rs3737184

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000305242.10(ODAD2):c.3121G>T(p.Ala1041Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0201 in 1,612,734 control chromosomes in the GnomAD database, including 2,642 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1041T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.022 ( 226 hom., cov: 32)

Exomes 𝑓: 0.020 ( 2416 hom. )

Consequence

ODAD2
ENST00000305242.10 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.41

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017198324).

BP6

Variant 10-27812526-C-A is Benign according to our data. Variant chr10-27812526-C-A is described in ClinVar as [Benign]. Clinvar id is 417179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODAD2	NM_018076.5 linkuse as main transcript	c.3121G>T	p.Ala1041Ser	missense_variant	20/20	ENST00000305242.10	NP_060546.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODAD2	ENST00000305242.10 linkuse as main transcript	c.3121G>T	p.Ala1041Ser	missense_variant	20/20	1	NM_018076.5	ENSP00000306410	P1	Q5T2S8-1

Frequencies

GnomAD3 genomes

AF:

0.0219

AC:

3331

AN:

152062

Hom.:

222

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00319

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0609

Gnomad ASJ

AF:

0.00289

Gnomad EAS

AF:

0.215

Gnomad SAS

AF:

0.116

Gnomad FIN

AF:

0.0383

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00206

Gnomad OTH

AF:

0.0192

GnomAD3 exomes

AF:

0.0505

AC:

12610

AN:

249854

Hom.:

990

AF XY:

0.0495

AC XY:

6686

AN XY:

135064

show subpopulations

Gnomad AFR exome

AF:

0.00278

Gnomad AMR exome

AF:

0.111

Gnomad ASJ exome

AF:

0.00239

Gnomad EAS exome

AF:

0.221

Gnomad SAS exome

AF:

0.112

Gnomad FIN exome

AF:

0.0374

Gnomad NFE exome

AF:

0.00252

Gnomad OTH exome

AF:

0.0374

GnomAD4 exome

AF:

0.0199

AC:

29010

AN:

1460554

Hom.:

2416

Cov.:

AF XY:

0.0220

AC XY:

16017

AN XY:

726570

show subpopulations

Gnomad4 AFR exome

AF:

0.00203

Gnomad4 AMR exome

AF:

0.104

Gnomad4 ASJ exome

AF:

0.00264

Gnomad4 EAS exome

AF:

0.255

Gnomad4 SAS exome

AF:

0.109

Gnomad4 FIN exome

AF:

0.0356

Gnomad4 NFE exome

AF:

0.00114

Gnomad4 OTH exome

AF:

0.0272

GnomAD4 genome

AF:

0.0219

AC:

3339

AN:

152180

Hom.:

226

Cov.:

AF XY:

0.0262

AC XY:

1949

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.00318

Gnomad4 AMR

AF:

0.0616

Gnomad4 ASJ

AF:

0.00289

Gnomad4 EAS

AF:

0.215

Gnomad4 SAS

AF:

0.116

Gnomad4 FIN

AF:

0.0383

Gnomad4 NFE

AF:

0.00206

Gnomad4 OTH

AF:

0.0185

Alfa

AF:

0.0117

Hom.:

262

Bravo

AF:

0.0232

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.00318

AC:

ESP6500EA

AF:

0.00186

AC:

ExAC

AF:

0.0478

AC:

5798

Asia WGS

AF:

0.152

AC:

528

AN:

3478

EpiCase

AF:

0.00174

EpiControl

AF:

0.00148

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Primary ciliary dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 01, 2016

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Primary ciliary dyskinesia 23

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.0035

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.84

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-1.5

REVEL

Uncertain

0.30

Sift

Benign

0.091

Sift4G

Benign

0.26

Polyphen

0.21

Vest4

0.15

MPC

0.25

ClinPred

0.014

GERP RS

4.9

Varity_R

0.14

gMVP

0.27

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over