rs529083217
Positions:
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_018139.3(DNAAF2):c.561C>T(p.Thr187=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000886 in 1,606,150 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00056 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00092 ( 23 hom. )
Consequence
DNAAF2
NM_018139.3 synonymous
NM_018139.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.314
Genes affected
DNAAF2 (HGNC:20188): (dynein axonemal assembly factor 2) This gene encodes a highly conserved protein involved in the preassembly of dynein arm complexes which power cilia. These complexes are found in some cilia and are assembled in the cytoplasm prior to transport for cilia formation. Mutations in this gene have been associated with primary ciliary dyskinesia. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]
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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=-0.38).
BP6
?
Variant 14-49634589-G-A is Benign according to our data. Variant chr14-49634589-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 261020.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-49634589-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-0.314 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000558 (85/152338) while in subpopulation SAS AF= 0.017 (82/4826). AF 95% confidence interval is 0.014. There are 1 homozygotes in gnomad4. There are 56 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 23 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAAF2 | NM_018139.3 | c.561C>T | p.Thr187= | synonymous_variant | 1/3 | ENST00000298292.13 | |
DNAAF2 | NM_001083908.2 | c.561C>T | p.Thr187= | synonymous_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAAF2 | ENST00000298292.13 | c.561C>T | p.Thr187= | synonymous_variant | 1/3 | 1 | NM_018139.3 | P2 | |
DNAAF2 | ENST00000406043.3 | c.561C>T | p.Thr187= | synonymous_variant | 1/2 | 1 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000565 AC: 86AN: 152220Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.00197 AC: 469AN: 237824Hom.: 11 AF XY: 0.00261 AC XY: 340AN XY: 130394
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GnomAD4 exome AF: 0.000920 AC: 1338AN: 1453812Hom.: 23 Cov.: 88 AF XY: 0.00134 AC XY: 973AN XY: 723550
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GnomAD4 genome ? AF: 0.000558 AC: 85AN: 152338Hom.: 1 Cov.: 33 AF XY: 0.000752 AC XY: 56AN XY: 74498
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 04, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 07, 2022 | This alteration is classified as likely 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. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Primary ciliary dyskinesia 10 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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