10-27968924-G-C

Position:

• chr10-27968924-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018076.5(ODAD2):​c.1237C>G​(p.Arg413Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.092 (402 hom., cov: 17)
  • Exomes 𝑓: 0.084 (1247 hom.)
• Consequence: ODAD2 NM_018076.5 missense, splice_region
• Scores: Splicing: ADA: 0.002123
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.594

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00283131).
• BP6: Variant 10-27968924-G-C is Benign according to our data. Variant chr10-27968924-G-C is described in ClinVar as [Benign]. Clinvar id is 241255.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODAD2	NM_018076.5	c.1237C>G	p.Arg413Gly	missense_variant, splice_region_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.1237C>G	p.Arg413Gly	missense_variant, splice_region_variant	9/20	1	NM_018076.5	ENSP00000306410.5

Frequencies

GnomAD3 genomes AF: 0.0919 AC: 11945 AN: 130030 Hom.: 402 Cov.: 17

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.0965

Gnomad ASJ AF: 0.0599

Gnomad EAS AF: 0.0112

Gnomad SAS AF: 0.0863

Gnomad FIN AF: 0.0553

Gnomad MID AF: 0.0646

Gnomad NFE AF: 0.0968

Gnomad OTH AF: 0.0881

GnomAD3 exomes AF: 0.0813 AC: 6008 AN: 73864 Hom.: 242 AF XY: 0.0803 AC XY: 2945 AN XY: 36688

Gnomad AFR exome AF: 0.108

Gnomad AMR exome AF: 0.112

Gnomad ASJ exome AF: 0.0497

Gnomad EAS exome AF: 0.00912

Gnomad SAS exome AF: 0.0846

Gnomad FIN exome AF: 0.0547

Gnomad NFE exome AF: 0.0944

Gnomad OTH exome AF: 0.0867

GnomAD4 exome AF: 0.0838 AC: 39388 AN: 469766 Hom.: 1247 Cov.: 5 AF XY: 0.0839 AC XY: 20962 AN XY: 249756

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.114

Gnomad4 ASJ exome AF: 0.0539

Gnomad4 EAS exome AF: 0.00825

Gnomad4 SAS exome AF: 0.0858

Gnomad4 FIN exome AF: 0.0585

Gnomad4 NFE exome AF: 0.0942

Gnomad4 OTH exome AF: 0.0825

GnomAD4 genome AF: 0.0918 AC: 11952 AN: 130150 Hom.: 402 Cov.: 17 AF XY: 0.0887 AC XY: 5553 AN XY: 62622

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.0966

Gnomad4 ASJ AF: 0.0599

Gnomad4 EAS AF: 0.0112

Gnomad4 SAS AF: 0.0866

Gnomad4 FIN AF: 0.0553

Gnomad4 NFE AF: 0.0967

Gnomad4 OTH AF: 0.0863

Alfa AF: 0.0394 Hom.: 28

ExAC AF: 0.0407 AC: 3186

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 12, 2019	- -

Primary ciliary dyskinesia Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 22, 2016

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. -

Primary ciliary dyskinesia 23 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 19, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	12
DANN	Benign	0.42
DEOGEN2	Benign	0.0060	T;T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.095	N
LIST_S2	Benign	0.45	T;T
MetaRNN	Benign	0.0028	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.024
Sift	Benign	0.11	T;T
Sift4G	Benign	0.13	T;D
Polyphen		0.089	B;.
Vest4		0.11
MPC		2.1
ClinPred		0.0014	T
GERP RS		2.0
Varity_R		0.058
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0021
dbscSNV1_RF	Benign	0.032
SpliceAI score (max)		0.030		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: rs57067036; hg19: chr10-28257853; COSMIC: COSV53462756;