chr19-48297076-G-A

Position:

• chr19-48297076-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.2024C>T​(p.Ser675Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0375 in 1,613,142 control chromosomes in the GnomAD database, including 1,204 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.044 (184 hom., cov: 32)
  • Exomes 𝑓: 0.037 (1020 hom.)
• Consequence: ODAD1 NM_001364171.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.684

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]

ODAD1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0040144324).
• BP6: Variant 19-48297076-G-A is Benign according to our data. Variant chr19-48297076-G-A is described in ClinVar as [Benign]. Clinvar id is 262497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-48297076-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODAD1	NM_001364171.2	c.2024C>T	p.Ser675Leu	missense_variant	16/16	ENST00000674294.1	NP_001351100.1
ODAD1	NM_144577.4	c.1913C>T	p.Ser638Leu	missense_variant	14/14		NP_653178.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODAD1	ENST00000674294.1	c.2024C>T	p.Ser675Leu	missense_variant	16/16		NM_001364171.2	ENSP00000501363.1

Frequencies

GnomAD3 genomes AF: 0.0445 AC: 6762 AN: 152032 Hom.: 185 Cov.: 32

Gnomad AFR AF: 0.0736

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0252

Gnomad ASJ AF: 0.0415

Gnomad EAS AF: 0.0285

Gnomad SAS AF: 0.0308

Gnomad FIN AF: 0.0177

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0375

Gnomad OTH AF: 0.0345

GnomAD3 exomes AF: 0.0359 AC: 9016 AN: 250804 Hom.: 204 AF XY: 0.0354 AC XY: 4804 AN XY: 135684

Gnomad AFR exome AF: 0.0789

Gnomad AMR exome AF: 0.0171

Gnomad ASJ exome AF: 0.0369

Gnomad EAS exome AF: 0.0315

Gnomad SAS exome AF: 0.0365

Gnomad FIN exome AF: 0.0181

Gnomad NFE exome AF: 0.0396

Gnomad OTH exome AF: 0.0316

GnomAD4 exome AF: 0.0368 AC: 53736 AN: 1460992 Hom.: 1020 Cov.: 34 AF XY: 0.0367 AC XY: 26700 AN XY: 726836

Gnomad4 AFR exome AF: 0.0727

Gnomad4 AMR exome AF: 0.0185

Gnomad4 ASJ exome AF: 0.0359

Gnomad4 EAS exome AF: 0.0315

Gnomad4 SAS exome AF: 0.0361

Gnomad4 FIN exome AF: 0.0180

Gnomad4 NFE exome AF: 0.0377

Gnomad4 OTH exome AF: 0.0353

GnomAD4 genome AF: 0.0444 AC: 6758 AN: 152150 Hom.: 184 Cov.: 32 AF XY: 0.0424 AC XY: 3157 AN XY: 74394

Gnomad4 AFR AF: 0.0734

Gnomad4 AMR AF: 0.0251

Gnomad4 ASJ AF: 0.0415

Gnomad4 EAS AF: 0.0287

Gnomad4 SAS AF: 0.0307

Gnomad4 FIN AF: 0.0177

Gnomad4 NFE AF: 0.0375

Gnomad4 OTH AF: 0.0342

Alfa AF: 0.0343 Hom.: 62

Bravo AF: 0.0471

TwinsUK AF: 0.0356 AC: 132

ALSPAC AF: 0.0379 AC: 146

ESP6500AA AF: 0.0760 AC: 335

ESP6500EA AF: 0.0399 AC: 343

ExAC AF: 0.0387 AC: 4694

Asia WGS AF: 0.0340 AC: 119 AN: 3478

EpiCase AF: 0.0404

EpiControl AF: 0.0379

ClinVar

Significance: 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	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Jul 21, 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:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 19, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.6
DANN	Benign	0.86
DEOGEN2	Benign	0.00066	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.085	N
LIST_S2	Benign	0.55	T
MetaRNN	Benign	0.0040	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.63	N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.050
Sift	Benign	0.59	T
Sift4G	Benign	1.0	T
Polyphen		0.026	B
Vest4		0.038
MPC		0.57
ClinPred		0.0032	T
GERP RS		0.47
Varity_R		0.032
gMVP		0.073

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: rs74925056; hg19: chr19-48800333;