VCV001372096.8 - ClinVar

NC_000009.11:g.(?_137534034)_(139440238_?)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_000009.11:g.(?_137534034)_(139440238_?)dup

Variation ID: 1372096 Accession: VCV001372096.8

Type and length

Duplication, 1,906,205 bp

Location

Cytogenetic: 9q34.3 9: 137534034-139440238 (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 28, 2022	Jun 9, 2024	Aug 20, 2021

HGVS

Nucleotide	Protein	Molecular consequence
NC_000009.11:g.(?_137534034)_(139440238_?)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.
COL5A1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	2675	3479
C9orf163	-	-	-	GRCh38 GRCh37	-	92
CAMSAP1		-	-	GRCh38 GRCh37	123	197
CARD9		-	-	GRCh38 GRCh37	514	609
DNLZ		-	-	GRCh38 GRCh37	-	79
ENTR1		-	-	GRCh38 GRCh37	43	136
FCN1		-	-	GRCh38 GRCh37	35	91
FCN2		-	-	GRCh38 GRCh37	37	94
GLT6D1		-	-	GRCh38 GRCh37	31	98
GPSM1		-	-	GRCh38 GRCh37	73	153

There are 21 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.
Ehlers-Danlos syndrome, classic type, 1	Uncertain significance (1)	criteria provided, single submitter	Mar 10, 2021	RCV001872736.6
Adams-Oliver syndrome 5	Uncertain significance (1)	criteria provided, single submitter	Aug 20, 2021	RCV003120731.4

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 (Aug 20, 2021)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Adams-Oliver syndrome 5 Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV003795027.2 First in ClinVar: Feb 13, 2023 Last updated: Nov 11, 2023	Publications: PubMed (1) PubMed: 29907982 Comment: A copy number gain of the genomic region encompassing the full coding sequence of the NOTCH1 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 NOTCH1 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 copy number gains of NOTCH1 have not been reported in the literature. However, larger copy number events that include this gene have been reported (PMID: 29907982). 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 (Mar 10, 2021)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Ehlers-Danlos syndrome, classic type, 1 Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV002141383.4 First in ClinVar: Mar 28, 2022 Last updated: Jun 09, 2024	Comment: 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 … (more) 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. This variant has not been reported in the literature in individuals with COL5A1-related disease. This variant results in a copy number gain of the genomic region encompassing the full coding sequence of the COL5A1 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. (less)

Comment:

A copy number gain of the genomic region encompassing the full coding sequence of the NOTCH1 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 copy number gains of NOTCH1 have not been reported in the literature. However, larger copy number events that include this gene have been reported (PMID: 29907982). 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:

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. This variant has not been reported in the literature in individuals with COL5A1-related disease. This variant results in a copy number gain of the genomic region encompassing the full coding sequence of the COL5A1 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.

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
Results of next-generation sequencing gene panel diagnostics including copy-number variation analysis in 810 patients suspected of heritable thoracic aortic disorders.	Overwater E	Human mutation	2018	PMID: 29907982

Text-mined citations for this variant ...

Record last updated Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NC_000009.11:g.(?_137534034)_(139440238_?)dup

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...