Variant rs114554656 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1

The NM_001364171.2(ODAD1):c.555C>T(p.Ile185=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000151 in 1,551,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00060 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

ODAD1
NM_001364171.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.56

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 19-48311595-G-A is Benign according to our data. Variant chr19-48311595-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 413796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.56 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000605 (92/152162) while in subpopulation AFR AF= 0.002 (83/41528). AF 95% confidence interval is 0.00165. There are 0 homozygotes in gnomad4. There are 47 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODAD1	NM_001364171.2 linkuse as main transcript	c.555C>T	p.Ile185=	synonymous_variant	7/16	ENST00000674294.1
ODAD1	NM_144577.4 linkuse as main transcript	c.444C>T	p.Ile148=	synonymous_variant	5/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODAD1	ENST00000674294.1 linkuse as main transcript	c.555C>T	p.Ile185=	synonymous_variant	7/16		NM_001364171.2	P2

Frequencies

GnomAD3 genomes

AF:

0.000612

AC:

AN:

152044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00200

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000961

GnomAD3 exomes

AF:

0.000173

AC:

AN:

156408

Hom.:

AF XY:

0.0000844

AC XY:

AN XY:

82918

show subpopulations

Gnomad AFR exome

AF:

0.00227

Gnomad AMR exome

AF:

0.000122

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000917

Gnomad SAS exome

AF:

0.0000878

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000496

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000102

AC:

143

AN:

1399030

Hom.:

Cov.:

AF XY:

0.0000898

AC XY:

AN XY:

690056

show subpopulations

Gnomad4 AFR exome

AF:

0.00260

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.0000406

Gnomad4 NFE exome

AF:

0.0000426

Gnomad4 OTH exome

AF:

0.000121

GnomAD4 genome

AF:

0.000605

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.000632

AC XY:

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.00200

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000951

Alfa

AF:

0.000344

Hom.:

Bravo

AF:

0.000729

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 12, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Aug 23, 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 disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 23, 2024

This variant is classified as likely 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

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.38

DANN

Benign

0.83

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over