NM_000492.4(CFTR):c.1052C>G (p.Thr351Ser) AND CFTR-related disorder

Germline classification:: Benign (3 submissions)
Last evaluated:: Apr 27, 2017
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:: RCV001158654.16

Allele description [Variation Report for NM_000492.4(CFTR):c.1052C>G (p.Thr351Ser)]

NM_000492.4(CFTR):c.1052C>G (p.Thr351Ser)

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.1052C>G (p.Thr351Ser)

HGVS:

NC_000007.14:g.117540282C>G
NG_016465.4:g.79499C>G
NM_000492.4:c.1052C>GMANE SELECT
NP_000483.3:p.Thr351Ser
NP_000483.3:p.Thr351Ser
LRG_663t1:c.1052C>G
LRG_663:g.79499C>G
LRG_663p1:p.Thr351Ser
NC_000007.13:g.117180336C>G
NM_000492.3:c.1052C>G
NM_000492.4:c.1052C>G
P13569:p.Thr351Ser

Protein change:

T351S

Links:

UniProtKB: P13569#VAR_009899; dbSNP: rs1800086

NCBI 1000 Genomes Browser:

rs1800086

Molecular consequence:

NM_000492.4:c.1052C>G - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

Normal function

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
SCV001320306	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Benign (Apr 27, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23951356, 23670503 Citation Link,
SCV002507465	Genome Diagnostics Laboratory, The Hospital for Sick Children	no assertion criteria provided	Likely pathogenic (May 28, 2020)	germline	clinical testing
SCV004117729	PreventionGenetics, part of Exact Sciences	no assertion criteria provided	Uncertain significance (Aug 19, 2024)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001320306

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Benign
(Apr 27, 2017)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link,

SCV002507465

Genome Diagnostics Laboratory, The Hospital for Sick Children

no assertion criteria provided

Likely pathogenic
(May 28, 2020)

germline

clinical testing

SCV004117729

PreventionGenetics, part of Exact Sciences

no assertion criteria provided

Uncertain significance
(Aug 19, 2024)

germline

clinical testing

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 conservative assessment of the major genetic causes of idiopathic chronic pancreatitis: data from a comprehensive analysis of PRSS1, SPINK1, CTRC and CFTR genes in 253 young French patients.

Masson E, Chen JM, Audrézet MP, Cooper DN, Férec C.

PLoS One. 2013;8(8):e73522. doi: 10.1371/journal.pone.0073522.

PubMed [citation]

PMID:: 23951356
PMCID:: PMC3738529

Diagnostic contribution of molecular analysis of the cystic fibrosis transmembrane conductance regulator gene in patients suspected of having mild or atypical cystic fibrosis.

Dal'Maso VB, Mallmann L, Siebert M, Simon L, Saraiva-Pereira ML, Dalcin Pde T.

J Bras Pneumol. 2013 Mar-Apr;39(2):181-9. English, Portuguese.

PubMed [citation]

PMID:: 23670503
PMCID:: PMC4075816

Details of each submission

From Illumina Laboratory Services, Illumina, SCV001320306.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

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. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.

#	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 Genome Diagnostics Laboratory, The Hospital for Sick Children, SCV002507465.1

#	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, SCV004117729.2

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

Description

The CFTR c.1052C>G variant is predicted to result in the amino acid substitution p.Thr351Ser. This variant has been reported in the heterozygous state in an individual with idiopathic chronic pancreatitis, an individual with CBAVD, and in an individual with clinical manifestations consistent with the spectrum of CF (Table S1, Masson. 2013. PubMed ID: 23951356; Larriba et al. 2005 PubMed ID: 16128988; Schrijver et al. 2005. PubMed ID: 15858154). This variant has also been reported in the compound heterozygous state with a p.Phe508del variant in an individual with CBAVD (Doerk et al. 1997. Table 3 PubMed ID: 9272157) and in the homozygous state (and in cis with another CFTR variant) in an individual with a CFTR-related disorder ( Table S3, Trujillano. 2013. PubMed ID: 23687349). In one individual with CF, this variant was one of three identified, and was in cis with a p.Phe508del variant (Dal'Maso et al. 2013 Table 3 PubMed ID: 23670503). To our knowledge, no functional or family studies are available to confirm the pathogenicity of the c.1052C>G change. This variant is reported in 0.068% of alleles in individuals of Ashkenazi Jewish descent in gnomAD. 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: Oct 26, 2024

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