NM_000268.4(NF2):c.648_649dup (p.Tyr217fs) AND Neurofibromatosis, type 2

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 27, 2020
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001382466.1

Allele description

NM_000268.4(NF2):c.648_649dup (p.Tyr217fs)

Gene:

NF2:NF2, moesin-ezrin-radixin like (MERLIN) tumor suppressor [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

22q12.2

Genomic location:

Preferred name:

NM_000268.4(NF2):c.648_649dup (p.Tyr217fs)

HGVS:

NC_000022.11:g.29658237_29658238dup
NG_009057.1:g.59682_59683dup
NM_000268.4:c.648_649dupMANE SELECT
NM_016418.5:c.648_649dup
NM_181825.3:c.648_649dup
NM_181828.3:c.522_523dup
NM_181829.3:c.525_526dup
NM_181830.3:c.399_400dup
NM_181831.3:c.399_400dup
NM_181832.3:c.648_649dup
NM_181833.3:c.447+15952_447+15953dup
NP_000259.1:p.Tyr217fs
NP_057502.2:p.Tyr217fs
NP_861546.1:p.Tyr217fs
NP_861966.1:p.Tyr175fs
NP_861967.1:p.Tyr176fs
NP_861968.1:p.Tyr134fs
NP_861969.1:p.Tyr134fs
NP_861970.1:p.Tyr217fs
LRG_511t2:c.648_649dup
LRG_511:g.59682_59683dup
LRG_511p2:p.Tyr217fs
NC_000022.10:g.30054224_30054225insTG
NC_000022.10:g.30054226_30054227dup
NR_156186.2:n.1130_1131dup

Protein change:

Y134fs

Links:

Molecular consequence:

NM_000268.4:c.648_649dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_016418.5:c.648_649dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_181825.3:c.648_649dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_181828.3:c.522_523dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_181829.3:c.525_526dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_181830.3:c.399_400dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_181831.3:c.399_400dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_181832.3:c.648_649dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_181833.3:c.447+15952_447+15953dup - intron variant - [Sequence Ontology: SO:0001627]
NR_156186.2:n.1130_1131dup - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001581240	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 27, 2020)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 9643284, 16983642, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001581240

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 27, 2020)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genotype/phenotype correlations in type 2 neurofibromatosis (NF2): evidence for more severe disease associated with truncating mutations.

Evans DG, Trueman L, Wallace A, Collins S, Strachan T.

J Med Genet. 1998 Jun;35(6):450-5. Erratum in: J Med Genet 1999 Jan;36(1):87.

PubMed [citation]

PMID:: 9643284
PMCID:: PMC1051337

Mutational spectrum of the NF2 gene: a meta-analysis of 12 years of research and diagnostic laboratory findings.

Ahronowitz I, Xin W, Kiely R, Sims K, MacCollin M, Nunes FP.

Hum Mutat. 2007 Jan;28(1):1-12.

PubMed [citation]

PMID:: 16983642

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001581240.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Tyr217Cysfs*4) in the NF2 gene. It is expected to result in an absent or 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Loss-of-function variants in NF2 are known to be pathogenic (PMID: 9643284, 16983642). For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 23, 2022

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