rs11006747

Variant names:

• chr10-27862006-A-C
• rs11006747
• NM_018076.5:c.2799+428T>G

Your query was ambiguous. Multiple possible variants found:

• chr10-27862006-A-C
• chr10-27862006-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018076.5(ODAD2):​c.2799+428T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 152,076 control chromosomes in the GnomAD database, including 23,730 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 0.54 (23730 hom., cov: 32)
• Consequence: ODAD2 NM_018076.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.199
• Publications: 7 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.634 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.2799+428T>G		intron	N/A	NP_060546.2
	ODAD2	NM_001290020.2		c.2799+428T>G		intron	N/A	NP_001276949.1	A0A140VKF7
	ODAD2	NM_001312689.2		c.1875+428T>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.2799+428T>G		intron	N/A	ENSP00000306410.5	Q5T2S8-1
	ODAD2	ENST00000673439.1		c.2799+428T>G		intron	N/A	ENSP00000500782.1	Q5T2S8-1
	ODAD2	ENST00000852623.1		c.2799+428T>G		intron	N/A	ENSP00000522682.1

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82501 AN: 151958 Hom.: 23720 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.782

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.580

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.639

Gnomad OTH AF: 0.581

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

GnomAD4 genome AF: 0.543 AC: 82550 AN: 152076 Hom.: 23730 Cov.: 32 AF XY: 0.542 AC XY: 40272 AN XY: 74326

African (AFR) AF: 0.346 AC: 14363 AN: 41482

American (AMR) AF: 0.617 AC: 9412 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.640 AC: 2223 AN: 3472

East Asian (EAS) AF: 0.426 AC: 2198 AN: 5156

South Asian (SAS) AF: 0.580 AC: 2798 AN: 4822

European-Finnish (FIN) AF: 0.568 AC: 6009 AN: 10586

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.639 AC: 43411 AN: 67972

Other (OTH) AF: 0.578 AC: 1224 AN: 2116

Alfa AF: 0.601 Hom.: 86577

Bravo AF: 0.535

Asia WGS AF: 0.442 AC: 1540 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.1
DANN	Benign	0.58
PhyloP100		0.20
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: rs11006747; hg19: chr10-28150935;