NM_018076.5:c.1709G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1

The NM_018076.5(ODAD2):c.1709G>A(p.Arg570Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000316 in 1,613,528 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R570W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00083 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00026 ( 0 hom. )

Consequence

ODAD2
NM_018076.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:5B:1

Conservation

PhyloP100: 0.385

Publications

4 publications found

Variant links:

Genes affected

ODAD2 (HGNC:25583): (outer dynein arm docking complex subunit 2) The protein encoded by this gene contains ten Armadillo repeat motifs (ARMs) and one HEAT repeat, and is thought to be involved in ciliary and flagellar movement. This protein has been shown to localize to the ciliary axonemes and at the ciliary base of respiratory cells. Studies indicate that mutations in this gene cause partial outer dynein arm (ODA) defects in respiratory cilia. The cilia of cells with mutations in this gene displayed either reduced ciliary beat frequency and amplitude, or, complete immotility. Some individuals with primary ciliary dyskensia (PCD) have been shown to have mutations in this gene. PCD is characterized by chronic airway disease and left/right body asymmetry defects. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]

ODAD2 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 23
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ODAD2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011244386).

BP6

Variant 10-27944256-C-T is Benign according to our data. Variant chr10-27944256-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 412251.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000828 (126/152234) while in subpopulation AMR AF = 0.00275 (42/15294). AF 95% confidence interval is 0.00209. There are 1 homozygotes in GnomAd4. There are 63 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018076.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ODAD2	NM_018076.5	MANE Select	c.1709G>A	p.Arg570Gln	missense	Exon 12 of 20	NP_060546.2
ODAD2	NM_001290020.2		c.1709G>A	p.Arg570Gln	missense	Exon 12 of 20	NP_001276949.1
ODAD2	NM_001312689.2		c.785G>A	p.Arg262Gln	missense	Exon 7 of 15	NP_001299618.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ODAD2	ENST00000305242.10	TSL:1 MANE Select	c.1709G>A	p.Arg570Gln	missense	Exon 12 of 20	ENSP00000306410.5
ODAD2	ENST00000673439.1		c.1709G>A	p.Arg570Gln	missense	Exon 12 of 20	ENSP00000500782.1
ODAD2	ENST00000672841.1		c.785G>A	p.Arg262Gln	missense	Exon 7 of 15	ENSP00000499983.1

Frequencies

GnomAD3 genomes

AF:

0.000828

AC:

126

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00138

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.000474

AC:

119

AN:

250946

AF XY:

0.000472

show subpopulations

Gnomad AFR exome

AF:

0.00209

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.000291

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000263

AC:

384

AN:

1461294

Hom.:

Cov.:

AF XY:

0.000270

AC XY:

196

AN XY:

726948

show subpopulations

African (AFR)

AF:

0.00149

AC:

AN:

33464

American (AMR)

AF:

0.00107

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39620

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86220

European-Finnish (FIN)

AF:

0.000187

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00258

AC:

AN:

5428

European-Non Finnish (NFE)

AF:

0.000193

AC:

215

AN:

1111954

Other (OTH)

AF:

0.000713

AC:

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

112

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.000828

AC:

126

AN:

152234

Hom.:

Cov.:

AF XY:

0.000846

AC XY:

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.00137

AC:

AN:

41546

American (AMR)

AF:

0.00275

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.000377

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000250

AC:

AN:

68012

Other (OTH)

AF:

0.00189

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000382

Hom.:

Bravo

AF:

0.000895

ESP6500AA

AF:

0.00340

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000437

AC:

EpiCase

AF:

0.000600

EpiControl

AF:

0.000771

ClinVar

ClinVar submissions as Germline

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Primary ciliary dyskinesia 23 (3)

not provided (2)

Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.052

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.092

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.83

M_CAP

Benign

0.012

MetaRNN

Benign

0.011

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PhyloP100

0.39

PrimateAI

Benign

0.21

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.057

Sift

Benign

0.066

Sift4G

Benign

0.074

Polyphen

0.14

Vest4

0.17

MVP

0.52

MPC

0.17

ClinPred

0.029

GERP RS

3.4

Varity_R

0.086

gMVP

0.37

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over