rs4405206

Positions:

Variant summary

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

The NM_018076.5(ODAD2):c.1028T>C(p.Ile343Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0687 in 1,613,718 control chromosomes in the GnomAD database, including 5,051 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. I343I) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.078 ( 622 hom., cov: 32)

Exomes 𝑓: 0.068 ( 4429 hom. )

Consequence

ODAD2
NM_018076.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.436

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=0.005333036).

BP6

Variant 10-27971222-A-G is Benign according to our data. Variant chr10-27971222-A-G is described in ClinVar as [Benign]. Clinvar id is 402396.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODAD2	NM_018076.5 linkuse as main transcript	c.1028T>C	p.Ile343Thr	missense_variant	8/20	ENST00000305242.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODAD2	ENST00000305242.10 linkuse as main transcript	c.1028T>C	p.Ile343Thr	missense_variant	8/20	1	NM_018076.5	P1	Q5T2S8-1

Frequencies

GnomAD3 genomes

AF:

0.0775

AC:

11787

AN:

152008

Hom.:

620

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0837

Gnomad AMI

AF:

0.129

Gnomad AMR

AF:

0.0879

Gnomad ASJ

AF:

0.120

Gnomad EAS

AF:

0.266

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.0277

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0578

Gnomad OTH

AF:

0.0969

GnomAD3 exomes

AF:

0.0856

AC:

21502

AN:

251140

Hom.:

1490

AF XY:

0.0863

AC XY:

11716

AN XY:

135724

show subpopulations

Gnomad AFR exome

AF:

0.0834

Gnomad AMR exome

AF:

0.0609

Gnomad ASJ exome

AF:

0.113

Gnomad EAS exome

AF:

0.288

Gnomad SAS exome

AF:

0.123

Gnomad FIN exome

AF:

0.0255

Gnomad NFE exome

AF:

0.0602

Gnomad OTH exome

AF:

0.0782

GnomAD4 exome

AF:

0.0678

AC:

99052

AN:

1461592

Hom.:

4429

Cov.:

AF XY:

0.0694

AC XY:

50447

AN XY:

727078

show subpopulations

Gnomad4 AFR exome

AF:

0.0844

Gnomad4 AMR exome

AF:

0.0637

Gnomad4 ASJ exome

AF:

0.115

Gnomad4 EAS exome

AF:

0.252

Gnomad4 SAS exome

AF:

0.118

Gnomad4 FIN exome

AF:

0.0259

Gnomad4 NFE exome

AF:

0.0571

Gnomad4 OTH exome

AF:

0.0792

GnomAD4 genome

AF:

0.0776

AC:

11805

AN:

152126

Hom.:

622

Cov.:

AF XY:

0.0801

AC XY:

5959

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0838

Gnomad4 AMR

AF:

0.0882

Gnomad4 ASJ

AF:

0.120

Gnomad4 EAS

AF:

0.267

Gnomad4 SAS

AF:

0.127

Gnomad4 FIN

AF:

0.0277

Gnomad4 NFE

AF:

0.0578

Gnomad4 OTH

AF:

0.0988

Alfa

AF:

0.0594

Hom.:

170

Bravo

AF:

0.0824

TwinsUK

AF:

0.0591

AC:

219

ALSPAC

AF:

0.0625

AC:

241

ESP6500AA

AF:

0.0881

AC:

388

ESP6500EA

AF:

0.0649

AC:

558

ExAC

AF:

0.0862

AC:

10460

Asia WGS

AF:

0.166

AC:

576

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia 23

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 30, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Primary ciliary dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 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. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.076

DANN

Benign

0.48

DEOGEN2

Benign

0.00086

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0073

LIST_S2

Benign

0.30

T;T

MetaRNN

Benign

0.0053

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;.

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.35

PROVEAN

Benign

0.22

N;N

REVEL

Benign

0.013

Sift

Benign

0.40

T;T

Sift4G

Benign

0.40

T;T

Polyphen

0.017

B;.

Vest4

0.0050

MPC

0.23

ClinPred

0.0041

GERP RS

-8.1

Varity_R

0.052

gMVP

0.18

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