NM_000268.4(NF2):c.191T>C (p.Leu64Pro) AND Neurofibromatosis, type 2

Clinical significance:Uncertain significance (Last evaluated: Jun 1, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001303321.1

Allele description [Variation Report for NM_000268.4(NF2):c.191T>C (p.Leu64Pro)]

NM_000268.4(NF2):c.191T>C (p.Leu64Pro)

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.191T>C (p.Leu64Pro)
HGVS:
  • NC_000022.11:g.29636827T>C
  • NG_009057.1:g.38272T>C
  • NM_000268.4:c.191T>CMANE SELECT
  • NM_016418.5:c.191T>C
  • NM_181825.3:c.191T>C
  • NM_181828.3:c.115-2263T>C
  • NM_181829.3:c.191T>C
  • NM_181830.3:c.115-5375T>C
  • NM_181831.3:c.115-5375T>C
  • NM_181832.3:c.191T>C
  • NM_181833.3:c.191T>C
  • NP_000259.1:p.Leu64Pro
  • NP_057502.2:p.Leu64Pro
  • NP_861546.1:p.Leu64Pro
  • NP_861967.1:p.Leu64Pro
  • NP_861970.1:p.Leu64Pro
  • NP_861971.1:p.Leu64Pro
  • LRG_511t2:c.191T>C
  • LRG_511:g.38272T>C
  • LRG_511p2:p.Leu64Pro
  • NC_000022.10:g.30032816T>C
  • NR_156186.2:n.673T>C
Protein change:
L64P
Links:
dbSNP: rs2065661430
NCBI 1000 Genomes Browser:
rs2065661430
Molecular consequence:
  • NM_181828.3:c.115-2263T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_181830.3:c.115-5375T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_181831.3:c.115-5375T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000268.4:c.191T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_016418.5:c.191T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181825.3:c.191T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181829.3:c.191T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181832.3:c.191T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181833.3:c.191T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_156186.2:n.673T>C - 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
SCV001492562Invitaecriteria provided, single submitter
Uncertain significance
(Jun 1, 2020)
germlineclinical testing

PubMed (9)
[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

In Silico Analysis of NF2 Gene Missense Mutations in Neurofibromatosis Type 2: From Genotype to Phenotype.

Heineman TE, Evans DG, Campagne F, Selesnick SH.

Otol Neurotol. 2015 Jun;36(5):908-14. doi: 10.1097/MAO.0000000000000639.

PubMed [citation]
PMID:
25931164

Neurofibromatosis type 2 French cohort analysis using a comprehensive NF2 molecular diagnostic strategy.

Pasmant E, Louvrier C, Luscan A, Cohen J, Laurendeau I, Vidaud M, Vidaud D, Goutagny S, Kalamarides M, Parfait B.

Neurochirurgie. 2018 Nov;64(5):335-341. doi: 10.1016/j.neuchi.2015.01.004. Epub 2015 Jun 12.

PubMed [citation]
PMID:
26073919
See all PubMed Citations (9)

Details of each submission

From Invitae, SCV001492562.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (9)

Description

This sequence change replaces leucine with proline at codon 64 of the NF2 protein (p.Leu64Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with neurofibromatosis type 2 (PMID: 25931164, 26073919). This variant has been reported to affect NF2 protein function (PMID: 24595234, 19451225, 11809806, 15598747, 9931334, 12695331). 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

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