NM_001369.3(DNAH5):c.11357G>A (p.Ser3786Asn) AND Primary ciliary dyskinesia

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Mar 25, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV002324925.4

Allele description [Variation Report for NM_001369.3(DNAH5):c.11357G>A (p.Ser3786Asn)]

NM_001369.3(DNAH5):c.11357G>A (p.Ser3786Asn)

Genes:

DNAH5:dynein axonemal heavy chain 5 [Gene - OMIM - HGNC]
LOC107457585:meiotic recombination hotspot J [Gene]

Variant type:

single nucleotide variant

Cytogenetic location:

5p15.2

Genomic location:

Preferred name:

NM_001369.3(DNAH5):c.11357G>A (p.Ser3786Asn)

HGVS:

NC_000005.10:g.13737350C>T
NG_013081.2:g.212131G>A
NG_046833.1:g.116C>T
NM_001369.3:c.11357G>AMANE SELECT
NP_001360.1:p.Ser3786Asn
NC_000005.9:g.13737459C>T
NM_001369.2:c.11357G>A

Protein change:

S3786N

Molecular consequence:

NM_001369.3:c.11357G>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
SCV002611024	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Mar 25, 2022)	germline	clinical testing	Citation Link,
SCV003525820	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 16, 2014)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002611024

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Mar 25, 2022)

germline

clinical testing

Citation Link,

SCV003525820

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 16, 2014)

germline

clinical testing

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

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

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 Ambry Genetics, SCV002611024.2

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

Description

The p.S3786N variant (also known as c.11357G>A), located in coding exon 66 of the DNAH5 gene, results from a G to A substitution at nucleotide position 11357. The serine at codon 3786 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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 Invitae, SCV003525820.1

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

Description

This sequence change has not been reported in the literature and is not listed in the polymorphism databases. This sequence change is predicted to result in an amino acid substitution (p.Ser3786Asn). ¬†The Ser3786 is a highly conserved residue, although algorithms developed to predict the impact of missense changes on protein function (AlignGVGD, SIFT, MutationTaster) provide conflicting results for the Ser3786Asn change. In summary, this a novel missense change with unknown impact on protein function. ¬†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: May 12, 2024

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