rs1305797678
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 16 ACMG points: 16P and 0B. PVS1PP5_Very_Strong
The NM_001369.3(DNAH5):c.9637delG(p.Ala3213LeufsTer8) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,728 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: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
DNAH5
NM_001369.3 frameshift
NM_001369.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.74
Publications
1 publications found
Genes affected
DNAH5 (HGNC:2950): (dynein axonemal heavy chain 5) This gene encodes a dynein protein, which is part of a microtubule-associated motor protein complex consisting of heavy, light, and intermediate chains. This protein is an axonemal heavy chain dynein. It functions as a force-generating protein with ATPase activity, whereby the release of ADP is thought to produce the force-producing power stroke. Mutations in this gene cause primary ciliary dyskinesia type 3, as well as Kartagener syndrome, which are both diseases due to ciliary defects. [provided by RefSeq, Oct 2009]
DNAH5 Gene-Disease associations (from GenCC):
- primary ciliary dyskinesia 3Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, ClinGen
- 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 16 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PP5
Variant 5-13769583-GC-G is Pathogenic according to our data. Variant chr5-13769583-GC-G is described in ClinVar as Pathogenic. ClinVar VariationId is 548647.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001369.3. 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 |
|---|---|---|---|---|---|---|---|---|---|
| DNAH5 | NM_001369.3 | MANE Select | c.9637delG | p.Ala3213LeufsTer8 | frameshift | Exon 57 of 79 | NP_001360.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| DNAH5 | ENST00000265104.5 | TSL:1 MANE Select | c.9637delG | p.Ala3213LeufsTer8 | frameshift | Exon 57 of 79 | ENSP00000265104.4 | ||
| DNAH5 | ENST00000681290.1 | c.9592delG | p.Ala3198LeufsTer8 | frameshift | Exon 57 of 79 | ENSP00000505288.1 | |||
| DNAH5 | ENST00000504001.3 | TSL:5 | n.349delG | non_coding_transcript_exon | Exon 3 of 5 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.00000796 AC: 2AN: 251244 AF XY: 0.00000736 show subpopulations
GnomAD2 exomes
AF:
AC:
2
AN:
251244
AF XY:
Gnomad AFR exome
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Gnomad AMR exome
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Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461728Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727176 show subpopulations
GnomAD4 exome
AF:
AC:
7
AN:
1461728
Hom.:
Cov.:
31
AF XY:
AC XY:
5
AN XY:
727176
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33468
American (AMR)
AF:
AC:
0
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26126
East Asian (EAS)
AF:
AC:
0
AN:
39692
South Asian (SAS)
AF:
AC:
0
AN:
86254
European-Finnish (FIN)
AF:
AC:
0
AN:
53418
Middle Eastern (MID)
AF:
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
AC:
7
AN:
1111902
Other (OTH)
AF:
AC:
0
AN:
60382
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions as Germline
Significance:Pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
2
-
-
Primary ciliary dyskinesia (2)
1
-
-
not provided (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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