rs12777433

Positions:

• chr10-27985204-T-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_018076.5(ODAD2):​c.390A>G​(p.Arg130=) 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:3
• Conservation: PhyloP100: 1.78

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]

LOC112268060 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODAD2	NM_018076.5	c.390A>G	p.Arg130=	synonymous_variant	4/20	ENST00000305242.10
LOC112268060	XR_002957065.1	n.86+1923T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODAD2	ENST00000305242.10	c.390A>G	p.Arg130=	synonymous_variant	4/20	1	NM_018076.5	P1
ODAD2	ENST00000673439.1	c.390A>G	p.Arg130=	synonymous_variant	4/20			P1
ODAD2	ENST00000434029.1	n.72A>G		non_coding_transcript_exon_variant	2/10	2

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

GnomAD3 exomes AF: 0.00167 AC: 205 AN: 122926 Hom.: 0 AF XY: 0.00146 AC XY: 98 AN XY: 66910

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 SAS 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

Gnomad4 AFR exome AF: 0.000410

Gnomad4 AMR exome AF: 0.00129

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000457

Gnomad4 NFE exome AF: 0.00320

Gnomad4 OTH exome AF: 0.00259

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

Gnomad4 AFR AF: 0.000617

Gnomad4 AMR AF: 0.00388

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000199

Gnomad4 NFE AF: 0.00263

Gnomad4 OTH AF: 0.00145

Alfa AF: 0.00223 Hom.: 0

Bravo AF: 0.00212

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 21, 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. -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 22, 2021

- -

Primary ciliary dyskinesia 23 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	11
DANN	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs12777433; hg19: chr10-28274133;