rs35461177

chr19-48297657-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.1514C>T(p.Pro505Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 1,509,240 control chromosomes in the GnomAD database, including 55,586 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin ClinVar. Synonymous variant affecting the same amino acid position (i.e. P505P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.23 (4244 hom., cov: 31)
  • Exomes 𝑓: 0.27 (51342 hom.)
• Consequence: ODAD1 NM_001364171.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.798

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=0.0045309663).
• BP6: Variant 19-48297657-G-A is Benign according to our data. Variant chr19-48297657-G-A is described in ClinVar as [Benign]. Clinvar id is 262489.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODAD1	NM_001364171.2	c.1514C>T	p.Pro505Leu	missense_variant	15/16	ENST00000674294.1
ODAD1	NM_144577.4	c.1403C>T	p.Pro468Leu	missense_variant	13/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODAD1	ENST00000674294.1	c.1514C>T	p.Pro505Leu	missense_variant	15/16		NM_001364171.2	P2

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34235 AN: 151846 Hom.: 4240 Cov.: 31

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.241

GnomAD3 exomes AF: 0.235 AC: 38118 AN: 162302 Hom.: 4690 AF XY: 0.235 AC XY: 20081 AN XY: 85526

Gnomad AFR exome AF: 0.122

Gnomad AMR exome AF: 0.216

Gnomad ASJ exome AF: 0.221

Gnomad EAS exome AF: 0.135

Gnomad SAS exome AF: 0.158

Gnomad FIN exome AF: 0.276

Gnomad NFE exome AF: 0.284

Gnomad OTH exome AF: 0.253

GnomAD4 exome AF: 0.270 AC: 366654 AN: 1357276 Hom.: 51342 Cov.: 35 AF XY: 0.267 AC XY: 177537 AN XY: 664430

Gnomad4 AFR exome AF: 0.114

Gnomad4 AMR exome AF: 0.216

Gnomad4 ASJ exome AF: 0.216

Gnomad4 EAS exome AF: 0.136

Gnomad4 SAS exome AF: 0.164

Gnomad4 FIN exome AF: 0.278

Gnomad4 NFE exome AF: 0.290

Gnomad4 OTH exome AF: 0.252

GnomAD4 genome AF: 0.225 AC: 34249 AN: 151964 Hom.: 4244 Cov.: 31 AF XY: 0.222 AC XY: 16513 AN XY: 74284

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.239

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.287

Gnomad4 OTH AF: 0.238

Alfa AF: 0.257 Hom.: 2411

Bravo AF: 0.219

TwinsUK AF: 0.305 AC: 1130

ALSPAC AF: 0.283 AC: 1089

ESP6500AA AF: 0.129 AC: 567

ESP6500EA AF: 0.285 AC: 2455

ExAC AF: 0.223 AC: 26611

Asia WGS AF: 0.139 AC: 485 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

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 07, 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 provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.73
Cadd	Benign	18
Dann	Uncertain	1.0
DEOGEN2	Benign	0.0028	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.63	T
MetaRNN	Benign	0.0045	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.0	L
MutationTaster	Benign	0.72	P
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.046
Sift	Benign	0.051	T
Sift4G	Uncertain	0.0080	D
Polyphen		0.61	P
Vest4		0.093
MPC		0.77
ClinPred		0.050	T
GERP RS		1.8
Varity_R		0.054
gMVP		0.067

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: rs35461177; hg19: chr19-48800914; COSMIC: COSV59555917;