NM_000268.4(NF2):c.1493_1494delinsCT (p.Phe498Ser) AND Neurofibromatosis, type 2

Clinical significance:Uncertain significance (Last evaluated: Mar 12, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001370566.1

Allele description [Variation Report for NM_000268.4(NF2):c.1493_1494delinsCT (p.Phe498Ser)]

NM_000268.4(NF2):c.1493_1494delinsCT (p.Phe498Ser)

Gene:
NF2:neurofibromin 2 [Gene - OMIM - HGNC]
Variant type:
Indel
Cytogenetic location:
22q12.2
Genomic location:
Preferred name:
NM_000268.4(NF2):c.1493_1494delinsCT (p.Phe498Ser)
HGVS:
  • NC_000022.11:g.29678242_29678243delinsCT
  • NG_009057.1:g.79687_79688delinsCT
  • NM_000268.4:c.1493_1494delinsCTMANE SELECT
  • NM_016418.5:c.1493_1494delinsCT
  • NM_181825.3:c.1493_1494delinsCT
  • NM_181828.3:c.1367_1368delinsCT
  • NM_181829.3:c.1370_1371delinsCT
  • NM_181830.3:c.1244_1245delinsCT
  • NM_181831.3:c.1244_1245delinsCT
  • NM_181832.3:c.1493_1494delinsCT
  • NM_181833.3:c.448-16510_448-16509delinsCT
  • NP_000259.1:p.Phe498Ser
  • NP_057502.2:p.Phe498Ser
  • NP_861546.1:p.Phe498Ser
  • NP_861966.1:p.Phe456Ser
  • NP_861967.1:p.Phe457Ser
  • NP_861968.1:p.Phe415Ser
  • NP_861969.1:p.Phe415Ser
  • NP_861970.1:p.Phe498Ser
  • LRG_511t2:c.1493_1494delinsCT
  • LRG_511:g.79687_79688delinsCT
  • LRG_511p2:p.Phe498Ser
  • NC_000022.10:g.30074231_30074232delinsCT
  • NR_156186.2:n.1975_1976delinsCT
Protein change:
F415S
Molecular consequence:
  • NM_181833.3:c.448-16510_448-16509delinsCT - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000268.4:c.1493_1494delinsCT - missense variant - [Sequence Ontology: SO:0001583]
  • NM_016418.5:c.1493_1494delinsCT - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181825.3:c.1493_1494delinsCT - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181828.3:c.1367_1368delinsCT - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181829.3:c.1370_1371delinsCT - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181830.3:c.1244_1245delinsCT - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181831.3:c.1244_1245delinsCT - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181832.3:c.1493_1494delinsCT - missense variant - [Sequence Ontology: SO:0001583]
  • NR_156186.2:n.1975_1976delinsCT - 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
SCV001567085Invitaecriteria provided, single submitter
Uncertain significance
(Mar 12, 2020)
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, SCV001567085.1

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

Description

This sequence change replaces phenylalanine with serine at codon 498 of the NF2 protein (p.Phe498Ser). The phenylalanine residue is highly conserved and there is a large physicochemical difference between phenylalanine and serine. 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: Not Available; PolyPhen-2: Benign; Align-GVGD: Not Available). 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: Apr 18, 2021

Support Center