Variant 16-84176028-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_178452.6(DNAAF1):c.1794C>G(p.Leu598=) 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:9

Conservation

PhyloP100: -2.50

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 163086.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-84176028-C-G is described in Lovd as [Benign].

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/exons	MANE	UniProt
DNAAF1	NM_178452.6 linkuse as main transcript	c.1794C>G	p.Leu598=	synonymous_variant	11/12	ENST00000378553.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAAF1	ENST00000378553.10 linkuse as main transcript	c.1794C>G	p.Leu598=	synonymous_variant	11/12	1	NM_178452.6	P1	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

GnomAD3 exomes

AF:

0.528

AC:

132579

AN:

251306

Hom.:

35301

AF XY:

0.529

AC XY:

71900

AN XY:

135848

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 SAS exome

AF:

0.585

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

Gnomad4 AFR exome

AF:

0.514

Gnomad4 AMR exome

AF:

0.580

Gnomad4 ASJ exome

AF:

0.526

Gnomad4 EAS exome

AF:

0.524

Gnomad4 SAS exome

AF:

0.581

Gnomad4 FIN exome

AF:

0.477

Gnomad4 NFE exome

AF:

0.504

Gnomad4 OTH exome

AF:

0.515

GnomAD4 genome

AF:

0.515

AC:

78209

AN:

151986

Hom.:

20081

Cov.:

AF XY:

0.516

AC XY:

38348

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.521

Gnomad4 AMR

AF:

0.553

Gnomad4 ASJ

AF:

0.528

Gnomad4 EAS

AF:

0.526

Gnomad4 SAS

AF:

0.583

Gnomad4 FIN

AF:

0.469

Gnomad4 NFE

AF:

0.501

Gnomad4 OTH

AF:

0.523

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:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia 13

Benign:4

Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Sep 21, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	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). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Primary ciliary dyskinesia

Benign:2

Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Dec 11, 2014	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. -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.034

DANN

Benign

0.44

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over