rs200324983
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP3BP6_Very_StrongBS1BS2
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
NM_001256715.2 intron
Scores
2
Clinical Significance
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]
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ACMG classification
Classification made for transcript
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. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAAF3 | NM_001256715.2 | c.1163+10G>T | intron_variant | ENST00000524407.7 | |||
DNAAF3-AS1 | XR_007067344.1 | n.137+444C>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAAF3 | ENST00000524407.7 | c.1163+10G>T | intron_variant | 1 | NM_001256715.2 | A2 | |||
DNAAF3-AS1 | ENST00000591665.1 | n.868C>A | non_coding_transcript_exon_variant | 2/5 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00227 AC: 345AN: 152102Hom.: 3 Cov.: 31
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GnomAD3 exomes AF: 0.00233 AC: 581AN: 249240Hom.: 2 AF XY: 0.00242 AC XY: 327AN XY: 135252
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GnomAD4 exome AF: 0.00350 AC: 5112AN: 1460826Hom.: 15 Cov.: 33 AF XY: 0.00351 AC XY: 2552AN XY: 726810
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Sep 04, 2023 | - - |
Primary ciliary dyskinesia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
DNAAF3-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 13, 2022 | 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
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Name
Calibrated prediction
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: 2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at