chr16-84165838-C-G

Position:

chr16-84165838-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000378553.10(DNAAF1):c.919C>G(p.Gln307Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0234 in 1,613,316 control chromosomes in the GnomAD database, including 599 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 101 hom., cov: 31)

Exomes 𝑓: 0.023 ( 498 hom. )

Consequence

DNAAF1
ENST00000378553.10 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.272

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020638406).

BP6

Variant 16-84165838-C-G is Benign according to our data. Variant chr16-84165838-C-G is described in ClinVar as [Benign]. Clinvar id is 163083.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-84165838-C-G is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0301 (4557/151586) while in subpopulation AFR AF= 0.0466 (1924/41284). AF 95% confidence interval is 0.0449. There are 101 homozygotes in gnomad4. There are 2253 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 101 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAAF1	NM_178452.6 linkuse as main transcript	c.919C>G	p.Gln307Glu	missense_variant	7/12	ENST00000378553.10	NP_848547.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAAF1	ENST00000378553.10 linkuse as main transcript	c.919C>G	p.Gln307Glu	missense_variant	7/12	1	NM_178452.6	ENSP00000367815	P1	Q8NEP3-1

Frequencies

GnomAD3 genomes

AF:

0.0300

AC:

4546

AN:

151466

Hom.:

100

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0464

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0100

Gnomad ASJ

AF:

0.0161

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000831

Gnomad FIN

AF:

0.0677

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0245

Gnomad OTH

AF:

0.0246

GnomAD3 exomes

AF:

0.0205

AC:

5153

AN:

251410

Hom.:

103

AF XY:

0.0196

AC XY:

2667

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.0452

Gnomad AMR exome

AF:

0.00781

Gnomad ASJ exome

AF:

0.0153

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00176

Gnomad FIN exome

AF:

0.0610

Gnomad NFE exome

AF:

0.0219

Gnomad OTH exome

AF:

0.0212

GnomAD4 exome

AF:

0.0227

AC:

33224

AN:

1461730

Hom.:

498

Cov.:

AF XY:

0.0222

AC XY:

16136

AN XY:

727154

show subpopulations

Gnomad4 AFR exome

AF:

0.0467

Gnomad4 AMR exome

AF:

0.00859

Gnomad4 ASJ exome

AF:

0.0153

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00189

Gnomad4 FIN exome

AF:

0.0615

Gnomad4 NFE exome

AF:

0.0235

Gnomad4 OTH exome

AF:

0.0204

GnomAD4 genome

AF:

0.0301

AC:

4557

AN:

151586

Hom.:

101

Cov.:

AF XY:

0.0304

AC XY:

2253

AN XY:

74058

show subpopulations

Gnomad4 AFR

AF:

0.0466

Gnomad4 AMR

AF:

0.00989

Gnomad4 ASJ

AF:

0.0161

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000832

Gnomad4 FIN

AF:

0.0677

Gnomad4 NFE

AF:

0.0244

Gnomad4 OTH

AF:

0.0243

Alfa

AF:

0.0223

Hom.:

Bravo

AF:

0.0261

TwinsUK

AF:

0.0213

AC:

ALSPAC

AF:

0.0249

AC:

ESP6500AA

AF:

0.0391

AC:

172

ESP6500EA

AF:

0.0236

AC:

203

ExAC

AF:

0.0202

AC:

2451

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	Gln307Glu in exon 7 of DNAAF1: This variant is not expected to have clinical sig nificance because it has been identified in 3.9% (172/4400) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs111472069). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 11, 2016	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 21, 2019	This variant is associated with the following publications: (PMID: 23599692) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2024	DNAAF1: BP4, BS1, BS2 -

Primary ciliary dyskinesia

Benign:2

Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Jul 09, 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	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Primary ciliary dyskinesia 13

Benign:2

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	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.78

CADD

Benign

4.0

DANN

Benign

0.22

DEOGEN2

Benign

0.0015

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.64

MetaRNN

Benign

0.0021

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.89

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.010

REVEL

Benign

0.092

Sift

Benign

0.57

Sift4G

Benign

0.88

Polyphen

0.0070

Vest4

0.029

MPC

0.021

ClinPred

0.0055

GERP RS

-2.5

Varity_R

0.055

gMVP

0.22

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