10-27944440-GA-GAA

Variant names:

• chr10-27944440-G-GA
• rs549508936
• NM_018076.5:c.1534-10dupT

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS1

The NM_018076.5(ODAD2):​c.1534-10dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00114 in 1,569,852 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00041 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (0 hom.)
• Consequence: ODAD2 NM_018076.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.393
• 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: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 10-27944440-G-GA is Benign according to our data. Variant chr10-27944440-G-GA is described in ClinVar as Benign. ClinVar VariationId is 541505.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000411 (62/150814) while in subpopulation NFE AF = 0.000725 (49/67612). AF 95% confidence interval is 0.000563. There are 0 homozygotes in GnomAd4. There are 25 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAD2	NM_018076.5	MANE Select	c.1534-10dupT		intron	N/A	NP_060546.2
	ODAD2	NM_001290020.2		c.1534-10dupT		intron	N/A	NP_001276949.1	A0A140VKF7
	ODAD2	NM_001312689.2		c.610-10dupT		intron	N/A	NP_001299618.1	A0A5F9ZH22

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAD2	ENST00000305242.10	TSL:1 MANE Select	c.1534-10_1534-9insT		intron	N/A	ENSP00000306410.5	Q5T2S8-1
	ODAD2	ENST00000673439.1		c.1534-10_1534-9insT		intron	N/A	ENSP00000500782.1	Q5T2S8-1
	ODAD2	ENST00000852623.1		c.1534-10_1534-9insT		intron	N/A	ENSP00000522682.1

Frequencies

GnomAD3 genomes AF: 0.000411 AC: 62 AN: 150700 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000292

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000660

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000725

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000587 AC: 126 AN: 214726 AF XY: 0.000498

Gnomad AFR exome AF: 0.000343

Gnomad AMR exome AF: 0.000467

Gnomad ASJ exome AF: 0.000119

Gnomad EAS exome AF: 0.000194

Gnomad FIN exome AF: 0.000364

Gnomad NFE exome AF: 0.000937

Gnomad OTH exome AF: 0.000392

GnomAD4 exome AF: 0.00122 AC: 1731 AN: 1419038 Hom.: 0 Cov.: 30 AF XY: 0.00108 AC XY: 766 AN XY: 706584

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000603 AC: 19 AN: 31506

American (AMR) AF: 0.000555 AC: 23 AN: 41460

Ashkenazi Jewish (ASJ) AF: 0.000238 AC: 6 AN: 25208

East Asian (EAS) AF: 0.000491 AC: 19 AN: 38668

South Asian (SAS) AF: 0.000337 AC: 28 AN: 83148

European-Finnish (FIN) AF: 0.000172 AC: 9 AN: 52332

Middle Eastern (MID) AF: 0.000719 AC: 4 AN: 5564

European-Non Finnish (NFE) AF: 0.00143 AC: 1550 AN: 1082660

Other (OTH) AF: 0.00125 AC: 73 AN: 58492

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000411 AC: 62 AN: 150814 Hom.: 0 Cov.: 32 AF XY: 0.000340 AC XY: 25 AN XY: 73626

African (AFR) AF: 0.000291 AC: 12 AN: 41182

American (AMR) AF: 0.0000660 AC: 1 AN: 15162

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4780

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10168

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.000725 AC: 49 AN: 67612

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00321 Hom.: 0

Bravo AF: 0.000393

Asia WGS AF: 0.00231 AC: 8 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Primary ciliary dyskinesia 23 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.39
Mutation Taster		=100/0	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: rs549508936; hg19: chr10-28233369;