rs200901816
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001369.3(DNAH5):c.13486C>T(p.Arg4496Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000502 in 1,613,838 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 (★★). Synonymous variant affecting the same amino acid position (i.e. R4496R) has been classified as Likely benign. 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 | UniProt |
---|---|---|---|---|---|---|---|
DNAH5 | NM_001369.3 | c.13486C>T | p.Arg4496Ter | stop_gained | 77/79 | ENST00000265104.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH5 | ENST00000265104.5 | c.13486C>T | p.Arg4496Ter | stop_gained | 77/79 | 1 | NM_001369.3 | P4 | |
DNAH5 | ENST00000681290.1 | c.13441C>T | p.Arg4481Ter | stop_gained | 77/79 | A1 | |||
DNAH5 | ENST00000683611.1 | n.819C>T | non_coding_transcript_exon_variant | 3/5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000658 AC: 10AN: 151898Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000597 AC: 15AN: 251178Hom.: 0 AF XY: 0.0000736 AC XY: 10AN XY: 135802
GnomAD4 exome AF: 0.0000486 AC: 71AN: 1461822Hom.: 0 Cov.: 34 AF XY: 0.0000481 AC XY: 35AN XY: 727216
GnomAD4 genome ? AF: 0.0000658 AC: 10AN: 152016Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74308
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Pathogenic:3
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | This sequence change creates a premature translational stop signal (p.Arg4496*) 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). This variant is present in population databases (rs200901816, gnomAD 0.009%). This premature translational stop signal has been observed in individuals with primary ciliary dyskinesia (PMID: 16627867, 19357118, 26139845). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 407248). For these reasons, this variant has been classified as Pathogenic. - |
Likely pathogenic, no assertion criteria provided | literature only | Yale Center for Mendelian Genomics, Yale University | Aug 01, 2018 | - - |
Primary ciliary dyskinesia 3 Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 22, 2021 | - - |
Pathogenic, criteria provided, single submitter | research | HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology | Sep 18, 2020 | ACMG codes:PVS1, PS4M, PM2, PM3 - |
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Apr 04, 2022 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Sep 02, 2021 | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Reported in ClinVar as a pathogenic variant (ClinVar Variant ID# 407248; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 31879361, 31980526, 31589614, 31772028, 28991257, 31765523, 31638833, 26139845, 19357118, 27637300, 16627867, 25525159) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at