NM_000492.4(CFTR):c.142_145del (p.Asn48fs) AND Cystic fibrosis

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Feb 8, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV002391801.4

Allele description [Variation Report for NM_000492.4(CFTR):c.142_145del (p.Asn48fs)]

NM_000492.4(CFTR):c.142_145del (p.Asn48fs)

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.142_145del (p.Asn48fs)

HGVS:

NC_000007.14:g.117504341_117504344del
NG_016465.4:g.43558_43561del
NM_000492.4:c.142_145delMANE SELECT
NP_000483.3:p.Asn48Tyrfs
NP_000483.3:p.Asn48fs
LRG_663t1:c.142_145del
LRG_663:g.43558_43561del
LRG_663p1:p.Asn48Tyrfs
NC_000007.13:g.117144394_117144397del
NC_000007.13:g.117144395_117144398del
NM_000492.3:c.142_145delAATC

Protein change:

N48fs

Molecular consequence:

NM_000492.4:c.142_145del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

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

Recent activity

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MAG: NADH dehydrogenase [Comamonadaceae bacterium CG2_30_60_41]
MAG: NADH dehydrogenase [Comamonadaceae bacterium CG2_30_60_41]
gi|1101172359|gb|OIP25603.1||gnl|WG Y|AUK52_00070

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002696613	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Aug 9, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV004295531	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 8, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 1695717, 7691345, 9725922, 26708955, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002696613

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Aug 9, 2016)

germline

clinical testing

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

Citation Link,

SCV004295531

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 8, 2023)

germline

clinical testing

PubMed (5)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A cluster of cystic fibrosis mutations in the first nucleotide-binding fold of the cystic fibrosis conductance regulator protein.

Cutting GR, Kasch LM, Rosenstein BJ, Zielenski J, Tsui LC, Antonarakis SE, Kazazian HH Jr.

Nature. 1990 Jul 26;346(6282):366-9.

PubMed [citation]

PMID:: 1695717

Molecular basis of defective anion transport in L cells expressing recombinant forms of CFTR.

Yang Y, Devor DC, Engelhardt JF, Ernst SA, Strong TV, Collins FS, Cohn JA, Frizzell RA, Wilson JM.

Hum Mol Genet. 1993 Aug;2(8):1253-61.

PubMed [citation]

PMID:: 7691345

See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV002696613.2

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

Description

The c.142_145delAATC pathogenic mutation, located in coding exon 2 of the CFTR gene, results from a deletion of 4 nucleotides at nucleotide positions 142 to 145, causing a translational frameshift with a predicted alternate stop codon (p.N48Yfs*42). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV004295531.1

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

Description

This sequence change creates a premature translational stop signal (p.Asn48Tyrfs*42) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of cystic fibrosis (PMID: 26708955). ClinVar contains an entry for this variant (Variation ID: 1772239). 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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