VCV000000360.1 - ClinVar

NC_000017.11:g.(?_31094927)_(31377677_?)del

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

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NC_000017.11:g.(?_31094927)_(31377677_?)del

Variation ID: 360 Accession: VCV000000360.1

Type and length

Deletion, 282,751 bp

Location

Cytogenetic: 17q11.2 17: 31094927-31377677 (GRCh38) [ 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	Aug 21, 2015	Aug 21, 2015	Jan 1, 2003

HGVS

Nucleotide	Protein	Molecular consequence
NC_000017.11:(?_31094927)_(31377677_?)del
NC_000017.11:g.(?_31094927)_(31377677_?)del

Protein change

Other names

NF1, DEL
DEL

Canonical SPDI

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

OMIM: 613113.0030 VarSome

Comment on variant

NCBI staff provided an HGVS expression for allelic variant 613113.0030 based on the description as a deletion including the complete gene. The location on GRCh38 (annotation release RS_2023_03) was used to define the boundary of the gene.

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.
NF1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh38 GRCh37	14121	14559
EVI2A		-	-	GRCh38 GRCh38 GRCh37	-	149
EVI2B		-	-	GRCh38 GRCh38 GRCh37	-	167
LOC108281169	-	-	-	GRCh38 GRCh38	-	30
LOC108281170	-	-	-	GRCh38 GRCh38	-	34
LOC108281180	-	-	-	GRCh38 GRCh38	-	36
LOC108281181	-	-	-	GRCh38 GRCh38	-	34
LOC108281182	-	-	-	GRCh38 GRCh38	-	37
LOC111811965	-	-	-	GRCh38 GRCh38	-	189
LOC125177454	-	-	-	GRCh38 GRCh38	-	31

There are 5 more genes affected by this variant. See the full set of genes in Variation Viewer (GRCh38).

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 1	Pathogenic (1)	no assertion criteria provided	Jan 1, 2003	RCV000000389.4

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 (Jan 01, 2003)	no assertion criteria provided Method: literature only	NEUROFIBROMATOSIS, TYPE I Affected status: not provided Allele origin: germline	OMIM Accession: SCV000020533.2 First in ClinVar: Apr 04, 2013 Last updated: Aug 21, 2015	Publications: PubMed (1) PubMed: 12483293 Comment on evidence: Upadhyaya et al. (2003) described a Portuguese family in which 3 members had clinical features of neurofibromatosis type I (NF1; 162200) and each had a … (more) Upadhyaya et al. (2003) described a Portuguese family in which 3 members had clinical features of neurofibromatosis type I (NF1; 162200) and each had a different underlying defect in the NF1 gene. A 12-year-old boy who had multiple cafe-au-lait spots on his trunk and legs as well as developmental delay had a heterozygous 1.5-Mb deletion including the entire NF1 gene. The mutation was associated with the maternally derived chromosomal haplotype. His 10-year-old brother, who exhibited multiple cafe-au-lait spots and macrocephaly but whose development was within the normal range, was heterozygous for a CGA-to-TGA transition in exon 22 of the NF1 gene, resulting in an arg1241-to-ter mutation (613113.0031). This mutation had previously been described; its recurrence was thought to have been mediated by 5-methylcytosine deamination because it occurred in a hypermutable CpG dinucleotide. The brothers' 26-year-old female first cousin once removed (a first cousin of their father) exhibited multiple cafe-au-lait spots, bilateral Lisch nodules, and multiple dermal neurofibromas. She also showed severe scoliosis and several plexiform neurofibromas in the clavicular region, but her development was within the normal range. She was found to carry a frameshift mutation, 5406insT (613113.0032), in exon 29 of the NF1 gene. None of the parents had any clinical evidence of NF1 and none had a mutation in the NF1 gene. There was also no evidence of mosaicism. Upadhyaya et al. (2003) speculated about the mechanism of this unusual situation. (less)

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.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Three different pathological lesions in the NF1 gene originating de novo in a family with neurofibromatosis type 1.	Upadhyaya M	Human genetics	2003	PMID: 12483293

Text-mined citations for this variant ...

Record last updated Apr 15, 2024

ClinVar Genomic variation as it relates to human health

NC_000017.11:g.(?_31094927)_(31377677_?)del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...