rs16981988

chr19-48318500-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001364171.2(ODAD1):c.247C>T(p.Arg83Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0254 in 1,551,582 control chromosomes in the GnomAD database, including 621 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.031 (99 hom., cov: 31)
  • Exomes 𝑓: 0.025 (522 hom.)
• Consequence: ODAD1 NM_001364171.2 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.350

Genes affected

ODAD1 (HGNC:26560): (outer dynein arm docking complex subunit 1) This gene encodes a coiled-coil domain-containing protein that is a component of the outer dynein arm docking complex in cilia cells. Mutations in this gene may cause primary ciliary dyskinesia 20. [provided by RefSeq, May 2013]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0030530393).
• BP6: Variant 19-48318500-G-A is Benign according to our data. Variant chr19-48318500-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 262487.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-48318500-G-A is described in Lovd as [Benign].
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODAD1	NM_001364171.2	c.247C>T	p.Arg83Trp	missense_variant	5/16	ENST00000674294.1
ODAD1	NM_144577.4	c.136C>T	p.Arg46Trp	missense_variant	3/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODAD1	ENST00000674294.1	c.247C>T	p.Arg83Trp	missense_variant	5/16		NM_001364171.2	P2

Frequencies

GnomAD3 genomes AF: 0.0314 AC: 4778 AN: 152108 Hom.: 98 Cov.: 31

Gnomad AFR AF: 0.0504

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.0258

Gnomad ASJ AF: 0.0473

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.0315

Gnomad FIN AF: 0.00858

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0253

Gnomad OTH AF: 0.0306

GnomAD3 exomes AF: 0.0258 AC: 4016 AN: 155636 Hom.: 62 AF XY: 0.0273 AC XY: 2254 AN XY: 82550

Gnomad AFR exome AF: 0.0512

Gnomad AMR exome AF: 0.0190

Gnomad ASJ exome AF: 0.0412

Gnomad EAS exome AF: 0.00376

Gnomad SAS exome AF: 0.0350

Gnomad FIN exome AF: 0.00884

Gnomad NFE exome AF: 0.0275

Gnomad OTH exome AF: 0.0354

GnomAD4 exome AF: 0.0248 AC: 34666 AN: 1399356 Hom.: 522 Cov.: 31 AF XY: 0.0254 AC XY: 17511 AN XY: 690188

Gnomad4 AFR exome AF: 0.0545

Gnomad4 AMR exome AF: 0.0214

Gnomad4 ASJ exome AF: 0.0399

Gnomad4 EAS exome AF: 0.00151

Gnomad4 SAS exome AF: 0.0349

Gnomad4 FIN exome AF: 0.00983

Gnomad4 NFE exome AF: 0.0237

Gnomad4 OTH exome AF: 0.0295

GnomAD4 genome AF: 0.0314 AC: 4786 AN: 152226 Hom.: 99 Cov.: 31 AF XY: 0.0311 AC XY: 2316 AN XY: 74424

Gnomad4 AFR AF: 0.0505

Gnomad4 AMR AF: 0.0258

Gnomad4 ASJ AF: 0.0473

Gnomad4 EAS AF: 0.00289

Gnomad4 SAS AF: 0.0315

Gnomad4 FIN AF: 0.00858

Gnomad4 NFE AF: 0.0253

Gnomad4 OTH AF: 0.0303

Alfa AF: 0.0278 Hom.: 126

Bravo AF: 0.0336

TwinsUK AF: 0.0232 AC: 86

ALSPAC AF: 0.0210 AC: 81

ESP6500AA AF: 0.0455 AC: 63

ESP6500EA AF: 0.0286 AC: 91

ExAC AF: 0.0289 AC: 745

Asia WGS AF: 0.0200 AC: 71 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Jul 08, 2016	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Primary ciliary dyskinesia 20 Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Nov 29, 2023

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 10, 2022

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.51
Cadd	Benign	22
Dann	Uncertain	1.0
DEOGEN2	Benign	0.038	T
Eigen	Benign	-0.070
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.54	D
LIST_S2	Uncertain	0.87	D
MetaRNN	Benign	0.0031	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
MutationTaster	Benign	0.50	D
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Benign	0.15
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.18
MPC		0.80
ClinPred		0.023	T
GERP RS		-0.63
Varity_R		0.14
gMVP		0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs16981988; hg19: chr19-48821757; COSMIC: COSV59557885; COSMIC: COSV59557885;