rs200360777

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1

The NM_001364171.2(ODAD1):c.522G>A(p.Ala174=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000928 in 1,551,164 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00078 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00094 ( 1 hom. )

Consequence

ODAD1
NM_001364171.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.15

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.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 19-48311628-C-T is Benign according to our data. Variant chr19-48311628-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 454971.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.15 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000775 (118/152210) while in subpopulation NFE AF= 0.00132 (90/68008). AF 95% confidence interval is 0.0011. There are 0 homozygotes in gnomad4. There are 53 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODAD1	NM_001364171.2 linkuse as main transcript	c.522G>A	p.Ala174=	synonymous_variant	7/16	ENST00000674294.1
ODAD1	NM_144577.4 linkuse as main transcript	c.411G>A	p.Ala137=	synonymous_variant	5/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODAD1	ENST00000674294.1 linkuse as main transcript	c.522G>A	p.Ala174=	synonymous_variant	7/16		NM_001364171.2	P2

Frequencies

GnomAD3 genomes

AF:

0.000776

AC:

118

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00132

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000941

AC:

147

AN:

156202

Hom.:

AF XY:

0.00115

AC XY:

AN XY:

82794

show subpopulations

Gnomad AFR exome

AF:

0.000379

Gnomad AMR exome

AF:

0.000405

Gnomad ASJ exome

AF:

0.00471

Gnomad EAS exome

AF:

0.000275

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000603

Gnomad NFE exome

AF:

0.00144

Gnomad OTH exome

AF:

0.000684

GnomAD4 exome

AF:

0.000945

AC:

1322

AN:

1398954

Hom.:

Cov.:

AF XY:

0.000951

AC XY:

656

AN XY:

690024

show subpopulations

Gnomad4 AFR exome

AF:

0.000158

Gnomad4 AMR exome

AF:

0.000392

Gnomad4 ASJ exome

AF:

0.00453

Gnomad4 EAS exome

AF:

0.000420

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000142

Gnomad4 NFE exome

AF:

0.00103

Gnomad4 OTH exome

AF:

0.000914

GnomAD4 genome

AF:

0.000775

AC:

118

AN:

152210

Hom.:

Cov.:

AF XY:

0.000712

AC XY:

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00132

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00116

Hom.:

Bravo

AF:

0.000774

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 18, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Feb 06, 2017	This alteration is classified as likely 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 provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2022

ODAD1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

Cadd

Benign

0.068

Dann

Benign

0.74

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