rs1240219568

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_018076.5(ODAD2):c.383C>G(p.Ala128Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000685 in 1,460,608 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A128T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000049 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000023 ( 0 hom. )

Consequence

ODAD2
NM_018076.5 missense, splice_region

Scores

Splicing: ADA: 0.2436

Clinical Significance

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

Conservation

PhyloP100: 3.02

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:

LOC112268060 (HGNC:):

LOC112268060 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.21313262).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAD2	NM_018076.5	MANE Select	c.383C>G	p.Ala128Gly	missense splice_region	Exon 4 of 20	NP_060546.2
	ODAD2	NM_001290020.2		c.383C>G	p.Ala128Gly	missense splice_region	Exon 4 of 20	NP_001276949.1	A0A140VKF7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ODAD2	ENST00000305242.10	TSL:1 MANE Select	c.383C>G	p.Ala128Gly	missense splice_region	Exon 4 of 20	ENSP00000306410.5	Q5T2S8-1
ODAD2	ENST00000673439.1		c.383C>G	p.Ala128Gly	missense splice_region	Exon 4 of 20	ENSP00000500782.1	Q5T2S8-1
ODAD2	ENST00000852623.1		c.383C>G	p.Ala128Gly	missense splice_region	Exon 4 of 20	ENSP00000522682.1

Frequencies

GnomAD3 genomes

AF:

0.0000490

AC:

AN:

142872

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000422

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:

0.00

Gnomad OTH

AF:

0.000511

GnomAD2 exomes

AF:

0.0000120

AC:

AN:

83490

AF XY:

0.0000222

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000104

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000228

AC:

AN:

1317736

Hom.:

Cov.:

AF XY:

0.00000309

AC XY:

AN XY:

647934

show subpopulations

African (AFR)

AF:

0.0000356

AC:

AN:

28104

American (AMR)

AF:

0.0000435

AC:

AN:

22976

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21898

East Asian (EAS)

AF:

0.00

AC:

AN:

34590

South Asian (SAS)

AF:

0.00

AC:

AN:

67578

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39174

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3700

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1045568

Other (OTH)

AF:

0.0000185

AC:

AN:

54148

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

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

AF:

0.0000490

AC:

AN:

142872

Hom.:

Cov.:

AF XY:

0.0000577

AC XY:

AN XY:

69266

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

38356

American (AMR)

AF:

0.000422

AC:

AN:

14218

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3356

East Asian (EAS)

AF:

0.00

AC:

AN:

4294

South Asian (SAS)

AF:

0.00

AC:

AN:

4354

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8956

Middle Eastern (MID)

AF:

0.00

AC:

AN:

304

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66194

Other (OTH)

AF:

0.000511

AC:

AN:

1956

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000523

Hom.:

Bravo

AF:

0.000102

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Primary ciliary dyskinesia (1)

Primary ciliary dyskinesia 23 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.087

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0065

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.70

M_CAP

Benign

0.033

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.67

MutationAssessor

Uncertain

2.3

PhyloP100

3.0

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.8

REVEL

Benign

0.089

Sift

Benign

0.065

Sift4G

Benign

0.10

Polyphen

0.96

Vest4

0.16

MutPred

0.31

Loss of helix (P = 0.0093)

MVP

0.74

MPC

0.19

ClinPred

0.48

GERP RS

5.0

Varity_R

0.11

gMVP

0.15

Mutation Taster

=278/22

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.24

dbscSNV1_RF

Benign

0.56

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over