NM_000268.4(NF2):c.1271G>T (p.Arg424Leu) AND Neurofibromatosis, type 2

Clinical significance:Uncertain significance (Last evaluated: May 21, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000558170.5

Allele description [Variation Report for NM_000268.4(NF2):c.1271G>T (p.Arg424Leu)]

NM_000268.4(NF2):c.1271G>T (p.Arg424Leu)

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.1271G>T (p.Arg424Leu)
HGVS:
  • NC_000022.11:g.29673417G>T
  • NG_009057.1:g.74862G>T
  • NM_000268.3:c.1271G>T
  • NM_000268.4:c.1271G>TMANE SELECT
  • NM_016418.5:c.1271G>T
  • NM_181825.3:c.1271G>T
  • NM_181828.3:c.1145G>T
  • NM_181829.3:c.1148G>T
  • NM_181830.3:c.1022G>T
  • NM_181831.3:c.1022G>T
  • NM_181832.3:c.1271G>T
  • NM_181833.3:c.448-21335G>T
  • NP_000259.1:p.Arg424Leu
  • NP_000259.1:p.Arg424Leu
  • NP_057502.2:p.Arg424Leu
  • NP_861546.1:p.Arg424Leu
  • NP_861966.1:p.Arg382Leu
  • NP_861967.1:p.Arg383Leu
  • NP_861968.1:p.Arg341Leu
  • NP_861969.1:p.Arg341Leu
  • NP_861970.1:p.Arg424Leu
  • LRG_511t1:c.1271G>T
  • LRG_511t2:c.1271G>T
  • LRG_511:g.74862G>T
  • LRG_511p1:p.Arg424Leu
  • LRG_511p2:p.Arg424Leu
  • NC_000022.10:g.30069406G>T
  • NR_156186.2:n.1753G>T
Protein change:
R341L
Links:
dbSNP: rs751182657
NCBI 1000 Genomes Browser:
rs751182657
Molecular consequence:
  • NM_181833.3:c.448-21335G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000268.3:c.1271G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000268.4:c.1271G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_016418.5:c.1271G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181825.3:c.1271G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181828.3:c.1145G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181829.3:c.1148G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181830.3:c.1022G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181831.3:c.1022G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181832.3:c.1271G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_156186.2:n.1753G>T - 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
SCV000628844Invitaecriteria provided, single submitter
Uncertain significance
(May 21, 2020)
germlineclinical testing

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

SCV001749323GenomeConnect - Invitae Patient Insights Networkno assertion providednot providedunknownphenotyping only

Summary from all submissions

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

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, SCV000628844.4

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

Description

This sequence change replaces arginine with leucine at codon 424 of the NF2 protein (p.Arg424Leu). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and leucine. This variant is present in population databases (rs751182657, ExAC 0.02%). This variant has not been reported in the literature in individuals with a NF2-related disease. 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: Tolerated; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C0). In summary, this variant has uncertain impact on NF2 function. 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

From GenomeConnect - Invitae Patient Insights Network, SCV001749323.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedphenotyping onlynot provided

Description

Variant interpreted as Uncertain significance and reported on 09-29-2017 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

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

Last Updated: Oct 30, 2021

Support Center