NM_001364171.2:c.856G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PP3BP6_Very_StrongBS1BS2

The NM_001364171.2(ODAD1):c.856G>A(p.Gly286Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00114 in 1,606,834 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0040 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00084 ( 6 hom. )

Consequence

ODAD1
NM_001364171.2 missense, splice_region

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.916

Publications

1 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 -15 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

BP6

Variant 19-48303782-C-T is Benign according to our data. Variant chr19-48303782-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 262505.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00395 (602/152336) while in subpopulation AFR AF = 0.011 (459/41582). AF 95% confidence interval is 0.0102. There are 3 homozygotes in GnomAd4. There are 278 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AR,AD gene

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.856G>A	p.Gly286Arg	missense splice_region	Exon 10 of 16	NP_001351100.1
	ODAD1	NM_144577.4		c.745G>A	p.Gly249Arg	missense splice_region	Exon 8 of 14	NP_653178.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ODAD1	ENST00000674294.1	MANE Select	c.856G>A	p.Gly286Arg	missense splice_region	Exon 10 of 16	ENSP00000501363.1
ODAD1	ENST00000315396.7	TSL:1	c.745G>A	p.Gly249Arg	missense splice_region	Exon 8 of 14	ENSP00000318429.7
ODAD1	ENST00000859784.1		c.856G>A	p.Gly286Arg	missense splice_region	Exon 9 of 15	ENSP00000529843.1

Frequencies

GnomAD3 genomes

AF:

0.00394

AC:

600

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0110

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00412

Gnomad ASJ

AF:

0.00835

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000500

Gnomad OTH

AF:

0.00526

GnomAD2 exomes

AF:

0.00170

AC:

413

AN:

243150

AF XY:

0.00143

show subpopulations

Gnomad AFR exome

AF:

0.0115

Gnomad AMR exome

AF:

0.00195

Gnomad ASJ exome

AF:

0.00704

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.000142

Gnomad NFE exome

AF:

0.000648

Gnomad OTH exome

AF:

0.00325

GnomAD4 exome

AF:

0.000840

AC:

1222

AN:

1454498

Hom.:

Cov.:

AF XY:

0.000809

AC XY:

585

AN XY:

723192

show subpopulations

African (AFR)

AF:

0.0103

AC:

345

AN:

33416

American (AMR)

AF:

0.00232

AC:

102

AN:

44000

Ashkenazi Jewish (ASJ)

AF:

0.00767

AC:

194

AN:

25292

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39690

South Asian (SAS)

AF:

0.0000823

AC:

AN:

85090

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

53070

Middle Eastern (MID)

AF:

0.00192

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

0.000382

AC:

423

AN:

1108140

Other (OTH)

AF:

0.00221

AC:

133

AN:

60082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

134

200

267

334

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<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:

0.00395

AC:

602

AN:

152336

Hom.:

Cov.:

AF XY:

0.00373

AC XY:

278

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.0110

AC:

459

AN:

41582

American (AMR)

AF:

0.00412

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00835

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000621

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000500

AC:

AN:

68028

Other (OTH)

AF:

0.00520

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

114

143

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:

0.00285

Hom.:

Bravo

AF:

0.00496

ESP6500AA

AF:

0.0109

AC:

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.00170

AC:

206

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

Primary ciliary dyskinesia (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.14

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.00014

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0069

LIST_S2

Benign

0.20

MetaRNN

Benign

0.0038

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.3

PhyloP100

-0.92

PrimateAI

Benign

0.24

PROVEAN

Benign

1.3

REVEL

Benign

0.013

Sift

Benign

0.59

Sift4G

Benign

0.41

Polyphen

0.0

Vest4

0.030

MutPred

0.23

Gain of MoRF binding (P = 0.0381)

MVP

0.21

MPC

0.24

ClinPred

0.00069

GERP RS

-2.6

Varity_R

0.049

gMVP

0.083

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.75

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.75

Position offset: -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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over