rs200353947
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PVS1_ModerateBP6_Very_StrongBS1BS2
The NM_181426.2(CCDC39):βc.2660_2661insTβ(p.Ser888IlefsTer6) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 1,613,166 control chromosomes in the GnomAD database, including 108 homozygotes. Variant has been reported in ClinVar as Likely benign (β β ).
Frequency
Genomes: π 0.0083 ( 9 hom., cov: 32)
Exomes π: 0.010 ( 99 hom. )
Consequence
CCDC39
NM_181426.2 frameshift
NM_181426.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.53
Genes affected
CCDC39 (HGNC:25244): (coiled-coil domain 39 molecular ruler complex subunit) The protein encoded by this gene is involved in the motility of cilia and flagella. The encoded protein is essential for the assembly of dynein regulatory and inner dynein arm complexes, which regulate ciliary beat. Defects in this gene are a cause of primary ciliary dyskinesia type 14 (CILD14). [provided by RefSeq, Jul 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0587 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
BP6
?
Variant 3-180616289-T-TA is Benign according to our data. Variant chr3-180616289-T-TA is described in ClinVar as [Likely_benign]. Clinvar id is 194994.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00827 (1259/152278) while in subpopulation NFE AF= 0.0121 (824/68020). AF 95% confidence interval is 0.0114. There are 9 homozygotes in gnomad4. There are 587 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 9 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCDC39 | NM_181426.2 | c.2660_2661insT | p.Ser888IlefsTer6 | frameshift_variant | 19/20 | ENST00000476379.6 | |
TTC14 | NM_001288582.2 | c.1775-1090dup | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCDC39 | ENST00000476379.6 | c.2660_2661insT | p.Ser888IlefsTer6 | frameshift_variant | 19/20 | 2 | NM_181426.2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00827 AC: 1259AN: 152160Hom.: 9 Cov.: 32
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GnomAD3 exomes AF: 0.00792 AC: 1970AN: 248856Hom.: 15 AF XY: 0.00783 AC XY: 1057AN XY: 134994
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GnomAD4 exome AF: 0.0104 AC: 15207AN: 1460888Hom.: 99 Cov.: 31 AF XY: 0.0103 AC XY: 7464AN XY: 726708
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GnomAD4 genome ? AF: 0.00827 AC: 1259AN: 152278Hom.: 9 Cov.: 32 AF XY: 0.00788 AC XY: 587AN XY: 74458
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 12, 2015 | - - |
Primary ciliary dyskinesia Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 14, 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. - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 02, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | CCDC39: BS1, BS2; TTC14: BS1, BS2 - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at