rs16981988

Positions:

chr19-48318500-G-A

Variant summary

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

The NM_001364171.2(ODAD1):c.247C>T(p.Arg83Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0254 in 1,551,582 control chromosomes in the GnomAD database, including 621 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 99 hom., cov: 31)

Exomes 𝑓: 0.025 ( 522 hom. )

Consequence

ODAD1
NM_001364171.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.350

Variant links:

Genes affected

ODAD1 (HGNC:26560): (outer dynein arm docking complex subunit 1) This gene encodes a coiled-coil domain-containing protein that is a component of the outer dynein arm docking complex in cilia cells. Mutations in this gene may cause primary ciliary dyskinesia 20. [provided by RefSeq, May 2013]

ODAD1 links:

ODAD1 (HGNC:):

ODAD1 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=0.0030530393).

BP6

Variant 19-48318500-G-A is Benign according to our data. Variant chr19-48318500-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 262487.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-48318500-G-A is described in Lovd as [Benign].

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODAD1	NM_001364171.2 linkuse as main transcript	c.247C>T	p.Arg83Trp	missense_variant	5/16	ENST00000674294.1	NP_001351100.1
ODAD1	NM_144577.4 linkuse as main transcript	c.136C>T	p.Arg46Trp	missense_variant	3/14		NP_653178.3	Q96M63-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODAD1	ENST00000674294.1 linkuse as main transcript	c.247C>T	p.Arg83Trp	missense_variant	5/16		NM_001364171.2	ENSP00000501363.1		A0A6I8PTZ2

Frequencies

GnomAD3 genomes

AF:

0.0314

AC:

4778

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0504

Gnomad AMI

AF:

0.0724

Gnomad AMR

AF:

0.0258

Gnomad ASJ

AF:

0.0473

Gnomad EAS

AF:

0.00289

Gnomad SAS

AF:

0.0315

Gnomad FIN

AF:

0.00858

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0253

Gnomad OTH

AF:

0.0306

GnomAD3 exomes

AF:

0.0258

AC:

4016

AN:

155636

Hom.:

AF XY:

0.0273

AC XY:

2254

AN XY:

82550

show subpopulations

Gnomad AFR exome

AF:

0.0512

Gnomad AMR exome

AF:

0.0190

Gnomad ASJ exome

AF:

0.0412

Gnomad EAS exome

AF:

0.00376

Gnomad SAS exome

AF:

0.0350

Gnomad FIN exome

AF:

0.00884

Gnomad NFE exome

AF:

0.0275

Gnomad OTH exome

AF:

0.0354

GnomAD4 exome

AF:

0.0248

AC:

34666

AN:

1399356

Hom.:

522

Cov.:

AF XY:

0.0254

AC XY:

17511

AN XY:

690188

show subpopulations

Gnomad4 AFR exome

AF:

0.0545

Gnomad4 AMR exome

AF:

0.0214

Gnomad4 ASJ exome

AF:

0.0399

Gnomad4 EAS exome

AF:

0.00151

Gnomad4 SAS exome

AF:

0.0349

Gnomad4 FIN exome

AF:

0.00983

Gnomad4 NFE exome

AF:

0.0237

Gnomad4 OTH exome

AF:

0.0295

GnomAD4 genome

AF:

0.0314

AC:

4786

AN:

152226

Hom.:

Cov.:

AF XY:

0.0311

AC XY:

2316

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0505

Gnomad4 AMR

AF:

0.0258

Gnomad4 ASJ

AF:

0.0473

Gnomad4 EAS

AF:

0.00289

Gnomad4 SAS

AF:

0.0315

Gnomad4 FIN

AF:

0.00858

Gnomad4 NFE

AF:

0.0253

Gnomad4 OTH

AF:

0.0303

Alfa

AF:

0.0278

Hom.:

126

Bravo

AF:

0.0336

TwinsUK

AF:

0.0232

AC:

ALSPAC

AF:

0.0210

AC:

ESP6500AA

AF:

0.0455

AC:

ESP6500EA

AF:

0.0286

AC:

ExAC

AF:

0.0289

AC:

745

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:2

Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Jul 08, 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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 10, 2022	See Variant Classification Assertion Criteria. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Primary ciliary dyskinesia 20

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Nov 29, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.038

Eigen

Benign

-0.070

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.54

LIST_S2

Uncertain

0.87

MetaRNN

Benign

0.0031

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

PrimateAI

Benign

0.48

PROVEAN

Pathogenic

-4.4

REVEL

Benign

0.15

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.0050

Polyphen

1.0

Vest4

0.18

MPC

0.80

ClinPred

0.023

GERP RS

-0.63

Varity_R

0.14

gMVP

0.49

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