rs61747754

chr19-48297494-C-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.1606G>T(p.Ala536Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 1,602,864 control chromosomes in the GnomAD database, including 22,199 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A536L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.14 (1762 hom., cov: 32)
  • Exomes 𝑓: 0.16 (20437 hom.)
• Consequence: ODAD1 NM_001364171.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.193

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=0.0024385154).
• BP6: Variant 19-48297494-C-A is Benign according to our data. Variant chr19-48297494-C-A is described in ClinVar as [Benign]. Clinvar id is 262491.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODAD1	NM_001364171.2	c.1606G>T	p.Ala536Ser	missense_variant	16/16	ENST00000674294.1
ODAD1	NM_144577.4	c.1495G>T	p.Ala499Ser	missense_variant	14/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODAD1	ENST00000674294.1	c.1606G>T	p.Ala536Ser	missense_variant	16/16		NM_001364171.2	P2

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21824 AN: 151942 Hom.: 1764 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.0986

Gnomad FIN AF: 0.0727

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.158

GnomAD3 exomes AF: 0.128 AC: 29332 AN: 229090 Hom.: 2220 AF XY: 0.131 AC XY: 16464 AN XY: 125248

Gnomad AFR exome AF: 0.131

Gnomad AMR exome AF: 0.0829

Gnomad ASJ exome AF: 0.252

Gnomad EAS exome AF: 0.000228

Gnomad SAS exome AF: 0.109

Gnomad FIN exome AF: 0.0715

Gnomad NFE exome AF: 0.167

Gnomad OTH exome AF: 0.155

GnomAD4 exome AF: 0.161 AC: 234267 AN: 1450804 Hom.: 20437 Cov.: 63 AF XY: 0.160 AC XY: 115309 AN XY: 721414

Gnomad4 AFR exome AF: 0.137

Gnomad4 AMR exome AF: 0.0900

Gnomad4 ASJ exome AF: 0.260

Gnomad4 EAS exome AF: 0.000278

Gnomad4 SAS exome AF: 0.112

Gnomad4 FIN exome AF: 0.0770

Gnomad4 NFE exome AF: 0.176

Gnomad4 OTH exome AF: 0.165

GnomAD4 genome AF: 0.144 AC: 21830 AN: 152060 Hom.: 1762 Cov.: 32 AF XY: 0.136 AC XY: 10104 AN XY: 74342

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0985

Gnomad4 FIN AF: 0.0727

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.157

Alfa AF: 0.169 Hom.: 2327

Bravo AF: 0.148

TwinsUK AF: 0.182 AC: 674

ALSPAC AF: 0.181 AC: 696

ESP6500AA AF: 0.138 AC: 607

ESP6500EA AF: 0.169 AC: 1445

ExAC AF: 0.123 AC: 14837

Asia WGS AF: 0.0460 AC: 162 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 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 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	0.086
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
Cadd	Benign	8.1
Dann	Benign	0.57
DEOGEN2	Benign	0.00079	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.40	T
MetaRNN	Benign	0.0024	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.34	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.18	N
REVEL	Benign	0.060
Sift	Benign	0.55	T
Sift4G	Benign	1.0	T
Polyphen		0.091	B
Vest4		0.041
MPC		0.21
ClinPred		0.0013	T
GERP RS		0.55
Varity_R		0.038
gMVP		0.061

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: rs61747754; hg19: chr19-48800751;