rs4405206

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018076.5(ODAD2):c.1028T>C(p.Ile343Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0687 in 1,613,718 control chromosomes in the GnomAD database, including 5,051 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. I343I) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.078 ( 622 hom., cov: 32)

Exomes 𝑓: 0.068 ( 4429 hom. )

Consequence

ODAD2
NM_018076.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.436

Publications

18 publications found

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 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 23
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ODAD2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005333036).

BP6

Variant 10-27971222-A-G is Benign according to our data. Variant chr10-27971222-A-G is described in ClinVar as Benign. ClinVar VariationId is 402396.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018076.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ODAD2	NM_018076.5	MANE Select	c.1028T>C	p.Ile343Thr	missense	Exon 8 of 20	NP_060546.2
ODAD2	NM_001290020.2		c.1028T>C	p.Ile343Thr	missense	Exon 8 of 20	NP_001276949.1
ODAD2	NM_001312689.2		c.104T>C	p.Ile35Thr	missense	Exon 3 of 15	NP_001299618.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ODAD2	ENST00000305242.10	TSL:1 MANE Select	c.1028T>C	p.Ile343Thr	missense	Exon 8 of 20	ENSP00000306410.5
ODAD2	ENST00000673439.1		c.1028T>C	p.Ile343Thr	missense	Exon 8 of 20	ENSP00000500782.1
ODAD2	ENST00000672841.1		c.104T>C	p.Ile35Thr	missense	Exon 3 of 15	ENSP00000499983.1

Frequencies

GnomAD3 genomes

AF:

0.0775

AC:

11787

AN:

152008

Hom.:

620

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0837

Gnomad AMI

AF:

0.129

Gnomad AMR

AF:

0.0879

Gnomad ASJ

AF:

0.120

Gnomad EAS

AF:

0.266

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.0277

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0578

Gnomad OTH

AF:

0.0969

GnomAD2 exomes

AF:

0.0856

AC:

21502

AN:

251140

AF XY:

0.0863

show subpopulations

Gnomad AFR exome

AF:

0.0834

Gnomad AMR exome

AF:

0.0609

Gnomad ASJ exome

AF:

0.113

Gnomad EAS exome

AF:

0.288

Gnomad FIN exome

AF:

0.0255

Gnomad NFE exome

AF:

0.0602

Gnomad OTH exome

AF:

0.0782

GnomAD4 exome

AF:

0.0678

AC:

99052

AN:

1461592

Hom.:

4429

Cov.:

AF XY:

0.0694

AC XY:

50447

AN XY:

727078

show subpopulations

African (AFR)

AF:

0.0844

AC:

2825

AN:

33462

American (AMR)

AF:

0.0637

AC:

2848

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.115

AC:

3009

AN:

26128

East Asian (EAS)

AF:

0.252

AC:

9985

AN:

39686

South Asian (SAS)

AF:

0.118

AC:

10176

AN:

86228

European-Finnish (FIN)

AF:

0.0259

AC:

1382

AN:

53410

Middle Eastern (MID)

AF:

0.0905

AC:

522

AN:

5768

European-Non Finnish (NFE)

AF:

0.0571

AC:

63524

AN:

1111822

Other (OTH)

AF:

0.0792

AC:

4781

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

4544

9088

13632

18176

22720

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2596

5192

7788

10384

12980

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0776

AC:

11805

AN:

152126

Hom.:

622

Cov.:

AF XY:

0.0801

AC XY:

5959

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.0838

AC:

3479

AN:

41492

American (AMR)

AF:

0.0882

AC:

1348

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.120

AC:

417

AN:

3470

East Asian (EAS)

AF:

0.267

AC:

1378

AN:

5164

South Asian (SAS)

AF:

0.127

AC:

612

AN:

4820

European-Finnish (FIN)

AF:

0.0277

AC:

293

AN:

10588

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0578

AC:

3928

AN:

67990

Other (OTH)

AF:

0.0988

AC:

209

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

541

1082

1623

2164

2705

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

134

268

402

536

670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0658

Hom.:

811

Bravo

AF:

0.0824

TwinsUK

AF:

0.0591

AC:

219

ALSPAC

AF:

0.0625

AC:

241

ESP6500AA

AF:

0.0881

AC:

388

ESP6500EA

AF:

0.0649

AC:

558

ExAC

AF:

0.0862

AC:

10460

Asia WGS

AF:

0.166

AC:

576

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Nov 27, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Primary ciliary dyskinesia 23

Benign:2

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency

Primary ciliary dyskinesia

Benign:1

Jul 09, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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.

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.076

(source)

DANN

Benign

0.48

DEOGEN2

Benign

0.00086

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0073

LIST_S2

Benign

0.30

MetaRNN

Benign

0.0053

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

PhyloP100

-0.44

PrimateAI

Benign

0.35

PROVEAN

Benign

0.22

REVEL

Benign

0.013

Sift

Benign

0.40

Sift4G

Benign

0.40

Polyphen

0.017

Vest4

0.0050

MPC

0.23

ClinPred

0.0041

GERP RS

-8.1

Varity_R

0.052

gMVP

0.18

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over