NM_001277115.2(DNAH11):c.4395_4398del (p.Ser1465fs) AND Primary ciliary dyskinesia

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jul 7, 2023
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:: RCV001215916.10

Allele description [Variation Report for NM_001277115.2(DNAH11):c.4395_4398del (p.Ser1465fs)]

NM_001277115.2(DNAH11):c.4395_4398del (p.Ser1465fs)

Gene:

DNAH11:dynein axonemal heavy chain 11 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

7p15.3

Genomic location:

Preferred name:

NM_001277115.2(DNAH11):c.4395_4398del (p.Ser1465fs)

HGVS:

NC_000007.14:g.21619969TCAG[1]
NG_012886.2:g.81755TCAG[1]
NM_001277115.2:c.4395_4398delMANE SELECT
NP_001264044.1:p.Ser1465fs
NC_000007.13:g.21659587TCAG[1]
NC_000007.13:g.21659587_21659590del
NM_001277115.1:c.4395_4398del
NM_001277115.1:c.4395_4398delTCAG

Protein change:

S1465fs

Links:

dbSNP: rs761764078

NCBI 1000 Genomes Browser:

rs761764078

Molecular consequence:

NM_001277115.2:c.4395_4398del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV001387685	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 7, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 18022865, 20513915, 22184204, 28492532
SCV002628779	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Feb 18, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001387685

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 7, 2023)

germline

clinical testing

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

SCV002628779

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Feb 18, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

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

Primary ciliary dyskinesia associated with normal axoneme ultrastructure is caused by DNAH11 mutations.

Schwabe GC, Hoffmann K, Loges NT, Birker D, Rossier C, de Santi MM, Olbrich H, Fliegauf M, Failly M, Liebers U, Collura M, Gaedicke G, Mundlos S, Wahn U, Blouin JL, Niggemann B, Omran H, Antonarakis SE, Bartoloni L.

Hum Mutat. 2008 Feb;29(2):289-98.

PubMed [citation]

PMID:: 18022865

New DNAH11 mutations in primary ciliary dyskinesia with normal axonemal ultrastructure.

Pifferi M, Michelucci A, Conidi ME, Cangiotti AM, Simi P, Macchia P, Boner AL.

Eur Respir J. 2010 Jun;35(6):1413-6. doi: 10.1183/09031936.00186209. No abstract available.

PubMed [citation]

PMID:: 20513915

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001387685.5

#	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.Ser1465Argfs*6) in the DNAH11 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DNAH11 are known to be pathogenic (PMID: 18022865, 20513915, 22184204). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 945304). This premature translational stop signal has been observed in individual(s) with primary ciliary dyskinesia (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database.

#	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 Ambry Genetics, SCV002628779.2

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

Description

The c.4395_4398delTCAG pathogenic mutation, located in coding exon 25 of the DNAH11 gene, results from a deletion of 4 nucleotides at nucleotide positions 4395 to 4398, causing a translational frameshift with a predicted alternate stop codon (p.S1465Rfs*6). This alteration was found in conjunction with another truncating mutation in DNAH11 in an individual with recurrent chest infections and rhinitis (Shoemark A et al. Eur Respir J, 2018 02;51:). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#	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 23, 2024

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