chr8-132572301-A-C
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Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_012472.6(DNAAF11):c.*5T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000172 in 1,611,750 control chromosomes in the GnomAD database, including 1 homozygotes. 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 0.00040 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00015 ( 1 hom. )
Consequence
DNAAF11
NM_012472.6 3_prime_UTR
NM_012472.6 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.701
Genes affected
DNAAF11 (HGNC:16725): (dynein axonemal assembly factor 11) The protein encoded by this gene contains several leucine-rich repeat domains and appears to be involved in the motility of cilia. Defects in this gene are a cause of primary ciliary dyskinesia-19 (CILD19). Alternative splicing of this gene results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 4, 11 and 22. [provided by RefSeq, Apr 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -7 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
Variant 8-132572301-A-C is Benign according to our data. Variant chr8-132572301-A-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 908936.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0004 (61/152322) while in subpopulation EAS AF= 0.00638 (33/5172). AF 95% confidence interval is 0.00467. There are 0 homozygotes in gnomad4. There are 25 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|---|---|---|---|---|---|---|
| DNAAF11 | NM_012472.6 | c.*5T>G | 3_prime_UTR_variant | 12/12 | ENST00000620350.5 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| DNAAF11 | ENST00000620350.5 | c.*5T>G | 3_prime_UTR_variant | 12/12 | 1 | NM_012472.6 | P1 |
Frequencies
GnomAD3 genomes 0.000368 AC: 56AN: 152204Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000418 AC: 104AN: 248902Hom.: 0 AF XY: 0.000409 AC XY: 55AN XY: 134550
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GnomAD4 exome AF: 0.000149 AC: 217AN: 1459428Hom.: 1 Cov.: 30 AF XY: 0.000139 AC XY: 101AN XY: 726050
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GnomAD4 genome 0.000400 AC: 61AN: 152322Hom.: 0 Cov.: 32 AF XY: 0.000336 AC XY: 25AN XY: 74482
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia 19 Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 15, 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. - |
Primary ciliary dyskinesia Benign:1
| Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 28, 2017 | 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. - |
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