16-84170124-G-A
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_178452.6(DNAAF1):c.1296G>A(p.Glu432Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Consequence
DNAAF1
NM_178452.6 synonymous
NM_178452.6 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.933
Publications
19 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: Likely_benign. The variant received -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP7
Synonymous conserved (PhyloP=-0.933 with no splicing effect.
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
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| DNAAF1 | NM_178452.6 | MANE Select | c.1296G>A | p.Glu432Glu | synonymous | Exon 8 of 12 | NP_848547.4 | ||
| DNAAF1 | NM_001318756.1 | c.588G>A | p.Glu196Glu | synonymous | Exon 4 of 8 | NP_001305685.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| DNAAF1 | ENST00000378553.10 | TSL:1 MANE Select | c.1296G>A | p.Glu432Glu | synonymous | Exon 8 of 12 | ENSP00000367815.5 | ||
| DNAAF1 | ENST00000563818.5 | TSL:2 | n.973G>A | non_coding_transcript_exon | Exon 4 of 8 | ||||
| DNAAF1 | ENST00000570298.5 | TSL:2 | n.1450G>A | non_coding_transcript_exon | Exon 8 of 11 |
Frequencies
GnomAD3 genomes 0.00000659 AC: 1AN: 151830Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
151830
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
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Gnomad NFE
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Gnomad OTH
AF:
GnomAD4 exome Cov.: 100
GnomAD4 exome
Cov.:
100
GnomAD4 genome 0.00000659 AC: 1AN: 151830Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74140 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
AF:
AC:
1
AN:
151830
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74140
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
41330
American (AMR)
AF:
AC:
1
AN:
15260
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3466
East Asian (EAS)
AF:
AC:
0
AN:
5160
South Asian (SAS)
AF:
AC:
0
AN:
4794
European-Finnish (FIN)
AF:
AC:
0
AN:
10568
Middle Eastern (MID)
AF:
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
AC:
0
AN:
67940
Other (OTH)
AF:
AC:
0
AN:
2088
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
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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