VCV001328108.4 - ClinVar

GRCh37/hg19 10p11.23-11.22(chr10:30624523-33688350)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 10p11.23-11.22(chr10:30624523-33688350)x1

Variation ID: 1328108 Accession: VCV001328108.4

Type and length

copy number loss, 3,063,828 bp

Location

Cytogenetic: 10p11.23-11.22 10: 30624523-33688350 (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	Dec 18, 2021	Dec 18, 2021	Nov 2, 2021

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.
ARHGAP12		-	-	GRCh38 GRCh37	47	61
CCDC7		-	-	GRCh38 GRCh37	39	57
EPC1		-	-	GRCh38 GRCh37	30	46
ITGB1		-	-	GRCh38 GRCh37	42	58
KIF5B		-	-	GRCh38 GRCh37	45	64
LYZL2		-	-	GRCh38 GRCh37	17	32
MAP3K8		-	-	GRCh38 GRCh37	182	198
MTPAP		-	-	GRCh38 GRCh37	324	373
NRP1		-	-	GRCh38 GRCh37	253	284
ZEB1		-	-	GRCh38 GRCh37	130	148

There is 1 more gene affected by this variant. See the full set of genes in Variation Viewer (GRCh37).

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	Nov 2, 2021	RCV001795544.4

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 (Nov 02, 2021)	criteria provided, single submitter (ICSL CNVClassificationCriteria Aug2020) Method: clinical testing	Not provided Affected status: unknown Allele origin: unknown	Illumina Laboratory Services, Illumina Accession: SCV002034747.1 First in ClinVar: Dec 18, 2021 Last updated: Dec 18, 2021	Publications: PubMed (2) PubMed: 19344873‚ 28742278 Comment: This CNV is a 3.1 Mb deletion of 10p11.23-p11.22, on chromosome 10, (seq[GRCh37]del(10)(p11.23-p11.22); chr10:30624523_33688350del), found in a de novo state. This CNV constitutes a loss … (more) This CNV is a 3.1 Mb deletion of 10p11.23-p11.22, on chromosome 10, (seq[GRCh37]del(10)(p11.23-p11.22); chr10:30624523_33688350del), found in a de novo state. This CNV constitutes a loss encompassing 11 protein-coding genes. Chaudhry et al. (2017) reported on a patient with a de novo 2.05 Mb loss that is fully encompassed within this CNV in a proband who had agenesis of the corpus callosum, developmental delay, facial dysmorphism, autism spectrum disorder, and posterior polymorphous corneal dystrophy. There are two individuals in the DECIPHER database with similar de novo deletions in this region (Firth et al. 2009). The features reported in these individuals varies and includes developmental delay, intellectual disability, hypotonia, hypertelorism, strabismus, blepharophimosis, 5th finger clinodactyly, patent ductus arteriosus, and short stature. Based on the collective evidence, this CNV is classified as pathogenic. (less)

Comment:

This CNV is a 3.1 Mb deletion of 10p11.23-p11.22, on chromosome 10, (seq[GRCh37]del(10)(p11.23-p11.22); chr10:30624523_33688350del), found in a de novo state. This CNV constitutes a loss encompassing 11 protein-coding genes. Chaudhry et al. (2017) reported on a patient with a de novo 2.05 Mb loss that is fully encompassed within this CNV in a proband who had agenesis of the corpus callosum, developmental delay, facial dysmorphism, autism spectrum disorder, and posterior polymorphous corneal dystrophy. There are two individuals in the DECIPHER database with similar de novo deletions in this region (Firth et al. 2009). The features reported in these individuals varies and includes developmental delay, intellectual disability, hypotonia, hypertelorism, strabismus, blepharophimosis, 5th finger clinodactyly, patent ductus arteriosus, and short stature. 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
Agenesis of the corpus callosum, developmental delay, autism spectrum disorder, facial dysmorphism, and posterior polymorphous corneal dystrophy associated with ZEB1 gene deletion.	Chaudhry A	American journal of medical genetics. Part A	2017	PMID: 28742278
DECIPHER: Database of Chromosomal Imbalance and Phenotype in Humans Using Ensembl Resources.	Firth HV	American journal of human genetics	2009	PMID: 19344873

Text-mined citations for this variant ...

Record last updated Apr 09, 2023

ClinVar Genomic variation as it relates to human health

GRCh37/hg19 10p11.23-11.22(chr10:30624523-33688350)x1

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...