NM_001369.2(DNAH5):c.9897+1G>C AND Primary ciliary dyskinesia

Clinical significance:Pathogenic (Last evaluated: Mar 12, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000689365.3

Allele description [Variation Report for NM_001369.2(DNAH5):c.9897+1G>C]

NM_001369.2(DNAH5):c.9897+1G>C

Gene:
DNAH5:dynein axonemal heavy chain 5 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
5p15.2
Genomic location:
Preferred name:
NM_001369.2(DNAH5):c.9897+1G>C
HGVS:
  • NC_000005.10:g.13768959C>G
  • NG_013081.1:g.180522G>C
  • NG_013081.2:g.180522G>C
  • NM_001369.2:c.9897+1G>C
  • NC_000005.9:g.13769068C>G
Links:
dbSNP: rs914675446
NCBI 1000 Genomes Browser:
rs914675446
Molecular consequence:
  • NM_001369.2:c.9897+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Primary ciliary dyskinesia (PCD)
Synonyms:
Polynesian bronchiectasis; Immotile cilia syndrome; Ciliary dyskinesia
Identifiers:
MONDO: MONDO:0016575; MedGen: C0008780; OMIM: PS244400; Human Phenotype Ontology: HP:0012265

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000817013Invitaecriteria provided, single submitter
Pathogenic
(Mar 12, 2019)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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 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 (4)

Details of each submission

From Invitae, SCV000817013.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change affects a donor splice site in intron 58 of the DNAH5 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant occurs with a pathogenic variant in DNAH5 in an individual with primary ciliary dyskinesia (Invitae). While it is unknown if these two variants are on the same or opposite chromosomes, this observation suggests the c.9897+1G>C substitution may contribute to the cause of disease. ClinVar contains an entry for this variant (Variation ID: 238978). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants 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). For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 14, 2021

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