NM_000268.4(NF2):c.1446G>A (p.Pro482=) AND Neurofibromatosis, type 2

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

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_000268.4(NF2):c.1446G>A (p.Pro482=)]

NM_000268.4(NF2):c.1446G>A (p.Pro482=)

NF2:NF2, moesin-ezrin-radixin like (MERLIN) tumor suppressor [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000268.4(NF2):c.1446G>A (p.Pro482=)
  • NC_000022.11:g.29674941G>A
  • NG_009057.1:g.76386G>A
  • NM_000268.3:c.1446G>A
  • NM_000268.4:c.1446G>AMANE SELECT
  • NM_016418.5:c.1446G>A
  • NM_181825.3:c.1446G>A
  • NM_181828.3:c.1320G>A
  • NM_181829.3:c.1323G>A
  • NM_181830.3:c.1197G>A
  • NM_181831.3:c.1197G>A
  • NM_181832.3:c.1446G>A
  • NM_181833.3:c.448-19811G>A
  • NP_000259.1:p.Pro482=
  • NP_000259.1:p.Pro482=
  • NP_057502.2:p.Pro482=
  • NP_861546.1:p.Pro482=
  • NP_861966.1:p.Pro440=
  • NP_861967.1:p.Pro441=
  • NP_861968.1:p.Pro399=
  • NP_861969.1:p.Pro399=
  • NP_861970.1:p.Pro482=
  • LRG_511t1:c.1446G>A
  • LRG_511t2:c.1446G>A
  • LRG_511:g.76386G>A
  • LRG_511p1:p.Pro482=
  • LRG_511p2:p.Pro482=
  • NC_000022.10:g.30070930G>A
  • NR_156186.2:n.1928G>A
dbSNP: rs753751373
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_181833.3:c.448-19811G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NR_156186.2:n.1928G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_000268.3:c.1446G>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_000268.4:c.1446G>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_016418.5:c.1446G>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_181825.3:c.1446G>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_181828.3:c.1320G>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_181829.3:c.1323G>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_181830.3:c.1197G>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_181831.3:c.1197G>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_181832.3:c.1446G>A - synonymous variant - [Sequence Ontology: SO:0001819]


Neurofibromatosis, type 2 (NF2)
NF 2; Neurofibromatosis central type; Acoustic schwannomas bilateral; See all synonyms [MedGen]
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)
SCV000553684Invitaecriteria provided, single submitter
Uncertain significance
(Jan 29, 2020)
germlineclinical testing

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

Summary from all submissions

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



Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]

Statistical features of human exons and their flanking regions.

Zhang MQ.

Hum Mol Genet. 1998 May;7(5):919-32.

PubMed [citation]
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000553684.6

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


This sequence change affects codon 482 of the NF2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the NF2 protein. This variant also falls at the last nucleotide of exon 13 of the NF2 coding sequence, which is part of the consensus splice site for this exon. Nucleotide substitutions within the consensus splice site are relatively common causes of aberrant splicing (PMID: 17576681, 9536098). This variant is present in population databases (rs753751373, ExAC 0.02%). This variant has not been reported in the literature in individuals with NF2-related disease. ClinVar contains an entry for this variant (Variation ID: 412215). 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.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

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