10-27812382-T-C

Variant names:

• chr10-27812382-T-C
• rs1061577
• NM_018076.5:c.*130A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018076.5(ODAD2):​c.*130A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 765,212 control chromosomes in the GnomAD database, including 6,600 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.098 (978 hom., cov: 33)
  • Exomes 𝑓: 0.13 (5622 hom.)
• Consequence: ODAD2 NM_018076.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.509
• Publications: 7 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: ClinGen, G2P, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 10-27812382-T-C is Benign according to our data. Variant chr10-27812382-T-C is described in ClinVar as Benign. ClinVar VariationId is 1222323.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018076.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAD2	NM_018076.5	MANE Select	c.*130A>G		3_prime_UTR	Exon 20 of 20	NP_060546.2
	ODAD2	NM_001290020.2		c.*130A>G		3_prime_UTR	Exon 20 of 20	NP_001276949.1	A0A140VKF7
	ODAD2	NM_001312689.2		c.*130A>G		3_prime_UTR	Exon 15 of 15	NP_001299618.1	A0A5F9ZH22

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAD2	ENST00000305242.10	TSL:1 MANE Select	c.*130A>G		3_prime_UTR	Exon 20 of 20	ENSP00000306410.5	Q5T2S8-1
	ODAD2	ENST00000673439.1		c.*130A>G		3_prime_UTR	Exon 20 of 20	ENSP00000500782.1	Q5T2S8-1
	ODAD2	ENST00000852623.1		c.*130A>G		3_prime_UTR	Exon 20 of 20	ENSP00000522682.1

Frequencies

GnomAD3 genomes AF: 0.0981 AC: 14923 AN: 152190 Hom.: 978 Cov.: 33

Gnomad AFR AF: 0.0258

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.0799

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.00211

Gnomad SAS AF: 0.0770

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.0913

GnomAD4 exome AF: 0.130 AC: 79807 AN: 612904 Hom.: 5622 Cov.: 8 AF XY: 0.128 AC XY: 41201 AN XY: 321164

African (AFR) AF: 0.0223 AC: 289 AN: 12974

American (AMR) AF: 0.0776 AC: 1037 AN: 13360

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 2126 AN: 17696

East Asian (EAS) AF: 0.000722 AC: 20 AN: 27690

South Asian (SAS) AF: 0.0872 AC: 4261 AN: 48846

European-Finnish (FIN) AF: 0.145 AC: 5738 AN: 39602

Middle Eastern (MID) AF: 0.0985 AC: 254 AN: 2578

European-Non Finnish (NFE) AF: 0.149 AC: 62329 AN: 418946

Other (OTH) AF: 0.120 AC: 3753 AN: 31212

GnomAD4 genome AF: 0.0980 AC: 14926 AN: 152308 Hom.: 978 Cov.: 33 AF XY: 0.0967 AC XY: 7203 AN XY: 74470

African (AFR) AF: 0.0257 AC: 1067 AN: 41584

American (AMR) AF: 0.0801 AC: 1225 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 445 AN: 3472

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5192

South Asian (SAS) AF: 0.0771 AC: 372 AN: 4828

European-Finnish (FIN) AF: 0.147 AC: 1554 AN: 10594

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9802 AN: 68020

Other (OTH) AF: 0.0908 AC: 192 AN: 2114

Alfa AF: 0.129 Hom.: 2179

Bravo AF: 0.0905

Asia WGS AF: 0.0390 AC: 134 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.0
DANN	Benign	0.51
PhyloP100		0.51
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs1061577; hg19: chr10-28101311; COSMIC: COSV59462963;