10-27961682-G-T

Variant names:

• chr10-27961682-G-T
• rs111982349
• NM_018076.5:c.1272C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000305242.10(ODAD2):​c.1272C>A​(p.Ser424Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S424S) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ODAD2 ENST00000305242.10 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.941
• Publications: 2 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2994559).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000305242.10. 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.1272C>A	p.Ser424Arg	missense	Exon 10 of 20	NP_060546.2
	ODAD2	NM_001290020.2		c.1272C>A	p.Ser424Arg	missense	Exon 10 of 20	NP_001276949.1
	ODAD2	NM_001312689.2		c.348C>A	p.Ser116Arg	missense	Exon 5 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.1272C>A	p.Ser424Arg	missense	Exon 10 of 20	ENSP00000306410.5
	ODAD2	ENST00000673439.1		c.1272C>A	p.Ser424Arg	missense	Exon 10 of 20	ENSP00000500782.1
	ODAD2	ENST00000672841.1		c.348C>A	p.Ser116Arg	missense	Exon 5 of 15	ENSP00000499983.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000403 AC: 1 AN: 248288 AF XY: 0.00000746

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000888

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.89e-7 AC: 1 AN: 1451402 Hom.: 0 Cov.: 27 AF XY: 0.00000138 AC XY: 1 AN XY: 722266

African (AFR) AF: 0.00 AC: 0 AN: 33058

American (AMR) AF: 0.00 AC: 0 AN: 43966

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25688

East Asian (EAS) AF: 0.00 AC: 0 AN: 39608

South Asian (SAS) AF: 0.00 AC: 0 AN: 84986

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53248

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5720

European-Non Finnish (NFE) AF: 9.05e-7 AC: 1 AN: 1105150

Other (OTH) AF: 0.00 AC: 0 AN: 59978

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 3

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Benign	0.00096	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.090	T
Eigen	Benign	-0.072
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		0.94
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.24
Sift	Benign	0.12	T
Sift4G	Uncertain	0.018	D
Polyphen		0.98	D
Vest4		0.66
MutPred		0.31		Loss of phosphorylation at S424 (P = 9e-04)
MVP		0.55
MPC		3.2
ClinPred		0.89	D
GERP RS		1.6
Varity_R		0.30
gMVP		0.38
Mutation Taster		=62/38	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: rs111982349; hg19: chr10-28250611;