chr10-27940680-C-T
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1
The NM_018076.5(ODAD2):c.1869G>A(p.Thr623=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000108 in 1,614,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00026 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000093 ( 0 hom. )
Consequence
ODAD2
NM_018076.5 synonymous
NM_018076.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.49
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 -15 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 10-27940680-C-T is Benign according to our data. Variant chr10-27940680-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 417180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-3.49 with no splicing effect.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000256 (39/152264) while in subpopulation AMR AF= 0.00209 (32/15302). AF 95% confidence interval is 0.00152. There are 0 homozygotes in gnomad4. There are 18 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| ODAD2 | NM_018076.5 | c.1869G>A | p.Thr623= | synonymous_variant | 13/20 | ENST00000305242.10 | NP_060546.2 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| ODAD2 | ENST00000305242.10 | c.1869G>A | p.Thr623= | synonymous_variant | 13/20 | 1 | NM_018076.5 | ENSP00000306410 | P1 |
Frequencies
GnomAD3 genomes 0.000256 AC: 39AN: 152146Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000143 AC: 36AN: 250970Hom.: 0 AF XY: 0.000214 AC XY: 29AN XY: 135610
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GnomAD4 exome AF: 0.0000930 AC: 136AN: 1461826Hom.: 0 Cov.: 31 AF XY: 0.000111 AC XY: 81AN XY: 727222
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GnomAD4 genome 0.000256 AC: 39AN: 152264Hom.: 0 Cov.: 31 AF XY: 0.000242 AC XY: 18AN XY: 74460
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
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 | Apr 23, 2021 | 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
| Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 10, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at