NM_001206927.2(DNAH8):c.253C>T (p.Arg85Ter) AND Primary ciliary dyskinesia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 21, 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:: RCV001225896.7

Allele description [Variation Report for NM_001206927.2(DNAH8):c.253C>T (p.Arg85Ter)]

NM_001206927.2(DNAH8):c.253C>T (p.Arg85Ter)

Genes:

LOC126859667:BRD4-independent group 4 enhancer GRCh37_chr6:38690326-38691525 [Gene]
DNAH8:dynein axonemal heavy chain 8 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p21.2

Genomic location:

Preferred name:

NM_001206927.2(DNAH8):c.253C>T (p.Arg85Ter)

HGVS:

NC_000006.12:g.38723062C>T
NG_041805.1:g.12722C>T
NM_001206927.2:c.253C>TMANE SELECT
NM_001371.4:c.-314C>T
NP_001193856.1:p.Arg85Ter
NC_000006.11:g.38690838C>T
NM_001206927.1:c.253C>T

Protein change:

R85*

Links:

dbSNP: rs545867507

NCBI 1000 Genomes Browser:

rs545867507

Molecular consequence:

NM_001371.4:c.-314C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001206927.2:c.253C>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV001398190	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 21, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 24307375, 32619401, 32681648, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001398190

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 21, 2023)

germline

clinical testing

PubMed (4)
[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

Robust diagnostic genetic testing using solution capture enrichment and a novel variant-filtering interface.

Watson CM, Crinnion LA, Morgan JE, Harrison SM, Diggle CP, Adlard J, Lindsay HA, Camm N, Charlton R, Sheridan E, Bonthron DT, Taylor GR, Carr IM.

Hum Mutat. 2014 Apr;35(4):434-41. doi: 10.1002/humu.22490.

PubMed [citation]

PMID:: 24307375
PMCID:: PMC4285299

Bi-allelic DNAH8 Variants Lead to Multiple Morphological Abnormalities of the Sperm Flagella and Primary Male Infertility.

Liu C, Miyata H, Gao Y, Sha Y, Tang S, Xu Z, Whitfield M, Patrat C, Wu H, Dulioust E, Tian S, Shimada K, Cong J, Noda T, Li H, Morohoshi A, Cazin C, Kherraf ZE, Arnoult C, Jin L, He X, Ray PF, et al.

Am J Hum Genet. 2020 Aug 6;107(2):330-341. doi: 10.1016/j.ajhg.2020.06.004. Epub 2020 Jul 2.

PubMed [citation]

PMID:: 32619401
PMCID:: PMC7413861

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001398190.5

#	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 creates a premature translational stop signal (p.Arg85*) in the DNAH8 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DNAH8 are known to be pathogenic (PMID: 24307375, 32619401, 32681648). This variant is present in population databases (rs545867507, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with DNAH8-related conditions. ClinVar contains an entry for this variant (Variation ID: 953583). 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

Last Updated: Sep 29, 2024

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