rs201056459
Positions:
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1
The NM_018139.3(DNAAF2):āc.1467T>Cā(p.Asp489=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000653 in 1,607,164 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 Likely benign (ā ā ).
Frequency
Genomes: š 0.000040 ( 0 hom., cov: 33)
Exomes š: 0.000068 ( 1 hom. )
Consequence
DNAAF2
NM_018139.3 synonymous
NM_018139.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.905
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 -15 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
?
Variant 14-49633683-A-G is Benign according to our data. Variant chr14-49633683-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 525529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.905 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.000068 (99/1455290) while in subpopulation SAS AF= 0.000894 (77/86110). AF 95% confidence interval is 0.000733. There are 1 homozygotes in gnomad4_exome. There are 74 alleles in male gnomad4_exome subpopulation. Median coverage is 92. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAAF2 | NM_018139.3 | c.1467T>C | p.Asp489= | synonymous_variant | 1/3 | ENST00000298292.13 | |
DNAAF2 | NM_001083908.2 | c.1467T>C | p.Asp489= | synonymous_variant | 1/2 | ||
DNAAF2 | NM_001378453.1 | c.-405T>C | 5_prime_UTR_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAAF2 | ENST00000298292.13 | c.1467T>C | p.Asp489= | synonymous_variant | 1/3 | 1 | NM_018139.3 | P2 | |
DNAAF2 | ENST00000406043.3 | c.1467T>C | p.Asp489= | synonymous_variant | 1/2 | 1 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000395 AC: 6AN: 151754Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000121 AC: 30AN: 247570Hom.: 1 AF XY: 0.000164 AC XY: 22AN XY: 134496
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GnomAD4 exome AF: 0.0000680 AC: 99AN: 1455290Hom.: 1 Cov.: 92 AF XY: 0.000102 AC XY: 74AN XY: 722958
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GnomAD4 genome ? AF: 0.0000395 AC: 6AN: 151874Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74236
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 03, 2023 | 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 | Sep 05, 2023 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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