NM_000268.4(NF2):c.599+1G>A AND Neurofibromatosis, type 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 7, 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:: RCV001947008.4

Allele description [Variation Report for NM_000268.4(NF2):c.599+1G>A]

NM_000268.4(NF2):c.599+1G>A

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.599+1G>A

HGVS:

NC_000022.11:g.29655677G>A
NG_009057.1:g.57122G>A
NM_000268.4:c.599+1G>AMANE SELECT
NM_001407053.1:c.485+1G>A
NM_001407054.1:c.476+1G>A
NM_001407055.1:c.473+1G>A
NM_001407056.1:c.485+1G>A
NM_001407057.1:c.599+1G>A
NM_001407058.1:c.476+1G>A
NM_001407059.1:c.599+1G>A
NM_001407060.1:c.599+1G>A
NM_001407062.1:c.476+1G>A
NM_001407063.1:c.350+1G>A
NM_001407064.1:c.350+1G>A
NM_001407065.1:c.65+1G>A
NM_001407066.1:c.599+1G>A
NM_001407067.1:c.368+1G>A
NM_016418.5:c.599+1G>A
NM_181825.3:c.599+1G>A
NM_181828.3:c.473+1G>A
NM_181829.3:c.476+1G>A
NM_181830.3:c.350+1G>A
NM_181831.3:c.350+1G>A
NM_181832.3:c.599+1G>A
NM_181833.3:c.447+13392G>A
LRG_511t1:c.599+1G>A
LRG_511t2:c.599+1G>A
LRG_511:g.57122G>A
NC_000022.10:g.30051666G>A
NM_000268.3:c.599+1G>A

Links:

dbSNP: rs1555993352

NCBI 1000 Genomes Browser:

rs1555993352

Molecular consequence:

NM_181833.3:c.447+13392G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000268.4:c.599+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407053.1:c.485+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407054.1:c.476+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407055.1:c.473+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407056.1:c.485+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407057.1:c.599+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407058.1:c.476+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407059.1:c.599+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407060.1:c.599+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407062.1:c.476+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407063.1:c.350+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407064.1:c.350+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407065.1:c.65+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407066.1:c.599+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407067.1:c.368+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_016418.5:c.599+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_181825.3:c.599+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_181828.3:c.473+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_181829.3:c.476+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_181830.3:c.350+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_181831.3:c.350+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_181832.3:c.599+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

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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PREDICTED: Homo sapiens G protein-coupled receptor kinase 2 (GRK2), transcript v...
PREDICTED: Homo sapiens G protein-coupled receptor kinase 2 (GRK2), transcript variant X1, mRNA
gi|2462523232|ref|XM_054367819.1|

Nucleotide
Klebsiella pneumoniae strain:RDZ41
Klebsiella pneumoniae strain:RDZ41
Klebsiella pneumoniae strain:RDZ41 Genome sequencing

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002245774	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 7, 2021)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 7759081, 16199547, 9643284, 16983642, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002245774

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 7, 2021)

germline

clinical testing

PubMed (5)
[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

Eleven novel mutations in the NF2 tumour suppressor gene.

Bourn D, Evans G, Mason S, Tekes S, Trueman L, Strachan T.

Hum Genet. 1995 May;95(5):572-4.

PubMed [citation]

PMID:: 7759081

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002245774.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant is also known as AGgt -> AGat599 +1. Disruption of this splice site has been observed in individuals with clinical features of NF2-related conditions (PMID: 7759081, 16983642; Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 6 of the NF2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and 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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