16-84176028-C-G

Variant names:

Variant summary

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

The NM_178452.6(DNAAF1):c.1794C>G(p.Leu598Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 1,613,586 control chromosomes in the GnomAD database, including 212,260 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 20081 hom., cov: 32)

Exomes 𝑓: 0.51 ( 192179 hom. )

Consequence

DNAAF1
NM_178452.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.50

Publications

26 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 16-84176028-C-G is Benign according to our data. Variant chr16-84176028-C-G is described in ClinVar as Benign. ClinVar VariationId is 163086.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.5 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF1	NM_178452.6 link	c.1794C>G	p.Leu598Leu	synonymous_variant	Exon 11 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.1794C>G	p.Leu598Leu	synonymous_variant	Exon 11 of 12	1	NM_178452.6	ENSP00000367815.5		Q8NEP3-1

Frequencies

GnomAD3 genomes

AF:

0.514

AC:

78113

AN:

151868

Hom.:

20039

Cov.:

show subpopulations

Gnomad AFR

AF:

0.520

Gnomad AMI

AF:

0.615

Gnomad AMR

AF:

0.552

Gnomad ASJ

AF:

0.528

Gnomad EAS

AF:

0.526

Gnomad SAS

AF:

0.583

Gnomad FIN

AF:

0.469

Gnomad MID

AF:

0.522

Gnomad NFE

AF:

0.501

Gnomad OTH

AF:

0.522

GnomAD2 exomes

AF:

0.528

AC:

132579

AN:

251306

AF XY:

0.529

show subpopulations

Gnomad AFR exome

AF:

0.517

Gnomad AMR exome

AF:

0.581

Gnomad ASJ exome

AF:

0.520

Gnomad EAS exome

AF:

0.522

Gnomad FIN exome

AF:

0.473

Gnomad NFE exome

AF:

0.509

Gnomad OTH exome

AF:

0.535

GnomAD4 exome

AF:

0.512

AC:

748190

AN:

1461600

Hom.:

192179

Cov.:

AF XY:

0.513

AC XY:

373279

AN XY:

727118

show subpopulations

African (AFR)

AF:

0.514

AC:

17198

AN:

33468

American (AMR)

AF:

0.580

AC:

25927

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.526

AC:

13734

AN:

26134

East Asian (EAS)

AF:

0.524

AC:

20789

AN:

39698

South Asian (SAS)

AF:

0.581

AC:

50142

AN:

86254

European-Finnish (FIN)

AF:

0.477

AC:

25443

AN:

53386

Middle Eastern (MID)

AF:

0.542

AC:

3126

AN:

5768

European-Non Finnish (NFE)

AF:

0.504

AC:

560710

AN:

1111790

Other (OTH)

AF:

0.515

AC:

31121

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

21739

43478

65218

86957

108696

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16410

32820

49230

65640

82050

<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:

0.515

AC:

78209

AN:

151986

Hom.:

20081

Cov.:

AF XY:

0.516

AC XY:

38348

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.521

AC:

21573

AN:

41430

American (AMR)

AF:

0.553

AC:

8457

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.528

AC:

1832

AN:

3472

East Asian (EAS)

AF:

0.526

AC:

2713

AN:

5160

South Asian (SAS)

AF:

0.583

AC:

2814

AN:

4824

European-Finnish (FIN)

AF:

0.469

AC:

4955

AN:

10564

Middle Eastern (MID)

AF:

0.514

AC:

151

AN:

294

European-Non Finnish (NFE)

AF:

0.501

AC:

34048

AN:

67936

Other (OTH)

AF:

0.523

AC:

1105

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

2011

4021

6032

8042

10053

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

704

1408

2112

2816

3520

<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:

0.469

Hom.:

4855

Bravo

AF:

0.521

Asia WGS

AF:

0.554

AC:

1925

AN:

3478

EpiCase

AF:

0.510

EpiControl

AF:

0.518

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia 13

Benign:4

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Sep 21, 2015

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

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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 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

Leu598Leu in exon 11 of DNAAF1: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 49.1% (4226/8600) of European American chromosomes from a broad population by the NHLBI Exome Sequ encing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2288019). -

Primary ciliary dyskinesia

Benign:2

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. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Nov 28, 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

-0.91

CADD

Benign

0.034

(source)

DANN

Benign

0.44

PhyloP100

-2.5

PromoterAI

0.0038

Neutral

(source)

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