VCV002692679.1 - ClinVar

NM_000268.4(NF2):c.16_17delinsTT (p.Ala6Phe)

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.

Uncertain significance

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.16_17delinsTT (p.Ala6Phe)

Variation ID: 2692679 Accession: VCV002692679.1

Type and length

Indel, 2 bp

Location

Cytogenetic: 22q12.2 22: 29604014-29604015 (GRCh38) [ NCBI UCSC ] 22: 30000003-30000004 (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 14, 2024	Feb 14, 2024	Nov 3, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_000268.4:c.16_17delinsTT MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000259.1:p.Ala6Phe	missense
NM_001407053.1:c.-215_-214delinsTT		5 prime UTR
NM_001407054.1:c.16_17delinsTT	NP_001393983.1:p.Ala6Phe	missense
NM_001407055.1:c.16_17delinsTT	NP_001393984.1:p.Ala6Phe	missense
NM_001407056.1:c.-215_-214delinsTT		5 prime UTR
NM_001407057.1:c.16_17delinsTT	NP_001393986.1:p.Ala6Phe	missense
NM_001407058.1:c.16_17delinsTT	NP_001393987.1:p.Ala6Phe	missense
NM_001407059.1:c.16_17delinsTT	NP_001393988.1:p.Ala6Phe	missense
NM_001407060.1:c.16_17delinsTT	NP_001393989.1:p.Ala6Phe	missense
NM_001407062.1:c.16_17delinsTT	NP_001393991.1:p.Ala6Phe	missense
NM_001407063.1:c.16_17delinsTT	NP_001393992.1:p.Ala6Phe	missense
NM_001407064.1:c.16_17delinsTT	NP_001393993.1:p.Ala6Phe	missense
NM_001407065.1:c.-625_-624delinsTT		5 prime UTR
NM_001407066.1:c.16_17delinsTT	NP_001393995.1:p.Ala6Phe	missense
NM_001407067.1:c.-241_-240delinsTT		5 prime UTR
NM_016418.5:c.16_17delinsTT	NP_057502.2:p.Ala6Phe	missense
NM_181825.3:c.16_17delinsTT	NP_861546.1:p.Ala6Phe	missense
NM_181828.3:c.16_17delinsTT	NP_861966.1:p.Ala6Phe	missense
NM_181829.3:c.16_17delinsTT	NP_861967.1:p.Ala6Phe	missense
NM_181830.3:c.16_17delinsTT	NP_861968.1:p.Ala6Phe	missense
NM_181831.3:c.16_17delinsTT	NP_861969.1:p.Ala6Phe	missense
NM_181832.3:c.16_17delinsTT	NP_861970.1:p.Ala6Phe	missense
NM_181833.3:c.16_17delinsTT	NP_861971.1:p.Ala6Phe	missense
NR_156186.2:n.382_383delGCinsTT
NR_176267.1:n.382_383delinsTT		non-coding transcript variant
NC_000022.11:g.29604014_29604015delinsTT
NC_000022.10:g.30000003_30000004delinsTT
NG_009057.1:g.5459_5460delinsTT
NG_201599.1:g.716_717delinsTT
LRG_511:g.5459_5460delinsTT
LRG_511t1:c.16_17delGCinsTT	LRG_511p1:p.Ala6Phe
LRG_511t2:c.16_17delinsTT	LRG_511p2:p.Ala6Phe

... more HGVS ... less HGVS

Protein change

A6F

Other names

Canonical SPDI

NC_000022.11:29604013:GC:TT

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	Uncertain significance (1)	criteria provided, single submitter	Nov 3, 2023	RCV003500870.3

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.
Uncertain significance (Nov 03, 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: SCV004245756.1 First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024	Comment: This variant, c.16_17delinsTT, is a complex sequence change that results in the deletion of 1 and insertion of 1 amino acid(s) in the NF2 protein … (more) This variant, c.16_17delinsTT, is a complex sequence change that results in the deletion of 1 and insertion of 1 amino acid(s) in the NF2 protein (p.Ala6Phe). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This variant has not been reported in the literature in individuals affected with NF2-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. 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. (less)

Comment:

This variant, c.16_17delinsTT, is a complex sequence change that results in the deletion of 1 and insertion of 1 amino acid(s) in the NF2 protein (p.Ala6Phe). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This variant has not been reported in the literature in individuals affected with NF2-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. 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.

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

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

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.16_17delinsTT (p.Ala6Phe)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...