VCV003339466.1 - ClinVar

NC_000007.13:g.(117235113_117242879)_(117251863_117254666)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.

(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

NC_000007.13:g.(117235113_117242879)_(117251863_117254666)del

Variation ID: 3339466 Accession: VCV003339466.1

Type and length

Deletion, 19,554 bp

Location

Cytogenetic: 7q31.2 7: 117235113-117254666 (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	Sep 17, 2024	Sep 16, 2024	Jul 18, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NC_000007.13:g.(117235113_117242879)_(117251863_117254666)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.
CFTR		-	-	GRCh38 GRCh37	3826	5201

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.
Cystic fibrosis	Pathogenic (1)	criteria provided, single submitter	Jul 18, 2024	RCV004699702.1

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 (Jul 18, 2024)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	Cystic fibrosis Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV005203470.1 First in ClinVar: Sep 16, 2024 Last updated: Sep 16, 2024	Publications: PubMed (6) PubMed: 15520400‚ 17594397‚ 15841482‚ 16990428‚ 16493442‚ 18280224 Comment: Variant summary: The variant involves the deletion of exons 16-20 in the CFTR gene (Legacy name CFTRdel 14b-17b). This Copy Number Variant (CNV) is expected … (more) Variant summary: The variant involves the deletion of exons 16-20 in the CFTR gene (Legacy name CFTRdel 14b-17b). This Copy Number Variant (CNV) is expected to alter the reading frame and predicted to result in a truncation or absence of the encoded protein due to nonsense mediated decay (NMD). A presumed nomenclature of c.(2619+1_2620-1)_(3367+1_3368-1)del has been designated for the purposes of this classification. The variant was absent in 21694 control chromosomes. c.(2619+1_2620-1)_(3367+1_3368-1)del has been reported in the literature in multiple individuals affected with Cystic Fibrosis (examples: Niel_2004, Chevalier-Porst_2005, Schneider_2006,Schneider_2007,Tomaiuolo_2008). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 15520400, 17594397, 15841482, 16990428, 16493442, 18280224). ClinVar contains an entry for this variant (Variation ID: 1275739). Based on the evidence outlined above, the variant was classified as pathogenic. (less)

Comment:

Variant summary: The variant involves the deletion of exons 16-20 in the CFTR gene (Legacy name CFTRdel 14b-17b). This Copy Number Variant (CNV) is expected to alter the reading frame and predicted to result in a truncation or absence of the encoded protein due to nonsense mediated decay (NMD). A presumed nomenclature of c.(2619+1_2620-1)_(3367+1_3368-1)del has been designated for the purposes of this classification. The variant was absent in 21694 control chromosomes. c.(2619+1_2620-1)_(3367+1_3368-1)del has been reported in the literature in multiple individuals affected with Cystic Fibrosis (examples: Niel_2004, Chevalier-Porst_2005, Schneider_2006,Schneider_2007,Tomaiuolo_2008). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 15520400, 17594397, 15841482, 16990428, 16493442, 18280224). ClinVar contains an entry for this variant (Variation ID: 1275739). Based on the evidence outlined above, the variant was 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
Epidemiology and a novel procedure for large scale analysis of CFTR rearrangements in classic and atypical CF patients: a multicentric Italian study.	Tomaiuolo R	Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society	2008	PMID: 18280224
Large deletions in the CFTR gene: clinics and genetics in Swiss patients with CF.	Schneider M	Clinical genetics	2007	PMID: 17594397
Detection of exon deletions within an entire gene (CFTR) by relative quantification on the LightCycler.	Schneider M	Clinical chemistry	2006	PMID: 16990428
Gross genomic rearrangements involving deletions in the CFTR gene: characterization of six new events from a large cohort of hitherto unidentified cystic fibrosis chromosomes and meta-analysis of the underlying mechanisms.	Férec C	European journal of human genetics : EJHG	2006	PMID: 16493442
Identification and characterization of three large deletions and a deletion/polymorphism in the CFTR gene.	Chevalier-Porst F	Human mutation	2005	PMID: 15841482
Rapid detection of CFTR gene rearrangements impacts on genetic counselling in cystic fibrosis.	Niel F	Journal of medical genetics	2004	PMID: 15520400

Text-mined citations for this variant ...

Record last updated Sep 30, 2024

ClinVar Genomic variation as it relates to human health

NC_000007.13:g.(117235113_117242879)_(117251863_117254666)del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...