rs766256391
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001206927.2(DNAH8):c.7866G>A(p.Trp2622Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000509 in 1,572,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001206927.2 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH8 | NM_001206927.2 | c.7866G>A | p.Trp2622Ter | stop_gained | 54/93 | ENST00000327475.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH8 | ENST00000327475.11 | c.7866G>A | p.Trp2622Ter | stop_gained | 54/93 | 5 | NM_001206927.2 | P2 | |
DNAH8 | ENST00000359357.7 | c.7215G>A | p.Trp2405Ter | stop_gained | 52/91 | 2 | A2 | ||
DNAH8 | ENST00000449981.6 | c.7866G>A | p.Trp2622Ter | stop_gained | 53/82 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152074Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000223 AC: 5AN: 224350Hom.: 0 AF XY: 0.0000246 AC XY: 3AN XY: 121816
GnomAD4 exome AF: 0.00000493 AC: 7AN: 1420622Hom.: 0 Cov.: 29 AF XY: 0.00000709 AC XY: 5AN XY: 705506
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152074Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74276
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 09, 2022 | ClinVar contains an entry for this variant (Variation ID: 407300). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with DNAH8-related conditions. This variant is present in population databases (rs766256391, gnomAD 0.02%). This sequence change creates a premature translational stop signal (p.Trp2622*) in the DNAH8 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DNAH8 are known to be pathogenic (PMID: 24307375, 32619401, 32681648). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at