NM_000268.4(NF2):c.874G>A (p.Val292Ile) AND Neurofibromatosis, type 2

Clinical significance:Uncertain significance (Last evaluated: Apr 22, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001215781.1

Allele description [Variation Report for NM_000268.4(NF2):c.874G>A (p.Val292Ile)]

NM_000268.4(NF2):c.874G>A (p.Val292Ile)

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.874G>A (p.Val292Ile)
HGVS:
  • NC_000022.11:g.29665053G>A
  • NG_009057.1:g.66498G>A
  • NM_000268.4:c.874G>AMANE SELECT
  • NM_016418.5:c.874G>A
  • NM_181825.3:c.874G>A
  • NM_181828.3:c.748G>A
  • NM_181829.3:c.751G>A
  • NM_181830.3:c.625G>A
  • NM_181831.3:c.625G>A
  • NM_181832.3:c.874G>A
  • NM_181833.3:c.447+22768G>A
  • NP_000259.1:p.Val292Ile
  • NP_057502.2:p.Val292Ile
  • NP_861546.1:p.Val292Ile
  • NP_861966.1:p.Val250Ile
  • NP_861967.1:p.Val251Ile
  • NP_861968.1:p.Val209Ile
  • NP_861969.1:p.Val209Ile
  • NP_861970.1:p.Val292Ile
  • LRG_511t1:c.874G>A
  • LRG_511t2:c.874G>A
  • LRG_511:g.66498G>A
  • LRG_511p2:p.Val292Ile
  • NC_000022.10:g.30061042G>A
  • NM_000268.3:c.874G>A
  • NR_156186.2:n.1356G>A
Protein change:
V209I
Links:
dbSNP: rs1442581021
NCBI 1000 Genomes Browser:
rs1442581021
Molecular consequence:
  • NM_181833.3:c.447+22768G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000268.4:c.874G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_016418.5:c.874G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181825.3:c.874G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181828.3:c.748G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181829.3:c.751G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181830.3:c.625G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181831.3:c.625G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181832.3:c.874G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_156186.2:n.1356G>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
SCV001387543Invitaecriteria provided, single submitter
Uncertain significance
(Apr 22, 2019)
germlineclinical testing

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

Summary from all submissions

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

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, SCV001387543.2

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

Description

This sequence change replaces valine with isoleucine at codon 292 of the NF2 protein (p.Val292Ile). The valine residue is moderately conserved and there is a small physicochemical difference between valine and isoleucine. 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 conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Tolerated; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C0). 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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