chr16-84154730-T-TG
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_178452.6(DNAAF1):c.508dup(p.Glu170GlyfsTer10) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,614,032 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. L169L) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_178452.6 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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAAF1 | NM_178452.6 | c.508dup | p.Glu170GlyfsTer10 | frameshift_variant | 4/12 | ENST00000378553.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAAF1 | ENST00000378553.10 | c.508dup | p.Glu170GlyfsTer10 | frameshift_variant | 4/12 | 1 | NM_178452.6 | P1 | |
DNAAF1 | ENST00000567918.5 | c.508dup | p.Glu170GlyfsTer10 | frameshift_variant, NMD_transcript_variant | 4/7 | 1 | |||
DNAAF1 | ENST00000570298.5 | n.662dup | non_coding_transcript_exon_variant | 4/11 | 2 | ||||
DNAAF1 | ENST00000563093.5 | c.508dup | p.Glu170GlyfsTer10 | frameshift_variant, NMD_transcript_variant | 4/11 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152140Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251488Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135918
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461892Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727248
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152140Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74320
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | May 26, 2017 | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in DNAAF1 are known to be pathogenic (PMID: 19944405, 19944400). This variant has been reported in an individual affected with primary ciliary dyskinesia (PMID: 19944405). ClinVar contains an entry for this variant (Variation ID: 266). This variant is present in population databases (rs754412679, ExAC 0.001%). This sequence change creates a premature translational stop signal (p.Glu170Glyfs*10) in the DNAAF1 gene. It is expected to result in an absent or disrupted protein product. - |
Primary ciliary dyskinesia 13 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 01, 2009 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at