VCV003245119.1 - ClinVar

NC_000009.11:g.(?_130374683)_(131329276_?)del

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.

Pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NC_000009.11:g.(?_130374683)_(131329276_?)del

Variation ID: 3245119 Accession: VCV003245119.1

Type and length

Deletion, 954,594 bp

Location

Cytogenetic: 9q34.11 9: 130374683-131329276 (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	Sep 11, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NC_000009.11:g.(?_130374683)_(131329276_?)del

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.
ENG		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	1106	1618
STXBP1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	1089	1184
AK1		-	-	GRCh38 GRCh37	-	103
BBLN	-	-	-	GRCh38 GRCh37	-	39
CDK9		-	-	GRCh38 GRCh37	23	61
CERCAM		-	-	GRCh38 GRCh37	54	100
CFAP157	-	-	-	GRCh38 GRCh37	-	115
CIZ1		-	-	GRCh38 GRCh37	339	434
COQ4		-	-	GRCh38 GRCh37	272	334
DNM1		-	-	GRCh38 GRCh37	623	913

There are 24 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, 31A	Pathogenic (1)	criteria provided, single submitter	Sep 11, 2023	RCV004581887.2
Early infantile epileptic encephalopathy with suppression bursts	Pathogenic (1)	criteria provided, single submitter	Sep 11, 2023	RCV004581888.2

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.
Pathogenic (Sep 11, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Early infantile epileptic encephalopathy with suppression bursts Affected status: unknown Allele origin: unknown	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV005067228.1 First in ClinVar: Jun 29, 2024 Last updated: Jun 29, 2024	Publications: PubMed (7) PubMed: 20887364‚ 26384463‚ 18469812‚ 22722545‚ 26514728‚ 26865513‚ 29264391 Comment: A gross deletion of the genomic region encompassing the full coding sequence of the STXBP1 gene has been identified. Loss-of-function variants in STXBP1 are known … (more) A gross deletion of the genomic region encompassing the full coding sequence of the STXBP1 gene has been identified. Loss-of-function variants in STXBP1 are known to be pathogenic (PMID: 20887364, 26384463). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. Isolated whole-gene deletions of STXBP1 have not been reported in the literature. However, larger copy number events that include this gene have been reported (PMID: 18469812, 22722545, 26514728, 26865513, 29264391; Invitae). For these reasons, this variant has been classified as Pathogenic. (less)
Pathogenic (Sep 11, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Developmental and epileptic encephalopathy, 31A Affected status: unknown Allele origin: unknown	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV005067374.1 First in ClinVar: Jun 29, 2024 Last updated: Jun 29, 2024	Publications: PubMed (1) PubMed: 34172529 Comment: A gross deletion of the genomic region encompassing the full coding sequence of the DNM1 gene has been identified. Loss-of-function variants in DNM1 are known … (more) A gross deletion of the genomic region encompassing the full coding sequence of the DNM1 gene has been identified. Loss-of-function variants in DNM1 are known to be pathogenic (PMID: 34172529). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. This variant has not been reported in the literature in individuals affected with DNM1-related conditions. For these reasons, this variant has been classified as Pathogenic. (less)

Comment:

A gross deletion of the genomic region encompassing the full coding sequence of the STXBP1 gene has been identified. Loss-of-function variants in STXBP1 are known to be pathogenic (PMID: 20887364, 26384463). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. Isolated whole-gene deletions of STXBP1 have not been reported in the literature. However, larger copy number events that include this gene have been reported (PMID: 18469812, 22722545, 26514728, 26865513, 29264391; Invitae). For these reasons, this variant has been classified as Pathogenic.

Comment:

A gross deletion of the genomic region encompassing the full coding sequence of the DNM1 gene has been identified. Loss-of-function variants in DNM1 are known to be pathogenic (PMID: 34172529). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. This variant has not been reported in the literature in individuals affected with DNM1-related conditions. For these reasons, this variant has been 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
Loss-of-function variants in DNM1 cause a specific form of developmental and epileptic encephalopathy only in biallelic state.	Yigit G	Journal of medical genetics	2022	PMID: 34172529
Germline and somatic mutations in STXBP1 with diverse neurodevelopmental phenotypes.	Uddin M	Neurology. Genetics	2017	PMID: 29264391
STXBP1 encephalopathy: A neurodevelopmental disorder including epilepsy.	Stamberger H	Neurology	2016	PMID: 26865513
Loss-of-function mutations of STXBP1 in patients with epileptic encephalopathy.	Yamamoto T	Brain & development	2016	PMID: 26384463
Epileptic patients with de novo STXBP1 mutations: Key clinical features based on 24 cases.	Di Meglio C	Epilepsia	2015	PMID: 26514728
Novel 9q34.11 gene deletions encompassing combinations of four Mendelian disease genes: STXBP1, SPTAN1, ENG, and TOR1A.	Campbell IM	Genetics in medicine : official journal of the American College of Medical Genetics	2012	PMID: 22722545
STXBP1 mutations in early infantile epileptic encephalopathy with suppression-burst pattern.	Saitsu H	Epilepsia	2010	PMID: 20887364
De novo mutations in the gene encoding STXBP1 (MUNC18-1) cause early infantile epileptic encephalopathy.	Saitsu H	Nature genetics	2008	PMID: 18469812

Text-mined citations for this variant ...

Record last updated Sep 30, 2024

ClinVar Genomic variation as it relates to human health

NC_000009.11:g.(?_130374683)_(131329276_?)del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...