Variant 10-27812594-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018076.5(ODAD2):c.3053A>G(p.Gln1018Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,460,484 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ODAD2
NM_018076.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.52

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.093726456).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODAD2	NM_018076.5 linkuse as main transcript	c.3053A>G	p.Gln1018Arg	missense_variant	20/20	ENST00000305242.10	NP_060546.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODAD2	ENST00000305242.10 linkuse as main transcript	c.3053A>G	p.Gln1018Arg	missense_variant	20/20	1	NM_018076.5	ENSP00000306410	P1	Q5T2S8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249272

Hom.:

AF XY:

0.00000742

AC XY:

AN XY:

134826

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1460484

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726568

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 07, 2023

The c.3053A>G (p.Q1018R) alteration is located in exon 20 (coding exon 19) of the ARMC4 gene. This alteration results from a A to G substitution at nucleotide position 3053, causing the glutamine (Q) at amino acid position 1018 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.0038

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.0023

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.26

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.030

MetaRNN

Benign

0.094

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.0

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.81

REVEL

Uncertain

0.33

Sift

Benign

0.47

Sift4G

Benign

0.42

Polyphen

0.0

Vest4

0.12

MutPred

0.41

Gain of phosphorylation at S1015 (P = 0.1056);

MVP

0.79

MPC

0.14

ClinPred

0.16

GERP RS

5.8

Varity_R

0.087

gMVP

0.16

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over