NM_000492.4(CFTR):c.1647T>G (p.Ser549Arg) AND CFTR-related disorder

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Dec 19, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001826538.3

Allele description [Variation Report for NM_000492.4(CFTR):c.1647T>G (p.Ser549Arg)]

NM_000492.4(CFTR):c.1647T>G (p.Ser549Arg)

Genes:

CFTR:CF transmembrane conductance regulator [Gene - OMIM - HGNC]
LOC111674475:CFTR intron 11 enhancer [Gene]

Variant type:

single nucleotide variant

Cytogenetic location:

7q31.2

Genomic location:

Preferred name:

NM_000492.4(CFTR):c.1647T>G (p.Ser549Arg)

Other names:

S549R (T->G)

HGVS:

NC_000007.14:g.117587801T>G
NG_016465.4:g.127018T>G
NG_056131.3:g.756T>G
NM_000492.4:c.1647T>GMANE SELECT
NP_000483.3:p.Ser549Arg
NP_000483.3:p.Ser549Arg
LRG_663t1:c.1647T>G
LRG_663:g.127018T>G
LRG_663p1:p.Ser549Arg
NC_000007.13:g.117227855T>G
NG_056131.1:g.125T>G
NM_000492.3:c.1647T>G
P13569:p.Ser549Arg

Protein change:

S549R; SER549ARG

Links:

PharmGKB: 1183960775; PharmGKB: 1183960775PA165950341; PharmGKB Clinical Annotation: 1183960775; UniProtKB: P13569#VAR_000178; OMIM: 602421.0012; dbSNP: rs121909005

NCBI 1000 Genomes Browser:

rs121909005

Molecular consequence:

NM_000492.4:c.1647T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: CFTR-related disorder (CFTR-RD)
Synonyms:: CFTR-related disorders; CFTR-related condition
Identifiers:

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002080631	Natera, Inc.	no assertion criteria provided	Pathogenic (Mar 17, 2017)	germline	clinical testing
SCV004731598	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 19, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002080631

Natera, Inc.

no assertion criteria provided

Pathogenic
(Mar 17, 2017)

germline

clinical testing

SCV004731598

PreventionGenetics, part of Exact Sciences

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Dec 19, 2023)

germline

clinical testing

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

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Natera, Inc., SCV002080631.1

#	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	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From PreventionGenetics, part of Exact Sciences, SCV004731598.1

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

Description

The CFTR c.1647T>G variant is predicted to result in the amino acid substitution p.Ser549Arg. This variant has been documented as causative for cystic fibrosis (Kerem et al. 1990. PubMed ID: 2236053; Table S2 - Sosnay et al. 2013. PubMed ID: 23974870; cftr2.org). This variant is reported in 0.0058% of alleles in individuals of Latino descent in gnomAD. In summary, this variant is interpreted 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: Jun 17, 2024

ClinVar

Relating variation to medicine