NM_001369.3(DNAH5):c.12734T>C (p.Met4245Thr) AND Primary ciliary dyskinesia

Clinical significance:Uncertain significance (Last evaluated: May 20, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000398612.4

Allele description [Variation Report for NM_001369.3(DNAH5):c.12734T>C (p.Met4245Thr)]

NM_001369.3(DNAH5):c.12734T>C (p.Met4245Thr)

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.12734T>C (p.Met4245Thr)
HGVS:
  • NC_000005.10:g.13716662A>G
  • NG_013081.2:g.232819T>C
  • NM_001369.2:c.12734T>C
  • NM_001369.3:c.12734T>CMANE SELECT
  • NP_001360.1:p.Met4245Thr
  • NP_001360.1:p.Met4245Thr
  • NC_000005.9:g.13716771A>G
Protein change:
M4245T
Links:
dbSNP: rs766597612
NCBI 1000 Genomes Browser:
rs766597612
Molecular consequence:
  • NM_001369.2:c.12734T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369.3:c.12734T>C - 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
SCV000546303Invitaecriteria provided, single submitter
Uncertain significance
(May 20, 2016)
germlineclinical testing

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

SCV001462285Natera, Inc.no assertion criteria providedUncertain significance
(Sep 16, 2020)
germlineclinical testing

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, SCV000546303.2

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

Description

This sequence change replaces methionine with threonine at codon 4245 of the DNAH5 protein (p.Met4245Thr). The methionine residue is highly conserved and there is a moderate physicochemical difference between methionine and threonine. This variant is present in population databases (rs766597612, ExAC 0.005%) but has not been reported in the literature in individuals with a DNAH5-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, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. 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 Natera, Inc., SCV001462285.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

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