17-44902645-CAGAG-CAGAGAG
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1_StrongPP5_Very_Strong
The NM_213607.3(DNAAF19):c.568_569dupAG(p.Ser190ArgfsTer19) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,826 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
DNAAF19
NM_213607.3 frameshift
NM_213607.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -3.23
Publications
2 publications found
Genes affected
DNAAF19 (HGNC:32700): (coiled-coil domain containing 103) Enables protein homodimerization activity. Involved in axonemal dynein complex assembly; cilium movement; and determination of left/right symmetry. Predicted to be located in axoneme. Predicted to be part of outer dynein arm. Implicated in primary ciliary dyskinesia 17. [provided by Alliance of Genome Resources, Apr 2022]
DNAAF19 Gene-Disease associations (from GenCC):
- primary ciliary dyskinesia 17Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Ambry Genetics, G2P, 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 does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.218 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
PP5
Variant 17-44902645-C-CAG is Pathogenic according to our data. Variant chr17-44902645-C-CAG is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 455029.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_213607.3. 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 |
|---|---|---|---|---|---|---|---|---|---|
| DNAAF19 | MANE Select | c.568_569dupAG | p.Ser190ArgfsTer19 | frameshift | Exon 4 of 4 | NP_998772.1 | Q8IW40-1 | ||
| DNAAF19 | c.568_569dupAG | p.Ser190ArgfsTer19 | frameshift | Exon 4 of 4 | NP_001245324.1 | Q8IW40-1 | |||
| DNAAF19 | c.568_569dupAG | p.Ser190ArgfsTer19 | frameshift | Exon 4 of 4 | NP_001245325.1 | Q8IW40-1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| DNAAF19 | TSL:1 MANE Select | c.568_569dupAG | p.Ser190ArgfsTer19 | frameshift | Exon 4 of 4 | ENSP00000391692.2 | Q8IW40-1 | ||
| DNAAF19 | TSL:2 | c.568_569dupAG | p.Ser190ArgfsTer19 | frameshift | Exon 4 of 4 | ENSP00000387252.1 | Q8IW40-1 | ||
| DNAAF19 | TSL:2 | c.568_569dupAG | p.Ser190ArgfsTer19 | frameshift | Exon 4 of 4 | ENSP00000350420.2 | F8W6J8 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.00 AC: 0AN: 249972 AF XY: 0.00
GnomAD2 exomes
AF:
AC:
0
AN:
249972
AF XY:
Gnomad AFR exome
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Gnomad AMR exome
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Gnomad ASJ exome
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Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
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GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461826Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 727222 show subpopulations
GnomAD4 exome
AF:
AC:
7
AN:
1461826
Hom.:
Cov.:
32
AF XY:
AC XY:
5
AN XY:
727222
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
1
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39698
South Asian (SAS)
AF:
AC:
0
AN:
86256
European-Finnish (FIN)
AF:
AC:
0
AN:
53404
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
6
AN:
1111964
Other (OTH)
AF:
AC:
0
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
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Allele balance
Age Distribution
Exome Het
Variant carriers
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GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
EpiCase
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EpiControl
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ClinVar
ClinVar submissions
View on ClinVar Significance:Likely pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
2
-
-
Primary ciliary dyskinesia 17 (2)
1
-
-
Primary ciliary dyskinesia (1)
1
-
-
Primary ciliary dyskinesia;C4022986:Absent inner and outer dynein arms;C4551493:Situs inversus (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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