19-48297073-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S676R) has been classified as Uncertain significance.

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

Publications

12 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: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
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: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 6 AR,AD gene

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.2027G>A	p.Ser676Asn	missense	Exon 16 of 16	NP_001351100.1	A0A6I8PTZ2
	ODAD1	NM_144577.4		c.1916G>A	p.Ser639Asn	missense	Exon 14 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.2027G>A	p.Ser676Asn	missense	Exon 16 of 16	ENSP00000501363.1	A0A6I8PTZ2
ODAD1	ENST00000315396.7	TSL:1	c.1916G>A	p.Ser639Asn	missense	Exon 14 of 14	ENSP00000318429.7	Q96M63-1
ODAD1	ENST00000859784.1		c.2087G>A	p.Ser696Asn	missense	Exon 15 of 15	ENSP00000529843.1

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

GnomAD2 exomes

AF:

0.00807

AC:

2025

AN:

250804

AF XY:

0.00826

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 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

African (AFR)

AF:

0.00254

AC:

AN:

33472

American (AMR)

AF:

0.00367

AC:

164

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00356

AC:

AN:

26124

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39692

South Asian (SAS)

AF:

0.00112

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00718

AC:

381

AN:

53048

Middle Eastern (MID)

AF:

0.00469

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.0159

AC:

17723

AN:

1111574

Other (OTH)

AF:

0.0116

AC:

701

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

1179

2358

3536

4715

5894

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

670

1340

2010

2680

3350

<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:

0.00849

AC:

1292

AN:

152210

Hom.:

Cov.:

AF XY:

0.00796

AC XY:

592

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.00238

AC:

AN:

41530

American (AMR)

AF:

0.00432

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.00124

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00895

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0147

AC:

997

AN:

67998

Other (OTH)

AF:

0.00854

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

123

185

246

308

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00847

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Primary ciliary dyskinesia (2)

not specified (1)

Primary ciliary dyskinesia 20 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

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

PhyloP100

2.9

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

Mutation Taster

=95/5

polymorphism

(source)

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

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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