NM_001369.3(DNAH5):c.4072G>A (p.Gly1358Ser) AND Primary ciliary dyskinesia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 22, 2024
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:: RCV000700755.4

Allele description [Variation Report for NM_001369.3(DNAH5):c.4072G>A (p.Gly1358Ser)]

NM_001369.3(DNAH5):c.4072G>A (p.Gly1358Ser)

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.4072G>A (p.Gly1358Ser)

HGVS:

NC_000005.10:g.13866264C>T
NG_013081.2:g.83217G>A
NM_001369.3:c.4072G>AMANE SELECT
NP_001360.1:p.Gly1358Ser
NP_001360.1:p.Gly1358Ser
NC_000005.9:g.13866373C>T
NM_001369.2:c.4072G>A

Protein change:

G1358S

Links:

dbSNP: rs752638332

NCBI 1000 Genomes Browser:

rs752638332

Molecular consequence:

NM_001369.3:c.4072G>A - 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
SCV000829526	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 22, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 32367404, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000829526

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 22, 2024)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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 exome-first approach to aid in the diagnosis of primary ciliary dyskinesia.

Shamseldin HE, Al Mogarri I, Alqwaiee MM, Alharbi AS, Baqais K, AlSaadi M, AlAnzi T, Alhashem A, Saghier A, Ameen W, Ibrahim N, Yang J, Abdulwahab F, Hashem M, Chivukula RR, Alkuraya FS.

Hum Genet. 2020 Oct;139(10):1273-1283. doi: 10.1007/s00439-020-02170-2. Epub 2020 May 4.

PubMed [citation]

PMID:: 32367404

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000829526.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1358 of the DNAH5 protein (p.Gly1358Ser). This variant is present in population databases (rs752638332, gnomAD 0.007%). This missense change has been observed in individual(s) with primary ciliary dyskinesia (PMID: 32367404). ClinVar contains an entry for this variant (Variation ID: 577895). 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) performed at Invitae indicates that this missense variant is not expected to disrupt DNAH5 protein function with a negative predictive value of 95%. 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.

#	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: Jul 15, 2024

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