NM_000268.4(NF2):c.15C>G (p.Ile5Met) AND Neurofibromatosis, type 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 13, 2023
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:: RCV000797514.8

Allele description [Variation Report for NM_000268.4(NF2):c.15C>G (p.Ile5Met)]

NM_000268.4(NF2):c.15C>G (p.Ile5Met)

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.15C>G (p.Ile5Met)

HGVS:

NC_000022.11:g.29604013C>G
NG_009057.1:g.5458C>G
NM_000268.4:c.15C>GMANE SELECT
NM_016418.5:c.15C>G
NM_181825.3:c.15C>G
NM_181828.3:c.15C>G
NM_181829.3:c.15C>G
NM_181830.3:c.15C>G
NM_181831.3:c.15C>G
NM_181832.3:c.15C>G
NM_181833.3:c.15C>G
NP_000259.1:p.Ile5Met
NP_000259.1:p.Ile5Met
NP_057502.2:p.Ile5Met
NP_861546.1:p.Ile5Met
NP_861966.1:p.Ile5Met
NP_861967.1:p.Ile5Met
NP_861968.1:p.Ile5Met
NP_861969.1:p.Ile5Met
NP_861970.1:p.Ile5Met
NP_861971.1:p.Ile5Met
LRG_511t1:c.15C>G
LRG_511t2:c.15C>G
LRG_511:g.5458C>G
LRG_511p1:p.Ile5Met
LRG_511p2:p.Ile5Met
NC_000022.10:g.30000002C>G
NM_000268.3:c.15C>G
NR_156186.2:n.381C>G

Protein change:

I5M

Links:

dbSNP: rs998779035

NCBI 1000 Genomes Browser:

rs998779035

Molecular consequence:

NM_000268.4:c.15C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_016418.5:c.15C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_181825.3:c.15C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_181828.3:c.15C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_181829.3:c.15C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_181830.3:c.15C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_181831.3:c.15C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_181832.3:c.15C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_181833.3:c.15C>G - missense variant - [Sequence Ontology: SO:0001583]
NR_156186.2:n.381C>G - 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
SCV000937074	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 13, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000937074

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 13, 2023)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000937074.6

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

Description

The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 643742). This variant has not been reported in the literature in individuals affected with NF2-related conditions. This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 5 of the NF2 protein (p.Ile5Met).

#	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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