rs117723546

Variant names:

• chr10-27971233-G-A
• rs117723546
• NM_018076.5:c.1017C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_018076.5(ODAD2):​c.1017C>T​(p.Leu339Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00549 in 1,613,904 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0037 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0057 (31 hom.)
• Consequence: ODAD2 NM_018076.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.111
• Publications: 1 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 10-27971233-G-A is Benign according to our data. Variant chr10-27971233-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 241254.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.111 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00367 (558/152226) while in subpopulation NFE AF = 0.00642 (437/68020). AF 95% confidence interval is 0.00593. There are 5 homozygotes in GnomAd4. There are 249 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 AD,AR gene

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.1017C>T	p.Leu339Leu	synonymous	Exon 8 of 20	NP_060546.2
	ODAD2	NM_001290020.2		c.1017C>T	p.Leu339Leu	synonymous	Exon 8 of 20	NP_001276949.1	A0A140VKF7
	ODAD2	NM_001312689.2		c.93C>T	p.Leu31Leu	synonymous	Exon 3 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.1017C>T	p.Leu339Leu	synonymous	Exon 8 of 20	ENSP00000306410.5	Q5T2S8-1
	ODAD2	ENST00000673439.1		c.1017C>T	p.Leu339Leu	synonymous	Exon 8 of 20	ENSP00000500782.1	Q5T2S8-1
	ODAD2	ENST00000852623.1		c.1017C>T	p.Leu339Leu	synonymous	Exon 8 of 20	ENSP00000522682.1

Frequencies

GnomAD3 genomes AF: 0.00367 AC: 558 AN: 152108 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00133

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00210

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00642

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00391 AC: 981 AN: 251114 AF XY: 0.00380

Gnomad AFR exome AF: 0.00123

Gnomad AMR exome AF: 0.00243

Gnomad ASJ exome AF: 0.00228

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00171

Gnomad NFE exome AF: 0.00688

Gnomad OTH exome AF: 0.00490

GnomAD4 exome AF: 0.00568 AC: 8302 AN: 1461678 Hom.: 31 Cov.: 31 AF XY: 0.00544 AC XY: 3953 AN XY: 727128

African (AFR) AF: 0.000867 AC: 29 AN: 33466

American (AMR) AF: 0.00257 AC: 115 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00172 AC: 45 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.000186 AC: 16 AN: 86248

European-Finnish (FIN) AF: 0.00155 AC: 83 AN: 53414

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5766

European-Non Finnish (NFE) AF: 0.00698 AC: 7763 AN: 1111882

Other (OTH) AF: 0.00411 AC: 248 AN: 60388

GnomAD4 genome AF: 0.00367 AC: 558 AN: 152226 Hom.: 5 Cov.: 32 AF XY: 0.00335 AC XY: 249 AN XY: 74424

African (AFR) AF: 0.00132 AC: 55 AN: 41536

American (AMR) AF: 0.00209 AC: 32 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00132 AC: 14 AN: 10598

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00642 AC: 437 AN: 68020

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.00542 Hom.: 0

Bravo AF: 0.00377

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Primary ciliary dyskinesia (1)
-	-	1	Primary ciliary dyskinesia 23 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.23
DANN	Benign	0.43
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism

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: rs117723546; hg19: chr10-28260162;