rs7260320

Positions:

Variant summary

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

The ENST00000524407.7(DNAAF3):c.666T>C(p.Ala222=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 750,756 control chromosomes in the GnomAD database, including 25,479 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 5891 hom., cov: 23)

Exomes 𝑓: 0.35 ( 19588 hom. )

Consequence

DNAAF3
ENST00000524407.7 splice_region, synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.00300

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 19-55161416-A-G is Benign according to our data. Variant chr19-55161416-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 257694.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-55161416-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.003 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.505 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.666T>C	p.Ala222=	splice_region_variant, synonymous_variant	7/12	ENST00000524407.7	NP_001243644.1
DNAAF3-AS1	XR_007067344.1 linkuse as main transcript	n.306+202A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAAF3	ENST00000524407.7 linkuse as main transcript	c.666T>C	p.Ala222=	splice_region_variant, synonymous_variant	7/12	1	NM_001256715.2	ENSP00000432046	A2	Q8N9W5-1
DNAAF3-AS1	ENST00000591665.1 linkuse as main transcript	n.1136+202A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.270

AC:

34601

AN:

128230

Hom.:

5876

Cov.:

show subpopulations

Gnomad AFR

AF:

0.511

Gnomad AMI

AF:

0.158

Gnomad AMR

AF:

0.198

Gnomad ASJ

AF:

0.278

Gnomad EAS

AF:

0.117

Gnomad SAS

AF:

0.181

Gnomad FIN

AF:

0.131

Gnomad MID

AF:

0.324

Gnomad NFE

AF:

0.167

Gnomad OTH

AF:

0.271

GnomAD3 exomes

AF:

0.184

AC:

33237

AN:

180944

Hom.:

3722

AF XY:

0.181

AC XY:

18128

AN XY:

100428

show subpopulations

Gnomad AFR exome

AF:

0.514

Gnomad AMR exome

AF:

0.144

Gnomad ASJ exome

AF:

0.292

Gnomad EAS exome

AF:

0.0935

Gnomad SAS exome

AF:

0.163

Gnomad FIN exome

AF:

0.105

Gnomad NFE exome

AF:

0.169

Gnomad OTH exome

AF:

0.219

GnomAD4 exome

AF:

0.349

AC:

217470

AN:

622406

Hom.:

19588

Cov.:

AF XY:

0.333

AC XY:

107367

AN XY:

322002

show subpopulations

Gnomad4 AFR exome

AF:

0.624

Gnomad4 AMR exome

AF:

0.189

Gnomad4 ASJ exome

AF:

0.413

Gnomad4 EAS exome

AF:

0.164

Gnomad4 SAS exome

AF:

0.187

Gnomad4 FIN exome

AF:

0.165

Gnomad4 NFE exome

AF:

0.379

Gnomad4 OTH exome

AF:

0.379

GnomAD4 genome

AF:

0.270

AC:

34661

AN:

128350

Hom.:

5891

Cov.:

AF XY:

0.265

AC XY:

16285

AN XY:

61544

show subpopulations

Gnomad4 AFR

AF:

0.511

Gnomad4 AMR

AF:

0.198

Gnomad4 ASJ

AF:

0.278

Gnomad4 EAS

AF:

0.116

Gnomad4 SAS

AF:

0.180

Gnomad4 FIN

AF:

0.131

Gnomad4 NFE

AF:

0.167

Gnomad4 OTH

AF:

0.273

Alfa

AF:

0.201

Hom.:

1655

Bravo

AF:

0.259

Asia WGS

AF:

0.162

AC:

563

AN:

3472

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	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
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	- -

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

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

- -

Hypertrophic cardiomyopathy

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

7.8

DANN

Benign

0.63

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