10-27812382-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018076.5(ODAD2):c.*130A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 765,212 control chromosomes in the GnomAD database, including 6,600 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.098 (978 hom., cov: 33)
  • Exomes 𝑓: 0.13 (5622 hom.)
• Consequence: ODAD2 NM_018076.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.509

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 10-27812382-T-C is Benign according to our data. Variant chr10-27812382-T-C is described in ClinVar as [Benign]. Clinvar id is 1222323.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODAD2	NM_018076.5	c.*130A>G		3_prime_UTR_variant	20/20	ENST00000305242.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODAD2	ENST00000305242.10	c.*130A>G		3_prime_UTR_variant	20/20	1	NM_018076.5	P1

Frequencies

GnomAD3 genomes AF: 0.0981 AC: 14923 AN: 152190 Hom.: 978 Cov.: 33

Gnomad AFR AF: 0.0258

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.0799

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.00211

Gnomad SAS AF: 0.0770

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.0913

GnomAD4 exome AF: 0.130 AC: 79807 AN: 612904 Hom.: 5622 Cov.: 8 AF XY: 0.128 AC XY: 41201 AN XY: 321164

Gnomad4 AFR exome AF: 0.0223

Gnomad4 AMR exome AF: 0.0776

Gnomad4 ASJ exome AF: 0.120

Gnomad4 EAS exome AF: 0.000722

Gnomad4 SAS exome AF: 0.0872

Gnomad4 FIN exome AF: 0.145

Gnomad4 NFE exome AF: 0.149

Gnomad4 OTH exome AF: 0.120

GnomAD4 genome AF: 0.0980 AC: 14926 AN: 152308 Hom.: 978 Cov.: 33 AF XY: 0.0967 AC XY: 7203 AN XY: 74470

Gnomad4 AFR AF: 0.0257

Gnomad4 AMR AF: 0.0801

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.0771

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.0908

Alfa AF: 0.133 Hom.: 1535

Bravo AF: 0.0905

Asia WGS AF: 0.0390 AC: 134 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 16, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	2.0
Dann	Benign	0.51

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: rs1061577; hg19: chr10-28101311; COSMIC: COSV59462963;