VCV000980153.2 - ClinVar

GRCh37/hg19 17q11.2(chr17:29039844-30412788)x1

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

GRCh37/hg19 17q11.2(chr17:29039844-30412788)x1

Variation ID: 980153 Accession: VCV000980153.2

Type and length

copy number loss, 1,372,945 bp

Location

Cytogenetic: 17q11.2 17: 29039844-30412788 (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 13, 2022	Feb 13, 2022	Mar 1, 2021

HGVS

Nucleotide	Protein	Molecular consequence
NC_000017.10:g.(?_29039844)_(30412788_?)del

Protein change

Other names

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

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.
NF1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh38 GRCh37	14135	14574
RNF135		No evidence available	No evidence available	GRCh38 GRCh38 GRCh37	91	153
SUZ12		No evidence available	No evidence available	GRCh38 GRCh37	133	182
ADAP2		-	-	GRCh38 GRCh38 GRCh37	25	87
ATAD5		-	-	GRCh38 GRCh37	132	193
COPRS	-	-	-	GRCh38 GRCh37	7	62
CRLF3		-	-	GRCh38 GRCh37	17	76
EVI2A		-	-	GRCh38 GRCh38 GRCh37	-	150
EVI2B		-	-	GRCh38 GRCh38 GRCh37	-	168
LRRC37B		-	-	GRCh38 GRCh37	70	108

There are 5 more genes affected by this variant. See the full set of genes in Variation Viewer (GRCh37) and ClinGen Dosage Sensitivity Map.

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.
not provided	Pathogenic (1)	no assertion criteria provided	Mar 1, 2021	RCV001259329.2

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 (Mar 01, 2021)	no assertion criteria provided Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Quest Diagnostics Nichols Institute San Juan Capistrano Accession: SCV001436298.2 First in ClinVar: Oct 07, 2020 Last updated: Feb 13, 2022	Comment: This deletion interval involves a number of OMIM/RefSeq annotated genes including NF1 and RNF135 and is expected to cause phenotypic and developmental abnormalities. This deletion … (more) This deletion interval involves a number of OMIM/RefSeq annotated genes including NF1 and RNF135 and is expected to cause phenotypic and developmental abnormalities. This deletion is consistent with the NF1 microdeletion syndrome or 17q11.2 deletion syndrome (OMIM 613675). Approximately 5 to 20% of all patients with neurofibromatosis type I carry a hemizygous deletion of approximately 1.4 Mb involving the NF1 gene and additional genes in its flanking regions. This syndrome is often characterized by a more severe phenotype than that observed in the majority of NF1 patients. In particular, patients with NF1 microdeletion often show variable facial dysmorphism, intellectual disability, developmental delay, an excessive number of early-onset neurofibromas, and an increased risk for malignant peripheral nerve sheath tumors. Loss of the RNF135 gene has been implicated in the overgrowth phenotype (OMIM 614192 ; characterized by increased postnatal height and weight, macrocephaly, variable learning disability, and dysmorphic facial features) that is part of this contiguous gene deletion syndrome. (less)

Comment:

This deletion interval involves a number of OMIM/RefSeq annotated genes including NF1 and RNF135 and is expected to cause phenotypic and developmental abnormalities. This deletion is consistent with the NF1 microdeletion syndrome or 17q11.2 deletion syndrome (OMIM 613675). Approximately 5 to 20% of all patients with neurofibromatosis type I carry a hemizygous deletion of approximately 1.4 Mb involving the NF1 gene and additional genes in its flanking regions. This syndrome is often characterized by a more severe phenotype than that observed in the majority of NF1 patients. In particular, patients with NF1 microdeletion often show variable facial dysmorphism, intellectual disability, developmental delay, an excessive number of early-onset neurofibromas, and an increased risk for malignant peripheral nerve sheath tumors. Loss of the RNF135 gene has been implicated in the overgrowth phenotype (OMIM 614192 ; characterized by increased postnatal height and weight, macrocephaly, variable learning disability, and dysmorphic facial features) that is part of this contiguous gene deletion syndrome.

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 Mar 26, 2023

ClinVar Genomic variation as it relates to human health

GRCh37/hg19 17q11.2(chr17:29039844-30412788)x1

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...