rs7920186

Variant names:

• chr10-27968923-C-T
• rs7920186
• NM_018076.5:c.1238G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-27968923-C-T
• chr10-27968923-C-A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 2P and 16B. PP3_Moderate BP6_Very_Strong BA1

The NM_018076.5(ODAD2):​c.1238G>A​(p.Arg413Gln) 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. 14/25 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to 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. R413G) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.12 (742 hom., cov: 16)
  • Exomes 𝑓: 0.11 (2223 hom.)
• Consequence: ODAD2 NM_018076.5 missense, splice_region
• Scores: Splicing: ADA: 0.9999
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.560
• Publications: 4 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 -14 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• BP6: Variant 10-27968923-C-T is Benign according to our data. Variant chr10-27968923-C-T is described in ClinVar as Benign. ClinVar VariationId is 541504.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.153 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.1238G>A	p.Arg413Gln	missense splice_region	Exon 9 of 20	NP_060546.2
	ODAD2	NM_001290020.2		c.1238G>A	p.Arg413Gln	missense splice_region	Exon 9 of 20	NP_001276949.1	A0A140VKF7
	ODAD2	NM_001312689.2		c.314G>A	p.Arg105Gln	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.1238G>A	p.Arg413Gln	missense splice_region	Exon 9 of 20	ENSP00000306410.5	Q5T2S8-1
	ODAD2	ENST00000673439.1		c.1238G>A	p.Arg413Gln	missense splice_region	Exon 9 of 20	ENSP00000500782.1	Q5T2S8-1
	ODAD2	ENST00000852623.1		c.1238G>A	p.Arg413Gln	missense splice_region	Exon 9 of 20	ENSP00000522682.1

Frequencies

GnomAD3 genomes AF: 0.118 AC: 15233 AN: 129232 Hom.: 734 Cov.: 16

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.0436

Gnomad AMR AF: 0.0772

Gnomad ASJ AF: 0.0897

Gnomad EAS AF: 0.00375

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.0987

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.101

GnomAD2 exomes AF: 0.0983 AC: 7234 AN: 73570 AF XY: 0.0982

Gnomad AFR exome AF: 0.156

Gnomad AMR exome AF: 0.0674

Gnomad ASJ exome AF: 0.0859

Gnomad EAS exome AF: 0.00210

Gnomad FIN exome AF: 0.116

Gnomad NFE exome AF: 0.119

Gnomad OTH exome AF: 0.0967

GnomAD4 exome AF: 0.109 AC: 51564 AN: 473844 Hom.: 2223 Cov.: 5 AF XY: 0.110 AC XY: 27792 AN XY: 251896

African (AFR) AF: 0.156 AC: 1897 AN: 12192

American (AMR) AF: 0.0646 AC: 1400 AN: 21678

Ashkenazi Jewish (ASJ) AF: 0.0912 AC: 1202 AN: 13180

East Asian (EAS) AF: 0.00298 AC: 91 AN: 30518

South Asian (SAS) AF: 0.120 AC: 5567 AN: 46464

European-Finnish (FIN) AF: 0.112 AC: 4743 AN: 42394

Middle Eastern (MID) AF: 0.112 AC: 209 AN: 1866

European-Non Finnish (NFE) AF: 0.120 AC: 33586 AN: 279632

Other (OTH) AF: 0.111 AC: 2869 AN: 25920

GnomAD4 genome AF: 0.118 AC: 15271 AN: 129338 Hom.: 742 Cov.: 16 AF XY: 0.116 AC XY: 7179 AN XY: 62150

African (AFR) AF: 0.156 AC: 5096 AN: 32618

American (AMR) AF: 0.0769 AC: 985 AN: 12812

Ashkenazi Jewish (ASJ) AF: 0.0897 AC: 268 AN: 2988

East Asian (EAS) AF: 0.00376 AC: 18 AN: 4786

South Asian (SAS) AF: 0.109 AC: 383 AN: 3524

European-Finnish (FIN) AF: 0.105 AC: 906 AN: 8640

Middle Eastern (MID) AF: 0.103 AC: 29 AN: 282

European-Non Finnish (NFE) AF: 0.121 AC: 7383 AN: 61176

Other (OTH) AF: 0.0998 AC: 166 AN: 1664

Alfa AF: 0.144 Hom.: 351

ExAC AF: 0.0563 AC: 4320

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	21
DANN	Benign	0.86
DEOGEN2	Benign	0.0025	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.55	T
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.56
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.033
Sift	Benign	0.14	T
Sift4G	Benign	0.17	T
Polyphen		0.51	P
Vest4		0.055
MPC		1.9
ClinPred		0.0030	T
GERP RS		2.0
Varity_R		0.10
gMVP		0.12
Mutation Taster		=95/5	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.95
SpliceAI score (max)		0.61		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.61		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7920186; hg19: chr10-28257852; COSMIC: COSV53462606;