VCV001180531.4 - ClinVar

GRCh37/hg19 2p24.3-24.1(chr2:15640273-19609496)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

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

GRCh37/hg19 2p24.3-24.1(chr2:15640273-19609496)x1

Variation ID: 1180531 Accession: VCV001180531.4

Type and length

copy number loss, 3,969,224 bp

Location

Cytogenetic: 2p24.3-24.1 2: 15640273-19609496 (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	Jul 24, 2021	Jul 24, 2021	Feb 6, 2020

HGVS

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.
MYCN		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	165	264
GEN1		Dosage sensitivity unlikely	No evidence available	GRCh38 GRCh37	613	641
CYRIA	-	-	-	GRCh38 GRCh37	7	33
DDX1		-	-	GRCh38 GRCh37	36	72
KCNS3		-	-	GRCh38 GRCh37	37	61
MSGN1		-	-	GRCh38 GRCh37	17	41
MYCNOS		-	-	GRCh38 GRCh37	-	99
NBAS		-	-	GRCh38 GRCh37	2382	2463
NT5C1B		-	-	GRCh38 GRCh37	-	80
NT5C1B-RDH14	-	-	-	GRCh38 GRCh37	-	113

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)	criteria provided, single submitter	Feb 6, 2020	RCV001537913.4

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 (Feb 06, 2020)	criteria provided, single submitter (ICSL CNVClassificationCriteria Jul2020Prior) Method: clinical testing	not provided Affected status: unknown Allele origin: unknown	Illumina Laboratory Services, Illumina Accession: SCV001754841.1 First in ClinVar: Jul 24, 2021 Last updated: Jul 24, 2021	Publications: PubMed (7) PubMed: 18470948‚ 19344873‚ 21224895‚ 21841781‚ 22842076‚ 24174537‚ 26582918 Comment: This CNV is a 4.0 Mb deletion of 2p24.3-p24.1 on chromosome 2, (seq[GRCh37]del(2)(2p24.3p24.1); chr2:g.15640273_19609496del), found in a de novo state. This CNV constitutes a loss … (more) This CNV is a 4.0 Mb deletion of 2p24.3-p24.1 on chromosome 2, (seq[GRCh37]del(2)(2p24.3p24.1); chr2:g.15640273_19609496del), found in a de novo state. This CNV constitutes a loss affecting 22 genes, including complete loss of the MYCN gene and with one of the breakpoints lying within the NBAS gene. MYCN haploinsufficiency is associated with Feingold syndrome, and deletions of the MYCN resulting from CNVs that overlap the proband's have been reported in individuals with features of Feingold syndrome, including microcephaly, intellectual disability, hearing impairment, micrognathia, brachymesophalangy of the second and the fifth fingers, and clinodactyly of the fifth finger (Marcelis et al. 2008; Cognet et al. 2011; Chen et al. 2012). This CNV has not been previously reported in control or clinical populations (Firth et al. 2009; Cooper et al. 2011; MacDonald et al 2014; Landrum et al. 2016). Based on the collective evidence, this CNV is classified as pathogenic. (less)

Comment:

This CNV is a 4.0 Mb deletion of 2p24.3-p24.1 on chromosome 2, (seq[GRCh37]del(2)(2p24.3p24.1); chr2:g.15640273_19609496del), found in a de novo state. This CNV constitutes a loss affecting 22 genes, including complete loss of the MYCN gene and with one of the breakpoints lying within the NBAS gene. MYCN haploinsufficiency is associated with Feingold syndrome, and deletions of the MYCN resulting from CNVs that overlap the proband's have been reported in individuals with features of Feingold syndrome, including microcephaly, intellectual disability, hearing impairment, micrognathia, brachymesophalangy of the second and the fifth fingers, and clinodactyly of the fifth finger (Marcelis et al. 2008; Cognet et al. 2011; Chen et al. 2012). This CNV has not been previously reported in control or clinical populations (Firth et al. 2009; Cooper et al. 2011; MacDonald et al 2014; Landrum et al. 2016). Based on the collective evidence, this CNV is 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
ClinVar: public archive of interpretations of clinically relevant variants.	Landrum MJ	Nucleic acids research	2016	PMID: 26582918
The Database of Genomic Variants: a curated collection of structural variation in the human genome.	MacDonald JR	Nucleic acids research	2014	PMID: 24174537
A de novo 4.4-Mb microdeletion in 2p24.3 → p24.2 in a girl with bilateral hearing impairment, microcephaly, digit abnormalities and Feingold syndrome.	Chen CP	European journal of medical genetics	2012	PMID: 22842076
A copy number variation morbidity map of developmental delay.	Cooper GM	Nature genetics	2011	PMID: 21841781
Dissection of the MYCN locus in Feingold syndrome and isolated oesophageal atresia.	Cognet M	European journal of human genetics : EJHG	2011	PMID: 21224895
DECIPHER: Database of Chromosomal Imbalance and Phenotype in Humans Using Ensembl Resources.	Firth HV	American journal of human genetics	2009	PMID: 19344873
Genotype-phenotype correlations in MYCN-related Feingold syndrome.	Marcelis CL	Human mutation	2008	PMID: 18470948

Text-mined citations for this variant ...

Record last updated Apr 09, 2023

ClinVar Genomic variation as it relates to human health

GRCh37/hg19 2p24.3-24.1(chr2:15640273-19609496)x1

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...