rs367799104

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_001364171.2(ODAD1):c.626G>A(p.Ser209Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000922 in 1,551,460 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S209R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000089 ( 0 hom. )

Consequence

ODAD1
NM_001364171.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:4B:1

Conservation

PhyloP100: 0.0850

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 20
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ODAD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04092297).

BP6

Variant 19-48306295-C-T is Benign according to our data. Variant chr19-48306295-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 262501.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364171.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAD1	NM_001364171.2	MANE Select	c.626G>A	p.Ser209Asn	missense	Exon 8 of 16	NP_001351100.1	A0A6I8PTZ2
	ODAD1	NM_144577.4		c.515G>A	p.Ser172Asn	missense	Exon 6 of 14	NP_653178.3	Q96M63-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ODAD1	ENST00000674294.1	MANE Select	c.626G>A	p.Ser209Asn	missense	Exon 8 of 16	ENSP00000501363.1	A0A6I8PTZ2
ODAD1	ENST00000315396.7	TSL:1	c.515G>A	p.Ser172Asn	missense	Exon 6 of 14	ENSP00000318429.7	Q96M63-1
ODAD1	ENST00000859784.1		c.626G>A	p.Ser209Asn	missense	Exon 7 of 15	ENSP00000529843.1

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000110

AC:

AN:

154894

AF XY:

0.000183

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000405

Gnomad ASJ exome

AF:

0.000235

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000133

Gnomad OTH exome

AF:

0.000229

GnomAD4 exome

AF:

0.0000893

AC:

125

AN:

1399278

Hom.:

Cov.:

AF XY:

0.0000971

AC XY:

AN XY:

690142

show subpopulations

African (AFR)

AF:

0.0000633

AC:

AN:

31596

American (AMR)

AF:

0.0000280

AC:

AN:

35700

Ashkenazi Jewish (ASJ)

AF:

0.000159

AC:

AN:

25168

East Asian (EAS)

AF:

0.00

AC:

AN:

35724

South Asian (SAS)

AF:

0.000240

AC:

AN:

79234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49286

Middle Eastern (MID)

AF:

0.000702

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.0000797

AC:

AN:

1078858

Other (OTH)

AF:

0.000155

AC:

AN:

58014

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000118

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41528

American (AMR)

AF:

0.0000655

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000415

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

67994

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000134

Hom.:

Bravo

AF:

0.000117

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000314

AC:

ExAC

AF:

0.000140

AC:

ClinVar

ClinVar submissions as Germline

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Primary ciliary dyskinesia (2)

Fraser syndrome 3 (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.78

CADD

Benign

1.9

(source)

DANN

Benign

0.58

DEOGEN2

Benign

0.0015

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.35

M_CAP

Benign

0.0080

MetaRNN

Benign

0.041

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.45

PhyloP100

0.085

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.38

REVEL

Benign

0.017

Sift

Benign

0.39

Sift4G

Benign

0.54

Polyphen

0.021

Vest4

0.067

MVP

0.13

MPC

0.19

ClinPred

0.016

GERP RS

-1.1

Varity_R

0.056

gMVP

0.092

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over