rs7893462

Variant names:

• chr10-27939936-A-G
• rs7893462
• NM_018076.5:c.2058T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-27939936-A-G
• chr10-27939936-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_018076.5(ODAD2):​c.2058T>C​(p.Asn686Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 1,608,196 control chromosomes in the GnomAD database, including 227,820 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (20574 hom., cov: 31)
  • Exomes 𝑓: 0.53 (207246 hom.)
• Consequence: ODAD2 NM_018076.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.620
• Publications: 22 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: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 10-27939936-A-G is Benign according to our data. Variant chr10-27939936-A-G is described in ClinVar as Benign. ClinVar VariationId is 260994.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.62 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODAD2	NM_018076.5	c.2058T>C	p.Asn686Asn	synonymous_variant	Exon 14 of 20	ENST00000305242.10	NP_060546.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODAD2	ENST00000305242.10	c.2058T>C	p.Asn686Asn	synonymous_variant	Exon 14 of 20	1	NM_018076.5	ENSP00000306410.5

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78457 AN: 151680 Hom.: 20557 Cov.: 31

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.640

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.555

GnomAD2 exomes AF: 0.535 AC: 132042 AN: 246658 AF XY: 0.542

Gnomad AFR exome AF: 0.450

Gnomad AMR exome AF: 0.515

Gnomad ASJ exome AF: 0.536

Gnomad EAS exome AF: 0.540

Gnomad FIN exome AF: 0.535

Gnomad NFE exome AF: 0.534

Gnomad OTH exome AF: 0.555

GnomAD4 exome AF: 0.532 AC: 774801 AN: 1456396 Hom.: 207246 Cov.: 37 AF XY: 0.535 AC XY: 387671 AN XY: 724654

African (AFR) AF: 0.453 AC: 15042 AN: 33218

American (AMR) AF: 0.522 AC: 22895 AN: 43862

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 13851 AN: 26006

East Asian (EAS) AF: 0.542 AC: 21281 AN: 39280

South Asian (SAS) AF: 0.602 AC: 51437 AN: 85504

European-Finnish (FIN) AF: 0.530 AC: 28279 AN: 53314

Middle Eastern (MID) AF: 0.645 AC: 3710 AN: 5750

European-Non Finnish (NFE) AF: 0.528 AC: 585902 AN: 1109310

Other (OTH) AF: 0.539 AC: 32404 AN: 60152

GnomAD4 genome AF: 0.517 AC: 78513 AN: 151800 Hom.: 20574 Cov.: 31 AF XY: 0.520 AC XY: 38595 AN XY: 74164

African (AFR) AF: 0.457 AC: 18882 AN: 41338

American (AMR) AF: 0.563 AC: 8602 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1843 AN: 3468

East Asian (EAS) AF: 0.529 AC: 2724 AN: 5148

South Asian (SAS) AF: 0.589 AC: 2835 AN: 4814

European-Finnish (FIN) AF: 0.521 AC: 5479 AN: 10510

Middle Eastern (MID) AF: 0.654 AC: 191 AN: 292

European-Non Finnish (NFE) AF: 0.533 AC: 36243 AN: 67948

Other (OTH) AF: 0.552 AC: 1163 AN: 2106

Alfa AF: 0.533 Hom.: 62929

Bravo AF: 0.515

Asia WGS AF: 0.510 AC: 1779 AN: 3478

EpiCase AF: 0.540

EpiControl AF: 0.547

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Primary ciliary dyskinesia 23 Benign:2

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia Benign:1

Jul 07, 2016

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.15
DANN	Benign	0.27
PhyloP100		-0.62
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: rs7893462; hg19: chr10-28228865;