chr7-21543087-CGCGGCTGCTAAGTAGCAGCAGGTGGGAGACTAGGGTCTGCGCTCGCGGCGACCGCGGAGGAGGGTGGGCGCCTGCGGAGGTGTCCTCGCTCACTTCGGGGGGCCCAGAGTCTCGGGTGAGGAGCCAGCCGGCCTCGCGTTCCCTCGGACGGTTGCCCAATGGCAGCCCAGGTGGCAGCCCGGGAGGCGCGAGACTTCAGAGAAGCCCCGACCCTTCGCCTAACCTCGGGGGCCGGCCTGGAGGCAGTGGGCGCTGTGGAGCTCGAGGAGGAGGAGGAGAACGAGGAGGAGGCGGCGGCCAGGAGAGCGCGGAGTTTCGCCCAAGACGCGCGGGTGCGCTTCCTCGGCGGCCGCCTGGCGATGATGCTGGGGTTCACGGAGGAGAAATGGAGCCAGTATTTGGAAAGCGAGGACAACCGGCAGGTTCTTGGGGAGTTTCTGGAAAGCACCAGCCCGGCTTGCCTTGTGTTTAGCTTCGCCGCCTCGGGGCGCCTTGCGGCTTCCC-GGCGCCCCG

Position:

chr7-21543087-CGCGGCTGCTAAGTAGCAGCAGGTGGGAGACTAGGGTCTGCGCTCGCGGCGACCGCGGAGGAGGGTGGGCGCCTGCGGAGGTGTCCTCGCTCACTTCGGGGGGCCCAGAGTCTCGGGTGAGGAGCCAGCCGGCCTCGCGTTCCCTCGGACGGTTGCCCAATGGCAGCCCAGGTGGCAGCCCGGGAGGCGCGAGACTTCAGAGAAGCCCCGACCCTTCGCCTAACCTCGGGGGCCGGCCTGGAGGCAGTGGGCGCTGTGGAGCTCGAGGAGGAGGAGGAGAACGAGGAGGAGGCGGCGGCCAGGAGAGCGCGGAGTTTCGCCCAAGACGCGCGGGTGCGCTTCCTCGGCGGCCGCCTGGCGATGATGCTGGGGTTCACGGAGGAGAAATGGAGCCAGTATTTGGAAAGCGAGGACAACCGGCAGGTTCTTGGGGAGTTTCTGGAAAGCACCAGCCCGGCTTGCCTTGTGTTTAGCTTCGCCGCCTCGGGGCGCCTTGCGGCTTCCC-GGCGCCCCG

Variant summary

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

The NM_001277115.2(DNAH11):c.-159_346delCGCGGCTGCTAAGTAGCAGCAGGTGGGAGACTAGGGTCTGCGCTCGCGGCGACCGCGGAGGAGGGTGGGCGCCTGCGGAGGTGTCCTCGCTCACTTCGGGGGGCCCAGAGTCTCGGGTGAGGAGCCAGCCGGCCTCGCGTTCCCTCGGACGGTTGCCCAATGGCAGCCCAGGTGGCAGCCCGGGAGGCGCGAGACTTCAGAGAAGCCCCGACCCTTCGCCTAACCTCGGGGGCCGGCCTGGAGGCAGTGGGCGCTGTGGAGCTCGAGGAGGAGGAGGAGAACGAGGAGGAGGCGGCGGCCAGGAGAGCGCGGAGTTTCGCCCAAGACGCGCGGGTGCGCTTCCTCGGCGGCCGCCTGGCGATGATGCTGGGGTTCACGGAGGAGAAATGGAGCCAGTATTTGGAAAGCGAGGACAACCGGCAGGTTCTTGGGGAGTTTCTGGAAAGCACCAGCCCGGCTTGCCTTGTGTTTAGCTTCGCCGCCTCGGGGCGCCTTGCGGCTTCCCinsGGCGCCCCG(p.Met1fs) variant causes a frameshift, start lost, synonymous 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 frameshift, start_lost, synonymous

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 1.14

Variant links:

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]

DNAH11 links:

DNAH11 (HGNC:):

DNAH11 links:

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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 14 pathogenic variants in the truncated region.

