rs16981988

Variant names:

Variant summary

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

The NM_001364171.2(ODAD1):c.247C>T(p.Arg83Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0254 in 1,551,582 control chromosomes in the GnomAD database, including 621 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 99 hom., cov: 31)

Exomes 𝑓: 0.025 ( 522 hom. )

Consequence

ODAD1
NM_001364171.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.350

Publications

11 publications found

Variant links:

Genes affected

ODAD1 (HGNC:26560): (outer dynein arm docking complex subunit 1) This gene encodes a coiled-coil domain-containing protein that is a component of the outer dynein arm docking complex in cilia cells. Mutations in this gene may cause primary ciliary dyskinesia 20. [provided by RefSeq, May 2013]

ODAD1 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 20
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ODAD1 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=0.0030530393).

BP6

Variant 19-48318500-G-A is Benign according to our data. Variant chr19-48318500-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 262487.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODAD1	NM_001364171.2 link	c.247C>T	p.Arg83Trp	missense_variant	Exon 5 of 16	ENST00000674294.1	NP_001351100.1
ODAD1	NM_144577.4 link	c.136C>T	p.Arg46Trp	missense_variant	Exon 3 of 14		NP_653178.3	Q96M63-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODAD1	ENST00000674294.1 link	c.247C>T	p.Arg83Trp	missense_variant	Exon 5 of 16		NM_001364171.2	ENSP00000501363.1		A0A6I8PTZ2

Frequencies

GnomAD3 genomes

AF:

0.0314

AC:

4778

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0504

Gnomad AMI

AF:

0.0724

Gnomad AMR

AF:

0.0258

Gnomad ASJ

AF:

0.0473

Gnomad EAS

AF:

0.00289

Gnomad SAS

AF:

0.0315

Gnomad FIN

AF:

0.00858

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0253

Gnomad OTH

AF:

0.0306

GnomAD2 exomes

AF:

0.0258

AC:

4016

AN:

155636

AF XY:

0.0273

show subpopulations

Gnomad AFR exome

AF:

0.0512

Gnomad AMR exome

AF:

0.0190

Gnomad ASJ exome

AF:

0.0412

Gnomad EAS exome

AF:

0.00376

Gnomad FIN exome

AF:

0.00884

Gnomad NFE exome

AF:

0.0275

Gnomad OTH exome

AF:

0.0354

GnomAD4 exome

AF:

0.0248

AC:

34666

AN:

1399356

Hom.:

522

Cov.:

AF XY:

0.0254

AC XY:

17511

AN XY:

690188

show subpopulations

African (AFR)

AF:

0.0545

AC:

1723

AN:

31598

American (AMR)

AF:

0.0214

AC:

765

AN:

35702

Ashkenazi Jewish (ASJ)

AF:

0.0399

AC:

1006

AN:

25182

East Asian (EAS)

AF:

0.00151

AC:

AN:

35738

South Asian (SAS)

AF:

0.0349

AC:

2768

AN:

79236

European-Finnish (FIN)

AF:

0.00983

AC:

484

AN:

49232

Middle Eastern (MID)

AF:

0.0993

AC:

566

AN:

5698

European-Non Finnish (NFE)

AF:

0.0237

AC:

25591

AN:

1078960

Other (OTH)

AF:

0.0295

AC:

1709

AN:

58010

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

1931

3863

5794

7726

9657

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

998

1996

2994

3992

4990

<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:

0.0314

AC:

4786

AN:

152226

Hom.:

Cov.:

AF XY:

0.0311

AC XY:

2316

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0505

AC:

2096

AN:

41542

American (AMR)

AF:

0.0258

AC:

394

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.0473

AC:

164

AN:

3468

East Asian (EAS)

AF:

0.00289

AC:

AN:

5184

South Asian (SAS)

AF:

0.0315

AC:

152

AN:

4822

European-Finnish (FIN)

AF:

0.00858

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.0782

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0253

AC:

1721

AN:

68014

Other (OTH)

AF:

0.0303

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

235

470

705

940

1175

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<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:

0.0279

Hom.:

244

Bravo

AF:

0.0336

TwinsUK

AF:

0.0232

AC:

ALSPAC

AF:

0.0210

AC:

ESP6500AA

AF:

0.0455

AC:

ESP6500EA

AF:

0.0286

AC:

ExAC

AF:

0.0289

AC:

745

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 08, 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. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 10, 2022

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

See Variant Classification Assertion Criteria. -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Primary ciliary dyskinesia 20

Benign:1

Nov 04, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

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

0.18

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.038

Eigen

Benign

-0.070

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.54

LIST_S2

Uncertain

0.87

MetaRNN

Benign

0.0031

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

PhyloP100

0.35

PrimateAI

Benign

0.48

PROVEAN

Pathogenic

-4.4

REVEL

Benign

0.15

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.0050

Polyphen

1.0

Vest4

0.18

MPC

0.80

ClinPred

0.023

GERP RS

-0.63

Varity_R

0.14

gMVP

0.49

Mutation Taster

=96/4

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

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