rs746242380
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_213607.3(CCDC103):c.566_569del(p.Glu189AlafsTer18) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000229 in 1,613,848 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. A186A) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000023 ( 0 hom. )
Consequence
CCDC103
NM_213607.3 frameshift
NM_213607.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.53
Genes affected
CCDC103 (HGNC:32700): (coiled-coil domain containing 103) Enables protein homodimerization activity. Involved in axonemal dynein complex assembly; cilium movement; and determination of left/right symmetry. Predicted to be located in axoneme. Predicted to be part of outer dynein arm. Implicated in primary ciliary dyskinesia 17. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.235 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 17-44902645-CAGAG-C is Pathogenic according to our data. Variant chr17-44902645-CAGAG-C is described in ClinVar as [Pathogenic]. Clinvar id is 1451307.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCDC103 | NM_213607.3 | c.566_569del | p.Glu189AlafsTer18 | frameshift_variant | 4/4 | ENST00000417826.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCDC103 | ENST00000417826.3 | c.566_569del | p.Glu189AlafsTer18 | frameshift_variant | 4/4 | 1 | NM_213607.3 | P1 | |
CCDC103 | ENST00000357776.6 | c.566_569del | p.Glu189AlafsTer18 | frameshift_variant | 4/4 | 2 | |||
CCDC103 | ENST00000410006.6 | c.566_569del | p.Glu189AlafsTer18 | frameshift_variant | 4/4 | 2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152016Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249972Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135204
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GnomAD4 exome AF: 0.0000226 AC: 33AN: 1461832Hom.: 0 AF XY: 0.0000275 AC XY: 20AN XY: 727224
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152016Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74240
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Apr 06, 2023 | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the CCDC103 protein in which other variant(s) (p.Ser190Argfs*19) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This premature translational stop signal has been observed in individual(s) with primary ciliary dyskinesia (Invitae). This variant is present in population databases (rs746242380, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Glu189Alafs*18) in the CCDC103 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 54 amino acid(s) of the CCDC103 protein. - |
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