rs1555526915
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_178452.6(DNAAF1):c.1814dupA(p.Asn605LysfsTer7) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,842 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: 0.0000014 ( 0 hom. )
Consequence
DNAAF1
NM_178452.6 frameshift
NM_178452.6 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -1.43
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: ClinGen, Labcorp Genetics (formerly Invitae)
- 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 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 16-84176045-C-CA is Pathogenic according to our data. Variant chr16-84176045-C-CA is described in ClinVar as Pathogenic. ClinVar VariationId is 455002.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.1814dupA | p.Asn605LysfsTer7 | frameshift | Exon 11 of 12 | NP_848547.4 | ||
| DNAAF1 | NM_001318756.1 | c.1106dupA | p.Asn369LysfsTer7 | 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.1814dupA | p.Asn605LysfsTer7 | frameshift | Exon 11 of 12 | ENSP00000367815.5 | Q8NEP3-1 | |
| DNAAF1 | ENST00000963697.1 | c.1820dupA | p.Asn607LysfsTer7 | frameshift | Exon 11 of 13 | ENSP00000633756.1 | |||
| DNAAF1 | ENST00000963694.1 | c.1814dupA | p.Asn605LysfsTer7 | frameshift | Exon 11 of 13 | ENSP00000633753.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461842Hom.: 0 Cov.: 56 AF XY: 0.00000275 AC XY: 2AN XY: 727222 show subpopulations
GnomAD4 exome
AF:
AC:
2
AN:
1461842
Hom.:
Cov.:
56
AF XY:
AC XY:
2
AN XY:
727222
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39698
South Asian (SAS)
AF:
AC:
0
AN:
86252
European-Finnish (FIN)
AF:
AC:
0
AN:
53402
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1111988
Other (OTH)
AF:
AC:
1
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
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
ClinVar
ClinVar submissions
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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