19-48303782-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP3BP6_Very_StrongBS1BS2

The NM_001364171.2(ODAD1):c.856G>A(p.Gly286Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00114 in 1,606,834 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0040 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00084 ( 6 hom. )

Consequence

ODAD1
NM_001364171.2 missense, splice_region

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.916

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 -15 ACMG points.

PP3

Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

BP6

Variant 19-48303782-C-T is Benign according to our data. Variant chr19-48303782-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 262505.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-48303782-C-T is described in Lovd as [Benign]. Variant chr19-48303782-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00395 (602/152336) while in subpopulation AFR AF= 0.011 (459/41582). AF 95% confidence interval is 0.0102. There are 3 homozygotes in gnomad4. There are 278 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODAD1	NM_001364171.2 link	c.856G>A	p.Gly286Arg	missense_variant, splice_region_variant	Exon 10 of 16	ENST00000674294.1	NP_001351100.1
ODAD1	NM_144577.4 link	c.745G>A	p.Gly249Arg	missense_variant, splice_region_variant	Exon 8 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.856G>A	p.Gly286Arg	missense_variant, splice_region_variant	Exon 10 of 16		NM_001364171.2	ENSP00000501363.1		A0A6I8PTZ2

Frequencies

GnomAD3 genomes

AF:

0.00394

AC:

600

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0110

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00412

Gnomad ASJ

AF:

0.00835

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000500

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00170

AC:

413

AN:

243150

Hom.:

AF XY:

0.00143

AC XY:

188

AN XY:

131182

show subpopulations

Gnomad AFR exome

AF:

0.0115

Gnomad AMR exome

AF:

0.00195

Gnomad ASJ exome

AF:

0.00704

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0000686

Gnomad FIN exome

AF:

0.000142

Gnomad NFE exome

AF:

0.000648

Gnomad OTH exome

AF:

0.00325

GnomAD4 exome

AF:

0.000840

AC:

1222

AN:

1454498

Hom.:

Cov.:

AF XY:

0.000809

AC XY:

585

AN XY:

723192

show subpopulations

Gnomad4 AFR exome

AF:

0.0103

Gnomad4 AMR exome

AF:

0.00232

Gnomad4 ASJ exome

AF:

0.00767

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000823

Gnomad4 FIN exome

AF:

0.0000942

Gnomad4 NFE exome

AF:

0.000382

Gnomad4 OTH exome

AF:

0.00221

GnomAD4 genome

AF:

0.00395

AC:

602

AN:

152336

Hom.:

Cov.:

AF XY:

0.00373

AC XY:

278

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0110

Gnomad4 AMR

AF:

0.00412

Gnomad4 ASJ

AF:

0.00835

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000500

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00285

Hom.:

Bravo

AF:

0.00496

ESP6500AA

AF:

0.0109

AC:

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.00170

AC:

206

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign/Likely 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: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Primary ciliary dyskinesia

Benign:2

Apr 04, 2017

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. -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

0.061

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.14

DANN

Benign

0.83

DEOGEN2

Benign

0.00014

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0069

LIST_S2

Benign

0.20

MetaRNN

Benign

0.0038

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.3

PrimateAI

Benign

0.24

PROVEAN

Benign

1.3

REVEL

Benign

0.013

Sift

Benign

0.59

Sift4G

Benign

0.41

Polyphen

0.0

Vest4

0.030

MutPred

0.23

Gain of MoRF binding (P = 0.0381);

MVP

0.21

MPC

0.24

ClinPred

0.00069

GERP RS

-2.6

Varity_R

0.049

gMVP

0.083

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.75

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.75

Position offset: -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