14-49634964-C-T
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_018139.3(DNAAF2):c.186G>A(p.Glu62=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: not found (cov: 36)
Exomes 𝑓: 0.0000050 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
DNAAF2
NM_018139.3 synonymous
NM_018139.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.11
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 -11 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
Variant 14-49634964-C-T is Benign according to our data. Variant chr14-49634964-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1781658.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1.11 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAAF2 | NM_018139.3 | c.186G>A | p.Glu62= | synonymous_variant | 1/3 | ENST00000298292.13 | |
DNAAF2 | NM_001083908.2 | c.186G>A | p.Glu62= | synonymous_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAAF2 | ENST00000298292.13 | c.186G>A | p.Glu62= | synonymous_variant | 1/3 | 1 | NM_018139.3 | P2 | |
DNAAF2 | ENST00000406043.3 | c.186G>A | p.Glu62= | synonymous_variant | 1/2 | 1 | A2 |
Frequencies
GnomAD3 genomes Cov.: 36
GnomAD3 genomes
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36
GnomAD3 exomes AF: 0.0000366 AC: 6AN: 163802Hom.: 0 AF XY: 0.0000225 AC XY: 2AN XY: 88932
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000497 AC: 7AN: 1408246Hom.: 0 Cov.: 111 AF XY: 0.00000431 AC XY: 3AN XY: 695788
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
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GnomAD4 genome Cov.: 36
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36
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 | May 11, 2020 | 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 12, 2024 | - - |
Computational scores
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Name
Calibrated prediction
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Prediction
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