rs759039864
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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):āc.423T>Cā(p.Tyr141=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000524 in 1,583,426 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.000040 ( 0 hom., cov: 32)
Exomes š: 0.000054 ( 2 hom. )
Consequence
ODAD2
NM_018076.5 synonymous
NM_018076.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.537
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=-0.86).
BP6
?
Variant 10-27985171-A-G is Benign according to our data. Variant chr10-27985171-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 474588.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.537 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0000538 (77/1431578) while in subpopulation AMR AF= 0.00169 (71/42044). AF 95% confidence interval is 0.00137. There are 2 homozygotes in gnomad4_exome. There are 26 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ODAD2 | NM_018076.5 | c.423T>C | p.Tyr141= | synonymous_variant | 4/20 | ENST00000305242.10 | |
LOC112268060 | XR_002957065.1 | n.86+1890A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ODAD2 | ENST00000305242.10 | c.423T>C | p.Tyr141= | synonymous_variant | 4/20 | 1 | NM_018076.5 | P1 | |
ODAD2 | ENST00000673439.1 | c.423T>C | p.Tyr141= | synonymous_variant | 4/20 | P1 | |||
ODAD2 | ENST00000434029.1 | n.105T>C | non_coding_transcript_exon_variant | 2/10 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000395 AC: 6AN: 151848Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000337 AC: 70AN: 207996Hom.: 2 AF XY: 0.000206 AC XY: 23AN XY: 111842
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GnomAD4 exome AF: 0.0000538 AC: 77AN: 1431578Hom.: 2 Cov.: 31 AF XY: 0.0000366 AC XY: 26AN XY: 710080
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GnomAD4 genome ? AF: 0.0000395 AC: 6AN: 151848Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4AN XY: 74170
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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
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 07, 2023 | This alteration is classified as likely 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. - |
Primary ciliary dyskinesia 23 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 27, 2023 | - - |
ODAD2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 29, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
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