rs149432727

Variant names:

• chr10-27961601-A-G
• rs149432727
• NM_018076.5:c.1353T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001290021.2(ODAD2):​c.-73T>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00148 in 1,611,886 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (4 hom.)
• Consequence: ODAD2 NM_001290021.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.00900
• 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: ClinGen, G2P, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 10-27961601-A-G is Benign according to our data. Variant chr10-27961601-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 241257.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0011 (168/152282) while in subpopulation NFE AF = 0.00194 (132/68022). AF 95% confidence interval is 0.00167. There are 0 homozygotes in GnomAd4. There are 64 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 4 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001290021.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAD2	NM_018076.5	MANE Select	c.1353T>C	p.Tyr451Tyr	synonymous	Exon 10 of 20	NP_060546.2
	ODAD2	NM_001290021.2		c.-73T>C		5_prime_UTR_premature_start_codon_gain	Exon 3 of 14	NP_001276950.1	Q5T2S8-2
	ODAD2	NM_001290020.2		c.1353T>C	p.Tyr451Tyr	synonymous	Exon 10 of 20	NP_001276949.1	A0A140VKF7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAD2	ENST00000305242.10	TSL:1 MANE Select	c.1353T>C	p.Tyr451Tyr	synonymous	Exon 10 of 20	ENSP00000306410.5	Q5T2S8-1
	ODAD2	ENST00000672877.1		c.-73T>C		5_prime_UTR_premature_start_codon_gain	Exon 3 of 14	ENSP00000500120.1	Q5T2S8-2
	ODAD2	ENST00000673439.1		c.1353T>C	p.Tyr451Tyr	synonymous	Exon 10 of 20	ENSP00000500782.1	Q5T2S8-1

Frequencies

GnomAD3 genomes AF: 0.00110 AC: 168 AN: 152164 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00194

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000938 AC: 235 AN: 250492 AF XY: 0.000983

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000958

Gnomad ASJ exome AF: 0.000598

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000926

Gnomad NFE exome AF: 0.00167

Gnomad OTH exome AF: 0.000492

GnomAD4 exome AF: 0.00152 AC: 2216 AN: 1459604 Hom.: 4 Cov.: 29 AF XY: 0.00143 AC XY: 1037 AN XY: 726108

African (AFR) AF: 0.000180 AC: 6 AN: 33410

American (AMR) AF: 0.000986 AC: 44 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.000575 AC: 15 AN: 26074

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86008

European-Finnish (FIN) AF: 0.000150 AC: 8 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5202

European-Non Finnish (NFE) AF: 0.00185 AC: 2054 AN: 1110926

Other (OTH) AF: 0.00146 AC: 88 AN: 60258

GnomAD4 genome AF: 0.00110 AC: 168 AN: 152282 Hom.: 0 Cov.: 32 AF XY: 0.000860 AC XY: 64 AN XY: 74454

African (AFR) AF: 0.000168 AC: 7 AN: 41552

American (AMR) AF: 0.00137 AC: 21 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00194 AC: 132 AN: 68022

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00144 Hom.: 0

Bravo AF: 0.00117

EpiCase AF: 0.00218

EpiControl AF: 0.00255

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	Primary ciliary dyskinesia 23 (2)
-	-	1	Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.81
DANN	Benign	0.33
PhyloP100		0.0090
Mutation Taster		=294/6	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: rs149432727; hg19: chr10-28250530;