rs754982008
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001369.3(DNAH5):āc.252T>Gā(p.Tyr84Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,864 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 ā ). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001369.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DNAH5 | NM_001369.3 | c.252T>G | p.Tyr84Ter | stop_gained | 3/79 | ENST00000265104.5 | NP_001360.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DNAH5 | ENST00000265104.5 | c.252T>G | p.Tyr84Ter | stop_gained | 3/79 | 1 | NM_001369.3 | ENSP00000265104 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152218Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250910Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135586
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461646Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5AN XY: 727140
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152218Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74362
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Mar 26, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 525260). This premature translational stop signal has been observed in individual(s) with primary ciliary dyskinesia (PMID: 16627867). This variant is present in population databases (rs754982008, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Tyr84*) in the DNAH5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DNAH5 are known to be pathogenic (PMID: 11788826, 16627867). - |
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 14, 2020 | The p.Y84* pathogenic mutation (also known as c.252T>G), located in coding exon 3 of the DNAH5 gene, results from a T to G substitution at nucleotide position 252. This changes the amino acid from a tyrosine to a stop codon within coding exon 3. This mutation was identified in an individual with primary ciliary dyskinesia and an outer dynein arm defect on electron microscopy; however, a second alteration was not detected (Hornef N et al. Am. J. Respir. Crit. Care Med., 2006 Jul;174:120-6). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at