NM_000268.4(NF2):c.1660_1661del (p.Arg554fs) AND Neurofibromatosis, type 2

Clinical significance:Uncertain significance (Last evaluated: Aug 2, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000804920.1

Allele description [Variation Report for NM_000268.4(NF2):c.1660_1661del (p.Arg554fs)]

NM_000268.4(NF2):c.1660_1661del (p.Arg554fs)

Gene:
NF2:NF2, moesin-ezrin-radixin like (MERLIN) tumor suppressor [Gene - OMIM - HGNC]
Variant type:
Microsatellite
Cytogenetic location:
22q12.2
Genomic location:
Preferred name:
NM_000268.4(NF2):c.1660_1661del (p.Arg554fs)
HGVS:
  • NC_000022.11:g.29681520AG[2]
  • NG_009057.1:g.82965AG[2]
  • NM_000268.4:c.1660_1661delMANE SELECT
  • NM_016418.5:c.1660_1661del
  • NM_181825.3:c.1660_1661del
  • NM_181828.3:c.1534_1535del
  • NM_181829.3:c.1537_1538del
  • NM_181830.3:c.1411_1412del
  • NM_181831.3:c.1411_1412del
  • NM_181832.3:c.1660_1661del
  • NM_181833.3:c.448-13232AG[2]
  • NP_000259.1:p.Arg554fs
  • NP_057502.2:p.Arg554fs
  • NP_861546.1:p.Arg554fs
  • NP_861966.1:p.Arg512fs
  • NP_861967.1:p.Arg513fs
  • NP_861968.1:p.Arg471fs
  • NP_861969.1:p.Arg471fs
  • NP_861970.1:p.Arg554fs
  • LRG_511t2:c.1660_1661del
  • LRG_511:g.82965AG[2]
  • LRG_511p2:p.Arg554fs
  • NC_000022.10:g.30077509AG[2]
  • NM_000268.3:c.1660_1661delAG
  • NR_156186.2:n.2138AG[2]
Protein change:
R471fs
Links:
dbSNP: rs1601666191
NCBI 1000 Genomes Browser:
rs1601666191
Molecular consequence:
  • NM_000268.4:c.1660_1661del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_016418.5:c.1660_1661del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_181825.3:c.1660_1661del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_181828.3:c.1534_1535del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_181829.3:c.1537_1538del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_181830.3:c.1411_1412del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_181831.3:c.1411_1412del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_181832.3:c.1660_1661del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_181833.3:c.448-13232AG[2] - intron variant - [Sequence Ontology: SO:0001627]
  • NR_156186.2:n.2138AG[2] - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000944858Invitaecriteria provided, single submitter
Uncertain significance
(Aug 2, 2018)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Tumor-suppression functions of merlin are independent of its role as an organizer of the actin cytoskeleton in Schwann cells.

Lallemand D, Saint-Amaux AL, Giovannini M.

J Cell Sci. 2009 Nov 15;122(Pt 22):4141-9. doi: 10.1242/jcs.045914.

PubMed [citation]
PMID:
19910496

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, SCV000944858.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change results in a premature translational stop signal in the NF2 gene (p.Arg554Glyfs*10). While this is not anticipated to result in nonsense mediated decay, it is expected to result in a truncated NF2 protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NF2-related disease. This variant disrupts the C-terminal domain of the NF2 protein, which contains a sub-domain composed of 47 amino acid residues (amino acids 532-579) thought to be involved in cell proliferation regulation. An experimental study has shown that deletion of these 47 amino acid residues abrogates the ability of the NF2 protein to inhibit cell proliferation in NF2-deficient cultured cells (PMID: 19910496). However, experimental studies and prediction algorithms are not available for this specific variant, and the functional significance of the disrupted amino acids is currently unknown. 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: Nov 27, 2021

Support Center