10-27944440-GA-GAA

Position:

• chr10-27944440-GA-GAA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 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

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 10-27944440-G-GA is Benign according to our data. Variant chr10-27944440-G-GA is described in ClinVar as [Benign]. Clinvar id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODAD2	NM_018076.5	c.1534-10dupT		intron_variant		ENST00000305242.10	NP_060546.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODAD2	ENST00000305242.10	c.1534-10dupT		intron_variant		1	NM_018076.5	ENSP00000306410.5

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

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

Gnomad4 AFR exome AF: 0.000603

Gnomad4 AMR exome AF: 0.000555

Gnomad4 ASJ exome AF: 0.000238

Gnomad4 EAS exome AF: 0.000491

Gnomad4 SAS exome AF: 0.000337

Gnomad4 FIN exome AF: 0.000172

Gnomad4 NFE exome AF: 0.00143

Gnomad4 OTH exome AF: 0.00125

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

Gnomad4 AFR AF: 0.000291

Gnomad4 AMR AF: 0.0000660

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000725

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000393

Asia WGS AF: 0.00231 AC: 8 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary ciliary dyskinesia 23 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs549508936; hg19: chr10-28233369;