10-27877047-A-G

Variant names:

• chr10-27877047-A-G
• rs1556641
• NM_018076.5:c.2611-14425T>C

Variant summary

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

The NM_018076.5(ODAD2):​c.2611-14425T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 151,844 control chromosomes in the GnomAD database, including 22,388 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 0.51 (22388 hom., cov: 31)
• Consequence: ODAD2 NM_018076.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.552
• Publications: 3 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.632 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.2611-14425T>C		intron	N/A	NP_060546.2
	ODAD2	NM_001290020.2		c.2611-14425T>C		intron	N/A	NP_001276949.1	A0A140VKF7
	ODAD2	NM_001312689.2		c.1687-14425T>C		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.2611-14425T>C		intron	N/A	ENSP00000306410.5	Q5T2S8-1
	ODAD2	ENST00000673439.1		c.2611-14425T>C		intron	N/A	ENSP00000500782.1	Q5T2S8-1
	ODAD2	ENST00000852623.1		c.2611-14425T>C		intron	N/A	ENSP00000522682.1

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78064 AN: 151726 Hom.: 22387 Cov.: 31

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.637

Gnomad OTH AF: 0.558

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

GnomAD4 genome AF: 0.514 AC: 78075 AN: 151844 Hom.: 22388 Cov.: 31 AF XY: 0.515 AC XY: 38170 AN XY: 74142

African (AFR) AF: 0.249 AC: 10315 AN: 41442

American (AMR) AF: 0.606 AC: 9241 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.640 AC: 2220 AN: 3470

East Asian (EAS) AF: 0.426 AC: 2202 AN: 5172

South Asian (SAS) AF: 0.579 AC: 2781 AN: 4800

European-Finnish (FIN) AF: 0.567 AC: 5938 AN: 10480

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.637 AC: 43291 AN: 67918

Other (OTH) AF: 0.555 AC: 1175 AN: 2116

Alfa AF: 0.560 Hom.: 3968

Bravo AF: 0.504

Asia WGS AF: 0.433 AC: 1508 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.85
PhyloP100		0.55
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: rs1556641; hg19: chr10-28165976;