NM_001369.3(DNAH5):c.5177T>C (p.Leu1726Pro) AND Primary ciliary dyskinesia

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Dec 13, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000525295.11

Allele description [Variation Report for NM_001369.3(DNAH5):c.5177T>C (p.Leu1726Pro)]

NM_001369.3(DNAH5):c.5177T>C (p.Leu1726Pro)

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.5177T>C (p.Leu1726Pro)

HGVS:

NC_000005.10:g.13844931A>G
NG_013081.2:g.104550T>C
NM_001369.3:c.5177T>CMANE SELECT
NP_001360.1:p.Leu1726Pro
NP_001360.1:p.Leu1726Pro
NC_000005.9:g.13845040A>G
NM_001369.2:c.5177T>C

Protein change:

L1726P

Links:

dbSNP: rs138890576

NCBI 1000 Genomes Browser:

rs138890576

Molecular consequence:

NM_001369.3:c.5177T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Primary ciliary dyskinesia
Synonyms:: Ciliary dyskinesia
Identifiers:: MONDO: MONDO:0016575; MedGen: C0008780; OMIM: PS244400; Human Phenotype Ontology: HP:0012265

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000624265	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 13, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 26228299, 26938784, 29453417, 28492532
SCV001457366	Natera, Inc.	no assertion criteria provided	Pathogenic (Sep 16, 2020)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000624265

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 13, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV001457366

Natera, Inc.

no assertion criteria provided

Pathogenic
(Sep 16, 2020)

germline

clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

An effective combination of sanger and next generation sequencing in diagnostics of primary ciliary dyskinesia.

Djakow J, Kramná L, Dušátková L, Uhlík J, Pursiheimo JP, Svobodová T, Pohunek P, Cinek O.

Pediatr Pulmonol. 2016 May;51(5):498-509. doi: 10.1002/ppul.23261. Epub 2015 Jul 30.

PubMed [citation]

PMID:: 26228299

A prospective evaluation of whole-exome sequencing as a first-tier molecular test in infants with suspected monogenic disorders.

Stark Z, Tan TY, Chong B, Brett GR, Yap P, Walsh M, Yeung A, Peters H, Mordaunt D, Cowie S, Amor DJ, Savarirayan R, McGillivray G, Downie L, Ekert PG, Theda C, James PA, Yaplito-Lee J, Ryan MM, Leventer RJ, Creed E, Macciocca I, et al.

Genet Med. 2016 Nov;18(11):1090-1096. doi: 10.1038/gim.2016.1. Epub 2016 Mar 3.

PubMed [citation]

PMID:: 26938784

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000624265.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1726 of the DNAH5 protein (p.Leu1726Pro). This variant is present in population databases (rs138890576, gnomAD 0.003%). This missense change has been observed in individual(s) with primary ciliary dyskinesia (PMID: 26228299, 26938784, 29453417; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 369664). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DNAH5 protein function. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Natera, Inc., SCV001457366.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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