rs35214636
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_178452.6(DNAAF1):āc.2109A>Gā(p.Gly703=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000872 in 1,614,036 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.0046 ( 6 hom., cov: 32)
Exomes š: 0.00048 ( 3 hom. )
Consequence
DNAAF1
NM_178452.6 synonymous
NM_178452.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.559
Genes affected
DNAAF1 (HGNC:30539): (dynein axonemal assembly factor 1) The protein encoded by this gene is cilium-specific and is required for the stability of the ciliary architecture. It is involved in the regulation of microtubule-based cilia and actin-based brush border microvilli. Mutations in this gene are associated with primary ciliary dyskinesia-13. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BP6
Variant 16-84177772-A-G is Benign according to our data. Variant chr16-84177772-A-G is described in ClinVar as [Benign]. Clinvar id is 242162.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-84177772-A-G is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-0.559 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00461 (702/152250) while in subpopulation AFR AF= 0.0161 (668/41532). AF 95% confidence interval is 0.0151. There are 6 homozygotes in gnomad4. There are 292 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 6 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAAF1 | NM_178452.6 | c.2109A>G | p.Gly703= | synonymous_variant | 12/12 | ENST00000378553.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAAF1 | ENST00000378553.10 | c.2109A>G | p.Gly703= | synonymous_variant | 12/12 | 1 | NM_178452.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00461 AC: 701AN: 152132Hom.: 6 Cov.: 32
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GnomAD3 exomes AF: 0.00119 AC: 298AN: 251414Hom.: 3 AF XY: 0.000773 AC XY: 105AN XY: 135892
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GnomAD4 exome AF: 0.000482 AC: 705AN: 1461786Hom.: 3 Cov.: 31 AF XY: 0.000407 AC XY: 296AN XY: 727202
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GnomAD4 genome AF: 0.00461 AC: 702AN: 152250Hom.: 6 Cov.: 32 AF XY: 0.00392 AC XY: 292AN XY: 74440
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia Benign:2
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 15, 2014 | 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 20, 2024 | - - |
Computational scores
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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