rs74925056

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_001364171.2(ODAD1):c.2024C>T(p.Ser675Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0375 in 1,613,142 control chromosomes in the GnomAD database, including 1,204 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S675S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.044 ( 184 hom., cov: 32)

Exomes 𝑓: 0.037 ( 1020 hom. )

Consequence

ODAD1
NM_001364171.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.684

Publications

12 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=0.0040144324).

BP6

Variant 19-48297076-G-A is Benign according to our data. Variant chr19-48297076-G-A is described in ClinVar as Benign. ClinVar VariationId is 262497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODAD1	NM_001364171.2 link	c.2024C>T	p.Ser675Leu	missense_variant	Exon 16 of 16	ENST00000674294.1	NP_001351100.1
ODAD1	NM_144577.4 link	c.1913C>T	p.Ser638Leu	missense_variant	Exon 14 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.2024C>T	p.Ser675Leu	missense_variant	Exon 16 of 16		NM_001364171.2	ENSP00000501363.1		A0A6I8PTZ2

Frequencies

GnomAD3 genomes

AF:

0.0445

AC:

6762

AN:

152032

Hom.:

185

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0736

Gnomad AMI

AF:

0.0691

Gnomad AMR

AF:

0.0252

Gnomad ASJ

AF:

0.0415

Gnomad EAS

AF:

0.0285

Gnomad SAS

AF:

0.0308

Gnomad FIN

AF:

0.0177

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0375

Gnomad OTH

AF:

0.0345

GnomAD2 exomes

AF:

0.0359

AC:

9016

AN:

250804

AF XY:

0.0354

show subpopulations

Gnomad AFR exome

AF:

0.0789

Gnomad AMR exome

AF:

0.0171

Gnomad ASJ exome

AF:

0.0369

Gnomad EAS exome

AF:

0.0315

Gnomad FIN exome

AF:

0.0181

Gnomad NFE exome

AF:

0.0396

Gnomad OTH exome

AF:

0.0316

GnomAD4 exome

AF:

0.0368

AC:

53736

AN:

1460992

Hom.:

1020

Cov.:

AF XY:

0.0367

AC XY:

26700

AN XY:

726836

show subpopulations

African (AFR)

AF:

0.0727

AC:

2433

AN:

33472

American (AMR)

AF:

0.0185

AC:

828

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0359

AC:

938

AN:

26124

East Asian (EAS)

AF:

0.0315

AC:

1250

AN:

39694

South Asian (SAS)

AF:

0.0361

AC:

3116

AN:

86244

European-Finnish (FIN)

AF:

0.0180

AC:

957

AN:

53034

Middle Eastern (MID)

AF:

0.0373

AC:

215

AN:

5758

European-Non Finnish (NFE)

AF:

0.0377

AC:

41868

AN:

1111584

Other (OTH)

AF:

0.0353

AC:

2131

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

3308

6617

9925

13234

16542

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1644

3288

4932

6576

8220

<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:

0.0444

AC:

6758

AN:

152150

Hom.:

184

Cov.:

AF XY:

0.0424

AC XY:

3157

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.0734

AC:

3046

AN:

41496

American (AMR)

AF:

0.0251

AC:

384

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0415

AC:

144

AN:

3472

East Asian (EAS)

AF:

0.0287

AC:

148

AN:

5148

South Asian (SAS)

AF:

0.0307

AC:

148

AN:

4826

European-Finnish (FIN)

AF:

0.0177

AC:

188

AN:

10622

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0375

AC:

2547

AN:

67996

Other (OTH)

AF:

0.0342

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

317

633

950

1266

1583

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

240

320

400

<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:

0.0395

Hom.:

222

Bravo

AF:

0.0471

TwinsUK

AF:

0.0356

AC:

132

ALSPAC

AF:

0.0379

AC:

146

ESP6500AA

AF:

0.0760

AC:

335

ESP6500EA

AF:

0.0399

AC:

343

ExAC

AF:

0.0387

AC:

4694

Asia WGS

AF:

0.0340

AC:

119

AN:

3478

EpiCase

AF:

0.0404

EpiControl

AF:

0.0379

ClinVar

Significance: Benign

Submissions summary: Benign:5

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 21, 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:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 19, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

0.080

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.74

CADD

Benign

7.6

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.00066

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.085

LIST_S2

Benign

0.55

MetaRNN

Benign

0.0040

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.63

PhyloP100

0.68

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.99

REVEL

Benign

0.050

Sift

Benign

0.59

Sift4G

Benign

1.0

Polyphen

0.026

Vest4

0.038

MPC

0.57

ClinPred

0.0032

GERP RS

0.47

Varity_R

0.032

gMVP

0.073

Mutation Taster

=100/0

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