Genetic Variant ODAD1:p.Arg52Ser (chr19-48318729-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001364171.2(ODAD1):c.154C>A(p.Arg52Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R52H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

ODAD1
NM_001364171.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.92

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33311236).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAD1	NM_001364171.2	MANE Select	c.154C>A	p.Arg52Ser	missense	Exon 4 of 16	NP_001351100.1
	ODAD1	NM_144577.4		c.43C>A	p.Arg15Ser	missense	Exon 2 of 14	NP_653178.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ODAD1	ENST00000674294.1	MANE Select	c.154C>A	p.Arg52Ser	missense	Exon 4 of 16	ENSP00000501363.1
ODAD1	ENST00000315396.7	TSL:1	c.43C>A	p.Arg15Ser	missense	Exon 2 of 14	ENSP00000318429.7
ODAD1	ENST00000474199.6	TSL:2	c.154C>A	p.Arg52Ser	missense	Exon 4 of 15	ENSP00000501357.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000643

AC:

AN:

155626

AF XY:

0.0000121

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000166

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.15e-7

AC:

AN:

1398324

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

689734

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31582

American (AMR)

AF:

0.00

AC:

AN:

35698

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25176

East Asian (EAS)

AF:

0.00

AC:

AN:

35736

South Asian (SAS)

AF:

0.00

AC:

AN:

79194

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49238

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

9.28e-7

AC:

AN:

1078040

Other (OTH)

AF:

0.00

AC:

AN:

57964

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.52

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0021

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.20

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.74

M_CAP

Benign

0.013

MetaRNN

Benign

0.33

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

PhyloP100

1.9

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.9

REVEL

Benign

0.13

Sift

Benign

0.060

Sift4G

Uncertain

0.058

Polyphen

1.0

Vest4

0.50

MutPred

0.37

Gain of ubiquitination at K10 (P = 0.0354)

MVP

0.31

MPC

0.81

ClinPred

0.78

GERP RS

3.6

Varity_R

0.14

gMVP

0.54

Mutation Taster

=83/17

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over