NM_000492.4(CFTR):c.1684G>A (p.Val562Ile) AND CFTR-related disorder

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Nov 30, 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:: RCV001163395.13

Allele description

NM_000492.4(CFTR):c.1684G>A (p.Val562Ile)

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.1684G>A (p.Val562Ile)

Other names:

NM_000492.3(CFTR):c.1684G>A(p.Val562Ile)

HGVS:

NC_000007.14:g.117590357G>A
NG_016465.4:g.129574G>A
NM_000492.4:c.1684G>AMANE SELECT
NP_000483.3:p.Val562Ile
NP_000483.3:p.Val562Ile
LRG_663t1:c.1684G>A
LRG_663:g.129574G>A
LRG_663p1:p.Val562Ile
NC_000007.13:g.117230411G>A
NM_000492.3:c.1684G>A
NM_000492.4:c.1684G>A
P13569:p.Val562Ile

Protein change:

V562I

Links:

UniProtKB: P13569#VAR_000187; dbSNP: rs1800097

NCBI 1000 Genomes Browser:

rs1800097

Molecular consequence:

NM_000492.4:c.1684G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001325427	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Apr 27, 2017)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 17572159, 23082198, 17331079, 18716917, 17098864, 24586523 Citation Link,
SCV004106449	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 30, 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

SCV001325427

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Uncertain significance
(Apr 27, 2017)

germline

clinical testing

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

Citation Link,

SCV004106449

PreventionGenetics, part of Exact Sciences

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Nov 30, 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

CFTR mutations in the Algerian population.

Loumi O, Ferec C, Mercier B, Creff J, Fercot B, Denine R, Grangaud JP.

J Cyst Fibros. 2008 Jan;7(1):54-9. Epub 2007 Jun 14.

PubMed [citation]

PMID:: 17572159

Measurements of CFTR-mediated Cl- secretion in human rectal biopsies constitute a robust biomarker for Cystic Fibrosis diagnosis and prognosis.

Sousa M, Servidoni MF, Vinagre AM, Ramalho AS, Bonadia LC, Felício V, Ribeiro MA, Uliyakina I, Marson FA, Kmit A, Cardoso SR, Ribeiro JD, Bertuzzo CS, Sousa L, Kunzelmann K, Ribeiro AF, Amaral MD.

PLoS One. 2012;7(10):e47708. doi: 10.1371/journal.pone.0047708. Epub 2012 Oct 17.

PubMed [citation]

PMID:: 23082198
PMCID:: PMC3474728

See all PubMed Citations (7)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV001325427.1

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

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

#	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, SCV004106449.2

#	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.1684G>A variant is predicted to result in the amino acid substitution p.Val562Ile. This variant was reported in a Moroccan patient with cystic fibrosis (Telleria et al. 1999. PubMed ID: 10447267). However, there was no further evidence that the p.Val562Ile variant was actually causative in this case. A later study reported cellular and genetic evidence that the p.Val562Ile variant may be benign (Roxo-Rosa et al. 2006. PubMed ID: 17098864). This variant is reported in 0.031% of alleles in individuals of Latino descent in gnomAD. In ClinVar, this variant has conflicting interpretations ranging from uncertain to likely benign (https://www.ncbi.nlm.nih.gov/clinvar/variation/35830/). While we suspect this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

#	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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