NM_001369.3(DNAH5):c.4961G>A (p.Arg1654Gln) AND Primary ciliary dyskinesia

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Jan 9, 2024
Review status:: criteria provided, conflicting classifications

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:: RCV000227048.14

Allele description [Variation Report for NM_001369.3(DNAH5):c.4961G>A (p.Arg1654Gln)]

NM_001369.3(DNAH5):c.4961G>A (p.Arg1654Gln)

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.4961G>A (p.Arg1654Gln)

HGVS:

NC_000005.10:g.13850805C>T
NG_013081.2:g.98676G>A
NM_001369.3:c.4961G>AMANE SELECT
NP_001360.1:p.Arg1654Gln
NP_001360.1:p.Arg1654Gln
NC_000005.9:g.13850914C>T
NM_001369.2:c.4961G>A

Protein change:

R1654Q

Links:

dbSNP: rs150868941

NCBI 1000 Genomes Browser:

rs150868941

Molecular consequence:

NM_001369.3:c.4961G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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
SCV000287082	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely benign (Jan 9, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001458595	Natera, Inc.	no assertion criteria provided	Uncertain significance (Jan 24, 2020)	germline	clinical testing
SCV002645755	Ambry Genetics	criteria provided, single submitter (Ambry General Variant Classification Scheme_2022)	Uncertain significance (Apr 3, 2017)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000287082

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely benign
(Jan 9, 2024)

germline

clinical testing

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

SCV001458595

Natera, Inc.

no assertion criteria provided

Uncertain significance
(Jan 24, 2020)

germline

clinical testing

SCV002645755

Ambry Genetics

criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)

Uncertain significance
(Apr 3, 2017)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	1	not provided	not provided	1	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 Invitae, SCV000287082.8

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

#	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., SCV001458595.1

#	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

From Ambry Genetics, SCV002645755.1

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

Description

The p.R1654Q variant (also known as c.4961G>A), located in coding exon 31 of the DNAH5 gene, results from a G to A substitution at nucleotide position 4961. The arginine at codon 1654 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. 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	1	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Apr 15, 2024

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