rs117723546
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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.1017C>T(p.Leu339Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00549 in 1,613,904 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0037 ( 5 hom., cov: 32)
Exomes 𝑓: 0.0057 ( 31 hom. )
Consequence
ODAD2
NM_018076.5 synonymous
NM_018076.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.111
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=-0.94).
BP6
Variant 10-27971233-G-A is Benign according to our data. Variant chr10-27971233-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 241254.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-27971233-G-A is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-0.111 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00367 (558/152226) while in subpopulation NFE AF= 0.00642 (437/68020). AF 95% confidence interval is 0.00593. There are 5 homozygotes in gnomad4. There are 249 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 5 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ODAD2 | NM_018076.5 | c.1017C>T | p.Leu339Leu | synonymous_variant | 8/20 | ENST00000305242.10 | NP_060546.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ODAD2 | ENST00000305242.10 | c.1017C>T | p.Leu339Leu | synonymous_variant | 8/20 | 1 | NM_018076.5 | ENSP00000306410.5 |
Frequencies
GnomAD3 genomes AF: 0.00367 AC: 558AN: 152108Hom.: 5 Cov.: 32
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GnomAD3 exomes AF: 0.00391 AC: 981AN: 251114Hom.: 2 AF XY: 0.00380 AC XY: 515AN XY: 135696
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GnomAD4 exome AF: 0.00568 AC: 8302AN: 1461678Hom.: 31 Cov.: 31 AF XY: 0.00544 AC XY: 3953AN XY: 727128
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GnomAD4 genome AF: 0.00367 AC: 558AN: 152226Hom.: 5 Cov.: 32 AF XY: 0.00335 AC XY: 249AN XY: 74424
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2020 | - - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2024 | ODAD2: BP4, BP7, BS2 - |
Primary ciliary dyskinesia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 27, 2016 | 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 | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 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