NM_015512.5(DNAH1):c.3460A>C (p.Lys1154Gln) AND multiple conditions

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Nov 20, 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:: RCV003765209.2

Allele description [Variation Report for NM_015512.5(DNAH1):c.3460A>C (p.Lys1154Gln)]

NM_015512.5(DNAH1):c.3460A>C (p.Lys1154Gln)

Gene:

DNAH1:dynein axonemal heavy chain 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p21.1

Genomic location:

Preferred name:

NM_015512.5(DNAH1):c.3460A>C (p.Lys1154Gln)

HGVS:

NC_000003.12:g.52353613A>C
NG_052911.1:g.42295A>C
NM_015512.5:c.3460A>CMANE SELECT
NP_056327.4:p.Lys1154Gln
NC_000003.11:g.52387629A>C
NM_015512.4:c.3460A>C

Protein change:

K1154Q; LYS1154GLN

Links:

OMIM: 603332.0005; dbSNP: rs544674332

NCBI 1000 Genomes Browser:

rs544674332

Molecular consequence:

NM_015512.5:c.3460A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Spermatogenic failure 18
Identifiers:: MONDO: MONDO:0054615; MedGen: C4539783; OMIM: 617576

Name:: Ciliary dyskinesia, primary, 37 (CILD37)
Synonyms:: CILIARY DYSKINESIA, PRIMARY, 37, WITH OR WITHOUT SITUS INVERSUS
Identifiers:: MONDO: MONDO:0033204; MedGen: C4539798; OMIM: 617577

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004569654	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Nov 20, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25927852, 32719396, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004569654

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Nov 20, 2023)

germline

clinical testing

PubMed (3)
[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

Variation in DNAH1 may contribute to primary ciliary dyskinesia.

Imtiaz F, Allam R, Ramzan K, Al-Sayed M.

BMC Med Genet. 2015 Mar 17;16:14. doi: 10.1186/s12881-015-0162-5.

PubMed [citation]

PMID:: 25927852
PMCID:: PMC4422061

A genomics approach to male infertility.

Alhathal N, Maddirevula S, Coskun S, Alali H, Assoum M, Morris T, Deek HA, Hamed SA, Alsuhaibani S, Mirdawi A, Ewida N, Al-Qahtani M, Ibrahim N, Abdulwahab F, Altaweel W, Dasouki MJ, Assiri A, Qabbaj W, Alkuraya FS.

Genet Med. 2020 Dec;22(12):1967-1975. doi: 10.1038/s41436-020-0916-0. Epub 2020 Jul 28.

PubMed [citation]

PMID:: 32719396

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004569654.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1154 of the DNAH1 protein (p.Lys1154Gln). This variant is present in population databases (rs544674332, gnomAD 0.004%). This missense change has been observed in individual(s) with male infertility and/or primary ciliary dyskinesia (PMID: 25927852, 32719396). ClinVar contains an entry for this variant (Variation ID: 209005). 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 expected to disrupt DNAH1 protein function with a positive predictive value of 80%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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: Oct 26, 2024

ClinVar

Relating variation to medicine