NM_000268.4(NF2):c.1738-4_1741delinsG AND Neurofibromatosis, type 2

Clinical significance:Uncertain significance (Last evaluated: Jun 24, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000549256.2

Allele description [Variation Report for NM_000268.4(NF2):c.1738-4_1741delinsG]

NM_000268.4(NF2):c.1738-4_1741delinsG

Gene:
NF2:NF2, moesin-ezrin-radixin like (MERLIN) tumor suppressor [Gene - OMIM - HGNC]
Variant type:
Indel
Cytogenetic location:
22q12.2
Genomic location:
Preferred name:
NM_000268.4(NF2):c.1738-4_1741delinsG
HGVS:
  • NC_000022.11:g.29694748_29694755delinsG
  • NG_009057.1:g.96193_96200delinsG
  • NM_000268.3:c.1738-4_1741delinsG
  • NM_000268.4:c.1738-4_1741delinsGMANE SELECT
  • NM_016418.5:c.*10-4_*13delinsG
  • NM_181828.3:c.*10-4_*13delinsG
  • NM_181829.3:c.*10-4_*13delinsG
  • NM_181830.3:c.*10-4_*13delinsG
  • NM_181832.3:c.*25-4_*28delinsG
  • NM_181833.3:c.448-4_451delinsG
  • LRG_511t1:c.1738-4_1741delinsG
  • LRG_511t2:c.*10-4_*13delinsG
  • LRG_511:g.96193_96200delinsG
  • NC_000022.10:g.30090737_30090744delinsG
Links:
dbSNP: rs1556008383
NCBI 1000 Genomes Browser:
rs1556008383
Molecular consequence:
  • NM_000268.3:c.1738-4_1741delinsG - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_000268.4:c.1738-4_1741delinsG - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_016418.5:c.*10-4_*13delinsG - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_181828.3:c.*10-4_*13delinsG - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_181829.3:c.*10-4_*13delinsG - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_181830.3:c.*10-4_*13delinsG - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_181832.3:c.*25-4_*28delinsG - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_181833.3:c.448-4_451delinsG - splice acceptor variant - [Sequence Ontology: SO:0001574]

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
SCV000628863Invitaecriteria provided, single submitter
Uncertain significance
(Jun 24, 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, SCV000628863.2

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

Description

This sequence change affects an acceptor splice site in the last intron (intron 15) of the NF2 gene. While this is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. 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. ClinVar contains an entry for this variant (Variation ID: 457909). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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: Oct 25, 2021

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