rs3737184

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.3121G>T(p.Ala1041Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0201 in 1,612,734 control chromosomes in the GnomAD database, including 2,642 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1041T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.022 ( 226 hom., cov: 32)

Exomes 𝑓: 0.020 ( 2416 hom. )

Consequence

ODAD2
NM_018076.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.41

Publications

11 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=0.0017198324).

BP6

Variant 10-27812526-C-A is Benign according to our data. Variant chr10-27812526-C-A is described in ClinVar as [Benign]. Clinvar id is 417179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODAD2	NM_018076.5 link	c.3121G>T	p.Ala1041Ser	missense_variant	Exon 20 of 20	ENST00000305242.10	NP_060546.2	Q5T2S8-1A0A140VKF7B7Z7Y0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODAD2	ENST00000305242.10 link	c.3121G>T	p.Ala1041Ser	missense_variant	Exon 20 of 20	1	NM_018076.5	ENSP00000306410.5		Q5T2S8-1

Frequencies

GnomAD3 genomes

AF:

0.0219

AC:

3331

AN:

152062

Hom.:

222

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00319

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0609

Gnomad ASJ

AF:

0.00289

Gnomad EAS

AF:

0.215

Gnomad SAS

AF:

0.116

Gnomad FIN

AF:

0.0383

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00206

Gnomad OTH

AF:

0.0192

GnomAD2 exomes

AF:

0.0505

AC:

12610

AN:

249854

AF XY:

0.0495

show subpopulations

Gnomad AFR exome

AF:

0.00278

Gnomad AMR exome

AF:

0.111

Gnomad ASJ exome

AF:

0.00239

Gnomad EAS exome

AF:

0.221

Gnomad FIN exome

AF:

0.0374

Gnomad NFE exome

AF:

0.00252

Gnomad OTH exome

AF:

0.0374

GnomAD4 exome

AF:

0.0199

AC:

29010

AN:

1460554

Hom.:

2416

Cov.:

AF XY:

0.0220

AC XY:

16017

AN XY:

726570

show subpopulations

African (AFR)

AF:

0.00203

AC:

AN:

33424

American (AMR)

AF:

0.104

AC:

4595

AN:

44290

Ashkenazi Jewish (ASJ)

AF:

0.00264

AC:

AN:

26120

East Asian (EAS)

AF:

0.255

AC:

10095

AN:

39626

South Asian (SAS)

AF:

0.109

AC:

9330

AN:

85870

European-Finnish (FIN)

AF:

0.0356

AC:

1900

AN:

53404

Middle Eastern (MID)

AF:

0.00694

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00114

AC:

1272

AN:

1111712

Other (OTH)

AF:

0.0272

AC:

1641

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

1172

2344

3517

4689

5861

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

354

708

1062

1416

1770

<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:

0.0219

AC:

3339

AN:

152180

Hom.:

226

Cov.:

AF XY:

0.0262

AC XY:

1949

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.00318

AC:

132

AN:

41540

American (AMR)

AF:

0.0616

AC:

942

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00289

AC:

AN:

3466

East Asian (EAS)

AF:

0.215

AC:

1111

AN:

5168

South Asian (SAS)

AF:

0.116

AC:

559

AN:

4808

European-Finnish (FIN)

AF:

0.0383

AC:

406

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00206

AC:

140

AN:

68006

Other (OTH)

AF:

0.0185

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

145

290

435

580

725

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<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:

0.0135

Hom.:

385

Bravo

AF:

0.0232

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.00318

AC:

ESP6500EA

AF:

0.00186

AC:

ExAC

AF:

0.0478

AC:

5798

Asia WGS

AF:

0.152

AC:

528

AN:

3478

EpiCase

AF:

0.00174

EpiControl

AF:

0.00148

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Primary ciliary dyskinesia

Benign:1

Aug 01, 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. -

Primary ciliary dyskinesia 23

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.12

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.0035

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.84

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

PhyloP100

3.4

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-1.5

REVEL

Uncertain

0.30

Sift

Benign

0.091

Sift4G

Benign

0.26

Polyphen

0.21

Vest4

0.15

MPC

0.25

ClinPred

0.014

GERP RS

4.9

Varity_R

0.14

gMVP

0.27

Mutation Taster

=92/8

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over