NM_000268.4(NF2):c.359T>C (p.Leu120Ser) AND Neurofibromatosis, type 2

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Aug 15, 2023
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:: RCV003067776.5

Allele description [Variation Report for NM_000268.4(NF2):c.359T>C (p.Leu120Ser)]

NM_000268.4(NF2):c.359T>C (p.Leu120Ser)

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.359T>C (p.Leu120Ser)

HGVS:

NC_000022.11:g.29639208T>C
NG_009057.1:g.40653T>C
NM_000268.4:c.359T>CMANE SELECT
NM_001407053.1:c.245T>C
NM_001407055.1:c.233T>C
NM_001407056.1:c.245T>C
NM_001407057.1:c.359T>C
NM_001407059.1:c.359T>C
NM_001407060.1:c.359T>C
NM_001407065.1:c.-282T>C
NM_001407066.1:c.359T>C
NM_001407067.1:c.128T>C
NM_016418.5:c.359T>C
NM_181825.3:c.359T>C
NM_181828.3:c.233T>C
NM_181829.3:c.240+2332T>C
NM_181830.3:c.115-2994T>C
NM_181831.3:c.115-2994T>C
NM_181832.3:c.359T>C
NM_181833.3:c.359T>C
NP_000259.1:p.Leu120Ser
NP_000259.1:p.Leu120Ser
NP_001393982.1:p.Leu82Ser
NP_001393984.1:p.Leu78Ser
NP_001393985.1:p.Leu82Ser
NP_001393986.1:p.Leu120Ser
NP_001393988.1:p.Leu120Ser
NP_001393989.1:p.Leu120Ser
NP_001393995.1:p.Leu120Ser
NP_001393996.1:p.Leu43Ser
NP_057502.2:p.Leu120Ser
NP_861546.1:p.Leu120Ser
NP_861966.1:p.Leu78Ser
NP_861970.1:p.Leu120Ser
NP_861971.1:p.Leu120Ser
LRG_511t1:c.359T>C
LRG_511t2:c.359T>C
LRG_511:g.40653T>C
LRG_511p1:p.Leu120Ser
LRG_511p2:p.Leu120Ser
NC_000022.10:g.30035197T>C
NM_000268.3:c.359T>C
NR_156186.2:n.841T>C

Protein change:

L120S

Molecular consequence:

NM_181829.3:c.240+2332T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_181830.3:c.115-2994T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_181831.3:c.115-2994T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000268.4:c.359T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407053.1:c.245T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407055.1:c.233T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407056.1:c.245T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407057.1:c.359T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407059.1:c.359T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407060.1:c.359T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407066.1:c.359T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407067.1:c.128T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_016418.5:c.359T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_181825.3:c.359T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_181828.3:c.233T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_181832.3:c.359T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_181833.3:c.359T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_156186.2:n.841T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

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

PREDICTED: Homo sapiens regulator of G protein signaling 11 (RGS11), transcript ...
PREDICTED: Homo sapiens regulator of G protein signaling 11 (RGS11), transcript variant X2, mRNA
gi|2217307995|ref|XM_011522720.3|

Nucleotide

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
SCV003460202	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 30, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004829781	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Aug 15, 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

SCV003460202

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 30, 2023)

germline

clinical testing

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

SCV004829781

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(Aug 15, 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	1	not provided	not provided	108544	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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003460202.2

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

Description

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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt NF2 protein function. ClinVar contains an entry for this variant (Variation ID: 2150849). This variant has not been reported in the literature in individuals affected with NF2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 120 of the NF2 protein (p.Leu120Ser).

#	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 All of Us Research Program, National Institutes of Health, SCV004829781.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	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	unknown	108544	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Oct 26, 2024

ClinVar

Relating variation to medicine