NM_001206927.2(DNAH8):c.4610G>T (p.Arg1537Leu) AND Primary ciliary dyskinesia

Clinical significance:Uncertain significance (Last evaluated: Oct 2, 2019)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000629265.4

Allele description [Variation Report for NM_001206927.2(DNAH8):c.4610G>T (p.Arg1537Leu)]

NM_001206927.2(DNAH8):c.4610G>T (p.Arg1537Leu)

Gene:
DNAH8:dynein axonemal heavy chain 8 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
6p21.2
Genomic location:
Preferred name:
NM_001206927.2(DNAH8):c.4610G>T (p.Arg1537Leu)
HGVS:
  • NC_000006.12:g.38842668G>T
  • NG_041805.1:g.132328G>T
  • NM_001206927.2:c.4610G>TMANE SELECT
  • NM_001371.4:c.3959G>T
  • NP_001193856.1:p.Arg1537Leu
  • NP_001362.2:p.Arg1320Leu
  • NC_000006.11:g.38810444G>T
  • NM_001206927.1:c.4610G>T
Protein change:
R1320L
Links:
dbSNP: rs375507271
NCBI 1000 Genomes Browser:
rs375507271
Molecular consequence:
  • NM_001206927.2:c.4610G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371.4:c.3959G>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

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
SCV000750200Invitaecriteria provided, single submitter
Uncertain significance
(Oct 2, 2019)
germlineclinical testing

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

SCV001431754UNC Molecular Genetics Laboratory,University of North Carolina at Chapel Hillcriteria provided, single submitter
Uncertain significance
(Oct 12, 2018)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown11not 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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Invitae, SCV000750200.3

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

Description

This sequence change replaces arginine with leucine at codon 1537 of the DNAH8 protein (p.Arg1537Leu). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and leucine. This variant is present in population databases (rs375507271, ExAC 0.002%). This variant has not been reported in the literature in individuals with DNAH8-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C0). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

From UNC Molecular Genetics Laboratory,University of North Carolina at Chapel Hill, SCV001431754.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing
(GTR000576399.1)
PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided
(GTR000576399.1)
1not provided1not provided

Last Updated: Aug 27, 2021

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