rs4615458
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001277115.2(DNAH11):āc.2454A>Gā(p.Ala818=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 1,613,416 control chromosomes in the GnomAD database, including 148,040 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.45 ( 16236 hom., cov: 31)
Exomes š: 0.42 ( 131804 hom. )
Consequence
DNAH11
NM_001277115.2 synonymous
NM_001277115.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.914
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 Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
Variant 7-21591364-A-G is Benign according to our data. Variant chr7-21591364-A-G is described in ClinVar as [Benign]. Clinvar id is 93684.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21591364-A-G is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-0.914 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DNAH11 | NM_001277115.2 | c.2454A>G | p.Ala818= | synonymous_variant | 14/82 | ENST00000409508.8 | NP_001264044.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DNAH11 | ENST00000409508.8 | c.2454A>G | p.Ala818= | synonymous_variant | 14/82 | 5 | NM_001277115.2 | ENSP00000475939 | P1 |
Frequencies
GnomAD3 genomes AF: 0.451 AC: 68478AN: 151740Hom.: 16205 Cov.: 31
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GnomAD3 exomes AF: 0.428 AC: 106424AN: 248642Hom.: 24398 AF XY: 0.428 AC XY: 57684AN XY: 134892
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GnomAD4 exome AF: 0.419 AC: 611928AN: 1461558Hom.: 131804 Cov.: 59 AF XY: 0.417 AC XY: 303393AN XY: 727058
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GnomAD4 genome AF: 0.451 AC: 68551AN: 151858Hom.: 16236 Cov.: 31 AF XY: 0.451 AC XY: 33499AN XY: 74226
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ClinVar
Significance: Benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 05, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 21, 2013 | Ala818Ala in exon 14 of DNAH11: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 48.2% (2040/4230) of African American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs4615458). - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Primary ciliary dyskinesia Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Primary ciliary dyskinesia 7 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 30, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 10, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at