rs74555138
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_018076.5(ODAD2):c.2979C>T(p.Asp993=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00248 in 1,614,028 control chromosomes in the GnomAD database, including 79 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.013 ( 43 hom., cov: 32)
Exomes 𝑓: 0.0014 ( 36 hom. )
Consequence
ODAD2
NM_018076.5 synonymous
NM_018076.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.255
Genes affected
ODAD2 (HGNC:25583): (outer dynein arm docking complex subunit 2) The protein encoded by this gene contains ten Armadillo repeat motifs (ARMs) and one HEAT repeat, and is thought to be involved in ciliary and flagellar movement. This protein has been shown to localize to the ciliary axonemes and at the ciliary base of respiratory cells. Studies indicate that mutations in this gene cause partial outer dynein arm (ODA) defects in respiratory cilia. The cilia of cells with mutations in this gene displayed either reduced ciliary beat frequency and amplitude, or, complete immotility. Some individuals with primary ciliary dyskensia (PCD) have been shown to have mutations in this gene. PCD is characterized by chronic airway disease and left/right body asymmetry defects. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 10-27860667-G-A is Benign according to our data. Variant chr10-27860667-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 241264.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.255 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0131 (2001/152204) while in subpopulation AFR AF= 0.0446 (1854/41524). AF 95% confidence interval is 0.043. There are 43 homozygotes in gnomad4. There are 955 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 43 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ODAD2 | NM_018076.5 | c.2979C>T | p.Asp993= | synonymous_variant | 19/20 | ENST00000305242.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ODAD2 | ENST00000305242.10 | c.2979C>T | p.Asp993= | synonymous_variant | 19/20 | 1 | NM_018076.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0130 AC: 1972AN: 152086Hom.: 38 Cov.: 32
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GnomAD3 exomes AF: 0.00347 AC: 872AN: 251178Hom.: 21 AF XY: 0.00255 AC XY: 346AN XY: 135760
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GnomAD4 exome AF: 0.00137 AC: 2004AN: 1461824Hom.: 36 Cov.: 31 AF XY: 0.00114 AC XY: 826AN XY: 727216
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GnomAD4 genome AF: 0.0131 AC: 2001AN: 152204Hom.: 43 Cov.: 32 AF XY: 0.0128 AC XY: 955AN XY: 74412
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 25, 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. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 11, 2020 | - - |
Primary ciliary dyskinesia 23 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
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