rs45519938
Positions:
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_001206927.2(DNAH8):c.5490C>A(p.Asp1830Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0126 in 1,613,428 control chromosomes in the GnomAD database, including 182 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.010 ( 17 hom., cov: 32)
Exomes 𝑓: 0.013 ( 165 hom. )
Consequence
DNAH8
NM_001206927.2 missense
NM_001206927.2 missense
Scores
1
5
8
Clinical Significance
Conservation
PhyloP100: 2.05
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.011568546).
BP6
?
Variant 6-38852717-C-A is Benign according to our data. Variant chr6-38852717-C-A is described in ClinVar as [Benign]. Clinvar id is 238652.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-38852717-C-A is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0102 (1548/152292) while in subpopulation NFE AF= 0.0155 (1053/68032). AF 95% confidence interval is 0.0147. There are 17 homozygotes in gnomad4. There are 772 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 17 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH8 | NM_001206927.2 | c.5490C>A | p.Asp1830Glu | missense_variant | 40/93 | ENST00000327475.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH8 | ENST00000327475.11 | c.5490C>A | p.Asp1830Glu | missense_variant | 40/93 | 5 | NM_001206927.2 | P2 | |
DNAH8 | ENST00000359357.7 | c.4839C>A | p.Asp1613Glu | missense_variant | 38/91 | 2 | A2 | ||
DNAH8 | ENST00000449981.6 | c.5490C>A | p.Asp1830Glu | missense_variant | 39/82 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0102 AC: 1548AN: 152174Hom.: 17 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
1548
AN:
152174
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
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0101 AC: 2545AN: 251038Hom.: 17 AF XY: 0.0103 AC XY: 1393AN XY: 135686
GnomAD3 exomes
AF:
AC:
2545
AN:
251038
Hom.:
AF XY:
AC XY:
1393
AN XY:
135686
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0129 AC: 18819AN: 1461136Hom.: 165 Cov.: 31 AF XY: 0.0127 AC XY: 9213AN XY: 726902
GnomAD4 exome
AF:
AC:
18819
AN:
1461136
Hom.:
Cov.:
31
AF XY:
AC XY:
9213
AN XY:
726902
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0102 AC: 1548AN: 152292Hom.: 17 Cov.: 32 AF XY: 0.0104 AC XY: 772AN XY: 74462
GnomAD4 genome
?
AF:
AC:
1548
AN:
152292
Hom.:
Cov.:
32
AF XY:
AC XY:
772
AN XY:
74462
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
43
ALSPAC
AF:
AC:
61
ESP6500AA
AF:
AC:
12
ESP6500EA
AF:
AC:
104
ExAC
?
AF:
AC:
1314
Asia WGS
AF:
AC:
1
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
REVEL
Benign
Polyphen
0.94
.;.;P
Vest4
MutPred
0.79
.;.;Gain of disorder (P = 0.1493);
MPC
0.43
ClinPred
T
GERP RS
Varity_R
gMVP
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