NM_001256715.2(DNAAF3):c.1044_1048+13del AND Primary ciliary dyskinesia

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Apr 22, 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:: RCV003652602.2

Allele description [Variation Report for NM_001256715.2(DNAAF3):c.1044_1048+13del]

NM_001256715.2(DNAAF3):c.1044_1048+13del

Genes:

LOC130065090:ATAC-STARR-seq lymphoblastoid silent region 11016 [Gene]
DNAAF3-AS1:DNAAF3 antisense RNA 1 [Gene - HGNC]
DNAAF3:dynein axonemal assembly factor 3 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

19q13.42

Genomic location:

Preferred name:

NM_001256715.2(DNAAF3):c.1044_1048+13del

HGVS:

NC_000019.10:g.55160637_55160654del
NG_007866.2:g.2089_2106del
NG_032759.1:g.11079_11096del
NG_142072.1:g.1_2insTCCCTGG
NG_199507.1:g.111_128del
NM_001256714.1:c.1248_1252+13del
NM_001256715.2:c.1044_1048+13delMANE SELECT
NM_001256716.2:c.882_886+13del
NM_178837.4:c.1185_1189+13del
LRG_432:g.2089_2106del
NC_000019.9:g.55671995_55672012del
NC_000019.9:g.55672005_55672022del

Molecular consequence:

NM_001256714.1:c.1248_1252+13del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001256715.2:c.1044_1048+13del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001256716.2:c.882_886+13del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_178837.4:c.1185_1189+13del - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

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

Recent activity

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SRX20487483 (1)
SRA
RNA polymerase factor sigma-54 [Peribacillus frigoritolerans]
RNA polymerase factor sigma-54 [Peribacillus frigoritolerans]
gb|MED3835085.1||gnl|WGS:JARMTR|P46 825

Protein
Carduus pycnocephalus isolate Tzarevo 2011 internal transcribed spacer 1, partia...
Carduus pycnocephalus isolate Tzarevo 2011 internal transcribed spacer 1, partial sequence; 5.8S ribosomal RNA gene, complete sequence; and internal transcribed spacer 2, partial sequence
gi|969535532|gb|KT363916.1|

Nucleotide
Carduus pycnocephalus voucher CAG-805 internal transcribed spacer 1, partial seq...
Carduus pycnocephalus voucher CAG-805 internal transcribed spacer 1, partial sequence; 5.8S ribosomal RNA gene and internal transcribed spacer 2, complete sequence; and large subunit ribosomal RNA gene, partial sequence
gi|1108638972|gb|KY242484.1|

Nucleotide
PREDICTED: Cucurbita pepo subsp. pepo PLASMODESMATA CALLOSE-BINDING PROTEIN 3-li...
PREDICTED: Cucurbita pepo subsp. pepo PLASMODESMATA CALLOSE-BINDING PROTEIN 3-like (LOC111798427), mRNA
gi|1333125725|ref|XM_023681557.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004449746	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Apr 22, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16199547, 22387996, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004449746

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Apr 22, 2023)

germline

clinical testing

PubMed (3)
[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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

Mutations in axonemal dynein assembly factor DNAAF3 cause primary ciliary dyskinesia.

Mitchison HM, Schmidts M, Loges NT, Freshour J, Dritsoula A, Hirst RA, O'Callaghan C, Blau H, Al Dabbagh M, Olbrich H, Beales PL, Yagi T, Mussaffi H, Chung EM, Omran H, Mitchell DR.

Nat Genet. 2012 Mar 4;44(4):381-9, S1-2. doi: 10.1038/ng.1106.

PubMed [citation]

PMID:: 22387996
PMCID:: PMC3315610

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004449746.1

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

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with DNAAF3-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant results in the deletion of part of exon 9 of the DNAAF3 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in DNAAF3 are known to be pathogenic (PMID: 22387996).

#	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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