rs35398031
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP6_Moderate
The NM_001369.3(DNAH5):c.3835-4_3835-3delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,600 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0 ( 0 hom., cov: 0)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
DNAH5
NM_001369.3 splice_region, intron
NM_001369.3 splice_region, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.454
Publications
8 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: G2P, ClinGen, 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: Uncertain_significance. The variant received 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 5-13867994-TAA-T is Benign according to our data. Variant chr5-13867994-TAA-T is described in ClinVar as Benign. ClinVar VariationId is 1554235.Status of the report is criteria_provided_single_submitter, 1 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.
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| DNAH5 | TSL:1 MANE Select | c.3835-4_3835-3delTT | splice_region intron | N/A | ENSP00000265104.4 | Q8TE73 | |||
| DNAH5 | c.3790-4_3790-3delTT | splice_region intron | N/A | ENSP00000505288.1 | A0A7P0Z455 | ||||
| DNAH5-AS1 | TSL:4 | n.253+7440_253+7441delAA | intron | N/A |
Frequencies
GnomAD3 genomes 0.00 AC: 0AN: 151466Hom.: 0 Cov.: 0
GnomAD3 genomes
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GnomAD2 exomes AF: 0.00 AC: 0AN: 239752 AF XY: 0.00
GnomAD2 exomes
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GnomAD4 exome AF: 6.90e-7 AC: 1AN: 1449600Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 721366 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
1
AN:
1449600
Hom.:
AF XY:
AC XY:
0
AN XY:
721366
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
33138
American (AMR)
AF:
AC:
0
AN:
44226
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25938
East Asian (EAS)
AF:
AC:
0
AN:
39344
South Asian (SAS)
AF:
AC:
0
AN:
85756
European-Finnish (FIN)
AF:
AC:
0
AN:
53122
Middle Eastern (MID)
AF:
AC:
0
AN:
5636
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1102586
Other (OTH)
AF:
AC:
0
AN:
59854
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 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
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Allele balance
Age Distribution
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Age
GnomAD4 genome 0.00 AC: 0AN: 151466Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 73910
GnomAD4 genome
Data not reliable, filtered out with message: AC0
AF:
AC:
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Cov.:
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73910
African (AFR)
AF:
AC:
0
AN:
41152
American (AMR)
AF:
AC:
0
AN:
15178
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3464
East Asian (EAS)
AF:
AC:
0
AN:
5184
South Asian (SAS)
AF:
AC:
0
AN:
4804
European-Finnish (FIN)
AF:
AC:
0
AN:
10492
Middle Eastern (MID)
AF:
AC:
0
AN:
308
European-Non Finnish (NFE)
AF:
AC:
0
AN:
67890
Other (OTH)
AF:
AC:
0
AN:
2082
Alfa
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Hom.:
ClinVar
ClinVar submissions
View on ClinVar Significance:Benign
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
-
1
Primary ciliary dyskinesia (1)
Computational scores
Source:
Name
Calibrated prediction
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Prediction
PhyloP100
Splicing
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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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