chr19-55159889-C-A

Variant names:

• chr19-55159889-C-A
• rs200324983
• NM_001256715.2:c.1163+10G>T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP3 BP6_Very_Strong BS1 BS2

The NM_001256715.2(DNAAF3):​c.1163+10G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00338 in 1,613,046 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0023 (4 hom., cov: 31)
  • Exomes 𝑓: 0.0035 (15 hom.)
• Consequence: DNAAF3 NM_001256715.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.554

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]

ENSG00000267110 (HGNC:):

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

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• PP3: Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• BP6: Variant 19-55159889-C-A is Benign according to our data. Variant chr19-55159889-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 238683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00228 (347/152220) while in subpopulation NFE AF= 0.00391 (266/67998). AF 95% confidence interval is 0.00353. There are 4 homozygotes in gnomad4. There are 159 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF3	NM_001256715.2	c.1163+10G>T		intron_variant	Intron 10 of 11	ENST00000524407.7	NP_001243644.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF3	ENST00000524407.7	c.1163+10G>T		intron_variant	Intron 10 of 11	1	NM_001256715.2	ENSP00000432046.3
ENSG00000267110	ENST00000587871.1	n.146+10G>T		intron_variant	Intron 2 of 8	5		ENSP00000473050.1

Frequencies

GnomAD3 genomes AF: 0.00227 AC: 345 AN: 152102 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00269

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00391

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00233 AC: 581 AN: 249240 Hom.: 2 AF XY: 0.00242 AC XY: 327 AN XY: 135252

Gnomad AFR exome AF: 0.000517

Gnomad AMR exome AF: 0.000753

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00180

Gnomad FIN exome AF: 0.000882

Gnomad NFE exome AF: 0.00410

Gnomad OTH exome AF: 0.00165

GnomAD4 exome AF: 0.00350 AC: 5112 AN: 1460826 Hom.: 15 Cov.: 33 AF XY: 0.00351 AC XY: 2552 AN XY: 726810

Gnomad4 AFR exome AF: 0.000598

Gnomad4 AMR exome AF: 0.00103

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00213

Gnomad4 FIN exome AF: 0.00101

Gnomad4 NFE exome AF: 0.00419

Gnomad4 OTH exome AF: 0.00252

GnomAD4 genome AF: 0.00228 AC: 347 AN: 152220 Hom.: 4 Cov.: 31 AF XY: 0.00214 AC XY: 159 AN XY: 74424

Gnomad4 AFR AF: 0.000506

Gnomad4 AMR AF: 0.00268

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00186

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.00391

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00152 Hom.: 0

Bravo AF: 0.00253

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia 2 Benign:1

Sep 04, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia Benign:1

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Aug 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

DNAAF3: BS2 -

DNAAF3-related disorder Benign:1

Jun 13, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.6
DANN	Benign	0.71
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.73		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.73		Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs200324983; hg19: chr19-55671257;