NM_000492.3(CFTR):c.1521_1523del (p.Phe508del) AND Congenital bilateral aplasia of vas deferens from CFTR mutation

Germline classification:: Pathogenic (1 submission)
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:: RCV003227599.8

Allele description [Variation Report for NM_000492.3(CFTR):c.1521_1523del (p.Phe508del)]

NM_000492.3(CFTR):c.1521_1523del (p.Phe508del)

Genes:

CFTR:CF transmembrane conductance regulator [Gene - OMIM - HGNC]
CFTR-AS1:CFTR antisense RNA 1 [Gene - HGNC]

Variant type:

Deletion

Cytogenetic location:

7q31.2

Genomic location:

Preferred name:

NM_000492.3(CFTR):c.1521_1523del (p.Phe508del)

Other names:

F508del; deltaF508; F508delF; DF508; Phe508del; DeltaF508; [delta]F508

HGVS:

NC_000007.13:g.117199645_117199647del
NC_000007.14:g.117559592_117559594del
NG_016465.4:g.98809_98811del
NM_000492.4:c.1521_1523delMANE SELECT
NP_000483.3:p.Phe508del
NP_000483.3:p.Phe508del
LRG_663t1:c.1521_1523del
LRG_663:g.98809_98811del
LRG_663p1:p.Phe508del
NC_000007.13:g.117199645_117199647del
NC_000007.13:g.117199646_117199648del
NC_000007.13:g.117199646_117199648del
NC_000007.13:g.117199646_117199648delCTT
NC_000007.14:g.117559592_117559594del
NC_000007.14:g.117559592_117559594delCTT
NG_016465.1:g.84630_84632delCTT
NM_000492.3:c.1520_1522del
NM_000492.3:c.1520_1522delTCT
NM_000492.3:c.1521_1523del
NM_000492.3:c.1521_1523delCTT
NM_000492.4:c.1520_1522delMANE SELECT
NM_000492.4:c.1520_1522delTCTMANE SELECT
NM_000492.4:c.1521_1523delCTTMANE SELECT

Protein change:

PHE508DEL

Links:

PharmGKB Clinical Annotation: 981755820; OMIM: 602421.0001; dbSNP: rs113993960

NCBI 1000 Genomes Browser:

rs113993960

Molecular consequence:

NM_000492.4:c.1521_1523del - inframe_deletion - [Sequence Ontology: SO:0001822]

Functional consequence:

loss_of_function_variant [Sequence Ontology: SO:0002054]

Observations:

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
SCV003925476	Lifecell International Pvt. Ltd	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24958810, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003925476

Lifecell International Pvt. Ltd

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
Asian	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Heterogeneous spectrum of mutations in CFTR gene from Indian patients with congenital absence of the vas deferens and their association with cystic fibrosis genetic modifiers.

Sharma H, Mavuduru RS, Singh SK, Prasad R.

Mol Hum Reprod. 2014 Sep;20(9):827-35. doi: 10.1093/molehr/gau047. Epub 2014 Jun 23.

PubMed [citation]

PMID:: 24958810

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 Lifecell International Pvt. Ltd, SCV003925476.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Asian	1	not provided	not provided	clinical testing	PubMed (2)

Description

A Heterozygous inframe indel variant c.1520_1522delTCT in Exon 11 of the CFTR gene that results in the amino acid substitution p.Phe508del was identified. The observed variant has a minor allele frequency of 0.00707/0.00800% in gnomAD exomes and genomes, respectively. The severity of the impact of this variant on the protein is medium, based on the effect of the protein and REVEL score . Rare Exome Variant Ensemble Learner (REVEL) is an ensembl method for predicting the pathogenicity of missense variants based on a combination of scores from 13 individual tools: MutPred, FATHMM v2.3, VEST 3.0, PolyPhen-2, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP++, SiPhy, phyloP, and phastCons. The REVEL score for an individual missense variant can range from 0 to 1, with higher scores reflecting greater likelihood that the variant is disease-causing. ClinVar has also classified this variant as Pathogenic. (Variant ID 7105). This variant has been previously reported for Indian patients with congenital absence of the vas deferens by Sharma H et al., 2014. Based on the above evidence this variant has been classified as Pathogenic according to the ACMG guidelines.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: May 1, 2024

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