VCV000999459.6 - ClinVar

NC_000020.10:g.(?_60831241)_(62664346_?)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.

(2)

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_000020.10:g.(?_60831241)_(62664346_?)dup

Variation ID: 999459 Accession: VCV000999459.6

Type and length

Duplication, 1,833,106 bp

Location

Cytogenetic: 20q13.33 20: 60831241-62664346 (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	Mar 7, 2021	Mar 14, 2021	Jun 9, 2020

HGVS

Nucleotide	Protein	Molecular consequence
NC_000020.10:g.(?_60831241)_(62664346_?)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.
KCNQ2		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh38 GRCh37	2152	2283
EEF1A2		No evidence available	No evidence available	GRCh38 GRCh37	506	667
ABHD16B		-	-	GRCh38 GRCh37	-	107
ADRM1		-	-	GRCh38 GRCh37	23	50
ARFGAP1		-	-	GRCh38 GRCh37	38	109
ARFRP1		-	-	GRCh38 GRCh37	17	73
BHLHE23		-	-	GRCh38 GRCh37	7	58
BIRC7		-	-	GRCh38 GRCh37	26	92
CABLES2		-	-	GRCh38 GRCh37	37	78
CHRNA4		-	-	GRCh38 GRCh37	883	1152

There are 41 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.
Developmental and epileptic encephalopathy, 33	Uncertain significance (1)	criteria provided, single submitter	Jun 9, 2020	RCV001295457.10
Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (1)	criteria provided, single submitter	Jun 9, 2020	RCV001316934.10

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 (Jun 09, 2020)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Developmental and epileptic encephalopathy, 33 Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001484377.1 First in ClinVar: Mar 07, 2021 Last updated: Mar 07, 2021	Publications: PubMed (1) PubMed: 25921748 Comment: This variant results in a copy number gain of the genomic region encompassing the full coding sequence of the EEF1A2 gene. The boundaries of this … (more) This variant results in a copy number gain of the genomic region encompassing the full coding sequence of the EEF1A2 gene. 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 copy number gains of EEF1A2 have not been reported in the literature. However, larger copy number events that include this gene have been reported (PMID: 25921748). 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)
Uncertain significance (Jun 09, 2020)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Early infantile epileptic encephalopathy with suppression bursts Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001507574.1 First in ClinVar: Mar 14, 2021 Last updated: Mar 14, 2021	Publications: PubMed (2) PubMed: 25921748‚ 30866059 Comment: This variant results in a copy number gain of the genomic region encompassing the full coding sequence of the KCNQ2 gene. The boundaries of this … (more) This variant results in a copy number gain of the genomic region encompassing the full coding sequence of the KCNQ2 gene. 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 copy number gains of KCNQ2 have not been reported in the literature. However, larger copy number events that include this gene have been reported (PMID: 25921748, 30866059). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acid(s) is currently unknown. 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:

This variant results in a copy number gain of the genomic region encompassing the full coding sequence of the EEF1A2 gene. 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 copy number gains of EEF1A2 have not been reported in the literature. However, larger copy number events that include this gene have been reported (PMID: 25921748). 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.

Comment:

This variant results in a copy number gain of the genomic region encompassing the full coding sequence of the KCNQ2 gene. 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 copy number gains of KCNQ2 have not been reported in the literature. However, larger copy number events that include this gene have been reported (PMID: 25921748, 30866059). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acid(s) is currently unknown. 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
Diagnostic implications of genetic copy number variation in epilepsy plus.	Coppola A	Epilepsia	2019	PMID: 30866059
Array-comparative genomic hybridization analysis of a cohort of Saudi patients with epilepsy.	Faheem M	CNS & neurological disorders drug targets	2015	PMID: 25921748

Text-mined citations for this variant ...

Record last updated Nov 10, 2024

ClinVar Genomic variation as it relates to human health

NC_000020.10:g.(?_60831241)_(62664346_?)dup

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...