NM_000268.4(NF2):c.1387G>T (p.Glu463Ter) AND Neurofibromatosis, type 2

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jul 30, 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:: RCV000003455.10

Allele description [Variation Report for NM_000268.4(NF2):c.1387G>T (p.Glu463Ter)]

NM_000268.4(NF2):c.1387G>T (p.Glu463Ter)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

22q12.2

Genomic location:

Preferred name:

NM_000268.4(NF2):c.1387G>T (p.Glu463Ter)

HGVS:

NC_000022.11:g.29674882G>T
NG_009057.1:g.76327G>T
NM_000268.4:c.1387G>TMANE SELECT
NM_016418.5:c.1387G>T
NM_181825.3:c.1387G>T
NM_181828.3:c.1261G>T
NM_181829.3:c.1264G>T
NM_181830.3:c.1138G>T
NM_181831.3:c.1138G>T
NM_181832.3:c.1387G>T
NM_181833.3:c.448-19870G>T
NP_000259.1:p.Glu463Ter
NP_057502.2:p.Glu463Ter
NP_861546.1:p.Glu463Ter
NP_861966.1:p.Glu421Ter
NP_861967.1:p.Glu422Ter
NP_861968.1:p.Glu380Ter
NP_861969.1:p.Glu380Ter
NP_861970.1:p.Glu463Ter
LRG_511t2:c.1387G>T
LRG_511:g.76327G>T
LRG_511p2:p.Glu463Ter
NC_000022.10:g.30070871G>T
NR_156186.2:n.1869G>T

Protein change:

E380*; GLU463TER

Links:

OMIM: 607379.0013; dbSNP: rs74315503

NCBI 1000 Genomes Browser:

rs74315503

Molecular consequence:

NM_181833.3:c.448-19870G>T - intron variant - [Sequence Ontology: SO:0001627]
NR_156186.2:n.1869G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000268.4:c.1387G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_016418.5:c.1387G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_181825.3:c.1387G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_181828.3:c.1261G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_181829.3:c.1264G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_181830.3:c.1138G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_181831.3:c.1138G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_181832.3:c.1387G>T - nonsense - [Sequence Ontology: SO:0001587]

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

Recent activity

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calcium homeostasis modulator protein 1 [Chlorocebus sabaeus]
calcium homeostasis modulator protein 1 [Chlorocebus sabaeus]
gi|635055977|ref|XP_007962204.1|

Protein
KIRREL2 [Bos mutus]
KIRREL2 [Bos mutus]
Gene ID:102269874

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000023613	OMIM	no assertion criteria provided	Pathogenic (Aug 1, 1994)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV001585179	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 30, 2020)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 9643284, 16983642, 7913580, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000023613

OMIM

no assertion criteria provided

Pathogenic
(Aug 1, 1994)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

SCV001585179

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 30, 2020)

germline

clinical testing

PubMed (4)
[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	not provided	not provided	not provided	not provided	not provided	not provided	literature only
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 (4)

Details of each submission

From OMIM, SCV000023613.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a study of 33 unrelated patients diagnosed with neurofibromatosis type II (SWNV; 101000), MacCollin et al. (1994) identified a G-to-T substitution at nucleotide 1387 in exon 13, resulting in a stop codon at position 463.

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001585179.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

Loss-of-function variants in NF2 are known to be pathogenic (PMID: 9643284, 16983642). For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with neurofibromatosis type 2 (PMID: 7913580). ClinVar contains an entry for this variant (Variation ID: 3294). This sequence change creates a premature translational stop signal (p.Glu463*) 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).

#	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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