NM_000268.4(NF2):c.1021C>T (p.Arg341Ter) AND Neurofibromatosis, type 2

Clinical significance:Pathogenic (Last evaluated: Sep 30, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000003453.5

Allele description [Variation Report for NM_000268.4(NF2):c.1021C>T (p.Arg341Ter)]

NM_000268.4(NF2):c.1021C>T (p.Arg341Ter)

Gene:
NF2:NF2, moesin-ezrin-radixin like (MERLIN) tumor suppressor [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
22q12.2
Genomic location:
Preferred name:
NM_000268.4(NF2):c.1021C>T (p.Arg341Ter)
HGVS:
  • NC_000022.11:g.29671847C>T
  • NG_009057.1:g.73292C>T
  • NM_000268.4:c.1021C>TMANE SELECT
  • NM_016418.5:c.1021C>T
  • NM_181825.3:c.1021C>T
  • NM_181828.3:c.895C>T
  • NM_181829.3:c.898C>T
  • NM_181830.3:c.772C>T
  • NM_181831.3:c.772C>T
  • NM_181832.3:c.1021C>T
  • NM_181833.3:c.448-22905C>T
  • NP_000259.1:p.Arg341Ter
  • NP_000259.1:p.Arg341Ter
  • NP_057502.2:p.Arg341Ter
  • NP_861546.1:p.Arg341Ter
  • NP_861966.1:p.Arg299Ter
  • NP_861967.1:p.Arg300Ter
  • NP_861968.1:p.Arg258Ter
  • NP_861969.1:p.Arg258Ter
  • NP_861970.1:p.Arg341Ter
  • LRG_511t1:c.1021C>T
  • LRG_511t2:c.1021C>T
  • LRG_511:g.73292C>T
  • LRG_511p1:p.Arg341Ter
  • LRG_511p2:p.Arg341Ter
  • NC_000022.10:g.30067836C>T
  • NM_000268.3:c.1021C>T
  • NR_156186.2:n.1503C>T
Protein change:
R258*; ARG341TER
Links:
OMIM: 607379.0011; dbSNP: rs74315499
NCBI 1000 Genomes Browser:
rs74315499
Molecular consequence:
  • NM_181833.3:c.448-22905C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NR_156186.2:n.1503C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_000268.4:c.1021C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_016418.5:c.1021C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_181825.3:c.1021C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_181828.3:c.895C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_181829.3:c.898C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_181830.3:c.772C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_181831.3:c.772C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_181832.3:c.1021C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Neurofibromatosis, type 2 (NF2)
Synonyms:
NF 2; Neurofibromatosis central type; Acoustic schwannomas bilateral; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007039; MedGen: C0027832; Orphanet: 637; OMIM: 101000

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000023611OMIMno assertion criteria providedPathogenic
(Aug 1, 1994)
germlineliterature only

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

SCV000553677Invitaecriteria provided, single submitter
Pathogenic
(Sep 30, 2020)
germlineclinical testing

PubMed (8)
[See all records that cite these PMIDs]

SCV000782126Center for Human Genetics, Inc,Center for Human Genetics, Inccriteria provided, single submitter
Pathogenic
(Nov 1, 2016)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2.

Rouleau GA, Merel P, Lutchman M, Sanson M, Zucman J, Marineau C, Hoang-Xuan K, Demczuk S, Desmaze C, Plougastel B, et al.

Nature. 1993 Jun 10;363(6429):515-21.

PubMed [citation]
PMID:
8379998

Molecular study of frequency of mosaicism in neurofibromatosis 2 patients with bilateral vestibular schwannomas.

Kluwe L, Mautner V, Heinrich B, Dezube R, Jacoby LB, Friedrich RE, MacCollin M.

J Med Genet. 2003 Feb;40(2):109-14.

PubMed [citation]
PMID:
12566519
PMCID:
PMC1735360
See all PubMed Citations (9)

Details of each submission

From OMIM, SCV000023611.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In a study of 33 unrelated patients with NF2 (101000), MacCollin et al. (1994) identified a C-to-T substitution at nucleotide 1021 in exon 11, resulting in a stop codon at position 341.

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

From Invitae, SCV000553677.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (8)

Description

This sequence change creates a premature translational stop signal (p.Arg341*) in the NF2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with neurofibromatosis type 2 (PMID: 8379998, 12566519, 21671232, 11809806, 7913580). Loss-of-function variants in NF2 are known to be pathogenic (PMID: 9643284, 16983642). For these reasons, this variant has been classified as Pathogenic.

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

From Center for Human Genetics, Inc,Center for Human Genetics, Inc, SCV000782126.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Dec 4, 2021

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