rs1556641

Positions:

• chr10-27877047-A-G
• chr10-27877047-A-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODAD2	NM_018076.5	c.2611-14425T>C		intron_variant		ENST00000305242.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODAD2	ENST00000305242.10	c.2611-14425T>C		intron_variant		1	NM_018076.5	P1

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

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.606

Gnomad4 ASJ AF: 0.640

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.579

Gnomad4 FIN AF: 0.567

Gnomad4 NFE AF: 0.637

Gnomad4 OTH AF: 0.555

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.85

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: rs1556641; hg19: chr10-28165976;