rs12777433

Variant names:

• chr10-27985204-T-C
• rs12777433
• NM_018076.5:c.390A>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_018076.5(ODAD2):​c.390A>G​(p.Arg130Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00258 in 1,510,956 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0018 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (6 hom.)
• Consequence: ODAD2 NM_018076.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.78
• 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

LOC112268060 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 10-27985204-T-C is Benign according to our data. Variant chr10-27985204-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 417181.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00178 (266/149350) while in subpopulation AMR AF = 0.00388 (58/14950). AF 95% confidence interval is 0.00308. There are 1 homozygotes in GnomAd4. There are 126 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 6 AD,AR gene

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.390A>G	p.Arg130Arg	synonymous	Exon 4 of 20	NP_060546.2
	ODAD2	NM_001290020.2		c.390A>G	p.Arg130Arg	synonymous	Exon 4 of 20	NP_001276949.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAD2	ENST00000305242.10	TSL:1 MANE Select	c.390A>G	p.Arg130Arg	synonymous	Exon 4 of 20	ENSP00000306410.5
	ODAD2	ENST00000673439.1		c.390A>G	p.Arg130Arg	synonymous	Exon 4 of 20	ENSP00000500782.1
	ODAD2	ENST00000852623.1		c.390A>G	p.Arg130Arg	synonymous	Exon 4 of 20	ENSP00000522682.1

Frequencies

GnomAD3 genomes AF: 0.00178 AC: 266 AN: 149256 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000618

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00388

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000199

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00263

Gnomad OTH AF: 0.00147

GnomAD2 exomes AF: 0.00167 AC: 205 AN: 122926 AF XY: 0.00146

Gnomad AFR exome AF: 0.000612

Gnomad AMR exome AF: 0.00167

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000686

Gnomad NFE exome AF: 0.00300

Gnomad OTH exome AF: 0.00248

GnomAD4 exome AF: 0.00267 AC: 3631 AN: 1361606 Hom.: 6 Cov.: 31 AF XY: 0.00249 AC XY: 1672 AN XY: 672610

African (AFR) AF: 0.000410 AC: 12 AN: 29274

American (AMR) AF: 0.00129 AC: 34 AN: 26392

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23358

East Asian (EAS) AF: 0.00 AC: 0 AN: 36820

South Asian (SAS) AF: 0.00 AC: 0 AN: 73104

European-Finnish (FIN) AF: 0.000457 AC: 20 AN: 43794

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3836

European-Non Finnish (NFE) AF: 0.00320 AC: 3420 AN: 1069010

Other (OTH) AF: 0.00259 AC: 145 AN: 56018

GnomAD4 genome AF: 0.00178 AC: 266 AN: 149350 Hom.: 1 Cov.: 32 AF XY: 0.00173 AC XY: 126 AN XY: 72834

African (AFR) AF: 0.000617 AC: 25 AN: 40528

American (AMR) AF: 0.00388 AC: 58 AN: 14950

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3442

East Asian (EAS) AF: 0.00 AC: 0 AN: 4882

South Asian (SAS) AF: 0.00 AC: 0 AN: 4654

European-Finnish (FIN) AF: 0.000199 AC: 2 AN: 10038

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

European-Non Finnish (NFE) AF: 0.00263 AC: 178 AN: 67588

Other (OTH) AF: 0.00145 AC: 3 AN: 2064

Alfa AF: 0.00218 Hom.: 0

Bravo AF: 0.00212

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	11
DANN	Benign	0.74
PhyloP100		1.8
Mutation Taster		=281/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.21		Position offset: 0

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

Other links and lift over

dbSNP: rs12777433; hg19: chr10-28274133;