rs763438877
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001206927.2(DNAH8):c.8870G>A(p.Arg2957His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000576 in 1,613,592 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2957C) has been classified 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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH8 | NM_001206927.2 | c.8870G>A | p.Arg2957His | missense_variant | 60/93 | ENST00000327475.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH8 | ENST00000327475.11 | c.8870G>A | p.Arg2957His | missense_variant | 60/93 | 5 | NM_001206927.2 | P2 | |
DNAH8 | ENST00000359357.7 | c.8219G>A | p.Arg2740His | missense_variant | 58/91 | 2 | A2 | ||
DNAH8 | ENST00000449981.6 | c.8870G>A | p.Arg2957His | missense_variant | 59/82 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000791 AC: 12AN: 151776Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000518 AC: 13AN: 251198Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135748
GnomAD4 exome AF: 0.0000554 AC: 81AN: 1461816Hom.: 0 Cov.: 31 AF XY: 0.0000509 AC XY: 37AN XY: 727206
GnomAD4 genome AF: 0.0000791 AC: 12AN: 151776Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74126
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 01, 2023 | The c.8870G>A (p.R2957H) alteration is located in exon 60 (coding exon 59) of the DNAH8 gene. This alteration results from a G to A substitution at nucleotide position 8870, causing the arginine (R) at amino acid position 2957 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Primary ciliary dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 04, 2024 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 2957 of the DNAH8 protein (p.Arg2957His). This variant is present in population databases (rs763438877, gnomAD 0.03%). 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: 525264). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Not Available"; Align-GVGD: "Not Available". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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