NM_000492.4(CFTR):c.1054C>T (p.Arg352Trp) AND Cystic fibrosis

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(2) (Last evaluated: Jul 22, 2021)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000029469.14

Allele description [Variation Report for NM_000492.4(CFTR):c.1054C>T (p.Arg352Trp)]

NM_000492.4(CFTR):c.1054C>T (p.Arg352Trp)

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.1054C>T (p.Arg352Trp)
HGVS:
  • NC_000007.14:g.117540284C>T
  • NG_016465.4:g.79501C>T
  • NM_000492.4:c.1054C>TMANE SELECT
  • NP_000483.3:p.Arg352Trp
  • NP_000483.3:p.Arg352Trp
  • LRG_663t1:c.1054C>T
  • LRG_663:g.79501C>T
  • LRG_663p1:p.Arg352Trp
  • NC_000007.13:g.117180338C>T
  • NM_000492.3:c.1054C>T
Protein change:
R352W
Links:
dbSNP: rs193922497
NCBI 1000 Genomes Browser:
rs193922497
Molecular consequence:
  • NM_000492.4:c.1054C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000074226Invitaecriteria provided, single submitter
Likely benign
(Nov 25, 2020)
germlineclinical testing

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

SCV000916179Illumina Clinical Services Laboratory,Illuminacriteria provided, single submitter
Uncertain significance
(Nov 6, 2018)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link,

SCV001822035Nilou-Genome Labcriteria provided, single submitter
Uncertain significance
(Jul 22, 2021)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenonot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

A 10-year large-scale cystic fibrosis carrier screening in the Italian population.

Picci L, Cameran M, Marangon O, Marzenta D, Ferrari S, Frigo AC, Scarpa M.

J Cyst Fibros. 2010 Jan;9(1):29-35. doi: 10.1016/j.jcf.2009.10.003. Epub 2009 Nov 7.

PubMed [citation]
PMID:
19897426
See all PubMed Citations (6)

Details of each submission

From Invitae, SCV000074226.8

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Illumina Clinical Services Laboratory,Illumina, SCV000916179.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

The CFTR c.1054C>T (p.Arg352Trp) variant is a missense variant that has been reported in at least four studies, in which it is found in a compound heterozygous state with a second variant in four individuals, including in one individual with congenital bilateral absence of the vas deferens and in three newborns who underwent additional screening for cystic fibrosis (CF) following abnormal newborn screening for this condition (McGinniss et al. 2005; Soultan et al. 2008; Lilley et al. 2010; Picci et al. 2010). Two of the newborns were found to carry the p.Arg352Trp variant in cis with another missense variant on one allele and a classic CF variant on the other allele. The CF status of these newborns is not known. Control data are unavailable for this variant, which is reported at a frequency of 0.004764 in the Latino population of the Exome Aggregation Consortium. The evidence for this variant is limited. The p.Arg352Trp variant is therefore classified as a variant of unknown significance but suspicious for pathogenicity for CFTR-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Nilou-Genome Lab, SCV001822035.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenonot providednot providednot providednot providednot providednot providednot provided

Last Updated: Dec 4, 2021

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