rs769691189
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001369.3(DNAH5):c.10910del(p.Leu3637ArgfsTer20) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,614,008 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. L3637L) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001369.3 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 |
---|---|---|---|---|---|---|---|
DNAH5 | NM_001369.3 | c.10910del | p.Leu3637ArgfsTer20 | frameshift_variant | 64/79 | ENST00000265104.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH5 | ENST00000265104.5 | c.10910del | p.Leu3637ArgfsTer20 | frameshift_variant | 64/79 | 1 | NM_001369.3 | P4 | |
DNAH5 | ENST00000681290.1 | c.10865del | p.Leu3622ArgfsTer20 | frameshift_variant | 64/79 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152138Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251010Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135640
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461752Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727186
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152256Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74438
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 08, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 407260). This variant has not been reported in the literature in individuals affected with DNAH5-related conditions. This variant is present in population databases (rs769691189, gnomAD 0.008%). This sequence change creates a premature translational stop signal (p.Leu3637Argfs*20) 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). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at