rs1555527001
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1PP5_Moderate
The NM_178452.6(DNAAF1):c.1937delT(p.Leu646ArgfsTer15) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,762 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
DNAAF1
NM_178452.6 frameshift
NM_178452.6 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.42
Publications
0 publications found
Genes affected
DNAAF1 (HGNC:30539): (dynein axonemal assembly factor 1) The protein encoded by this gene is cilium-specific and is required for the stability of the ciliary architecture. It is involved in the regulation of microtubule-based cilia and actin-based brush border microvilli. Mutations in this gene are associated with primary ciliary dyskinesia-13. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]
DNAAF1 Gene-Disease associations (from GenCC):
- primary ciliary dyskinesia 13Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia
- primary ciliary dyskinesiaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 10 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PP5
Variant 16-84176170-CT-C is Pathogenic according to our data. Variant chr16-84176170-CT-C is described in ClinVar as Pathogenic. ClinVar VariationId is 525389.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_178452.6. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| DNAAF1 | NM_178452.6 | MANE Select | c.1937delT | p.Leu646ArgfsTer15 | frameshift | Exon 11 of 12 | NP_848547.4 | ||
| DNAAF1 | NM_001318756.1 | c.1229delT | p.Leu410ArgfsTer15 | frameshift | Exon 7 of 8 | NP_001305685.1 | Q8NEP3-2 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| DNAAF1 | ENST00000378553.10 | TSL:1 MANE Select | c.1937delT | p.Leu646ArgfsTer15 | frameshift | Exon 11 of 12 | ENSP00000367815.5 | Q8NEP3-1 | |
| DNAAF1 | ENST00000963697.1 | c.1943delT | p.Leu648ArgfsTer15 | frameshift | Exon 11 of 13 | ENSP00000633756.1 | |||
| DNAAF1 | ENST00000963694.1 | c.1937delT | p.Leu646ArgfsTer15 | frameshift | Exon 11 of 13 | ENSP00000633753.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461762Hom.: 0 Cov.: 65 AF XY: 0.00000825 AC XY: 6AN XY: 727180 show subpopulations
GnomAD4 exome
AF:
AC:
9
AN:
1461762
Hom.:
Cov.:
65
AF XY:
AC XY:
6
AN XY:
727180
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33476
American (AMR)
AF:
AC:
0
AN:
44716
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26132
East Asian (EAS)
AF:
AC:
0
AN:
39696
South Asian (SAS)
AF:
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
53316
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
9
AN:
1112006
Other (OTH)
AF:
AC:
0
AN:
60394
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.492
Heterozygous variant carriers
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Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
33
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
Primary ciliary dyskinesia (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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