chr17-11598517-CGGGCCGCGCTCGCGGCGGAGAA-AACGCGGATGGGGAACCCGGCGCCGAC

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate

The NM_001372.4(DNAH9):​c.19_41delCGGGCCGCGCTCGCGGCGGAGAAinsAACGCGGATGGGGAACCCGGCGCCGAC​(p.Arg7fs) variant causes a frameshift, missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 31)

Consequence

DNAH9
NM_001372.4 frameshift, missense

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 0.786
Variant links:
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 Likely_pathogenic. 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 8 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 17-11598517-CGGGCCGCGCTCGCGGCGGAGAA-AACGCGGATGGGGAACCCGGCGCCGAC is Pathogenic according to our data. Variant chr17-11598517-CGGGCCGCGCTCGCGGCGGAGAA-AACGCGGATGGGGAACCCGGCGCCGAC is described in ClinVar as [Pathogenic]. Clinvar id is 1992905.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DNAH9NM_001372.4 linkc.19_41delCGGGCCGCGCTCGCGGCGGAGAAinsAACGCGGATGGGGAACCCGGCGCCGAC p.Arg7fs frameshift_variant, missense_variant 1/69 ENST00000262442.9 NP_001363.2 Q9NYC9-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DNAH9ENST00000262442.9 linkc.19_41delCGGGCCGCGCTCGCGGCGGAGAAinsAACGCGGATGGGGAACCCGGCGCCGAC p.Arg7fs frameshift_variant, missense_variant 1/691 NM_001372.4 ENSP00000262442.3 Q9NYC9-1
DNAH9ENST00000579406.1 linkn.46_68delCGGGCCGCGCTCGCGGCGGAGAAinsAACGCGGATGGGGAACCCGGCGCCGAC non_coding_transcript_exon_variant 1/81
DNAH9ENST00000454412.6 linkc.19_41delCGGGCCGCGCTCGCGGCGGAGAAinsAACGCGGATGGGGAACCCGGCGCCGAC p.Arg7fs frameshift_variant, missense_variant 1/685 ENSP00000414874.2 E7EP17
DNAH9ENST00000579828.5 linkc.19_41delCGGGCCGCGCTCGCGGCGGAGAAinsAACGCGGATGGGGAACCCGGCGCCGAC p.Arg7fs frameshift_variant, missense_variant 1/42 ENSP00000463782.1 J3QQK8

Frequencies

GnomAD3 genomes
Cov.:
31
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
31

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Pathogenic:1
Pathogenic, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpMay 19, 2022For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with DNAH9-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg7Asnfs*46) in the DNAH9 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DNAH9 are known to be pathogenic (PMID: 30471718). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-11501834; API