chr10-27983896-C-A

Variant names:

• chr10-27983896-C-A
• NM_018076.5:c.766G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018076.5(ODAD2):​c.766G>T​(p.Asp256Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,850 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ODAD2 NM_018076.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.57

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]

LOC112268060 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODAD2	NM_018076.5	c.766G>T	p.Asp256Tyr	missense_variant	Exon 6 of 20	ENST00000305242.10	NP_060546.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODAD2	ENST00000305242.10	c.766G>T	p.Asp256Tyr	missense_variant	Exon 6 of 20	1	NM_018076.5	ENSP00000306410.5
ODAD2	ENST00000673439.1	c.766G>T	p.Asp256Tyr	missense_variant	Exon 6 of 20			ENSP00000500782.1
ODAD2	ENST00000434029.1	n.448G>T		non_coding_transcript_exon_variant	Exon 4 of 10	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459850 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726160

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.25
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;T
Eigen	Uncertain	0.38
Eigen_PC	Benign	0.22
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.080	D
MetaRNN	Uncertain	0.73	D;D
MetaSVM	Uncertain	0.070	D
MutationAssessor	Uncertain	2.9	M;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-5.6	D;D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		1.0	D;.
Vest4		0.93
MutPred		0.44		Loss of solvent accessibility (P = 0.0152);.;
MVP		0.82
MPC		0.81
ClinPred		0.99	D
GERP RS		4.5
Varity_R		0.75
gMVP		0.95

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-28272825;