rs552527338

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_018076.5(ODAD2):c.1219G>A(p.Gly407Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 19)

Exomes 𝑓: 0.000031 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ODAD2
NM_018076.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.550

Publications

0 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: ClinGen, G2P, 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010136485).

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	UniProt
ODAD2	NM_018076.5	MANE Select	c.1219G>A	p.Gly407Arg	missense	Exon 9 of 20	NP_060546.2
ODAD2	NM_001290020.2		c.1219G>A	p.Gly407Arg	missense	Exon 9 of 20	NP_001276949.1	A0A140VKF7
ODAD2	NM_001312689.2		c.295G>A	p.Gly99Arg	missense	Exon 4 of 15	NP_001299618.1	A0A5F9ZH22

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ODAD2	ENST00000305242.10	TSL:1 MANE Select	c.1219G>A	p.Gly407Arg	missense	Exon 9 of 20	ENSP00000306410.5	Q5T2S8-1
ODAD2	ENST00000673439.1		c.1219G>A	p.Gly407Arg	missense	Exon 9 of 20	ENSP00000500782.1	Q5T2S8-1
ODAD2	ENST00000852623.1		c.1219G>A	p.Gly407Arg	missense	Exon 9 of 20	ENSP00000522682.1

Frequencies

GnomAD3 genomes

AF:

0.000334

AC:

AN:

137882

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00117

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000466

Gnomad OTH

AF:

0.000561

GnomAD2 exomes

AF:

0.000101

AC:

AN:

79594

AF XY:

0.000101

show subpopulations

Gnomad AFR exome

AF:

0.000861

Gnomad AMR exome

AF:

0.0000863

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000324

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000315

AC:

AN:

508490

Hom.:

Cov.:

AF XY:

0.0000295

AC XY:

AN XY:

270912

show subpopulations

African (AFR)

AF:

0.000374

AC:

AN:

13386

American (AMR)

AF:

0.0000437

AC:

AN:

22896

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14522

East Asian (EAS)

AF:

0.00

AC:

AN:

31200

South Asian (SAS)

AF:

0.0000205

AC:

AN:

48798

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44318

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2008

European-Non Finnish (NFE)

AF:

0.0000263

AC:

AN:

303622

Other (OTH)

AF:

0.0000360

AC:

AN:

27740

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000333

AC:

AN:

137996

Hom.:

Cov.:

AF XY:

0.000361

AC XY:

AN XY:

66506

show subpopulations

African (AFR)

AF:

0.00117

AC:

AN:

36036

American (AMR)

AF:

0.00

AC:

AN:

13408

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3280

East Asian (EAS)

AF:

0.00

AC:

AN:

4892

South Asian (SAS)

AF:

0.00

AC:

AN:

3866

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9220

Middle Eastern (MID)

AF:

0.00

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.0000466

AC:

AN:

64334

Other (OTH)

AF:

0.000554

AC:

AN:

1806

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

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:

0.000169

Hom.:

ExAC

AF:

0.0000997

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Primary ciliary dyskinesia 23 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Benign

0.74

DEOGEN2

Benign

0.0029

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.68

M_CAP

Benign

0.0070

MetaRNN

Benign

0.010

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.8

PhyloP100

0.55

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.2

REVEL

Benign

0.20

Sift

Benign

0.043

Sift4G

Benign

0.085

Polyphen

0.019

Vest4

0.23

MutPred

0.45

Loss of methylation at R408 (P = 0.0408)

MVP

0.44

MPC

1.9

ClinPred

0.012

GERP RS

3.0

Varity_R

0.062

gMVP

0.32

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over