NM_001364171.2:c.1097G>A

Variant names:

Variant summary

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

The NM_001364171.2(ODAD1):c.1097G>A(p.Arg366His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0328 in 1,613,962 control chromosomes in the GnomAD database, including 1,045 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R366C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.024 ( 65 hom., cov: 32)

Exomes 𝑓: 0.034 ( 980 hom. )

Consequence

ODAD1
NM_001364171.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.237

Publications

9 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=0.003387034).

BP6

Variant 19-48302837-C-T is Benign according to our data. Variant chr19-48302837-C-T is described in ClinVar as Benign. ClinVar VariationId is 262510.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 = 0.0242 (3692/152298) while in subpopulation NFE AF = 0.0365 (2481/68026). AF 95% confidence interval is 0.0353. There are 65 homozygotes in GnomAd4. There are 1742 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 65 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODAD1	NM_001364171.2 link	c.1097G>A	p.Arg366His	missense_variant	Exon 12 of 16	ENST00000674294.1	NP_001351100.1
ODAD1	NM_144577.4 link	c.986G>A	p.Arg329His	missense_variant	Exon 10 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.1097G>A	p.Arg366His	missense_variant	Exon 12 of 16		NM_001364171.2	ENSP00000501363.1		A0A6I8PTZ2

Frequencies

GnomAD3 genomes

AF:

0.0242

AC:

3687

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00702

Gnomad AMI

AF:

0.0746

Gnomad AMR

AF:

0.0330

Gnomad ASJ

AF:

0.0173

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0110

Gnomad FIN

AF:

0.0173

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0365

Gnomad OTH

AF:

0.0201

GnomAD2 exomes

AF:

0.0255

AC:

6395

AN:

250922

AF XY:

0.0251

show subpopulations

Gnomad AFR exome

AF:

0.00580

Gnomad AMR exome

AF:

0.0388

Gnomad ASJ exome

AF:

0.0193

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0180

Gnomad NFE exome

AF:

0.0344

Gnomad OTH exome

AF:

0.0250

GnomAD4 exome

AF:

0.0337

AC:

49224

AN:

1461664

Hom.:

980

Cov.:

AF XY:

0.0330

AC XY:

23996

AN XY:

727124

show subpopulations

African (AFR)

AF:

0.00594

AC:

199

AN:

33480

American (AMR)

AF:

0.0406

AC:

1817

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0199

AC:

520

AN:

26120

East Asian (EAS)

AF:

0.000126

AC:

AN:

39700

South Asian (SAS)

AF:

0.00966

AC:

833

AN:

86258

European-Finnish (FIN)

AF:

0.0176

AC:

937

AN:

53306

Middle Eastern (MID)

AF:

0.00711

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0389

AC:

43254

AN:

1111930

Other (OTH)

AF:

0.0268

AC:

1618

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

2689

5378

8066

10755

13444

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1628

3256

4884

6512

8140

<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:

0.0242

AC:

3692

AN:

152298

Hom.:

Cov.:

AF XY:

0.0234

AC XY:

1742

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.00700

AC:

291

AN:

41572

American (AMR)

AF:

0.0332

AC:

508

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0173

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5178

South Asian (SAS)

AF:

0.0112

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0173

AC:

184

AN:

10614

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0365

AC:

2481

AN:

68026

Other (OTH)

AF:

0.0199

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

202

404

607

809

1011

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<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:

0.0314

Hom.:

206

Bravo

AF:

0.0249

TwinsUK

AF:

0.0445

AC:

165

ALSPAC

AF:

0.0355

AC:

137

ESP6500AA

AF:

0.00704

AC:

ESP6500EA

AF:

0.0377

AC:

324

ExAC

AF:

0.0240

AC:

2915

Asia WGS

AF:

0.00779

AC:

AN:

3478

EpiCase

AF:

0.0302

EpiControl

AF:

0.0337

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 07, 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

- -

Oct 12, 2020

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

0.079

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.77

CADD

Benign

7.6

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.0015

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0048

LIST_S2

Benign

0.59

MetaRNN

Benign

0.0034

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

-0.24

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.3

REVEL

Benign

0.015

Sift

Benign

0.25

Sift4G

Benign

0.26

Polyphen

0.026

Vest4

0.081

MPC

0.31

ClinPred

0.015

GERP RS

-1.1

Varity_R

0.027

gMVP

0.12

Mutation Taster

=95/5

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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