5-13794044-GCTCT-G
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001369.3(DNAH5):c.7898_7901del(p.Glu2633AlafsTer19) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,768 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. E2633E) 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.7898_7901del | p.Glu2633AlafsTer19 | frameshift_variant | 48/79 | ENST00000265104.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH5 | ENST00000265104.5 | c.7898_7901del | p.Glu2633AlafsTer19 | frameshift_variant | 48/79 | 1 | NM_001369.3 | P4 | |
DNAH5 | ENST00000681290.1 | c.7853_7856del | p.Glu2618AlafsTer19 | frameshift_variant | 48/79 | A1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251100Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135710
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461768Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 727182
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2023 | This variant is present in population databases (no rsID available, gnomAD 0.002%). This sequence change creates a premature translational stop signal (p.Glu2633Alafs*19) 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 premature translational stop signal has been observed in individual(s) with primary ciliary dyskinesia (PMID: 25186273). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 454805). This variant is also known as 7897_7902delAGAG. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at