rs200815756
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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):c.644G>A(p.Gly215Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000346 in 1,613,620 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00030 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00035 ( 1 hom. )
Consequence
DNAH8
NM_001206927.2 missense
NM_001206927.2 missense
Scores
6
8
Clinical Significance
Conservation
PhyloP100: 5.51
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=0.08723989).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH8 | NM_001206927.2 | c.644G>A | p.Gly215Glu | missense_variant | 5/93 | ENST00000327475.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH8 | ENST00000327475.11 | c.644G>A | p.Gly215Glu | missense_variant | 5/93 | 5 | NM_001206927.2 | P2 | |
DNAH8 | ENST00000373278.8 | c.644G>A | p.Gly215Glu | missense_variant | 5/5 | 1 | |||
DNAH8 | ENST00000449981.6 | c.644G>A | p.Gly215Glu | missense_variant | 4/82 | 5 | |||
DNAH8 | ENST00000359357.7 | c.-8G>A | 5_prime_UTR_variant | 3/91 | 2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000302 AC: 46AN: 152070Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000446 AC: 112AN: 251058Hom.: 0 AF XY: 0.000509 AC XY: 69AN XY: 135686
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GnomAD4 exome AF: 0.000350 AC: 512AN: 1461550Hom.: 1 Cov.: 32 AF XY: 0.000362 AC XY: 263AN XY: 727080
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GnomAD4 genome ? AF: 0.000302 AC: 46AN: 152070Hom.: 0 Cov.: 32 AF XY: 0.000202 AC XY: 15AN XY: 74260
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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 | Dec 11, 2023 | This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 215 of the DNAH8 protein (p.Gly215Glu). This variant is present in population databases (rs200815756, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with DNAH8-related conditions. ClinVar contains an entry for this variant (Variation ID: 576883). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
REVEL
Uncertain
Polyphen
1.0
.;D;.
Vest4
MVP
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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