ClinVar Genomic variation as it relates to human health
NM_012144.4(DNAI1):c.1644G>A (p.Trp548Ter)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_012144.4(DNAI1):c.1644G>A (p.Trp548Ter)
Variation ID: 240854 Accession: VCV000240854.21
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 9p13.3 9: 34514468 (GRCh38) [ NCBI UCSC ] 9: 34514466 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Jul 1, 2016 May 1, 2024 Jan 25, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_012144.4:c.1644G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_036276.1:p.Trp548Ter nonsense NM_001281428.2:c.1656G>A NP_001268357.1:p.Trp552Ter nonsense NM_012144.2:c.1644G>A NC_000009.12:g.34514468G>A NC_000009.11:g.34514466G>A NG_008127.1:g.60656G>A - Protein change
- W548*, W552*
- Other names
- -
- Canonical SPDI
- NC_000009.12:34514467:G:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00003
The Genome Aggregation Database (gnomAD), exomes 0.00004
Trans-Omics for Precision Medicine (TOPMed) 0.00005
The Genome Aggregation Database (gnomAD) 0.00006
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00015
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
---|---|---|---|---|---|---|
HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
DNAI1 | - | - |
GRCh38 GRCh37 |
880 | 961 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
---|---|---|---|---|
Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
Jan 25, 2024 | RCV000231603.14 | |
Pathogenic/Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Oct 31, 2018 | RCV000763195.8 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
---|---|---|---|---|---|
Pathogenic
(Oct 31, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Kartagener syndrome
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV000893808.1
First in ClinVar: Mar 31, 2019 Last updated: Mar 31, 2019 |
|
|
Likely pathogenic
(Oct 31, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Kartagener syndrome
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000916256.1
First in ClinVar: May 27, 2019 Last updated: May 27, 2019 |
Comment:
The DNAI1 c.1644G>A (p.Trp548Ter) variant is a stop-gained variant that is predicted to result in a premature termination of the protein. The p.Trp548Ter variant has … (more)
The DNAI1 c.1644G>A (p.Trp548Ter) variant is a stop-gained variant that is predicted to result in a premature termination of the protein. The p.Trp548Ter variant has been reported in a compound heterozygous state in two patients with neonatal respiratory distress and sinusitis as well as outer dynein arm defect on electron microscopy (Zariwala et al. 2006; Berg et al. 2011). Family studies for one patient found the p.Trp548Ter variant was inherited from the healthy father. The variant was absent from 113 control subjects and is reported at a frequency of 0.000071 in the European (non-Finnish) population of the Genome Aggregation Database. Based on the evidence in the literature and the potential impact of stop-gained variants, the p.Trp548Ter variant is classified as likely pathogenic for primary ciliary dyskinesia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. (less)
|
|
Pathogenic
(Dec 30, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Primary ciliary dyskinesia
Affected status: yes
Allele origin:
germline
|
UNC Molecular Genetics Laboratory, University of North Carolina at Chapel Hill
Accession: SCV001431609.2
First in ClinVar: Sep 14, 2020 Last updated: May 10, 2021 |
|
|
Pathogenic
(Jan 25, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Primary ciliary dyskinesia
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000289874.8
First in ClinVar: Jul 01, 2016 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Trp548*) in the DNAI1 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Trp548*) in the DNAI1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DNAI1 are known to be pathogenic (PMID: 16858015, 29363216). This variant is present in population databases (rs200669099, gnomAD 0.007%). This premature translational stop signal has been observed in individuals with primary ciliary dyskinesia (PMID: 16858015, 21270641). ClinVar contains an entry for this variant (Variation ID: 240854). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
Pathogenic
(Mar 08, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Primary ciliary dyskinesia
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002704003.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The p.W548* pathogenic mutation (also known as c.1644G>A), located in coding exon 17 of the DNAI1 gene, results from a G to A substitution at … (more)
The p.W548* pathogenic mutation (also known as c.1644G>A), located in coding exon 17 of the DNAI1 gene, results from a G to A substitution at nucleotide position 1644. This changes the amino acid from a tryptophan to a stop codon within coding exon 17. This mutation was confirmed in trans with a second DNAI1 mutation in an individual with primary ciliary dykinesia and outer dynein arm defects on electron microscopy (Zariwala MA et al. Am. J. Respir. Crit. Care Med., 2006 Oct;174:858-66). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
|
|
Pathogenic
(Dec 14, 2020)
|
no assertion criteria provided
Method: clinical testing
|
Primary ciliary dyskinesia
Affected status: unknown
Allele origin:
germline
|
Natera, Inc.
Accession: SCV002085171.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
|
Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Diagnostic yield of a targeted gene panel in primary ciliary dyskinesia patients. | Paff T | Human mutation | 2018 | PMID: 29363216 |
Next generation massively parallel sequencing of targeted exomes to identify genetic mutations in primary ciliary dyskinesia: implications for application to clinical testing. | Berg JS | Genetics in medicine : official journal of the American College of Medical Genetics | 2011 | PMID: 21270641 |
Mutations of DNAI1 in primary ciliary dyskinesia: evidence of founder effect in a common mutation. | Zariwala MA | American journal of respiratory and critical care medicine | 2006 | PMID: 16858015 |
Text-mined citations for rs200669099 ...
HelpRecord last updated May 01, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.