rs2365725

Positions:

chr19-55161102-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001256715.2(DNAAF3):c.875A>G(p.Glu292Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 1,543,812 control chromosomes in the GnomAD database, including 25,671 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 6211 hom., cov: 32)

Exomes 𝑓: 0.15 ( 19460 hom. )

Consequence

DNAAF3
NM_001256715.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: 0.950

Variant links:

Genes affected

DNAAF3 (HGNC:30492): (dynein axonemal assembly factor 3) The protein encoded by this gene is required for the assembly of axonemal inner and outer dynein arms and plays a role in assembling dynein complexes for transport into cilia. Defects in this gene are a cause of primary ciliary dyskinesia type 2 (CILD2). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]

DNAAF3 links:

DNAAF3-AS1 (HGNC:55292): (DNAAF3 antisense RNA 1)

DNAAF3-AS1 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=3.026724E-4).

BP6

Variant 19-55161102-T-C is Benign according to our data. Variant chr19-55161102-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 257676.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-55161102-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAAF3	NM_001256715.2 linkuse as main transcript	c.875A>G	p.Glu292Gly	missense_variant	8/12	ENST00000524407.7	NP_001243644.1
DNAAF3-AS1	XR_007067344.1 linkuse as main transcript	n.194T>C		non_coding_transcript_exon_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAAF3	ENST00000524407.7 linkuse as main transcript	c.875A>G	p.Glu292Gly	missense_variant	8/12	1	NM_001256715.2	ENSP00000432046	A2	Q8N9W5-1
DNAAF3-AS1	ENST00000591665.1 linkuse as main transcript	n.1024T>C		non_coding_transcript_exon_variant	3/5	2

Frequencies

GnomAD3 genomes

AF:

0.240

AC:

36390

AN:

151792

Hom.:

6195

Cov.:

show subpopulations

Gnomad AFR

AF:

0.484

Gnomad AMI

AF:

0.147

Gnomad AMR

AF:

0.165

Gnomad ASJ

AF:

0.258

Gnomad EAS

AF:

0.0832

Gnomad SAS

AF:

0.136

Gnomad FIN

AF:

0.0990

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.149

Gnomad OTH

AF:

0.240

GnomAD3 exomes

AF:

0.159

AC:

23233

AN:

146054

Hom.:

2449

AF XY:

0.157

AC XY:

12384

AN XY:

78706

show subpopulations

Gnomad AFR exome

AF:

0.491

Gnomad AMR exome

AF:

0.117

Gnomad ASJ exome

AF:

0.251

Gnomad EAS exome

AF:

0.0796

Gnomad SAS exome

AF:

0.137

Gnomad FIN exome

AF:

0.0948

Gnomad NFE exome

AF:

0.156

Gnomad OTH exome

AF:

0.198

GnomAD4 exome

AF:

0.155

AC:

215579

AN:

1391902

Hom.:

19460

Cov.:

AF XY:

0.154

AC XY:

105741

AN XY:

686722

show subpopulations

Gnomad4 AFR exome

AF:

0.498

Gnomad4 AMR exome

AF:

0.126

Gnomad4 ASJ exome

AF:

0.254

Gnomad4 EAS exome

AF:

0.0513

Gnomad4 SAS exome

AF:

0.137

Gnomad4 FIN exome

AF:

0.105

Gnomad4 NFE exome

AF:

0.148

Gnomad4 OTH exome

AF:

0.182

GnomAD4 genome

AF:

0.240

AC:

36452

AN:

151910

Hom.:

6211

Cov.:

AF XY:

0.231

AC XY:

17183

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.484

Gnomad4 AMR

AF:

0.165

Gnomad4 ASJ

AF:

0.258

Gnomad4 EAS

AF:

0.0828

Gnomad4 SAS

AF:

0.136

Gnomad4 FIN

AF:

0.0990

Gnomad4 NFE

AF:

0.149

Gnomad4 OTH

AF:

0.242

Alfa

AF:

0.173

Hom.:

5389

Bravo

AF:

0.259

TwinsUK

AF:

0.156

AC:

580

ALSPAC

AF:

0.140

AC:

541

ESP6500AA

AF:

0.367

AC:

1334

ESP6500EA

AF:

0.123

AC:

922

ExAC

AF:

0.0889

AC:

6989

Asia WGS

AF:

0.164

AC:

569

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:3

Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Jul 15, 2016	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	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Primary ciliary dyskinesia 2

Benign:2

Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Sep 21, 2015	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

Familial Hypertrophic Cardiomyopathy with Wolff-Parkinson-White Syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Dilated Cardiomyopathy, Recessive

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Familial restrictive cardiomyopathy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Hypertrophic cardiomyopathy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.044

.;T;.;.

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.53

T;T;T;T

MetaRNN

Benign

0.00030

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.4

.;M;.;.

MutationTaster

Benign

1.0

P;P;P;P;P;P;P

PrimateAI

Benign

0.36

PROVEAN

Pathogenic

-4.6

D;.;.;D

REVEL

Benign

0.088

Sift

Uncertain

0.013

D;.;.;D

Sift4G

Uncertain

0.031

D;D;D;D

Polyphen

0.76

.;P;.;.

Vest4

0.072

MPC

0.52

ClinPred

0.027

GERP RS

3.2

Varity_R

0.10

gMVP

0.56

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