NM_001369.3(DNAH5):c.2772del (p.Thr924_Leu925insTer) AND Primary ciliary dyskinesia

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jan 19, 2024
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:: RCV000557562.12

Allele description [Variation Report for NM_001369.3(DNAH5):c.2772del (p.Thr924_Leu925insTer)]

NM_001369.3(DNAH5):c.2772del (p.Thr924_Leu925insTer)

Gene:

DNAH5:dynein axonemal heavy chain 5 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

5p15.2

Genomic location:

Preferred name:

NM_001369.3(DNAH5):c.2772del (p.Thr924_Leu925insTer)

HGVS:

NC_000005.10:g.13885201del
NG_013081.2:g.64281del
NM_001369.3:c.2772delMANE SELECT
NP_001360.1:p.Thr924_Leu925insTer
NP_001360.1:p.Thr924_Leu925insTer
NC_000005.9:g.13885309del
NC_000005.9:g.13885310del
NM_001369.2:c.2772del
NM_001369.2:c.2772delC

Links:

dbSNP: rs1554090622

NCBI 1000 Genomes Browser:

rs1554090622

Molecular consequence:

NM_001369.3:c.2772del - 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

Recent activity

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PREDICTED: Homo sapiens family with sequence similarity 86 member B1 (FAM86B1), ...
PREDICTED: Homo sapiens family with sequence similarity 86 member B1 (FAM86B1), transcript variant X12, mRNA
gi|2217373574|ref|XM_011543842.4|

Nucleotide
PREDICTED: Homo sapiens family with sequence similarity 86 member B1 (FAM86B1), ...
PREDICTED: Homo sapiens family with sequence similarity 86 member B1 (FAM86B1), transcript variant X10, mRNA
gi|2217373572|ref|XM_017013917.3|

Nucleotide
Mus musculus syntaxin binding protein 6 (amisyn) (Stxbp6), transcript variant 4,...
Mus musculus syntaxin binding protein 6 (amisyn) (Stxbp6), transcript variant 4, mRNA
gi|2289229149|ref|NM_001411383.1|

Nucleotide
syntaxin-binding protein 6 isoform 1 [Mus musculus]
syntaxin-binding protein 6 isoform 1 [Mus musculus]
gi|2289229095|ref|NP_001398310.1|

Protein
beta-arrestin-2 isoform X2 [Mus musculus]
beta-arrestin-2 isoform X2 [Mus musculus]
gi|1907081169|ref|XP_036012467.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000624239	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 19, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 11788826, 16627867, 28492532
SCV002106424	Yale Center for Mendelian Genomics, Yale University - Yale Center for Mendelian Genomics	no assertion criteria provided	Likely pathogenic (Aug 1, 2018)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV002746567	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Sep 12, 2016)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000624239

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 19, 2024)

germline

clinical testing

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

SCV002106424

Yale Center for Mendelian Genomics, Yale University - Yale Center for Mendelian Genomics

no assertion criteria provided

Likely pathogenic
(Aug 1, 2018)

germline

literature only

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

SCV002746567

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Sep 12, 2016)

germline

clinical testing

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Mutations in DNAH5 cause primary ciliary dyskinesia and randomization of left-right asymmetry.

Olbrich H, Häffner K, Kispert A, Völkel A, Volz A, Sasmaz G, Reinhardt R, Hennig S, Lehrach H, Konietzko N, Zariwala M, Noone PG, Knowles M, Mitchison HM, Meeks M, Chung EM, Hildebrandt F, Sudbrak R, Omran H.

Nat Genet. 2002 Feb;30(2):143-4. Epub 2002 Jan 14.

PubMed [citation]

PMID:: 11788826

DNAH5 mutations are a common cause of primary ciliary dyskinesia with outer dynein arm defects.

Hornef N, Olbrich H, Horvath J, Zariwala MA, Fliegauf M, Loges NT, Wildhaber J, Noone PG, Kennedy M, Antonarakis SE, Blouin JL, Bartoloni L, Nüsslein T, Ahrens P, Griese M, Kuhl H, Sudbrak R, Knowles MR, Reinhardt R, Omran H.

Am J Respir Crit Care Med. 2006 Jul 15;174(2):120-6. Epub 2006 Apr 20.

PubMed [citation]

PMID:: 16627867
PMCID:: PMC2662904

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000624239.7

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

Description

This sequence change creates a premature translational stop signal (p.Leu925*) in the DNAH5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DNAH5 are known to be pathogenic (PMID: 11788826, 16627867). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with DNAH5-related conditions. ClinVar contains an entry for this variant (Variation ID: 454761). 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

From Yale Center for Mendelian Genomics, Yale University - Yale Center for Mendelian Genomics, SCV002106424.1

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

#	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 Ambry Genetics, SCV002746567.2

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

Description

The c.2772delC pathogenic mutation, located in coding exon 19 of the DNAH5 gene, results from a deletion of one nucleotide at nucleotide position 2772, causing a translational frameshift with a predicted alternate stop codon (p.L925*). 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: Oct 8, 2024

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