Genetic Variant ODAD1:p.Glu48Asp (chr19-48318739-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000674294.1(ODAD1):c.144A>C(p.Glu48Asp) 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 1,399,022 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. Synonymous variant affecting the same amino acid position (i.e. E48E) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

ODAD1
ENST00000674294.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.97

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17818713).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000674294.1. 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.144A>C	p.Glu48Asp	missense	Exon 4 of 16	NP_001351100.1
	ODAD1	NM_144577.4		c.33A>C	p.Glu11Asp	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.144A>C	p.Glu48Asp	missense	Exon 4 of 16	ENSP00000501363.1
ODAD1	ENST00000315396.7	TSL:1	c.33A>C	p.Glu11Asp	missense	Exon 2 of 14	ENSP00000318429.7
ODAD1	ENST00000474199.6	TSL:2	c.144A>C	p.Glu48Asp	missense	Exon 4 of 15	ENSP00000501357.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.15e-7

AC:

AN:

1399022

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

690056

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31596

American (AMR)

AF:

0.00

AC:

AN:

35696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25178

East Asian (EAS)

AF:

0.00

AC:

AN:

35738

South Asian (SAS)

AF:

0.0000126

AC:

AN:

79220

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49240

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078658

Other (OTH)

AF:

0.00

AC:

AN:

57998

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

Benign

0.27

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0084

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.73

M_CAP

Benign

0.017

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.6

PhyloP100

-2.0

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.10

Sift

Uncertain

0.018

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.28

MutPred

0.18

Loss of ubiquitination at K10 (P = 0.0777)

MVP

0.24

MPC

0.73

ClinPred

0.95

GERP RS

-4.0

Varity_R

0.25

gMVP

0.42

Mutation Taster

=92/8

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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