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	Protein	UniProt
DNAH11	NM_001277115.2 linkuse as main transcript	c.-159_346delCGCGGCTGCTAAGTAGCAGCAGGTGGGAGACTAGGGTCTGCGCTCGCGGCGACCGCGGAGGAGGGTGGGCGCCTGCGGAGGTGTCCTCGCTCACTTCGGGGGGCCCAGAGTCTCGGGTGAGGAGCCAGCCGGCCTCGCGTTCCCTCGGACGGTTGCCCAATGGCAGCCCAGGTGGCAGCCCGGGAGGCGCGAGACTTCAGAGAAGCCCCGACCCTTCGCCTAACCTCGGGGGCCGGCCTGGAGGCAGTGGGCGCTGTGGAGCTCGAGGAGGAGGAGGAGAACGAGGAGGAGGCGGCGGCCAGGAGAGCGCGGAGTTTCGCCCAAGACGCGCGGGTGCGCTTCCTCGGCGGCCGCCTGGCGATGATGCTGGGGTTCACGGAGGAGAAATGGAGCCAGTATTTGGAAAGCGAGGACAACCGGCAGGTTCTTGGGGAGTTTCTGGAAAGCACCAGCCCGGCTTGCCTTGTGTTTAGCTTCGCCGCCTCGGGGCGCCTTGCGGCTTCCCinsGGCGCCCCG	p.Met1fs	frameshift_variant, start_lost, synonymous_variant	1/82	ENST00000409508.8	NP_001264044.1	Q96DT5Q96NT7H9NAJ8H9NAJ7
DNAH11	NM_001277115.2 linkuse as main transcript	c.-159_346delCGCGGCTGCTAAGTAGCAGCAGGTGGGAGACTAGGGTCTGCGCTCGCGGCGACCGCGGAGGAGGGTGGGCGCCTGCGGAGGTGTCCTCGCTCACTTCGGGGGGCCCAGAGTCTCGGGTGAGGAGCCAGCCGGCCTCGCGTTCCCTCGGACGGTTGCCCAATGGCAGCCCAGGTGGCAGCCCGGGAGGCGCGAGACTTCAGAGAAGCCCCGACCCTTCGCCTAACCTCGGGGGCCGGCCTGGAGGCAGTGGGCGCTGTGGAGCTCGAGGAGGAGGAGGAGAACGAGGAGGAGGCGGCGGCCAGGAGAGCGCGGAGTTTCGCCCAAGACGCGCGGGTGCGCTTCCTCGGCGGCCGCCTGGCGATGATGCTGGGGTTCACGGAGGAGAAATGGAGCCAGTATTTGGAAAGCGAGGACAACCGGCAGGTTCTTGGGGAGTTTCTGGAAAGCACCAGCCCGGCTTGCCTTGTGTTTAGCTTCGCCGCCTCGGGGCGCCTTGCGGCTTCCCinsGGCGCCCCG		5_prime_UTR_variant	1/82	ENST00000409508.8	NP_001264044.1	Q96DT5Q96NT7H9NAJ8H9NAJ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DNAH11	ENST00000409508.8 linkuse as main transcript	c.-159_346delCGCGGCTGCTAAGTAGCAGCAGGTGGGAGACTAGGGTCTGCGCTCGCGGCGACCGCGGAGGAGGGTGGGCGCCTGCGGAGGTGTCCTCGCTCACTTCGGGGGGCCCAGAGTCTCGGGTGAGGAGCCAGCCGGCCTCGCGTTCCCTCGGACGGTTGCCCAATGGCAGCCCAGGTGGCAGCCCGGGAGGCGCGAGACTTCAGAGAAGCCCCGACCCTTCGCCTAACCTCGGGGGCCGGCCTGGAGGCAGTGGGCGCTGTGGAGCTCGAGGAGGAGGAGGAGAACGAGGAGGAGGCGGCGGCCAGGAGAGCGCGGAGTTTCGCCCAAGACGCGCGGGTGCGCTTCCTCGGCGGCCGCCTGGCGATGATGCTGGGGTTCACGGAGGAGAAATGGAGCCAGTATTTGGAAAGCGAGGACAACCGGCAGGTTCTTGGGGAGTTTCTGGAAAGCACCAGCCCGGCTTGCCTTGTGTTTAGCTTCGCCGCCTCGGGGCGCCTTGCGGCTTCCCinsGGCGCCCCG	p.Met1fs	frameshift_variant, start_lost, synonymous_variant	1/82	5	NM_001277115.2	ENSP00000475939.1	Q96DT5
