rs1286999429

Variant names:

• chr10-27985216-C-A
• rs1286999429
• NM_018076.5:c.383-5G>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_018076.5(ODAD2):​c.383-5G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00188 in 1,112,320 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0011 (0 hom., cov: 28)
  • Exomes 𝑓: 0.0019 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ODAD2 NM_018076.5 splice_region, intron
• Scores: Splicing: ADA: 0.00003664
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.22
• Publications: 0 publications found

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]

ODAD2 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 23

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

LOC112268060 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 10-27985216-C-A is Benign according to our data. Variant chr10-27985216-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 474587.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODAD2	NM_018076.5	c.383-5G>T		splice_region_variant, intron_variant	Intron 3 of 19	ENST00000305242.10	NP_060546.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODAD2	ENST00000305242.10	c.383-5G>T		splice_region_variant, intron_variant	Intron 3 of 19	1	NM_018076.5	ENSP00000306410.5
ODAD2	ENST00000673439.1	c.383-5G>T		splice_region_variant, intron_variant	Intron 3 of 19			ENSP00000500782.1
ODAD2	ENST00000434029.1	n.65-5G>T		splice_region_variant, intron_variant	Intron 1 of 9	2

Frequencies

GnomAD3 genomes AF: 0.00111 AC: 137 AN: 123172 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.000914

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000574

Gnomad ASJ AF: 0.000335

Gnomad EAS AF: 0.000213

Gnomad SAS AF: 0.000248

Gnomad FIN AF: 0.00907

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000673

Gnomad OTH AF: 0.000608

GnomAD4 exome AF: 0.00188 AC: 2088 AN: 1112320 Hom.: 0 Cov.: 21 AF XY: 0.00223 AC XY: 1213 AN XY: 545120

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00152 AC: 37 AN: 24406

American (AMR) AF: 0.00621 AC: 106 AN: 17082

Ashkenazi Jewish (ASJ) AF: 0.00250 AC: 44 AN: 17574

East Asian (EAS) AF: 0.00441 AC: 136 AN: 30816

South Asian (SAS) AF: 0.00936 AC: 460 AN: 49158

European-Finnish (FIN) AF: 0.00254 AC: 75 AN: 29524

Middle Eastern (MID) AF: 0.00316 AC: 10 AN: 3164

European-Non Finnish (NFE) AF: 0.00127 AC: 1138 AN: 894542

Other (OTH) AF: 0.00178 AC: 82 AN: 46054

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00111 AC: 137 AN: 123182 Hom.: 0 Cov.: 28 AF XY: 0.00131 AC XY: 77 AN XY: 58956

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000912 AC: 31 AN: 33980

American (AMR) AF: 0.000573 AC: 7 AN: 12208

Ashkenazi Jewish (ASJ) AF: 0.000335 AC: 1 AN: 2984

East Asian (EAS) AF: 0.000214 AC: 1 AN: 4668

South Asian (SAS) AF: 0.000249 AC: 1 AN: 4016

European-Finnish (FIN) AF: 0.00907 AC: 57 AN: 6284

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 242

European-Non Finnish (NFE) AF: 0.000673 AC: 38 AN: 56424

Other (OTH) AF: 0.000602 AC: 1 AN: 1660

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00270 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary ciliary dyskinesia 23 Benign:1

May 08, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.050
DANN	Benign	0.49
PhyloP100		-1.2
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000037
dbscSNV1_RF	Benign	0.0060
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

Other links and lift over

dbSNP: rs1286999429; hg19: chr10-28274145;