rs7260371

chr19-55161201-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001256715.2(DNAAF3):c.790-14C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 1,580,790 control chromosomes in the GnomAD database, including 25,997 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 (6171 hom., cov: 32)
  • Exomes 𝑓: 0.15 (19826 hom.)
• Consequence: DNAAF3 NM_001256715.2 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 0.698

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

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 19-55161201-G-A is Benign according to our data. Variant chr19-55161201-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 257695.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-55161201-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAAF3	NM_001256715.2	c.790-14C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000524407.7
DNAAF3-AS1	XR_007067344.1	n.293G>A		non_coding_transcript_exon_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAAF3	ENST00000524407.7	c.790-14C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001256715.2	A2
DNAAF3-AS1	ENST00000591665.1	n.1123G>A		non_coding_transcript_exon_variant	3/5	2

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36326 AN: 152062 Hom.: 6155 Cov.: 32

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.0819

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.0986

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.239

GnomAD3 exomes AF: 0.158 AC: 31552 AN: 199496 Hom.: 3312 AF XY: 0.157 AC XY: 16962 AN XY: 108356

Gnomad AFR exome AF: 0.491

Gnomad AMR exome AF: 0.112

Gnomad ASJ exome AF: 0.251

Gnomad EAS exome AF: 0.0767

Gnomad SAS exome AF: 0.135

Gnomad FIN exome AF: 0.0973

Gnomad NFE exome AF: 0.152

Gnomad OTH exome AF: 0.191

GnomAD4 exome AF: 0.154 AC: 220387 AN: 1428608 Hom.: 19826 Cov.: 39 AF XY: 0.153 AC XY: 108401 AN XY: 706786

Gnomad4 AFR exome AF: 0.495

Gnomad4 AMR exome AF: 0.120

Gnomad4 ASJ exome AF: 0.252

Gnomad4 EAS exome AF: 0.0516

Gnomad4 SAS exome AF: 0.137

Gnomad4 FIN exome AF: 0.105

Gnomad4 NFE exome AF: 0.148

Gnomad4 OTH exome AF: 0.181

GnomAD4 genome AF: 0.239 AC: 36388 AN: 152182 Hom.: 6171 Cov.: 32 AF XY: 0.231 AC XY: 17155 AN XY: 74424

Gnomad4 AFR AF: 0.482

Gnomad4 AMR AF: 0.164

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.0817

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.0986

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.241

Alfa AF: 0.203 Hom.: 771

Bravo AF: 0.258

Asia WGS AF: 0.164 AC: 569 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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	-	- -

Primary ciliary dyskinesia Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

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

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

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	-0.80
Cadd	Benign	7.5
Dann	Benign	0.86

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

Other links and lift over

dbSNP: rs7260371; hg19: chr19-55672569; COSMIC: COSV61277233; COSMIC: COSV61277233;