DNAH11	ENST00000409508 linkuse as main transcript	c.-159_346delCGCGGCTGCTAAGTAGCAGCAGGTGGGAGACTAGGGTCTGCGCTCGCGGCGACCGCGGAGGAGGGTGGGCGCCTGCGGAGGTGTCCTCGCTCACTTCGGGGGGCCCAGAGTCTCGGGTGAGGAGCCAGCCGGCCTCGCGTTCCCTCGGACGGTTGCCCAATGGCAGCCCAGGTGGCAGCCCGGGAGGCGCGAGACTTCAGAGAAGCCCCGACCCTTCGCCTAACCTCGGGGGCCGGCCTGGAGGCAGTGGGCGCTGTGGAGCTCGAGGAGGAGGAGGAGAACGAGGAGGAGGCGGCGGCCAGGAGAGCGCGGAGTTTCGCCCAAGACGCGCGGGTGCGCTTCCTCGGCGGCCGCCTGGCGATGATGCTGGGGTTCACGGAGGAGAAATGGAGCCAGTATTTGGAAAGCGAGGACAACCGGCAGGTTCTTGGGGAGTTTCTGGAAAGCACCAGCCCGGCTTGCCTTGTGTTTAGCTTCGCCGCCTCGGGGCGCCTTGCGGCTTCCCinsGGCGCCCCG		5_prime_UTR_variant	1/82	5	NM_001277115.2	ENSP00000475939.1	Q96DT5
DNAH11	ENST00000607050.1 linkuse as main transcript	n.-359_146delCGCGGCTGCTAAGTAGCAGCAGGTGGGAGACTAGGGTCTGCGCTCGCGGCGACCGCGGAGGAGGGTGGGCGCCTGCGGAGGTGTCCTCGCTCACTTCGGGGGGCCCAGAGTCTCGGGTGAGGAGCCAGCCGGCCTCGCGTTCCCTCGGACGGTTGCCCAATGGCAGCCCAGGTGGCAGCCCGGGAGGCGCGAGACTTCAGAGAAGCCCCGACCCTTCGCCTAACCTCGGGGGCCGGCCTGGAGGCAGTGGGCGCTGTGGAGCTCGAGGAGGAGGAGGAGAACGAGGAGGAGGCGGCGGCCAGGAGAGCGCGGAGTTTCGCCCAAGACGCGCGGGTGCGCTTCCTCGGCGGCCGCCTGGCGATGATGCTGGGGTTCACGGAGGAGAAATGGAGCCAGTATTTGGAAAGCGAGGACAACCGGCAGGTTCTTGGGGAGTTTCTGGAAAGCACCAGCCCGGCTTGCCTTGTGTTTAGCTTCGCCGCCTCGGGGCGCCTTGCGGCTTCCCinsGGCGCCCCG		non_coding_transcript_exon_variant	1/2	3
DNAH11	ENST00000607050.1 linkuse as main transcript	n.-359_146delCGCGGCTGCTAAGTAGCAGCAGGTGGGAGACTAGGGTCTGCGCTCGCGGCGACCGCGGAGGAGGGTGGGCGCCTGCGGAGGTGTCCTCGCTCACTTCGGGGGGCCCAGAGTCTCGGGTGAGGAGCCAGCCGGCCTCGCGTTCCCTCGGACGGTTGCCCAATGGCAGCCCAGGTGGCAGCCCGGGAGGCGCGAGACTTCAGAGAAGCCCCGACCCTTCGCCTAACCTCGGGGGCCGGCCTGGAGGCAGTGGGCGCTGTGGAGCTCGAGGAGGAGGAGGAGAACGAGGAGGAGGCGGCGGCCAGGAGAGCGCGGAGTTTCGCCCAAGACGCGCGGGTGCGCTTCCTCGGCGGCCGCCTGGCGATGATGCTGGGGTTCACGGAGGAGAAATGGAGCCAGTATTTGGAAAGCGAGGACAACCGGCAGGTTCTTGGGGAGTTTCTGGAAAGCACCAGCCCGGCTTGCCTTGTGTTTAGCTTCGCCGCCTCGGGGCGCCTTGCGGCTTCCCinsGGCGCCCCG		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

Cov.:

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

Cov.:

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

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: 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.