chr19-48297464-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.1636G>A(p.Ala546Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00177 in 1,600,422 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A546A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0090 ( 17 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 27 hom. )

Consequence

ODAD1
NM_001364171.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -2.04

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: 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=0.002634257).

BP6

Variant 19-48297464-C-T is Benign according to our data. Variant chr19-48297464-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 241873.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00895 (1363/152214) while in subpopulation AFR AF = 0.0312 (1295/41522). AF 95% confidence interval is 0.0298. There are 17 homozygotes in GnomAd4. There are 647 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 17 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.1636G>A	p.Ala546Thr	missense	Exon 16 of 16	NP_001351100.1	A0A6I8PTZ2
	ODAD1	NM_144577.4		c.1525G>A	p.Ala509Thr	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.1636G>A	p.Ala546Thr	missense	Exon 16 of 16	ENSP00000501363.1	A0A6I8PTZ2
ODAD1	ENST00000315396.7	TSL:1	c.1525G>A	p.Ala509Thr	missense	Exon 14 of 14	ENSP00000318429.7	Q96M63-1
ODAD1	ENST00000859784.1		c.1696G>A	p.Ala566Thr	missense	Exon 15 of 15	ENSP00000529843.1

Frequencies

GnomAD3 genomes

AF:

0.00894

AC:

1360

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0312

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00861

GnomAD2 exomes

AF:

0.00237

AC:

546

AN:

230062

AF XY:

0.00172

show subpopulations

Gnomad AFR exome

AF:

0.0322

Gnomad AMR exome

AF:

0.00128

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000105

Gnomad OTH exome

AF:

0.000894

GnomAD4 exome

AF:

0.00102

AC:

1476

AN:

1448208

Hom.:

Cov.:

AF XY:

0.000933

AC XY:

672

AN XY:

720558

show subpopulations

African (AFR)

AF:

0.0347

AC:

1155

AN:

33238

American (AMR)

AF:

0.00160

AC:

AN:

43652

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25600

East Asian (EAS)

AF:

0.00

AC:

AN:

39630

South Asian (SAS)

AF:

0.000782

AC:

AN:

85632

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46044

Middle Eastern (MID)

AF:

0.00250

AC:

AN:

5594

European-Non Finnish (NFE)

AF:

0.0000451

AC:

AN:

1108934

Other (OTH)

AF:

0.00200

AC:

120

AN:

59884

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

155

232

310

387

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

144

180

<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:

0.00895

AC:

1363

AN:

152214

Hom.:

Cov.:

AF XY:

0.00869

AC XY:

647

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0312

AC:

1295

AN:

41522

American (AMR)

AF:

0.00248

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00104

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

67994

Other (OTH)

AF:

0.00852

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

126

189

252

315

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:

0.00358

Hom.:

Bravo

AF:

0.0101

ESP6500AA

AF:

0.0323

AC:

142

ESP6500EA

AF:

0.000350

AC:

ExAC

AF:

0.00277

AC:

332

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

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

0.077

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.0060

(source)

DANN

Benign

0.45

DEOGEN2

Benign

0.0024

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0087

LIST_S2

Benign

0.29

MetaRNN

Benign

0.0026

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.34

PhyloP100

-2.0

PrimateAI

Benign

0.25

PROVEAN

Benign

0.060

REVEL

Benign

0.017

Sift

Benign

0.64

Sift4G

Benign

0.21

Polyphen

0.41

Vest4

0.10

MVP

0.16

MPC

0.19

ClinPred

0.0018

GERP RS

-4.3

Varity_R

0.025

gMVP

0.075

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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