NM_018076.5(ODAD2):c.2219G>A (p.Trp740Ter) AND Primary ciliary dyskinesia 23

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Oct 14, 2021
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:: RCV000234856.7

Allele description

NM_018076.5(ODAD2):c.2219G>A (p.Trp740Ter)

Gene:

ODAD2:outer dynein arm docking complex subunit 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10p12.1

Genomic location:

Preferred name:

NM_018076.5(ODAD2):c.2219G>A (p.Trp740Ter)

HGVS:

NC_000010.11:g.27936759C>T
NG_042820.1:g.67292G>A
NM_001290020.2:c.2219G>A
NM_001290021.2:c.794G>A
NM_001312689.2:c.1295G>A
NM_018076.5:c.2219G>AMANE SELECT
NP_001276949.1:p.Trp740Ter
NP_001276950.1:p.Trp265Ter
NP_001299618.1:p.Trp432Ter
NP_060546.2:p.Trp740Ter
NC_000010.10:g.28225688C>T
NM_018076.2:c.2219G>A

Protein change:

W265*

Links:

dbSNP: rs201213030

NCBI 1000 Genomes Browser:

rs201213030

Molecular consequence:

NM_001290020.2:c.2219G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001290021.2:c.794G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001312689.2:c.1295G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_018076.5:c.2219G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Primary ciliary dyskinesia 23 (CILD23)
Synonyms:: CILIARY DYSKINESIA, PRIMARY, 23, WITH OR WITHOUT SITUS INVERSUS
Identifiers:: MONDO: MONDO:0014193; MedGen: C3809548; Orphanet: 244; OMIM: 615451

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000291986	Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	criteria provided, single submitter (Hjeij et al. (Am J Hum Genet. 2013))	Pathogenic (Apr 3, 2013)	germline	research	PubMed (3) [See all records that cite these PMIDs] 23806086, 24088041, 23849778
SCV001200315	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 14, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23849778, 28492532
SCV001251485	UNC Molecular Genetics Laboratory, University of North Carolina at Chapel Hill - NSIGHT-NC NEXUS	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic	germline	research	PubMed (2) [See all records that cite these PMIDs] 23849778, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000291986

Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine

criteria provided, single submitter

(Hjeij et al. (Am J Hum Genet. 2013))

Pathogenic
(Apr 3, 2013)

germline

research

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

SCV001200315

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 14, 2021)

germline

clinical testing

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

SCV001251485

UNC Molecular Genetics Laboratory, University of North Carolina at Chapel Hill - NSIGHT-NC NEXUS

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic

germline

research

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
not provided	germline	yes	1	1	not provided	135	yes	research
not provided	germline	no	1	not provided	not provided	not provided	not provided	research
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Exome sequencing resolves apparent incidental findings and reveals further complexity of SH3TC2 variant alleles causing Charcot-Marie-Tooth neuropathy.

Lupski JR, Gonzaga-Jauregui C, Yang Y, Bainbridge MN, Jhangiani S, Buhay CJ, Kovar CL, Wang M, Hawes AC, Reid JG, Eng C, Muzny DM, Gibbs RA.

Genome Med. 2013;5(6):57. doi: 10.1186/gm461.

PubMed [citation]

PMID:: 23806086
PMCID:: PMC3706849

Clinical whole-exome sequencing for the diagnosis of mendelian disorders.

Yang Y, Muzny DM, Reid JG, Bainbridge MN, Willis A, Ward PA, Braxton A, Beuten J, Xia F, Niu Z, Hardison M, Person R, Bekheirnia MR, Leduc MS, Kirby A, Pham P, Scull J, Wang M, Ding Y, Plon SE, Lupski JR, Beaudet AL, et al.

N Engl J Med. 2013 Oct 17;369(16):1502-11. doi: 10.1056/NEJMoa1306555. Epub 2013 Oct 2.

PubMed [citation]

PMID:: 24088041
PMCID:: PMC4211433

See all PubMed Citations (5)

Details of each submission

From Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine, SCV000291986.1

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

Description

This compound heterzygous mutation was predicted to be loss-of-function.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	135	not provided	not provided		1	not provided	1	not provided

From Invitae, SCV001200315.5

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

Description

For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with primary ciliary dyskinesia (PMID: 23849778). This variant is present in population databases (rs201213030, ExAC 0.01%). This sequence change creates a premature translational stop signal (p.Trp740*) in the ARMC4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ARMC4 are known to be pathogenic (PMID: 23849778).

#	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

From UNC Molecular Genetics Laboratory, University of North Carolina at Chapel Hill - NSIGHT-NC NEXUS, SCV001251485.1

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

Description

The ARMC4 c.2219G>A (p.W740*) nonsense variant is predicted to result in an absent or aberrant protein. This variant has been reported in one individual with primary ciliary dyskinesia (PMID 23849778).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Feb 14, 2024

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