NM_000268.4(NF2):c.1490del (p.Ser497fs) AND Neurofibromatosis, type 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 8, 2021
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:: RCV001923927.4

Allele description [Variation Report for NM_000268.4(NF2):c.1490del (p.Ser497fs)]

NM_000268.4(NF2):c.1490del (p.Ser497fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

22q12.2

Genomic location:

Preferred name:

NM_000268.4(NF2):c.1490del (p.Ser497fs)

HGVS:

NC_000022.11:g.29678239del
NG_009057.1:g.79684del
NM_000268.4:c.1490delMANE SELECT
NM_016418.5:c.1490del
NM_181825.3:c.1490del
NM_181828.3:c.1364del
NM_181829.3:c.1367del
NM_181830.3:c.1241del
NM_181831.3:c.1241del
NM_181832.3:c.1490del
NM_181833.3:c.448-16513del
NP_000259.1:p.Ser497fs
NP_057502.2:p.Ser497fs
NP_861546.1:p.Ser497fs
NP_861966.1:p.Ser455fs
NP_861967.1:p.Ser456fs
NP_861968.1:p.Ser414fs
NP_861969.1:p.Ser414fs
NP_861970.1:p.Ser497fs
LRG_511t2:c.1490del
LRG_511:g.79684del
LRG_511p2:p.Ser497fs
NC_000022.10:g.30074228del
NR_156186.2:n.1972del

Protein change:

S414fs

Links:

dbSNP: rs2147108214

NCBI 1000 Genomes Browser:

rs2147108214

Molecular consequence:

NM_000268.4:c.1490del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_016418.5:c.1490del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_181825.3:c.1490del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_181828.3:c.1364del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_181829.3:c.1367del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_181830.3:c.1241del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_181831.3:c.1241del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_181832.3:c.1490del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_181833.3:c.448-16513del - intron variant - [Sequence Ontology: SO:0001627]
NR_156186.2:n.1972del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Neurofibromatosis, type 2 (SWNV)
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
SCV002191856	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 8, 2021)	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

SCV002191856

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 8, 2021)

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002191856.3

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with NF2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ser497Thrfs*18) in the NF2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NF2 are known to be pathogenic (PMID: 9643284, 16983642).

#	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: Sep 29, 2024

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