rs148990251
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6BP7BS1
The NM_178452.6(DNAAF1):c.1350G>A(p.Pro450=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000172 in 1,611,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00017 ( 0 hom. )
Consequence
DNAAF1
NM_178452.6 synonymous
NM_178452.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.57
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 -8 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
?
Variant 16-84170178-G-A is Benign according to our data. Variant chr16-84170178-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 242157.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=1}. Variant chr16-84170178-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-1.58 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000165 (241/1460106) while in subpopulation MID AF= 0.000697 (4/5736). AF 95% confidence interval is 0.000371. There are 0 homozygotes in gnomad4_exome. There are 125 alleles in male gnomad4_exome subpopulation. Median coverage is 94. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAAF1 | NM_178452.6 | c.1350G>A | p.Pro450= | synonymous_variant | 8/12 | ENST00000378553.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAAF1 | ENST00000378553.10 | c.1350G>A | p.Pro450= | synonymous_variant | 8/12 | 1 | NM_178452.6 | P1 | |
DNAAF1 | ENST00000563818.5 | n.1027G>A | non_coding_transcript_exon_variant | 4/8 | 2 | ||||
DNAAF1 | ENST00000570298.5 | n.1504G>A | non_coding_transcript_exon_variant | 8/11 | 2 | ||||
DNAAF1 | ENST00000563093.5 | c.1226-64G>A | intron_variant, NMD_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000244 AC: 37AN: 151568Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000112 AC: 28AN: 250870Hom.: 0 AF XY: 0.000140 AC XY: 19AN XY: 135708
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GnomAD4 exome AF: 0.000165 AC: 241AN: 1460106Hom.: 0 Cov.: 94 AF XY: 0.000172 AC XY: 125AN XY: 726404
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GnomAD4 genome ? AF: 0.000244 AC: 37AN: 151682Hom.: 0 Cov.: 32 AF XY: 0.000270 AC XY: 20AN XY: 74156
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 05, 2015 | 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. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Primary ciliary dyskinesia 13 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
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