rs57067036

Variant names:

• chr10-27968924-G-A
• rs57067036
• NM_018076.5:c.1237C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-27968924-G-A
• chr10-27968924-G-C

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.1237C>T​(p.Arg413Trp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 17/24 in silico tools predict 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R413Q) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., cov: 17)
  • Exomes 𝑓: 0.000046 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ODAD2 NM_018076.5 missense, splice_region
• Scores: Splicing: ADA: 0.002873
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.594
• Publications: 3 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009609461).
• BP6: Variant 10-27968924-G-A is Benign according to our data. Variant chr10-27968924-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3882565.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1237C>T	p.Arg413Trp	missense splice_region	Exon 9 of 20	NP_060546.2
	ODAD2	NM_001290020.2		c.1237C>T	p.Arg413Trp	missense splice_region	Exon 9 of 20	NP_001276949.1	A0A140VKF7
	ODAD2	NM_001312689.2		c.313C>T	p.Arg105Trp	missense splice_region	Exon 4 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.1237C>T	p.Arg413Trp	missense splice_region	Exon 9 of 20	ENSP00000306410.5	Q5T2S8-1
	ODAD2	ENST00000673439.1		c.1237C>T	p.Arg413Trp	missense splice_region	Exon 9 of 20	ENSP00000500782.1	Q5T2S8-1
	ODAD2	ENST00000852623.1		c.1237C>T	p.Arg413Trp	missense splice_region	Exon 9 of 20	ENSP00000522682.1

Frequencies

GnomAD3 genomes AF: 0.000167 AC: 22 AN: 131484 Hom.: 0 Cov.: 17

Gnomad AFR AF: 0.000588

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000779

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000163

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000149 AC: 11 AN: 73864 AF XY: 0.000218

Gnomad AFR exome AF: 0.00109

Gnomad AMR exome AF: 0.0000890

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000234

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000463

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000462 AC: 22 AN: 475702 Hom.: 0 Cov.: 5 AF XY: 0.0000553 AC XY: 14 AN XY: 253036

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

African (AFR) AF: 0.00111 AC: 14 AN: 12576

American (AMR) AF: 0.0000916 AC: 2 AN: 21834

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13766

East Asian (EAS) AF: 0.0000656 AC: 2 AN: 30482

South Asian (SAS) AF: 0.00 AC: 0 AN: 46742

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1900

European-Non Finnish (NFE) AF: 0.0000107 AC: 3 AN: 279816

Other (OTH) AF: 0.0000382 AC: 1 AN: 26182

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000385747), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000167 AC: 22 AN: 131604 Hom.: 0 Cov.: 17 AF XY: 0.000142 AC XY: 9 AN XY: 63240

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

African (AFR) AF: 0.000586 AC: 20 AN: 34138

American (AMR) AF: 0.0000778 AC: 1 AN: 12856

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3144

East Asian (EAS) AF: 0.00 AC: 0 AN: 4822

South Asian (SAS) AF: 0.00 AC: 0 AN: 3566

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8796

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 276

European-Non Finnish (NFE) AF: 0.0000163 AC: 1 AN: 61494

Other (OTH) AF: 0.00 AC: 0 AN: 1684

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000583022), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 28

ExAC AF: 0.000192 AC: 15

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	20
DANN	Benign	0.86
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.0096	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.59
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.16
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.99	D
Vest4		0.26
MutPred		0.36		Loss of methylation at R408 (P = 0.0385)
MVP		0.48
MPC		2.2
ClinPred		0.042	T
GERP RS		2.0
Varity_R		0.097
gMVP		0.22
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0029
dbscSNV1_RF	Benign	0.11
SpliceAI score (max)		0.030		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: rs57067036; hg19: chr10-28257853;