rs760459837
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001206927.2(DNAH8):c.10744dupA(p.Ile3582AsnfsTer8) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,496 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001206927.2 frameshift
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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DNAH8 | NM_001206927.2 | c.10744dupA | p.Ile3582AsnfsTer8 | frameshift_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.10744dupA | p.Ile3582AsnfsTer8 | frameshift_variant | Exon 72 of 93 | 5 | NM_001206927.2 | ENSP00000333363.7 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 250972Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135648
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461496Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 727038
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Pathogenic:1
This sequence change creates a premature translational stop signal (p.Ile3582Asnfs*8) 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). This variant is present in population databases (rs760459837, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with DNAH8-related conditions. For these reasons, this variant has been classified as Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at