chr17-74299827-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_023036.6(DNAI2):c.834C>T(p.Thr278Thr) 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

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 9
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DNAI2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 163167.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
DNAI2	NM_023036.6 link	c.834C>T	p.Thr278Thr	synonymous_variant	Exon 7 of 14	ENST00000311014.11	NP_075462.3	Q9GZS0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAI2	ENST00000311014.11 link	c.834C>T	p.Thr278Thr	synonymous_variant	Exon 7 of 14	1	NM_023036.6	ENSP00000308312.6		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

GnomAD2 exomes

AF:

0.138

AC:

34550

AN:

250330

AF XY:

0.144

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 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

African (AFR)

AF:

0.0314

AC:

1051

AN:

33480

American (AMR)

AF:

0.0668

AC:

2989

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.127

AC:

3318

AN:

26136

East Asian (EAS)

AF:

0.00108

AC:

AN:

39700

South Asian (SAS)

AF:

0.135

AC:

11615

AN:

86244

European-Finnish (FIN)

AF:

0.197

AC:

10409

AN:

52844

Middle Eastern (MID)

AF:

0.114

AC:

657

AN:

5768

European-Non Finnish (NFE)

AF:

0.196

AC:

217669

AN:

1111936

Other (OTH)

AF:

0.146

AC:

8792

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

12798

25596

38394

51192

63990

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7412

14824

22236

29648

37060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.127

AC:

19313

AN:

152090

Hom.:

1593

Cov.:

AF XY:

0.125

AC XY:

9294

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.0374

AC:

1555

AN:

41532

American (AMR)

AF:

0.0943

AC:

1441

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.135

AC:

469

AN:

3470

East Asian (EAS)

AF:

0.00328

AC:

AN:

5184

South Asian (SAS)

AF:

0.126

AC:

605

AN:

4810

European-Finnish (FIN)

AF:

0.196

AC:

2065

AN:

10558

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.188

AC:

12786

AN:

67944

Other (OTH)

AF:

0.111

AC:

233

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

810

1621

2431

3242

4052

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

224

448

672

896

1120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.155

Hom.:

1901

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

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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). -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Primary ciliary dyskinesia 9

Benign:3

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Primary ciliary dyskinesia

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Dec 10, 2014

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.18

(source)

DANN

Benign

0.66

PhyloP100

-6.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over