10-27897177-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018076.5(ODAD2):c.2610+10486A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 151,808 control chromosomes in the GnomAD database, including 33,721 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.66 (33721 hom., cov: 30)
• Consequence: ODAD2 NM_018076.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.497

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODAD2	NM_018076.5	c.2610+10486A>G		intron_variant		ENST00000305242.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODAD2	ENST00000305242.10	c.2610+10486A>G		intron_variant		1	NM_018076.5	P1

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100597 AN: 151690 Hom.: 33688 Cov.: 30

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.729

Gnomad ASJ AF: 0.680

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.694

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.680

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.663 AC: 100682 AN: 151808 Hom.: 33721 Cov.: 30 AF XY: 0.662 AC XY: 49127 AN XY: 74194

Gnomad4 AFR AF: 0.593

Gnomad4 AMR AF: 0.728

Gnomad4 ASJ AF: 0.680

Gnomad4 EAS AF: 0.532

Gnomad4 SAS AF: 0.694

Gnomad4 FIN AF: 0.636

Gnomad4 NFE AF: 0.699

Gnomad4 OTH AF: 0.677

Alfa AF: 0.701 Hom.: 35745

Bravo AF: 0.667

Asia WGS AF: 0.585 AC: 2038 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	4.6
Dann	Benign	0.68

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

Other links and lift over

dbSNP: rs1413772; hg19: chr10-28186106;