VCV002838602.1 - ClinVar

NM_000268.4(NF2):c.1514del (p.Leu505fs)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(1)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000268.4(NF2):c.1514del (p.Leu505fs)

Variation ID: 2838602 Accession: VCV002838602.1

Type and length

Deletion, 1 bp

Location

Cytogenetic: 22q12.2 22: 29678263 (GRCh38) [ NCBI UCSC ] 22: 30074252 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Feb 20, 2024	Feb 20, 2024	Feb 18, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_000268.4:c.1514del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000259.1:p.Leu505fs	frameshift
NM_001407053.1:c.1400del	NP_001393982.1:p.Leu467fs	frameshift
NM_001407054.1:c.1391del	NP_001393983.1:p.Leu464fs	frameshift
NM_001407055.1:c.1388del	NP_001393984.1:p.Leu463fs	frameshift
NM_001407056.1:c.1400del	NP_001393985.1:p.Leu467fs	frameshift
NM_001407057.1:c.1379del	NP_001393986.1:p.Leu460fs	frameshift
NM_001407058.1:c.1391del	NP_001393987.1:p.Leu464fs	frameshift
NM_001407059.1:c.1379del	NP_001393988.1:p.Leu460fs	frameshift
NM_001407060.1:c.1514del	NP_001393989.1:p.Leu505fs	frameshift
NM_001407062.1:c.1256del	NP_001393991.1:p.Leu419fs	frameshift
NM_001407063.1:c.1265del	NP_001393992.1:p.Leu422fs	frameshift
NM_001407064.1:c.1265del	NP_001393993.1:p.Leu422fs	frameshift
NM_001407065.1:c.980del	NP_001393994.1:p.Leu327fs	frameshift
NM_001407066.1:c.1514del	NP_001393995.1:p.Leu505fs	frameshift
NM_001407067.1:c.1283del	NP_001393996.1:p.Leu428fs	frameshift
NM_016418.5:c.1514del	NP_057502.2:p.Leu505fs	frameshift
NM_181825.3:c.1514del	NP_861546.1:p.Leu505fs	frameshift
NM_181828.3:c.1388del	NP_861966.1:p.Leu463fs	frameshift
NM_181829.3:c.1391del	NP_861967.1:p.Leu464fs	frameshift
NM_181830.3:c.1265del	NP_861968.1:p.Leu422fs	frameshift
NM_181831.3:c.1265del	NP_861969.1:p.Leu422fs	frameshift
NM_181832.3:c.1514del	NP_861970.1:p.Leu505fs	frameshift
NM_181833.3:c.448-16489del		intron variant
NR_156186.2:n.1996delT
NR_176267.1:n.1062del		non-coding transcript variant
NC_000022.11:g.29678263del
NC_000022.10:g.30074252del
NG_009057.1:g.79708del
LRG_511:g.79708del
LRG_511t1:c.1514del	LRG_511p1:p.Leu505Argfs
LRG_511t2:c.1514del	LRG_511p2:p.Leu505fs

... more HGVS ... less HGVS

Protein change

L460fs, L467fs, L428fs, L463fs, L327fs, L419fs, L422fs, L464fs, L505fs

Other names

Canonical SPDI

NC_000022.11:29678262:T:

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
NF2		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	2084	2132

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Neurofibromatosis, type 2	Pathogenic (1)	criteria provided, single submitter	Feb 18, 2023	RCV003608147.2

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Feb 18, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Neurofibromatosis, type 2 Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV004434755.1 First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024	Publications: PubMed (2) PubMed: 9643284‚ 16983642 Comment: This sequence change creates a premature translational stop signal (p.Leu505Argfs10) in the NF2 gene. It is expected to result in an absent or disrupted protein … (more) This sequence change creates a premature translational stop signal (p.Leu505Argfs10) 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NF2-related conditions. For these reasons, this variant has been classified as Pathogenic. (less)

Comment:

This sequence change creates a premature translational stop signal (p.Leu505Argfs*10) 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NF2-related conditions. For these reasons, this variant has been classified as Pathogenic.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Mutational spectrum of the NF2 gene: a meta-analysis of 12 years of research and diagnostic laboratory findings.	Ahronowitz I	Human mutation	2007	PMID: 16983642
Genotype/phenotype correlations in type 2 neurofibromatosis (NF2): evidence for more severe disease associated with truncating mutations.	Evans DG	Journal of medical genetics	1998	PMID: 9643284

Text-mined citations for this variant ...

Record last updated Sep 30, 2024

ClinVar Genomic variation as it relates to human health

NM_000268.4(NF2):c.1514del (p.Leu505fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...