rs117723546

chr10-27971233-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_018076.5(ODAD2):c.1017C>T(p.Leu339=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00549 in 1,613,904 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0037 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0057 (31 hom.)
• Consequence: ODAD2 NM_018076.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.111

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 Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 10-27971233-G-A is Benign according to our data. Variant chr10-27971233-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 241254.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-27971233-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.111 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00367 (558/152226) while in subpopulation NFE AF= 0.00642 (437/68020). AF 95% confidence interval is 0.00593. There are 5 homozygotes in gnomad4. There are 249 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODAD2	NM_018076.5	c.1017C>T	p.Leu339=	synonymous_variant	8/20	ENST00000305242.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODAD2	ENST00000305242.10	c.1017C>T	p.Leu339=	synonymous_variant	8/20	1	NM_018076.5	P1

Frequencies

GnomAD3 genomes AF: 0.00367 AC: 558 AN: 152108 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00133

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00210

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00642

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00391 AC: 981 AN: 251114 Hom.: 2 AF XY: 0.00380 AC XY: 515 AN XY: 135696

Gnomad AFR exome AF: 0.00123

Gnomad AMR exome AF: 0.00243

Gnomad ASJ exome AF: 0.00228

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000196

Gnomad FIN exome AF: 0.00171

Gnomad NFE exome AF: 0.00688

Gnomad OTH exome AF: 0.00490

GnomAD4 exome AF: 0.00568 AC: 8302 AN: 1461678 Hom.: 31 Cov.: 31 AF XY: 0.00544 AC XY: 3953 AN XY: 727128

Gnomad4 AFR exome AF: 0.000867

Gnomad4 AMR exome AF: 0.00257

Gnomad4 ASJ exome AF: 0.00172

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000186

Gnomad4 FIN exome AF: 0.00155

Gnomad4 NFE exome AF: 0.00698

Gnomad4 OTH exome AF: 0.00411

GnomAD4 genome AF: 0.00367 AC: 558 AN: 152226 Hom.: 5 Cov.: 32 AF XY: 0.00335 AC XY: 249 AN XY: 74424

Gnomad4 AFR AF: 0.00132

Gnomad4 AMR AF: 0.00209

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00132

Gnomad4 NFE AF: 0.00642

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00542 Hom.: 0

Bravo AF: 0.00377

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	ODAD2: BP4, BP7, BS2 -

Primary ciliary dyskinesia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 27, 2016

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Primary ciliary dyskinesia 23 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.23
Dann	Benign	0.43

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: rs117723546; hg19: chr10-28260162;