19-55159457-T-C

Position:

chr19-55159457-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.1239-8A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 1,612,414 control chromosomes in the GnomAD database, including 65,011 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 13146 hom., cov: 32)

Exomes 𝑓: 0.24 ( 51865 hom. )

Consequence

DNAAF3
NM_001256715.2 splice_region, intron

Scores

Splicing: ADA: 0.00002193

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -2.43

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:

ENSG00000267110 (HGNC:):

ENSG00000267110 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 (BayesDel_noAF=-0.92).

BP6

Variant 19-55159457-T-C is Benign according to our data. Variant chr19-55159457-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 257684.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-55159457-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.649 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.1239-8A>G		splice_region_variant, intron_variant		ENST00000524407.7	NP_001243644.1	Q8N9W5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAAF3	ENST00000524407.7 linkuse as main transcript	c.1239-8A>G		splice_region_variant, intron_variant		1	NM_001256715.2	ENSP00000432046.3		Q8N9W5-1
ENSG00000267110	ENST00000587871.1 linkuse as main transcript	n.222-8A>G		splice_region_variant, intron_variant		5		ENSP00000473050.1		M0R381

Frequencies

GnomAD3 genomes

AF:

0.365

AC:

55473

AN:

151980

Hom.:

13106

Cov.:

show subpopulations

Gnomad AFR

AF:

0.655

Gnomad AMI

AF:

0.147

Gnomad AMR

AF:

0.404

Gnomad ASJ

AF:

0.215

Gnomad EAS

AF:

0.440

Gnomad SAS

AF:

0.441

Gnomad FIN

AF:

0.227

Gnomad MID

AF:

0.318

Gnomad NFE

AF:

0.201

Gnomad OTH

AF:

0.360

GnomAD3 exomes

AF:

0.323

AC:

80248

AN:

248766

Hom.:

15869

AF XY:

0.314

AC XY:

42334

AN XY:

134946

show subpopulations

Gnomad AFR exome

AF:

0.670

Gnomad AMR exome

AF:

0.496

Gnomad ASJ exome

AF:

0.213

Gnomad EAS exome

AF:

0.422

Gnomad SAS exome

AF:

0.422

Gnomad FIN exome

AF:

0.226

Gnomad NFE exome

AF:

0.208

Gnomad OTH exome

AF:

0.313

GnomAD4 exome

AF:

0.244

AC:

356674

AN:

1460316

Hom.:

51865

Cov.:

AF XY:

0.247

AC XY:

179529

AN XY:

726174

show subpopulations

Gnomad4 AFR exome

AF:

0.673

Gnomad4 AMR exome

AF:

0.490

Gnomad4 ASJ exome

AF:

0.214

Gnomad4 EAS exome

AF:

0.421

Gnomad4 SAS exome

AF:

0.414

Gnomad4 FIN exome

AF:

0.232

Gnomad4 NFE exome

AF:

0.201

Gnomad4 OTH exome

AF:

0.281

GnomAD4 genome

AF:

0.365

AC:

55581

AN:

152098

Hom.:

13146

Cov.:

AF XY:

0.367

AC XY:

27290

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.655

Gnomad4 AMR

AF:

0.405

Gnomad4 ASJ

AF:

0.215

Gnomad4 EAS

AF:

0.440

Gnomad4 SAS

AF:

0.440

Gnomad4 FIN

AF:

0.227

Gnomad4 NFE

AF:

0.201

Gnomad4 OTH

AF:

0.366

Alfa

AF:

0.264

Hom.:

3563

Bravo

AF:

0.391

Asia WGS

AF:

0.521

AC:

1808

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia 2

Benign:3

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	-	- -
Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Sep 21, 2015	- -

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 -

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 05, 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

- -

Primary ciliary dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

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

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.53

DANN

Benign

0.54

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000022

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.040

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