NM_000268.4(NF2):c.1013G>A (p.Arg338His) AND Neurofibromatosis, type 2

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

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000632652.2

Allele description [Variation Report for NM_000268.4(NF2):c.1013G>A (p.Arg338His)]

NM_000268.4(NF2):c.1013G>A (p.Arg338His)

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.1013G>A (p.Arg338His)
HGVS:
  • NC_000022.11:g.29671839G>A
  • NG_009057.1:g.73284G>A
  • NM_000268.3:c.1013G>A
  • NM_000268.4:c.1013G>AMANE SELECT
  • NM_016418.5:c.1013G>A
  • NM_181825.3:c.1013G>A
  • NM_181828.3:c.887G>A
  • NM_181829.3:c.890G>A
  • NM_181830.3:c.764G>A
  • NM_181831.3:c.764G>A
  • NM_181832.3:c.1013G>A
  • NM_181833.3:c.448-22913G>A
  • NP_000259.1:p.Arg338His
  • NP_000259.1:p.Arg338His
  • NP_057502.2:p.Arg338His
  • NP_861546.1:p.Arg338His
  • NP_861966.1:p.Arg296His
  • NP_861967.1:p.Arg297His
  • NP_861968.1:p.Arg255His
  • NP_861969.1:p.Arg255His
  • NP_861970.1:p.Arg338His
  • LRG_511t1:c.1013G>A
  • LRG_511t2:c.1013G>A
  • LRG_511:g.73284G>A
  • LRG_511p1:p.Arg338His
  • LRG_511p2:p.Arg338His
  • NC_000022.10:g.30067828G>A
  • NR_156186.2:n.1495G>A
Protein change:
R255H
Links:
dbSNP: rs768053145
NCBI 1000 Genomes Browser:
rs768053145
Molecular consequence:
  • NM_181833.3:c.448-22913G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000268.3:c.1013G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000268.4:c.1013G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_016418.5:c.1013G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181825.3:c.1013G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181828.3:c.887G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181829.3:c.890G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181830.3:c.764G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181831.3:c.764G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181832.3:c.1013G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_156186.2:n.1495G>A - 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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000753838Invitaecriteria provided, single submitter
Uncertain significance
(Jan 3, 2018)
germlineclinical testing

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

SCV000839518Mendelicscriteria provided, single submitter
Uncertain significance
(Jul 2, 2018)
unknownclinical testing

Citation Link

Summary from all submissions

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

Citations

PubMed

[Phenotype-genotype study in 154 French NF2 mutation carriers].

Demange L, De Moncuit C, Thomas G, Olschwang S.

Rev Neurol (Paris). 2007 Nov;163(11):1031-8. French.

PubMed [citation]
PMID:
18033041

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, SCV000753838.1

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

Description

This sequence change replaces arginine with histidine at codon 338 of the NF2 protein (p.Arg338His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs768053145, ExAC 0.01%). This variant has been reported in an individual affected with neurofibromatosis type 2 (PMID: 18033041). 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 tolerated, 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

From Mendelics, SCV000839518.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

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