NM_021147.5(CCNO):c.248_252dup (p.Gly85fs) AND Primary ciliary dyskinesia 29

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Apr 26, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000128540.13

Allele description [Variation Report for NM_021147.5(CCNO):c.248_252dup (p.Gly85fs)]

NM_021147.5(CCNO):c.248_252dup (p.Gly85fs)

Genes:

LOC129993895:ATAC-STARR-seq lymphoblastoid silent region 16013 [Gene]
CCNO:cyclin O [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

5q11.2

Genomic location:

Preferred name:

NM_021147.5(CCNO):c.248_252dup (p.Gly85fs)

HGVS:

NC_000005.10:g.55233275_55233279dup
NG_034201.1:g.5442_5446dup
NM_021147.5:c.248_252dupMANE SELECT
NP_066970.3:p.Gly85fs
NC_000005.9:g.54529099_54529100insGGGCA
NC_000005.9:g.54529103_54529107dup
NM_021147.4:c.248_252dupTGCCC
NP_066970.3:p.Gly85CysfsTer11
NR_125346.2:n.333_337dup
NR_125347.2:n.333_337dup

Protein change:

G85fs

Links:

OMIM: 607752.0001; dbSNP: rs587777498

NCBI 1000 Genomes Browser:

rs587777498

Molecular consequence:

NM_021147.5:c.248_252dup - frameshift variant - [Sequence Ontology: SO:0001589]
NR_125346.2:n.333_337dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_125347.2:n.333_337dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Name:: Primary ciliary dyskinesia 29
Synonyms:: CILIARY DYSKINESIA, PRIMARY, 29, WITHOUT SITUS INVERSUS
Identifiers:: MONDO: MONDO:0014378; MedGen: C4014534; Orphanet: 244; OMIM: 615872

Recent activity

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Caenorhabditis elegans Asparagine--tRNA ligase, cytoplasmic (nars-1), mRNA
Caenorhabditis elegans Asparagine--tRNA ligase, cytoplasmic (nars-1), mRNA
gi|1972230270|ref|NM_001026234.8|

Nucleotide
Caenorhabditis elegans YTH domain-containing protein (Y67D8C.6), partial mRNA
Caenorhabditis elegans YTH domain-containing protein (Y67D8C.6), partial mRNA
gi|1734328577|ref|NM_067886.2|

Nucleotide
Caenorhabditis elegans YitH/HolE acetyltransferase (GNAT) domain-containing prot...
Caenorhabditis elegans YitH/HolE acetyltransferase (GNAT) domain-containing protein (ZK228.3), mRNA
gi|1845979036|ref|NM_075213.6|

Nucleotide
Vacuolar protein sorting-associated protein 55 homolog [Caenorhabditis elegans]
Vacuolar protein sorting-associated protein 55 homolog [Caenorhabditis elegans]
gi|32564911|ref|NP_495238.2|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000172183	OMIM	no assertion criteria provided	Pathogenic (Jun 1, 2014)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV001499909	Beijing Key Laboratry for Genetics of Birth Defects, Beijing Children's Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 20, 2020)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 24747639, 30067075, 32367404, 25741868
SCV002058645	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 3, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] PMID:24747639,
SCV002798505	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 26, 2022)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	1	not provided	not provided	1	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
East Asia	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in CCNO result in congenital mucociliary clearance disorder with reduced generation of multiple motile cilia.

Wallmeier J, Al-Mutairi DA, Chen CT, Loges NT, Pennekamp P, Menchen T, Ma L, Shamseldin HE, Olbrich H, Dougherty GW, Werner C, Alsabah BH, Köhler G, Jaspers M, Boon M, Griese M, Schmitt-Grohé S, Zimmermann T, Koerner-Rettberg C, Horak E, Kintner C, Alkuraya FS, et al.

Nat Genet. 2014 Jun;46(6):646-51. doi: 10.1038/ng.2961. Epub 2014 Apr 20.

PubMed [citation]

PMID:: 24747639

Primary Ciliary Dyskinesia: Longitudinal Study of Lung Disease by Ultrastructure Defect and Genotype.

Davis SD, Rosenfeld M, Lee HS, Ferkol TW, Sagel SD, Dell SD, Milla C, Pittman JE, Shapiro AJ, Sullivan KM, Nykamp KR, Krischer JP, Zariwala MA, Knowles MR, Leigh MW.

Am J Respir Crit Care Med. 2019 Jan 15;199(2):190-198. doi: 10.1164/rccm.201803-0548OC.

PubMed [citation]

PMID:: 30067075
PMCID:: PMC6353004

See all PubMed Citations (4)

Details of each submission

From OMIM, SCV000172183.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In 4 affected members of a consanguineous Kuwaiti family with primary ciliary dyskinesia-29 (CILD29; 615872), Wallmeier et al. (2014) identified a homozygous 5-bp duplication (c.248_252dupTGCCC) in exon 1 of the CCNO gene, resulting in a frameshift and premature termination (Gly85CysfsTer10). The mutation, which was found by whole-exome sequencing, segregated with the disorder in the family and was not present in the 1000 Genomes Project database. One additional patient was found to be compound heterozygous for the c.248_252dupTGCCC mutation and a 2-bp deletion in exon 2 (c.481_482delCT; 607752.0006), resulting in a frameshift and premature termination (Leu161GlyfsTer72).

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

From Beijing Key Laboratry for Genetics of Birth Defects, Beijing Children's Hospital, SCV001499909.1

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

#	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

From 3billion, SCV002058645.1

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

Description

Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). Functional studies provide strong evidence of the variant having a damaging effect on the gene or gene product (PMID:24747639, PS3_S). The variant has been reported at least twice as pathogenic/likely pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000139599, PMID:24747639). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000034, PM2_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.

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

From Fulgent Genetics, Fulgent Genetics, SCV002798505.1

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

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

Last Updated: Nov 10, 2024

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