Genetic Variant ODAD3:c.366+7G>A (chr19-11430892-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_145045.5(ODAD3):c.366+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0225 in 1,613,976 control chromosomes in the GnomAD database, including 1,862 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.065 ( 807 hom., cov: 30)

Exomes 𝑓: 0.018 ( 1055 hom. )

Consequence

ODAD3
NM_145045.5 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.647

Publications

10 publications found

Variant links:

Genes affected

ODAD3 (HGNC:28303): (outer dynein arm docking complex subunit 3) This gene encodes a protein containing coiled-coil domains. The encoded protein functions in outer dynein arm assembly and is required for motile cilia function. Mutations in this gene result in primary ciliary dyskinesia. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2014]

ODAD3 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 30
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ODAD3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (Cadd=1.288).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ODAD3	NM_145045.5 link	c.366+7G>A	splice_region_variant, intron_variant	Intron 2 of 12	ENST00000356392.9	NP_659482.3	A5D8V7-1B3KPH7
ODAD3	NM_001302453.1 link	c.204+7G>A	splice_region_variant, intron_variant	Intron 2 of 12		NP_001289382.1	A5D8V7-2
ODAD3	NM_001302454.2 link	c.366+7G>A	splice_region_variant, intron_variant	Intron 2 of 10		NP_001289383.1	K7EN59
ODAD3	XM_017026241.2 link	c.366+7G>A	splice_region_variant, intron_variant	Intron 2 of 8		XP_016881730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODAD3	ENST00000356392.9 link	c.366+7G>A		splice_region_variant, intron_variant	Intron 2 of 12	1	NM_145045.5	ENSP00000348757.3		A5D8V7-1

Frequencies

GnomAD3 genomes

AF:

0.0651

AC:

9891

AN:

152028

Hom.:

804

Cov.:

show subpopulations

Gnomad AFR

AF:

0.181

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0332

Gnomad ASJ

AF:

0.0109

Gnomad EAS

AF:

0.125

Gnomad SAS

AF:

0.0313

Gnomad FIN

AF:

0.0257

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.00937

Gnomad OTH

AF:

0.0578

GnomAD4 exome

AF:

0.0181

AC:

26460

AN:

1461830

Hom.:

1055

Cov.:

AF XY:

0.0180

AC XY:

13079

AN XY:

727202

show subpopulations

African (AFR)

AF:

0.186

AC:

6229

AN:

33478

American (AMR)

AF:

0.0172

AC:

770

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0141

AC:

368

AN:

26134

East Asian (EAS)

AF:

0.101

AC:

3998

AN:

39696

South Asian (SAS)

AF:

0.0303

AC:

2614

AN:

86258

European-Finnish (FIN)

AF:

0.0254

AC:

1359

AN:

53412

Middle Eastern (MID)

AF:

0.0239

AC:

138

AN:

5768

European-Non Finnish (NFE)

AF:

0.00806

AC:

8961

AN:

1111966

Other (OTH)

AF:

0.0335

AC:

2023

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

1546

3092

4637

6183

7729

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

494

988

1482

1976

2470

<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:

0.0652

AC:

9918

AN:

152146

Hom.:

807

Cov.:

AF XY:

0.0639

AC XY:

4757

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.182

AC:

7533

AN:

41482

American (AMR)

AF:

0.0331

AC:

506

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.0109

AC:

AN:

3472

East Asian (EAS)

AF:

0.125

AC:

645

AN:

5168

South Asian (SAS)

AF:

0.0305

AC:

147

AN:

4816

European-Finnish (FIN)

AF:

0.0257

AC:

273

AN:

10608

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00937

AC:

637

AN:

68008

Other (OTH)

AF:

0.0581

AC:

123

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

418

836

1253

1671

2089

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

208

312

416

520

<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:

0.0255

Hom.:

411

Bravo

AF:

0.0705

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

CADD

Benign

1.3

(source)

PhyloP100

-0.65

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over