rs6966525
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.188G>Cā(p.Gly63Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000587 in 1,558,042 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.0031 ( 3 hom., cov: 33)
Exomes š: 0.00031 ( 1 hom. )
Consequence
DNAH11
NM_001277115.2 missense
NM_001277115.2 missense
Scores
1
11
Clinical Significance
Conservation
PhyloP100: 4.60
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=0.0055802763).
BP6
?
Variant 7-21543433-G-C is Benign according to our data. Variant chr7-21543433-G-C is described in ClinVar as [Benign]. Clinvar id is 257876.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 = 0.00311 (474/152366) while in subpopulation AFR AF= 0.0108 (450/41602). AF 95% confidence interval is 0.00999. There are 3 homozygotes in gnomad4. There are 222 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH11 | NM_001277115.2 | c.188G>C | p.Gly63Ala | missense_variant | 1/82 | ENST00000409508.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH11 | ENST00000409508.8 | c.188G>C | p.Gly63Ala | missense_variant | 1/82 | 5 | NM_001277115.2 | P1 | |
DNAH11 | ENST00000607050.1 | upstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00307 AC: 468AN: 152248Hom.: 3 Cov.: 33
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GnomAD3 exomes AF: 0.000683 AC: 112AN: 163904Hom.: 1 AF XY: 0.000527 AC XY: 46AN XY: 87324
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GnomAD4 exome AF: 0.000314 AC: 441AN: 1405676Hom.: 1 Cov.: 35 AF XY: 0.000284 AC XY: 197AN XY: 693908
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GnomAD4 genome ? AF: 0.00311 AC: 474AN: 152366Hom.: 3 Cov.: 33 AF XY: 0.00298 AC XY: 222AN XY: 74514
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia Benign:2
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 14, 2016 | 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 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T;T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N
PrimateAI
Uncertain
T
Polyphen
0.95
.;.;P
Vest4
MVP
ClinPred
T
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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