NM_000268.4(NF2):c.1396C>T (p.Arg466Ter) AND Neurofibromatosis, type 2

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Feb 21, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000003456.12

Allele description [Variation Report for NM_000268.4(NF2):c.1396C>T (p.Arg466Ter)]

NM_000268.4(NF2):c.1396C>T (p.Arg466Ter)

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.1396C>T (p.Arg466Ter)

HGVS:

NC_000022.11:g.29674891C>T
NG_009057.1:g.76336C>T
NM_000268.4:c.1396C>TMANE SELECT
NM_016418.5:c.1396C>T
NM_181825.3:c.1396C>T
NM_181828.3:c.1270C>T
NM_181829.3:c.1273C>T
NM_181830.3:c.1147C>T
NM_181831.3:c.1147C>T
NM_181832.3:c.1396C>T
NM_181833.3:c.448-19861C>T
NP_000259.1:p.Arg466Ter
NP_000259.1:p.Arg466Ter
NP_057502.2:p.Arg466Ter
NP_861546.1:p.Arg466Ter
NP_861966.1:p.Arg424Ter
NP_861967.1:p.Arg425Ter
NP_861968.1:p.Arg383Ter
NP_861969.1:p.Arg383Ter
NP_861970.1:p.Arg466Ter
LRG_511t1:c.1396C>T
LRG_511t2:c.1396C>T
LRG_511:g.76336C>T
LRG_511p1:p.Arg466Ter
LRG_511p2:p.Arg466Ter
NC_000022.10:g.30070880C>T
NM_000268.3:c.1396C>T
NM_000268.4:c.1396C>T
NR_156186.2:n.1878C>T

Protein change:

R383*; ARG466TER

Links:

OMIM: 607379.0014; dbSNP: rs74315504

NCBI 1000 Genomes Browser:

rs74315504

Molecular consequence:

NM_181833.3:c.448-19861C>T - intron variant - [Sequence Ontology: SO:0001627]
NR_156186.2:n.1878C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000268.4:c.1396C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_016418.5:c.1396C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_181825.3:c.1396C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_181828.3:c.1270C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_181829.3:c.1273C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_181830.3:c.1147C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_181831.3:c.1147C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_181832.3:c.1396C>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

Clear Turn Off Turn On

Clinical Review Report: Migalastat (Galafold)
Clinical Review Report: Migalastat (Galafold)

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000023614	OMIM	no assertion criteria provided	Pathogenic (Aug 1, 1994)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000753832	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 21, 2022)	germline	clinical testing	PubMed (10) [See all records that cite these PMIDs] 7913580, 8012353, 12566519, 18033041, 18766994, 24815379, 26066488, 9643284, 16983642, 28492532
SCV000782127	Center for Human Genetics, Inc, Center for Human Genetics, Inc	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 1, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002045427	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 7, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutational analysis of patients with neurofibromatosis 2.

MacCollin M, Ramesh V, Jacoby LB, Louis DN, Rubio MP, Pulaski K, Trofatter JA, Short MP, Bove C, Eldridge R, et al.

Am J Hum Genet. 1994 Aug;55(2):314-20.

PubMed [citation]

PMID:: 7913580
PMCID:: PMC1918355

Exon scanning for mutation of the NF2 gene in schwannomas.

Jacoby LB, MacCollin M, Louis DN, Mohney T, Rubio MP, Pulaski K, Trofatter JA, Kley N, Seizinger B, Ramesh V, et al.

Hum Mol Genet. 1994 Mar;3(3):413-9.

PubMed [citation]

PMID:: 8012353

See all PubMed Citations (11)

Details of each submission

From OMIM, SCV000023614.2

#	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 with neurofibromatosis type II (SWNV; 101000), MacCollin et al. (1994) identified a C-to-T substitution at nucleotide 1396 in exon 13, resulting in a stop codon at position 466.

#	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, SCV000753832.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (10)

Description

ClinVar contains an entry for this variant (Variation ID: 3295). For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with neurofibromatosis type 2 (PMID: 7913580, 8012353, 12566519, 18033041, 18766994, 24815379, 26066488). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg466*) 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

From Center for Human Genetics, Inc, Center for Human Genetics, Inc, SCV000782127.1

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

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

From Genome-Nilou Lab, SCV002045427.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine