rs1286999429

Positions:

• chr10-27985216-C-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_018076.5(ODAD2):​c.383-5G>T 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 0.00188 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, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00003664
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.22

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 -10 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.
• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00188 (2088/1112320) while in subpopulation SAS AF= 0.00936 (460/49158). AF 95% confidence interval is 0.00865. There are 0 homozygotes in gnomad4_exome. There are 1213 alleles in male gnomad4_exome subpopulation. Median coverage is 21. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODAD2	NM_018076.5	c.383-5G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000305242.10	NP_060546.2
LOC112268060	XR_002957065.1	n.86+1935C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODAD2	ENST00000305242.10	c.383-5G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_018076.5	ENSP00000306410	P1
ODAD2	ENST00000673439.1	c.383-5G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant				ENSP00000500782	P1
ODAD2	ENST00000434029.1	n.65-5G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 137 AN: 123172 Hom.: 0 Cov.: 28 FAILED QC

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

Gnomad4 AFR exome AF: 0.00152

Gnomad4 AMR exome AF: 0.00621

Gnomad4 ASJ exome AF: 0.00250

Gnomad4 EAS exome AF: 0.00441

Gnomad4 SAS exome AF: 0.00936

Gnomad4 FIN exome AF: 0.00254

Gnomad4 NFE exome AF: 0.00127

Gnomad4 OTH exome AF: 0.00178

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

Gnomad4 AFR AF: 0.000912

Gnomad4 AMR AF: 0.000573

Gnomad4 ASJ AF: 0.000335

Gnomad4 EAS AF: 0.000214

Gnomad4 SAS AF: 0.000249

Gnomad4 FIN AF: 0.00907

Gnomad4 NFE AF: 0.000673

Gnomad4 OTH AF: 0.000602

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

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.050
DANN	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs1286999429; hg19: chr10-28274145;