rs35461177

Positions:

chr19-48297657-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.1514C>T(p.Pro505Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 1,509,240 control chromosomes in the GnomAD database, including 55,586 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4244 hom., cov: 31)

Exomes 𝑓: 0.27 ( 51342 hom. )

Consequence

ODAD1
NM_001364171.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.798

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=0.0045309663).

BP6

Variant 19-48297657-G-A is Benign according to our data. Variant chr19-48297657-G-A is described in ClinVar as [Benign]. Clinvar id is 262489.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.283 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.1514C>T	p.Pro505Leu	missense_variant	15/16	ENST00000674294.1	NP_001351100.1
ODAD1	NM_144577.4 linkuse as main transcript	c.1403C>T	p.Pro468Leu	missense_variant	13/14		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.1514C>T	p.Pro505Leu	missense_variant	15/16		NM_001364171.2	ENSP00000501363.1		A0A6I8PTZ2

Frequencies

GnomAD3 genomes

AF:

0.225

AC:

34235

AN:

151846

Hom.:

4240

Cov.:

show subpopulations

Gnomad AFR

AF:

0.125

Gnomad AMI

AF:

0.280

Gnomad AMR

AF:

0.239

Gnomad ASJ

AF:

0.203

Gnomad EAS

AF:

0.139

Gnomad SAS

AF:

0.164

Gnomad FIN

AF:

0.274

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.287

Gnomad OTH

AF:

0.241

GnomAD3 exomes

AF:

0.235

AC:

38118

AN:

162302

Hom.:

4690

AF XY:

0.235

AC XY:

20081

AN XY:

85526

show subpopulations

Gnomad AFR exome

AF:

0.122

Gnomad AMR exome

AF:

0.216

Gnomad ASJ exome

AF:

0.221

Gnomad EAS exome

AF:

0.135

Gnomad SAS exome

AF:

0.158

Gnomad FIN exome

AF:

0.276

Gnomad NFE exome

AF:

0.284

Gnomad OTH exome

AF:

0.253

GnomAD4 exome

AF:

0.270

AC:

366654

AN:

1357276

Hom.:

51342

Cov.:

AF XY:

0.267

AC XY:

177537

AN XY:

664430

show subpopulations

Gnomad4 AFR exome

AF:

0.114

Gnomad4 AMR exome

AF:

0.216

Gnomad4 ASJ exome

AF:

0.216

Gnomad4 EAS exome

AF:

0.136

Gnomad4 SAS exome

AF:

0.164

Gnomad4 FIN exome

AF:

0.278

Gnomad4 NFE exome

AF:

0.290

Gnomad4 OTH exome

AF:

0.252

GnomAD4 genome

AF:

0.225

AC:

34249

AN:

151964

Hom.:

4244

Cov.:

AF XY:

0.222

AC XY:

16513

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.125

Gnomad4 AMR

AF:

0.239

Gnomad4 ASJ

AF:

0.203

Gnomad4 EAS

AF:

0.138

Gnomad4 SAS

AF:

0.166

Gnomad4 FIN

AF:

0.274

Gnomad4 NFE

AF:

0.287

Gnomad4 OTH

AF:

0.238

Alfa

AF:

0.257

Hom.:

2411

Bravo

AF:

0.219

TwinsUK

AF:

0.305

AC:

1130

ALSPAC

AF:

0.283

AC:

1089

ESP6500AA

AF:

0.129

AC:

567

ESP6500EA

AF:

0.285

AC:

2455

ExAC

AF:

0.223

AC:

26611

Asia WGS

AF:

0.139

AC:

485

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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 -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Primary ciliary dyskinesia

Benign:2

Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Jul 07, 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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0028

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.63

MetaRNN

Benign

0.0045

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.0

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.046

Sift

Benign

0.051

Sift4G

Uncertain

0.0080

Polyphen

0.61

Vest4

0.093

MPC

0.77

ClinPred

0.050

GERP RS

1.8

Varity_R

0.054

gMVP

0.067

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