10-27812561-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1

The NM_018076.5(ODAD2):c.3086C>T(p.Ser1029Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000221 in 1,613,140 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 2 hom. )

Consequence

ODAD2
NM_018076.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 5.85

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.018236786).

BP6

Variant 10-27812561-G-A is Benign according to our data. Variant chr10-27812561-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 417175.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=2, Benign=1}.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00107 (163/152262) while in subpopulation AFR AF= 0.00371 (154/41538). AF 95% confidence interval is 0.00323. There are 0 homozygotes in gnomad4. There are 70 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODAD2	NM_018076.5 linkuse as main transcript	c.3086C>T	p.Ser1029Phe	missense_variant	20/20	ENST00000305242.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODAD2	ENST00000305242.10 linkuse as main transcript	c.3086C>T	p.Ser1029Phe	missense_variant	20/20	1	NM_018076.5	P1	Q5T2S8-1

Frequencies

GnomAD3 genomes

AF:

0.00105

AC:

160

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00365

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

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:

0.000959

GnomAD3 exomes

AF:

0.000272

AC:

AN:

250250

Hom.:

AF XY:

0.000207

AC XY:

AN XY:

135278

show subpopulations

Gnomad AFR exome

AF:

0.00333

Gnomad AMR exome

AF:

0.000234

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000132

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000132

AC:

193

AN:

1460878

Hom.:

Cov.:

AF XY:

0.000100

AC XY:

AN XY:

726716

show subpopulations

Gnomad4 AFR exome

AF:

0.00458

Gnomad4 AMR exome

AF:

0.000203

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000698

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000381

GnomAD4 genome

AF:

0.00107

AC:

163

AN:

152262

Hom.:

Cov.:

AF XY:

0.000940

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00371

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000949

Alfa

AF:

0.000181

Hom.:

Bravo

AF:

0.00120

ESP6500AA

AF:

0.00295

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000346

AC:

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	Baylor Genetics	Jul 01, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Dec 28, 2023	- -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Jan 31, 2022

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Primary ciliary dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 14, 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. -

ODAD2-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 18, 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

0.29

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Uncertain

0.0

Cadd

Pathogenic

Dann

Benign

0.95

DEOGEN2

Benign

0.019

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.94

M_CAP

Pathogenic

0.31

MetaRNN

Benign

0.018

MetaSVM

Pathogenic

1.0

MutationAssessor

Uncertain

2.0

MutationTaster

Benign

1.0

D;D;N

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-3.2

REVEL

Pathogenic

0.65

Sift

Benign

0.050

Sift4G

Uncertain

0.060

Polyphen

0.92

Vest4

0.25

MVP

0.93

MPC

0.22

ClinPred

0.067

GERP RS

5.7

Varity_R

0.33

gMVP

0.37

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