rs201203284

Positions:

• chr10-27907784-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_018076.5(ODAD2):​c.2496-7A>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00152 in 1,590,070 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (3 hom.)
• Consequence: ODAD2 NM_018076.5 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00003916
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.148

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 10-27907784-T-C is Benign according to our data. Variant chr10-27907784-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 241262.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00131 (200/152316) while in subpopulation NFE AF= 0.00172 (117/68028). AF 95% confidence interval is 0.00147. There are 2 homozygotes in gnomad4. There are 97 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODAD2	NM_018076.5	c.2496-7A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000305242.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODAD2	ENST00000305242.10	c.2496-7A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_018076.5	P1

Frequencies

GnomAD3 genomes AF: 0.00131 AC: 200 AN: 152198 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00264

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00172

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00135 AC: 339 AN: 250576 Hom.: 0 AF XY: 0.00124 AC XY: 168 AN XY: 135396

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000870

Gnomad ASJ exome AF: 0.00437

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00245

Gnomad NFE exome AF: 0.00171

Gnomad OTH exome AF: 0.00245

GnomAD4 exome AF: 0.00154 AC: 2213 AN: 1437754 Hom.: 3 Cov.: 26 AF XY: 0.00146 AC XY: 1049 AN XY: 716938

Gnomad4 AFR exome AF: 0.000152

Gnomad4 AMR exome AF: 0.000873

Gnomad4 ASJ exome AF: 0.00493

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000233

Gnomad4 FIN exome AF: 0.00206

Gnomad4 NFE exome AF: 0.00167

Gnomad4 OTH exome AF: 0.00176

GnomAD4 genome AF: 0.00131 AC: 200 AN: 152316 Hom.: 2 Cov.: 33 AF XY: 0.00130 AC XY: 97 AN XY: 74468

Gnomad4 AFR AF: 0.000265

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.00634

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00264

Gnomad4 NFE AF: 0.00172

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00165 Hom.: 0

Bravo AF: 0.00111

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary ciliary dyskinesia 23 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.43
DANN	Benign	0.36

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000039
dbscSNV1_RF	Benign	0.058
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: rs201203284; hg19: chr10-28196713;