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NM_000492.4(CFTR):c.2280G>A (p.Thr760=) AND not specified

Germline classification:
Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:
Aug 28, 2019
Review status:
criteria provided, conflicting classifications
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:
RCV000781288.12

Allele description [Variation Report for NM_000492.4(CFTR):c.2280G>A (p.Thr760=)]

NM_000492.4(CFTR):c.2280G>A (p.Thr760=)

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.2280G>A (p.Thr760=)
HGVS:
  • NC_000007.14:g.117592447G>A
  • NG_016465.4:g.131664G>A
  • NM_000492.4:c.2280G>AMANE SELECT
  • NP_000483.3:p.Thr760=
  • NP_000483.3:p.Thr760=
  • LRG_663t1:c.2280G>A
  • LRG_663:g.131664G>A
  • LRG_663p1:p.Thr760=
  • NC_000007.13:g.117232501G>A
  • NM_000492.3:c.2280G>A
Links:
dbSNP: rs138634146
NCBI 1000 Genomes Browser:
rs138634146
Molecular consequence:
  • NM_000492.4:c.2280G>A - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000919201Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Likely benign
(Aug 28, 2019) 		germlineclinical testing

Citation Link,

SCV001160049ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process)		Uncertain significance
(Oct 31, 2018) 		germlineclinical testing

Citation Link

Help

Summary from all submissions

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

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000919201.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV001160049.1

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

Description

The CFTR c.2280G>A; p.Thr760Thr variant (rs138634146) is reported in the literature in a single individual affected with chronic pancreatitis (Midha 2010). This variant is observed on only 10 chromosomes in the Genome Aggregation Database, indicating it is not a common polymorphism. This is a synonymous variant in a weakly conserved nucleotide, and computational analyses (Alamut v.2.11) predict that this variant does not alter splicing. When this variant was transfected into cultured bronchial epithelial cells (CFBE41o-) derived from a CF patient homozygous for p.Phe508del, expression analyses suggested the p.Thr760Thr variant led to a reduction in CFTR mRNA, although the amount of CFTR protein was within normal parameters for the cell type (Kirchner 2017). Due to limited information, the clinical significance of the p.Thr760Thr variant is uncertain at this time. References: Kirchner S et al. Alteration of protein function by a silent polymorphism linked to tRNA abundance. PLoS Biol. 2017 May 16;15(5):e2000779. Midha S et al. Idiopathic chronic pancreatitis in India: phenotypic characterisation and strong genetic susceptibility due to SPINK1 and CFTR gene mutations. Gut. 2010 Jun;59(6):800-7.

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

Last Updated: Sep 29, 2024