rs772835642
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001206927.2(DNAH8):c.10691G>A(p.Arg3564Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000185 in 1,461,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001206927.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DNAH8 | NM_001206927.2 | c.10691G>A | p.Arg3564Gln | missense_variant | Exon 72 of 93 | ENST00000327475.11 | NP_001193856.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DNAH8 | ENST00000327475.11 | c.10691G>A | p.Arg3564Gln | missense_variant | Exon 72 of 93 | 5 | NM_001206927.2 | ENSP00000333363.7 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000319 AC: 8AN: 250592Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135450
GnomAD4 exome AF: 0.0000185 AC: 27AN: 1461226Hom.: 0 Cov.: 30 AF XY: 0.0000206 AC XY: 15AN XY: 726900
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1
This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 3564 of the DNAH8 protein (p.Arg3564Gln). This variant is present in population databases (rs772835642, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with DNAH8-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt DNAH8 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at