rs150362958
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_001256715.2(DNAAF3):c.6C>T(p.Thr2=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 1,613,794 control chromosomes in the GnomAD database, including 131 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0082 ( 13 hom., cov: 32)
Exomes 𝑓: 0.012 ( 118 hom. )
Consequence
DNAAF3
NM_001256715.2 synonymous
NM_001256715.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.661
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 -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
?
Variant 19-55166408-G-A is Benign according to our data. Variant chr19-55166408-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 238684.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-55166408-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=0.661 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00817 (1244/152248) while in subpopulation NFE AF= 0.0145 (985/68020). AF 95% confidence interval is 0.0137. There are 13 homozygotes in gnomad4. There are 561 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 13 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAAF3 | NM_001256715.2 | c.6C>T | p.Thr2= | synonymous_variant | 2/12 | ENST00000524407.7 | |
DNAAF3-AS1 | XR_007067344.1 | n.946G>A | non_coding_transcript_exon_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAAF3 | ENST00000524407.7 | c.6C>T | p.Thr2= | synonymous_variant | 2/12 | 1 | NM_001256715.2 | A2 | |
DNAAF3-AS1 | ENST00000591665.1 | n.1186+3607G>A | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00818 AC: 1244AN: 152130Hom.: 13 Cov.: 32
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GnomAD3 exomes AF: 0.00789 AC: 1959AN: 248134Hom.: 14 AF XY: 0.00786 AC XY: 1059AN XY: 134756
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GnomAD4 exome AF: 0.0122 AC: 17818AN: 1461546Hom.: 118 Cov.: 33 AF XY: 0.0120 AC XY: 8733AN XY: 727052
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
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 - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Primary ciliary dyskinesia Benign:2
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 18, 2019 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 28, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | DNAAF3: BP4, BP7, BS1, BS2 - |
Primary ciliary dyskinesia 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 22, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at