rs768447289
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_018076.5(ODAD2):c.1076G>A(p.Trp359Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,766 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_018076.5 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 |
---|---|---|---|---|---|---|---|
ODAD2 | NM_018076.5 | c.1076G>A | p.Trp359Ter | stop_gained | 8/20 | ENST00000305242.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ODAD2 | ENST00000305242.10 | c.1076G>A | p.Trp359Ter | stop_gained | 8/20 | 1 | NM_018076.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152070Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251124Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135712
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461696Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 727144
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152070Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74300
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia 23 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 21, 2018 | This sequence change creates a premature translational stop signal (p.Trp359*) in the ARMC4 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs768447289, ExAC 0.006%). This variant has not been reported in the literature in individuals with ARMC4-related disease. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Loss-of-function variants in ARMC4 are known to be pathogenic (PMID: 23849778). 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