VCV003245523.1 - ClinVar

NC_000008.10:g.(?_11351220)_(11710963_?)dup

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.

Uncertain significance

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NC_000008.10:g.(?_11351220)_(11710963_?)dup

Variation ID: 3245523 Accession: VCV003245523.1

Type and length

Duplication, 359,744 bp

Location

Cytogenetic: 8p23.1 8: 11351220-11710963 (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	Jun 30, 2024	Jun 29, 2024	Dec 22, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NC_000008.10:g.(?_11351220)_(11710963_?)dup

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
BLK		-	-	GRCh38 GRCh38 GRCh37	299	475
FDFT1		-	-	GRCh38 GRCh38 GRCh37	88	223
NEIL2		-	-	GRCh38 GRCh38 GRCh37	51	172

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.
Atrioventricular septal defect 4	Uncertain significance (1)	criteria provided, single submitter	Dec 22, 2023	RCV004583284.2

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.
Uncertain significance (Dec 22, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Atrioventricular septal defect 4 Affected status: unknown Allele origin: unknown	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV005062895.1 First in ClinVar: Jun 29, 2024 Last updated: Jun 29, 2024	Publications: PubMed (7) PubMed: 19353638‚ 21933911‚ 22318994‚ 24127225‚ 25205790‚ 25516202‚ 32748548 Comment: A copy number gain of the genomic region encompassing the full coding sequence of the GATA4 gene has been identified. The boundaries of this event … (more) A copy number gain of the genomic region encompassing the full coding sequence of the GATA4 gene has been identified. The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. As the precise location of this event is unknown, it may be in tandem or it may be located elsewhere in the genome. Isolated whole-gene gains of GATA4 have not been reported in the literature. However, larger copy number events that include this gene have been reported (PMID: 19353638, 21933911, 22318994, 24127225, 25205790, 25516202, 32748548). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)

Comment:

A copy number gain of the genomic region encompassing the full coding sequence of the GATA4 gene has been identified. The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. As the precise location of this event is unknown, it may be in tandem or it may be located elsewhere in the genome. Isolated whole-gene gains of GATA4 have not been reported in the literature. However, larger copy number events that include this gene have been reported (PMID: 19353638, 21933911, 22318994, 24127225, 25205790, 25516202, 32748548). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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
Rare deleterious variants of NOTCH1, GATA4, SMAD6, and ROBO4 are enriched in BAV with early onset complications but not in BAV with heritable thoracic aortic disease.	Musfee FI	Molecular genetics & genomic medicine	2020	PMID: 32748548
Chromosome microarray testing for patients with congenital heart defects reveals novel disease causing loci and high diagnostic yield.	Geng J	BMC genomics	2014	PMID: 25516202
Increased frequency of de novo copy number variants in congenital heart disease by integrative analysis of single nucleotide polymorphism array and exome sequence data.	Glessner JT	Circulation research	2014	PMID: 25205790
Identification of novel candidate gene loci and increased sex chromosome aneuploidy among infants with conotruncal heart defects.	Osoegawa K	American journal of medical genetics. Part A	2014	PMID: 24127225
Human gene copy number spectra analysis in congenital heart malformations.	Tomita-Mitchell A	Physiological genomics	2012	PMID: 22318994
Cardiac defects are infrequent findings in individuals with 8p23.1 genomic duplications containing GATA4.	Yu S	Circulation. Cardiovascular genetics	2011	PMID: 21933911
A duplication including GATA4 does not co-segregate with congenital heart defects.	Joziasse IC	American journal of medical genetics. Part A	2009	PMID: 19353638

Text-mined citations for this variant ...

Record last updated Sep 30, 2024

ClinVar Genomic variation as it relates to human health

NC_000008.10:g.(?_11351220)_(11710963_?)dup

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...