rs373354778
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_001277115.2(DNAH11):āc.5475A>Gā(p.Gln1825=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000106 in 1,608,346 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.000026 ( 0 hom., cov: 33)
Exomes š: 0.0000089 ( 0 hom. )
Consequence
DNAH11
NM_001277115.2 synonymous
NM_001277115.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.29
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 Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
Variant 7-21683798-A-G is Benign according to our data. Variant chr7-21683798-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 454686.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=-1.29 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| DNAH11 | NM_001277115.2 | c.5475A>G | p.Gln1825= | synonymous_variant | 32/82 | ENST00000409508.8 | NP_001264044.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| DNAH11 | ENST00000409508.8 | c.5475A>G | p.Gln1825= | synonymous_variant | 32/82 | 5 | NM_001277115.2 | ENSP00000475939 | P1 |
Frequencies
GnomAD3 genomes 0.0000263 AC: 4AN: 152130Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000245 AC: 6AN: 245200Hom.: 0 AF XY: 0.0000150 AC XY: 2AN XY: 132946
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GnomAD4 exome AF: 0.00000893 AC: 13AN: 1456098Hom.: 0 Cov.: 30 AF XY: 0.0000124 AC XY: 9AN XY: 723918
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GnomAD4 genome 0.0000263 AC: 4AN: 152248Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74436
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 30, 2020 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
| Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 11, 2017 | This sequence change affects codon 1825 of the DNAH11 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the DNAH11 protein. This variant is present in population databases (rs373354778, ExAC 0.03%). This variant has not been reported in the literature in individuals with DNAH11-related disease. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
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