chr17-11598539-A-ACGCGGATGGGGAACCCGGCGCCGAC
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 8P and 16B. PVS1BP6_Very_StrongBS1BS2
The NM_001372.4(DNAH9):c.44_68dup(p.Arg24GlyfsTer36) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0253 in 1,404,952 control chromosomes in the GnomAD database, including 589 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.022 ( 60 hom., cov: 31)
Exomes 𝑓: 0.026 ( 529 hom. )
Consequence
DNAH9
NM_001372.4 frameshift
NM_001372.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.735
Genes affected
DNAH9 (HGNC:2953): (dynein axonemal heavy chain 9) This gene encodes the heavy chain subunit of axonemal dynein, a large multi-subunit molecular motor. Axonemal dynein attaches to microtubules and hydrolyzes ATP to mediate the movement of cilia and flagella. The gene expresses at least two transcript variants; additional variants have been described, but their full length nature has not been determined. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 58 pathogenic variants in the truncated region.
BP6
?
Variant 17-11598539-A-ACGCGGATGGGGAACCCGGCGCCGAC is Benign according to our data. Variant chr17-11598539-A-ACGCGGATGGGGAACCCGGCGCCGAC is described in ClinVar as [Likely_benign]. Clinvar id is 774512.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0224 (3404/152144) while in subpopulation NFE AF= 0.0286 (1947/67968). AF 95% confidence interval is 0.0276. There are 60 homozygotes in gnomad4. There are 1777 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 60 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH9 | NM_001372.4 | c.44_68dup | p.Arg24GlyfsTer36 | frameshift_variant | 1/69 | ENST00000262442.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH9 | ENST00000262442.9 | c.44_68dup | p.Arg24GlyfsTer36 | frameshift_variant | 1/69 | 1 | NM_001372.4 | P1 | |
DNAH9 | ENST00000579406.1 | n.71_95dup | non_coding_transcript_exon_variant | 1/8 | 1 | ||||
DNAH9 | ENST00000454412.6 | c.44_68dup | p.Arg24GlyfsTer36 | frameshift_variant | 1/68 | 5 | |||
DNAH9 | ENST00000579828.5 | c.44_68dup | p.Arg24GlyfsTer36 | frameshift_variant | 1/4 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0224 AC: 3406AN: 152032Hom.: 60 Cov.: 31
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GnomAD3 exomes AF: 0.00162 AC: 48AN: 29620Hom.: 1 AF XY: 0.00185 AC XY: 32AN XY: 17272
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GnomAD4 exome AF: 0.0256 AC: 32099AN: 1252808Hom.: 529 Cov.: 33 AF XY: 0.0253 AC XY: 15509AN XY: 611886
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GnomAD4 genome ? AF: 0.0224 AC: 3404AN: 152144Hom.: 60 Cov.: 31 AF XY: 0.0239 AC XY: 1777AN XY: 74388
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 19, 2020 | - - |
DNAH9-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 24, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at