NM_018076.5:c.1237C>G

Variant names:

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.1237C>G(p.Arg413Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R413Q) has been classified as Benign.

Frequency

Genomes: 𝑓 0.092 ( 402 hom., cov: 17)

Exomes 𝑓: 0.084 ( 1247 hom. )

Consequence

ODAD2
NM_018076.5 missense, splice_region

Scores

Splicing: ADA: 0.002123

Clinical Significance

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

Conservation

PhyloP100: 0.594

Publications

3 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=0.00283131).

BP6

Variant 10-27968924-G-C is Benign according to our data. Variant chr10-27968924-G-C is described in ClinVar as Benign. ClinVar VariationId is 241255.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODAD2	NM_018076.5 link	c.1237C>G	p.Arg413Gly	missense_variant, splice_region_variant	Exon 9 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.1237C>G	p.Arg413Gly	missense_variant, splice_region_variant	Exon 9 of 20	1	NM_018076.5	ENSP00000306410.5		Q5T2S8-1

Frequencies

GnomAD3 genomes

AF:

0.0919

AC:

11945

AN:

130030

Hom.:

402

Cov.:

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.130

Gnomad AMR

AF:

0.0965

Gnomad ASJ

AF:

0.0599

Gnomad EAS

AF:

0.0112

Gnomad SAS

AF:

0.0863

Gnomad FIN

AF:

0.0553

Gnomad MID

AF:

0.0646

Gnomad NFE

AF:

0.0968

Gnomad OTH

AF:

0.0881

GnomAD2 exomes

AF:

0.0813

AC:

6008

AN:

73864

AF XY:

0.0803

show subpopulations

Gnomad AFR exome

AF:

0.108

Gnomad AMR exome

AF:

0.112

Gnomad ASJ exome

AF:

0.0497

Gnomad EAS exome

AF:

0.00912

Gnomad FIN exome

AF:

0.0547

Gnomad NFE exome

AF:

0.0944

Gnomad OTH exome

AF:

0.0867

GnomAD4 exome

AF:

0.0838

AC:

39388

AN:

469766

Hom.:

1247

Cov.:

AF XY:

0.0839

AC XY:

20962

AN XY:

249756

show subpopulations

African (AFR)

AF:

0.104

AC:

1295

AN:

12472

American (AMR)

AF:

0.114

AC:

2463

AN:

21672

Ashkenazi Jewish (ASJ)

AF:

0.0539

AC:

732

AN:

13580

East Asian (EAS)

AF:

0.00825

AC:

251

AN:

30426

South Asian (SAS)

AF:

0.0858

AC:

3916

AN:

45646

European-Finnish (FIN)

AF:

0.0585

AC:

2452

AN:

41904

Middle Eastern (MID)

AF:

0.0584

AC:

110

AN:

1882

European-Non Finnish (NFE)

AF:

0.0942

AC:

26035

AN:

276318

Other (OTH)

AF:

0.0825

AC:

2134

AN:

25866

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

1436

2871

4307

5742

7178

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

182

364

546

728

910

<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:

0.0918

AC:

11952

AN:

130150

Hom.:

402

Cov.:

AF XY:

0.0887

AC XY:

5553

AN XY:

62622

show subpopulations

African (AFR)

AF:

0.105

AC:

3557

AN:

33840

American (AMR)

AF:

0.0966

AC:

1231

AN:

12742

Ashkenazi Jewish (ASJ)

AF:

0.0599

AC:

185

AN:

3088

East Asian (EAS)

AF:

0.0112

AC:

AN:

4812

South Asian (SAS)

AF:

0.0866

AC:

303

AN:

3500

European-Finnish (FIN)

AF:

0.0553

AC:

480

AN:

8684

Middle Eastern (MID)

AF:

0.0620

AC:

AN:

274

European-Non Finnish (NFE)

AF:

0.0967

AC:

5875

AN:

60726

Other (OTH)

AF:

0.0863

AC:

144

AN:

1668

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

400

799

1199

1598

1998

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:

0.0394

Hom.:

ExAC

AF:

0.0407

AC:

3186

ClinVar

Significance: Benign

Submissions summary: Benign:4

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

- -

Feb 12, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Primary ciliary dyskinesia

Benign:1

Jun 22, 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

Jan 23, 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

0.10

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.42

DEOGEN2

Benign

0.0060

T;T

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.095

LIST_S2

Benign

0.45

T;T

MetaRNN

Benign

0.0028

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

L;.

PhyloP100

0.59

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.024

Sift

Benign

0.11

T;T

Sift4G

Benign

0.13

T;D

Polyphen

0.089

B;.

Vest4

0.11

MPC

2.1

ClinPred

0.0014

GERP RS

2.0

Varity_R

0.058

gMVP

0.15

Mutation Taster

=95/5

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0021

dbscSNV1_RF

Benign

0.032

SpliceAI score (max)

0.030

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