NM_000492.4(CFTR):c.4056G>T (p.Gln1352His) AND none provided

Clinical significance:Pathogenic (Last evaluated: Jan 23, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001282161.2

Allele description [Variation Report for NM_000492.4(CFTR):c.4056G>T (p.Gln1352His)]

NM_000492.4(CFTR):c.4056G>T (p.Gln1352His)

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.4056G>T (p.Gln1352His)
HGVS:
  • NC_000007.14:g.117664780G>T
  • NG_016465.4:g.203997G>T
  • NM_000492.3:c.4056G>T
  • NM_000492.4:c.4056G>TMANE SELECT
  • NP_000483.3:p.Gln1352His
  • NP_000483.3:p.Gln1352His
  • LRG_663t1:c.4056G>T
  • LRG_663:g.203997G>T
  • LRG_663p1:p.Gln1352His
  • NC_000007.13:g.117304834G>T
Protein change:
Q1352H
Links:
dbSNP: rs113857788
NCBI 1000 Genomes Browser:
rs113857788
Molecular consequence:
  • NM_000492.3:c.4056G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000492.4:c.4056G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
none provided
Identifiers:
MedGen: CN235283

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000885195ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratoriescriteria provided, single submitter
Pathogenic
(Jan 23, 2020)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV000885195.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The CFTR c.4056G>T; p.Gln1352His variant (rs113857788), and another variant resulting in the same amino acid change (c.4056G>C; p.Gln1352His), are reported in the literature in multiple individuals affected with CFTR-related disorders such as pancreatitis and congenital bilateral absence of the vas deferens (Anzai 2003, Claustres 2017, Lee 2003, Ratbi 2007). The p.Gln1352His variant is also reported to be enriched in Asian pancreatitis patients compared to unaffected individuals (Claustres 2005, Kondo 2015, Nakano 2015). Expression of the variant protein in a cell line reveals a significant reduction in mature CFTR protein detected compared to wildtype (Lee 2003). The c.4056G>T; p.Gln1352His variant is reported in ClinVar (Variation ID: 35882), and is found in the general population with an overall allele frequency of 0.006% (17/282620 alleles) in the Genome Aggregation Database. The glutamine at residue 1352 is highly conserved and computational algorithms (PolyPhen-2, SIFT) predict that the variant is deleterious. Based on available information, this variant is considered to be mildly pathogenic. References: Anzai C et al. CFTR gene mutations in Japanese individuals with congenital bilateral absence of the vas deferens. J Cyst Fibros. 2003; 2(1):14-8. Claustres M et al. Molecular pathology of the CFTR locus in male infertility. Reprod Biomed Online. 2005 Jan;10(1):14-41. Claustres M et al. CFTR-France, a national relational patient database for sharing genetic and phenotypic data associated with rare CFTR variants. Hum Mutat. 2017 Oct;38(10):1297-1315. Kondo S et al. Functional characteristics of L1156F-CFTR associated with alcoholic chronic pancreatitis in Japanese. Am J Physiol Gastrointest Liver Physiol. 2015 Aug 15;309(4):G260-9. Lee J et al. A haplotype-based molecular analysis of CFTR mutations associated with respiratory and pancreatic diseases. Hum Mol Genet. 2003; 12(18):2321-32. Nakano E et al. Targeted next-generation sequencing effectively analyzed the cystic fibrosis transmembrane conductance regulator gene in pancreatitis. Dig Dis Sci. 2015 May;60(5):1297-307. Ratbi I et al. Detection of cystic fibrosis transmembrane conductance regulator (CFTR) gene rearrangements enriches the mutation spectrum in congenital bilateral absence of the vas deferens and impacts on genetic counselling. Hum Reprod. 2007; 22(5):1285-91.

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

Last Updated: Nov 11, 2021

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