rs7920186

Positions:

chr10-27968923-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PP3_ModerateBP6_Very_StrongBA1

The NM_018076.5(ODAD2):c.1238G>A(p.Arg413Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R413G) has been classified as Benign.

Frequency

Genomes: 𝑓 0.12 ( 742 hom., cov: 16)

Exomes 𝑓: 0.11 ( 2223 hom. )

Consequence

ODAD2
NM_018076.5 missense, splice_region

Scores

Splicing: ADA: 0.9999

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.560

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 -14 ACMG points.

PP3

Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

BP6

Variant 10-27968923-C-T is Benign according to our data. Variant chr10-27968923-C-T is described in ClinVar as [Benign]. Clinvar id is 541504.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.153 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.1238G>A	p.Arg413Gln	missense_variant, splice_region_variant	9/20	ENST00000305242.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODAD2	ENST00000305242.10 linkuse as main transcript	c.1238G>A	p.Arg413Gln	missense_variant, splice_region_variant	9/20	1	NM_018076.5	P1	Q5T2S8-1

Frequencies

GnomAD3 genomes

AF:

0.118

AC:

15233

AN:

129232

Hom.:

734

Cov.:

show subpopulations

Gnomad AFR

AF:

0.156

Gnomad AMI

AF:

0.0436

Gnomad AMR

AF:

0.0772

Gnomad ASJ

AF:

0.0897

Gnomad EAS

AF:

0.00375

Gnomad SAS

AF:

0.108

Gnomad FIN

AF:

0.105

Gnomad MID

AF:

0.0987

Gnomad NFE

AF:

0.121

Gnomad OTH

AF:

0.101

GnomAD3 exomes

AF:

0.0983

AC:

7234

AN:

73570

Hom.:

347

AF XY:

0.0982

AC XY:

3592

AN XY:

36582

show subpopulations

Gnomad AFR exome

AF:

0.156

Gnomad AMR exome

AF:

0.0674

Gnomad ASJ exome

AF:

0.0859

Gnomad EAS exome

AF:

0.00210

Gnomad SAS exome

AF:

0.113

Gnomad FIN exome

AF:

0.116

Gnomad NFE exome

AF:

0.119

Gnomad OTH exome

AF:

0.0967

GnomAD4 exome

AF:

0.109

AC:

51564

AN:

473844

Hom.:

2223

Cov.:

AF XY:

0.110

AC XY:

27792

AN XY:

251896

show subpopulations

Gnomad4 AFR exome

AF:

0.156

Gnomad4 AMR exome

AF:

0.0646

Gnomad4 ASJ exome

AF:

0.0912

Gnomad4 EAS exome

AF:

0.00298

Gnomad4 SAS exome

AF:

0.120

Gnomad4 FIN exome

AF:

0.112

Gnomad4 NFE exome

AF:

0.120

Gnomad4 OTH exome

AF:

0.111

GnomAD4 genome

AF:

0.118

AC:

15271

AN:

129338

Hom.:

742

Cov.:

AF XY:

0.116

AC XY:

7179

AN XY:

62150

show subpopulations

Gnomad4 AFR

AF:

0.156

Gnomad4 AMR

AF:

0.0769

Gnomad4 ASJ

AF:

0.0897

Gnomad4 EAS

AF:

0.00376

Gnomad4 SAS

AF:

0.109

Gnomad4 FIN

AF:

0.105

Gnomad4 NFE

AF:

0.121

Gnomad4 OTH

AF:

0.0998

Alfa

AF:

0.144

Hom.:

351

ExAC

AF:

0.0563

AC:

4320

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 06, 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

Dec 17, 2018

- -

Primary ciliary dyskinesia 23

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.0025

T;T

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.55

T;T

MetaRNN

Benign

0.0014

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;.

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.73

N;N

REVEL

Benign

0.033

Sift

Benign

0.14

T;T

Sift4G

Benign

0.17

T;T

Polyphen

0.51

P;.

Vest4

0.055

MPC

1.9

ClinPred

0.0030

GERP RS

2.0

Varity_R

0.10

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.95

SpliceAI score (max)

0.61

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.61

Position offset: 0

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