rs150723128

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_018076.5(ODAD2):c.1207T>A(p.Ser403Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 18)

Exomes 𝑓: 0.0020 ( 7 hom. )

Consequence

ODAD2
NM_018076.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.715

Publications

1 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=0.0062865317).

BP6

Variant 10-27968954-A-T is Benign according to our data. Variant chr10-27968954-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 412248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00146 (203/138584) while in subpopulation NFE AF = 0.00251 (162/64574). AF 95% confidence interval is 0.00219. There are 0 homozygotes in GnomAd4. There are 90 alleles in the male GnomAd4 subpopulation. Median coverage is 18. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 7 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODAD2	NM_018076.5 link	c.1207T>A	p.Ser403Thr	missense_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.1207T>A	p.Ser403Thr	missense_variant	Exon 9 of 20	1	NM_018076.5	ENSP00000306410.5		Q5T2S8-1

Frequencies

GnomAD3 genomes

AF:

0.00147

AC:

203

AN:

138468

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000167

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000818

Gnomad ASJ

AF:

0.00122

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00183

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00251

Gnomad OTH

AF:

0.00168

GnomAD2 exomes

AF:

0.00143

AC:

118

AN:

82242

AF XY:

0.00127

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000854

Gnomad ASJ exome

AF:

0.00296

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00163

Gnomad NFE exome

AF:

0.00253

Gnomad OTH exome

AF:

0.00129

GnomAD4 exome

AF:

0.00204

AC:

1073

AN:

525054

Hom.:

Cov.:

AF XY:

0.00204

AC XY:

571

AN XY:

279828

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

13742

American (AMR)

AF:

0.000859

AC:

AN:

23282

Ashkenazi Jewish (ASJ)

AF:

0.00196

AC:

AN:

14824

East Asian (EAS)

AF:

0.00

AC:

AN:

31562

South Asian (SAS)

AF:

0.00

AC:

AN:

49426

European-Finnish (FIN)

AF:

0.00271

AC:

122

AN:

45026

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2076

European-Non Finnish (NFE)

AF:

0.00273

AC:

865

AN:

316696

Other (OTH)

AF:

0.00130

AC:

AN:

28420

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

136

181

226

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00146

AC:

203

AN:

138584

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

AN XY:

66866

show subpopulations

African (AFR)

AF:

0.000166

AC:

AN:

36154

American (AMR)

AF:

0.000817

AC:

AN:

13466

Ashkenazi Jewish (ASJ)

AF:

0.00122

AC:

AN:

3284

East Asian (EAS)

AF:

0.00

AC:

AN:

4896

South Asian (SAS)

AF:

0.00

AC:

AN:

3956

European-Finnish (FIN)

AF:

0.00183

AC:

AN:

9284

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00251

AC:

162

AN:

64574

Other (OTH)

AF:

0.00166

AC:

AN:

1804

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00356

Hom.:

ExAC

AF:

0.000751

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:1

Jun 09, 2017

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

May 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ODAD2: BP4 -

Primary ciliary dyskinesia 23

Benign:1

Dec 02, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

ODAD2-related disorder

Benign:1

Apr 19, 2024

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.51

CADD

Benign

4.0

(source)

DANN

Benign

0.49

DEOGEN2

Benign

0.0032

T;T

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.63

T;T

M_CAP

Benign

0.0051

MetaRNN

Benign

0.0063

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;.

PhyloP100

0.71

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.75

N;N

REVEL

Benign

0.028

Sift

Benign

0.24

T;T

Sift4G

Benign

0.11

T;T

Polyphen

0.012

B;.

Vest4

0.26

MVP

0.34

MPC

1.6

ClinPred

0.0080

GERP RS

2.7

Varity_R

0.062

gMVP

0.16

Mutation Taster

=94/6

polymorphism

(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