In summary, this variant is a rare missense change with uncertain impact on protein function. While it is absent from the population and reported in an affected individual, the available evidence is currently insufficient to determine its role 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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