NM_012472.6:c.598_599delAA
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_012472.6(DNAAF11):c.598_599delAA(p.Lys200GlufsTer3) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,613,846 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: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000015 ( 0 hom. )
Consequence
DNAAF11
NM_012472.6 frameshift
NM_012472.6 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.59
Publications
3 publications found
Genes affected
DNAAF11 (HGNC:16725): (dynein axonemal assembly factor 11) The protein encoded by this gene contains several leucine-rich repeat domains and appears to be involved in the motility of cilia. Defects in this gene are a cause of primary ciliary dyskinesia-19 (CILD19). Alternative splicing of this gene results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 4, 11 and 22. [provided by RefSeq, Apr 2016]
DNAAF11 Gene-Disease associations (from GenCC):
- primary ciliary dyskinesia 19Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), ClinGen
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 18 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 8-132632793-CTT-C is Pathogenic according to our data. Variant chr8-132632793-CTT-C is described in ClinVar as Pathogenic. ClinVar VariationId is 39794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_012472.6. 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 |
|---|---|---|---|---|---|---|---|---|---|
| DNAAF11 | MANE Select | c.598_599delAA | p.Lys200GlufsTer3 | frameshift | Exon 5 of 12 | NP_036604.2 | |||
| DNAAF11 | c.598_599delAA | p.Lys200GlufsTer3 | frameshift | Exon 5 of 11 | NP_001308890.1 | ||||
| DNAAF11 | c.352_353delAA | p.Lys118GlufsTer3 | frameshift | Exon 3 of 10 | NP_001308891.1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| DNAAF11 | TSL:1 MANE Select | c.598_599delAA | p.Lys200GlufsTer3 | frameshift | Exon 5 of 12 | ENSP00000484634.1 | Q86X45-1 | ||
| DNAAF11 | TSL:1 | c.598_599delAA | p.Lys200GlufsTer3 | frameshift | Exon 5 of 12 | ENSP00000429791.1 | Q86X45-1 | ||
| DNAAF11 | TSL:1 | c.598_599delAA | p.Lys200GlufsTer3 | frameshift | Exon 5 of 13 | ENSP00000250173.2 | G5EA20 |
Frequencies
GnomAD3 genomes 0.0000131 AC: 2AN: 152142Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
2
AN:
152142
Hom.:
Cov.:
32
Gnomad AFR
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GnomAD2 exomes AF: 0.0000199 AC: 5AN: 251384 AF XY: 0.0000221 show subpopulations
GnomAD2 exomes
AF:
AC:
5
AN:
251384
AF XY:
Gnomad AFR exome
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GnomAD4 exome AF: 0.0000151 AC: 22AN: 1461704Hom.: 0 AF XY: 0.0000179 AC XY: 13AN XY: 727166 show subpopulations
GnomAD4 exome
AF:
AC:
22
AN:
1461704
Hom.:
AF XY:
AC XY:
13
AN XY:
727166
show subpopulations
African (AFR)
AF:
AC:
2
AN:
33474
American (AMR)
AF:
AC:
1
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26130
East Asian (EAS)
AF:
AC:
0
AN:
39674
South Asian (SAS)
AF:
AC:
2
AN:
86252
European-Finnish (FIN)
AF:
AC:
0
AN:
53408
Middle Eastern (MID)
AF:
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
AC:
15
AN:
1111886
Other (OTH)
AF:
AC:
2
AN:
60390
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.468
Heterozygous variant carriers
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Allele balance
Age Distribution
Exome Het
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Age
GnomAD4 genome 0.0000131 AC: 2AN: 152142Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74328 show subpopulations
GnomAD4 genome
AF:
AC:
2
AN:
152142
Hom.:
Cov.:
32
AF XY:
AC XY:
2
AN XY:
74328
show subpopulations
African (AFR)
AF:
AC:
1
AN:
41430
American (AMR)
AF:
AC:
0
AN:
15270
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3468
East Asian (EAS)
AF:
AC:
1
AN:
5200
South Asian (SAS)
AF:
AC:
0
AN:
4826
European-Finnish (FIN)
AF:
AC:
0
AN:
10618
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68010
Other (OTH)
AF:
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.550
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
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0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
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ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
3
-
-
Primary ciliary dyskinesia 19 (4)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
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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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