VCV001808721.1 - ClinVar

GRCh37/hg19 8p23.3-23.1(chr8:158049-10965627)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 8p23.3-23.1(chr8:158049-10965627)x1

Variation ID: 1808721 Accession: VCV001808721.1

Type and length

copy number loss, -

Location

Cytogenetic: 8p23.3-23.1 8: 158049-10965627 (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 31, 2022	Dec 31, 2022	Jun 28, 2022

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.
CSMD1		Little evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	518	830
DLGAP2		No evidence available	No evidence available	GRCh38 GRCh38 GRCh38 GRCh38 GRCh38 GRCh38 GRCh37	110	289
MFHAS1		No evidence available	No evidence available	GRCh38 GRCh38 GRCh37	105	242
AGPAT5		-	-	GRCh38 GRCh38 GRCh37	23	150
ANGPT2		-	-	GRCh38 GRCh37	-	238
ARHGEF10		-	-	GRCh38 GRCh38 GRCh37	712	901
C8orf74	-	-	-	GRCh38 GRCh38 GRCh37	5	131
CLDN23		-	-	GRCh38 GRCh38 GRCh37	30	162
CLN8		-	-	GRCh38 GRCh38 GRCh37	543	705
DEFA1		-	-	GRCh38 GRCh38 GRCh37	-	107

There are 45 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	Jun 28, 2022	RCV002474566.1

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 (Jun 28, 2022)	criteria provided, single submitter (ACMG/ClinGen CNV Guidelines, 2019) Method: clinical testing	not provided Affected status: unknown Allele origin: unknown	Quest Diagnostics Nichols Institute San Juan Capistrano Accession: SCV002771962.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022	Comment: The copy number loss of 8p23.3p23.1 involves numerous protein-coding genes, five of which are associated with phenotypes in OMIM. Smaller copy number losses, fully contained … (more) The copy number loss of 8p23.3p23.1 involves numerous protein-coding genes, five of which are associated with phenotypes in OMIM. Smaller copy number losses, fully contained within the current interval, have been identified in individuals with developmental delay, intellectual disability, neurobehavioral disorders, and/or craniofacial abnormalities (Burnside 2013, Shi 2017). Additionally, larger, overlapping deletions extending proximal to the current interval have been associated with the recurrent 8p23.1 deletion syndrome. 8p23.1 deletion syndrome is characterized by developmental impairments, intellectual disability, microcephaly, congenital heart disease, diaphragmatic hernia, hypospadias, and behavioral abnormalities (Ballarati 2011, Priest 2016, Shimokawa 2005). Of note, GATA4 (OMIM 600576) and NEIL2 (OMIM 608933), genes which are the candidate genes for cardiac defects and congenital diaphragmatic hernia, are not within the present interval (Keitges 2013). While hemizygous deletions of this specific interval have not yet been associated with a clinical phenotype, there are no similar copy number losses of this region in the general populations of the Database of Genomic Variants. Thus, based on current medical literature and gene content, this copy number variant (CNV) is classified as pathogenic. References: Ballarati et al., Eur J Med Genet. Jan-Feb 2011;54(1):55-9. PMID: 20969981 Burnside et al., Am J Med Genet A. 2013 Apr;161A(4):822-8. PMID: 23495222 Keitges et al., Am J Med Genet A. 2013 Jul;161A(7):1755-8. PMID: 23696316 Priest et al., PLoS Genet. 2016 Apr 8;12(4):e1005963. PMID: 27058611 Shi et al., Mol Med Rep. 2017 Nov;16(5):6837-6845. PMID: 28901431 Shimokawa et al., Am J Med Genet A. 2005 Jul 1;136(1):49-51. PMID: 15937941 (less)

Comment:

The copy number loss of 8p23.3p23.1 involves numerous protein-coding genes, five of which are associated with phenotypes in OMIM. Smaller copy number losses, fully contained within the current interval, have been identified in individuals with developmental delay, intellectual disability, neurobehavioral disorders, and/or craniofacial abnormalities (Burnside 2013, Shi 2017). Additionally, larger, overlapping deletions extending proximal to the current interval have been associated with the recurrent 8p23.1 deletion syndrome. 8p23.1 deletion syndrome is characterized by developmental impairments, intellectual disability, microcephaly, congenital heart disease, diaphragmatic hernia, hypospadias, and behavioral abnormalities (Ballarati 2011, Priest 2016, Shimokawa 2005). Of note, GATA4 (OMIM 600576) and NEIL2 (OMIM 608933), genes which are the candidate genes for cardiac defects and congenital diaphragmatic hernia, are not within the present interval (Keitges 2013). While hemizygous deletions of this specific interval have not yet been associated with a clinical phenotype, there are no similar copy number losses of this region in the general populations of the Database of Genomic Variants. Thus, based on current medical literature and gene content, this copy number variant (CNV) is classified as pathogenic. References: Ballarati et al., Eur J Med Genet. Jan-Feb 2011;54(1):55-9. PMID: 20969981 Burnside et al., Am J Med Genet A. 2013 Apr;161A(4):822-8. PMID: 23495222 Keitges et al., Am J Med Genet A. 2013 Jul;161A(7):1755-8. PMID: 23696316 Priest et al., PLoS Genet. 2016 Apr 8;12(4):e1005963. PMID: 27058611 Shi et al., Mol Med Rep. 2017 Nov;16(5):6837-6845. PMID: 28901431 Shimokawa et al., Am J Med Genet A. 2005 Jul 1;136(1):49-51. PMID: 15937941

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 8p23.3-23.1(chr8:158049-10965627)x1

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...