rs60176657

chr19-55159621-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.1164-14C>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 0.0533 in 1,612,500 control chromosomes in the GnomAD database, including 6,897 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.068 (808 hom., cov: 33)
  • Exomes 𝑓: 0.052 (6089 hom.)
• Consequence: DNAAF3 NM_001256715.2 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.275

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=-0.72).
• BP6: Variant 19-55159621-G-A is Benign according to our data. Variant chr19-55159621-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 257682.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-55159621-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAAF3	NM_001256715.2	c.1164-14C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000524407.7
DNAAF3-AS1	XR_007067344.1	n.137+176G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAAF3	ENST00000524407.7	c.1164-14C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001256715.2	A2
DNAAF3-AS1	ENST00000591665.1	n.600G>A		non_coding_transcript_exon_variant	2/5	2

Frequencies

GnomAD3 genomes AF: 0.0677 AC: 10299 AN: 152146 Hom.: 797 Cov.: 33

Gnomad AFR AF: 0.0663

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.0352

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.0277

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0266

Gnomad OTH AF: 0.0775

GnomAD3 exomes AF: 0.107 AC: 26410 AN: 246984 Hom.: 3556 AF XY: 0.0965 AC XY: 12934 AN XY: 134040

Gnomad AFR exome AF: 0.0684

Gnomad AMR exome AF: 0.371

Gnomad ASJ exome AF: 0.0332

Gnomad EAS exome AF: 0.220

Gnomad SAS exome AF: 0.139

Gnomad FIN exome AF: 0.0309

Gnomad NFE exome AF: 0.0272

Gnomad OTH exome AF: 0.0803

GnomAD4 exome AF: 0.0518 AC: 75646 AN: 1460236 Hom.: 6089 Cov.: 34 AF XY: 0.0525 AC XY: 38153 AN XY: 726356

Gnomad4 AFR exome AF: 0.0674

Gnomad4 AMR exome AF: 0.357

Gnomad4 ASJ exome AF: 0.0351

Gnomad4 EAS exome AF: 0.242

Gnomad4 SAS exome AF: 0.134

Gnomad4 FIN exome AF: 0.0327

Gnomad4 NFE exome AF: 0.0269

Gnomad4 OTH exome AF: 0.0604

GnomAD4 genome AF: 0.0679 AC: 10332 AN: 152264 Hom.: 808 Cov.: 33 AF XY: 0.0727 AC XY: 5413 AN XY: 74454

Gnomad4 AFR AF: 0.0663

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.0352

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.0277

Gnomad4 NFE AF: 0.0266

Gnomad4 OTH AF: 0.0781

Alfa AF: 0.0471 Hom.: 69

Bravo AF: 0.0829

Asia WGS AF: 0.199 AC: 690 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

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 -

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

Invitae

Jan 31, 2024

- -

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	-0.72
Cadd	Benign	5.6
Dann	Benign	0.90

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: rs60176657; hg19: chr19-55670989; COSMIC: COSV61275226; COSMIC: COSV61275226;