7-21773945-G-GA
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001277115.2(DNAH11):c.9288dupA(p.Glu3097fs) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000447 in 1,566,272 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: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000035 ( 0 hom. )
Consequence
DNAH11
NM_001277115.2 frameshift
NM_001277115.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.81
Genes affected
DNAH11 (HGNC:2942): (dynein axonemal heavy chain 11) This gene encodes a ciliary outer dynein arm protein and is a member of the dynein heavy chain family. It is a microtubule-dependent motor ATPase and has been reported to be involved in the movement of respiratory cilia. Mutations in this gene have been implicated in causing Kartagener Syndrome (a combination of situs inversus totalis and Primary Ciliary Dyskinesia (PCD), also called Immotile Cilia Syndrome 1 (ICS1)) and male sterility. [provided by RefSeq, Mar 2013]
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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 7-21773945-G-GA is Pathogenic according to our data. Variant chr7-21773945-G-GA is described in ClinVar as [Pathogenic]. Clinvar id is 454719.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DNAH11 | ENST00000409508.8 | c.9288dupA | p.Glu3097fs | frameshift_variant | 56/82 | 5 | NM_001277115.2 | ENSP00000475939.1 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151840Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000353 AC: 5AN: 1414432Hom.: 0 Cov.: 32 AF XY: 0.00000143 AC XY: 1AN XY: 701598
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GnomAD4 genome AF: 0.0000132 AC: 2AN: 151840Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74144
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 17, 2023 | This sequence change creates a premature translational stop signal (p.Glu3097Argfs*37) in the DNAH11 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DNAH11 are known to be pathogenic (PMID: 18022865, 20513915, 22184204). This variant is present in population databases (rs771781357, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with DNAH11-related conditions. ClinVar contains an entry for this variant (Variation ID: 454719). For these reasons, this variant has been classified as Pathogenic. - |
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at