rs587776910
Variant names:
Variant summary
Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_213607.3(DNAAF19):c.383dupG(p.Pro129SerfsTer25) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000657 in 152,284 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Consequence
DNAAF19
NM_213607.3 frameshift
NM_213607.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.08
Publications
3 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, Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P
- primary ciliary dyskinesiaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_pathogenic. The variant received 7 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. There are 8 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 17-44902466-T-TG is Pathogenic according to our data. Variant chr17-44902466-T-TG is described in ClinVar as Pathogenic. ClinVar VariationId is 31697.Status of the report is no_assertion_criteria_provided, 0 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
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| DNAAF19 | NM_213607.3 | MANE Select | c.383dupG | p.Pro129SerfsTer25 | frameshift | Exon 4 of 4 | NP_998772.1 | ||
| DNAAF19 | NM_001258395.2 | c.383dupG | p.Pro129SerfsTer25 | frameshift | Exon 4 of 4 | NP_001245324.1 | |||
| DNAAF19 | NM_001258396.2 | c.383dupG | p.Pro129SerfsTer25 | frameshift | Exon 4 of 4 | NP_001245325.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CCDC103 | ENST00000417826.3 | TSL:1 MANE Select | c.383dupG | p.Pro129SerfsTer25 | frameshift | Exon 4 of 4 | ENSP00000391692.2 | ||
| CCDC103 | ENST00000410006.6 | TSL:2 | c.383dupG | p.Pro129SerfsTer25 | frameshift | Exon 4 of 4 | ENSP00000387252.1 | ||
| CCDC103 | ENST00000357776.6 | TSL:2 | c.383dupG | p.Pro129SerfsTer25 | frameshift | Exon 4 of 4 | ENSP00000350420.2 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152166Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152166
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
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Gnomad ASJ
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Gnomad EAS
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Gnomad SAS
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Gnomad FIN
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Gnomad MID
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Gnomad NFE
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Gnomad OTH
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GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome 0.00000657 AC: 1AN: 152284Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74474 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152284
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74474
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41574
American (AMR)
AF:
AC:
0
AN:
15304
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3468
East Asian (EAS)
AF:
AC:
0
AN:
5174
South Asian (SAS)
AF:
AC:
0
AN:
4830
European-Finnish (FIN)
AF:
AC:
0
AN:
10612
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
1
AN:
68000
Other (OTH)
AF:
AC:
0
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
ClinVar
ClinVar submissions as Germline
Significance:Pathogenic
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
1
-
-
Primary ciliary dyskinesia 17 (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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