NC_000005.10:g.13844961C>G AND Primary ciliary dyskinesia

Clinical significance:Pathogenic (Last evaluated: Apr 23, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001202749.2

Allele description [Variation Report for NC_000005.10:g.13844961C>G]

NC_000005.10:g.13844961C>G

Gene:
DNAH5:dynein axonemal heavy chain 5 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
5p15.2
Genomic location:
Preferred name:
NC_000005.10:g.13844961C>G
HGVS:
  • NC_000005.10:g.13844961C>G
  • NG_013081.1:g.104520G>C
  • NG_013081.2:g.104520G>C
  • NP_001360.1:p.Arg1716Pro
  • NC_000005.9:g.13845070C>G
  • NM_001369.2:c.5147G>C
Protein change:
R1716P

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
SCV001373875Invitaecriteria provided, single submitter
Pathogenic
(Apr 23, 2020)
germlineclinical testing

PubMed (3)
[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

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

Primary Ciliary Dyskinesia: Longitudinal Study of Lung Disease by Ultrastructure Defect and Genotype.

Davis SD, Rosenfeld M, Lee HS, Ferkol TW, Sagel SD, Dell SD, Milla C, Pittman JE, Shapiro AJ, Sullivan KM, Nykamp KR, Krischer JP, Zariwala MA, Knowles MR, Leigh MW.

Am J Respir Crit Care Med. 2019 Jan 15;199(2):190-198. doi: 10.1164/rccm.201803-0548OC.

PubMed [citation]
PMID:
30067075
PMCID:
PMC6353004
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001373875.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces arginine with proline at codon 1716 of the DNAH5 protein (p.Arg1716Pro). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of primary ciliary dyskinesia (PMID: 30067075, Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C0). This variant disrupts the p.Arg1716 amino acid residue in DNAH5. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16627867, 30067075). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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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