rs9908476

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_023036.6(DNAI2):c.1644C>A(p.Ala548Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0321 in 1,612,522 control chromosomes in the GnomAD database, including 954 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A548A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.039 ( 126 hom., cov: 33)

Exomes 𝑓: 0.031 ( 828 hom. )

Consequence

DNAI2
NM_023036.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -2.68

Publications

2 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:

LOC105371891 (HGNC:):

LOC105371891 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 17-74312152-C-A is Benign according to our data. Variant chr17-74312152-C-A is described in ClinVar as Benign. ClinVar VariationId is 163170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.68 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAI2	NM_023036.6 link	c.1644C>A	p.Ala548Ala	synonymous_variant	Exon 12 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.1644C>A	p.Ala548Ala	synonymous_variant	Exon 12 of 14	1	NM_023036.6	ENSP00000308312.6		Q9GZS0-1

Frequencies

GnomAD3 genomes

AF:

0.0389

AC:

5891

AN:

151510

Hom.:

125

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0567

Gnomad AMI

AF:

0.0176

Gnomad AMR

AF:

0.0320

Gnomad ASJ

AF:

0.0346

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.0332

Gnomad FIN

AF:

0.0385

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0332

Gnomad OTH

AF:

0.0470

GnomAD2 exomes

AF:

0.0312

AC:

7785

AN:

249636

AF XY:

0.0316

show subpopulations

Gnomad AFR exome

AF:

0.0574

Gnomad AMR exome

AF:

0.0176

Gnomad ASJ exome

AF:

0.0394

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0365

Gnomad NFE exome

AF:

0.0339

Gnomad OTH exome

AF:

0.0325

GnomAD4 exome

AF:

0.0314

AC:

45845

AN:

1460894

Hom.:

828

Cov.:

AF XY:

0.0313

AC XY:

22780

AN XY:

726706

show subpopulations

African (AFR)

AF:

0.0582

AC:

1948

AN:

33446

American (AMR)

AF:

0.0198

AC:

886

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.0383

AC:

1001

AN:

26116

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39662

South Asian (SAS)

AF:

0.0357

AC:

3077

AN:

86224

European-Finnish (FIN)

AF:

0.0355

AC:

1890

AN:

53244

Middle Eastern (MID)

AF:

0.0547

AC:

311

AN:

5684

European-Non Finnish (NFE)

AF:

0.0312

AC:

34644

AN:

1111524

Other (OTH)

AF:

0.0346

AC:

2085

AN:

60304

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

2790

5581

8371

11162

13952

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1286

2572

3858

5144

6430

<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:

0.0389

AC:

5902

AN:

151628

Hom.:

126

Cov.:

AF XY:

0.0378

AC XY:

2800

AN XY:

74092

show subpopulations

African (AFR)

AF:

0.0568

AC:

2347

AN:

41340

American (AMR)

AF:

0.0320

AC:

486

AN:

15208

Ashkenazi Jewish (ASJ)

AF:

0.0346

AC:

120

AN:

3468

East Asian (EAS)

AF:

0.000196

AC:

AN:

5108

South Asian (SAS)

AF:

0.0328

AC:

157

AN:

4792

European-Finnish (FIN)

AF:

0.0385

AC:

403

AN:

10466

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0332

AC:

2258

AN:

67936

Other (OTH)

AF:

0.0465

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

294

589

883

1178

1472

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

198

264

330

<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:

0.0278

Hom.:

Bravo

AF:

0.0391

EpiCase

AF:

0.0361

EpiControl

AF:

0.0355

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:3

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 24, 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 specified

Benign:2

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

Ala548Ala in exon 12 of DNAI2: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 5.7% (252/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs9908476). -

Primary ciliary dyskinesia 9

Benign:2

Jan 13, 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. -

Mar 06, 2017

Counsyl

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. -

not provided

Benign:2

Feb 21, 2019

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

-0.43

CADD

Benign

0.059

(source)

DANN

Benign

0.78

PhyloP100

-2.7

Mutation Taster

=100/0

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

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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