NM_000492.4(CFTR):c.2977G>T (p.Asp993Tyr) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 1, 2023
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:: RCV003155058.1

Allele description [Variation Report for NM_000492.4(CFTR):c.2977G>T (p.Asp993Tyr)]

NM_000492.4(CFTR):c.2977G>T (p.Asp993Tyr)

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.2977G>T (p.Asp993Tyr)

HGVS:

NC_000007.14:g.117606742G>T
NG_016465.4:g.145959G>T
NM_000492.4:c.2977G>TMANE SELECT
NP_000483.3:p.Asp993Tyr
NP_000483.3:p.Asp993Tyr
LRG_663t1:c.2977G>T
LRG_663:g.145959G>T
LRG_663p1:p.Asp993Tyr
NC_000007.13:g.117246796G>T
NM_000492.3:c.2977G>T

Protein change:

D993Y

Links:

dbSNP: rs397508468

NCBI 1000 Genomes Browser:

rs397508468

Molecular consequence:

NM_000492.4:c.2977G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003844824	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Feb 1, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 10923036, 15698946, 15463906 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003844824

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Feb 1, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

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

Spectrum of CFTR mutations in cystic fibrosis and in congenital absence of the vas deferens in France.

Claustres M, Guittard C, Bozon D, Chevalier F, Verlingue C, Ferec C, Girodon E, Cazeneuve C, Bienvenu T, Lalau G, Dumur V, Feldmann D, Bieth E, Blayau M, Clavel C, Creveaux I, Malinge MC, Monnier N, Malzac P, Mittre H, Chomel JC, Bonnefont JP, et al.

Hum Mutat. 2000;16(2):143-56.

PubMed [citation]

PMID:: 10923036

High heterogeneity of CFTR mutations and unexpected low incidence of cystic fibrosis in the Mediterranean France.

des Georges M, Guittard C, Altiéri JP, Templin C, Sarles J, Sarda P, Claustres M.

J Cyst Fibros. 2004 Dec;3(4):265-72.

PubMed [citation]

PMID:: 15698946

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV003844824.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

Variant summary: CFTR c.2977G>T (p.Asp993Tyr) results in a non-conservative amino acid change located in the ABC transporter type 1, transmembrane domain (IPR011527) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251120 control chromosomes (gnomAD). c.2977G>T has been reported in the literature in individuals affected with Cystic Fibrosis (e.g. Claustres_2000, des Georges_2004, Dugueperoux_2004). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One ClinVar submitter has assessed the variant since 2014: the variant was classified as pathogenic. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.

#	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: May 1, 2024

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