rs79119693
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2
The NM_001277115.2(DNAH11):āc.4455A>Gā(p.Leu1485=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00154 in 1,608,380 control chromosomes in the GnomAD database, including 33 homozygotes. 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 0.0083 ( 17 hom., cov: 32)
Exomes š: 0.00084 ( 16 hom. )
Consequence
DNAH11
NM_001277115.2 synonymous
NM_001277115.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.385
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 -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
Variant 7-21620033-A-G is Benign according to our data. Variant chr7-21620033-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 238919.We mark this variant Likely_benign, oryginal submissions are: {Benign=3, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=-0.385 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00829 (1263/152318) while in subpopulation AFR AF= 0.0281 (1168/41574). AF 95% confidence interval is 0.0268. There are 17 homozygotes in gnomad4. There are 598 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 17 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH11 | NM_001277115.2 | c.4455A>G | p.Leu1485= | synonymous_variant | 25/82 | ENST00000409508.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH11 | ENST00000409508.8 | c.4455A>G | p.Leu1485= | synonymous_variant | 25/82 | 5 | NM_001277115.2 | P1 | |
DNAH11 | ENST00000465593.1 | n.481A>G | non_coding_transcript_exon_variant | 3/4 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00828 AC: 1260AN: 152200Hom.: 17 Cov.: 32
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GnomAD3 exomes AF: 0.00218 AC: 533AN: 245010Hom.: 7 AF XY: 0.00182 AC XY: 242AN XY: 132758
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GnomAD4 exome AF: 0.000836 AC: 1217AN: 1456062Hom.: 16 Cov.: 30 AF XY: 0.000705 AC XY: 510AN XY: 723764
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GnomAD4 genome AF: 0.00829 AC: 1263AN: 152318Hom.: 17 Cov.: 32 AF XY: 0.00803 AC XY: 598AN XY: 74486
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1Benign:2
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 15, 2017 | This alteration is classified as 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. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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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