NM_181426.2(CCDC39):c.2497_2498del (p.Gln833fs) AND Primary ciliary dyskinesia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 14, 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:: RCV000529219.18

Allele description [Variation Report for NM_181426.2(CCDC39):c.2497_2498del (p.Gln833fs)]

NM_181426.2(CCDC39):c.2497_2498del (p.Gln833fs)

Genes:

CCDC39:coiled-coil domain 39 molecular ruler complex subunit [Gene - OMIM - HGNC]
TTC14:tetratricopeptide repeat domain 14 [Gene - HGNC]

Variant type:

Deletion

Cytogenetic location:

3q26.33

Genomic location:

Preferred name:

NM_181426.2(CCDC39):c.2497_2498del (p.Gln833fs)

HGVS:

NC_000003.11:g.180334392_180334393del
NC_000003.12:g.180616605_180616606del
NG_029581.1:g.67891_67892del
NM_001288582.2:c.1775-775_1775-774del
NM_181426.2:c.2497_2498delMANE SELECT
NP_852091.1:p.Gln833fs
NC_000003.11:g.180334392_180334393del
NC_000003.11:g.180334392_180334393delTG
NC_000003.11:g.180334393_180334394del
NM_181426.1:c.2497_2498del
NM_181426.1:c.2497_2498delCA

Protein change:

Q833fs

Links:

dbSNP: rs1007345781

NCBI 1000 Genomes Browser:

rs1007345781

Molecular consequence:

NM_181426.2:c.2497_2498del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001288582.2:c.1775-775_1775-774del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Primary ciliary dyskinesia
Synonyms:: Ciliary dyskinesia
Identifiers:: MONDO: MONDO:0016575; MedGen: C0008780; OMIM: PS244400; Human Phenotype Ontology: HP:0012265

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000624546	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 14, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 21131972, 23255504, 23891469, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000624546

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 14, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

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

CCDC39 is required for assembly of inner dynein arms and the dynein regulatory complex and for normal ciliary motility in humans and dogs.

Merveille AC, Davis EE, Becker-Heck A, Legendre M, Amirav I, Bataille G, Belmont J, Beydon N, Billen F, Clément A, Clercx C, Coste A, Crosbie R, de Blic J, Deleuze S, Duquesnoy P, Escalier D, Escudier E, Fliegauf M, Horvath J, Hill K, Jorissen M, et al.

Nat Genet. 2011 Jan;43(1):72-8. doi: 10.1038/ng.726. Epub 2010 Dec 5.

PubMed [citation]

PMID:: 21131972
PMCID:: PMC3509786

Mutations in CCDC39 and CCDC40 are the major cause of primary ciliary dyskinesia with axonemal disorganization and absent inner dynein arms.

Antony D, Becker-Heck A, Zariwala MA, Schmidts M, Onoufriadis A, Forouhan M, Wilson R, Taylor-Cox T, Dewar A, Jackson C, Goggin P, Loges NT, Olbrich H, Jaspers M, Jorissen M, Leigh MW, Wolf WE, Daniels ML, Noone PG, Ferkol TW, Sagel SD, Rosenfeld M, et al.

Hum Mutat. 2013 Mar;34(3):462-72. doi: 10.1002/humu.22261. Epub 2013 Feb 11.

PubMed [citation]

PMID:: 23255504
PMCID:: PMC3630464

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000624546.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Gln833Valfs*6) in the CCDC39 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CCDC39 are known to be pathogenic (PMID: 21131972, 23255504). This variant is present in population databases (no rsID available, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with primary ciliary dyskinesia (PMID: 23891469). ClinVar contains an entry for this variant (Variation ID: 455019). For these reasons, this variant has been classified as 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: Jun 17, 2024

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