19-48297073-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001364171.2(ODAD1):c.2027G>A(p.Ser676Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0127 in 1,613,208 control chromosomes in the GnomAD database, including 161 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0085 ( 6 hom., cov: 32)

Exomes 𝑓: 0.013 ( 155 hom. )

Consequence

ODAD1
NM_001364171.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 2.91

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:

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=0.008137494).

BP6

Variant 19-48297073-C-T is Benign according to our data. Variant chr19-48297073-C-T is described in ClinVar as [Benign]. Clinvar id is 241876.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00849 (1292/152210) while in subpopulation NFE AF= 0.0147 (997/67998). AF 95% confidence interval is 0.0139. There are 6 homozygotes in gnomad4. There are 592 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODAD1	NM_001364171.2 link	c.2027G>A	p.Ser676Asn	missense_variant	Exon 16 of 16	ENST00000674294.1	NP_001351100.1
ODAD1	NM_144577.4 link	c.1916G>A	p.Ser639Asn	missense_variant	Exon 14 of 14		NP_653178.3	Q96M63-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODAD1	ENST00000674294.1 link	c.2027G>A	p.Ser676Asn	missense_variant	Exon 16 of 16		NM_001364171.2	ENSP00000501363.1		A0A6I8PTZ2

Frequencies

GnomAD3 genomes

AF:

0.00849

AC:

1292

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00239

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00432

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00895

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0147

Gnomad OTH

AF:

0.00863

GnomAD3 exomes

AF:

0.00807

AC:

2025

AN:

250804

Hom.:

AF XY:

0.00826

AC XY:

1121

AN XY:

135674

show subpopulations

Gnomad AFR exome

AF:

0.00253

Gnomad AMR exome

AF:

0.00365

Gnomad ASJ exome

AF:

0.00338

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00114

Gnomad FIN exome

AF:

0.00649

Gnomad NFE exome

AF:

0.0140

Gnomad OTH exome

AF:

0.00898

GnomAD4 exome

AF:

0.0132

AC:

19274

AN:

1460998

Hom.:

155

Cov.:

AF XY:

0.0128

AC XY:

9279

AN XY:

726842

show subpopulations

Gnomad4 AFR exome

AF:

0.00254

Gnomad4 AMR exome

AF:

0.00367

Gnomad4 ASJ exome

AF:

0.00356

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00112

Gnomad4 FIN exome

AF:

0.00718

Gnomad4 NFE exome

AF:

0.0159

Gnomad4 OTH exome

AF:

0.0116

GnomAD4 genome

AF:

0.00849

AC:

1292

AN:

152210

Hom.:

Cov.:

AF XY:

0.00796

AC XY:

592

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.00238

Gnomad4 AMR

AF:

0.00432

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00895

Gnomad4 NFE

AF:

0.0147

Gnomad4 OTH

AF:

0.00854

Alfa

AF:

0.0102

Hom.:

Bravo

AF:

0.00804

TwinsUK

AF:

0.0186

AC:

ALSPAC

AF:

0.0158

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.0137

AC:

118

ExAC

AF:

0.00789

AC:

958

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0144

EpiControl

AF:

0.0148

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ODAD1: BP4, BS1, BS2 -

Feb 27, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 26, 2016

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia 20

Benign:1

Sep 16, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.016

Eigen

Benign

0.048

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.49

MetaRNN

Benign

0.0081

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.1

REVEL

Benign

0.14

Sift

Benign

0.070

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.28

MVP

0.40

MPC

0.53

ClinPred

0.023

GERP RS

3.9

Varity_R

0.095

gMVP

0.19

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