NM_000268.4(NF2):c.947T>G (p.Leu316Trp) AND Neurofibromatosis, type 2

Clinical significance:Uncertain significance (Last evaluated: Oct 29, 2020)

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:
RCV000534581.6

Allele description [Variation Report for NM_000268.4(NF2):c.947T>G (p.Leu316Trp)]

NM_000268.4(NF2):c.947T>G (p.Leu316Trp)

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.947T>G (p.Leu316Trp)
HGVS:
  • NC_000022.11:g.29668394T>G
  • NG_009057.1:g.69839T>G
  • NM_000268.4:c.947T>GMANE SELECT
  • NM_016418.5:c.947T>G
  • NM_181825.3:c.947T>G
  • NM_181828.3:c.821T>G
  • NM_181829.3:c.824T>G
  • NM_181830.3:c.698T>G
  • NM_181831.3:c.698T>G
  • NM_181832.3:c.947T>G
  • NM_181833.3:c.447+26109T>G
  • NP_000259.1:p.Leu316Trp
  • NP_000259.1:p.Leu316Trp
  • NP_057502.2:p.Leu316Trp
  • NP_861546.1:p.Leu316Trp
  • NP_861966.1:p.Leu274Trp
  • NP_861967.1:p.Leu275Trp
  • NP_861968.1:p.Leu233Trp
  • NP_861969.1:p.Leu233Trp
  • NP_861970.1:p.Leu316Trp
  • LRG_511t1:c.947T>G
  • LRG_511t2:c.947T>G
  • LRG_511:g.69839T>G
  • LRG_511p1:p.Leu316Trp
  • LRG_511p2:p.Leu316Trp
  • NC_000022.10:g.30064383T>G
  • NM_000268.3:c.947T>G
  • NR_156186.2:n.1429T>G
Protein change:
L233W
Links:
dbSNP: rs750633919
NCBI 1000 Genomes Browser:
rs750633919
Molecular consequence:
  • NM_181833.3:c.447+26109T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000268.4:c.947T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_016418.5:c.947T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181825.3:c.947T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181828.3:c.821T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181829.3:c.824T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181830.3:c.698T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181831.3:c.698T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181832.3:c.947T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_156186.2:n.1429T>G - 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
SCV000628888Invitaecriteria provided, single submitter
Uncertain significance
(Oct 29, 2020)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV000839517Mendelicscriteria 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

Mutational spectrum of the NF2 gene: a meta-analysis of 12 years of research and diagnostic laboratory findings.

Ahronowitz I, Xin W, Kiely R, Sims K, MacCollin M, Nunes FP.

Hum Mutat. 2007 Jan;28(1):1-12.

PubMed [citation]
PMID:
16983642

A functional association between merlin and HEI10, a cell cycle regulator.

Grönholm M, Muranen T, Toby GG, Utermark T, Hanemann CO, Golemis EA, Carpén O.

Oncogene. 2006 Jul 27;25(32):4389-98. Epub 2006 Mar 13.

PubMed [citation]
PMID:
16532029
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000628888.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces leucine with tryptophan at codon 316 of the NF2 protein (p.Leu316Trp). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and tryptophan. This variant is present in population databases (rs750633919, ExAC 0.02%). This variant has been reported in an individual affected with bilateral vestibular schwannomas (PMID: 16983642). ClinVar contains an entry for this variant (Variation ID: 380975). Experimental studies using a yeast two-hybrid screen have shown that this missense change does not affect the binding interaction between Merlin (the protein encoded by NF2) and HEI10 (a cell cycle regulator) (PMID: 16532029). 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, SCV000839517.1

#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: Dec 4, 2021

Support Center