17-74305293-A-G

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.1062A>G(p.Glu354Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 1,613,914 control chromosomes in the GnomAD database, including 284,557 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 20533 hom., cov: 32)

Exomes 𝑓: 0.59 ( 264024 hom. )

Consequence

DNAI2
NM_023036.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.14

Publications

23 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=-0.52).

BP6

Variant 17-74305293-A-G is Benign according to our data. Variant chr17-74305293-A-G is described in ClinVar as Benign. ClinVar VariationId is 163168.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.14 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAI2	NM_023036.6 link	c.1062A>G	p.Glu354Glu	synonymous_variant	Exon 9 of 14	ENST00000311014.11	NP_075462.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAI2	ENST00000311014.11 link	c.1062A>G	p.Glu354Glu	synonymous_variant	Exon 9 of 14	1	NM_023036.6	ENSP00000308312.6

Frequencies

GnomAD3 genomes

AF:

0.505

AC:

76674

AN:

151922

Hom.:

20532

Cov.:

show subpopulations

Gnomad AFR

AF:

0.349

Gnomad AMI

AF:

0.578

Gnomad AMR

AF:

0.410

Gnomad ASJ

AF:

0.530

Gnomad EAS

AF:

0.256

Gnomad SAS

AF:

0.508

Gnomad FIN

AF:

0.580

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.626

Gnomad OTH

AF:

0.487

GnomAD2 exomes

AF:

0.516

AC:

129774

AN:

251462

AF XY:

0.531

show subpopulations

Gnomad AFR exome

AF:

0.349

Gnomad AMR exome

AF:

0.327

Gnomad ASJ exome

AF:

0.527

Gnomad EAS exome

AF:

0.248

Gnomad FIN exome

AF:

0.591

Gnomad NFE exome

AF:

0.623

Gnomad OTH exome

AF:

0.538

GnomAD4 exome

AF:

0.593

AC:

867065

AN:

1461874

Hom.:

264024

Cov.:

AF XY:

0.593

AC XY:

431264

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.340

AC:

11397

AN:

33476

American (AMR)

AF:

0.338

AC:

15124

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.526

AC:

13736

AN:

26136

East Asian (EAS)

AF:

0.262

AC:

10385

AN:

39700

South Asian (SAS)

AF:

0.522

AC:

45030

AN:

86258

European-Finnish (FIN)

AF:

0.595

AC:

31811

AN:

53420

Middle Eastern (MID)

AF:

0.474

AC:

2732

AN:

5768

European-Non Finnish (NFE)

AF:

0.633

AC:

703885

AN:

1111996

Other (OTH)

AF:

0.546

AC:

32965

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

22019

44039

66058

88078

110097

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18430

36860

55290

73720

92150

<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:

0.504

AC:

76682

AN:

152040

Hom.:

20533

Cov.:

AF XY:

0.498

AC XY:

36981

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.348

AC:

14451

AN:

41470

American (AMR)

AF:

0.410

AC:

6258

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.530

AC:

1839

AN:

3470

East Asian (EAS)

AF:

0.255

AC:

1312

AN:

5140

South Asian (SAS)

AF:

0.510

AC:

2462

AN:

4828

European-Finnish (FIN)

AF:

0.580

AC:

6130

AN:

10574

Middle Eastern (MID)

AF:

0.408

AC:

120

AN:

294

European-Non Finnish (NFE)

AF:

0.626

AC:

42562

AN:

67968

Other (OTH)

AF:

0.486

AC:

1022

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1874

3748

5621

7495

9369

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

682

1364

2046

2728

3410

<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:

0.579

Hom.:

116192

Bravo

AF:

0.483

Asia WGS

AF:

0.373

AC:

1303

AN:

3478

EpiCase

AF:

0.607

EpiControl

AF:

0.615

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

Glu354Glu in exon 9 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 37.8% (3255/8600) of European American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs8073660). -

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. -

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

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 11, 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

Nov 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

8.3

(source)

DANN

Benign

0.75

PhyloP100

2.1

Mutation Taster

=91/9

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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