NM_000268.4(NF2):c.293C>A (p.Ala98Asp) AND Neurofibromatosis, type 2

Clinical significance:Uncertain significance (Last evaluated: May 16, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000470208.1

Allele description [Variation Report for NM_000268.4(NF2):c.293C>A (p.Ala98Asp)]

NM_000268.4(NF2):c.293C>A (p.Ala98Asp)

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.293C>A (p.Ala98Asp)
HGVS:
  • NC_000022.11:g.29639142C>A
  • NG_009057.1:g.40587C>A
  • NM_000268.3:c.293C>A
  • NM_000268.4:c.293C>AMANE SELECT
  • NM_016418.5:c.293C>A
  • NM_181825.3:c.293C>A
  • NM_181828.3:c.167C>A
  • NM_181829.3:c.240+2266C>A
  • NM_181830.3:c.115-3060C>A
  • NM_181831.3:c.115-3060C>A
  • NM_181832.3:c.293C>A
  • NM_181833.3:c.293C>A
  • NP_000259.1:p.Ala98Asp
  • NP_000259.1:p.Ala98Asp
  • NP_057502.2:p.Ala98Asp
  • NP_861546.1:p.Ala98Asp
  • NP_861966.1:p.Ala56Asp
  • NP_861970.1:p.Ala98Asp
  • NP_861971.1:p.Ala98Asp
  • LRG_511t1:c.293C>A
  • LRG_511t2:c.293C>A
  • LRG_511:g.40587C>A
  • LRG_511p1:p.Ala98Asp
  • LRG_511p2:p.Ala98Asp
  • NC_000022.10:g.30035131C>A
  • NR_156186.2:n.775C>A
Protein change:
A56D
Links:
dbSNP: rs1060503668
NCBI 1000 Genomes Browser:
rs1060503668
Molecular consequence:
  • NM_181829.3:c.240+2266C>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_181830.3:c.115-3060C>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_181831.3:c.115-3060C>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000268.3:c.293C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000268.4:c.293C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_016418.5:c.293C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181825.3:c.293C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181828.3:c.167C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181832.3:c.293C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181833.3:c.293C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_156186.2:n.775C>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
SCV000553668Invitaecriteria provided, single submitter
Uncertain significance
(May 16, 2016)
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, SCV000553668.2

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

Description

This sequence change replaces alanine with aspartic acid at codon 98 of the NF2 protein (p.Ala98Asp). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and aspartic acid. This variant is not present in population databases (ExAC no frequency) and 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. In summary, this variant is a novel missense change with uncertain impact on protein function. 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: Oct 24, 2021

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