rs1554062097
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001369.3(DNAH5):c.6932_6935del(p.Asp2311GlyfsTer14) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
DNAH5
NM_001369.3 frameshift
NM_001369.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.24
Genes affected
DNAH5 (HGNC:2950): (dynein axonemal heavy chain 5) This gene encodes a dynein protein, which is part of a microtubule-associated motor protein complex consisting of heavy, light, and intermediate chains. This protein is an axonemal heavy chain dynein. It functions as a force-generating protein with ATPase activity, whereby the release of ADP is thought to produce the force-producing power stroke. Mutations in this gene cause primary ciliary dyskinesia type 3, as well as Kartagener syndrome, which are both diseases due to ciliary defects. [provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 5-13817600-CCAGT-C is Pathogenic according to our data. Variant chr5-13817600-CCAGT-C is described in ClinVar as [Pathogenic]. Clinvar id is 454796.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH5 | NM_001369.3 | c.6932_6935del | p.Asp2311GlyfsTer14 | frameshift_variant | 42/79 | ENST00000265104.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH5 | ENST00000265104.5 | c.6932_6935del | p.Asp2311GlyfsTer14 | frameshift_variant | 42/79 | 1 | NM_001369.3 | P4 | |
DNAH5 | ENST00000681290.1 | c.6887_6890del | p.Asp2296GlyfsTer14 | frameshift_variant | 42/79 | A1 | |||
DNAH5 | ENST00000683090.1 | n.1863_1866del | non_coding_transcript_exon_variant | 7/7 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461850Hom.: 0 AF XY: 0.00000413 AC XY: 3AN XY: 727226
GnomAD4 exome
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | May 16, 2023 | This premature translational stop signal has been observed in individual(s) with clinical features of primary ciliary dyskinesia (PMID: 30067075). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 454796). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asp2311Glyfs*14) 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). - |
Likely pathogenic, no assertion criteria provided | literature only | Yale Center for Mendelian Genomics, Yale University | Aug 01, 2018 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at