7-21543087-CGCGGCTGCTAAGTAGCAGCAGGTGGGAGACTAGGGTCTGCGCTCGCGGCGACCGCGGAGGAGGGTGGGCGCCTGCGGAGGTGTCCTCGCTCACTTCGGGGGGCCCAGAGTCTCGGGTGAGGAGCCAGCCGGCCTCGCGTTCCCTCGGACGGTTGCCCAATGGCAGCCCAGGTGGCAGCCCGGGAGGCGCGAGACTTCAGAGAAGCCCCGACCCTTCGCCTAACCTCGGGGGCCGGCCTGGAGGCAGTGGGCGCTGTGGAGCTCGAGGAGGAGGAGGAGAACGAGGAGGAGGCGGCGGCCAGGAGAGCGCGGAGTTTCGCCCAAGACGCGCGGGTGCGCTTCCTCGGCGGCCGCCTGGCGATGATGCTGGGGTTCACGGAGGAGAAATGGAGCCAGTATTTGGAAAGCGAGGACAACCGGCAGGTTCTTGGGGAGTTTCTGGAAAGCACCAGCCCGGCTTGCCTTGTGTTTAGCTTCGCCGCCTCGGGGCGCCTTGCGGCTTCCC-GGCGCCCCG
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001277115.2(DNAH11):c.-159_346delinsGGCGCCCCG variant causes a start lost, 5 prime UTR 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: 33)
Consequence
DNAH11
NM_001277115.2 start_lost, 5_prime_UTR
NM_001277115.2 start_lost, 5_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.14
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Start lost variant, no new inframe start found.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 7-21543087-CGCGGCTGCTAAGTAGCAGCAGGTGGGAGACTAGGGTCTGCGCTCGCGGCGACCGCGGAGGAGGGTGGGCGCCTGCGGAGGTGTCCTCGCTCACTTCGGGGGGCCCAGAGTCTCGGGTGAGGAGCCAGCCGGCCTCGCGTTCCCTCGGACGGTTGCCCAATGGCAGCCCAGGTGGCAGCCCGGGAGGCGCGAGACTTCAGAGAAGCCCCGACCCTTCGCCTAACCTCGGGGGCCGGCCTGGAGGCAGTGGGCGCTGTGGAGCTCGAGGAGGAGGAGGAGAACGAGGAGGAGGCGGCGGCCAGGAGAGCGCGGAGTTTCGCCCAAGACGCGCGGGTGCGCTTCCTCGGCGGCCGCCTGGCGATGATGCTGGGGTTCACGGAGGAGAAATGGAGCCAGTATTTGGAAAGCGAGGACAACCGGCAGGTTCTTGGGGAGTTTCTGGAAAGCACCAGCCCGGCTTGCCTTGTGTTTAGCTTCGCCGCCTCGGGGCGCCTTGCGGCTTCCC-GGCGCCCCG is Pathogenic according to our data. Variant chr7-21543087-CGCGGCTGCTAAGTAGCAGCAGGTGGGAGACTAGGGTCTGCGCTCGCGGCGACCGCGGAGGAGGGTGGGCGCCTGCGGAGGTGTCCTCGCTCACTTCGGGGGGCCCAGAGTCTCGGGTGAGGAGCCAGCCGGCCTCGCGTTCCCTCGGACGGTTGCCCAATGGCAGCCCAGGTGGCAGCCCGGGAGGCGCGAGACTTCAGAGAAGCCCCGACCCTTCGCCTAACCTCGGGGGCCGGCCTGGAGGCAGTGGGCGCTGTGGAGCTCGAGGAGGAGGAGGAGAACGAGGAGGAGGCGGCGGCCAGGAGAGCGCGGAGTTTCGCCCAAGACGCGCGGGTGCGCTTCCTCGGCGGCCGCCTGGCGATGATGCTGGGGTTCACGGAGGAGAAATGGAGCCAGTATTTGGAAAGCGAGGACAACCGGCAGGTTCTTGGGGAGTTTCTGGAAAGCACCAGCCCGGCTTGCCTTGTGTTTAGCTTCGCCGCCTCGGGGCGCCTTGCGGCTTCCC-GGCGCCCCG is described in ClinVar as [Pathogenic]. Clinvar id is 2855244.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH11 | NM_001277115.2 | c.-159_346delinsGGCGCCCCG | start_lost, 5_prime_UTR_variant | 1/82 | ENST00000409508.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH11 | ENST00000409508.8 | c.-159_346delinsGGCGCCCCG | start_lost, 5_prime_UTR_variant | 1/82 | 5 | NM_001277115.2 | P1 | ||
DNAH11 | ENST00000607050.1 | non_coding_transcript_exon_variant | 1/2 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
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 | Invitae | Apr 11, 2023 | For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with DNAH11-related conditions. This variant results in the deletion of part of exon 1 (c.-159_346delinsGGCGCCCCG) of 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). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.