rs143215183

Positions:

chr10-27981519-C-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_018076.5(ODAD2):c.883G>C(p.Val295Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00168 in 1,534,874 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 5 hom. )

Consequence

ODAD2
NM_018076.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:3

Conservation

PhyloP100: 1.36

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015191466).

BP6

Variant 10-27981519-C-G is Benign according to our data. Variant chr10-27981519-C-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 241266.We mark this variant Likely_benign, oryginal submissions are: {Benign=2, Uncertain_significance=2}. Variant chr10-27981519-C-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0013 (198/152172) while in subpopulation NFE AF= 0.00212 (144/67992). AF 95% confidence interval is 0.00184. There are 0 homozygotes in gnomad4. There are 94 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODAD2	NM_018076.5 linkuse as main transcript	c.883G>C	p.Val295Leu	missense_variant	7/20	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.883G>C	p.Val295Leu	missense_variant	7/20	1	NM_018076.5	ENSP00000306410	P1	Q5T2S8-1

Frequencies

GnomAD3 genomes

AF:

0.00130

AC:

198

AN:

152054

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.000378

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00212

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00154

AC:

282

AN:

182870

Hom.:

AF XY:

0.00159

AC XY:

161

AN XY:

101118

show subpopulations

Gnomad AFR exome

AF:

0.000248

Gnomad AMR exome

AF:

0.000747

Gnomad ASJ exome

AF:

0.00380

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000303

Gnomad FIN exome

AF:

0.000344

Gnomad NFE exome

AF:

0.00235

Gnomad OTH exome

AF:

0.00201

GnomAD4 exome

AF:

0.00173

AC:

2388

AN:

1382702

Hom.:

Cov.:

AF XY:

0.00172

AC XY:

1177

AN XY:

685788

show subpopulations

Gnomad4 AFR exome

AF:

0.000214

Gnomad4 AMR exome

AF:

0.00116

Gnomad4 ASJ exome

AF:

0.00401

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000308

Gnomad4 FIN exome

AF:

0.000493

Gnomad4 NFE exome

AF:

0.00194

Gnomad4 OTH exome

AF:

0.00158

GnomAD4 genome

AF:

0.00130

AC:

198

AN:

152172

Hom.:

Cov.:

AF XY:

0.00126

AC XY:

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.000378

Gnomad4 NFE

AF:

0.00212

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00213

Hom.:

Bravo

AF:

0.00132

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00268

AC:

ExAC

AF:

0.00164

AC:

199

Asia WGS

AF:

0.000578

AC:

AN:

3472

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia 23

Uncertain:1Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	Genetics and Molecular Pathology, SA Pathology	Oct 03, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2016

- -

Primary ciliary dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 16, 2017

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. -

ODAD2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 04, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0055

T;T

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.74

T;T

M_CAP

Benign

0.028

MetaRNN

Benign

0.015

T;T

MetaSVM

Benign

-0.74

MutationAssessor

Uncertain

2.9

M;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.12

Sift

Uncertain

0.011

D;D

Sift4G

Uncertain

0.019

D;D

Polyphen

0.93

P;.

Vest4

0.33

MVP

0.62

MPC

0.34

ClinPred

0.028

GERP RS

3.1

Varity_R

0.19

gMVP

0.78

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