19-48304144-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001364171.2(ODAD1):c.666-4G>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 0.265 in 1,596,794 control chromosomes in the GnomAD database, including 58,330 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4245 hom., cov: 32)

Exomes 𝑓: 0.27 ( 54085 hom. )

Consequence

ODAD1
NM_001364171.2 splice_region, intron

Scores

Splicing: ADA: 0.00008480

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.27

Publications

7 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 (BayesDel_noAF=-0.66).

BP6

Variant 19-48304144-C-T is Benign according to our data. Variant chr19-48304144-C-T is described in ClinVar as [Benign]. Clinvar id is 262503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODAD1	NM_001364171.2 link	c.666-4G>A		splice_region_variant, intron_variant	Intron 8 of 15	ENST00000674294.1	NP_001351100.1
ODAD1	NM_144577.4 link	c.555-4G>A		splice_region_variant, intron_variant	Intron 6 of 13		NP_653178.3	Q96M63-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ODAD1	ENST00000674294.1 link	c.666-4G>A	splice_region_variant, intron_variant	Intron 8 of 15		NM_001364171.2	ENSP00000501363.1	A0A6I8PTZ2
ODAD1	ENST00000315396.7 link	c.555-4G>A	splice_region_variant, intron_variant	Intron 6 of 13	1		ENSP00000318429.7	Q96M63-1
ODAD1	ENST00000474199.6 link	c.666-4G>A	splice_region_variant, intron_variant	Intron 8 of 14	2		ENSP00000501357.1	A0A6I8PTY8
ODAD1	ENST00000674207.1 link	n.*374-4G>A	splice_region_variant, intron_variant	Intron 6 of 12			ENSP00000501374.1	A0A6I8PL46

Frequencies

GnomAD3 genomes

AF:

0.226

AC:

34289

AN:

151882

Hom.:

4241

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.280

Gnomad AMR

AF:

0.240

Gnomad ASJ

AF:

0.203

Gnomad EAS

AF:

0.142

Gnomad SAS

AF:

0.164

Gnomad FIN

AF:

0.276

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.286

Gnomad OTH

AF:

0.238

GnomAD2 exomes

AF:

0.236

AC:

56894

AN:

241302

AF XY:

0.235

show subpopulations

Gnomad AFR exome

AF:

0.126

Gnomad AMR exome

AF:

0.212

Gnomad ASJ exome

AF:

0.215

Gnomad EAS exome

AF:

0.140

Gnomad FIN exome

AF:

0.282

Gnomad NFE exome

AF:

0.286

Gnomad OTH exome

AF:

0.252

GnomAD4 exome

AF:

0.269

AC:

388508

AN:

1444796

Hom.:

54085

Cov.:

AF XY:

0.266

AC XY:

190656

AN XY:

717010

show subpopulations

African (AFR)

AF:

0.117

AC:

3887

AN:

33190

American (AMR)

AF:

0.214

AC:

9494

AN:

44290

Ashkenazi Jewish (ASJ)

AF:

0.217

AC:

5601

AN:

25816

East Asian (EAS)

AF:

0.138

AC:

5412

AN:

39154

South Asian (SAS)

AF:

0.166

AC:

14229

AN:

85738

European-Finnish (FIN)

AF:

0.285

AC:

13641

AN:

47946

Middle Eastern (MID)

AF:

0.200

AC:

1124

AN:

5620

European-Non Finnish (NFE)

AF:

0.290

AC:

319971

AN:

1103370

Other (OTH)

AF:

0.254

AC:

15149

AN:

59672

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

14420

28840

43260

57680

72100

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10440

20880

31320

41760

52200

<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:

0.226

AC:

34303

AN:

151998

Hom.:

4245

Cov.:

AF XY:

0.223

AC XY:

16534

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.126

AC:

5212

AN:

41506

American (AMR)

AF:

0.240

AC:

3665

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.203

AC:

704

AN:

3468

East Asian (EAS)

AF:

0.141

AC:

729

AN:

5156

South Asian (SAS)

AF:

0.166

AC:

797

AN:

4794

European-Finnish (FIN)

AF:

0.276

AC:

2905

AN:

10538

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.286

AC:

19469

AN:

67966

Other (OTH)

AF:

0.236

AC:

497

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

1297

2594

3890

5187

6484

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

348

696

1044

1392

1740

<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:

0.208

Hom.:

1121

Bravo

AF:

0.219

Asia WGS

AF:

0.142

AC:

494

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Primary ciliary dyskinesia

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 07, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

5.4

(source)

DANN

Benign

0.82

PhyloP100

1.3

Mutation Taster

=95/5

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000085

dbscSNV1_RF

Benign

0.0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over