rs531033796

Positions:

• chr10-27968933-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The ENST00000305242.10(ODAD2):​c.1228C>G​(p.Gln410Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0011 (4 hom., cov: 18)
  • Exomes 𝑓: 0.00012 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: ODAD2 ENST00000305242.10 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.19

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 (MetaRNN=0.0077064335).
• BP6: Variant 10-27968933-G-C is Benign according to our data. Variant chr10-27968933-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 412249.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODAD2	NM_018076.5	c.1228C>G	p.Gln410Glu	missense_variant	9/20	ENST00000305242.10	NP_060546.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODAD2	ENST00000305242.10	c.1228C>G	p.Gln410Glu	missense_variant	9/20	1	NM_018076.5	ENSP00000306410	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 144 AN: 136990 Hom.: 4 Cov.: 18 FAILED QC

Gnomad AFR AF: 0.00370

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000376

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000469

Gnomad OTH AF: 0.00227

GnomAD3 exomes AF: 0.000426 AC: 33 AN: 77478 Hom.: 0 AF XY: 0.000285 AC XY: 11 AN XY: 38540

Gnomad AFR exome AF: 0.00441

Gnomad AMR exome AF: 0.000173

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000443

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000121 AC: 60 AN: 496474 Hom.: 1 Cov.: 5 AF XY: 0.0000832 AC XY: 22 AN XY: 264466

Gnomad4 AFR exome AF: 0.00358

Gnomad4 AMR exome AF: 0.000176

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000207

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.000294

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00106 AC: 146 AN: 137098 Hom.: 4 Cov.: 18 AF XY: 0.00108 AC XY: 71 AN XY: 65966

Gnomad4 AFR AF: 0.00375

Gnomad4 AMR AF: 0.000376

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000469

Gnomad4 OTH AF: 0.00224

Alfa AF: 0.00126 Hom.: 0

ExAC AF: 0.000174 AC: 15

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 17, 2018

This alteration is classified as likely 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. -

Primary ciliary dyskinesia 23 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 09, 2022

- -

ODAD2-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 05, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	6.8
DANN	Benign	0.19
DEOGEN2	Benign	0.0038	T;T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.0077	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;.
MutationTaster	Benign	0.99	D;N;N;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.14	N;N
REVEL	Benign	0.12
Sift	Benign	0.41	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.011	B;.
Vest4		0.19
MVP		0.40
MPC		1.8
ClinPred		0.017	T
GERP RS		3.9
Varity_R		0.046
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs531033796; hg19: chr10-28257862;