rs147478795
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001277115.2(DNAH11):āc.8362C>Gā(p.His2788Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000793 in 1,611,142 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.0044 ( 6 hom., cov: 33)
Exomes š: 0.00042 ( 6 hom. )
Consequence
DNAH11
NM_001277115.2 missense
NM_001277115.2 missense
Scores
1
5
6
Clinical Significance
Conservation
PhyloP100: 4.00
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0115222335).
BP6
?
Variant 7-21744915-C-G is Benign according to our data. Variant chr7-21744915-C-G is described in ClinVar as [Benign]. Clinvar id is 238934.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00439 (669/152314) while in subpopulation AFR AF= 0.0153 (638/41564). AF 95% confidence interval is 0.0144. There are 6 homozygotes in gnomad4. There are 313 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 6 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH11 | NM_001277115.2 | c.8362C>G | p.His2788Asp | missense_variant | 51/82 | ENST00000409508.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH11 | ENST00000409508.8 | c.8362C>G | p.His2788Asp | missense_variant | 51/82 | 5 | NM_001277115.2 | P1 | |
DNAH11 | ENST00000605912.1 | c.520C>G | p.His174Asp | missense_variant | 4/4 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00440 AC: 669AN: 152196Hom.: 6 Cov.: 33
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GnomAD3 exomes AF: 0.000939 AC: 229AN: 243920Hom.: 4 AF XY: 0.000644 AC XY: 85AN XY: 132050
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GnomAD4 exome AF: 0.000417 AC: 609AN: 1458828Hom.: 6 Cov.: 31 AF XY: 0.000325 AC XY: 236AN XY: 725274
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GnomAD4 genome ? AF: 0.00439 AC: 669AN: 152314Hom.: 6 Cov.: 33 AF XY: 0.00420 AC XY: 313AN XY: 74490
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 02, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Primary ciliary dyskinesia Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 17, 2015 | 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. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 20, 2021 | This variant is associated with the following publications: (PMID: 24450482) - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Uncertain
T
Vest4
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
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