10-27968924-G-C

Variant names:

• chr10-27968924-G-C
• rs57067036
• NM_018076.5:c.1237C>G

Variant summary

Our verdict is Benign. The variant received -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. 17/23 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R413Q) has been classified 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
• Publications: 3 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: ClinGen, G2P, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018076.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAD2	NM_018076.5	MANE Select	c.1237C>G	p.Arg413Gly	missense splice_region	Exon 9 of 20	NP_060546.2
	ODAD2	NM_001290020.2		c.1237C>G	p.Arg413Gly	missense splice_region	Exon 9 of 20	NP_001276949.1	A0A140VKF7
	ODAD2	NM_001312689.2		c.313C>G	p.Arg105Gly	missense splice_region	Exon 4 of 15	NP_001299618.1	A0A5F9ZH22

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAD2	ENST00000305242.10	TSL:1 MANE Select	c.1237C>G	p.Arg413Gly	missense splice_region	Exon 9 of 20	ENSP00000306410.5	Q5T2S8-1
	ODAD2	ENST00000673439.1		c.1237C>G	p.Arg413Gly	missense splice_region	Exon 9 of 20	ENSP00000500782.1	Q5T2S8-1
	ODAD2	ENST00000852623.1		c.1237C>G	p.Arg413Gly	missense splice_region	Exon 9 of 20	ENSP00000522682.1

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

GnomAD2 exomes AF: 0.0813 AC: 6008 AN: 73864 AF XY: 0.0803

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 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

African (AFR) AF: 0.104 AC: 1295 AN: 12472

American (AMR) AF: 0.114 AC: 2463 AN: 21672

Ashkenazi Jewish (ASJ) AF: 0.0539 AC: 732 AN: 13580

East Asian (EAS) AF: 0.00825 AC: 251 AN: 30426

South Asian (SAS) AF: 0.0858 AC: 3916 AN: 45646

European-Finnish (FIN) AF: 0.0585 AC: 2452 AN: 41904

Middle Eastern (MID) AF: 0.0584 AC: 110 AN: 1882

European-Non Finnish (NFE) AF: 0.0942 AC: 26035 AN: 276318

Other (OTH) AF: 0.0825 AC: 2134 AN: 25866

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

African (AFR) AF: 0.105 AC: 3557 AN: 33840

American (AMR) AF: 0.0966 AC: 1231 AN: 12742

Ashkenazi Jewish (ASJ) AF: 0.0599 AC: 185 AN: 3088

East Asian (EAS) AF: 0.0112 AC: 54 AN: 4812

South Asian (SAS) AF: 0.0866 AC: 303 AN: 3500

European-Finnish (FIN) AF: 0.0553 AC: 480 AN: 8684

Middle Eastern (MID) AF: 0.0620 AC: 17 AN: 274

European-Non Finnish (NFE) AF: 0.0967 AC: 5875 AN: 60726

Other (OTH) AF: 0.0863 AC: 144 AN: 1668

Alfa AF: 0.0394 Hom.: 28

ExAC AF: 0.0407 AC: 3186

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Primary ciliary dyskinesia (1)
-	-	1	Primary ciliary dyskinesia 23 (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.095	N
LIST_S2	Benign	0.45	T
MetaRNN	Benign	0.0028	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.59
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.024
Sift	Benign	0.11	T
Sift4G	Benign	0.13	T
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
Mutation Taster		=95/5	polymorphism (auto)

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

Other links and lift over

dbSNP: rs57067036; hg19: chr10-28257853; COSMIC: COSV53462756;