NM_000492.4(CFTR):c.2463_2464del (p.Ser821fs) AND Cystic fibrosis

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Mar 17, 2017
Review status:: 3 stars out of maximum of 4 stars
reviewed by expert panel

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000551959.10

Allele description [Variation Report for NM_000492.4(CFTR):c.2463_2464del (p.Ser821fs)]

NM_000492.4(CFTR):c.2463_2464del (p.Ser821fs)

Gene:

CFTR:CF transmembrane conductance regulator [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

7q31.2

Genomic location:

Preferred name:

NM_000492.4(CFTR):c.2463_2464del (p.Ser821fs)

Other names:

2594delGT

HGVS:

NC_000007.14:g.117592630_117592631del
NG_016465.4:g.131847_131848del
NM_000492.4:c.2463_2464delMANE SELECT
NP_000483.3:p.Ser821fs
NP_000483.3:p.Ser821fs
LRG_663t1:c.2463_2464del
LRG_663:g.131847_131848del
LRG_663p1:p.Ser821fs
NC_000007.13:g.117232683_117232684del
NC_000007.13:g.117232684_117232685del
NM_000492.3:c.2463_2464del
NM_000492.3:c.2463_2464del
NM_000492.3:c.2463_2464delTG
p.Ser821ArgfsX4

Protein change:

S821fs

Links:

dbSNP: rs797045156

NCBI 1000 Genomes Browser:

rs797045156

Molecular consequence:

NM_000492.4:c.2463_2464del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Cystic fibrosis (CF)
Synonyms:: Mucoviscidosis
Identifiers:: MONDO: MONDO:0009061; MedGen: C0010674; Orphanet: 586; OMIM: 219700

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000245879	CFTR2 - CFTR2	reviewed by expert panel (Sosnay PR et al. (Nat Genet 2013))	Pathogenic (Mar 17, 2017)	germline	research	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV000625735	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 15, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 12000363, 1695717, 7691345, 9725922, 28492532
SCV001132363	Counsyl	no assertion criteria provided	Pathogenic (Nov 8, 2017)	unknown	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000245879

CFTR2 - CFTR2

reviewed by expert panel

(Sosnay PR et al. (Nat Genet 2013))

Pathogenic
(Mar 17, 2017)

germline

research

PubMed (1)
[See all records that cite this PMID]

Citation Link,

SCV000625735

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 15, 2022)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV001132363

Counsyl

no assertion criteria provided

Pathogenic
(Nov 8, 2017)

unknown

clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	research
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene.

Sosnay PR, Siklosi KR, Van Goor F, Kaniecki K, Yu H, Sharma N, Ramalho AS, Amaral MD, Dorfman R, Zielenski J, Masica DL, Karchin R, Millen L, Thomas PJ, Patrinos GP, Corey M, Lewis MH, Rommens JM, Castellani C, Penland CM, Cutting GR.

Nat Genet. 2013 Oct;45(10):1160-7. doi: 10.1038/ng.2745. Epub 2013 Aug 25.

PubMed [citation]

PMID:: 23974870
PMCID:: PMC3874936

Complete screening of the CFTR gene in Argentine cystic fibrosis patients.

Visich A, Zielenski J, Castaños C, Diez G, Grenoville M, Segal E, Barreiro C, Tsui LC, Chertkoff L.

Clin Genet. 2002 Mar;61(3):207-13. Erratum in: Clin Genet. 2002 Oct;62(4):343.

PubMed [citation]

PMID:: 12000363

See all PubMed Citations (6)

Details of each submission

From CFTR2 - CFTR2, SCV000245879.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000625735.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 455767). This premature translational stop signal has been observed in individual(s) with cystic fibrosis (PMID: 12000363). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This sequence change creates a premature translational stop signal (p.Ser821Argfs*4) 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).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Counsyl, SCV001132363.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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