chr10-27853365-T-TATAAATAAATAAATAA

Position:

• chr10-27853365-T-TATAAATAAATAAATAA

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

The NM_018076.5(ODAD2):​c.3021+7259_3021+7260insTTATTTATTTATTTAT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.025 (147 hom., cov: 0)
  • Exomes 𝑓: 0.00098 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: ODAD2 NM_018076.5 intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.208

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 -9 ACMG points.

• BP6: Variant 10-27853365-T-TATAAATAAATAAATAA is Benign according to our data. Variant chr10-27853365-T-TATAAATAAATAAATAA is described in ClinVar as [Benign]. Clinvar id is 3056408.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODAD2	NM_018076.5	c.3021+7259_3021+7260insTTATTTATTTATTTAT		intron_variant		ENST00000305242.10	NP_060546.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODAD2	ENST00000305242.10	c.3021+7259_3021+7260insTTATTTATTTATTTAT		intron_variant		1	NM_018076.5	ENSP00000306410	P1

Frequencies

GnomAD3 genomes AF: 0.0249 AC: 3676 AN: 147810 Hom.: 147 Cov.: 0

Gnomad AFR AF: 0.0830

Gnomad AMI AF: 0.00226

Gnomad AMR AF: 0.00920

Gnomad ASJ AF: 0.00408

Gnomad EAS AF: 0.000592

Gnomad SAS AF: 0.000434

Gnomad FIN AF: 0.00573

Gnomad MID AF: 0.0133

Gnomad NFE AF: 0.00161

Gnomad OTH AF: 0.0158

GnomAD3 exomes AF: 0.000271 AC: 7 AN: 25874 Hom.: 0 AF XY: 0.000396 AC XY: 6 AN XY: 15162

Gnomad AFR exome AF: 0.00151

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00104

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000182

Gnomad FIN exome AF: 0.00191

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000984 AC: 111 AN: 112822 Hom.: 2 Cov.: 0 AF XY: 0.00102 AC XY: 72 AN XY: 70716

Gnomad4 AFR exome AF: 0.0164

Gnomad4 AMR exome AF: 0.000549

Gnomad4 ASJ exome AF: 0.00228

Gnomad4 EAS exome AF: 0.000733

Gnomad4 SAS exome AF: 0.0000977

Gnomad4 FIN exome AF: 0.00210

Gnomad4 NFE exome AF: 0.000678

Gnomad4 OTH exome AF: 0.00188

GnomAD4 genome AF: 0.0249 AC: 3685 AN: 147916 Hom.: 147 Cov.: 0 AF XY: 0.0241 AC XY: 1737 AN XY: 71952

Gnomad4 AFR AF: 0.0830

Gnomad4 AMR AF: 0.00912

Gnomad4 ASJ AF: 0.00408

Gnomad4 EAS AF: 0.000593

Gnomad4 SAS AF: 0.000435

Gnomad4 FIN AF: 0.00573

Gnomad4 NFE AF: 0.00161

Gnomad4 OTH AF: 0.0156

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

ODAD2-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 20, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs143299831; hg19: chr10-28142294;