VCV000053532.7 - ClinVar

NM_000492.4(CFTR):c.263T>A (p.Leu88Ter)

Germline

Top reviewed classifications are shown here.

Submission summary:

6 submissions

5 submitters

2 conditions

Reviewed by expert panel

Pathogenic

Mar 2017 by CFTR2

for Cystic fibrosis

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000492.4(CFTR):c.263T>A (p.Leu88Ter)

Variation ID: 53532 Accession: VCV000053532.7

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 7q31.2 7: 117509132 (GRCh38) [ NCBI UCSC ] 7: 117149186 (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	Jan 7, 2018	Feb 14, 2024	Mar 17, 2017

HGVS

Nucleotide	Protein	Molecular consequence
NM_000492.4:c.263T>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000483.3:p.Leu88Ter	nonsense
NC_000007.14:g.117509132T>A
NC_000007.13:g.117149186T>A
NG_016465.4:g.48349T>A
NG_062452.1:g.770T>A
LRG_663:g.48349T>A
LRG_663t1:c.263T>A	LRG_663p1:p.Leu88Ter

... more HGVS ... less HGVS

Protein change

L88*

Other names

Canonical SPDI

NC_000007.14:117509131:T:A

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

ClinGen: CA326872 dbSNP: rs397508412 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	3840	5222

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 (4)	reviewed by expert panel	Mar 17, 2017	RCV000576641.9
CFTR-related disorder	Pathogenic (2)	no assertion criteria provided	Jul 30, 2020	RCV001826643.4

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.
Pathogenic (Mar 17, 2017)	reviewed by expert panel (Sosnay PR et al. (Nat Genet 2013)) Method: research	Cystic fibrosis Affected status: yes Allele origin: germline	CFTR2 Study: CFTR2 Accession: SCV000677617.1 First in ClinVar: Jan 07, 2018 Last updated: Jan 07, 2018	Other databases https://cftr2.org https://cftr2.org
Pathogenic (Jul 30, 2020)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Cystic fibrosis Affected status: unknown Allele origin: germline	Genome Diagnostics Laboratory, The Hospital for Sick Children Accession: SCV002507358.1 First in ClinVar: May 16, 2022 Last updated: May 16, 2022
Pathogenic (Dec 16, 2021)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Cystic fibrosis Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV003440210.2 First in ClinVar: Feb 07, 2023 Last updated: Feb 14, 2024	Publications: PubMed (6) PubMed: 1284542‚ 18955805‚ 23302613‚ 1695717‚ 7691345‚ 9725922 Comment: For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 53532). This premature translational stop signal … (more) For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 53532). This premature translational stop signal has been observed in individuals with cystic fibrosis (PMID: 1284542, 18955805, 23302613). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu88*) in the CFTR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CFTR are known to be pathogenic (PMID: 1695717, 7691345, 9725922). (less)
Pathogenic (Mar 17, 2017)	no assertion criteria provided Method: clinical testing	CFTR-related disorders Affected status: unknown Allele origin: germline	Natera, Inc. Accession: SCV002080100.1 First in ClinVar: Feb 13, 2022 Last updated: Feb 13, 2022
Pathogenic (Jul 30, 2020)	no assertion criteria provided Method: clinical testing	CFTR-related disorders Affected status: unknown Allele origin: germline	Genome Diagnostics Laboratory, The Hospital for Sick Children Accession: SCV002507442.1 First in ClinVar: May 16, 2022 Last updated: May 16, 2022
not provided (-)	no classification provided Method: literature only	CFTR-related disorders Affected status: yes Allele origin: germline	ClinVar Staff, National Center for Biotechnology Information (NCBI) Accession: SCV000679008.1 First in ClinVar: Jan 24, 2018 Last updated: Jan 24, 2018	Publications: PubMed (1) PubMed: 7512860

Comment:

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 53532). This premature translational stop signal has been observed in individuals with cystic fibrosis (PMID: 1284542, 18955805, 23302613). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu88*) in the CFTR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CFTR are known to be pathogenic (PMID: 1695717, 7691345, 9725922).

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
[Clinical manifestations and gene analysis of 2 Chinese children with cystic fibrosis].	Liu JR	Zhonghua er ke za zhi = Chinese journal of pediatrics	2012	PMID: 23302613
Identification of a novel mutation of CFTR gene in a Korean patient with cystic fibrosis.	Ko JM	Journal of Korean medical science	2008	PMID: 18955805
Relation between mutations of the cystic fibrosis gene and idiopathic pancreatitis.	Cohn JA	The New England journal of medicine	1998	PMID: 9725922
Identification of six novel mutations in the CFTR gene of patients from Bulgaria by screening the twenty seven exons and exon/intron boundaries using DGGE and direct DNA sequencing.	Savov A	Human molecular genetics	1994	PMID: 7512860
Molecular basis of defective anion transport in L cells expressing recombinant forms of CFTR.	Yang Y	Human molecular genetics	1993	PMID: 7691345
Identification of a novel nonsense mutation (L88X) in exon 3 of the cystic fibrosis transmembrane conductance regulator gene in a native Korean cystic fibrosis chromosome.	Macek M Jr	Human mutation	1992	PMID: 1284542
A cluster of cystic fibrosis mutations in the first nucleotide-binding fold of the cystic fibrosis conductance regulator protein.	Cutting GR	Nature	1990	PMID: 1695717
https://cftr2.org	-	-	-	-

Text-mined citations for rs397508412 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 25, 2024

ClinVar Genomic variation as it relates to human health

NM_000492.4(CFTR):c.263T>A (p.Leu88Ter)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs397508412 ...