VCV002684522.1 - ClinVar

GRCh37/hg19 8p23.1-22(chr8:8093169-14526969)x3

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 8p23.1-22(chr8:8093169-14526969)x3

Variation ID: 2684522 Accession: VCV002684522.1

Type and length

copy number gain, -

Location

Cytogenetic: 8p23.1-22 8: 8093169-14526969 (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	Jan 26, 2024	Jan 26, 2024	Jun 14, 2023

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.
GATA4		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh38 GRCh37	808	931
CTSB		No evidence available	No evidence available	GRCh38 GRCh38 GRCh37	116	254
MFHAS1		No evidence available	No evidence available	GRCh38 GRCh38 GRCh37	105	242
BLK		-	-	GRCh38 GRCh38 GRCh37	299	475
C8orf48	-	-	-	GRCh38 GRCh37	1	113
C8orf74	-	-	-	GRCh38 GRCh38 GRCh37	5	131
CLDN23		-	-	GRCh38 GRCh38 GRCh37	30	162
DEFB130A	-	-	-	GRCh38 GRCh38 GRCh37	-	67
DEFB134	-	-	-	GRCh38 GRCh38 GRCh37	9	114
DEFB135	-	-	-	GRCh38 GRCh38 GRCh37	17	127

There are 26 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 14, 2023	RCV003484718.1

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 14, 2023)	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: SCV004230579.1 First in ClinVar: Jan 26, 2024 Last updated: Jan 26, 2024	Comment: The gain of 8p23.1p22 involves several protein-coding genes and fully encompasses the recurrent region involved in 8p23.1 duplication syndrome, which is associated with a variable … (more) The gain of 8p23.1p22 involves several protein-coding genes and fully encompasses the recurrent region involved in 8p23.1 duplication syndrome, which is associated with a variable clinical presentation (Barber 2015, Okur 2021, Rehm 2015, Weber 2014, Yu 2010). The phenotypic features of this syndrome are proposed to be related to additional copies of the candidate genes SOX7 (OMIM 612202) and GATA4 (Barber 2015, Zhang 2013). Therefore, based on gene content and current medical literature, this copy number variant (CNV) is classified as pathogenic with variable expressivity. _x000D__x000D_ References: Barber et al., Am J Med Genet A. 2015 Sep;167A(9):2052-64. PMID: 26097203 Okur et al., Genet Med. 2021 Dec;23(12):2342-2351. PMID: 34282301 Rehm et al., N Engl J Med. 2015 Jun 4;372(23):2235-42. PMID: 26014595; ISCA-37423 Weber et al., Mol Cytogenet. 2014 Dec 9;7(1):94. PMID: 25520754 Yu et al., Eur J Hum Genet. 2010 Oct;18(10):1114-20. PMID: 20461109_x000D__x000D_ (less)

Comment:

The gain of 8p23.1p22 involves several protein-coding genes and fully encompasses the recurrent region involved in 8p23.1 duplication syndrome, which is associated with a variable clinical presentation (Barber 2015, Okur 2021, Rehm 2015, Weber 2014, Yu 2010). The phenotypic features of this syndrome are proposed to be related to additional copies of the candidate genes SOX7 (OMIM 612202) and GATA4 (Barber 2015, Zhang 2013). Therefore, based on gene content and current medical literature, this copy number variant (CNV) is classified as pathogenic with variable expressivity. _x000D__x000D_ References: Barber et al., Am J Med Genet A. 2015 Sep;167A(9):2052-64. PMID: 26097203 Okur et al., Genet Med. 2021 Dec;23(12):2342-2351. PMID: 34282301 Rehm et al., N Engl J Med. 2015 Jun 4;372(23):2235-42. PMID: 26014595; ISCA-37423 Weber et al., Mol Cytogenet. 2014 Dec 9;7(1):94. PMID: 25520754 Yu et al., Eur J Hum Genet. 2010 Oct;18(10):1114-20. PMID: 20461109_x000D__x000D_

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 Sep 01, 2024

ClinVar Genomic variation as it relates to human health

GRCh37/hg19 8p23.1-22(chr8:8093169-14526969)x3

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...