rs950490534
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_017802.4(DNAAF5):āc.2346C>Gā(p.Tyr782*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000366 in 1,614,140 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 (ā ). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_017802.4 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DNAAF5 | NM_017802.4 | c.2346C>G | p.Tyr782* | stop_gained | 12/13 | ENST00000297440.11 | NP_060272.3 | |
DNAAF5 | XM_024446813.2 | c.2239+4897C>G | intron_variant | XP_024302581.1 | ||||
DNAAF5 | NR_075098.2 | n.2306C>G | non_coding_transcript_exon_variant | 12/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DNAAF5 | ENST00000297440.11 | c.2346C>G | p.Tyr782* | stop_gained | 12/13 | 1 | NM_017802.4 | ENSP00000297440.6 | ||
DNAAF5 | ENST00000403952.3 | c.621C>G | p.Tyr207* | stop_gained | 5/6 | 1 | ENSP00000384884.3 | |||
DNAAF5 | ENST00000440747.5 | c.1749C>G | p.Tyr583* | stop_gained | 12/13 | 2 | ENSP00000403165.1 | |||
DNAAF5 | ENST00000461576.1 | n.156C>G | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152274Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251412Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135882
GnomAD4 exome AF: 0.0000390 AC: 57AN: 1461866Hom.: 0 Cov.: 31 AF XY: 0.0000371 AC XY: 27AN XY: 727230
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152274Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74400
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 11, 2020 | This sequence change creates a premature translational stop signal (p.Tyr782*) in the DNAAF5 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with DNAAF5-related disease. ClinVar contains an entry for this variant (Variation ID: 454860). Loss-of-function variants in DNAAF5 are known to be pathogenic (PMID: 24307375, 25232951). 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