VCV001180505.4 - ClinVar

GRCh37/hg19 15q26.1-26.3(chr15:92335751-102399741)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 15q26.1-26.3(chr15:92335751-102399741)x1

Variation ID: 1180505 Accession: VCV001180505.4

Type and length

copy number loss, 10,063,991 bp

Location

Cytogenetic: 15q26.1-26.3 15: 92335751-102399741 (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 20, 2019

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.
CHD2		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	2085	2199
IGF1R		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	1025	1171
NR2F2		No evidence available	No evidence available	GRCh38 GRCh37	123	182
ADAMTS17		-	-	GRCh38 GRCh37	1211	1325
ALDH1A3		-	-	GRCh38 GRCh37	36	227
ARRDC4		-	-	GRCh38 GRCh37	30	99
ASB7		-	-	GRCh38 GRCh37	14	111
C15orf32	-	-	-	GRCh38 GRCh37	-	39
CERS3		-	-	GRCh38 GRCh37	85	203
CHSY1		-	-	GRCh38 GRCh37	190	332

There are 21 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 20, 2019	RCV001537887.4

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 20, 2019)	criteria provided, single submitter (ICSL CNVClassificationCriteria Jul2020Prior) Method: clinical testing	not provided Affected status: unknown Allele origin: unknown	Illumina Laboratory Services, Illumina Accession: SCV001754815.1 First in ClinVar: Jul 24, 2021 Last updated: Jul 24, 2021	Publications: PubMed (7) PubMed: 21242650‚ 22065603‚ 23603061‚ 25691414‚ 25924833‚ 27826649‚ 29142763 Comment: This CNV is a 10 Mb deletion of 15q26.1-q26.3, on chromosome 15, (seq[GRCh37]del(15)(q26.1q26.3); chr15:g.92335751-102399741del), found in a de novo state. This CNV constitutes a loss … (more) This CNV is a 10 Mb deletion of 15q26.1-q26.3, on chromosome 15, (seq[GRCh37]del(15)(q26.1q26.3); chr15:g.92335751-102399741del), found in a de novo state. This CNV constitutes a loss encompassing at least 70 genes and overlaps the 15q26 terminal deletion syndrome. The loss includes deletion of the IGF1R gene, which has been proposed as a candidate gene for several of the phenotypes associated with terminal deletions of 15q26 (O'Riordan et al. 2016). Growth hormone therapy in individuals affected with growth hormone resistance due to terminal 15q26 deletion has resulted in a moderate to dramatic response (Ho et al. 2015; Mahmoud et al. 2017). This CNV has not been reported in controls. Based on the collective evidence, this CNV is classified as pathogenic. (less)

Comment:

This CNV is a 10 Mb deletion of 15q26.1-q26.3, on chromosome 15, (seq[GRCh37]del(15)(q26.1q26.3); chr15:g.92335751-102399741del), found in a de novo state. This CNV constitutes a loss encompassing at least 70 genes and overlaps the 15q26 terminal deletion syndrome. The loss includes deletion of the IGF1R gene, which has been proposed as a candidate gene for several of the phenotypes associated with terminal deletions of 15q26 (O'Riordan et al. 2016). Growth hormone therapy in individuals affected with growth hormone resistance due to terminal 15q26 deletion has resulted in a moderate to dramatic response (Ho et al. 2015; Mahmoud et al. 2017). This CNV has not been reported in controls. 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
Array Characterization of Prenatally Diagnosed 15q26 Microdeletion and 2q37.1 Duplication: Report of a New Case with Multicystic Kidneys and Review of the Literature.	Kammoun M	Journal of pediatric genetics	2017	PMID: 29142763
Expanding the clinical spectrum of chromosome 15q26 terminal deletions associated with IGF-1 resistance.	O'Riordan AM	European journal of pediatrics	2017	PMID: 27826649
Recombinant Human Growth Hormone Therapy in Children with Chromosome 15q26 Deletion.	Ho SC	Hormone research in paediatrics	2015	PMID: 25924833
Recurrent enlarged nuchal translucency: first trimester presentation of a familial 15q26→qter deletion.	Reiss R	American journal of medical genetics. Part A	2015	PMID: 25691414
Variable behavioural phenotypes of patients with monosomies of 15q26 and a review of 16 cases.	Poot M	European journal of medical genetics	2013	PMID: 23603061
Short stature due to 15q26 microdeletion involving IGF1R: report of an additional case and review of the literature.	Rudaks LI	American journal of medical genetics. Part A	2011	PMID: 22065603
Identification of chromosome 15q26 terminal deletion with telomere sequences and its bearing on genotype-phenotype analysis.	Dateki S	Endocrine journal	2011	PMID: 21242650

Text-mined citations for this variant ...

Record last updated Apr 09, 2023

ClinVar Genomic variation as it relates to human health

GRCh37/hg19 15q26.1-26.3(chr15:92335751-102399741)x1

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...