chr10-27968923-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/25 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.

• 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PP3: Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODAD2	NM_018076.5	c.1238G>T	p.Arg413Leu	missense_variant, splice_region_variant	Exon 9 of 20	ENST00000305242.10	NP_060546.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODAD2	ENST00000305242.10	c.1238G>T	p.Arg413Leu	missense_variant, splice_region_variant	Exon 9 of 20	1	NM_018076.5	ENSP00000306410.5

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

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: 0.00000356

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 16

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.11
Sift	Benign	0.083	T;T
Sift4G	Uncertain	0.037	D;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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-28257852;