chr19-48302720-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.1214G>A(p.Arg405Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 1,612,084 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0066 ( 11 hom., cov: 32)

Exomes 𝑓: 0.00075 ( 9 hom. )

Consequence

ODAD1
NM_001364171.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.482

Publications

3 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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034305155).

BP6

Variant 19-48302720-C-T is Benign according to our data. Variant chr19-48302720-C-T is described in ClinVar as Benign. ClinVar VariationId is 241868.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 = 0.00665 (1013/152332) while in subpopulation AFR AF = 0.023 (954/41566). AF 95% confidence interval is 0.0217. There are 11 homozygotes in GnomAd4. There are 478 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 11 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.1214G>A	p.Arg405Gln	missense	Exon 12 of 16	NP_001351100.1
	ODAD1	NM_144577.4		c.1103G>A	p.Arg368Gln	missense	Exon 10 of 14	NP_653178.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ODAD1	ENST00000674294.1	MANE Select	c.1214G>A	p.Arg405Gln	missense	Exon 12 of 16	ENSP00000501363.1
ODAD1	ENST00000315396.7	TSL:1	c.1103G>A	p.Arg368Gln	missense	Exon 10 of 14	ENSP00000318429.7
ODAD1	ENST00000859784.1		c.1274G>A	p.Arg425Gln	missense	Exon 11 of 15	ENSP00000529843.1

Frequencies

GnomAD3 genomes

AF:

0.00664

AC:

1011

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0230

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.00191

AC:

471

AN:

247064

AF XY:

0.00145

show subpopulations

Gnomad AFR exome

AF:

0.0238

Gnomad AMR exome

AF:

0.00171

Gnomad ASJ exome

AF:

0.000101

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000189

Gnomad OTH exome

AF:

0.00149

GnomAD4 exome

AF:

0.000749

AC:

1094

AN:

1459752

Hom.:

Cov.:

AF XY:

0.000635

AC XY:

461

AN XY:

726314

show subpopulations

African (AFR)

AF:

0.0226

AC:

755

AN:

33478

American (AMR)

AF:

0.00168

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26126

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51422

Middle Eastern (MID)

AF:

0.00156

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.000134

AC:

149

AN:

1111938

Other (OTH)

AF:

0.00162

AC:

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

116

173

231

289

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<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:

0.00665

AC:

1013

AN:

152332

Hom.:

Cov.:

AF XY:

0.00642

AC XY:

478

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.0230

AC:

954

AN:

41566

American (AMR)

AF:

0.00262

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

68034

Other (OTH)

AF:

0.00473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

104

156

208

260

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00610

Hom.:

Bravo

AF:

0.00739

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0188

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00214

AC:

260

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Primary ciliary dyskinesia (2)

Primary ciliary dyskinesia 20 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.73

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0011

Eigen

Benign

-0.97

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.64

MetaRNN

Benign

0.0034

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.4

PhyloP100

0.48

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.1

REVEL

Benign

0.031

Sift

Benign

0.12

Sift4G

Benign

0.15

Polyphen

0.79

Vest4

0.38

MVP

0.17

MPC

0.33

ClinPred

0.0097

GERP RS

-1.0

Varity_R

0.034

gMVP

0.18

Mutation Taster

=99/1

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