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NM_000492.4(CFTR):c.3672T>A (p.Asn1224Lys) AND not provided

Germline classification:
Uncertain significance (3 submissions)
Last evaluated:
Mar 6, 2024
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:
RCV000588038.11

Allele description [Variation Report for NM_000492.4(CFTR):c.3672T>A (p.Asn1224Lys)]

NM_000492.4(CFTR):c.3672T>A (p.Asn1224Lys)

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.3672T>A (p.Asn1224Lys)
HGVS:
  • NC_000007.14:g.117627725T>A
  • NG_016465.4:g.166942T>A
  • NM_000492.4:c.3672T>AMANE SELECT
  • NP_000483.3:p.Asn1224Lys
  • NP_000483.3:p.Asn1224Lys
  • LRG_663t1:c.3672T>A
  • LRG_663:g.166942T>A
  • LRG_663p1:p.Asn1224Lys
  • NC_000007.13:g.117267779T>A
  • NM_000492.3:c.3672T>A
  • NM_000492.4:c.3672T>A
Protein change:
N1224K
Links:
dbSNP: rs371475225
NCBI 1000 Genomes Browser:
rs371475225
Molecular consequence:
  • NM_000492.4:c.3672T>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000885176ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process)		Uncertain significance
(Feb 6, 2018) 		germlineclinical testing

Citation Link,

SCV004224093Mayo Clinic Laboratories, Mayo Clinic
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Dec 30, 2022) 		germlineclinical testing

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

SCV005325754GeneDx
criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)		Uncertain significance
(Mar 6, 2024) 		germlineclinical testing

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot providednot providednot providedclinical testing
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Amniotic fluid digestive enzyme analysis is useful for identifying CFTR gene mutations of unclear significance.

Oca F, Dreux S, Gérard B, Simon-Bouy B, de Becdelièvre A, Ferec C, Girodon E, Muller F.

Clin Chem. 2009 Dec;55(12):2214-7. doi: 10.1373/clinchem.2009.133298. Epub 2009 Oct 15.

PubMed [citation]
PMID:
19833837

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 ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV000885176.1

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

Description

The CFTR c.3672T>A; p.Asn1224Lys variant (rs371475225) has been observed in trans with a common pathogenic CFTR variant (F508del) in an individual exhibiting no clinical signs of cystic fibrosis (Oca 2009). This variant is observed in the general population at an overall frequency of 0.02% (49/244772 alleles) in the Genome Aggregation Database. The asparagine at codon 1224 is weakly conserved and computational algorithms (SIFT, PolyPhen2, MutationTaster) predict this variant to be tolerated. However, given the lack of clinical and functional data, the significance of this variant cannot be determined with certainty. References: Oca F et al. Amniotic fluid digestive enzyme analysis is useful for identifying CFTR gene mutations of unclear significance. Clin Chem. 2009 Dec;55(12):2214-7.

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

From Mayo Clinic Laboratories, Mayo Clinic, SCV004224093.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (2)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided1not providednot providednot provided

From GeneDx, SCV005325754.1

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

Description

In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 19833837, 26214305)

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

Last Updated: Nov 10, 2024