10-27897177-T-C

Variant names:

• chr10-27897177-T-C
• rs1413772
• NM_018076.5:c.2610+10486A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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: ClinGen, G2P, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAD2	NM_018076.5	MANE Select	c.2610+10486A>G		intron	N/A	NP_060546.2
	ODAD2	NM_001290020.2		c.2610+10486A>G		intron	N/A	NP_001276949.1	A0A140VKF7
	ODAD2	NM_001312689.2		c.1686+10486A>G		intron	N/A	NP_001299618.1	A0A5F9ZH22

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAD2	ENST00000305242.10	TSL:1 MANE Select	c.2610+10486A>G		intron	N/A	ENSP00000306410.5	Q5T2S8-1
	ODAD2	ENST00000673439.1		c.2610+10486A>G		intron	N/A	ENSP00000500782.1	Q5T2S8-1
	ODAD2	ENST00000852623.1		c.2610+10486A>G		intron	N/A	ENSP00000522682.1

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

African (AFR) AF: 0.593 AC: 24546 AN: 41368

American (AMR) AF: 0.728 AC: 11118 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.680 AC: 2358 AN: 3466

East Asian (EAS) AF: 0.532 AC: 2726 AN: 5128

South Asian (SAS) AF: 0.694 AC: 3337 AN: 4806

European-Finnish (FIN) AF: 0.636 AC: 6706 AN: 10548

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.699 AC: 47507 AN: 67926

Other (OTH) AF: 0.677 AC: 1424 AN: 2102

Alfa AF: 0.696 Hom.: 46414

Bravo AF: 0.667

Asia WGS AF: 0.585 AC: 2038 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.6
DANN	Benign	0.68
PhyloP100		-0.50
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1413772; hg19: chr10-28186106;