rs140569195

Variant names:

• chr10-27944256-C-A
• rs140569195
• NM_018076.5:c.1709G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-27944256-C-A
• chr10-27944256-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018076.5(ODAD2):​c.1709G>T​(p.Arg570Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,294 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R570Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ODAD2 NM_018076.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.385
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1709G>T	p.Arg570Leu	missense	Exon 12 of 20	NP_060546.2
	ODAD2	NM_001290020.2		c.1709G>T	p.Arg570Leu	missense	Exon 12 of 20	NP_001276949.1
	ODAD2	NM_001312689.2		c.785G>T	p.Arg262Leu	missense	Exon 7 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.1709G>T	p.Arg570Leu	missense	Exon 12 of 20	ENSP00000306410.5
	ODAD2	ENST00000673439.1		c.1709G>T	p.Arg570Leu	missense	Exon 12 of 20	ENSP00000500782.1
	ODAD2	ENST00000672841.1		c.785G>T	p.Arg262Leu	missense	Exon 7 of 15	ENSP00000499983.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461294 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726948

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39620

South Asian (SAS) AF: 0.00 AC: 0 AN: 86220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5428

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111954

Other (OTH) AF: 0.00 AC: 0 AN: 60346

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	13
DANN	Uncertain	1.0
DEOGEN2	Benign	0.049	T
Eigen	Benign	-0.024
Eigen_PC	Benign	-0.026
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.059	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		0.39
PrimateAI	Benign	0.22	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Benign	0.20
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.53	P
Vest4		0.54
MutPred		0.52		Loss of methylation at K566 (P = 0.0328)
MVP		0.63
MPC		0.36
ClinPred		0.97	D
GERP RS		3.4
Varity_R		0.22
gMVP		0.57
Mutation Taster		=53/47	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs140569195; hg19: chr10-28233185; COSMIC: COSV100536698; COSMIC: COSV100536698;