rs748250611
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_001277115.2(DNAH11):c.126G>A(p.Glu42=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000131 in 1,551,500 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: 𝑓 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00014 ( 0 hom. )
Consequence
DNAH11
NM_001277115.2 synonymous
NM_001277115.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.235
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=-0.53).
BP6
?
Variant 7-21543371-G-A is Benign according to our data. Variant chr7-21543371-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 238895.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BP7
?
Synonymous conserved (PhyloP=0.235 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH11 | NM_001277115.2 | c.126G>A | p.Glu42= | synonymous_variant | 1/82 | ENST00000409508.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH11 | ENST00000409508.8 | c.126G>A | p.Glu42= | synonymous_variant | 1/82 | 5 | NM_001277115.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000525 AC: 8AN: 152252Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000647 AC: 10AN: 154578Hom.: 0 AF XY: 0.0000488 AC XY: 4AN XY: 81894
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GnomAD4 exome AF: 0.000140 AC: 196AN: 1399248Hom.: 0 Cov.: 35 AF XY: 0.000145 AC XY: 100AN XY: 690158
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GnomAD4 genome ? AF: 0.0000525 AC: 8AN: 152252Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74382
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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
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Apr 02, 2022 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
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Dann
Benign
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at