NM_001206927.2:c.11430_11432delAAG
Variant summary
Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_001206927.2(DNAH8):c.11430_11432delAAG(p.Arg3811del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00000561 in 1,605,312 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
DNAH8
NM_001206927.2 disruptive_inframe_deletion
NM_001206927.2 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.44
Publications
0 publications found
Genes affected
DNAH8 (HGNC:2952): (dynein axonemal heavy chain 8) The protein encoded by this gene is a heavy chain of an axonemal dynein involved in sperm and respiratory cilia motility. Axonemal dyneins generate force through hydrolysis of ATP and binding to microtubules. [provided by RefSeq, Jan 2012]
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_001206927.2. Strenght limited to Supporting due to length of the change: 1aa.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001206927.2. 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 |
|---|---|---|---|---|---|---|---|---|---|
| DNAH8 | MANE Select | c.11430_11432delAAG | p.Arg3811del | disruptive_inframe_deletion | Exon 76 of 93 | NP_001193856.1 | A0A075B6F3 | ||
| DNAH8 | c.10779_10781delAAG | p.Arg3594del | disruptive_inframe_deletion | Exon 75 of 92 | NP_001362.2 | Q96JB1-1 | |||
| DNAH8-AS1 | n.160+4325_160+4327delCTT | intron | N/A |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| DNAH8 | TSL:5 MANE Select | c.11430_11432delAAG | p.Arg3811del | disruptive_inframe_deletion | Exon 76 of 93 | ENSP00000333363.7 | A0A075B6F3 | ||
| DNAH8 | TSL:2 | c.10779_10781delAAG | p.Arg3594del | disruptive_inframe_deletion | Exon 74 of 91 | ENSP00000352312.3 | Q96JB1-1 | ||
| DNAH8 | TSL:5 | c.11430_11432delAAG | p.Arg3811del | disruptive_inframe_deletion | Exon 75 of 82 | ENSP00000415331.2 | H0Y7V4 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152116Hom.: 0 Cov.: 31 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152116
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
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Gnomad SAS
AF:
Gnomad FIN
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Gnomad MID
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Gnomad NFE
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Gnomad OTH
AF:
GnomAD2 exomes AF: 0.0000166 AC: 4AN: 240952 AF XY: 0.00000767 show subpopulations
GnomAD2 exomes
AF:
AC:
4
AN:
240952
AF XY:
Gnomad AFR exome
AF:
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: 0.00000551 AC: 8AN: 1453196Hom.: 0 AF XY: 0.00000415 AC XY: 3AN XY: 722566 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
8
AN:
1453196
Hom.:
AF XY:
AC XY:
3
AN XY:
722566
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:
33060
American (AMR)
AF:
AC:
8
AN:
43146
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25910
East Asian (EAS)
AF:
AC:
0
AN:
39264
South Asian (SAS)
AF:
AC:
0
AN:
84032
European-Finnish (FIN)
AF:
AC:
0
AN:
53226
Middle Eastern (MID)
AF:
AC:
0
AN:
5728
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1108764
Other (OTH)
AF:
AC:
0
AN:
60066
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000173310), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.400
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
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10
<30
30-35
35-40
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>80
Age
GnomAD4 genome 0.00000657 AC: 1AN: 152116Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74304 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152116
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
74304
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41414
American (AMR)
AF:
AC:
1
AN:
15260
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5204
South Asian (SAS)
AF:
AC:
0
AN:
4824
European-Finnish (FIN)
AF:
AC:
0
AN:
10612
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68014
Other (OTH)
AF:
AC:
0
AN:
2090
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
Alfa
AF:
Hom.:
ClinVar
ClinVar submissions
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
Primary ciliary dyskinesia (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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