Variant rs34159194 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_023036.6(DNAI2):c.834C>T(p.Thr278=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 1,613,300 control chromosomes in the GnomAD database, including 25,959 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1593 hom., cov: 32)

Exomes 𝑓: 0.18 ( 24366 hom. )

Consequence

DNAI2
NM_023036.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -6.05

Variant links:

Genes affected

DNAI2 (HGNC:18744): (dynein axonemal intermediate chain 2) The protein encoded by this gene belongs to the dynein intermediate chain family, and is part of the dynein complex of respiratory cilia and sperm flagella. Mutations in this gene are associated with primary ciliary dyskinesia type 9. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Mar 2010]

DNAI2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 17-74299827-C-T is Benign according to our data. Variant chr17-74299827-C-T is described in ClinVar as [Benign]. Clinvar id is 163167.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-74299827-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-6.05 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAI2	NM_023036.6 linkuse as main transcript	c.834C>T	p.Thr278=	synonymous_variant	7/14	ENST00000311014.11	NP_075462.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAI2	ENST00000311014.11 linkuse as main transcript	c.834C>T	p.Thr278=	synonymous_variant	7/14	1	NM_023036.6	ENSP00000308312	P2	Q9GZS0-1

Frequencies

GnomAD3 genomes

AF:

0.127

AC:

19313

AN:

151972

Hom.:

1593

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0376

Gnomad AMI

AF:

0.129

Gnomad AMR

AF:

0.0945

Gnomad ASJ

AF:

0.135

Gnomad EAS

AF:

0.00327

Gnomad SAS

AF:

0.124

Gnomad FIN

AF:

0.196

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.188

Gnomad OTH

AF:

0.112

GnomAD3 exomes

AF:

0.138

AC:

34550

AN:

250330

Hom.:

3003

AF XY:

0.144

AC XY:

19443

AN XY:

135358

show subpopulations

Gnomad AFR exome

AF:

0.0351

Gnomad AMR exome

AF:

0.0644

Gnomad ASJ exome

AF:

0.125

Gnomad EAS exome

AF:

0.00234

Gnomad SAS exome

AF:

0.133

Gnomad FIN exome

AF:

0.196

Gnomad NFE exome

AF:

0.189

Gnomad OTH exome

AF:

0.138

GnomAD4 exome

AF:

0.176

AC:

256543

AN:

1461210

Hom.:

24366

Cov.:

AF XY:

0.175

AC XY:

127412

AN XY:

726880

show subpopulations

Gnomad4 AFR exome

AF:

0.0314

Gnomad4 AMR exome

AF:

0.0668

Gnomad4 ASJ exome

AF:

0.127

Gnomad4 EAS exome

AF:

0.00108

Gnomad4 SAS exome

AF:

0.135

Gnomad4 FIN exome

AF:

0.197

Gnomad4 NFE exome

AF:

0.196

Gnomad4 OTH exome

AF:

0.146

GnomAD4 genome

AF:

0.127

AC:

19313

AN:

152090

Hom.:

1593

Cov.:

AF XY:

0.125

AC XY:

9294

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.0374

Gnomad4 AMR

AF:

0.0943

Gnomad4 ASJ

AF:

0.135

Gnomad4 EAS

AF:

0.00328

Gnomad4 SAS

AF:

0.126

Gnomad4 FIN

AF:

0.196

Gnomad4 NFE

AF:

0.188

Gnomad4 OTH

AF:

0.111

Alfa

AF:

0.163

Hom.:

1484

Bravo

AF:

0.114

Asia WGS

AF:

0.0560

AC:

196

AN:

3478

EpiCase

AF:

0.174

EpiControl

AF:

0.170

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	Thr278Thr in exon 7 of DNAI2: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 18.7% (1612/8600) of European American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs34159194). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Primary ciliary dyskinesia 9

Benign:3

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -

Primary ciliary dyskinesia

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Dec 10, 2014	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. -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.18

DANN

Benign

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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