Variant rs779459076 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PM4_SupportingBS1_Supporting

The NM_001364171.2(ODAD1):c.498_499insCGT(p.Phe166_Asp167insArg) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000524 in 1,549,544 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00055 ( 0 hom. )

Consequence

ODAD1
NM_001364171.2 inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:4

Conservation

PhyloP100: 0.749

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM4

Nonframeshift variant in NON repetitive region in NM_001364171.2. Strenght limited to Supporting due to length of the change: 1aa.

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.000555 (775/1397324) while in subpopulation NFE AF= 0.00069 (743/1077114). AF 95% confidence interval is 0.000649. There are 0 homozygotes in gnomad4_exome. There are 358 alleles in male gnomad4_exome subpopulation. Median coverage is 29. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODAD1	NM_001364171.2 linkuse as main transcript	c.498_499insCGT	p.Phe166_Asp167insArg	inframe_insertion	7/16	ENST00000674294.1
ODAD1	NM_144577.4 linkuse as main transcript	c.387_388insCGT	p.Phe129_Asp130insArg	inframe_insertion	5/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODAD1	ENST00000674294.1 linkuse as main transcript	c.498_499insCGT	p.Phe166_Asp167insArg	inframe_insertion	7/16		NM_001364171.2	P2

Frequencies

GnomAD3 genomes

AF:

0.000243

AC:

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000276

AC:

AN:

155956

Hom.:

AF XY:

0.000145

AC XY:

AN XY:

82686

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000810

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000679

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000555

AC:

775

AN:

1397324

Hom.:

Cov.:

AF XY:

0.000519

AC XY:

358

AN XY:

689318

show subpopulations

Gnomad4 AFR exome

AF:

0.0000317

Gnomad4 AMR exome

AF:

0.000168

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.000101

Gnomad4 NFE exome

AF:

0.000690

Gnomad4 OTH exome

AF:

0.000328

GnomAD4 genome

AF:

0.000243

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000485

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000587

Hom.:

Bravo

AF:

0.000291

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	Invitae	Jul 05, 2022	This variant, c.387_388insCGT, results in the insertion of 1 amino acid(s) of the CCDC114 protein (p.Phe129_Asp130insArg), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs779459076, gnomAD 0.06%). This variant has been observed in individual(s) with primary ciliary dyskinesia (PMID: 32111882). This variant is also known as rs779459076, C/CACG ‚àí/R. ClinVar contains an entry for this variant (Variation ID: 406183). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Uncertain significance, criteria provided, single submitter	clinical testing	Ambry Genetics	Nov 01, 2017	The c.387_388insCGT variant (also known as p.F129_D130insR), located in coding exon 4 of the CCDC114 gene, results from an in-frame CGT insertion at nucleotide positions 387 to 388. This results in the insertion of an extra arginine residue between codons 129 and 130. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -

ODAD1-related disorder

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 19, 2023

The ODAD1 c.387_388insCGT variant is predicted to result in an in-frame amino acid insertion (p.Phe129_Asp130insArg). This variant has been reported in the homozygous state in an individual with primary ciliary dyskinesia (patient SI13, Postema MC et al 2020. PubMed ID: 32111882). This variant is reported in 0.063% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Primary ciliary dyskinesia 20

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Jan 14, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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