NM_000492.4(CFTR):c.164+2T>C AND Cystic fibrosis

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Dec 8, 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:: RCV000577099.5

Allele description [Variation Report for NM_000492.4(CFTR):c.164+2T>C]

NM_000492.4(CFTR):c.164+2T>C

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

7q31.2

Genomic location:

Preferred name:

NM_000492.4(CFTR):c.164+2T>C

HGVS:

NC_000007.14:g.117504365T>C
NG_016465.4:g.43582T>C
NM_000492.4:c.164+2T>CMANE SELECT
LRG_663t1:c.164+2T>C
LRG_663:g.43582T>C
NC_000007.13:g.117144419T>C
NM_000492.3:c.164+2T>C

Links:

dbSNP: rs121908800

NCBI 1000 Genomes Browser:

rs121908800

Molecular consequence:

NM_000492.4:c.164+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

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

Recent activity

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Rattus norvegicus ras homolog family member A (Rhoa), mRNA
Rattus norvegicus ras homolog family member A (Rhoa), mRNA
gi|148747294|ref|NM_057132.3|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000679116	ClinVar Staff, National Center for Biotechnology Information (NCBI)	no classification provided	not provided	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000924235	CFTR2	reviewed by expert panel (Sosnay PR et al. (Nat Genet 2013))	Pathogenic (Dec 8, 2017)	germline	research	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV004295532	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 29, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 15365999, 16199547, 1695717, 7691345, 9725922, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000679116

ClinVar Staff, National Center for Biotechnology Information (NCBI)

no classification provided

not provided

germline

literature only

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

SCV000924235

CFTR2

reviewed by expert panel

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

Pathogenic
(Dec 8, 2017)

germline

research

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

Citation Link,

SCV004295532

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 29, 2023)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

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, literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Complete and rapid scanning of the cystic fibrosis transmembrane conductance regulator (CFTR) gene by denaturing high-performance liquid chromatography (D-HPLC): major implications for genetic counselling.

Le Maréchal C, Audrézet MP, Quéré I, Raguénès O, Langonné S, Férec C.

Hum Genet. 2001 Apr;108(4):290-8.

PubMed [citation]

PMID:: 11379874

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

See all PubMed Citations (8)

Details of each submission

From ClinVar Staff, National Center for Biotechnology Information (NCBI), SCV000679116.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	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 CFTR2, SCV000924235.1

#	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, SCV004295532.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 53306). Disruption of this splice site has been observed in individual(s) with cystic fibrosis (PMID: 15365999). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 2 of the CFTR gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CFTR are known to be pathogenic (PMID: 1695717, 7691345, 9725922). For these reasons, this variant has been classified as Pathogenic.

#	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

Last Updated: Sep 29, 2024

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