rs145629439

chr19-48303998-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001364171.2(ODAD1):c.808G>A(p.Asp270Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000784 in 1,614,204 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0010 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00076 (9 hom.)
• Consequence: ODAD1 NM_001364171.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.74

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=0.010653675).
• BP6: Variant 19-48303998-C-T is Benign according to our data. Variant chr19-48303998-C-T is described in ClinVar as [Benign]. Clinvar id is 413797.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00101 (154/152350) while in subpopulation EAS AF= 0.0128 (66/5174). AF 95% confidence interval is 0.0103. There are 0 homozygotes in gnomad4. There are 101 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODAD1	NM_001364171.2	c.808G>A	p.Asp270Asn	missense_variant	9/16	ENST00000674294.1
ODAD1	NM_144577.4	c.697G>A	p.Asp233Asn	missense_variant	7/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODAD1	ENST00000674294.1	c.808G>A	p.Asp270Asn	missense_variant	9/16		NM_001364171.2	P2
ODAD1	ENST00000315396.7	c.697G>A	p.Asp233Asn	missense_variant	7/14	1		A2
ODAD1	ENST00000474199.6	c.808G>A	p.Asp270Asn	missense_variant	9/15	2		A2
ODAD1	ENST00000674207.1	c.*516G>A		3_prime_UTR_variant, NMD_transcript_variant	7/13

Frequencies

GnomAD3 genomes AF: 0.00101 AC: 154 AN: 152232 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0127

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00583

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00175 AC: 439 AN: 251378 Hom.: 5 AF XY: 0.00168 AC XY: 228 AN XY: 135870

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.0132

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00559

Gnomad NFE exome AF: 0.000484

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.000761 AC: 1112 AN: 1461854 Hom.: 9 Cov.: 33 AF XY: 0.000765 AC XY: 556 AN XY: 727232

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.000459

Gnomad4 EAS exome AF: 0.0128

Gnomad4 SAS exome AF: 0.000186

Gnomad4 FIN exome AF: 0.00592

Gnomad4 NFE exome AF: 0.000170

Gnomad4 OTH exome AF: 0.00109

GnomAD4 genome AF: 0.00101 AC: 154 AN: 152350 Hom.: 0 Cov.: 33 AF XY: 0.00136 AC XY: 101 AN XY: 74506

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0128

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00583

Gnomad4 NFE AF: 0.000367

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000686 Hom.: 0

Bravo AF: 0.000552

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.00177 AC: 215

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Jan 11, 2021	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. -

ODAD1-related condition Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 03, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.66
Cadd	Benign	20
Dann	Uncertain	1.0
DEOGEN2	Benign	0.035	T
Eigen	Benign	0.037
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.76	T
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.093
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.016	D
Polyphen		0.99	D
Vest4		0.28
MVP		0.32
MPC		0.70
ClinPred		0.057	T
GERP RS		3.4
Varity_R		0.11
gMVP		0.11

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: rs145629439; hg19: chr19-48807255; COSMIC: COSV59558128; COSMIC: COSV59558128;