19-48297657-G-A

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.1514C>T(p.Pro505Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 1,509,240 control chromosomes in the GnomAD database, including 55,586 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Synonymous variant affecting the same amino acid position (i.e. P505P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.23 ( 4244 hom., cov: 31)

Exomes 𝑓: 0.27 ( 51342 hom. )

Consequence

ODAD1
NM_001364171.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.798

Publications

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

ODAD1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001364171.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0045309663).

BP6

Variant 19-48297657-G-A is Benign according to our data. Variant chr19-48297657-G-A is described in ClinVar as Benign. ClinVar VariationId is 262489.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364171.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAD1	NM_001364171.2	MANE Select	c.1514C>T	p.Pro505Leu	missense	Exon 15 of 16	NP_001351100.1	A0A6I8PTZ2
	ODAD1	NM_144577.4		c.1403C>T	p.Pro468Leu	missense	Exon 13 of 14	NP_653178.3	Q96M63-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ODAD1	ENST00000674294.1	MANE Select	c.1514C>T	p.Pro505Leu	missense	Exon 15 of 16	ENSP00000501363.1	A0A6I8PTZ2
ODAD1	ENST00000315396.7	TSL:1	c.1403C>T	p.Pro468Leu	missense	Exon 13 of 14	ENSP00000318429.7	Q96M63-1
ODAD1	ENST00000859784.1		c.1574C>T	p.Pro525Leu	missense	Exon 14 of 15	ENSP00000529843.1

Frequencies

GnomAD3 genomes

AF:

0.225

AC:

34235

AN:

151846

Hom.:

4240

Cov.:

show subpopulations

Gnomad AFR

AF:

0.125

Gnomad AMI

AF:

0.280

Gnomad AMR

AF:

0.239

Gnomad ASJ

AF:

0.203

Gnomad EAS

AF:

0.139

Gnomad SAS

AF:

0.164

Gnomad FIN

AF:

0.274

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.287

Gnomad OTH

AF:

0.241

GnomAD2 exomes

AF:

0.235

AC:

38118

AN:

162302

AF XY:

0.235

show subpopulations

Gnomad AFR exome

AF:

0.122

Gnomad AMR exome

AF:

0.216

Gnomad ASJ exome

AF:

0.221

Gnomad EAS exome

AF:

0.135

Gnomad FIN exome

AF:

0.276

Gnomad NFE exome

AF:

0.284

Gnomad OTH exome

AF:

0.253

GnomAD4 exome

AF:

0.270

AC:

366654

AN:

1357276

Hom.:

51342

Cov.:

AF XY:

0.267

AC XY:

177537

AN XY:

664430

show subpopulations

African (AFR)

AF:

0.114

AC:

3424

AN:

30002

American (AMR)

AF:

0.216

AC:

5963

AN:

27554

Ashkenazi Jewish (ASJ)

AF:

0.216

AC:

4245

AN:

19622

East Asian (EAS)

AF:

0.136

AC:

5236

AN:

38574

South Asian (SAS)

AF:

0.164

AC:

11384

AN:

69556

European-Finnish (FIN)

AF:

0.278

AC:

13751

AN:

49398

Middle Eastern (MID)

AF:

0.198

AC:

1048

AN:

5286

European-Non Finnish (NFE)

AF:

0.290

AC:

307559

AN:

1061554

Other (OTH)

AF:

0.252

AC:

14044

AN:

55730

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

12613

25226

37840

50453

63066

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10342

20684

31026

41368

51710

<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:

0.225

AC:

34249

AN:

151964

Hom.:

4244

Cov.:

AF XY:

0.222

AC XY:

16513

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.125

AC:

5186

AN:

41466

American (AMR)

AF:

0.239

AC:

3654

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.203

AC:

703

AN:

3468

East Asian (EAS)

AF:

0.138

AC:

712

AN:

5142

South Asian (SAS)

AF:

0.166

AC:

801

AN:

4816

European-Finnish (FIN)

AF:

0.274

AC:

2897

AN:

10566

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.287

AC:

19468

AN:

67930

Other (OTH)

AF:

0.238

AC:

502

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1304

2608

3913

5217

6521

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

350

700

1050

1400

1750

<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:

0.257

Hom.:

3182

Bravo

AF:

0.219

Asia WGS

AF:

0.139

AC:

485

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

not provided (2)

Primary ciliary dyskinesia (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.73

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0028

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.63

MetaRNN

Benign

0.0045

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.0

PhyloP100

0.80

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.046

Sift

Benign

0.051

Sift4G

Uncertain

0.0080

Varity_R

0.054

gMVP

0.067

Mutation Taster

=98/2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over