dbSNP rs549508936: ODAD2:c.1534-10delT (chr10-27944440-GA-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_018076.5(ODAD2):c.1534-10delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000287 in 1,427,994 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ODAD2
NM_018076.5 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.393

Publications

0 publications found

Variant links:

Genes affected

ODAD2 (HGNC:25583): (outer dynein arm docking complex subunit 2) The protein encoded by this gene contains ten Armadillo repeat motifs (ARMs) and one HEAT repeat, and is thought to be involved in ciliary and flagellar movement. This protein has been shown to localize to the ciliary axonemes and at the ciliary base of respiratory cells. Studies indicate that mutations in this gene cause partial outer dynein arm (ODA) defects in respiratory cilia. The cilia of cells with mutations in this gene displayed either reduced ciliary beat frequency and amplitude, or, complete immotility. Some individuals with primary ciliary dyskensia (PCD) have been shown to have mutations in this gene. PCD is characterized by chronic airway disease and left/right body asymmetry defects. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]

ODAD2 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 23
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae)
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ODAD2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP6

Variant 10-27944440-GA-G is Benign according to our data. Variant chr10-27944440-GA-G is described in ClinVar as Benign. ClinVar VariationId is 474574.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018076.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ODAD2	NM_018076.5	MANE Select	c.1534-10delT	intron	N/A	NP_060546.2
ODAD2	NM_001290020.2		c.1534-10delT	intron	N/A	NP_001276949.1	A0A140VKF7
ODAD2	NM_001312689.2		c.610-10delT	intron	N/A	NP_001299618.1	A0A5F9ZH22

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ODAD2	ENST00000305242.10	TSL:1 MANE Select	c.1534-10delT	intron	N/A	ENSP00000306410.5	Q5T2S8-1
ODAD2	ENST00000673439.1		c.1534-10delT	intron	N/A	ENSP00000500782.1	Q5T2S8-1
ODAD2	ENST00000852623.1		c.1534-10delT	intron	N/A	ENSP00000522682.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

150704

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000419

AC:

AN:

214726

AF XY:

0.0000344

show subpopulations

Gnomad AFR exome

AF:

0.0000686

Gnomad AMR exome

AF:

0.000108

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000403

Gnomad OTH exome

AF:

0.000196

GnomAD4 exome

AF:

0.0000287

AC:

AN:

1427994

Hom.:

Cov.:

AF XY:

0.0000380

AC XY:

AN XY:

711012

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000631

AC:

AN:

31712

American (AMR)

AF:

0.0000718

AC:

AN:

41774

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25374

East Asian (EAS)

AF:

0.00

AC:

AN:

38912

South Asian (SAS)

AF:

0.0000120

AC:

AN:

83636

European-Finnish (FIN)

AF:

0.0000380

AC:

AN:

52654

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5578

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

1089504

Other (OTH)

AF:

0.0000170

AC:

AN:

58850

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000992502), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.352

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

150704

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73502

African (AFR)

AF:

0.00

AC:

AN:

41062

American (AMR)

AF:

0.00

AC:

AN:

15142

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4786

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10168

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67622

Other (OTH)

AF:

0.00

AC:

AN:

2072

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Primary ciliary dyskinesia 23 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over