rs531033796

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_018076.5(ODAD2):c.1228C>G(p.Gln410Glu) 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 0.0011 ( 4 hom., cov: 18)

Exomes 𝑓: 0.00012 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

ODAD2
NM_018076.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.19

Publications

0 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0077064335).

BP6

Variant 10-27968933-G-C is Benign according to our data. Variant chr10-27968933-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 412249.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODAD2	NM_018076.5 link	c.1228C>G	p.Gln410Glu	missense_variant	Exon 9 of 20	ENST00000305242.10	NP_060546.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODAD2	ENST00000305242.10 link	c.1228C>G	p.Gln410Glu	missense_variant	Exon 9 of 20	1	NM_018076.5	ENSP00000306410.5

Frequencies

GnomAD3 genomes

AF:

0.00105

AC:

144

AN:

136990

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00370

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000376

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000469

Gnomad OTH

AF:

0.00227

GnomAD2 exomes

AF:

0.000426

AC:

AN:

77478

AF XY:

0.000285

show subpopulations

Gnomad AFR exome

AF:

0.00441

Gnomad AMR exome

AF:

0.000173

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000443

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000121

AC:

AN:

496474

Hom.:

Cov.:

AF XY:

0.0000832

AC XY:

AN XY:

264466

show subpopulations

African (AFR)

AF:

0.00358

AC:

AN:

13114

American (AMR)

AF:

0.000176

AC:

AN:

22670

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14386

East Asian (EAS)

AF:

0.00

AC:

AN:

31002

South Asian (SAS)

AF:

0.0000207

AC:

AN:

48306

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43852

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1988

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

293970

Other (OTH)

AF:

0.000294

AC:

AN:

27186

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00106

AC:

146

AN:

137098

Hom.:

Cov.:

AF XY:

0.00108

AC XY:

AN XY:

65966

show subpopulations

African (AFR)

AF:

0.00375

AC:

134

AN:

35752

American (AMR)

AF:

0.000376

AC:

AN:

13314

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3252

East Asian (EAS)

AF:

0.00

AC:

AN:

4876

South Asian (SAS)

AF:

0.00

AC:

AN:

3808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9162

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0000469

AC:

AN:

64002

Other (OTH)

AF:

0.00224

AC:

AN:

1788

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00126

Hom.:

ExAC

AF:

0.000174

AC:

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

Jan 17, 2018

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. -

Primary ciliary dyskinesia 23

Benign:1

Feb 14, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

ODAD2-related disorder

Benign:1

Mar 05, 2020

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

0.081

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.43

CADD

Benign

6.8

(source)

DANN

Benign

0.19

DEOGEN2

Benign

0.0038

T;T

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.70

T;T

M_CAP

Benign

0.0056

MetaRNN

Benign

0.0077

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;.

PhyloP100

2.2

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.14

N;N

REVEL

Benign

0.12

Sift

Benign

0.41

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.011

B;.

Vest4

0.19

MVP

0.40

MPC

1.8

ClinPred

0.017

GERP RS

3.9

Varity_R

0.046

gMVP

0.18

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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