NM_000492.4(CFTR):c.2939T>A (p.Ile980Lys) AND Congenital bilateral aplasia of vas deferens from CFTR mutation

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jul 12, 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:: RCV000586046.3

Allele description [Variation Report for NM_000492.4(CFTR):c.2939T>A (p.Ile980Lys)]

NM_000492.4(CFTR):c.2939T>A (p.Ile980Lys)

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.2939T>A (p.Ile980Lys)

HGVS:

NC_000007.14:g.117606704T>A
NG_016465.4:g.145921T>A
NM_000492.4:c.2939T>AMANE SELECT
NP_000483.3:p.Ile980Lys
NP_000483.3:p.Ile980Lys
LRG_663t1:c.2939T>A
LRG_663:g.145921T>A
LRG_663p1:p.Ile980Lys
NC_000007.13:g.117246758T>A
NM_000492.3:c.2939T>A

Protein change:

I980K

Links:

dbSNP: rs397508463

NCBI 1000 Genomes Browser:

rs397508463

Molecular consequence:

NM_000492.4:c.2939T>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Congenital bilateral aplasia of vas deferens from CFTR mutation (CBAVD)
Identifiers:: MONDO: MONDO:0010178; MedGen: C0403814; Orphanet: 48; OMIM: 277180

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000696937	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Jul 12, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 9272157, 10923036, 20059485, 21520337, 8947061, 11101688, 8829643 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000696937

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Jul 12, 2023)

germline

clinical testing

PubMed (7)
[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

Distinct spectrum of CFTR gene mutations in congenital absence of vas deferens.

Dörk T, Dworniczak B, Aulehla-Scholz C, Wieczorek D, Böhm I, Mayerova A, Seydewitz HH, Nieschlag E, Meschede D, Horst J, Pander HJ, Sperling H, Ratjen F, Passarge E, Schmidtke J, Stuhrmann M.

Hum Genet. 1997 Sep;100(3-4):365-77.

PubMed [citation]

PMID:: 9272157

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

See all PubMed Citations (7)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000696937.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

Variant summary: CFTR c.2939T>A (p.Ile980Lys) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 7.9e-06 in 251838 control chromosomes. c.2939T>A has been reported in the literature in individuals affected with features of Congenital Bilateral Absence Of The Vas Deferens and/or Cystic Fibrosis/CFTR-related disorders (example, Bienvenu_1997, Claustres_2000, Hubert_1996, Jezequel_2000, Steiner_2011). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 8829643, 10923036, 20059485, 9272157, 8947061, 11101688, 21520337). Six submitters inclusing the CFTR-France database have cited clinical-significance assessments for this variant to ClinVar after 2014. Multiple submitters reported the variant with conflicting assessments (LP, n=4; VUS, n=2). Based on the evidence outlined above, the variant was classified as likely 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: Sep 29, 2024

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