rs12777433

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_018076.5(ODAD2):c.390A>G(p.Arg130Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00258 in 1,510,956 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 6 hom. )

Consequence

ODAD2
NM_018076.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.78

Variant links:

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]

ODAD2 links:

LOC112268060 (HGNC:):

LOC112268060 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 10-27985204-T-C is Benign according to our data. Variant chr10-27985204-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 417181.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00178 (266/149350) while in subpopulation AMR AF= 0.00388 (58/14950). AF 95% confidence interval is 0.00308. There are 1 homozygotes in gnomad4. There are 126 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODAD2	NM_018076.5 link	c.390A>G	p.Arg130Arg	synonymous_variant	Exon 4 of 20	ENST00000305242.10	NP_060546.2	Q5T2S8-1A0A140VKF7B7Z7Y0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ODAD2	ENST00000305242.10 link	c.390A>G	p.Arg130Arg	synonymous_variant	Exon 4 of 20	1	NM_018076.5	ENSP00000306410.5	Q5T2S8-1
ODAD2	ENST00000673439.1 link	c.390A>G	p.Arg130Arg	synonymous_variant	Exon 4 of 20			ENSP00000500782.1	Q5T2S8-1
ODAD2	ENST00000434029.1 link	n.72A>G		non_coding_transcript_exon_variant	Exon 2 of 10	2

Frequencies

GnomAD3 genomes

AF:

0.00178

AC:

266

AN:

149256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000618

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00388

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000199

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00263

Gnomad OTH

AF:

0.00147

GnomAD3 exomes

AF:

0.00167

AC:

205

AN:

122926

Hom.:

AF XY:

0.00146

AC XY:

AN XY:

66910

show subpopulations

Gnomad AFR exome

AF:

0.000612

Gnomad AMR exome

AF:

0.00167

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000686

Gnomad NFE exome

AF:

0.00300

Gnomad OTH exome

AF:

0.00248

GnomAD4 exome

AF:

0.00267

AC:

3631

AN:

1361606

Hom.:

Cov.:

AF XY:

0.00249

AC XY:

1672

AN XY:

672610

show subpopulations

Gnomad4 AFR exome

AF:

0.000410

Gnomad4 AMR exome

AF:

0.00129

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000457

Gnomad4 NFE exome

AF:

0.00320

Gnomad4 OTH exome

AF:

0.00259

GnomAD4 genome

AF:

0.00178

AC:

266

AN:

149350

Hom.:

Cov.:

AF XY:

0.00173

AC XY:

126

AN XY:

72834

show subpopulations

Gnomad4 AFR

AF:

0.000617

Gnomad4 AMR

AF:

0.00388

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000199

Gnomad4 NFE

AF:

0.00263

Gnomad4 OTH

AF:

0.00145

Alfa

AF:

0.00223

Hom.:

Bravo

AF:

0.00212

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:1

Jul 21, 2016

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

not provided

Benign:1

Feb 22, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia 23

Benign:1

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.21

Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over