NM_001369.3(DNAH5):c.5710-2A>G AND Primary ciliary dyskinesia

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Dec 28, 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:: RCV000532226.10

Allele description [Variation Report for NM_001369.3(DNAH5):c.5710-2A>G]

NM_001369.3(DNAH5):c.5710-2A>G

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

5p15.2

Genomic location:

Preferred name:

NM_001369.3(DNAH5):c.5710-2A>G

HGVS:

NC_000005.10:g.13839530T>C
NG_013081.2:g.109951A>G
NM_001369.3:c.5710-2A>GMANE SELECT
NC_000005.9:g.13839639T>C
NM_001369.2:c.5710-2A>G

Links:

dbSNP: rs548521732

NCBI 1000 Genomes Browser:

rs548521732

Molecular consequence:

NM_001369.3:c.5710-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

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
SCV000624274	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 28, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 16199547, 11788826, 16627867, 19357118, 27637300, 28492532
SCV001457358	Natera, Inc.	no assertion criteria provided	Pathogenic (Sep 16, 2020)	germline	clinical testing
SCV002106428	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]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000624274

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 28, 2023)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

SCV001457358

Natera, Inc.

no assertion criteria provided

Pathogenic
(Sep 16, 2020)

germline

clinical testing

SCV002106428

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]

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
not provided	germline	yes	1	not provided	not provided	not provided	not provided	literature only

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 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

See all PubMed Citations (7)

Details of each submission

From Invitae, SCV000624274.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change affects an acceptor splice site in intron 34 of the DNAH5 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 DNAH5 are known to be pathogenic (PMID: 11788826, 16627867). This variant is present in population databases (rs548521732, gnomAD 0.02%). Disruption of this splice site has been observed in individual(s) with primary ciliary dyskinesia (PMID: 19357118, 27637300). ClinVar contains an entry for this variant (Variation ID: 454788). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 Natera, Inc., SCV001457358.1

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

#	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, SCV002106428.1

#	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

Last Updated: Jul 15, 2024

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