rs769310274
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001206927.2(DNAH8):āc.2716A>Gā(p.Thr906Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000559 in 1,608,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000039 ( 0 hom., cov: 32)
Exomes š: 0.0000021 ( 0 hom. )
Consequence
DNAH8
NM_001206927.2 missense
NM_001206927.2 missense
Scores
3
15
Clinical Significance
Conservation
PhyloP100: 4.93
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 made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.19203925).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH8 | NM_001206927.2 | c.2716A>G | p.Thr906Ala | missense_variant | 20/93 | ENST00000327475.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH8 | ENST00000327475.11 | c.2716A>G | p.Thr906Ala | missense_variant | 20/93 | 5 | NM_001206927.2 | P2 | |
DNAH8 | ENST00000359357.7 | c.2065A>G | p.Thr689Ala | missense_variant | 18/91 | 2 | A2 | ||
DNAH8 | ENST00000449981.6 | c.2716A>G | p.Thr906Ala | missense_variant | 19/82 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152214Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000122 AC: 3AN: 246434Hom.: 0 AF XY: 0.00000751 AC XY: 1AN XY: 133138
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GnomAD4 exome AF: 0.00000206 AC: 3AN: 1456694Hom.: 0 Cov.: 29 AF XY: 0.00000276 AC XY: 2AN XY: 724606
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GnomAD4 genome AF: 0.0000394 AC: 6AN: 152214Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74364
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 06, 2018 | Algorithms developed to predict the effect of missense changes on protein structure and function agree on the potential impact of this missense change (SIFT: "Tolerated"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with DNAH8-related disease. This variant is present in population databases (rs769310274, ExAC 0.01%). This sequence change replaces threonine with alanine at codon 906 of the DNAH8 protein (p.Thr906Ala). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and alanine. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;.;L
MutationTaster
Benign
N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
.;N;N
REVEL
Benign
Sift
Uncertain
.;D;D
Polyphen
0.0080
.;.;B
Vest4
MutPred
0.48
.;.;Gain of loop (P = 0.0851);
MVP
MPC
0.14
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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