rs17856705

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_178452.6(DNAAF1):c.1178A>G(p.Lys393Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 1,613,638 control chromosomes in the GnomAD database, including 158,604 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 11560 hom., cov: 33)

Exomes 𝑓: 0.44 ( 147044 hom. )

Consequence

DNAAF1
NM_178452.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.0210

Publications

27 publications found

Variant links:

Genes affected

DNAAF1 (HGNC:30539): (dynein axonemal assembly factor 1) The protein encoded by this gene is cilium-specific and is required for the stability of the ciliary architecture. It is involved in the regulation of microtubule-based cilia and actin-based brush border microvilli. Mutations in this gene are associated with primary ciliary dyskinesia-13. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

DNAAF1 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 13
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DNAAF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.163822E-4).

BP6

Variant 16-84170006-A-G is Benign according to our data. Variant chr16-84170006-A-G is described in ClinVar as Benign. ClinVar VariationId is 226572.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF1	NM_178452.6 link	c.1178A>G	p.Lys393Arg	missense_variant	Exon 8 of 12	ENST00000378553.10	NP_848547.4	Q8NEP3-1A0A140VJN4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF1	ENST00000378553.10 link	c.1178A>G	p.Lys393Arg	missense_variant	Exon 8 of 12	1	NM_178452.6	ENSP00000367815.5		Q8NEP3-1

Frequencies

GnomAD3 genomes

AF:

0.377

AC:

57381

AN:

152070

Hom.:

11549

Cov.:

show subpopulations

Gnomad AFR

AF:

0.227

Gnomad AMI

AF:

0.487

Gnomad AMR

AF:

0.404

Gnomad ASJ

AF:

0.386

Gnomad EAS

AF:

0.332

Gnomad SAS

AF:

0.304

Gnomad FIN

AF:

0.444

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.460

Gnomad OTH

AF:

0.368

GnomAD2 exomes

AF:

0.402

AC:

101023

AN:

251180

AF XY:

0.402

show subpopulations

Gnomad AFR exome

AF:

0.218

Gnomad AMR exome

AF:

0.411

Gnomad ASJ exome

AF:

0.381

Gnomad EAS exome

AF:

0.342

Gnomad FIN exome

AF:

0.441

Gnomad NFE exome

AF:

0.456

Gnomad OTH exome

AF:

0.408

GnomAD4 exome

AF:

0.444

AC:

649027

AN:

1461448

Hom.:

147044

Cov.:

AF XY:

0.439

AC XY:

319329

AN XY:

727012

show subpopulations

African (AFR)

AF:

0.217

AC:

7271

AN:

33470

American (AMR)

AF:

0.411

AC:

18380

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.383

AC:

10020

AN:

26136

East Asian (EAS)

AF:

0.332

AC:

13184

AN:

39698

South Asian (SAS)

AF:

0.306

AC:

26410

AN:

86242

European-Finnish (FIN)

AF:

0.443

AC:

23670

AN:

53410

Middle Eastern (MID)

AF:

0.353

AC:

1933

AN:

5470

European-Non Finnish (NFE)

AF:

0.471

AC:

523183

AN:

1111956

Other (OTH)

AF:

0.414

AC:

24976

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

26211

52421

78632

104842

131053

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15450

30900

46350

61800

77250

<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:

0.377

AC:

57415

AN:

152190

Hom.:

11560

Cov.:

AF XY:

0.375

AC XY:

27891

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.227

AC:

9444

AN:

41556

American (AMR)

AF:

0.405

AC:

6194

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.386

AC:

1338

AN:

3470

East Asian (EAS)

AF:

0.332

AC:

1716

AN:

5164

South Asian (SAS)

AF:

0.304

AC:

1468

AN:

4828

European-Finnish (FIN)

AF:

0.444

AC:

4702

AN:

10592

Middle Eastern (MID)

AF:

0.310

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.460

AC:

31251

AN:

67968

Other (OTH)

AF:

0.364

AC:

769

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1850

3699

5549

7398

9248

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

556

1112

1668

2224

2780

<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:

0.421

Hom.:

42767

Bravo

AF:

0.369

TwinsUK

AF:

0.476

AC:

1764

ALSPAC

AF:

0.473

AC:

1822

ESP6500AA

AF:

0.225

AC:

991

ESP6500EA

AF:

0.457

AC:

3932

ExAC

AF:

0.400

AC:

48528

Asia WGS

AF:

0.286

AC:

994

AN:

3478

EpiCase

AF:

0.442

EpiControl

AF:

0.445

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

May 05, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Lys393Arg in exon 8 of DNAAF1: This variant is not expected to have clinical s ignificance it has been identified in 45% (30157/66644) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs17856705). -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

Benign:2

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. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Primary ciliary dyskinesia 13

Benign:2

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 19, 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

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.1

(source)

DANN

Benign

0.67

DEOGEN2

Benign

0.0066

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.41

MetaRNN

Benign

0.00012

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.1

PhyloP100

-0.021

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.48

REVEL

Benign

0.055

Sift

Benign

0.22

Sift4G

Benign

0.44

Polyphen

0.0010

Vest4

0.025

MPC

0.019

ClinPred

0.0016

GERP RS

0.13

Varity_R

0.025

gMVP

0.055

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