Genetic Variant ODAD2:p.Asn686Lys (chr10-27939936-A-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018076.5(ODAD2):c.2058T>A(p.Asn686Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N686N) has been classified as Benign.

Frequency

Genomes: not found (cov: 31)

Consequence

ODAD2
NM_018076.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.620

Publications

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

ODAD2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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	HGVSp	Effect	Exon Rank	Protein
ODAD2	NM_018076.5	MANE Select	c.2058T>A	p.Asn686Lys	missense	Exon 14 of 20	NP_060546.2
ODAD2	NM_001290020.2		c.2058T>A	p.Asn686Lys	missense	Exon 14 of 20	NP_001276949.1
ODAD2	NM_001312689.2		c.1134T>A	p.Asn378Lys	missense	Exon 9 of 15	NP_001299618.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ODAD2	ENST00000305242.10	TSL:1 MANE Select	c.2058T>A	p.Asn686Lys	missense	Exon 14 of 20	ENSP00000306410.5
ODAD2	ENST00000673439.1		c.2058T>A	p.Asn686Lys	missense	Exon 14 of 20	ENSP00000500782.1
ODAD2	ENST00000672841.1		c.1134T>A	p.Asn378Lys	missense	Exon 9 of 15	ENSP00000499983.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

62929

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.67

BayesDel_addAF

Benign

-0.084

BayesDel_noAF

Benign

-0.36

CADD

Benign

4.0

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.081

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.77

M_CAP

Uncertain

0.10

MetaRNN

Uncertain

0.60

MetaSVM

Benign

-0.34

MutationAssessor

Uncertain

2.5

PhyloP100

-0.62

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-4.9

REVEL

Benign

0.25

Sift

Uncertain

0.024

Sift4G

Uncertain

0.030

Polyphen

0.19

Vest4

0.47

MutPred

0.37

Gain of ubiquitination at N686 (P = 0.0155)

MVP

0.32

MPC

0.36

ClinPred

0.98

GERP RS

-2.7

Varity_R

0.50

gMVP

0.53

Mutation Taster

=62/38

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

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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