rs111982349

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_018076.5(ODAD2):c.1272C>T(p.Ser424=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00358 in 1,603,544 control chromosomes in the GnomAD database, including 145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 88 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 57 hom. )

Consequence

ODAD2
NM_018076.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.941

Variant links:

Genes affected

ODAD2 (HGNC:25583): (outer dynein arm docking complex subunit 2) The protein encoded by this gene contains ten Armadillo repeat motifs (ARMs) and one HEAT repeat, and is thought to be involved in ciliary and flagellar movement. This protein has been shown to localize to the ciliary axonemes and at the ciliary base of respiratory cells. Studies indicate that mutations in this gene cause partial outer dynein arm (ODA) defects in respiratory cilia. The cilia of cells with mutations in this gene displayed either reduced ciliary beat frequency and amplitude, or, complete immotility. Some individuals with primary ciliary dyskensia (PCD) have been shown to have mutations in this gene. PCD is characterized by chronic airway disease and left/right body asymmetry defects. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]

ODAD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 10-27961682-G-A is Benign according to our data. Variant chr10-27961682-G-A is described in ClinVar as [Benign]. Clinvar id is 241256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.941 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODAD2	NM_018076.5 linkuse as main transcript	c.1272C>T	p.Ser424=	synonymous_variant	10/20	ENST00000305242.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODAD2	ENST00000305242.10 linkuse as main transcript	c.1272C>T	p.Ser424=	synonymous_variant	10/20	1	NM_018076.5	P1	Q5T2S8-1

Frequencies

GnomAD3 genomes

AF:

0.0189

AC:

2869

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0664

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00543

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00815

GnomAD3 exomes

AF:

0.00487

AC:

1208

AN:

248288

Hom.:

AF XY:

0.00350

AC XY:

469

AN XY:

134134

show subpopulations

Gnomad AFR exome

AF:

0.0644

Gnomad AMR exome

AF:

0.00270

Gnomad ASJ exome

AF:

0.00132

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000335

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000409

Gnomad OTH exome

AF:

0.00283

GnomAD4 exome

AF:

0.00197

AC:

2856

AN:

1451358

Hom.:

Cov.:

AF XY:

0.00180

AC XY:

1301

AN XY:

722240

show subpopulations

Gnomad4 AFR exome

AF:

0.0660

Gnomad4 AMR exome

AF:

0.00316

Gnomad4 ASJ exome

AF:

0.00125

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000177

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000174

Gnomad4 OTH exome

AF:

0.00457

GnomAD4 genome

AF:

0.0189

AC:

2881

AN:

152186

Hom.:

Cov.:

AF XY:

0.0178

AC XY:

1325

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0665

Gnomad4 AMR

AF:

0.00536

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00806

Alfa

AF:

0.00894

Hom.:

Bravo

AF:

0.0219

Asia WGS

AF:

0.00636

AC:

AN:

3476

EpiCase

AF:

0.000491

EpiControl

AF:

0.000653

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 19, 2021	- -

Primary ciliary dyskinesia 23

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 21, 2022	- -

Primary ciliary dyskinesia

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

2.6

DANN

Benign

0.40

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