NM_001369.3(DNAH5):c.13774C>T (p.Arg4592Ter) AND Primary ciliary dyskinesia

Clinical significance:Likely pathogenic (Last evaluated: Aug 21, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001376959.1

Allele description [Variation Report for NM_001369.3(DNAH5):c.13774C>T (p.Arg4592Ter)]

NM_001369.3(DNAH5):c.13774C>T (p.Arg4592Ter)

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.13774C>T (p.Arg4592Ter)
HGVS:
  • NC_000005.10:g.13692085G>A
  • NG_013081.2:g.257396C>T
  • NM_001369.3:c.13774C>TMANE SELECT
  • NP_001360.1:p.Arg4592Ter
  • NC_000005.9:g.13692194G>A
Protein change:
R4592*
Molecular consequence:
  • NM_001369.3:c.13774C>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV001574167Invitaecriteria provided, single submitter
Likely pathogenic
(Aug 21, 2020)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV001574167.1

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

Description

This sequence change results in a premature translational stop signal in the DNAH5 gene (p.Arg4592*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 33 amino acids of the DNAH5 protein. This variant is present in population databases (rs758112779, ExAC 0.02%). This variant has been observed in combination with another DNAH5 variant in an individual affected with primary ciliary dyskinesia (Invitae). This variant disrupts a region of the protein in which other variant(s) (p.Cys4621Tyr) have been observed in individuals with DNAH5-related conditions (Invitae). This suggests that this may be a clinically significant region of the DNAH5 protein. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Jun 14, 2021

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