rs7920186

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_018076.5(ODAD2):​c.1238G>T​(p.Arg413Leu) 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. 15/26 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R413Q) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 16)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ODAD2 NM_018076.5 missense, splice_region
• Scores: Splicing: ADA: 0.9987
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.560
• Publications: 0 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: Uncertain_significance. The variant received 1 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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAD2	NM_018076.5	MANE Select	c.1238G>T	p.Arg413Leu	missense splice_region	Exon 9 of 20	NP_060546.2
	ODAD2	NM_001290020.2		c.1238G>T	p.Arg413Leu	missense splice_region	Exon 9 of 20	NP_001276949.1
	ODAD2	NM_001312689.2		c.314G>T	p.Arg105Leu	missense splice_region	Exon 4 of 15	NP_001299618.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAD2	ENST00000305242.10	TSL:1 MANE Select	c.1238G>T	p.Arg413Leu	missense splice_region	Exon 9 of 20	ENSP00000306410.5
	ODAD2	ENST00000673439.1		c.1238G>T	p.Arg413Leu	missense splice_region	Exon 9 of 20	ENSP00000500782.1
	ODAD2	ENST00000672841.1		c.314G>T	p.Arg105Leu	missense splice_region	Exon 4 of 15	ENSP00000499983.1

Frequencies

GnomAD3 genomes Cov.: 16

GnomAD4 exome AF: 0.00000210 AC: 1 AN: 476768 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 253568

African (AFR) AF: 0.00 AC: 0 AN: 12342

American (AMR) AF: 0.00 AC: 0 AN: 21754

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13554

East Asian (EAS) AF: 0.00 AC: 0 AN: 30528

South Asian (SAS) AF: 0.00 AC: 0 AN: 47134

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42512

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1884

European-Non Finnish (NFE) AF: 0.00000356 AC: 1 AN: 280918

Other (OTH) AF: 0.00 AC: 0 AN: 26142

GnomAD4 genome Cov.: 16

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	21
DANN	Benign	0.39
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.56
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.11
Sift	Benign	0.083	T
Sift4G	Uncertain	0.037	D
Polyphen		0.0080	B
Vest4		0.29
MutPred		0.36		Loss of MoRF binding (P = 0.0189)
MVP		0.43
MPC		2.0
ClinPred		0.084	T
GERP RS		2.0
Varity_R		0.12
gMVP		0.19
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.93
SpliceAI score (max)		0.70		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.70		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;