NM_001369.2(DNAH5):c.8387A>G (p.Asp2796Gly) AND Primary ciliary dyskinesia

Clinical significance:Likely pathogenic (Last evaluated: Sep 18, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000469527.4

Allele description [Variation Report for NM_001369.2(DNAH5):c.8387A>G (p.Asp2796Gly)]

NM_001369.2(DNAH5):c.8387A>G (p.Asp2796Gly)

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.8387A>G (p.Asp2796Gly)
HGVS:
  • NC_000005.10:g.13792055T>C
  • NG_013081.1:g.157426A>G
  • NG_013081.2:g.157426A>G
  • NM_001369.2:c.8387A>G
  • NP_001360.1:p.Asp2796Gly
  • NC_000005.9:g.13792164T>C
Protein change:
D2796G
Links:
dbSNP: rs727502974
NCBI 1000 Genomes Browser:
rs727502974
Molecular consequence:
  • NM_001369.2:c.8387A>G - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000546328Invitaecriteria provided, single submitter
Likely pathogenic
(Sep 18, 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, SCV000546328.5

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

Description

This sequence change replaces aspartic acid with glycine at codon 2796 of the DNAH5 protein (p.Asp2796Gly). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been observed on the opposite chromosome (in trans) from another pathogenic variant in an individual affected with primary ciliary dyskinesia (Invitae). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 163140). 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: Possibly Damaging; Align-GVGD: Class C0). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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: Jul 7, 2021

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